Exhibit 10.1
Confidential Materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.
AGREEMENT
This Agreement is made effective as of the 27/th/ day of November, 2002 by and
between CURIS INC., a Delaware corporation, having a place of business at 61
Moulton St., Cambridge, Massachusetts 02138 ("CURIS"), and Ortho Biotech
Products, L.P., a New Jersey limited partnership, having a place of business at
Route 22 East, P.O. Box 6914, Bridgewater, New Jersey, 08807-0914 ("OBI"). CURIS
and OBI are each referred to by name or as a "Party" or, collectively, as
"Parties". References to "CURIS" and "OBI" shall include their respective
Affiliates (hereinafter defined), where appropriate under the terms of this
Agreement.
RECITALS
1. CURIS has on-going research and certain product development and clinical
development capabilities and has identified a lead compound, BMP-7 with the
potential to be further developed for the treatment of renal disease and related
disorders or disorders of the nervous system, from acute or chronic insults.
2. OBI possesses research, development and commercialization capabilities,
as well as proprietary technology in a broad range of therapeutic fields.
3. CURIS desire to license BMP-7 to OBI so that OBI may develop and
commercialize BMP-7 for all indications, except certain orthopedic and dental
indications.
NOW, THEREFORE, in consideration of the premises and mutual covenants
herein contained, and for other good and valuable consideration, the receipt and
sufficiency of which are hereby acknowledged, the Parties hereto agree as
follows:
ARTICLE I - DEFINITIONS
When used in this Agreement, each of the following terms, when capitalized,
shall have the meaning set forth below. The term shall have the same meaning
whether the singular or plural form is used.
"BMP-7" means BMP-7 protein and nucleic acid and all variants, derivatives,
fragments, antibodies, and agonists thereto and vectors and hosts containing the
foregoing.
"Bone Disease Field" means the prevention or treatment of Osteoporosis,
Osteomalacia, and Paget's Disease other than (i) by the local application of
5
Licensed Products in an insoluble formulation directly on bone or joint tissue
for local, as opposed to general or systemic, effect and (ii) the treatment of
fractures regardless of whether they result from Osteoporosis, Osteomalacia and
Paget's Disease.
"Cell Line" means the cells and related biological materials that are useful in
the production of BMP-7.
"Combination Product" means a product sold by OBI which contains one or more
Additional Components in addition to a Licensed Product.
"Contract Year" means a year of 365 days (or 366 days in a leap year) beginning
on the Effective Date and ending one (1) year thereafter and so on year-by-year.
"Control" or "Controlled" means possession of the ability to grant a license or
sublicense as provided for herein without violating the terms of any agreement
or other arrangements with any Third Party.
"CURIS Know-How" means Information which is within the Control of CURIS.
Notwithstanding anything herein to the contrary, CURIS Know-How excludes
published CURIS Patents.
"CURIS Patent Rights" means the rights granted by any governmental authority
under a Patent relating to a Licensed Product, which Patent is owned, co-owned
or Controlled by CURIS during the term of this Agreement. CURIS Patents include
but are not limited to Primary Third Party Patent Rights and Secondary Third
Party Patent Rights. Patents that relate to CURIS Patent Rights are listed in
Schedules A, B, C, D and E.
"Date of First Sale" means the date on which OBI (or an Affiliate) first sells a
Licensed Product to an unaffiliated Third Party in an arms length commercial
transaction.
"Dollars" or "$" means lawful money of the United States in immediately
available funds.
"Drug Approval Application" means an application for Regulatory Approval
required before commercial sale or use of a Licensed Product as a drug in a
regulatory jurisdiction.
"Effective Date" means the date first written above.
"EMEA" means the European Medicines Evaluation Agency or any successor agency.
6
"FDA" means the United States Food and Drug Administration or any successor
agency.
"Field" means the development, use, manufacture, distribution, marketing and
sale of Licensed Products for all uses and applications of BMP-7 excluding (i)
treatment, repair or replacement of bone and joint tissue, including without
limitation, meniscus and articular cartilage and ligaments and tendons, but
excluding the Bone Disease Field, and (ii) treatment, repair or replacement of
the tooth, dentin, alveolar bone, cementum, enamel, gingiva (to the extent, but
only to the extent, the gingiva functions as part of the apparatus holding the
tooth to the jaw) and /or periodontal ligament, but excluding the treatment of
Oral Ulcerations or any other disease or disorder of the tissues of the mouth
not involving the tooth, dentin, bone (including alveolar bone), cementum,
enamel, gingiva (to the extent but only to the extent the gingiva functions as
part of the apparatus holding the tooth to the jaw), ligament (including the
periodontal ligament), tendon and/or cartilage.
"First Proof of Principle Clinical Study or First POP" means the first OBI proof
of principle program in which BMP-7 is evaluated for a Renal Indication and is
selected by OBI for further clinical development, produced in quantity under GMP
conditions, preclinical toxicology studies are performed, and the first
administration to human subjects is performed.
"Generic Equivalent" means a compound that is being sold in a country without
infringing a CURIS Patent covering a composition of matter of the Licensed
Product being sold hereunder by OBI, which would have infringed such CURIS
Patent or Program Patent if such CURIS Patent or Program Patent containing a
Valid Patent Claim were in force in that country.
"IND" means an investigational new drug application filed with the FDA as more
fully defined in 21 C.F.R. (S)312.3 or its equivalent in any country.
"Information" means information, generally not known to the public, relating to
the Field and including (i) techniques and data, including, but not limited to,
screens, models, inventions, practices, methods, knowledge, know-how, skill,
experience, test data including pharmacological, toxicological and clinical test
data, analytical and quality control data, marketing, pricing, distribution,
costs, sales, manufacturing data, and patent and legal data or descriptions (to
the extent that disclosure thereof would not result in loss or waiver of
privilege or similar protection) and (ii) compounds, compositions of matter,
assays and biological materials.
"Licensed Product" means any form or dosage of BMP-7 for pharmaceutical use in
humans or other animals or for any other use.
7
"Ludwig Agreement" is the Agreement among Creative Biomolecules, Inc., The
Ludwig Institute for Cancer Research and the Japanese Research Foundation for
Cancer Research dated June 1, 1997.
"Ludwig Patent Rights" means those Patents co-owned by CURIS and Ludwig
Institute listed in Schedule C
"Major European Country" means Great Britain, France, Germany, Italy, or Spain.
"NDA" means a New Drug Application and all supplements filed pursuant to the
requirements of the FDA, including all documents, data and other information
concerning a Licensed Product which are necessary for or included in, FDA
approval to market a Licensed Product as more fully defined in 21 C.F.R.
(S)314.50 et. seq.
"Net Sales" means consistent with generally accepted accounting principles and
OBI worldwide practices and procedures, consistently applied with respect to a
Licensed Product, which contain as its active ingredients only BMP-7, the amount
invoiced by OBI for sales of Licensed Products to a Third Party in the
Territory, less estimates which will be adjusted to actual on a periodic basis
(no less frequently than annually) of: (i), discounts, including cash discounts,
discounts to managed care or similar organizations or government organizations,
rebates paid, credit, accrued or actually taken, including government rebates
such as Medicaid charge backs or rebates, and retroactive price reductions or
allowances actually allowed or granted from the billed amount, and commercially
reasonable and customary fees paid to distributors (other than to a distributor
that is an Affiliate of OBI), but not any fees or discounts paid to Copromotion
Partners, (ii) credits or allowances actually granted upon claims, rejections or
returns of such sales of Licensed Products, including recalls, regardless of OBI
requesting such recalls, (iii) taxes, duties or other governmental charges
levied on or measured by the billing amount when included in billing, as
adjusted for rebates, charge-backs, and refunds, and (iv) freight, postage,
shipping and insurance charges paid for delivery of such Licensed Products, to
the extent billed, and (v) provisions for uncollectable accounts determined in
accordance with U.S. generally accepted accounting practices consistently
applied to all products of OBI, provided, however, that if collected at a later
date such amounts will be added to Net Sales in the quarter in which it is
received; and with respect to Licensed Products that OBI has elected to
sublicense to a Third Party, the amounts received by OBI in the form of
royalties from such Third Parties, except for in the instance of further
sublicense by OBI of rights granted to Curis by Stryker Corporation. In such
instance, Net Sales must be computed by reference to Net Sales of OBI's
sublicensee, not by reference to royalties paid OBI.
With respect to Combination Products, Net Sales for such Combination Product
sold by OBI will be calculated by determining the relative value provided by the
8
Licensed Product to the Combination Product. The general process and guidance to
be followed in each market/country where a Combination Product is to be launched
will be to determine weighted average net price per unit across all dosage forms
of the combination product in that market in the 12 months preceding
introduction of the combination product as well as the weighted average net
price per unit across all dosage forms of additional components deemed to be key
ingredients that are sold in that particular market in the 12 months preceding
launch of the Combination Product.
Further guidance for determining Net Sales of Licensed Product would be to
multiply actual Net Sales for such Combination Product by the fraction A/(A+B)
where A is the Price of the Collaboration Compound if the Licensed Product is
sold separately, and B is the total Price of any Additional Components in the
Combination Product if sold separately. If, on a country-by-country basis,
either the Licensed Product or the Additional Components in the Combination
Product are not sold separately in said country, Net Sales for the purpose of
determining royalties of the Combination Product shall be calculated by
multiplying actual Net Sales of such Combination Product by the fraction A/C
where A is the Price of the Licensed Product, if sold separately, and C is the
Price of the Combination Product.
In all cases the computation of Net Sales for the purpose of determining
royalties shall be determined by the parties to this Agreement in good faith
based on the relative value of the Collaboration Compound and the Additional
Components that are part of the Combination Product. This also includes the
potential if, for any particular country, neither the Licensed Product nor the
Additional Components of the Combination Product are sold separately in said
country. Notwithstanding anything herein to the contrary, there will be no
deductions from Net Sales of any fees paid or discounts granted to a Copromotion
Partner for co-promoting a Licensed Product such as, for example, marketing
fees.
"Neural Indication" means central or peripheral nervous system disorder caused
by acute injury including stroke and/or other trauma or a chronic condition
including those conditions that are a consequence of a neuronal degeneration.
"Oral Ulcerations" means the formation of lesions on the surface of skin lining
the oral cavity caused by loss of tissue but does not include Periodontal
Disease (as defined below) or any other disease or disorder involving the tooth,
dentin, bone (including alveolar bone), cementum, enamel, gingiva (to the
extent, but only to the extent, the gingiva functions as part of the apparatus
holding the tooth to the jaw), ligament (including the periodontal ligament),
tendon and/or cartilage.
"Patent" means (i) valid and enforceable Letters Patent, including any
extension, registration, confirmation, reissue, continuation, divisional,
continuation-in-part, re-examination or renewal thereof and (ii) pending
applications for Letters
9
Patents.
"Patent Costs" means the reasonable fees and expenses paid to outside legal
counsel and other Third Parties, and filing and maintenance expenses, incurred
in connection with the establishment and maintenance of rights under Patents.
"Periodontal Disease" means degeneration of the apparatus holding the tooth to
the jaw involving damage to any or all of the gingiva (to the extent, but only
to the extent, the gingiva functions as part of the apparatus holding the tooth
to the jaw), alveolar bone, cementum, enamel and periodontal ligament.
"Phase I" shall mean the portion of the clinical development program which
provides for the first introduction into humans of a Licensed Product, including
small scale clinical studies conducted in normal volunteers or patients to get
information of Licensed Product safety, tolerability, pharmacological activity
or pharmacokinetics, as more fully defined in 21 C.F.R. 312.21 (a). Such studies
may include well controlled clinical studies in patients or volunteers lasting
up to six (6) weeks per study.
"Phase II" shall mean that portion of the clinical development program beyond
Phase I, which provides for the definitive, well controlled clinical trials of a
Licensed Product in patients, including clinical studies conducted in patients
and designated to indicate clinical efficacy safety, as well as to obtain an
indication of the dosage regimen required as more fully defined in 21 C.F. R.
312.21(b).
"Phase III" shall mean that portion of the clinical development program beyond
Phase II, which provides for large scale clinical studies conducted in a
sufficient number of patients to establish the clinical efficacy of a Licensed
Product for one or more indications and its safety, as more fully defined in 21
C.F.R. 312.21 (c).
"Primary Third Party Patent Rights" means the rights granted to CURIS under
Stryker Corporation Patents recited in Schedule B, Genetics Institute Patents
listed in Schedule E and those co-owned Patents recited in Schedules C and D.
"R&D Agreements" means the research and development agreements that consist of
Material Transfer Agreements and Collaboration Agreements as listed in Schedule
F.
"Regulatory Approval" shall mean all official approvals by government, pricing
or health authorities in a country (or super-national organizations, such as the
EMEA) which are required for first use or sale, including, importation,
manufacture (where manufacture is required), and if required, approvals for
pricing or reimbursement of a pharmaceutical product in such country.
10
"Renal Indication" means a treatment directed to acute or chronic renal
disorders and related disorders including, but not limited to, renal
osteodystrophy and vascular calcification.
"Replacement Compound" shall have the meaning described in Section 5.2.
"Research" means all work performed by the Parties or on their behalf directed
towards or in connection with the discovery, identification and synthesis of
Licensed Product during the term of the Agreement.
"Royalty Reporting Period" means the three month period ending on or about the
exact dates of March 31, June 30, September 30 or December 31 of any year, with
the beginning determined by Johnson & Johnson's calendar quarters.
"Secondary Third Party Patent Rights" means the rights granted to CURIS, under
Third Party Patents owned or Controlled by such Third Party, by virtue of an R&D
Agreement between CURIS and a Third Party to make, use or sell BMP-7.
"Sublicensee" shall mean, with respect to a particular Licensed Product, a Third
Party to whom OBI or CURIS has granted a license or sublicense under any OBI
Patents or CURIS Patents to make, use and sell such Licensed Product. As used in
this Agreement, "Sublicensee" shall also include a Third Party to whom OBI has
granted the right to distribute a Licensed Product, provided that such Third
Party is responsible for marketing and promotion of such Licensed Product within
its distribution territory."Territory" means all the countries of the world.
"Third Party" means any entity other than CURIS, OBI or any Affiliates of CURIS
or OBI.
"Third Party Agreements" mean those Agreements listed in Schedule G.
"Valid Patent Claim" means a claim in any unexpired CURIS Patent, which has
matured into an issued patent which has not been held invalid by a non-appealed
or unappealable decision by a court or other appropriate body of competent
jurisdiction and claims BMP-7 or its use. The scope of a Valid Patent Claim
shall be limited to its terms as set forth in the Patent itself and as further
defined by any court, body or law of competent jurisdiction. For the purpose of
royalty determination and payment, any claim being prosecuted in a pending
patent application shall be deemed to be the equivalent of a Valid Patent Claim
of an issued, unexpired patent, provided it is not pending for greater than six
(6) years from the filing date of the patent application in which case it shall
cease being a Valid Patent Claim until the patent issues.
ARTICLE II - PRODUCT DEVELOPMENT
11
2.1 OBI's Development Responsibilities. OBI shall have the sole right to
develop Licensed Product in the Field through First POP, Phases I, II and III,
including but not limited to, preparing, filing and exclusively owning all Drug
Approval Applications and obtaining and exclusively owning all Regulatory
Approvals in the Territory. In this regard, OBI agrees to carry out development
of Licensed Product consistent with its normal business practices regarding a
compound of similar commercial potential.
2.2 CURIS' Responsibilities. Promptly after the Effective Date, CURIS shall
transfer all Information relating to Licensed Product to OBI.
ARTICLE III - COMMERCIALIZATION
3.1 OBI's Marketing Obligations For Licensed Products. All business decisions,
including, but not limited to, the design, sale, price and promotion of Licensed
Products under this Agreement and the decisions whether to market or not market
any particular Licensed Product shall be within the sole discretion of OBI. Any
marketing of a Licensed Product in one market or country shall not obligate OBI
to market said Licensed Product in any other market or country. Furthermore, OBI
makes no representation or warranty that the marketing of a Licensed Product
shall be the exclusive means by which OBI will participate in any therapeutic
field. In marketing any Licensed Product, OBI will use efforts that are
consistent with the efforts it uses in commercializing its own pharmaceutical
products (that are similar with regard to, for example, market potential, price
per treatment, patient population and competitive position).
3.2 Trademarks. OBI shall select its own trademarks under which it will market
Licensed Product and shall solely own such trademarks.
ARTICLE IV - LICENSE GRANTS
4.1 Patent Licenses for BMP-7 and Licensed Products. As of the Effective Date
and to the extent CURIS possesses exclusive rights itself and the right to
sublicense CURIS hereby grants to OBI and its Affiliates an exclusive royalty
bearing, worldwide license under CURIS Patent Rights with a right to grant
sublicenses, to the extent that CURIS is able to grant such right to sublicense,
to make, have made, use, import, offer for sale, sell, distribute and have sold
Licensed Product in the Field. In the event CURIS does not possess exclusive
rights to such CURIS Patent Rights, CURIS grants OBI the foregoing license on a
non-exclusive basis but, in either case, exclusive as to CURIS.
4.2 CURIS agrees for the term of this Agreement not to make, use or sell in the
Field or to grant a license to a Third Party to make, use or sell in the Field a
product which is or includes a protein sharing at least 50% amino acid sequence
identity with the Carboxy-terminal 7-cysteine domain sequence of the BMP-7 (a
12
"50% Homolog") or any truncated or species variant form of such 50% Homolog or
homodimeric, heterodimeric or chimeric form of the 50% Homolog or any polyclonal
or monoclonal antibodies to the 50% Homolog or DNA or RNA encoding the 50%
Homolog.
ARTICLE V - PAYMENTS
In consideration of the assignments, rights and licenses granted under this
Agreement, OBI agrees to pay CURIS as follows:
5.1 Upfront Payment. OBI agrees to pay to CURIS a non-refundable upfront
payment of $3,500,000 by same day wire transfer within fifteen (15) business
days of the date of execution of this Agreement by both Parties.
5.2 Milestones.
(a) OBI agrees to make the following payments to CURIS upon the first
occurrence of each milestone event for the Licensed Product. If a Licensed
Product is replaced by OBI with another Licensed Product (a "Replacement
Compound"), OBI shall not be obligated to make the same milestone payments for
the Replacement Compound as it already made in connection with the Licensed
Product which was replaced. It is understood that in no event shall OBI be
obligated to make the payment due on any milestone more than once with respect
to the same Licensed Product (or its Replacement Compound) in connection with
either the Renal Indication or the Neural Indication, regardless of the number
of indications with the Renal Indication or Neural Indication for which such
Licensed Product is developed.
(b) The amounts shown are the amounts to be received by CURIS, net of any
withholding taxes, due on every milestone payment, which shall be the
responsibility of OBI.
(c) Upon the achievement of the following milestones in connection with a
Renal Indication for Licensed Product as follows:
(i) $[**] upon acceptance by FDA or the regulatory authority of a
Major European Country of the first IND (or its foreign equivalent);
(ii) $[**] upon completion of the First POP and an affirmative
decision by OBP to continue a post-POP development program for Regulatory
Approval;
(iii) $[**] upon the dosing of the 10th patient in the first Phase III
clinical trial;
(iv) $30,000,000 upon the US Regulatory Approval of the Licensed
Product; and
13
(v) $[**] upon EMEA Regulatory Approval or approval in the first
Major European Country of Licensed Product.
(d) Upon the achievement of the following milestones in connection with a
Neural Indication for Licensed Product as follows:
(i) $[**] upon the dosing of the 10th patient in the first Phase III
clinical trial;
(ii) $[**] upon US Regulatory Approval of Licensed Product; and
(iii) $[**] upon EMEA Regulatory Approval or approval in the
first Major European Country of Licensed Product.
5.3 Earned Royalties For Licensed Products.
(a) OBI shall pay CURIS a royalty of [**]% of Net Sales of Licensed Product
sold by or for OBI, its Affiliates or Sublicensees.
(b) Royalties shall be paid in respect of a given Licensed Product, on
country-by-country basis, for a period of the later of (i) ten (10) years from
the Date of First Sale of the Licensed Product in a given country or (ii) the
expiration of the last to expire of any Valid Patent Claim covering the Licensed
Product in such country, provided that, if in any Royalty Reporting Period
during such period, (1) a third Party commences selling a Product which is a
Generic Equivalent of the Licensed Product in a country in the Territory and (2)
such Unlicensed Unit Sales (as defined below) amount to the following
percentages of OBI's Unit Sales in units of the Licensed Product in such country
in the same Royalty Reporting Period, the royalty rate applied in such country
shall be reduced by the following percentages, as long as the Unlicensed Unit
Sales amount to the particular percentage of OBI's unit sales in units of the
Licensed Product in such country in the same Royalty Reporting Period.
Unlicensed Unit Sales as a Royalty Rate Reduction*
(% of OBI Unit Sales) (% of Royalty Rate)
less than [**]% [**]%
[**]% - [**]% [**]%
more than [**]% [**]%
For purposes of this Section 6.5 (b) "Unlicensed Unit Sales" and "OBI Unit
Sales" shall be deemed to mean the total grams of BMP-7 contained in the Third
Party product (irrespective of dosage form) and the Licensed Product
(irrespective of dosage form), respectively, as reflected on the label of each
such Licensed Product and Third Party product; and (ii) Unlicensed Unit Sales
shall be determined by the sales reports of IMS America Ltd. of Plymouth
Meeting,
14
Pennsylvania ("IMS") or any successor to IMS or any other independent sales
auditing firm selected by OBI and reasonably acceptable to CURIS. OBI shall bear
all costs of providing CURIS with such information. If OBI is entitled to a
royalty reduction based on Unlicensed Unit Sales pursuant to this Section 5.3(b)
for any Royalty Reporting Period, OBI shall submit the sales report of IMS or
such other independent firm, as applicable, for the relevant Royalty Reporting
Period to CURIS, together with OBI's or its Sublicensees' sales report for the
relevant Royalty Reporting Period. Such sales reports for each Royalty Reporting
Period in which OBI is entitled to such royalty reduction shall be submitted
with the royalty report for such Royalty Reporting Period submitted pursuant to
Section 5.7.
5.4 Third Party Patents. If a Patent or Patents of a Third Party should be in
force in any country during the term of this Agreement covering the manufacture,
use or sale of any Licensed Product, and if it should prove in OBI's reasonable
judgment, after consultation with CURIS, impractical or impossible for OBI or
any Affiliate to continue the activity or activities licensed hereunder without
obtaining a royalty bearing license from such Third Party under such Patent or
Patents in said country, then OBI shall be entitled to a credit against the
royalty payments due under Section 5.3 of an amount equal to the royalty paid to
such Third Party, not to exceed [**] percent ([**]%) of the royalty due under
this Agreement, arising from the manufacture, use or sale of the Licensed
Product in said country. Notwithstanding the above, the royalty due to CURIS
under Section 5.3 shall never be reduced by more than [**] percent ([**]%).
5.5 Compulsory License. If at any time and from time to time a Third Party in
any country shall, under the right of a compulsory license granted or ordered to
be granted by a competent governmental authority, manufacture, use or sell any
Licensed Product, with respect to which royalties would be payable pursuant to
Section 5.3 hereof, then OBI may reduce the royalty on sales in such country of
such Licensed Product, to an amount no greater than the amount payable by said
Third Party as consideration for the compulsory license, except that the royalty
payable to CURIS shall not be reduced to less than [**] percent ([**]%) of the
amount that would be payable to CURIS in such country under provisions of
Section 5.4, and in no event lower than [**].
5.6 Currency Restrictions. Except as herein provided in this Section 5.6, all
royalties shall be paid in Dollars. If, at any time, legal restrictions prevent
the prompt remittance of part of or all royalties with respect to any country
where Licensed Products are sold, OBI shall document such restrictions to CURIS
and shall then have the right and option to make such payments by depositing the
amount thereof in local currency to CURIS' accounts in a bank or depository
designated by CURIS in such country.
5.7 Reports and Records.
15
(a) During the term of this Agreement and commencing with the Date of First
Sale of a Licensed Product, OBI shall furnish, or cause to be furnished to
CURIS, written reports, including royalty payment due, within thirty (30) days
following the end of each calendar quarter for which royalties are due, showing:
(i) the Net Sales of each Licensed Product sold by each of OBI, its
Affiliates and its Sublicensees in each country of the Territory, during the
calendar quarter and the total for all quarters of the current Calendar Year;
(ii) the units of each product form of each Licensed Product sold by
each of OBI, its Affiliates and its Sublicensees in each country of the
Territory, during the calendar quarter and the total for all quarters of the
current Calendar Year;
(iii) the royalties payable in Dollars, which shall have accrued
hereunder in respect to such Net Sales;
(iv) the royalties, if any, paid or due to be paid to each Third Party
under provisions of this Agreement on Net Sales during the calendar quarter.
(b) All payments to be made by OBI to CURIS shall be made in Dollars by
same day wire transfer within thirty (30) days following the end of each
calendar quarter, except as provided in Section 5.6. In the case of sales
outside the United States, royalty payments by OBI to CURIS shall be converted
to Dollars in accordance with OBI's current customary and usual procedures for
calculating same which are the following: the rate of currency conversion shall
be calculated using a simple monthly period average of the end "spot rates"
provided by Brown Brothers Harriman, 59 Wall Street, NY, NY 10005, for each
quarter, or if such rates are not available, the same computation using the spot
rates as published by a leading United States commercial bank for such
accounting period. These methods of conversion are consistent with OBI's current
accounting methods. OBI shall give CURIS prompt written notice of any proposed
changes to OBI's customary and usual procedures for currency conversion, which
shall only apply after such notice has been delivered to and approved by CURIS,
provided that such changes continue to maintain a set methodology for currency
conversion.
(c) Each report shall be made within thirty (30) days from the end of each
calendar quarter. OBI shall keep accurate records in sufficient detail to enable
royalties and other payments payable hereunder to be determined. OBI shall be
responsible for all royalties and late payments that are due to CURIS that have
not been paid by OBI, its Affiliates and Sublicensees.
(d) OBI shall maintain complete and accurate records, in accordance with
U.S. generally accepted accounting practices, which are relevant to costs,
16
expenses and payments under this Agreement and such records shall be open during
reasonable business hours for a period of five (5) years from creation of
individual records for examination at CURIS' expense and not more often than
once each year by a certified public accountant or other representative selected
by CURIS and acceptable to OBI for the sole purpose of verifying the correctness
of calculations or such costs, expenses or payments made under this Agreement.
In the absence of material discrepancies (in excess of 2%) in any request for
reimbursement resulting from such audit, the accounting expense shall be paid by
CURIS. If material discrepancies do result, OBI shall bear the reasonable audit
expense. Any records or accounting information received from OBI shall be
Confidential Information for purposes of Article VII.
(e) OBI shall grant access to such records to Stryker Corporation's
independent accountant for purposes of auditing Net Sales which is used in the
computation of royalties due Stryker Corporation, by CURIS, subject to any
obligations of confidentiality that Stryker has to CURIS which shall also apply
to OBI.
5.8 Taxes.
(a) OBI will make all payments to CURIS under this Agreement without
deduction or withholding for taxes except to the extent that any such deduction
or withholding is required by law in effect at the time of payment.
(b) Any tax required to be withheld on amounts payable under this Agreement
will promptly be paid by OBI on behalf of CURIS to the appropriate governmental
authority, and OBI will furnish CURIS with proof of payment of such tax. Any
such tax required to be withheld will be an expense of and borne by CURIS.
(c) OBI and CURIS will cooperate with respect to all documentation required
by any taxing authority or reasonably requested by OBI to secure a reduction in
the rate of applicable withholding taxes.
(d) If OBI had a duty to withhold taxes in connection with any payment it
made to CURIS under this Agreement but OBI failed to withhold, and such taxes
were assessed against and paid by OBI, then CURIS will indemnify and hold
harmless OBI from and against such taxes (including interest). If OBI makes a
claim under this Section 5.8 (d), it will comply with the obligations imposed by
Section 5.8 (b) as if OBI had withheld taxes from a payment to Curis.
5.9 Sublicenses. Should any sublicenses granted hereunder by OBI result in CURIS
owing Biogen, Inc, Genetics Institute or any party under the Ludwig Agreement,
additional royalties, milestone payments or other payments that it would not
have otherwise owed such parties, but for such sublicense, OBI shall
17
be responsible for any such additional expenses and shall compensate CURIS
accordingly.
ARTICLE VI - MANUFACTURE
6.1 OBI's Responsibility. OBI shall be solely responsible for making or having
made Licensed Products.
ARTICLE VII - PUBLICATIONS
7.1 Confidentiality; Exceptions. Except to the extent expressly authorized by
this Agreement or otherwise agreed in writing, CURIS agrees that, for the time
royalties are due and for five (5) years thereafter, CURIS shall keep
confidential and shall not publish or otherwise disclose or use for any purpose
other than as provided for in this Agreement any Information and other
confidential and proprietary information and materials furnished to it by or for
OBI including but not limited to royalty reports and other financial
information, except to the extent that it can be established by CURIS that such
Confidential Information:
(i) was in the lawful knowledge and possession of the receiving
Party prior to the time it was disclosed to, or learned by, the receiving Party,
or was otherwise developed independently by the receiving Party, as evidenced by
written records kept in the ordinary course of business, or other documentary
proof of actual use by the receiving Party;
(ii) was generally available to the public or otherwise part of the
public domain at the time of its disclosure to the receiving Party;
(iii) became generally available to the public or otherwise part of
the public domain after its disclosure and other than through any act or
omission of the receiving Party in breach of this Agreement; or
(iv) was disclosed to the receiving Party, other than under an
obligation of confidentiality, by a Third Party who had no obligation to the
disclosing Party not to disclose such information to others.
7.2 Authorized Disclosure. Except as expressly provided otherwise in this
Agreement, CURIS may disclose Confidential Information of OBI as follows: (i) to
Third Parties under appropriate terms and conditions including confidentiality
provisions substantially equivalent to those in this Agreement as is reasonably
necessary to exercise the rights granted herein; provided, however, that if
CURIS is required by law or regulation to make any such disclosure of OBI's
Confidential Information it will give reasonable advance notice to OBI of such
disclosure requirement will use its reasonable efforts to secure confidential
treatment of such Confidential Information required to be disclosed.
7.3 Publications. Notwithstanding any other provision of this Agreement,
including, but not limited to the provisions of Section 7.4, CURIS may not
publish the results of any of its or its Third Party collaborator's research and
development
18
activities relating to BMP-7 in the Field without the prior written consent of
OBI, provided, however, publication permitted under R&D Agreements already in
force shall not be restricted if permitted in such Agreements.
7.4 Public Announcements. Neither Party shall originate any publicity, news
release or public announcements, written or oral, whether to the public or
press, stockholders or otherwise, relating to this Agreement, including its
existence, the subject matter to which it relates, performance under it or any
of its terms, to any amendment hereto or performances hereunder without the
prior written consent of the other Party, save only such announcements that are
required by law to be made or that are otherwise agreed by the Parties. All such
announcements shall be brief and factual. If a Party decides to make an
announcement required by law, it will give the other Party at least ten (10)
business days advance notice, where possible, of the text of the announcement so
that the other Party will have an opportunity to comment upon the announcement.
To the extent that the receiving Party reasonably requests that any information
in the materials proposed to be disclosed or deleted, the disclosing Party shall
request confidential treatment of such information pursuant to Rule 406 of the
Securities Act of 1933 or Rule 24b-2 of the Securities Exchange Act of 1934 as
amended, as applicable (or any other applicable regulation relating to the
confidential treatment of information) so that there be omitted from the
materials that are publicly filed any information that the receiving Party
reasonably requests to be deleted, unless in the opinion of the disclosing
Party's legal counsel such Confidential Information is legally required to be
fully disclosed. Except for customary discussions with current or prospective
investors and analysts, or at securities, industry or similar conferences or as
required under applicable laws or regulations or as advised by CURIS' counsel,
each Party shall give the other Party a reasonable opportunity (not to exceed 10
days) to review the content of any oral announcement before it is made.
Notwithstanding the foregoing, however, where urgent, unusual and rare
circumstances require immediate disclosure in the opinion of the Party's
counsel, the Party will, unless impossible because of legal reasons, provide at
least three (3) days advance notice. Notwithstanding the above, the Parties
agree that CURIS may announce the signing of this Agreement, the achievement of
each milestone in this Agreement.
ARTICLE VIII - PURCHASED ASSETS AND OWNERSHIP OF INTELLECTUAL PROPERTY AND
PATENT RIGHTS
8.1 Purchased Assets. On the Effective Date, CURIS shall sell, transfer,
assign, convey and deliver, or cause to be sold, transferred, assigned, conveyed
19
and delivered, to OBI all of CURIS' right, title and interest in the assets
listed below (the "Purchased Assets"):
a. CURIS Know-How
b. biological, pharmaceutical and medical materials and supplies relating
to BMPs, including the Cell Lines.
c. assays for detection of BMP-7
d. books, records, files, correspondence, data, reports, and other
information, whether in written, electronic or other form, including, product
specifications, quality control records and manuals, research and development
files, records and laboratory books
e. rights, claims or causes of action accruing on or after the Effective
Date under or with respect to the Purchased Assets
f. R&D Agreements as described in Schedule F, but only under the following
conditions:
The Parties agree that the R&D Agreements will be assigned to OBI, at OBI's
request, following the Effective Date. To the extent that assignment of any R&D
Agreement requires Third Party consent, CURIS agrees to use commercially
reasonable efforts to obtain any and all such Third Party consents. To the
extent that OBI does not elect assignment of an R&D Agreement or if the Third
Party consent cannot be obtained, all CURIS' rights including Patent and
know-how under the R&D Agreement shall be licensed to OBI pursuant to the terms
of Section 4.1 of this Agreement. OBI shall also have the option to obtain
assignment of one or more Third Party Agreements after the Effective Date and
CURIS hereby agrees to effect such assignment upon request from OBI. CURIS shall
bear the costs associated with any such assignments.
8.2. Patent Prosecution and Related Matters. Following the Effective Date, OBI
shall be responsible for and shall bear the responsibilities and Patent Costs of
filing, prosecuting and maintaining all CURIS Patents incurred after the
Effective Date, to the same extent that CURIS currently bears such
responsibilities and costs prior to the Effective Date. It is understood that
CURIS and therefore OBI hereunder have no obligation to pay Patent Costs
associated with the Patents listed in Schedule B, which Patent Costs are solely
borne by Stryker Corporation. CURIS shall execute (or cause to be executed) all
documents that are necessary to permit OBI to file, prosecute and maintain the
CURIS Patents, except for those listed on Schedule B, at no charge, including
but not limited to powers of attorney. If any such executions cannot be secured
after reasonable efforts, CURIS hereby appoints OBI as its attorney in fact to
take all actions OBI deems reasonably necessary to exercise the rights set forth
20
in this Section 8.2. As of the Effective Date, OBI shall have the exclusive
right to respond to, defend or prosecute any actions, challenges, infringements,
invalidity, oppositions, reexaminations, misappropriations or proceedings by or
against a Third Party alleging infringement, misappropriation or violation of
any of the CURIS Patent Rights , to the extent that CURIS has the right to
respond to, defend or prosecute any of the foregoing by or against a Third Party
alleging infringement, misappropriation or violation of such CURIS Patent
Rights. In such event, CURIS shall cooperate with OBI and their respective legal
counsel, join in suits or actions that may be brought by OBI and be available at
OBI's reasonable requests to be an expert witness or otherwise to assist in such
proceedings. CURIS also agrees to promptly provide OBI with any notices or
communications it receives from Stryker under any of the Stryker Agreements (as
described in Schedule G) or from a Third Party under other Agreement relating to
any of the CURIS Patents licensed hereunder including notices or communications
relating to infringement or validity of such Patents or Oppositions filed
against such Patents.
ARTICLE IX - REPRESENTATIONS AND WARRANTIES; EXCLUSIVITY.
9.1 Representations and Warranties. Each of the Parties hereby represents and
warrants and covenants as follows: This Agreement is a legal and valid
obligation binding upon such Party and enforceable in accordance with its terms.
The execution, delivery and performance of the Agreement by such Party does not
conflict with any agreement, instrument or understanding, oral or written, to
which it is a Party or by which it is bound, nor violate any law or regulation
of any court, governmental body or administrative or other agency having
jurisdiction over it.
CURIS owns or otherwise Controls all of the rights, title and interest in and to
CURIS Know-How.
9.2 Patents and Know-How Warranties. To the best of its knowledge as of the
Effective Date, CURIS represents and warrants that (i) any Patent, know-how or
other intellectual property right owned or controlled by CURIS that is
applicable to this Agreement is not currently being infringed by any Third
Party, and (ii) that the practice of such rights does not infringe any valid
property right of any Third Party and (iii) that it has the right to license
and/or sublicense the Curis Patents listed in Schedules A, B, C, D and E and
(iv) that the Patents listed in Schedules A,B,C,D and E are the entire patent
estate that relate to BMP-7 in the Field to which CURIS has the right to license
or assign.
9.3 CURIS Representations and Warranties.
Curis represents and warrants to OBI and agrees as follows:
(a) That inventions that were created by Third Parties pursuant to the R&D
Agreements, of which Curis had notice and exercised its rights prior to the
21
Effective Date, have resulted in patents that are either owned by Curis or
co-owned by Curis and are listed as Curis Patents on Schedules A, C and D.
(b) That all inventions that were created prior to the Effective Date or
those inventions that may be created after the Effective Date, under the R&D
Agreements, in either instance, which Curis had no notice of prior to the
Effective Date, are subject to J&J's rights that are granted to it by Curis,
under this Agreement, pursuant to Section 4.1 (which describes the license to
Curis Licensed Third Party Patent Rights) and Section 8.1 (g) (which describes
the process whereby Curis agrees to assign R&D Agreements to J&J, at J&J's
election).
(c) That Curis has granted no rights, under the Curis Patent Rights or
Ludwig Patent Rights to Third Parties pursuant to the R&D Agreements, except to
the extent that such Third Parties are co-owners of a Curis Patent as of the
Effective Date and as listed in this Agreement.
(d) That Curis has no payment or funding obligations to Third Parties under
the R&D Agreements or the Ludwig Agreement.
(e) That any other obligation, or liability, such as indemnification, that
may exist under the R&D Agreements, is the sole responsibility of Curis.
(f) That there are no restrictions in any of the Third Party Agreements of
Schedule G or R & D Agreements of Schedule F that would restrict OBI from using
its technology.
ARTICLE X TERM AND TERMINATION
10.1. Term. This Agreement shall commence on the Effective Date and shall
remain in effect until the expiration of OBI's obligation to pay royalties for
any Licensed Product, unless earlier terminated as provided in this Article X.
10.2 Termination For Breach. Either Party may terminate this Agreement in the
event the other Party shall have materially breached or defaulted in the
performance of any of its material obligations hereunder, and such default shall
have continued for ninety (90) days after written notice thereof was provided to
the breaching party by the non-breaching party. Any termination shall become
effective at the end of such ninety (90) day period unless the breaching party
(or any other party on its behalf) has cured any such breach or default prior to
the expiration of the ninety (90) day period.
10.3 Termination For Bankruptcy. Either Party hereto shall have the right to
terminate this Agreement forthwith by written notice to the other Party (i) if
the other Party is declared insolvent or bankrupt by a court of competent
jurisdiction, (ii) if a voluntary or involuntary petition in bankruptcy is filed
in any court of
22
competent jurisdiction against the other Party and such petition is not
dismissed within ninety (90) days after filing, or (iii) if the other Party
shall make or execute an assignment of substantially all of its assets for the
benefit of creditors.
10.4 Results of Termination by OBI for Cause. In the event of termination of
this Agreement by OBI pursuant to Sections 10.2 or 10.3, the licenses granted to
OBI in Article V hereof, shall survive termination. In addition, the royalties
rates recited in Paragraph 5.4 shall each be amended and reduced by 50%.
Sections 5.3 through 6.9, and all relevant definitions in Article I shall
survive termination.
10.5 Results of Termination by CURIS for Cause. In the event of termination of
this Agreement by CURIS pursuant to Sections 10.2, 10.3 or 10.6, the licenses
granted to OBI hereunder shall terminate. Upon such termination, OBI shall
provide CURIS at no cost to CURIS copies of all OBI internal reports, reports
from Third Parties, and notes of communications and correspondence with and
reports submitted to regulatory agencies pertaining to Licensed Products.
10.6 Termination by OBI. OBI shall have the right to terminate this Agreement
for any reason upon ninety (90) days written notice to CURIS.
10.7 OBI shall have the right to terminate this Agreement upon thirty days prior
written notice should CURIS breach the representation and warranty recited in
section 9.3 (f). In the event of termination under this Section 10.7, OBI shall
receive a credit for any payments made to CURIS hereunder as of the date of
termination, which OBI may apply to any future Agreement that the Parties may
enter into. In addition, should the breach by CURIS of such representation and
warranty result in any liabilities to OBI under any lawsuit brought by a Third
Party against OBI relating to OBI's alleged violation of any the restrictions
referred to in the representation and warranty in section 9.3 (f), CURS shall
indemnify and hold harmless OBI for any damages suffered by OBI and it's
attorney's fees in defending such lawsuit.
10.8 Surviving Rights. Sections 5.8, 5.9, 7.1 and 7.2 and any relevant
definitions in Article I shall survive the expiration and any termination of
this Agreement for any reason.
10.9 Accrued Rights, Surviving Obligations. Termination, relinquishment or
expiration of the Agreement for any reason shall be without prejudice to any
obligations which shall have accrued prior to such termination, relinquishment
or expiration, including, without limitation, the payment obligations under
Section 2.5 and Article 6 hereof and any and all damages arising from any breach
hereunder. Such termination, relinquishment or expiration shall not relieve
either Party from obligations that are expressly indicated to survive
termination or expiration of the Agreement.
23
10.10 Termination Not Sole Remedy. Termination is not the sole remedy under this
Agreement and, whether or not termination is effected, all other remedies will
remain available except as agreed to otherwise herein.
ARTICLE XI - INDEMNIFICATION
11.1 Research and Development Indemnification. Each Party (the "Indemnifying
Party") shall indemnify, defend and hold the other Party (the "Indemnified
Party") harmless from and against any and all liabilities, claims, damages,
costs, expenses or money judgments incurred by or rendered against the
Indemnified Party and its Affiliates incurred in the defense or settlement of a
Third Party lawsuit or in a satisfaction of a Third Party judgment arising out
of any injuries to person and/or damage to property resulting from (i) negligent
acts of the Indemnifying Party performed in carrying out the Research hereunder,
including failure by the Indemnifying Party to provide the Indemnified Party
with any Information of the Indemnifying Party's which, if timely received,
would have avoided injury, death or damage, provided such failure to provide
such know-how is due to negligence of the part of the Indemnifying Party, and
(ii) personal injury to the Indemnified Party employees or agents or damage to
the Indemnified Party's property resulting from acts performed by, under the
direction of, or at the request of the Indemnifying Party in carrying out
activities contemplated by this Agreement.
11.2 Indemnification for Licensed Products. With respect to Licensed Products
covered by this Agreement:
(a) OBI hereby agrees to save, defend and hold CURIS and its agents,
directors, officers and employees harmless from and against any and all suits,
claims, actions, demands, liabilities, expenses and/or loss, including
reasonable legal expense and attorney's fees ("Losses") resulting directly from
the manufacture, use, handling, storage, sale or other disposition of chemical
agents or Licensed Products by OBI, its Affiliates and agents except to the
extent such Losses result from the negligence of CURIS.
(b) In the event that CURIS is seeking indemnification under Sections 11.1
or 11.2(a), it shall inform OBI of a claim as soon as reasonably practicable
after it receives notice of the claim, shall permit OBI to assume direction and
control of the defense of the claim (including the right to settle the claim
solely for monetary consideration), and shall cooperate as requested (at the
expense of OBI) in the defense of the claim.
(c) CURIS hereby agrees to save, defend and hold OBI and its agents,
directors, officers and employees harmless from and against any and all suits,
claims, actions, demands, liabilities, expenses and/or loss, including
reasonable legal expense and attorneys' fees ("Losses") resulting directly from
the manufacture, use, handling, storage, sale or other disposition of chemical
agents
24
or Licensed Products by CURIS, its Affiliates, agents or Sublicensees, except to
the extent such Losses result from the negligence of OBI.
(d) CURIS agrees to save, defend and hold OBI and its agents, directors,
officers and employees harmless from and against any and all suits, claims,
actions, demands, liabilities, expenses and/or loss, including reasonable legal
expense and attorney's fees ("Losses") resulting directly from any breach of the
representations and warranties described in Section 9.3.
(e) In the event OBI is seeking indemnification under Sections 11.1 or
11.2(c), it shall inform CURIS of a claim as soon as reasonably practicable
after it receives notice of the claim, shall permit CURIS to assume direction
and control of the defense of the claim (including the right to settle the claim
solely for monetary consideration), and shall cooperate as requested (at the
expense of CURIS) in the defense of the claim.
ARTICLE XII - DISPUTE RESOLUTION
12.1 Dispute Resolution and Arbitration. In the case of any disputes between the
Parties arising from this Agreement, and in case this Agreement does not provide
a solution for how to resolve such disputes, the Parties shall discuss and
negotiate in good faith a solution acceptable to both Parties and in the spirit
of this Agreement. If after negotiating in good faith pursuant to the foregoing
sentence, the Parties fail to reach agreement within sixty (60) days, then the
President of CURIS and the President of OBI shall discuss in good faith an
appropriate resolution to the dispute. If these executives fail, after good
faith discussions, to reach an amicable agreement within sixty (60) days, then
either Party may upon written notice to the other submit the dispute to binding
arbitration pursuant to Section 12.2.
12.2 Arbitration. Any claim, dispute or controversy arising out of or in
connection with or relating to this Agreement, (including, without limitation,
disputes with respect to the rights and obligations of the Parties following
termination) not settled by the procedures set forth in Section 13.1 above or
the breach or alleged breach of a material provision of this Agreement shall be
adjudicated by arbitration in accordance with the Arbitration Proceedings as set
forth in Exhibit A attached hereto.
ARTICLE XIII - MISCELLANEOUS
13.1 Relationship of Parties. For the purposes of this Agreement, each party is
an independent contractor and not an agent or employee of the other party.
Neither party shall have authority to make any statements, representations, or
commitments of any kind, or to take any action which shall be binding on the
25
other party, except as may be explicitly provided for herein or authorized in
writing.
13.2 Counterparts. This Agreement may be executed in two or more counterparts,
each of which shall be deemed an original, and all of which together shall be
deemed to be one and the same instrument.
13.3 Headings. All headings in this Agreement are for convenience only and
shall not affect the meaning of any provision hereof.
13.4 Binding Effect. This Agreement shall inure to the benefit of and be
binding upon the parties and their respective lawful successors and assigns.
13.5 Assignment. Neither party may assign this Agreement without the prior
written consent of the other party, except that a party may assign this
Agreement to an Affiliate or to a successor in connection with the merger,
consolidation, or sale of all or substantially all of its assets or that portion
of its business pertaining to the subject matter of this Agreement.
13.6 Amendment and Waiver. This Agreement may be amended, supplemented, or
otherwise modified at any time, but only by means of a written instrument signed
by both parties. Any waiver of any rights or failure to act in a specific
instance shall relate only to such instance and shall not be construed as an
agreement to waive any rights or fail to act in any other instance, whether or
not similar.
13.7 Governing Law. This Agreement and the legal relations among the parties
shall be governed by and construed in accordance with the laws of the State of
New York, USA, irrespective of any choice of laws or conflict of laws
principles.
13.8 Severability. In the event that any provision of this Agreement shall,
for any reason, be held to be invalid or unenforceable in any respect, such
invalidity or unenforceability shall not affect any other provision hereof, and
this Agreement shall be construed as if such invalid or unenforceable provision
had not been included herein.
13.9 Entire Agreement. This Agreement constitutes the entire agreement
between the parties with respect to the subject matter hereof and supersedes any
and all prior or contemporaneous oral and prior written agreements and
understandings.
13.10 Advice of Counsel. OBI and CURIS have each consulted counsel of their
choice regarding this Agreement, and each acknowledges and agrees that this
Agreement shall not be deemed to have been drafted by one party or another and
will be construed accordingly.
26
13.11 Consents Not Unreasonably Withheld. Whenever provision is made in this
Agreement for either Party to secure the consent or approval of the other, that
consent or approval shall not unreasonably be withheld, and whenever in this
Agreement provision is made for one Party to object to or disapprove a matter,
such objection or disapproval shall not unreasonably be exercised.
13.12 Retained Rights. Nothing in this Agreement shall limit in any respect the
right of either Party to conduct research and development with respect to and
market products outside the Field using such Party's know-how.
13.13 Force Majeure. Neither Party shall lose any rights hereunder or be liable
to the other Party for damages or losses on account of failure of performance by
the defaulting Party if the failure is occasioned by government action, war,
fire, explosion, flood, strike, lockout, embargo, act of God, or any other
similar cause beyond the control of the defaulting Party, provided that the
Party claiming force majeure has exerted all reasonable efforts to avoid or
remedy such force majeure; provided, however, that in no event shall a Party be
required to settle any labor dispute or disturbance. Notwithstanding the
foregoing, this Section 14.13 shall not operate to relieve either Party from
performance of any obligation for more than ninety (90) days.
13.14 Further Actions. Each Party agrees to execute, acknowledge and deliver
such further instruments, and to do all such other acts, as may be necessary or
appropriate in order to carry out the purposes and intent of this Agreement.
13.15 No Trademark Rights. Except as otherwise provided herein, no right,
express or implied, is granted by the Agreement to use in any manner the name
"CURIS" or "OBI", or any other trade name or trademark of the other Party or its
Affiliates in connection with the performance of the Agreement.
13.16 Notices. All notices hereunder shall be in writing and shall be deemed
given if delivered personally or by facsimile transmission (receipt verified),
email (receipt acknowledged), mailed by registered or certified mail (return
receipt requested), postage prepaid, or sent by express courier service, to the
Parties at the following address (or at such other address for a Party as shall
be specified by like notice; provided, that notices of a change of address shall
be effective only upon receipt thereof). If to CURIS,
addressed to:
CURIS Inc.
61 Moulton Street
Cambridge, MA 02138
Attention: General Counsel
Facsimile: 617.492.8287
Email: bpotthoff@curis.com
27
If to OBI:
addressed to:
Ortho Biotech Products, L.P.
Route 22 East
P.O. Box 6914
Bridgewater, NJ 0880709814
Attention: President
Facsimile:
Email:
With a copy to: Office of General Counsel
Johnson & Johnson
One Johnson & Johnson Plaza
New Brunswick, NJ 08933
Facsimile: 732-524-2788
Email: pjohnson@corus.jnj.com
Each of the Parties consent to the personal jurisdiction of the U.S. Federal
Courts and agree to accept any legal process served upon such Party at the
addresses specified above for such Party.
13.17 Waiver. Except as specifically provided for herein, the waiver from time
to time by either of the Parties of any of their rights or their failure to
exercise any remedy shall not operate or be construed as a continuing waiver of
same or of any other of such Party's rights or remedies provided in this
Agreement.
13.18 Compliance with Laws. The Parties shall comply with all applicable laws,
rules, regulations and orders of the United States and applicable European
countries and supra-governmental organizations and all jurisdictions and any
agency or court thereof in connection with this Agreement and the transactions
contemplated thereby.
13.19 Bankruptcy. All rights and licenses granted under or pursuant to this
Agreement by each Party as a licensor are, and shall otherwise be deemed to be,
for purposes of Section 365(n) of Title ll, U.S. Code (the "Bankruptcy Code"),
licenses of rights to "intellectual property" as defined under section 101(35A)
of the Bankruptcy Code. The Parties agree that each licensee of such rights
under this Agreement, shall retain and may fully exercise all rights and
elections it would have in the case of a licensor bankruptcy under the
Bankruptcy Code.
28
Each Party agrees during the term of this Agreement to create or maintain
current copies, or if not amenable to copying, detailed descriptions or other
appropriate embodiments, of all such intellectual property licensed to the other
Party.
13.20 Confidential Treatment. CURIS agrees to give this Agreement "Confidential
Treatment" in any filings it makes with the U.S. Securities & Exchange
Commission including redacting all financial terms, except to the extent that
(a) such financial information is disclosed in CURIS financial statements and
(b) that the financial information has been previously disclosed in the press
release that has been approved by OBI
13.21 Governmental Authority Consents. No consents of any Governmental Authority
having jurisdiction over CURIS is required to be obtained by CURIS in order to
authorize the execution by CURIS of this Agreement or the performance by CURIS
of the terms hereof and consents, if any, required pursuant to the HSR Act.
29
IN WITNESS WHEREOF, the undersigned have duly executed and delivered this
Agreement as a sealed instrument effective as of the date first above written.
ORTHO BIOTECH PRODUCTS, L.P.
by: Ortho Biotech, Inc. its general partner
/S/ Gary M. Reedy
- --------------------------
By: Gary M. Reedy
President
CURIS, INC.
/S/ Daniel R. Passeri
- --------------------------
By: Daniel R. Passeri
President and CEO
30
Exhibit A
Dispute Resolution
a. Any dispute, claim or controversy arising from or related in any way to this
Agreement or the interpretation, application, breach, termination or validity
thereof, including any claim of inducement of this Agreement by fraud or
otherwise, will be submitted for resolution to arbitration pursuant to the rules
then pertaining of the CPR Institute for Dispute Resolution for Non-Administered
Arbitration (available at www.cpradr.org/arb-rules.htm), or successor ("CPR"),
except where those rules conflict with these provisions, in which case these
provisions control. The arbitration will be held in New York City, New York.
b. The panel shall consist of three arbitrators chosen from the CPR Panels of
Distinguished Neutrals (or, by agreement, from another provider of arbitrators)
each of whom is a lawyer with at least 15 years experience with a law firm or
corporate law department of over 25 lawyers or who was a judge of a court of
general jurisdiction. In the event the aggregate damages sought by the claimant
are stated to be less than $5 million, and the aggregate damages sought by the
counterclaimant are stated to be less than $5 million, and neither side seeks
equitable relief, then a single arbitrator shall be chosen, having the same
qualifications and experience specified above. Each arbitrator shall be neutral,
independent, disinterested, impartial and shall abide by The CPR-Georgetown
Commission Proposed Model Rule for the Lawyer as Neutral available at
www.cpradr.org/cpr-george.html.
c. The parties agree to cooperate (1) to attempt to select the arbitrator(s) by
agreement within 45 days of initiation of the arbitration, including jointly
interviewing the final candidates, (2) to meet with the arbitrator(s) within 45
days of selection and (3) to agree at that meeting or before upon procedures for
discovery and as to the conduct of the hearing which will result in the hearing
being concluded within no more than nine (9) months after selection of the
arbitrator(s) and in the award being rendered within 60 days of the conclusion
of the hearings, or of any post-hearing briefing, which briefing will be
completed by both sides within 45 days after the conclusion of the hearings.
d. In the event the parties cannot agree upon selection of the arbitrator(s),
the CPR will select arbitrator(s) as follows: CPR shall provide the parties with
a list of no less than 25 proposed arbitrators (15 if a single arbitrator is to
be selected) having the credentials referenced above. Within 25 days of
receiving such list, the parties shall rank at least 65% of the proposed
arbitrators on the initial CPR list, after exercising cause challenges. The
parties may then interview the five candidates (three if a single arbitrator is
to be selected) with the highest combined rankings for no more than one hour
each and, following the interviews, may exercise one peremptory challenge each.
The panel will consist of the remaining three candidates (or one, if one
arbitrator is to be selected) with the highest combined rankings. In the event
these procedures fail to result in selection of the required number of
arbitrators, CPR shall select the appropriate number of arbitrators from among
the members of the various CPR Panels of
31
Distinguished Neutrals, allowing each side challenges for cause and three
peremptory challenges each.
e. In the event the parties cannot agree upon procedures for discovery and
conduct of the hearing meeting the schedule set forth in paragraph c above, then
the arbitrator(s) shall set dates for the hearing, any post-hearing briefing,
and the issuance of the award in accord with the paragraph c schedule. The
arbitrator(s) shall provide for discovery according to those time limits, giving
recognition to the understanding of the parties that they contemplate reasonable
discovery, including document demands and depositions, but that such discovery
be limited so that the paragraph c schedule may be met without difficulty. In no
event will the arbitrator(s), absent agreement of the parties, allow more than a
total of ten days for the hearing or permit either side to obtain more than a
total of 40 hours of deposition testimony from all witnesses, including both
fact and expert witnesses, or serve more than 20 individual requests for
documents, including subparts, or 20 individual requests for admission or
interrogatories, including subparts. Multiple hearing days will be scheduled
consecutively to the greatest extent possible.
f. The arbitrator(s) must render their award by application of the substantive
law of New York and are not free to apply "amiable compositeur" or "natural
justice and equity." The arbitrator(s) shall render a written opinion setting
forth findings of fact and conclusions of law with the reasons therefor stated.
A transcript of the evidence adduced at the hearing shall be made and shall,
upon request, be made available to either party. The arbitrator(s) shall have
power to exclude evidence on grounds of hearsay, prejudice beyond its probative
value, redundancy, or irrelevance and no award shall be overturned by reason of
such ruling on evidence. To the extent possible, the arbitration hearings and
award will be maintained in confidence.
g. In the event the panel's award exceeds $5 million in monetary damages or
includes or consists of equitable relief, or rejects a claim in excess of that
amount or for that relief, then the losing party may obtain review of the
arbitrators' award or decision by a single appellate arbitrator (the "Appeal
Arbitrator") selected from the CPR Panels of Distinguished Neutrals by agreement
or, failing agreement within seven working days, pursuant to the selection
procedures specified in paragraph d above. If CPR cannot provide such services,
the parties will together select another provider of arbitration services that
can. No Appeal Arbitrator shall be selected unless he or she can commit to
rendering a decision within forty-five days following oral argument as provided
in this paragraph. Any such review must be initiated within thirty (30) days
following the rendering of the award referenced in f above.
h. The Appeal Arbitrator will make the same review of the arbitration panel's
ruling and its bases that the U.S. Court of Appeals of the Circuit where the
arbitration hearings are held would make of findings of fact and conclusions of
law rendered by a district court after a bench trial and then modify, vacate or
affirm the arbitration panel's award or decision accordingly, or remand to the
panel for further proceedings. The Appeal Arbitrator will consider only the
arbitration panel's findings of fact and conclusions of law, pertinent portions
of
32
the hearing transcript and evidentiary record as submitted by the parties,
opening and reply briefs of the party pursuing the review, and the answering
brief of the opposing party, plus a total of no more than four (4) hours of oral
argument evenly divided between the parties. The party seeking review must
submit its opening brief and any reply brief within seventy-five (75) and one
hundred thirty (130) days, respectively, following the date of the award under
review, whereas the opposing party must submit its responsive brief within one
hundred ten (110) days of that date. Oral argument shall take place within five
(5) months after the date of the award under review, and the Appeal Arbitrator
shall render a decision within forty-five (45) days following oral argument.
That decision will be final and not subject to further review, except pursuant
to the Federal Arbitration Act.
i. The parties consent to the jurisdiction of the Federal District Court for the
district in which the arbitration is held for the enforcement of these
provisions and the entry of judgment on any award rendered hereunder (including
after review by the Appeal Arbitrator where such an appeal is pursued). Should
such court for any reason lack jurisdiction, any court with jurisdiction shall
act in the same fashion.
j. Each party has the right before or, if the arbitrator(s) cannot hear the
matter within an acceptable period, during the arbitration to seek and obtain
from the appropriate court provisional remedies such as attachment, preliminary
injunction, replevin, etc. to avoid irreparable harm, maintain the status quo,
or preserve the subject matter of the arbitration.
k. EACH PARTY HERETO WAIVES ITS RIGHT TO TRIAL OF ANY ISSUE BY JURY.
l. EACH PARTY HERETO WAIVES ANY CLAIM TO PUNITIVE, EXEMPLARY OR MULTIPLIED
DAMAGES FROM THE OTHER.
m. EACH PARTY HERETO WAIVES ANY CLAIM OF CONSEQUENTIAL DAMAGES FROM THE OTHER.
n. EACH PARTY HERETO WAIVES ANY CLAIM FOR ATTORNEYS' FEES AND COSTS AND
PREJUDGMENT INTEREST FROM THE OTHER.
33
SCHEDULE A
Curis BMP Portfolio (Worldwide) Licensed to Stryker
Curis Case No. CRP No. Title Filing Date Serial No. Status Patent No. Assignee Country
of Filing
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002AU CRP-052AU Protein Induced Morphogenesis 03/11/1992 17543/92 Issued 660,019 Curis AU
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002BE CRP-052BE Protein Induced Morphogenesis 03/11/1992 92910260.6 In Opposition 0 575555 B1 Curis BE
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002BR CRP-052CPBR Protein-Induced Morphogenesis 05/09/1997 PI1100736-2 Pending Curis BR
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002CA CRP-052CA Protein Induced Morphogenesis 03/11/1992 2,104,678 Allowed 2,104,678 Curis CA
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002CAD CRP-052AUD Protein Induced Morphogenesis 03/11/1992 2,363,965 Pending Curis CA
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002CH CRP-052CH Protein Induced Morphogenesis 03/11/1992 92910260.6 In Opposition 0 575555 B1 Curis CH
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002CP2US CRP-052CN Protein Induced Morphogenesis 03/01/1995 08/396,684 Pending Curis US
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002CPC2 CRP-052 Protein-Induced Tissue
Morphogenesis 03/14/1995 08/404,113 Pending Curis US
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002CPC2DIV CRP-052 Methods of inducing liver
tissue growth with
Morphogenesis 12/15/1999 09/464,206 Pending Curis US
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002DE CRP-052DE Protein Induced Morphogenesis 03/11/1992 92910260.6 In Opposition 69231946.8-08 Curis DE
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002DK CRP-052DK Protein Induced Morphogenesis 03/11/1992 92910260.6 In Opposition 0 575555 B1 Curis DK
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002EP CRP-052EP Protein Induced Morphogenesis 03/11/1992 92910260.6 In Opposition 0 575555 B1 Curis EP
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002ES CRP-052ES Protein Induced Morphogenesis 03/11/1992 92910260.6 In Opposition 0 575555 B1 Curis ES
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002FR CRP-052FR Protein Induced Morphogenesis 03/11/1992 92910260.6 In Opposition 0 575555 B1 Curis FR
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002GB CRP-052GB Protein Induced Morphogenesis 03/11/1992 92910260.6 In Opposition 0 575555 B1 Curis UK
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002GR CRP-052GR Protein Induced Morphogenesis 03/11/1992 92910260.6 In Opposition 0 575555 B1 Curis GR
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002IT CRP-052IT Protein Induced Morphogenesis 03/11/1992 92910260.6 In Opposition 0 575555 B1 Curis IT
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002JP CRP-052JP Protein Induced Morphogenesis 03/11/1992 04-509427 Pending Curis JP
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002LU CRP-052LU Protein Induced Morphogenesis 03/11/1992 92910260.6 In Opposition 0 575555 B1 Curis LU
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002MC CRP-052MC Protein Induced Morphogenesis 03/11/1992 92910260.6 In Opposition 0 575555 B1 Curis MC
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002NL CRP-052NL Protein Induced Morphogenesis 03/11/1992 92910260.6 In Opposition 0 575555 B1 Curis NL
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002PC CRP-052PC Protein Induced Morphogenesis 03/11/1992 PCT/US92/01968 Completed
National Stage Curis PCT
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-002SE CRP-052SE Protein Induced Morphogenesis 03/11/1992 92910260.6 In Opposition 0 575555 B1 Curis SE
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-003AT CRP-052AT Morphogen-Induced Modulation of
Inflammatory Response 08/28/1992 92919544.4 In Opposition 0 601 106 B1 Curis AT
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-003AU CRP-059AU Morphogen-Induced Modulation of
Inflammatory Response 08/28/1992 25645/92 Issued 669127 Curis AU
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-003BE CRP-059BE Morphogen-Induced Modulation of
Inflammatory Response 08/28/1992 92919544.4 In Opposition 0 601 106 B1 Curis BE
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-003CA CRP-059CA Morphogen-Induced Modulation of
Inflammatory Response 08/28/1992 2,116,562 Issued 2116562 Curis CA
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-003CH CRP-059CH Morphogen-Induced Modulation
of Inflammatory Response 08/28/1992 92919544.4 In Opposition 0 601 106 B1 Curis CH
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-003CN CRP-059CN Method for Reducing
Extravasation of Effector Cells 05/15/1995 08/440,894 Issued 6,288,031 Curis US
Page 1 of 10
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-003CPFW2 CRP-059CPFW2 Method for modulating inflammatory 05/22/1995 08/445,467 Issued 6,077,823 Curis US
response
- ------------------------------------------------------------------------------------------------------------------------------------
CBM- CRP-059Div Method for reducing tissue damage 06/20/2000 09/597,517 Pending Curis US
003CPFW2DIV associate with ischemia-reperfusion
or hypoxia injury
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-003DE CRP-059DE Morphogen-Induced Modulation of 08/28/1992 92919544.4 In Opposition 0601106 Curis DE
Inflammatory Response B1
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-003EP CRP-059EP Morphogen-Induced Modulation of 08/28/1992 92919544.4 In Opposition 0601106 Curis EP
Inflammatory Response B1
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-003ES CRP-059ES Morphogen-Induced Modulation of 08/28/1992 92919544.4 In Opposition 0601106 Curis ES
Inflammatory Response B1
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-003FR CRP-059FR Morphogen-Induced Modulation of 08/28/1992 92919544.4 In Opposition 0601106 Curis FR
Inflammatory Response B1
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-003FWC2 CRP-059FW2 Method for modulating inflammatory 03/30/1995 08/414,033 Issued 6,194,376 Curis US
response comprising administering
morphogen
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-003GB CRP-059GB Morphogen-Induced Modulation of 08/28/1992 92919544.4 In Opposition 0601106 Curis UK
Inflammatory Response B1
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-003IE CRP-059IE Morphogen-Induced Modulation of 08/28/1992 92919544.4 In Opposition 0601106 Curis IE
Inflammatory Response B1
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-003IT CRP-059IT Morphogen-Induced Modulation of 08/28/1992 92919544.4 In Opposition 0601106 Curis IT
Inflammatory Response B1
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-003JP CRP-059JP Method for modulating inflammatory 08/28/1992 05-505344 Pending Curis JP
response following ischemic
reperfusion injury
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-003LU CRP-059LU Morphogen-Induced Modulation of 08/28/1992 92919544.4 In Opposition 0601106 Curis LU
Inflammatory Response B1
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-003MC CRP-059MC Morphogen-Induced Modulation of 08/28/1992 92919544.4 In Opposition 0601106 Curis MC
Inflammatory Response B1
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-003PC CRP-059PC Method for modulating inflammatory 08/28/1992 PCT/US93/04692 Completed Curis PCT
response following ischemic National
reperfusion injury Stage
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-004AU CRP-070AU Morphogen Induced Nerve Regeneration 07/29/1993 47971/93 Issued 681,594 Curis AU
and Repair
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-004C2DV CRP-070DV Morphogen-Induced Nerve Regeneration 05/31/1995 08/456,033 Allowed Curis US
and Repair
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-004C2US CRP-070FW2 Morphogen Induced Nerve Regeneration 06/16/1994 08/260,675 Pending Curis US
and Repair
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-004C3US CRP-070FWCN2 Morphogen-Induced Nerve Regeneration 09/25/1997 08/937,756 Pending Curis US
and Repair
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-004CA CRP-070CA Morphogen Induced Nerve Regeneration 07/29/1993 2,141,554 Allowed CA
and Repair
Page 2 of 10
Schedule A
Curis BMP Portfolio (Worldwide) Licensed to Stryker
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-004EP CRP-070EP Morphogen Induced Nerve Regeneration 07/29/1993 93918560.9 Pending Curis EP
and Repair
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-004JP CRP-070JP Morphogen Induced Nerve Regeneration 07/29/1993 6-505485 Pending Curis JP
and Repair
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-004PC CRP-070PC Morphogen Induced Nerve Regeneration 07/29/1993 PCT/US93/07231 Completed Curis PCT
and Repair National Stage
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-008 CRP-128 Methods and Compositions for the 09/25/1997 08/938,622 Allowed Curis US
Treatment and Prevention of
Parkinson's Disease
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-010EP CRP-141EP Methods and Compositions for 01/21/1999 99903241 Pending EP 1047443 Curis EP
Enhancing Cognitive Function Using
Morphogenic Proteins
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-010PC CRP-141PC Methods and Compositions for 01/21/1999 PCT/US99/01232 Completed Curis PCT
Enhancing Cognitive Function Using National Stage
Morphogenic Proteins
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-010US CRP-141 Methods and Compositions for 01/23/1998 09/012,846 Pending Curis US
Enhancing Cognitive Function Using
Morphogenic Proteins
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-011US CRP-155 Methods and Compositions for the 09/25/1997 08/937,755 Pending Curis US
Treatment of Motor Neuron Injury and
Neuropathy
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-013AUD2 CRP-118AUD2 Morphogen Treatment for Chronic Renal 05/06/1997 38887/01 Pending Curis AU
Failure
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-013CA CRP-118CA Morphogen Treatment for Chronic Renal 05/06/1997 2,254,954 Pending Curis CA
Failure
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-013CPA CRP-118CPA Morphogen Treatment for Chronic Renal 05/06/1996 08/643,321 Allowed Curis US
Failure
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-013CUS CRP-118 Morphogen Treatment for Chronic Renal 08/28/2002 Not yet assigned Pending Curis US
Failure
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-013EP CRP-118EP Morphogen Treatment for Chronic Renal 05/06/1997 97922726.1 Pending Curis EP
Failure
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-013JP CRP-118JP Morphogen Treatment for Chronic Renal 05/06/1997 9-540211 Pending Curis JP
Failure
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-013PC CRP-118PC Morphogen Treatment for Chronic Renal 05/06/1997 PCT/US97/07816 Completed Curis PCT
Failure National Stage
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-014AU CRP-144AU Therapies for Acute Renal Failure 05/05/1998 72443/98 Issued 743510 Curis AU
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-014AUD CRP-144AU Therapies for Acute Renal Failure 05/05/1998 34339/02 Pending 743510 Curis AU
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-014CA CRP-144CA Therapies for Acute Renal Failure 05/05/1998 2,289,123 Pending Curis CA
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-014EP CRP-144EP Therapies for Acute Renal Failure 05/05/1998 98919715.7 Pending Curis EP
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-014JP CRP-144JP Therapies for Acute Renal Failure 05/05/1998 10-548048 Pending Curis JP
Page 3 of 10
Curis BMP Portfolio (Worldwide) Licensed to Stryker
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-014PC CRP-144PC Therapies for Acute Renal failure 05/05/1998 PCT/US98/03197 Completed Curis PCT
National
Stage
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-014US CRP-144 Therapies for acute renal failure 05/05/1998 09/445,328 Pending Curis US
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-015AUD CRP-145AUD Novel Therapies for Chronic Renal Failure 05/06/1997 71419/00 Pending Curis AU
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-015AUD2 CRP-145AUD2 Novel Therapies for Chronic Renal Failure 05/06/1997 Pending Curis AU
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-015CA CRP-145CA Novel Therapies for Chronic Renal Failure 05/06/1997 2,254,953 Pending Curis CA
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-015EP CRP-145EP Novel Therapies for Chronic Renal Failure 05/06/1997 97923567.8 Pending Curis EP
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-015JP CRP-145JP Novel Therapies for Chronic Renal Failure 05/06/1997 9-540150 Pending Curis JP
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-015PC CRP-145PC Therapies for Chronic Renal Failure 05/06/1997 PCT/US97/07655 Completed Curis PCT
National
Stage
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-015US CRP-145 Novel Therapies for Chronic Renal Failure 02/11/2000 08/851,628 Pending Curis US
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-016FW2 CRP-068 Morphogen Treatment of Organ Transplants 06/07/1995 08/480,515 Issued 6,090,776 Curis US
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-017AT CRP-072AT Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis AT
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-017AU CRP-072AU Morphogen Induced Liver Regeneration 09/16/1993 51623/93 Issued 681,356 Curis AU
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-017CA CRP-072CA Morphogen Induced Liver Regeneration 09/16/1993 2,144,514 Issued 2,144,514 Curis CA
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-017CH CRP-072CH Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis CH
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-017DE CRP-072DE Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis DE
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-017DK CRP-072DK Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis DK
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-017EP CRP-072EP Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis EP
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-017ES CRP-072ES Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis ES
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-017FR CRP-072FR Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis FR
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-017FW2 CRP-072FW2 Morphogen Induced Liver Regeneration 05/22/1995 08/445,468 Issued 5,849,686 Curis US
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-017GR CRP-072GR Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis GR
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-017IE CRP-072IE Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis IE
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-017IT CRP-072IT Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis IT
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-017JP CRP-072JP Morphogen Induced Liver Regerneration 09/16/1993 06-508342 Pending Curis JP
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-017LU CRP-072LU Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis LU
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-017MC CRP-072MC Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis MC
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-017NL CRP-072NL Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis NL
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-017PC CRP-072PC Morphogen Induced Liver Regeneration 09/16/1993 PCT/US93/08808 Completed Curis PCT
National
Stage
Page 4 of 10
Curis BMP Portfolio (Worldwide) Licensed to Stryker
- ---------------------------------------------------------------------------------------------------------------------------------
CBM-017PT CRP-072PT Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis PT
- ---------------------------------------------------------------------------------------------------------------------------------
CBM-017SE CRP-072SE Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis SE
- ---------------------------------------------------------------------------------------------------------------------------------
CBM-017UK CRP-072UK Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis UK
- ---------------------------------------------------------------------------------------------------------------------------------
CBM-018CN CRP-074CN Morphogen treatment of Gastrointestinal 06/05/1995 08/462,623 Issued 5,739,107 Curis US
Ulcers
- ---------------------------------------------------------------------------------------------------------------------------------
CBM-018DV CRP-074DV Morphogen Treatment for Limiting 06/05/1995 08/461,113 Issued 6,399,569 Curis US
Proliferation of Epithelial Cells
- ---------------------------------------------------------------------------------------------------------------------------------
CBM-018FW2 CRP-074FW2 Morphogen Treatment of Gastrointestinal 06/05/1995 08/461,397 Issued 5,972,884 Curis US
Ulcers
- ---------------------------------------------------------------------------------------------------------------------------------
CBM-019 CPUS CRP-123 Treatment of Mammalian Myocardium with 12/03/1999 09/331,375 Pending Curis US
Morphogen Locally, Or with
Morphogenically-Treated Myogenic
Precursor Cells
- ---------------------------------------------------------------------------------------------------------------------------------
CBM-019AU CRP-123AU Treatment of Mammalian Myocardium with 12/19/1997 57119/98 Issued 741350 Curis AU
Morphogen Locally, Or with
Morphogenically-Treated Myogenic
Precursor Cells
- ---------------------------------------------------------------------------------------------------------------------------------
CBM-019CA CRP-123CA Treatment of Mammalian Myocardium with 12/19/1997 2,275,436 Pending Curis CA
Morphogen Locally, Or with
Morphogenically-Treated Myogenic
Precursor Cells
- ---------------------------------------------------------------------------------------------------------------------------------
CBM-019EP CRP-123EP Treatment of Mammalian Myocardium with 12/19/1997 97953356.9 Pending Curis EP
Morphogen Locally, Or with
Morphogenically-Treated Myogenic
Precursor Cells
- ---------------------------------------------------------------------------------------------------------------------------------
CBM-019JP CRP-123JP Treatment of Mammalian Myocardium with 12/19/1997 10-528998 Pending Curis JP
Morphogen Locally, Or with
Morphogenically-Treated Myogenic
Precursor Cells
- ---------------------------------------------------------------------------------------------------------------------------------
CBM-020CP2AU CRP-160CP2AU Methods for Maintaining or Restoring 12/16/1998 19218/99 Pending Curis AU
Tissue-Appropriate Phenotype of Soft
Tissue Cells
- ---------------------------------------------------------------------------------------------------------------------------------
CBM-020CP2CA CRP-160CP2CA Methods for Maintaining or Restoring 12/16/1998 2,314,821 Pending Curis CA
Tissue-Appropriate Phenotype of Soft
Tissue Cells
- ---------------------------------------------------------------------------------------------------------------------------------
CBM-020CP2EP CRP-160CP2EP Methods for Maintaining or Restoring 12/16/1998 98964007.3 Pending 1 040 126 Curis EP
Tissue-Appropriate Phenotype of Soft
Tissue Cells
- ---------------------------------------------------------------------------------------------------------------------------------
CBM-020CP2JP CRP-16OCP2JP Methods for Maintaining or Restoring 12/16/1998 2000-539059 Pending Curis JP
Tissue-Appropriate Phenotype of Soft
Tissue Cells
Page 5 of 10
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-020CP2PC CRP-160CP2PC Methods for Maintaining or 12/16/1998 PCT/US98/26788 Completed Curis PCT
Restoring Tissue-Appropriate National
Phenotype of Soft Tissue Cells Stage
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-020CP2US CRP-160CP2US Methods for Maintaining or 12/16/1998 09/581,770 Pending Curis US
Restoring Tissue-Appropriate
Phenotype of Soft Tissue Cells
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-021CIP CRP-166 CIP Method for Alleviating Cancer 11/13/1998 09/191,239 Pending Curis US
Symptoms
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-021CPCA~ CRP-166CPCA Method for Alleviating Cancer 11/12/1999 2,349,038 Pending Curis CA
Symptoms
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-021CPEP~ CRP-166CPEP Method for Alleviating Cancer 11/12/1999 99958892.4 Pending 1,131,087 Curis EP
Symptoms
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-021CPJP~ CRP-166CPJP Method for Alleviating Cancer 11/12/1999 2000-582058 Pending Curis JP
Symptoms
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-021CPPC~ CRP-166CPPC Method for Alleviating Cancer 11/12/1999 PCT/US99/26636 Completed Curis PCT
Symptoms National
Stage
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-022AU CRP-060AU Osteogenic Proteins in the 08/28/1992 31762/93 Issued 670558 Curis AU
Treatment of Bone Diseases
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-022CA CRP-060CA Treatment to prevent loss of 08/28/1992 2,116,559 Pending Curis CA
and/or increase bone mass in
metabolic bone diseases
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-022CN CRP-060CN Treatment to prevent loss of 03/20/1995 08/406,672 Issued 5,674,844 Curis US
and/or increase bone mass in
metabolic bone diseases
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-022CP FWC CN CRP-060CPFWC CN Treatment to Prevent Loss of 10/13/1998 09/170,936 Issued 6,333,312 Curis US
and/or Increase Bone Mass in
Metabolic Bone Diseases
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-022CPFWC CN2 CRP-060CPFWC CN2 Treatment to Prevent Loss of 09/13/2001 09/952,318 Pending Curis US
and/or Increase Bone Mass in
Metabolic Bone Diseases
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-022EP CRP-060EP Treatment to prevent loss of 08/28/1992 93900497.4 Pending Curis EP
and/or increase bone mass in
metabolic bone diseases
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-022JP CRP-060JP Treatment to prevent loss of 08/28/1992 05-506066 Pending Curis JP
and/or increase bone mass in
metabolic bone diseases
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-022PC CRP-060PC Osteogenic Proteins in the 08/28/1992 PCT/US92/07432 Completed Curis PCT
Treatment of Bone Diseases National
Stage
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-035AT CRP-058AT Morphogenic Protein 08/28/1992 92921799 Issued EP 0601129 Curis AT
Screening Method B1
Page 6 of 10
SCHEDULE A
Curis BMP Portfolio (Worldwide) Licensed to Stryker
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035AU CRP-058AU Morphogenic Protein Screening Method 08/28/1992 28624/92 Issued 678,345 Curis AU
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035AUDV CRP-058AUDV Morphogenic Protein Screening Method 08/28/1992 36040/97 Issued 696,364 Curis AU
II
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035BE CRP-058BE Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 Curis BE
B1
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035CA CRP-058CA Morphogenic Protein Screening Method 08/28/1992 2,116,560 Issued 2,116,156 Curis CA
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035CH CRP-058CH Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 Curis CH
B1
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035CN CRP-058 Morphogenic Protein Screening Method 05/26/1995 08/451,953 Issued 5,741,641 Curis US
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035CN2 CRP-058 Method of Diagnosing Renal Tissue 05/06/1996 08/643,563 Issued 5,707,810 Curis US
Damage or Disease
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035CNDV CRP-058 Morphogenic Protein Screening Method 08/15/1997 08/912,088 Issued 5,994,131 Curis US
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035CPC CRP-058CPC Morphogenic Protein Screening Method 08/28/1992 PCT/US92/07359 Completed Curis PCT
National
Stage
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035CPFW CRP-058 Morphogenic Protein Screening Method 07/20/1994 08/278,729 Issued 5,650,276 Curis US
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035DE CRP-058DE Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 Curis DE
B1
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035DK CRP-058DK Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 Curis DK
B1
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035EP CRP-058EP Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 Curis EP
B1
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035EPD CRP-058EPDV Morphogenic Protein Screening Method 08/28/1992 97202681.9 Pending Curis EP
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035EPD2 CRP-058EPDIV Morphogenic Protein Screening Method 08/28/1992 100232.8 Pending 1 033 574 Curis EP
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035ES CRP-058 Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 ES
B1
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035FR CRP-058 Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 FR
B1
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035GB CRP-058 Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 UK
B1
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035GR CRP-058 Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 GR
B1
- -------------------------------------------------------------------------------------------------------------------------------
CBM-035IE CRP-058 Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 IE
B1
Page 7 of 10
SCHEDULE A
Curis BMP Portfolio (Worldwide) Licensed to Slryker
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-035IT CRP-058 Morphogenic Protein Screening Method 8/28/1992 92921799 Issued EP 0601129 IT
B1
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-035JP CRP-058JP Morphogenic Protein Screening Method 8/28/1992 05-505345 Pending Curis JP
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-035LU CRP-058 Morphogenic Protein Screening Method 8/28/1992 92921799 Issued EP 0601129 LU
B1
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-035MC CRP-058 Morphogenic Protein Screening Method 8/28/1992 92921799 Issued EP 0601129 MC
B1
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-035NL CRP-058 Morphogenic Protein Screening Method 8/28/1992 92921799 Issued EP 0601129 NL
B1
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-036DV1 CRP-073 Morphogen Cell Surface Receptor 6/2/1995 08/459,009 Issued 5,861,479 Curis US
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-036DV2 CRP-073 Novel Morphogen Cell Surface Receptor 6/2/1995 08/459,951 Issued 6,093,547 Curis US
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-036FW CRP-073 Morphogen Cell Surface Receptor 12/16/1994 08/357,533 Issued 5,831,050 Curis US
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-037AU CRP-091AU Methods and Compositions for 6/7/1995 28223/95 Issued 703445 AU
Modulating Protein Expression
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-037AUD CRP-091AUD Methods and Compositions for 6/24/1999 36757/99 Allowed 743067 AU
Modulating Protein Expression
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-037AUD2 CRP-091AUD2 Methods and Compositions for 4/17/2002 34387/02 Pending AU
Modulating Protein Expression
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-037CA CRP-091CA Methods and Compositions for 6/7/1995 2,191,583 Pending CA
Modulating Protein Expression
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-037CP CRP-091CP Methods and Compositions for 6/7/1995 08/486,343 Issued 6,071,695 Curis US
Modulating Morphogenic Protein
Expression
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-037EP CRP-091EP Methods and Compositions for 6/7/1995 95923784.3 Pending EP
Modulating Protein Expression
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-037JP CRP-091JP Methods and Compositions for 6/7/1995 8-501323 Pending JP
Modulating Protein Expression
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-037PC CRP-091PC Methods and Compositions for 6/7/1995 PCT/US95/07349 Completed Curis PCT
Modulating Protein Expression National
Stage
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-038 CRP-107 Methods and Compositions for 7/26/1995 08/507,598 Issued 5,834,188 Curis US
Identifying Morphogen Analogs
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-039 CRP-116 Morphogen-Responsive Regulatory 7/26/1995 08/507,750 Issued 5,932,716 Curis US
Elements
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-039DV CRP-116DV Methods and Compositions for 6/11/1997 08/872,859 Issued 6,110,460 Curis US
Identifying Morphogen Analogs
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-040 CRP-126CP Methods and Compositions for 12/12/1996 08/764,522 Issued 6,090,544 Curis US
Identifying Morphogen Analogs
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-040Div CRP-126CPD1 Methods and Compositions for 7/10/2000 09/613,177 Pending Curis US
Identifying Morphogen Analogs
Page 8 of 10
SCHEDULE A
Curis BMP Portfolio (Worldwide) Licensed to Stryker
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-041 CRP-127 Methods and Compositions for 12/12/1996 08/764,528 Issued 6,103,491 Curis US
Identifying Morphogen Analogs
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-041Div CRP-127 Methods and Compositions for 08/14/2000 09/638,489 Pending Curis US
Identifying Morphogen Analogs
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-043 CRP-148 Modulators Of Morphogen Expression 11/15/1999 09/423,821 Pending Curis US
And Methods Of Identifying The Same
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-043AU CRP-148AU Modulators Of Morphogen Expression 05/28/1998 77073/98 Issued 745514 Curis AU
And Methods Of Identifying The Same
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-043CA CRP-148CA Modulators Of Morphogen Expression 05/28/1998 2,291,510 Pending Curis CA
And Methods Of Identifying The Same
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-043EP CRP-148EP Modulators Of Morphogen Expression 05/28/1998 98925035.2 Pending Curis EP
And Methods Of Identifying The Same
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-043JP CRP-148JP Modulators Of Morphogen Expression 05/28/1998 11-500978 Pending Curis JP
And Methods Of Identifying The Same
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-043PC CRP-148PC Modulators Of Morphogen Expression 05/28/1998 PCT/US98/11025 Completed Curis PCT
And Methods Of Identifying The Same National Stage
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-058 US CRP-131 Morphogens and GDNF/NGF 09/09/1998 09/508,254 Pending Curis US
Neurotrophic Factors.
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-058AU CRP-131AU Morphogens and GDNF/NGF 09/09/1998 94759/98 Issued 749454 Curis AU
Neurotrophic Factors.
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-058CA CRP-131CA Synergistic Effects of OP/BMP 09/09/1998 2,303,460 Pending Curis CA
Morphogens and GDNF/NGF
Neurotrophic Factors.
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-058EP CRP-131EP Morphogens and GDNF/NGF 09/09/1998 98948122.1 Pending Curis EP
Neurotrophic Factors.
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-058HK CRP-131HK Morphogens and GDNF/NGF 09/09/1998 108400.7 Pending Curis HK
Neurotrophic Factors.
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-058JP CRP-131JP Morphogens and GDNF/NGF 09/09/1998 2000-510457 Pending Curis JP
Neurotrophic Factors.
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-058PC CRP-131PC Morphogens and GDNF/NGF 09/09/1998 PCT/US98/18772 Completed Curis PCT
Neurotrophic Factors. National Stage
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-070CA CRP-125CA Methods for Tissue Morphogenesis and 05/29/1998 2,291,514 Pending Curis CA
Methods for Evaluating Morphogenic
Activity
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-070EP CRP-125EP Methods for Tissue Morphogenesis and 05/29/1998 98926115.1 Pending Curis EP
Methods for Evaluating Morphogenic
Activity
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-070JP CRP-125JP Methods for Tissue Morphogenesis and 05/29/1998 11-500923 Pending Curis JP
Methods for Evaluating Morphogenic
Activity
Page 9 of 10
SCHEDULE A
Curis BMP Portfolio (Worldwide) Licensed to Stryker
CBM-070PC CRP-125PC Methods for Tissue Morphogenesis and 5/29/1998 PCT/US98/10909 Completed Curis PCT
Methods for Evaluating Morphogenic National
Activity Stage
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-070US CRP-165US Methods for Tissue Morphogenesis and 5/29/1998 09/423,943 Pending Curis US
Methods for Evaluating Morphogenic
Activity
- ------------------------------------------------------------------------------------------------------------------------------------
CUR-566CP2US Morphogen Analogs of Bone 06/06/2002 10/164,279 Pending Curis US
Morphogenic Proteins
- ------------------------------------------------------------------------------------------------------------------------------------
CUR-566CPUS Morphogen Analogs of Bone 04/10/2002 60/371,298 Pending Curis US
Morphogenic Proteins
- ------------------------------------------------------------------------------------------------------------------------------------
CUR-566US Morphogen Analogs of OP-1 02/05/2002 60/354,820 Pending Curis US
- ------------------------------------------------------------------------------------------------------------------------------------
Page 10 of 10
Schedule B
Curis BMP Portfolio (Worldwide) Licensed from Stryker
Stryker Case No. CRP No. Title Filing Date Serial No. Status Patent No. Assignee Country of
Filing
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001 Osteogenic Proteins and Polypeptides 04/08/1988 07/179,406 Issued 4,968,590 Stryker US
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001AT Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker AT
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001AT4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker AT
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001AU1 Osteogenic Devices 04/07/1989 35305/89 Issued 618,357 Stryker AU
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001AU2 Biosynthetic Osteogenic Proteins and 04/07/1989 34449/89 Issued 628,050 Stryker AU
Osteogenic Devices Containing Them
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001AU4 Osteogenic Devices 10/15/1990 66481/90 Issued 648,997 Stryker AU
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001BE1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker BE
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001BE4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker BE
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001CA1 Osteogenic Devices 04/07/1989 596,143 Pending Stryker CA
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001CA1DV Osteogenic Devices 04/07/1989 617,121 Pending Stryker CA
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001CA2 Biosynthetic Osteogenic Proteins and 04/07/1989 596,144 Issued 1,338,663 Stryker CA
Osteogenic Devices Containing Them
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001CA4 Osteogenic Devices 10/15/1990 2,042,577-6 Pending Stryker CA
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001CH1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker CH
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001CP2 Osteogenic Device 02/23/1989 07/315,342 Issued 5,011,691 Stryker US
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001CP2DV2 Osteogenic Proteins 09/24/1992 07/950,229 Issued 5,324,819 Stryker US
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001CP2DV3 Cartilage and Bone-Inducing Proteins 11/01/1993 08/145,812 Issued 5,750,651 Stryker US
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001CP2DVFW Osteogenic Proteins 12/22/1992 07/995,345 Issued 5,258,494 Stryker US
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001CP6 Osteogenic Proteins 02/21/1992 07/841,646 Issued 5,266,683 Stryker US
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001CP6DV2 Antibodies to Osteogenic Proteins 11/01/1993 08/147,023 Issued 5,468,845 Stryker US
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001CP6DV3 Method of Selectively Extracting 05/23/1995 08/447,570 Issued 5,714,589 Stryker US
Osteogenic Protein
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001CP6DV4 Nucleic Acids Encoding
Osteogenic Proteins 05/23/1995 08/449,700 Issued 5,863,758 Stryker US
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001DE1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker DE
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001DE4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker DE
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001DK4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker DE
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001DV2 Osteogenic Devices 01/28/1992 07/827,052 Issued 5,250,302 Stryker US
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001EP1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker EP
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001EP1DV Osteogenic Proteins 07/07/1995 95 20 1872.9 Allowed Stryker EP
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001EP2DV Biosynthetic Osteogenic Proteins and 04/07/1989 96 20 0044.4 Allowed Stryker EP
Osteogenic Devices Containing Them
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001EP4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker EP
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001ES4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker ES
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001FR1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker FR
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001FR4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker FR
- -----------------------------------------------------------------------------------------------------------------------------------
STK-001GB1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker GB
Page 1 of 7
Schedule B
Curis BMP Portfolio (Worldwide) Licensed from Stryker
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001GB4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker UK
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001GR4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker GR
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001IT1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker IT
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001IT4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker IT
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001JP1 Osteogenic Devices 04/07/1989 1-504771 Issued 2522568 Stryker JP
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001JP1DV Osteogenic Devices 04/07/1989 Aug-35 Issued 2933867 Stryker JP
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001JP2DV Osteogenic Devices 04/07/1989 7-263371 Pending Stryker JP
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001JP4 Osteogenic Devices 10/15/1990 515578/90 Issued 2845346 Stryker JP
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001JP4DV Osteogenic Devices 07/02/1997 177440/97 Pending Stryker JP
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001JP4DV2 Osteogenic Devices 08/24/2000 200-254562 Pending Stryker JP
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001JP4DV3 Osteogenic Devices Not yet assigned Pending Stryker JP
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001LU1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker LU
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001LU4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker LU
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001NL1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker NL
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001NL4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker NL
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001PC1 Osteogenic Devices 04/07/1989 PCT/US89/01453 Completed Stryker PCT
National
Stage
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001PC2 Biosynthetic Osteogenic Proteins and 04/07/1989 PCT/US89/01469 Completed Stryker PCT
Osteogenic Devices Containing Them National
Stage
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001PC4 Osteogenic Devices 10/15/1990 PCT/US90/05903 Completed Stryker PCT
National
Stage
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001SE1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker SE
- ------------------------------------------------------------------------------------------------------------------------------------
STK-001SE4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker SE
- ------------------------------------------------------------------------------------------------------------------------------------
STK-008 Nucleotide Sequences Encoding 01/20/1995 08/375,901 Issued 6,261,835 Stryker US
Osteogenic Proteins
- ------------------------------------------------------------------------------------------------------------------------------------
STK-008CN DNA sequences encoding osteogenic 01/03/2001 09/754,831 Pending Stryker US
protein
- ------------------------------------------------------------------------------------------------------------------------------------
STK-009 Method for Recombinant Production of 01/20/1995 08/376,731 Issued 5,670,336 Stryker US
Osteogenic Protein OP-1
- ------------------------------------------------------------------------------------------------------------------------------------
STK-042AU Bone Collagen Matrix for Xenogenic 02/22/1990 51747/90 Issued 627,850 AU
Implants
- ------------------------------------------------------------------------------------------------------------------------------------
STK-042CA Bone Collagen Matrix for Xenogenic 02/22/1990 2,027,259-7 Issued 2,027,259-7 CA
Implants
- ------------------------------------------------------------------------------------------------------------------------------------
STK-042DE Bone Collagen Matrix for Xenogenic 02/22/1990 90 90 4002.4 Issued 0 411 105 DE
Implants
- ------------------------------------------------------------------------------------------------------------------------------------
STK-042EP Bone Collagen Matrix for Xenogenic 02/22/1990 90 90 4002.4 Issued 0 411 105 EP
Implants
Page 2 of 7
Schedule B
Curis BMP Portfolio (Worldwide) Licensed from Stryker
- -----------------------------------------------------------------------------------------------------------------------------------
STK-042FR Bone Collagen Matrix for Xenogenic 02/22/1990 90 90 4002.4 Issued 0 411 105 FR
Implants
- -----------------------------------------------------------------------------------------------------------------------------------
STK-042GB Bone Collagen Matrix for Xenogenic 02/22/1990 90 90 4002.4 Issued 0 411 105 UK
Implants
- -----------------------------------------------------------------------------------------------------------------------------------
STK-042IT Bone Collagen Matrix for Xenogenic 02/22/1990 90 90 4002.4 Issued 0 411 105 IT
Implants
- -----------------------------------------------------------------------------------------------------------------------------------
STK-042JP Bone Collagen Matrix for Xenogenic 02/22/1990 504059/90 Issued 2113455 JP
Implants
- -----------------------------------------------------------------------------------------------------------------------------------
STK-042PC Bone Collagen Matrix for Xenogenic 02/22/1990 PCT/US90/00912 Completed PCT
Implants National
Stage
- -----------------------------------------------------------------------------------------------------------------------------------
STK-049AU Synthetic Bone Matrix 05/22/1991 79614/91 Issued 639,574 AU
- -----------------------------------------------------------------------------------------------------------------------------------
STK-049CA Synthetic Bone Matrix 05/22/1991 2,082,946-0 Issued 2,082,946 CA
- -----------------------------------------------------------------------------------------------------------------------------------
STK-049EP Synthetic Bone Matrix 05/22/1991 91 91 1588.1 Grant 0 608 211 EP
- -----------------------------------------------------------------------------------------------------------------------------------
STK-049JP Synthetic Bone Matrix 05/22/1991 03-510269 Issued 2679409 JP
- -----------------------------------------------------------------------------------------------------------------------------------
STK-049PC Synthetic Bone Matrix 05/22/1991 PCT/US91/03603 Completed PCT
National
Stage
- -----------------------------------------------------------------------------------------------------------------------------------
STK-056AU Osteogenic Peptides 10/18/1991 89000/91 Issued 663,689 AU
- -----------------------------------------------------------------------------------------------------------------------------------
STK-056CA Osteogenic Peptides 10/18/1991 2,094,027 Issued 2,094,027 CA
- -----------------------------------------------------------------------------------------------------------------------------------
STK-056DE Osteogenic Proteins 10/18/1991 91 91 9612.1 Issued 0 643 767 DE
- -----------------------------------------------------------------------------------------------------------------------------------
STK-056EP Osteogenic Proteins 10/18/1991 91 91 9612.1 Issued 0 643 767 EP
- -----------------------------------------------------------------------------------------------------------------------------------
STK-056FR Osteogenic Proteins 10/18/1991 91 91 9612.1 Issued 0 643 767 FR
- -----------------------------------------------------------------------------------------------------------------------------------
STK-056GB Osteogenic Proteins 10/18/1991 91 91 9612.1 Issued 0 643 767 UK
- -----------------------------------------------------------------------------------------------------------------------------------
STK-056IT Osteogenic Proteins 10/18/1991 91 91 9612.1 Issued 0 643 767 IT
- -----------------------------------------------------------------------------------------------------------------------------------
STK-056JP Osteogenic Peptides 10/18/1991 03-518322 Pending JP
- -----------------------------------------------------------------------------------------------------------------------------------
STK-056JPDV Osteogenic Peptides 10/18/1991 10-352101 Pending JP
- -----------------------------------------------------------------------------------------------------------------------------------
STK-056PC Osteogenic Peptides 10/18/1991 PCT/US91/07635 Completed PCT
National
Stage
- -----------------------------------------------------------------------------------------------------------------------------------
STK-058AU CRP-076AU OP-3 Induced Morphogenesis 11/02/1993 55900/94 Issued 681,362 Stryker AU
- -----------------------------------------------------------------------------------------------------------------------------------
STK-058CA CRP-076CA OP-3 Induced Morphogenesis 11/02/1993 2,147,598 Pending Stryker CA
- -----------------------------------------------------------------------------------------------------------------------------------
STK-058DV CRP-076DV OP-3 Induced Morphogenesis 06/07/1995 08/479,666 Issued 5,652,337 Stryker US
- -----------------------------------------------------------------------------------------------------------------------------------
STK-058DV2 CRP-076DV2 OP-3 Induced Morphogenesis 07/28/1997 08/901,200 Issued 5,854,071 Stryker US
- -----------------------------------------------------------------------------------------------------------------------------------
STK-058DV3 CRP-076DV3 OP-3-Induced Morphogenesis 12/23/1998 09/219,391 Issued 6,153,583 Stryker US
- -----------------------------------------------------------------------------------------------------------------------------------
STK-058EP CRP-076EP OP-3 Induced Morphogenesis 11/02/1993 94 90 1244.7 Pending 0672064 A Stryker EP
- -----------------------------------------------------------------------------------------------------------------------------------
STK-058FW CRP-076FW Nucleic Acid Encoding a Novel 06/07/1995 08/480,528 Issued 5,652,118 Stryker US
Morphogenic Protein OP-3
Page 3 of 7
Schedule B
Curis BMP Portfolio (Worldwide) Licensed from Stryker
- ------------------------------------------------------------------------------------------------------------------------------------
STK-058JP CRP-076JP OP-3 Induced Morphogenesis 11/02/1993 6-511392 Pending Stryker JP
- ------------------------------------------------------------------------------------------------------------------------------------
STK-059 CRP-080 Single Chain Analogs of the TGF-Beta 10/01/1998 08/478,097 Issued 6,040,431 Stryker US
Superfamily (Morphons)
- ------------------------------------------------------------------------------------------------------------------------------------
STK-059PC CPR-080PC Single Chain Analogs of the TGF-B 06/06/1996 PCT/US96/09293 Completed Stryker PCT
Superfamily (Morphons) National
Stage
- ------------------------------------------------------------------------------------------------------------------------------------
STK-059AU CRP-080AU Single Chain Analogs of the TGF-B 06/06/1996 61570/96 Issued 717811 Stryker AU
Superfamily (Morphogen)
- ------------------------------------------------------------------------------------------------------------------------------------
STK-059AUDV CRP-080AUDV Single Chain Analogs of the TGF-B 06/06/1996 43748/00 Pending Stryker AU
Superfamily (Morphogen)
- ------------------------------------------------------------------------------------------------------------------------------------
STK-059CA CRP-080CA Single Chain Analogs TGF-B Superfamily 06/06/1996 2,223,292 Pending Stryker CA
(Morphogen)
- ------------------------------------------------------------------------------------------------------------------------------------
STK-059CN CRP-080CN Single Chain Analogs of the TGF-Beta 02/02/2000 09/496,398 Pending Stryker US
Superfamily (Morphons)
- ------------------------------------------------------------------------------------------------------------------------------------
STK-059EP CRP-080EP Single Chain Analogs of the TGF-B 06/06/1996 96 9 1 9162.6 Pending 833844 Stryker EP
Superfamily (Morphogen)
- ------------------------------------------------------------------------------------------------------------------------------------
STK-059JP CPR-080JP Single Chain Analogs of the TGF-B 06/06/1996 09-501647 Pending 11-510686 Stryker JP
Superfamily (Morphogen)
- ------------------------------------------------------------------------------------------------------------------------------------
STK-060AU CRP-081 Novel Morphogenic Protein Compositions 07/29/1993 47951/93 Issued 678,380 Stryker AU
of Matter
- ------------------------------------------------------------------------------------------------------------------------------------
STK-060CA CRP-081 - Novel Morphogenic Protein Compositions 07/29/1993 2,141,555 Pending Stryker CA
of Matter
- ------------------------------------------------------------------------------------------------------------------------------------
STK-060DV CRP-081 Novel Morphogenic Protein Compositions 06/02/1995 08/459,346 Issued 5,834,179 Stryker US
of Matter
- ------------------------------------------------------------------------------------------------------------------------------------
STK-060DVCN CRP-081 Novel Morphogenic Protein Compositions 07/08/1997 08/889,419 Issued 6,071,708 Stryker US
of Matter
- ------------------------------------------------------------------------------------------------------------------------------------
STK-060EP CRP-081 Novel Morphogenic Protein Compositions 07/29/1993 93918529.4 Pending 0652953 A Stryker EP
of Matter
- ------------------------------------------------------------------------------------------------------------------------------------
STK-060FW CRP-081FW Novel Morphogenic Protein Compositions 03/13/1995 08/402,542 Issued 6,395,883 Curis US
of Matter
- ------------------------------------------------------------------------------------------------------------------------------------
STK-060JP CRP-081 Novel Morphogenic Protein Compositions 07/29/1993 6-505462 Pending Stryker JP
of Matter
- ------------------------------------------------------------------------------------------------------------------------------------
STK-060KR CRP-081 Novel Morphogenic Protein Compositions 07/29/1993 700360/1995 Pending Stryker KR
of Matter
- ------------------------------------------------------------------------------------------------------------------------------------
STK-060PC CPR-081PC Novel Morphogenic Protein Compositions 07/29/1993 PCT/US93/07189 Completed Stryker PCT
of Matter National
Stage
- ------------------------------------------------------------------------------------------------------------------------------------
STK-061 CRP-082 Lipid Modified Serum Free Media 09/22/1993 08/124,676 Issued 5,631,159 Stryker US
of Matter
- ------------------------------------------------------------------------------------------------------------------------------------
STK-061AU CRP-082 Lipid Modified Serum Free Media 09/21/1994 80717/94 Issued 698633 Stryker AU
of Matter
- ------------------------------------------------------------------------------------------------------------------------------------
STK-061CA CRP-082 Lipid Modified Serum Free Media 09/21/1994 2,170,761 Issued 2,170,761 Stryker CA
of Matter
- ------------------------------------------------------------------------------------------------------------------------------------
Page 4 of 7
Schedule B
Curis BMP Portfolio (Worldwide) Licensed from Stryker
- -------------------------------------------------------------------------------------------------------------------------------
STK-061DE CRP-082 Lipid Modified Serum Free Media 09/21/1994 94 93 1761.4 Issued 0 720 648 Stryker DE
- -------------------------------------------------------------------------------------------------------------------------------
STK-061EP CRP-082 Lipid Modified Serum Free Media 09/21/1994 94 93 1761.4 Issued 0 720 648 Stryker EP
- -------------------------------------------------------------------------------------------------------------------------------
STK-061FR CRP-082 Lipid Modified Serum Free Media 09/21/1994 94 93 1761.4 Issued 0 720 648 Stryker FR
- -------------------------------------------------------------------------------------------------------------------------------
STK-061GB CRP-082 Lipid Modified Serum Free Media 09/21/1994 94 93 1761.4 Issued 0 720 648 Stryker UK
- -------------------------------------------------------------------------------------------------------------------------------
STK-061IT CRP-082 Lipid Modified Serum Free Media 09/21/1994 94 93 1761.4 Issued 0 720 648 Stryker IT
- -------------------------------------------------------------------------------------------------------------------------------
STK-061JP CRP-082 Lipid Modified Serum Free Media 09/21/1994 7-509936 Pending Stryker JP
- -------------------------------------------------------------------------------------------------------------------------------
STK-061PC CRP-082 Lipid Modified Serum Free Media 09/21/1994 PCT/US94/10736 Completed Stryker PCT
National
Stage
- -------------------------------------------------------------------------------------------------------------------------------
STK-062 CRP-084 Methods and Compositions for High 10/25/1993 08/143,497 Issued 5,585,237 Stryker US
Protein Production from Recombinant
DNA
- -------------------------------------------------------------------------------------------------------------------------------
STK-062AU CRP-084 Methods and Compositions for High 10/21/1994 80859/94 Issued 685188 Stryker AU
Protein Production from Recombinant
DNA
- -------------------------------------------------------------------------------------------------------------------------------
STK-062CA CRP-084 Methods and Compositions for High 10/21/1994 2,171,759 Pending Stryker CA
Protein Production from Recombinant
DNA
- -------------------------------------------------------------------------------------------------------------------------------
STK-062DV CRP-084 Methods and Compositions for High 06/05/1995 08/461,666 Issued 5,614,385 Stryker US
Protein Production from Recombinant
DNA
- -------------------------------------------------------------------------------------------------------------------------------
STK-062DVCN CRP-084 Methods and Compositions for High 11/27/1996 08/757,300 Issued 5,712,119 Stryker US
Protein Production from Recombinant
DNA
- -------------------------------------------------------------------------------------------------------------------------------
STK-062EP CRP-084 Methods and Compositions for High 10/21/1994 94 93 1958.6 Pending Stryker EP
Protein Production from Recombinant
DNA
- -------------------------------------------------------------------------------------------------------------------------------
STK-062JP CRP-084 Methods and Compositions for High 10/21/1994 7-512727 Pending Stryker JP
Protein Production from Recombinant
DNA
- -------------------------------------------------------------------------------------------------------------------------------
STK-062PC CRP-084 Methods and Compositions for High 10/21/1994 PCT/US94/12063 Completed Stryker PCT
Protein Production from Recombinant National
DNA Stage
- -------------------------------------------------------------------------------------------------------------------------------
STK-064 CRP-096 Compositions and Methods for 03/04/1994 08/206,864 Issued 5,610,021 Stryker US
Identification and Use of Soluble
Complex Forms of Osteogenic Proteins
- -------------------------------------------------------------------------------------------------------------------------------
STK-064AU CRP-096 Methods and Compositions for 03/04/1994 63588/94 Issued 682,176 AU
Recombinant Osteogenic Protein
Production
Page 5 of 7
Schedule B
Curis BMP Portfolio (Worldwide) Licensed from Stryker
- -----------------------------------------------------------------------------------------------------------------------------------
STK-064CA CRP-096 Methods and Compositions for 03/04/1994 2,157,387 Issued 2,157,387 CA
Recombinant Osteogenic Protein
Production
- -----------------------------------------------------------------------------------------------------------------------------------
STK-064EP CRP-096 Methods and Compositions for 03/04/1994 94 91 0830.2 Pending EP
Recombinant Osteogenic Protein
Production
- -----------------------------------------------------------------------------------------------------------------------------------
STK-064JP CRP-096 Methods and Compositions for 03/04/1994 6-520181 Pending JP
Recombinant Osteogenic Protein
Production
- -----------------------------------------------------------------------------------------------------------------------------------
STK-064PC CRP-096 Method and Compositions for 03/04/1994 PCT/US94/02335 Completed PCT
Recombinant Osteogenic Protein National
Production Stage
- -----------------------------------------------------------------------------------------------------------------------------------
STK-075 Modified TGF-Beta Superfamily Proteins 08/16/1999 09/375,333 Pending Stryker US
- -----------------------------------------------------------------------------------------------------------------------------------
STK-075AU Modified TGF-Beta Superfamily Proteins 10/07/1999 11039/00 Pending Stryker AU
- -----------------------------------------------------------------------------------------------------------------------------------
STK-075CA Modified TGF-Beta Superfamily Proteins 10/07/1999 2,345,024 Pending Stryker CA
- -----------------------------------------------------------------------------------------------------------------------------------
STK-075EP Modified TGF-Beta Superfamily Proteins 10/07/1999 99954772.2 Pending Stryker EP
- -----------------------------------------------------------------------------------------------------------------------------------
STK-075JP Modified TGF-Beta Superfamily Proteins 10/07/1999 2000-574560 Pending Stryker JP
- -----------------------------------------------------------------------------------------------------------------------------------
STK-075PC Modified TGF-Beta Superfamily Proteins 10/07/1999 PCT/US99/23372 Completed Stryker PCT
National
Stage
- -----------------------------------------------------------------------------------------------------------------------------------
STK-076 Modified Proteins and DNAs of the TGF- 08/16/1999 09/374,958 Pending Stryker US
Beta Superfamily, Including Morphogenic
Proteins
- -----------------------------------------------------------------------------------------------------------------------------------
STK-076AU Modified Proteins and DNAs of the TGF- 10/07/1999 11038/00 Pending Stryker AU
Beta Superfamily, Including Morphogenic
Proteins
- -----------------------------------------------------------------------------------------------------------------------------------
STK-076CA Modified Proteins and DNAs of the TGF- 10/07/1999 2,344,974 Pending Stryker CA
Beta Superfamily, Including Morphogenic
Proteins
- -----------------------------------------------------------------------------------------------------------------------------------
STK-076EP Modified Proteins and DNAs of the TGF- 10/07/1999 99954771.4 Pending Stryker EP
Beta Superfamily, Including Morphogenic
Proteins
- -----------------------------------------------------------------------------------------------------------------------------------
STK-076JP Modified Proteins and DNAs of the TGF- 10/07/1999 2000-574702 Pending Stryker JP
Beta Superfamily, Including Morphogenic
Proteins
Page 6 of 7
Schedule B
Curis BMP Portfolio (Worldwide) Licensed from Stryker
- ----------------------------------------------------------------------------------------------------------
STK-076PC Modified Proteins and DNAs of the TGF- 10/07/1999 PCT/US99/23371 Completed Stryker PCT
Beta Superfamily, including Morphogenic National
Proteins Stage
- ----------------------------------------------------------------------------------------------------------
STK-077 Modified Proteins and DNAs of the TGF- 08/16/1999 09/374,936 Pending Stryker US
Beta Superfamily, including Modified
Morphogenic Proteins
- ----------------------------------------------------------------------------------------------------------
STK-077AU Modified Proteins and DNAs of the TGF- 10/07/1999 11037/00 Pending Stryker AU
Beta Superfamily, including Modified
Morphogenic Proteins
- ----------------------------------------------------------------------------------------------------------
STK-077CA Modified Proteins and DNAs of the TGF- 10/07/1999 2,345,287 Pending Stryker CA
Beta Superfamily, including Modified
Morphogenic Proteins
- ----------------------------------------------------------------------------------------------------------
STK-077EP Modified Proteins and DNAs of the TGF- 10/07/1999 99954770.6 Pending Stryker EP
Beta Superfamily, including Modified
Morphogenic Proteins
- ----------------------------------------------------------------------------------------------------------
STK-077JP Modified Proteins and DNAs of the TGF- 10/07/1999 2000-574686 Pending Stryker JP
Beta Superfamily, including Modified
Morphogenic Proteins
- ----------------------------------------------------------------------------------------------------------
STK-077PC Modified Proteins and DNAs of the TGF- 10/07/1999 PCT/US99/23370 Completed Stryker PCT
Beta Superfamily, including Modified National
Morphogenic Proteins Stage
- ----------------------------------------------------------------------------------------------------------
Page 7 of 7
Schedule C
Curis BMP Patent Portfolio (Worldwide) Co-Owned with
Ludwig Institute for Cancer Research and Licensed to Stryker Corporation
Country
of
Curis Case No. CRP No. Title Filing Date Serial No. Status Patent No. Assignee Filing
- ----------------------------------------------------------------------------------------------------------------------------------
CBM-023CP1US CRP-097CP1 Morphogen Protein 06/02/1995 08/448,371 Allowed Curis, Ludwig US
Specific Cell Institute for
Surface Receptors Cancer Research
and Uses Therefor
- ----------------------------------------------------------------------------------------------------------------------------------
CBM-023CP1CUS CRP-097CP1C Morphogen Protein 10/18/2001 09/982,543 Pending Curis, Ludwig US
Specific Cell Institute for
Surface Receptors Cancer Research
and Uses Therefor
- ----------------------------------------------------------------------------------------------------------------------------------
CBM-023CP2US CRP-097CP2 Methods of antagonizing 06/02/1995 08/481,337 Issued 5,863,738 Curis, Ludwig US
OP-1 binding to a Institute for
Cell Surface receptor Cancer Research
utilizing ALK
polypeptides
- ----------------------------------------------------------------------------------------------------------------------------------
CBM-023PC CRP-097PC Morphogen Protein 04/28/1995 PCT/US95/05467 Completed Curis, Ludwig PCT
Specific Cell National Institute for
Surface Receptors Stage Cancer Research
and Uses Therefor
- ----------------------------------------------------------------------------------------------------------------------------------
CBM-023AU CRP-097AU Morphogenic Protein 04/28/1995 24662/95 Issued 702163 Curis, Ludwig AU
Specific Cell Institute for
Surface Receptors Cancer Research
and Uses Therefor
- ----------------------------------------------------------------------------------------------------------------------------------
CBM-023CA CRP-097CA Morphogen Protein 04/28/1995 2,187,902 Pending Curis, Ludwig CA
Specific Cell Institute for
Surface Receptors Cancer Research
and Uses Therefor
- ----------------------------------------------------------------------------------------------------------------------------------
CBM-023EP CRP-097EP Morphogen Protein 04/28/1995 95918920 Pending Curis, Ludwig EP
Specific Cell Institute for
Surface Receptors Cancer Research
and Uses Therefor
- ----------------------------------------------------------------------------------------------------------------------------------
CBM-023JP CRP-097JP Morphogenic Protein 04/28/1995 7-528497 Pending Curis, Ludwig JP
Specific Cell Institute for
Surface Receptors Cancer Research
and Uses Therefor
- ----------------------------------------------------------------------------------------------------------------------------------
CBM-024US CRP-117 Method and Device for 08/13/1996 08/696,268 Issued 5,968,752 Curis, Ludwig US
Identifying an OP-1 Institute for
Analog Which Binds Cancer Research
An Alk-1 Receptor
- ----------------------------------------------------------------------------------------------------------------------------------
CBM-024PC CRP-117PC Binding of OP-1 08/13/1996 PCT/US97/12078 Completed Curis, Ludwig PCT
and Analogs Thereof National Institute for
to the Cell surface Stage Cancer Research
Receptor ALK-1 and
Analogs Thereof
- ----------------------------------------------------------------------------------------------------------------------------------
CBM-024EP CRP-117EP Binding of Osteogenic 08/13/1996 96928166.6 Pending Curis, Ludwig EP
Protein (OP-1) Institute for
and Analogs Thereof Cancer Research
to the Cell Surface
Receptor ALK-1 and
Analogs Thereof
- ----------------------------------------------------------------------------------------------------------------------------------
CBM-024JP CRP-117JP Binding of Osteogenic 08/13/1996 9-509445 Pending Curis, Ludwig JP
Protein (OP-1) Institute for
and Analogs Thereof Cancer Research
to the Cell Surface
Receptor ALK-1 and
Analogs Thereof
- ----------------------------------------------------------------------------------------------------------------------------------
Page 1 of 1
Schedule D
Curis BMP Patent Portfolio (Worldwide) Co-Owned with Other Institutions and
Licensed to Stryker Corporation (except as indicated)
- -----------------------------------------------------------------------------------------------------------------------------------
Country
Curis Case No. CRP No. Title Filing Date Serial No. Status Patent No. Assignee of Filing
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-005 CP US* CRP-069 Methods for Enhancing 03/21/1997 08/828,281 Issued 6407060 Curis, MGH US
Functional Recovery
Following Central Nervous
System Ischemia or Trauma
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-005 CPCUS* CRP-069 Methods for Enhancing 02/01/2002 10/062,370 Pending Curis, MGH US
Functional Recovery
Following Central Nervous
System Ischemia or Trauma
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-005AU* CRP-069AU Methods for Enhancing 03/21/1997 25823/97 Issued 725341 Curis, MGH AU
Functional Recovery
Following Central Nervous
System Ischemia or Trauma
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-005CA* CRP-069CA Methods for Enhancing 03/21/1997 2,249,596 Pending Curis, MGH CA
Functional Recovery
Following Central Nervous
System Ischemia or Trauma
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-005PC* CRP-069PC Methods for Enhancing 03/21/1997 PCT/US97/04177 Completed Curis, MGH PCT
Functional Recovery National
Following Central Nervous Stage
System Ischemia or Trauma
- -----------------------------------------------------------------------------------------------------------------------------------
CBM-005EP* CRP-069EP Methods for Enhancing 03/21/1997 97917532 Pending Curis, MGH EP
Functional Recovery
Following Central Nervous
System Ischemia or Trauma
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-005JP* CRP-069JP Methods for Enhancing 03/21/1997 9-533583 Pending Curis, MGH JP
Functional Recovery
Following Central Nervous
System Ischemia or Trauma
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-007US* CRP-098 Morphogen Induced Dendritic 08/18/1994 08/292,782 Pending Curis, SUNY US
Growth at Buffalo
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-066 C2US* CRP-102 Computer System and Methods 02/22/2001 09/791,946 Pending Curis, US
for Producing Analogs of Brandeis
Human OP-1 (as amended) University
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-066 CPFWUS* CRP-102 Computer System and Methods 01/22/1997 08/786,284 Issued 6,273,598 Curis, US
for Producing Analogs of B1 Brandeis
Human OP-1 (as amended) University
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-066AU* CRP-102AU Computer Systems and Methods 01/22/1997 22449/97 Issued 725295 Curis, AU
and Compositions for Brandeis
Producing Morphogen Analogs University
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-066AUD* CRP-102AUD Computer Systems and Methods 07/22/1997 53497/00 Pending Curis, AU
and Compositions for Brandeis
Producing Morphogen Analogs University
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-066CA* CRP-102CA Computer Systems and Methods 01/22/1997 2,244,228 Pending Curis, CA
and Compositions for Brandeis
Producing Morphogen Analogs University
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-066EP* CRP-102EP Computer Systems and Methods 01/22/1997 97905604.1 Pending Curis, EP
and Compositions for Brandeis
Producing Morphogen Analogs University
- ------------------------------------------------------------------------------------------------------------------------------------
Page 1 of 2
Schedule D
Curis BMP Patent Portfolio (Worldwide) Co-Owned with Other
Institutions and Licensed to Stryker Corporation (except as indicated)
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-066JP* CRP-102JP Computer Systems and Methods 01/22/1997 09-526303 Pending Curis, Brandeis JP
and Compositions for University
Producing Morphogen Analogs
- ------------------------------------------------------------------------------------------------------------------------------------
CBM-066PC* CRP-102PC Computer Systems and Methods 01/22/1997 PCT/US97/01071 Completed National Curis, Brandeis PCT
and Compositions for Stage University
Producing Morphogen Analogs
- ------------------------------------------------------------------------------------------------------------------------------------
CUR-599US# Cojoint Administration of 08/28/2002 60/406,431 Pending Curis, Washington US
Morphogens and ACE Univ. (St. Louis)
Inhibitors in Treatment of
Chronic Renal Failure
- ------------------------------------------------------------------------------------------------------------------------------------
* Licensed to Stryker
# Not Licensed to Stryker
Page 2 of 2
SCHEDULE E
Curis Patent Portfolio Licensed from American Home Products (Worldwide)
- ------------------------------------------------------------------------------------------------------------------------------------
Country of
Curis Case No Filing Date Serial No Title Status Patent No Issue Date Filing
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001 US 07/01/1986 06/880,776 Abandoned
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001AT 06/30/1987 87905023 Novel osteoinductive compositions Issued 141928 09/15/1996 AT
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001AU 06/30/1987 77835 Novel osteoinductive compositions Issued 613314 08/01/1991 AU
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001CP2US 03/26/1987 07/031,346 Osteoinductive factors -- BMP-1
protease 4,877,864 10/31/1989 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001CPUS 12/17/1986 06/943,332 Abandoned
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001DE 06/30/1987 3751887 Novel osteoinductive compositions Issued 3751887 10/02/1996 DE
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001DK 02/29/1988 1062 Novel osteoinductive compositions Issued 172275 02/16/1998 DK
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001EP 06/30/1987 87905023 Novel osteoinductive compositions Issued 313578 08/28/1996 EP
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001ES 06/30/1987 8701909 Novel osteoinductive compositions Issued 2007625 07/01/1989 ES
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001GR 06/30/1987 871028 Novel osteoinductive compositions Issued 871028 01/11/1988 GR
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001IE 06/29/1987 1739 Novel osteoinductive compositions Issued 75881 09/24/1997 IE
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001IL 06/26/1987 83003 Novel osteoinductive compositions Issued 83003 12/20/1987 IL
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001JP 06/30/1987 504617/87 Novel osteoinductive compositions Issued 2500241T2 02/01/1990 JP
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001KR 02/29/1988 700231/88 Novel osteoinductive compositions Issued 9705583 KR
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001MX 06/30/1987 7140 Novel osteoinductive compositions Issued 170919 09/22/1993 MX
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001MXDIV 09/21/1993 93/5743 Novel osteoinductive compositions MX
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001MY 06/30/1987 PI-8700921 Novel osteoinductive compositions Issued 102505 MX
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001NO 02/29/1988 88071 Novel osteoinductive compositions Issued 309531 02/12/2001 NO
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001NODiv 02/29/1988 88071 Novel osteoinductive compositions Issued 310029 05/07/2001 NO
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001NODiv2 02/29/1988 88071 Novel osteoinductive compositions Issued 310030 05/07/2001 NO
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001NZ 06/30/1987 220894 Novel osteoinductive compositions Issued 220894 NZ
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001PC 06/30/1987 PCT/US87/01537 Novel osteoinductive compositions Completed
National
Stage PCT
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001PH 07/01/1987 35484 Novel osteoinductive compositions PH
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001PT 07/01/1987 85225 Novel osteoinductive compositions Issued 85225 PT
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001TW 07/29/1987 76104439 Novel osteoinductive compositions Issued 45626 PT
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-001ZA 06/29/1987 87/4681 Novel osteoinductive compositions Issued 87/4681 ZA
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-002 07/31/1990 07/5561,496 DNA sequences encoding BMP-1
products 5,108,922 04/28/1992 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-003CPUS 03/20/1987 07/179,100 DNA sequences encoding
osteoinductive products 5,013,649 05/07/1991 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-004 PC 04/07/1989 PCT/US89/01464 DNA sequences encoding BMP-3 Completed
National
Stage PCT
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-004 US 04/08/1988 179,197 DNA sequences encoding BMP-3 Abandoned US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-004AU 04/07/1989 34487 DNA sequences encoding BMP-3 Issued 645244 AU
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-004CPUS 04/26/1991 692,827 DNA sequences encoding BMP-3 5,116,738 05/26/1992 US
- ------------------------------------------------------------------------------------------------------------------------------------
Page 1 of 8
SCHEDULE E
Curis Patent Portfolio Licensed from American Home Products (Worldwide)
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-004EP 04/07/1989 89904945.6 DNA sequences encoding BMP-3 408649 A1 EP
AHP-004JP 04/07/1989 504776/89 DNA sequences encoding BMP-3 Issued 3503649 T2 08/15/1991 EP
AHP-004KR 12/07/1989 702291/89 DNA sequences encoding BMP-3 Issued 08/15/1991 KR
AHP-005 06/23/1989 07/370,547 DNA sequences encoding
BMP-5 proteins Abandoned 5,106,748 04/21/1992 US
AHP-005 03/28/1989 329,610 DNA sequenes encoding
BMP-5 proteins Abandoned US
AHP-005CPC2Div 06/05/1995 08/469,935 Bone morphogenetic protein
5 (BMP-5) compositions Issued 5,635,373 06/03/1997 US
AHP-005CPC2DivCP 01/23/1997 08/788,729 Methods of Administering
BMP-5 Proteins Issued 5,939,388 08/17/1999 US
AHP-005CPC2US 09/07/1993 08/116,425 Bone morphogenetic protein
5 (BMP-5) compositions Issued 5,543,394 08/06/1996 US
AHP-005CPEP 09/26/1991 91917761 Bone morphogenetic protein
5 (BMP-5) compositions Completed National Stage 550625 A1 EP
AHP-005CPPC 09/26/1991 PCT/US91/07069 Bone morphogenetic protein
5 (BMP-5) compositions Completed National Stage PCT
AHP-005CPUS 09/26/1990 588,227 Bone morphogenetic protein
5 (BMP-5) compositions Abandoned US
AHP-006 03/07/1990 07/490,033 DNA sequences encoding
BMP-6 proteins 5,187,076 02/16/1993 US
AHP-006D2C2 11/09/1998 09/189,157 BMP-6 Proteins Issued 6,207,813 03/27/2001 US
AHP-006D2C2DV 03/23/2001 09/816,299 BMP-6 Proteins Pending US
AHP-006D2CUS 06/05/1995 08/469,936 BMP-6 Issued 5,849,880 12/15/1998 US
AHP-006D2US 05/27/1994 08/251,069 BMP-6 proteins Issued 5,459,047 10/17/1995 US
AHP-007 US 11/17/1989 07/438,919 DNA Encoding BMP-7 Protein 5,141,905 08/25/1992 US
AHP-007CPAU 03/27/1990 53577/90 Osteoinductive Compositions AU
AHP-007CPCA 03/27/1990 2939518.5 Osteoinductive Compositions CA
AHP-007CPEP 03/27/1990 90805830.7 Osteoinductive Compositions EP
AHP-007CPJP 03/27/1990 505549/90 Osteoinductive Compositions JP
AHP-007CPKR 03/27/1990 702523/90 Osteoinductive Compositions KR
AHP-007CPPC 03/27/1990 PCT/US90/01630 Osteoinductive Compositions PCT
AHP-008 US 09/24/1991 07/764,731 Methods for producing BMP-7s 5,366,875 11/22/1994 US
AHP-009 US 03/18/1991 655,579 BMP-2 Products Issued 5,618,924 04/08/1997 US
AHP-010 US 07/11/1989 07/387,537 DNA sequences encoding the
osteoinductive proteins Issued 5,166,058 11/24/1992
AHP-010AU 08/19/1994 78682 Neural Regeneration using Human
Bone Morphogenetic Proteins Issued 677866 05/08/1997 AU
Page 2 of 8
SCHEDULE E
Curis Patent Portfolio Licensed from American Home Products (Worldwide)
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-010CA 08/19/1994 2,169,191 Neural Regeneration using Human 05/08/1997 CA
Bone Morphogenetic Proteins
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-010CP2C2US 06/12/2001 09/804,625 BMP-4 Products Pending 06/12/2001 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-010CP2CUS 09/09/1997 08/925,779 BMP-4 Products Issued 6,245,889 06/12/2001 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-010CP2US 06/14/1991 07/721,847 BMP products Issued 6,150,328 11/21/2000 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-010EP 08/19/1994 94929728 Neural Regeneration using Human Pending 716610 05/08/1997 EP
Bone Morphogenetic Proteins
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-010FI 08/19/1994 960809 Neural Regeneration using Human Pending 05/08/1997 FI
Bone Morphogenetic Proteins
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-010JP 08/19/1994 507663 Neural Regeneration using Human Issued 9501932 T2 05/08/1997 JP
Bone Morphogenetic Proteins
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-010NO 08/19/1994 960711 Neural Regeneration using Human 05/08/1997 NO
Bone Morphogenetic Proteins
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-010OAPI 08/19/1994 60780 Neural Regeneration using Human 05/08/1997 OAPI
Bone Morphogenetic Proteins
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-010PC 08/19/1994 PCT/US94/09330 Neural Regeneration using Human Completed PCT
Bone Morphogenetic Proteins National
Stage
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-011 09/07/1993 118,363 Compositions comprising bone Issued 5,631,142 05/20/1997 US
morphogenetic protein -2 (BMP-2)
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-012 09/05/1997 08/927,124 BMP-3 Products Issued 6,177,406 01/23/2001 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-013 US 04/02/1991 07/679,451 Production of recombinant bone- Issued 5,318,898 06/07/1994 US
inducing proteins
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-013PC 03/27/1992 PCT/US92/02474 Improved production of PCT
recombinant bone-inducing proteins
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-014 US 01/27/1994 08/187,921 Production of bone-inducing Issued 5,516,654 05/14/1996 US
proteins
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-015 US 06/18/1990 07/539,756 Osteoinductive pharmaceutical Issued 5,364,839 11/15/1994 US
formulations
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-015AT 06/18/1991 Osteoinductive pharmaceutical AT
formulations
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-015CA 06/18/1991 2,085,750 Osteoinductive pharmaceutical CA
formulations
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-015CA 06/18/1991 2085750 Osteoinductive pharmaceutical 535091 CA
formulations
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-015DE 06/18/1991 91911720.1 Osteoinductive pharmaceutical 535091 DE
formulations
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-015DK 06/18/1991 91911720.1 Osteoinductive pharmaceutical 535091 DK
formulations
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-015EP 06/18/1991 91911720.1 Osteoinductive pharmaceutical 535091 EP
formulations
Page 3 of 8
SCHEDULE E
Curis Patent Portfolio Licensed from American Home Products (Worldwide)
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-015GB 06/18/1991 Osteoinductive pharmaceutical formulations GB
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-015JP 06/18/1991 511544/91 Osteoinductive pharmaceutical formulations JP
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-015PC 06/18/1991 PCT/US91/04337 Osteoinductive pharmaceutical formulations PCT
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-016 US 09/19/1994 08/308,787 Formulations for delivery of osteogenic proteins Issued 5,520,923 05/28/1996 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-016AU 07/24/1995 31042/95 Formulations for delivery of osteogenic proteins AU
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-016PC 07/24/1995 PCT/US95/09325 Formulations for delivery of osteogenic proteins PCT
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-017 US 12/07/1993 08/163,877 Mutants of bone morphogenetic proteins Issued 5,399,677 03/21/1995 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-017EP 11/15/1994 95903116.2 Mutants of bone morphogenetic proteins EP
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-017PC 11/15/1994 PCT/US94/13181 Mutants of bone morphogenetic proteins PCT
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-018 US 09/10/1993 08/119,772 Formulations for delivery of osteogenic proteins Issued 5,385,887 01/31/1995 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-018AU 09/02/1994 79537/94 Formulations for delivery of osteogenic proteins 695374B2 AU
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-018AU 09/02/1994 79537/94 Formulations for delivery of osteogenic proteins AU
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-018CA 09/02/1994 2,169,362 Formulations for delivery of osteogenic proteins CA
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-018EP 09/02/1994 961037 Formulations for delivery of osteogenic proteins EP
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-018FI 09/02/1994 961037 Formulations for delivery of osteogenic proteins FI
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-018JP 09/02/1994 508729 Formulations for delivery of osteogenic proteins 9502368T2 JP
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-018JP 09/02/1994 508729/1995 Formulations for delivery of osteogenic proteins JP
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-018KR 03/08/1996 701202/1996 Formulations for delivery of osteogenic proteins KR
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-018NO 09/02/1994 P960905 Formulations for delivery of osteogenic proteins NO
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-018PC 09/02/1994 PCT/US94/09870 Formulations for delivery of osteogenic proteins PCT
Page 4 of 8
SCHEDULE E
Curis Patent Portfolio Licensed from American Home Products (Worldwide)
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-019 US 10/11/1991 07/776,514 Formulations of blood clot-polymer
matrix for delivery of osteogenic
proteins 5,171,579 12/15/1992 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-019AU 10/09/1992 27885/92 Formulations of blood clot-polymer
matrix for delivery of osteogenic
proteins AU
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-019EP 10/09/1992 92921634.9 Formulations of blood clot-polymer
matrix for delivery of osteogenic
proteins 608313 EP
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-019JP 10/09/1992 507211/93 Formulations of blood clot-polymer
matrix for delivery of osteogenic
proteins JP
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-019KR 10/09/1992 701180/94 Formulations of blood clot-polymer
matrix for delivery of osteogenic
proteins KR
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-019MX 10/09/1992 92/5805 Formulations of blood clot-polymer
matrix for delivery of osteogenic
proteins MX
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-019PC 10/09/1992 PCT/US92/08628 Formulations of blood clot-polymer Completed
matrix for delivery of osteogenic National
proteins Stage PCT
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-020CPUS 05/05/1995 08/435,120 Neural regeneration using human
bone morphogenetic proteins Issued 5,756,457 05/26/1998 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-021CPAU 05/12/1994 69107 BMP-10 compositions Issued 677849 05/08/1997 AU
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-021CPBR 05/12/1994 9406716 BMP-10 compositions BR
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-021CPDiv 05/30/1995 08/453,942 Bone morphogenetic protein-10
(BMP-10) compositions Issued 5,703,043 12/30/1997 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-021CPDivCon 09/10/1997 08/926,885 Antibodies to bone morphogenetic
protein-10 (BMP-10) Issued 5,932,216 08/03/1999 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-021CPEP 05/12/1994 94917363 BMP-10 compositions 698095 EP
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-021CPFI 05/12/1994 955420 BMP-10 compositions FI
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-021CPJP 05/12/1994 525699 BMP-10 compositions 9501305 T2 02/10/1997 JP
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-021CPKR 05/12/1994 9574837 BMP-10 compositions 231640 B1 12/01/1999 JP
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-021CPNO 05/12/1994 954525 BMP-10 compositions NO
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-021CPOA 05/12/1994 60736 BMP-10 compositions OA
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-021CPPC 05/12/1994 PCT/US94/05290 BMP-10 compositions Completed
National
Stage PCT
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-021CPUS 05/20/1994 247,908 DNA molecules encoding bone
morphogenetic protein-10 Issued 5,637,480 06/10/1997
Page 5 of 8
SCHEDULE E
Curis Patent Portfolio Licensed from American Home Products (Worldwide)
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-021CPUS 05/20/1994 247,908 DNA molecules encoding bone Issued 5,637,480 06/10/1997
morphogenetic protein-10
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-022 CP3CUS 10/06/1994 08/319,831 Bone and cartilage inductive proteins Pending US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-022 CP3US 11/26/1991 07/800,364 Bone and cartilage inductive proteins Issued 5,688,678 11/18/1997 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-022AT 05/15/1991 9.19111E+13 Bone and cartilage inductive proteins Issued 12/15/2001 AT
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-022CA 05/15/1991 2082941 Bone and cartilage inductive proteins 12/15/2001 CA
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-022DE 05/15/1991 69132823 Bone and cartilage inductive proteins Issued 69132823 01/03/2002 DE
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-022EP 05/15/1991 91911807 Bone and cartilage inductive proteins Issued 536186 11/21/2001 EP
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-022JP 05/15/1991 510213 Bone and cartilage inductive proteins Issued 6500991 T2 01/27/1994 JP
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-022JPD 01/24/2001 2001016118 Bone and cartilage inductive proteins 2001245682 A2 01/27/1994 JP
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-022PC 05/15/1991 PCT/US91/03388 Bone and cartilage inductive proteins Completed PCT
National
Stage
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-023CP2CUS 06/06/1994 08/750,222 BMP-9 compositions Issued 6,034,061 03/07/2000 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-023CP2PC 06/05/1995 PCT/US95/07084 BMP-9 compositions Completed PCT
National
Stage
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-023CP2US 06/06/1994 08/254,353 BMP-9 compositions Issued 6,287,816 B1 09/11/2001 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-023CPUS 06/25/1992 08/050,132 BMP-9 compositions Issued 5,661,007 08/26/1997 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-023PC 06/25/1992 PCT/US92/05374 BMP-9 compositions Completed PCT
National
Stage
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-024EP 06/22/1992 92914339 Pharmaceutical formulations 591392B1 EP
of osteogeneic proteins
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-024PC 06/22/1992 PCT/US92/05309 Pharmaceutical formulations
of osteogenic proteins PCT
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-024US 06/22/1992 08/081,378 Pharmaceutical formulations Issued 5,597,897 01/28/1997 US
of osteogeneic proteins
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-025CP2CUS 06/06/1995 469,411 Recombinant bone morphogenetic 6,190,880 02/20/2001 US
protein heterodimers
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-025CP2US 11/27/1992 07/989,847 Recombinant bone morphogenetic protein Issued 5,866,364 02/02/1999 US
heterodimers, compositions and
methods of use
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-025PC 11/02/1992 PCT/US92/09430 Recombinant bone morphogenetic protein PCT
heterodimers, compositions and
methods of use
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-026CP4DivUS 808,324 Tendon-inducing compositions Issued 6,284,872 09/04/2001 US
Page 6 of 8
SCHEDULE E
Curis Patent Portfolio Licensed from American Home Products (Worldwide)
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-026CP4US 12/22/1994 362,670 Methods of inducing formation Issued 5,658,882 08/19/1997 US
of tendon and/or ligament
tissue comprising administering
BMP-12, BMp-13 and/or MP-52
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-026CP5US 11/02/1994 08/333,576 BMP-12 and BMP-13 proteins Issued 6,027,919 06,27,0919 US
and DNA encoding them
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-026PC 12/06/1994 PCT/US94/14030 BMP-12, BMP-13 and tendon- Completed PCT
inducing compositions National
thereof Stage
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-027 US 09/17/1993 08/123,934 Activin receptors-like Issued 6,291,206 09/18/2001 US
kinase (ALK) belonging
to the TGF receptor
family and/or the BMP
receptor family
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-027PC 09/07/1994 PCT/US94/10080 Activin receptors-like Completed
kinase (ALK) belonging National
to the TGF receptor Stage
family and/or the BMP
receptor family
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-028CPDiv 05/30/1995 452,772 BMP-11 compositions Issued 5,700,911 12/23/1997 PCT
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-028CPDivCPC2US 11/07/1997 919,850 Neuronal uses of BMP-11 Issued 6,340,668 01/22/2001 PCT
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-028CPUS 05/20/1994 08/247,907 BMP-11 compositions Issued 5,639,638 06/17/1997 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-028PC 05/12/1994 PCT/US94/05288 BMP-11 compositions Completed PCT
National
Stage
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-029PC 01/27/1995 PCT/US95/01110 Methods and compositions Completed PCT
for treatment of periodontal National
disease and repair of Stage
periodontal lesions
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-029US 01/27/1995 379,813 Methods and compositions PCT
for treatment of periodontal
disease and repair of
periodontal lesions
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-030 01/12/1994 PCT/US94/00657 GDF-5 Completed PCT
National
Stage
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-030 US 01/12/1994 455,559 GDF-5 Issued 5801014 09/01/1998 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-030 US 09/01/1998 145,060 GDF-5 Issued 6245896 06/12/2001 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-031 PC 07/08/1994 PCT/US94/07762 GDF-6 Completed US
National
Stage
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-031 US 04/15/1996 581,529 GDF-6 Issued 5,770,444 06/23/1998 US
- ------------------------------------------------------------------------------------------------------------------------------------
AHP-032 US 04/15/1996 581,528 GDF-7 Issued 5,986,058 11/16/1999 US
Page 7 of 8
SCHEDULE E
Curis Patent Portfolio Licensed from American Home Products (Worldwide)
- --------------------------------------------------------------------------------
AHP-032PC 07/08/1994 PCT/US94/07799 GDF-7 Completed PCT
National
Stage
- --------------------------------------------------------------------------------
Page 8 of 8
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
MATERIAL TRANSFER AGREEMENTS
- ------------------------------------------------------------------------------------------------------------------------------------
Burger, Elisabeth Academic Center for Dentistry Amsterdam MTA 9/6/91 Stryker; Dentin: Embryonic Long
bone development
- ------------------------------------------------------------------------------------------------------------------------------------
Minnear, Fred Albany Medical College MTA 4/20/98 Morphogens; Lung: lung cell-based
assays
- ------------------------------------------------------------------------------------------------------------------------------------
Minnear, Fred Albany Medical College MTA 10/1/98 Morphogens; Lung: cell-based
assays
- ------------------------------------------------------------------------------------------------------------------------------------
Mehler, Mark Albert Einstein Coll Medicine. MTA 3/31/94 Morphogens: in vivo studies on
cytokins, receptors and proteins
- ------------------------------------------------------------------------------------------------------------------------------------
Frenz, Dorothy Albert Einstein College of Medicine MTA 6/16/98 Morphogens; Ocular: role of BMPs
in otic capsule formation in the
mouse inner ear
- ------------------------------------------------------------------------------------------------------------------------------------
Laurencin, Cato Allegheny University Hospital MTA 9/30/97 Osteoporosis: effect of OP-1 on
cellular activity and phenotypic
expression of senescent
osteoblasts in osteoporosis
- ------------------------------------------------------------------------------------------------------------------------------------
MacPhee, Martin American Red Cross MTA 10/6/92 Morphogens; Wound healing: examine
the efficacy of Fibrin Sealant,
supplemented with PDGF-bb, EGF-1
or OP-1 in promoting wound healing
- ------------------------------------------------------------------------------------------------------------------------------------
Hruska, Keith Barnes Jewish Hospital MTA 3/13/97 Renal: Chronic failure & renal
osteodystrophy
- ------------------------------------------------------------------------------------------------------------------------------------
Hruska, Keith Barnes Jewish Hospital MTA 4/2/99 Renal: Chronic failure & renal
osteodystrophy - amendment to
expand sample
- ------------------------------------------------------------------------------------------------------------------------------------
Hruska, Keith Barnes Jewish Hospital MTA 11/28/01 Research pertaining to the
mechanisms of action of BMP-7 with
respect to preservation of renal
and vascular structure and
function in animal disease models
- ------------------------------------------------------------------------------------------------------------------------------------
Beresford, Jon Bath Institute MTA 6/29/94 Morphogens: regulation of MSX2
homeobox genes in transfected
cells
- ------------------------------------------------------------------------------------------------------------------------------------
Kim, Isaac Yi Baylor College MTA 3/11/99 Morphogens; Cancer: the role of
BMP-6 and morphogenic proteins in
the treatment of prostate and
other cancers - amendment
- ------------------------------------------------------------------------------------------------------------------------------------
Kim, Isaac Yi Baylor College MTA 3/4/98 Morphogens; Cancer: OP-1 in (renal
& prostate) carcinoma
- ------------------------------------------------------------------------------------------------------------------------------------
Morton, Ronald Baylor College of Medicine MTA 3/4/98 Morphogens; Cancer: OP-1 in
carcinomas (renal & prostate)
- ------------------------------------------------------------------------------------------------------------------------------------
Rosen, Jeffrey Baylor College of Medicine MTA 5/26/93 Morphogens: mammary glands
- ------------------------------------------------------------------------------------------------------------------------------------
Ratan, Rajiv Beth Israel Deaconess Hospital MTA 6/19/99 Neuro: The transcriptional
regulation of cell death and
survival factors in neuronal
cultures
- ------------------------------------------------------------------------------------------------------------------------------------
Sukhatme, Vikas Beth Israel Deaconess Hospital MTA 11/22/93 Renal: Delivery of OP-1 for
chronic renal disease
- ------------------------------------------------------------------------------------------------------------------------------------
Page 1 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Suva, Larry Beth Israel Deaconess Hospital MTA 3/22/93 Small Molecules: Characterization of
the cbfa1 gene promoter
- ------------------------------------------------------------------------------------------------------------------------------------
Hollenberg, Tony Beth Israel Deaconess Medical Center MTA 6/3/99 Morphogens: The role of morphogens in
the thyroid
- ------------------------------------------------------------------------------------------------------------------------------------
LaMont, J. Thomas Beth Israel Deaconess Medical Center MTA 4/27/99 Morphogen: Gastro: Role of morphogens
in intestinal inflammation
- ------------------------------------------------------------------------------------------------------------------------------------
Pothoulakis, Beth Israel Deaconess Medical Center MTA 6/19/99 Morphogens: Gastro: screen the BMPs in
Charalabos a model of bowel inflammation
- ------------------------------------------------------------------------------------------------------------------------------------
Muller-Beckmann, B. Boehringer Mannheim GmbH MTA 3/25/94 Osteoporosis: model systems
- ------------------------------------------------------------------------------------------------------------------------------------
Wulff, Karl Boerhringer Mannheim MTA 3/25/94
- ------------------------------------------------------------------------------------------------------------------------------------
Stafford, Walter Boston BioMedical Research Institute MTA 11/15/94 Formulations: Efforts to Characterize
the Physical State of OP-1 in
Solution: Effects of PH, Protein,
Buffer components
- ------------------------------------------------------------------------------------------------------------------------------------
- --------------- Boston Scientific Corporation MTA 9/22/99
- ------------------------------------------------------------------------------------------------------------------------------------
Farmer, Steve Boston University MTA 8/28/95 Morphogens: adipogenesis and
myogenesis and overall tissue
morphogenesis
- ------------------------------------------------------------------------------------------------------------------------------------
Graves, Dana Boston University MTA 3/25/99 Morphogens: adipogenesis and
myogenesis; effect of OP-1 on
osteoblastic cells (amendment)
- ------------------------------------------------------------------------------------------------------------------------------------
Graves, Dana Boston University MTA 11/8/95 Morphogens: adipogenesis
and myogenesis; effect of OP-1 on
osteoblastic cells
- ------------------------------------------------------------------------------------------------------------------------------------
Gerstenfeld, Louis Boston University Medical School MTA 2/1/00 Molecular Therapeutics: transcrptional
factors determining osteogenesis, for
use in developing BMP analogs for soft
tissue therapeutics
- ------------------------------------------------------------------------------------------------------------------------------------
Carlson, William Brandeis University MTA 10/30/92
- ------------------------------------------------------------------------------------------------------------------------------------
Carlson, William Brandeis University MTA 1/21/93 Small Molecule: Structure
determination of OP-1
- ------------------------------------------------------------------------------------------------------------------------------------
Ren, Ruibao Brandeis University MTA 2/20/98 Morphogens; Hematopoiesis: OP-1 in
hematopoiesis & leukemogenesis
- ------------------------------------------------------------------------------------------------------------------------------------
Sen, Ranjan Brandeis University MTA 6/1/98 Small Molecule: Plasmids and Extracts
- ------------------------------------------------------------------------------------------------------------------------------------
Maas, Richard Brigham & Woman's Hospital MTA 12/1/95 Morphogens; Ocular: OP-1 in ocular
development
- ------------------------------------------------------------------------------------------------------------------------------------
MacKenzie, Harold Brigham & Women's Hospital MTA 9/8/99 Renal: Effect of sBMP-7 treatment +/-
enalapril beginning 5 weeks after
5/6 nephrectomy
- ------------------------------------------------------------------------------------------------------------------------------------
Nigam, Sanjay Brigham & Women's Hospital MTA 6/19/96 Renal: nephrogenic differentiation
- ------------------------------------------------------------------------------------------------------------------------------------
Page 2 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Sayegh, Mohamed Hassan Brigham & Women's Hospital MTA 5/19/99 Renal: role of BMPs in the regulation of allo- and
auto-immune responses using in vitro and in vivo models
- ------------------------------------------------------------------------------------------------------------------------------------
Fausto, Nelson Brown University MTA 7/16/91 Morphogens; Liver: the role of OP-1 in liver cell
differentiation and liver regeneration
- ------------------------------------------------------------------------------------------------------------------------------------
Patterson, Paul CA Institute of Tech. MTA 10/16/95 Neuro: differentiate between dendrite bearing or
dendrite-less neurons & response to OP-1
- ------------------------------------------------------------------------------------------------------------------------------------
Garcia Castro, Martin California Institute of MTA 6/30/99 Morphogens: to the role of morphogens on the induction
Technology of Neural Crest cells during development
- ------------------------------------------------------------------------------------------------------------------------------------
Wise, Donald Cambridge Scientific Inc. MTA 5/12/93 Formulations: OP-1 and biodegradable polymers
- ------------------------------------------------------------------------------------------------------------------------------------
Lein, Pamela Canisius College MTA 8/14/97 Neuro: Dendritic growth in sympathetic neurons
- ------------------------------------------------------------------------------------------------------------------------------------
Ballock, R. Tracy Case Western Reserve MTA 6/2/95 Neuro: Effectiveness of OP-1 on the development of
University neurons in culture
- ------------------------------------------------------------------------------------------------------------------------------------
Hopfer, Ulrich Case Western Reserve MTA 2/2/00
University
- ------------------------------------------------------------------------------------------------------------------------------------
ten Dijke, Peter Catholic University MTA 2/16/94 Small Molecules: OP-1 receptors & interactions with
ligands
- ------------------------------------------------------------------------------------------------------------------------------------
D'Amore, Patricia Children's Hospital MTA 10/22/90 Morphogens: effect of OP-1 on cultured smooth muscle
cells, endothelial vessel cells, other cells
- ------------------------------------------------------------------------------------------------------------------------------------
D'Amore, Patricia Children's Hospital MTA 5/4/98 Morphogens: growth & differentiation factor effects on
vascular development
- ------------------------------------------------------------------------------------------------------------------------------------
D'Amore, Patricia Children's Hospital MTA 9/22/88
- ------------------------------------------------------------------------------------------------------------------------------------
D'Amore, Patricia Children's Hospital MTA 7/28/98 Morphogens: growth & differentiation factor effects on
vascular development
- ------------------------------------------------------------------------------------------------------------------------------------
Golden, Jeff Children's Hospital - MTA 9/16/98 Morphogens; Development: the role of OP-1 in the
Philadelphia developing chick embryo on dorsal-ventral patterning
of the forebrain
- ------------------------------------------------------------------------------------------------------------------------------------
Greenberg, Michael Children's Hospital-Boston MTA 10/9/97 Neuro: role of OP-1 in growth and differentiation
- ------------------------------------------------------------------------------------------------------------------------------------
Harris, William Children's Hospital-Boston MTA 11/1/93 Renal: IMCD cells (MTA); Role of OP-1 in kidney and
brain (SRA)
- ------------------------------------------------------------------------------------------------------------------------------------
Hauschka, Peter Children's Hospital-Boston MTA 9/11/90 Osteoporosis: Basic research on the mechanisms of
Osteogenic protein action in bone
- ------------------------------------------------------------------------------------------------------------------------------------
Klagsbrun, Michael Children's Hospital-Boston MTA 12/10/98 Morphogens: Effect of BMPs on the expression of
neuropilin in a number of cell types including
endothelial, tumor and neuronal cells
- ------------------------------------------------------------------------------------------------------------------------------------
Kreidber, Jordan Children's Hospital-Boston MTA 11/6/95 Morphogens: In situ hybridization /test for OP-1
expression in WT-1 mutant embryos
- ------------------------------------------------------------------------------------------------------------------------------------
Page 3 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Smith, Lois Children's Hospital-Boston MTA 12/2/98 Ocular: the role of OP-1 and related morphogens in
ocular repair and regeneration during development and
disease
- ------------------------------------------------------------------------------------------------------------------------------------
Kohtz, Jhumku Children's Memorial Institute MTA 4/27/99 Morphogen: the role of BMPs in forebrain development
for Education and Research
- ------------------------------------------------------------------------------------------------------------------------------------
Muschler, George Cleveland Clinic Foundation MTA 2/7/94 Stryker: effect of OP-1 in the isolation of
osteoblastic cells from primary bone aspirates
- ------------------------------------------------------------------------------------------------------------------------------------
Nawa, Hiroyuki Cold Spring Harbor Lab MTA 3/7/95 Neuro: factors regulating neuronal plasticity in
developing brain
- ------------------------------------------------------------------------------------------------------------------------------------
Svoboda, Karel Cold Spring Harbor Laboratory MTA 6/19/99 Neuro: to the effects of BMPs on the dynamics of
dendritic spine and filopodia formation/retraction in
hippocampal neurons
- ------------------------------------------------------------------------------------------------------------------------------------
Le Douarin, Nicole College de France MTA 4/26/98 Morphogens: embryological development
- ------------------------------------------------------------------------------------------------------------------------------------
Chen, Theresa College of Notre Dame MTA 3/9/98 Osteoporosis: OP-1 & Skeleton Aging
- ------------------------------------------------------------------------------------------------------------------------------------
Chen, Theresa College of Notre Dame MTA 1/27/98 Osteoporosis: OP-1 & Skeleton Aging
- ------------------------------------------------------------------------------------------------------------------------------------
Barasch, Jon Columbia University MTA 8/29/96 Renal: role of OP-1 in nephrogenic induction
- ------------------------------------------------------------------------------------------------------------------------------------
Dodd, Jane Columbia University MTA 3/20/98 Neuro: role of OP-1, BMP-6 and GDF's in neurogenesis,
in particular forebrain patterning in central nervous
system & axonal guidance in spinal cord
- ------------------------------------------------------------------------------------------------------------------------------------
Jessell, Thomas Columbia University (Howard MTA 9/16/96 Neuro: role of OP-1 in neural tube induction and
Hughes Institute) differentiation
- ------------------------------------------------------------------------------------------------------------------------------------
Beall, Melissa Cornell University MTA 9/22/99 Molecular Therapeutics: Analysis of Schistomsoma
mansoni TGF-B-like type I receptor SmRK1 and it's
role in BMP signalling
- ------------------------------------------------------------------------------------------------------------------------------------
Silver, Randi Cornell University MTA 10/21/96 Renal: role of OP-1 on ion transport and acid/base
balance in the principal and inercalated cells of
cortical collecting duct
- ------------------------------------------------------------------------------------------------------------------------------------
Pearce, Edward J. Cornell University, College of MTA 9/22/99 Research on Schistomsoma mansoni TGF-Beta-like
Veterinary Medicine receptor, SmRK1, and the potential role of these
factors as ligands for the parasite receptor
- ------------------------------------------------------------------------------------------------------------------------------------
Gee, Connie Dana Farber Cancer Institute MTA 3/25/91 Small Molecule: effect of OP-1 on pp60c-src protein
tryrosine kinase activity in macrophage cultures -
isolation of OP-1 receptors
- ------------------------------------------------------------------------------------------------------------------------------------
Franzen, Asa Dept. of Genetics & Pathology, MTA 3/13/00 : BMP-7 cDNAs pertaining to BMP expression in
Unit of Pathology, Rudbecklab, anaplastic thyroid carcinoma cell lines
Uppsala Sweden
- ------------------------------------------------------------------------------------------------------------------------------------
Page 4 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
- --------------- Diacrin, Inc. MTA 8/15/99 Morphogens: the expansion of liver cell lines in
vitro for therapeutic uses
- ------------------------------------------------------------------------------------------------------------------------------------
- --------------- Diacrin, Inc. MTA 8/15/99 Morphogens: expansion of liver cell lines in vitro
for therapeutic uses
- ------------------------------------------------------------------------------------------------------------------------------------
Dean, Richard Diatech, Inc. MTA 11/26/90 Morphogens: in vivo imaging of target tissues in
animal models
- ------------------------------------------------------------------------------------------------------------------------------------
Quarles, L. Darryl Duke University Medical MTA 8/18/93 Morphogens: role of OP-1 in ostoeblast cell lines and
Center helix-loop-helix proteins
- ------------------------------------------------------------------------------------------------------------------------------------
Wang, Xiao-Fan Duke University Medical MTA 10/10/95 Small Molecules: signal pathways of TGF-B superfamily
Center members
- ------------------------------------------------------------------------------------------------------------------------------------
Prochiantz, Alain Ecole Normale Superieure MTA 10/20/98 Small Molecule: Role of BMPs in regulation of
homeogene expression during neuronal development
- ------------------------------------------------------------------------------------------------------------------------------------
- --------------- Eli Lilly and Company MTA 7/31/98 Neuro: Stroke studies
- ------------------------------------------------------------------------------------------------------------------------------------
Benedetti, Luca Fidia Advanced Biopolymers MTA 2/8/93 Formulations: hyaluronic acid polymers
- ------------------------------------------------------------------------------------------------------------------------------------
- --------------- Fisions Applied Sensor MTA 11/11/93 Assay development: development of assays to
Technologies quatntiate OP-1
- ------------------------------------------------------------------------------------------------------------------------------------
Bernstein, Erwin Fred Hutchinson Cancer Center MTA 6/10/94 Morphogens: hemopoietic stem cells
- ------------------------------------------------------------------------------------------------------------------------------------
Funa, Keiko Goteborg University MTA 7/29/99 Neuro: The effect of morphogens on dopaminergic
neurons in culture and in animal models of
Parkinson's Disease (amendment for expanded sample)
- ------------------------------------------------------------------------------------------------------------------------------------
Funa, Keiko Goteborg University MTA 6/18/99 Neuro: The effect of morphogens on dopaminergic
neurons in culture and in animal models of
Parkinson's Disease
- ------------------------------------------------------------------------------------------------------------------------------------
Funa, Keiko Goteborg University, Institute MTA 12/28/00 To use BMP in rat model of Parkinson's Disease
of Anatomy and Cell Biology
- ------------------------------------------------------------------------------------------------------------------------------------
Kojima, Itaru Gunma University MTA 11/25/97 Renal: OP-1 on the tubulogenesis of the kidney
- ------------------------------------------------------------------------------------------------------------------------------------
Davis, Kevin Hammersmith Hospital MTA 3/25/93
- ------------------------------------------------------------------------------------------------------------------------------------
Shoskes, Daniel Harbor-UCLA Medical Center MTA 2/3/00 Renal: studies on the effect of BMP-7 in established
models of oxidant stress
- ------------------------------------------------------------------------------------------------------------------------------------
Bignami, Amico Harvard Medical School MTA 10/9/90 Neuro: localization of OP-1 and BMP-2 in nerve tissue
- ------------------------------------------------------------------------------------------------------------------------------------
Hollenbeck, Peter Harvard Medical School MTA 7/26/96 Neuro: intracellular transport in neurons
- ------------------------------------------------------------------------------------------------------------------------------------
Lassar, Andrew Harvard Medical School MTA 12/22/98 Morphogens: role of BMPs in somite chondrogenesis of
the developing chick embryo
- ------------------------------------------------------------------------------------------------------------------------------------
Tabin, Cliff Harvard Medical School MTA 12/22/98 Morphogens: Role of GDF5 and GDF6 in bone development
and limb patterning in the developing chick
- ------------------------------------------------------------------------------------------------------------------------------------
Page 5 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Whitman, Malcolm Harvard Medical School MTA 12/22/98 Small Molecule: the role of BMP's in the regulation
or modification of cell specification and
differentiation during frog embryogenesis
- ------------------------------------------------------------------------------------------------------------------------------------
Whitman, Malcom Harvard Medical School MTA 1/4/01 Role of BMP signaling in frog embryos
- ------------------------------------------------------------------------------------------------------------------------------------
Robertson, Elizabeth Harvard University MTA 10/11/99 Morphogens: Use of BMP-7/LacZ Transgenic Mouse for
characterization of OP-1 expression and screening
of morphogen analogs
- ------------------------------------------------------------------------------------------------------------------------------------
Robertson, Elizabeth Harvard University MTA 8/22/95 Morphogens: effects of OP-1 during embryonic
development
- ------------------------------------------------------------------------------------------------------------------------------------
Robertson, Elizabeth Harvard University MTA 12/8/98 Morphogens: Use of BMP-7/LacZ Transgenic Mouse for
characterization of OP-1 expression and screening
of morphogen analogs
- ------------------------------------------------------------------------------------------------------------------------------------
Bar-Shavit, Zvi Hebrew University MTA 9/28/93 Osteoporosis: Modulation of proenkephalin expression
in osteoblasts
- ------------------------------------------------------------------------------------------------------------------------------------
Rao, D. Sudhaker Henry Ford Hospital MTA 11/15/95 Renal: study OP-1 as marker of renal osteodystrophy
and renal function
- ------------------------------------------------------------------------------------------------------------------------------------
Lechleider, Robert Henry M. Jackson MTA 6/17/99 Small Molecules: The role of Smads in vascular and
Foundation for hematopoietic biology
Advancement of
Military Medicine
- ------------------------------------------------------------------------------------------------------------------------------------
Rosenblum, Norman Hospital for Sick MTA 12/2/98 Renal: Role of OP-1 in branching morphogenesis
Children during kidney development - amendment
- ------------------------------------------------------------------------------------------------------------------------------------
Rosenblum, Norman Hospital for Sick MTA 1/26/96 Renal: Role of OP-1 in branching morphogenesis
Children during kidney development
- ----------------------------------------------------------------------------------------------------------------------------------
Wrana, Jeff Hospital for Sick MTA 7/10/95 Small Molecule: OP-1 signaling pathways; smads;
Children Amendment to NDA 12/3/97
- ------------------------------------------------------------------------------------------------------------------------------------
Pelletier, Jean-Pierre Hospital Notre-Dame MTA 10/18/88 Cartilage: involvement of metalloprotease in the
destruction of the extracellular matrix of human
osteoarthritis cartilage (TIMP gene)
- ------------------------------------------------------------------------------------------------------------------------------------
Miralles, F. Hospital Robert Debre MTA 11/23/97 Morphogens: OP-1 in pancreatic differentiation
- ------------------------------------------------------------------------------------------------------------------------------------
Goff, Stephen Howard Hughes Medical MTA 8/28/98 Morphogens; Hematopoesis: the role of Abelson
Institute/Columbia tyrosine kinase in response to BMP's
University
- ------------------------------------------------------------------------------------------------------------------------------------
Vander Eynder-Van Hubrecht Laboratory MTA 3/20/95 Morphogens: role of OP-1 in mouse mesoderm induction
Raay, A.J.M. using tissue culture studies
- ------------------------------------------------------------------------------------------------------------------------------------
Binderman, Itzhak ICHILOV Hospital MTA 3/5/91 Dental: Role of OP-1 in tooth regeneration in dogs
- ------------------------------------------------------------------------------------------------------------------------------------
Massey, Richard IGEN, Inc MTA 6/10/96 Process Development: receipt of materials to
quantitate matrix containing bovine OP-1
- ------------------------------------------------------------------------------------------------------------------------------------
Page 6 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Wharton, John Imperial College of Medicine MTA 10/5/00 To study the effects of BMP-4 and BMP-7 on the
pulmonary artery smooth muscle cells derived from
patients with primary and secondary pulumonary
hypertension and controls
- ------------------------------------------------------------------------------------------------------------------------------------
Broxmeyer, Hal Indiana University MTA 6/2/99 Morphogens: Hematopoesis: Role of morphogens on
hematopoietic precursor cells in vitro
- ------------------------------------------------------------------------------------------------------------------------------------
Chen, Yan Indiana University School of MTA 6/2/99 Small Molecule: the involvement of Smads in morphogen
Medicine signaling and the development morphogens for soft
tissue applications
- ------------------------------------------------------------------------------------------------------------------------------------
Ronco, P. Inserm U64-Hopit Tevon MTA 10/19/95 Renal: OP-1 pattern expression in human glomerular
defects
- ------------------------------------------------------------------------------------------------------------------------------------
Sautier, Jean-Michel Institut Biomedical des MTA 1/6/99 Small Molecule: phenotypic changes in response to
Cordeliers BMPs for the purpose of developing screening assays
for BMP activity in soft tissue applications
- ------------------------------------------------------------------------------------------------------------------------------------
Mallein-Gerin, Institut de Biologie et Chimie MTA 1/25/96 Morphogens: role of OP-1 in immortilized cell lines
Frederic des Proteines
- ------------------------------------------------------------------------------------------------------------------------------------
Nifuji, Akira Institut Pasteur MTA 12/10/92 Morphogens: role of OP-1 in the differentiation of
osteogenic / chondrogenic C1 cells
- ------------------------------------------------------------------------------------------------------------------------------------
Querol, Sergie Institute de Recerca Oncologica MTA 6/28/99 Morphogen: The role of morphogens in proliferation
and differentiation of stem cells
- ------------------------------------------------------------------------------------------------------------------------------------
Krokan, Hans Institute of Cancer Research MTA 2/8/00 Morphogens:cancer: To study the role of BMP's
and Molecular Biology induction of apoptosis and growth arrest of myeloma
cells
- ------------------------------------------------------------------------------------------------------------------------------------
Ishii, Shunsuke Institute of Phy.& Chem. MTA 1/16/96 Small Molecules: role of OP-1 on several
Research, Riken Tsukuba transcription factors involved in cellular growth
Center control
- ------------------------------------------------------------------------------------------------------------------------------------
Bovolenta, Paola Instituto Cajal MTA 6/5/98 Morphogens; Ocular: Effect of OP-1 on expression of
Otx2 in retina
- ------------------------------------------------------------------------------------------------------------------------------------
Tokunaga, Hideo Iwate Medical University MTA 3/19/01 Expression of BMP-7 in Human Renal Cell Carcinomal
Cell Lines
- ------------------------------------------------------------------------------------------------------------------------------------
Johnson, Ken Jackson Research Lab MTA 3/28/95 Morphogens: OP-1 cDNA probes
- ------------------------------------------------------------------------------------------------------------------------------------
Jos van Kampen, G.P. Jan van Breemen Inst MTA 9/10/93 Cartilage: in vitro model of osteoarthritis
- ------------------------------------------------------------------------------------------------------------------------------------
Shimomura, Ryuichi Japan Tobacco Inc. MTA 6/3/94 Osteoporosis: model systems
- ------------------------------------------------------------------------------------------------------------------------------------
Miyazono, Kohei Japanese Foundation for MTA 12/16/98 Small Molecules: BMP receptors (amendment)
Cancer Research
- ------------------------------------------------------------------------------------------------------------------------------------
Miyazono, Kohei Japanese Foundation for MTA 9/26/96 Small Molecules: BMP receptors
Cancer Research
- ------------------------------------------------------------------------------------------------------------------------------------
Page 7 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Lein, Pamela Johns Hopkins MTA 5/26/99 Neuro: The role of morphogens in dendrite formation
- ------------------------------------------------------------------------------------------------------------------------------------
Campochiaro, Peter Johns Hopkins Hospital MTA 10/22/98 Morphogens; Ocular: The role of morphogens in
ocular pathologies
- ------------------------------------------------------------------------------------------------------------------------------------
Adler, Ruben Johns Hopkins University MTA 4/15/99 Morphogens; Ocular: Role of BMPs in retinal
development
- ------------------------------------------------------------------------------------------------------------------------------------
Racusen, Lorraine Johns Hopkins University MTA 8/30/95 Morphogens: Adeno-12 SV40 HPT (from Johns Hopkins)
- ------------------------------------------------------------------------------------------------------------------------------------
Reddi, A.H. Johns Hopkins University MTA 7/13/92 Stryker and Osteoporosis: femoral head study
- ------------------------------------------------------------------------------------------------------------------------------------
Rothstein, Jeffery Johns Hopkins University MTA 5/25/99 Neuro: The role of Morphogens in the treatment of ALS
- ------------------------------------------------------------------------------------------------------------------------------------
Shapiro, Jay Johns Hopkins University MTA 5/9/94 Osteoporosis: effects of hOP-1 on control osteoblasts
and osteoblasts from patients with osteogenesis
- ------------------------------------------------------------------------------------------------------------------------------------
Sakou, Takashi Kagoshima University MTA 4/14/95 Osteoporosis: expression of OP-1 and receptors in
OPLL patients
- ------------------------------------------------------------------------------------------------------------------------------------
Sakou, Takashi Kagoshima University MTA 3/16/98 Osteoporosis: mechanism of fracture healing and bone
formation with regards osteoporosis and other
metabolic bone diseases
- ------------------------------------------------------------------------------------------------------------------------------------
Lee, Chang-Ho Kangnung National University MTA 2/10/96 Osteoporosis: osteoblast differentiation
- ------------------------------------------------------------------------------------------------------------------------------------
Kouegawa, Junick Kirin Brewery Co., Ltd. MTA 11/11/93 Osteoporosis: model systems
- ------------------------------------------------------------------------------------------------------------------------------------
Sakamoto, Choitsu Kobe University School of MTA 6/27/96 Morphogens; Gastrointestinal: role of OP-1 in
Medicine mechanism of GI ulcer healing; follistatin-like cell
surface OP-1 binding protein
- ------------------------------------------------------------------------------------------------------------------------------------
Abe, Shin-ichi Kumamoto University MTA 2/8/00 Renal: BMP-7 and BMP-6 to be used to test activity on
the testes by using in vitro culture system.
- ------------------------------------------------------------------------------------------------------------------------------------
Kitamoto, Yasunori Kumamoto University MTA 12/8/97 Renal: OP-1 in metanephric mesenchyme differentiation
to glomerulogenesis
- ------------------------------------------------------------------------------------------------------------------------------------
Ito, Yoshiaki Kyoto University MTA 11/12/98 Small Molecule: PEBP2aA/Cbfa1 expression in
osteoblast progenitors and osteoblasts in vitro and
in vivo
- ------------------------------------------------------------------------------------------------------------------------------------
Nijweide, Peter Lab. of Cell Biol. & Hist. MTA 11/8/91 Cartilage: effect of OP-1 on osteoclast formation and
the differentiation of osteoblasts, cartilage cells
and osteocytes in vitro
- ------------------------------------------------------------------------------------------------------------------------------------
Wall, Nancy Lawrence University MTA 2/28/98 Morphogens: the effects of BMP-7 on differentiation,
cell proliferation and apoptosis of 1st and 2nd
branchial arch mesenchyme in chick embryos
- ------------------------------------------------------------------------------------------------------------------------------------
McColl, Shaun Le Centre Hospitalier MTA 8/16/91 Morphogens: expression of OP-1 by synoviocytes
- ------------------------------------------------------------------------------------------------------------------------------------
Baylink, David Loma Linda University MTA 1/24/92 Osteoporosis: development of serum assays to assess
bone metabolism;
- ------------------------------------------------------------------------------------------------------------------------------------
Page 8 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Baylink, David Loma Linda University MTA 10/1/90 Osteoporosis: role of OP-1 on the growth and
maintenance of human osteoblasts in vitro
- ------------------------------------------------------------------------------------------------------------------------------------
Bidani, Anil K. Loyola University-Chicago, VA MTA 1/8/97 Renal: role of OP-1 in the mechanisms of
Hospital @ Hines progressive glomerular injury and nephron
loss
- ------------------------------------------------------------------------------------------------------------------------------------
ten Dijke, Peter Ludwig Institute for Cancer MTA 8/3/93 Small Molecule: Alks cDNA's
Research
- ------------------------------------------------------------------------------------------------------------------------------------
ten Dijke, Peter Ludwig Institute for Cancer MTA 10/13/92 Small Molecule: TGFb receptors & signalling
Research molecules; binding assays on cells
transfected with clones
- ------------------------------------------------------------------------------------------------------------------------------------
Heinegard, Dick Lund University MTA 1/29/96 Morphogens: interaction between OP-1 and
matrix proteins
- ------------------------------------------------------------------------------------------------------------------------------------
Karsenty, Gerard M.D. Anderson Cancer Center MTA 10/11/96 Use of morphogenic proteins, BMP-2,3,6,7,8
and GDF 5,6, and 7 in experimental studies
relating to osteoblast differentiation.
- ------------------------------------------------------------------------------------------------------------------------------------
Thorlacius, Henrik Malmo University Hospital MTA 8/8/98 Morphogens; Angiogenesis: Role of BMP on
angiogenesis in vitro
- ------------------------------------------------------------------------------------------------------------------------------------
Thorlacius, Henrik Malmo University Hospital MTA 7/18/98 Morphogens; Angiogenesis: Role of BMP on
angiogenesis in vitro
- ------------------------------------------------------------------------------------------------------------------------------------
- --------------- Marion Merrell Dow MTA 5/5/93 Osteoporosis: model systems
- ------------------------------------------------------------------------------------------------------------------------------------
Behar, Oded Massachusetts General MTA 12/15/97 Morphogens: Interactions between semaphorins
Hospital and BMPs
- ------------------------------------------------------------------------------------------------------------------------------------
Bonventre, Joseph Massachusetts General MTA 10/10/91 Renal: Role of OP-1 in recovery from acute
Hospital renal failure
- ------------------------------------------------------------------------------------------------------------------------------------
DiFiglia, Marian Massachusetts General MTA 3/18/93 Neuro: localization of OP-1 expression in the
Hospital brain and it's role in neuronal growth
(Huntington's & Parkinson's disease)
- ------------------------------------------------------------------------------------------------------------------------------------
Drummond, Iain Massachusetts General MTA 12/19/97 Renal: Kidney development in fish
Hospital
- ------------------------------------------------------------------------------------------------------------------------------------
Finklestein, Seth Massachusetts General MTA 7/17/91 Neuro: role of OP-1 in stroke/brain injury
Hospital
- ------------------------------------------------------------------------------------------------------------------------------------
Katagiri, Take Massachusetts General MTA 4/1/98 Osteoporosis: endochondral
Hospital ossification/interaction with PTHrP & PTH
- ------------------------------------------------------------------------------------------------------------------------------------
Schneyer, Alan Massachusetts General MTA 4/16/96 Morphogens: role of OP-1 in tissue formation
Hospital and embryonic development
- ------------------------------------------------------------------------------------------------------------------------------------
Wang, Tongwen Massachusetts General MTA 12/9/97 Small Molecule: Characterization of signal
Hospital transduction pathway of OP-1 & activation of
signaling proteins such as Smads & Myx
- ------------------------------------------------------------------------------------------------------------------------------------
Page 9 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF FFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Sklar, Robert Massachusetts General MTA 10/10/91 Morphogens: effect of BMP's on human muscle
Hospital-East development in vitro
- ------------------------------------------------------------------------------------------------------------------------------------
Schneider, Gerald Massachusetts Institute of MTA 3/3/93 Neuro: axon regeneration
Technology
- ------------------------------------------------------------------------------------------------------------------------------------
Rohrer, Hermann Max-Planck Institute for Brain MTA 1/3/94 Neuro: sympathetic neurons
Research
- ------------------------------------------------------------------------------------------------------------------------------------
Rohrer, Hermann Max-Planck Institute for Brain MTA 3/15/99 Neuro: sympathetic neurons - (amendment)
Research
- ------------------------------------------------------------------------------------------------------------------------------------
Kessel, Michael Max-Planck-Institut fur MTA 5/31/99 Neuro: role of BMPs in neural plate development
Biophysikalische Chemie
- ------------------------------------------------------------------------------------------------------------------------------------
Bolander, Mark Mayo Clinic MTA 8/1/91 Stryker: expression of OP-1 in the fracture callous
- ------------------------------------------------------------------------------------------------------------------------------------
Schwartz, Robert Mayo Clinic MTA 7/20/94 Morphogens; Cardiovascular: effect of OP-1 in pig
coronary arteries and myocardium injuries
- ------------------------------------------------------------------------------------------------------------------------------------
Kumar, Rajiv Mayo Foundation MTA 12/15/95 Renal: chronic renal failure animal models
- ------------------------------------------------------------------------------------------------------------------------------------
Riggs, B. Lawrence Mayo Foundation MTA 12/18/98 Osteoporosis: Effect of BMPs in models of
osteoporosis using a conditionally immortalized
human marrow stromal cell line
- ------------------------------------------------------------------------------------------------------------------------------------
de Crommbrugge, MD Anderson Cancer Center MTA 1/15/92 Small Molecule: TGFb receptors
Benoit
- ------------------------------------------------------------------------------------------------------------------------------------
Pavenstadt, Hermann Med. Universitatesklinik MTA 2/28/01 Study involves work on the biological role of
Freiburg, Department of podocytes, the effects of OP-1 on podocytes function
Nephrology by stimulating podocytes with OP-1 and perform cDNA
expression analysis, and whether OP-1 prevents
proteinuria in a mouse model of glomerulonephritis
- ------------------------------------------------------------------------------------------------------------------------------------
Lucas, Paul Medical Center-Central GA MTA 5/7/92
- ------------------------------------------------------------------------------------------------------------------------------------
Abd-Al-Fattah, Anwar Medical College of VA MTA 11/11/91 Morphogens; Cardiovascular: cardiac myocyte
regeneration
- ------------------------------------------------------------------------------------------------------------------------------------
Wornom, Isaac Medical College of VA MTA 9/18/90 Stryker; Cranio-facial: effect of OP-1 on onlay bone
grafts to the facial skeleton in rabbits
- ------------------------------------------------------------------------------------------------------------------------------------
Furley, Placzek Medical Research Council MTA 11/29/94 Morphogens: induction of floorplate by notochord
- ------------------------------------------------------------------------------------------------------------------------------------
Triffitt, James Medical Research Council MTA 4/2/91 Osteoporosis: role of OP-1 in bone differentiation
- ------------------------------------------------------------------------------------------------------------------------------------
Nakaoka, Takashi Medical University of South MTA 9/10/97 Morphogens; Cardiovascular: vascular smooth muscle
Carolina proliferation
- ------------------------------------------------------------------------------------------------------------------------------------
Massague, Joan Memorial Sloan-Kettering MTA 7/9/93 Small Molecule: Small Molecule: TGFb Receptors
- ------------------------------------------------------------------------------------------------------------------------------------
Page 10 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Detmer, Kristina Mercer University School MTA 7/27/99 Morphogens: the effects of morphogens on the
of Medicine differentiation of human hematopoietic progenitor cells
- ------------------------------------------------------------------------------------------------------------------------------------
Detmer, Kristina Mercer University School MTA 4/30/96 Morphogens: role of OP-1 in skin development
of Medicine
- ------------------------------------------------------------------------------------------------------------------------------------
Young, Henry Mercer University School MTA 3/25/92
of Medicine
- ------------------------------------------------------------------------------------------------------------------------------------
Rodan, Gideon Merck & Co., Inc. MTA 2/10/94 Osteoporosis: model systems
- ------------------------------------------------------------------------------------------------------------------------------------
Seyfried, Christoph Merck KgaA Biomedical MTA 6/19/00 : evaluation of mBMP-7 in stroke models
Research
- ------------------------------------------------------------------------------------------------------------------------------------
Paredes, Ana Miami Children's Hospital MTA 6/10/98 Renal: effect of rhOP-1 in bone cells from
Research Institute children with chronic renal failure
- ------------------------------------------------------------------------------------------------------------------------------------
Paredes, Ana Miami Children's Hospital MTA 8/27/97 Renal: effect of OP-1 on acute renal failure
Research Institute
- -----------------------------------------------------------------------------------------------------------------------------------
Khouri, Roger Miami Hand Center MTA 8/28/96 Cartilage: repair of bone and cartilage
- ------------------------------------------------------------------------------------------------------------------------------------
Miles, Inc., Miles Inc. MTA 1/11/93 Osteoporosis: model systems
- ------------------------------------------------------------------------------------------------------------------------------------
Hobson, Grace Namours Research MTA 11/25/95 Osteoporosis: Effect of OP-1 on the treatment of
certain bone diseases characterized by abnormal bone
growth
- ------------------------------------------------------------------------------------------------------------------------------------
Covarrubias, Luis National Autonomous Univ. MTA 8/12/98 Morphogens: Effect of BMPs on cell proliferation,
of Mexico differentiation and survival using model systems of
EFG responsive neuro progenator cells and epidermal cells
- ------------------------------------------------------------------------------------------------------------------------------------
Ruscetti, Francis National Cancer Institute MTA 11/13/90
- ------------------------------------------------------------------------------------------------------------------------------------
Liang, Tony National Institute for Aging MTA 12/12/95 Osteoporosis: Ability of OP-1 to induce osteoblast
lineage in marrow ablation models
- ------------------------------------------------------------------------------------------------------------------------------------
Ueno, Naoto National Institute for Basic MTA 10/23/98 Small Molecule: Determination of binding constant
Biology of OP-1 to follistatin by surface plasm on resonance
- ------------------------------------------------------------------------------------------------------------------------------------
Smith, James National Institute for Medical MTA 3/22/94 Morphogens: Effect of OP-1 in it's ability to induce
Research mesoderm
- ------------------------------------------------------------------------------------------------------------------------------------
Donkersloot, Jacob / National Institute of Dental MTA 12/13/95 Cartilage: Production of recombinant cartilage-derived
Luyten, Frank Research morphogenetic proteins and evalution of their biological
functions
- ------------------------------------------------------------------------------------------------------------------------------------
Kopp, Jeffrey National Institute of Health MTA 6/1/98 Renal: Role of OPs in renal development and
disease - amendment
- ------------------------------------------------------------------------------------------------------------------------------------
Kopp, Jeffrey National Institute of Health MTA 4/22/99 Renal: Over-expression of BMP7 in the liver modulates
hepatocyte proliferation or recovery of differentiated
function following partial hepatectomy
- ------------------------------------------------------------------------------------------------------------------------------------
Page 11 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Kopp, Jeffrey National Institute of Health MTA 10/5/96 Renal: Role of OPs in renal
development and disease
- ------------------------------------------------------------------------------------------------------------------------------------
Kneller, Robert National Institute of Health, NCI MTA 12/26/95 Osteoporosis: Effect of OP-1
in stimulating bone
formation and differentiation
- ------------------------------------------------------------------------------------------------------------------------------------
Donovan, Peter NCI: Advanced Bioscience Lab., Inc. MTA 7/1/98 Renal: The effects of OP-1 on
embryonic mysenchymal tubual
differentiation
- ------------------------------------------------------------------------------------------------------------------------------------
Scharp, David Neocrin Company MTA 10/4/96 Assay development:
Encapsulated cells
- ------------------------------------------------------------------------------------------------------------------------------------
ten dijke, Peter Netherlands Cancer Institute MTA 8/28/02 Molecular Therapeutics:
characterization of BMP
signaling path
- ------------------------------------------------------------------------------------------------------------------------------------
ten dijke, Peter Netherlands Cancer Institute MTA 5/16/00 Molecular Therapeutics:
characterization of BMP
signaling path
- ------------------------------------------------------------------------------------------------------------------------------------
Pereira, Miercio New England Medical Center MTA 10/13/95 Small Molecules: OP-1 and
activin signalling in
trypanosome invasion of cells
- ------------------------------------------------------------------------------------------------------------------------------------
Newman, Stuart New York Medical Coll MTA 4/13/92 Morphogens: role of OP-1 on
limb-bud mesenchymal
differentiation with respect
to pattern formation
- ------------------------------------------------------------------------------------------------------------------------------------
LeRoux, Peter New York University MTA 8/11/97 Neuro: role of OP-1in neurons
in culture
- ------------------------------------------------------------------------------------------------------------------------------------
Fishell, Gordon New York University Medical Center MTA 7/21/98 Morphogens: the role of OP-1
in development &
regionalization of
telencephalon
- ------------------------------------------------------------------------------------------------------------------------------------
Nawa, Hiroyuki Nigata University MTA 7/24/95 Neuro: factors regulating
neuronal plasticity in
developing brain
- ------------------------------------------------------------------------------------------------------------------------------------
Roberts, Anita NIH MTA 8/13/98 Small Molecule: Target gene
regulation by BMP-7
- ------------------------------------------------------------------------------------------------------------------------------------
Miller, William North Carolina State University MTA 12/4/98 Small Molecule: role of BMPs
in stimulating follicle-
stimulating hormone expression
- ------------------------------------------------------------------------------------------------------------------------------------
Stern, Paula Northwestern University MTA 12/16/94 Osteoporosis: Role of OP-1 in
remodeling
- ------------------------------------------------------------------------------------------------------------------------------------
Woodruff, Teresa Northwestern University MTA 9/13/99 Morphogens, Reproduction: the
mechanism of BMP regulation of
FSH expression in the
pituitary.
- ------------------------------------------------------------------------------------------------------------------------------------
Sauter, Andre Novartis Pharma AG MTA 2/23/99 Neuro: Novartis's internal
evaluation of the use of OP-1
in Novartis's stroke model
- ------------------------------------------------------------------------------------------------------------------------------------
Hollinger, Jeffrey Oregon Health Sciences University MTA 6/5/98 Morphogens; Liver: OP-1 in
hepatic repair & regeneration
- ------------------------------------------------------------------------------------------------------------------------------------
Hollinger, Jeffrey Oregon Health Sciences University MTA 8/19/98 Morphogens; Liver: OP-1 in
hepatic repair & regeneration
- ------------------------------------------------------------------------------------------------------------------------------------
Hollinger, Jeffrey Oregon Health Sciences University MTA 3/23/98 Morphogens; Liver: OP-1 in
hepatic repair & regeneration
- ------------------------------------------------------------------------------------------------------------------------------------
Withers, Ginger Oregon Health Sciences University MTA 5/13/99 Neuro: the role of morphogens
in the expression of dendritic
and synaptic structural
plasticity
- ------------------------------------------------------------------------------------------------------------------------------------
Page 12 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Komori, Toshihisa Osaka University Medical MTA 5/16/97 Osteoporosis: Role of OP-1 in osteogenesis
School
- ------------------------------------------------------------------------------------------------------------------------------------
Gordon, Neal Perseptive Biosystems MTA 4/7/94 Assay Development: Construction of affinity columns
- ------------------------------------------------------------------------------------------------------------------------------------
Flowers, John Protein Polymer Technologies MTA 1/21/94 Morphogens: Extracellular matrix components for hard
and soft tissue repair and regeneration
- ------------------------------------------------------------------------------------------------------------------------------------
Ashton, Brian R. Jones & A. Hunt Hospital MTA 3/19/92 Osteoporosis: Role of OP-1 in marrow differentiation
and marrow induced endochondral bone formation in vivo
- ------------------------------------------------------------------------------------------------------------------------------------
Essery, John R.W. Johnson Pharmaceutical MTA 3/14/94 Osteoporosis: model systems for bone and mineral
Res. Institute metabolism
- ------------------------------------------------------------------------------------------------------------------------------------
Bizios, Rena Rensselaer Polyt Institute MTA 10/13/93 Osteoporosis: Role of OP-1 on osteoblast proliferation
and cell population motility on substrates modified
with covalently-bound bioactive, adhesive peptides.
- ------------------------------------------------------------------------------------------------------------------------------------
Schwartz, Edith Rhode Island Hospital MTA 12/19/91 Osteoporosis: Study the effects of OP-1 on osteoblast
cell lines
- ------------------------------------------------------------------------------------------------------------------------------------
Rivas, Miriam Rockefeller University MTA 7/13/98 Morphogens: the role of OP-1 in psoriatic skin
- ------------------------------------------------------------------------------------------------------------------------------------
McK. Ciombor, Deborah Roger Williams Hospital MTA 1/5/94 Morphogens: mesenchymal cell differentition
- ------------------------------------------------------------------------------------------------------------------------------------
Rehbein, Steven Roswell Park Cancer Institute MTA 1/14/94 Morphogens; Hematopoiesis: differentiation of
hemopoietic progenitor cells in vitro
- ------------------------------------------------------------------------------------------------------------------------------------
Chester, Kerry Royal Free Hospital MTA 1/16/95 Cancer: tumor imaging
- ------------------------------------------------------------------------------------------------------------------------------------
Kruse, Friedrich Ruprecht-Karls-Universitat MTA 7/5/98 Morphogens; Ocular: Role of OP-1 and BMP-5 in cornea
Heidelberg development
- ------------------------------------------------------------------------------------------------------------------------------------
Kuettner, Klaus Rush-Presb-St. Luke's MTA 5/3/93 Cartilage: role of OP-1 in cell metabolism and
differentiation of chondrocytes or modulation of their
phenotype
- ------------------------------------------------------------------------------------------------------------------------------------
Wientroub, Shlomo Sackler School of Medicine MTA 3/8/92 Morphogens: Effect of OP-1 mouse marrow celll ines
- ------------------------------------------------------------------------------------------------------------------------------------
Tschannen, Ronald Sandoz Pharma Ltd. MTA 4/14/94 Osteoporosis: models systems
- ------------------------------------------------------------------------------------------------------------------------------------
Saeki, Masanori Sankyo Co., Ltd. MTA 11/1/93 Osteoporosis: models systems
- ------------------------------------------------------------------------------------------------------------------------------------
Halpain, Shelley Scripps Research Institute MTA 10/22/98 Neuro: the effect of BMPs on MAP2 and the dendritic
cytoskelton
- ------------------------------------------------------------------------------------------------------------------------------------
- --------------- Shield Diagnostics Ltd MTA 1/19/94 Assay Development: development of assays to quantitate
OP-1
- ------------------------------------------------------------------------------------------------------------------------------------
Walsh, Kenneth St. Elizabeth's Medical Center MTA 11/17/98 Morphogens; Cardiac: Effect of BMPs on pressure
overload cardiac hypertrophy
- ------------------------------------------------------------------------------------------------------------------------------------
Page 13 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF FFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Martin, Kevin St. Louis University MTA 4/22/99 Renal: studies on the relationship between BMP
expression and circulating levels and metabolic bone
pathologies seen in renal disease, for the purpose
of generating systemic therapies for osteoporosis
- ------------------------------------------------------------------------------------------------------------------------------------
Martin, Kevin St. Louis University MTA 3/18/99 Renal: studies on the relationship between BMP
expression and circulating levels and metabolic bone
pathologies seen in renal disease, for the purpose
of generating systemic therapies for osteoporosis
- ------------------------------------------------------------------------------------------------------------------------------------
Barres, Barbara Stanford University MTA 9/20/95 Neural: development of neuronal and glial cells in
culture
- ------------------------------------------------------------------------------------------------------------------------------------
Hsueh, Aaron Stanford University Medical Center MTA 4/21/99 Morphogen: the effects of BMPs on ovarian follicle
development
- ------------------------------------------------------------------------------------------------------------------------------------
Cho, Moon-Il State University of New York at MTA 6/10/99 Small Molecule: the development of in vitro assays
Buffalo using periodontal ligament fibroblast cell lines, to
facilitate the development of soft tissue
applications for CDMPs
- ------------------------------------------------------------------------------------------------------------------------------------
Rohrer, Lucia Swiss Federal Institute of MTA 8/5/98 Morphogens: Role of BMPs in blood vessel formation
Technology Zurich by endothelial cells
- ------------------------------------------------------------------------------------------------------------------------------------
Brand, Thomas Technische University Brschwg MTA 10/4/95 Morphogens; Cardiovascular: early heart dev.
- ------------------------------------------------------------------------------------------------------------------------------------
Ishizuka, Seiichi Teijin Institute MTA 8/23/94 Osteoporosis: role of OP-1 in bone formation by
vitamin D3 analogues in vitro and in vivo
- ------------------------------------------------------------------------------------------------------------------------------------
Bleiberg, Ilan Telaviv University/Sackler School MTA 12/23/93 Morphogens: effects of OP-1 on clonal cell lines of
of Medicine DBM implants
- ------------------------------------------------------------------------------------------------------------------------------------
Sires, Bryan The Eye Institute MTA 6/24/93 Ocular: role of OP-1 in choriodal osetomas in eyes
- ------------------------------------------------------------------------------------------------------------------------------------
Oakley, Robert The George Washington University MTA 8/11/99 Morphogens: Studies on cell death in the developing
Medical Center chick limb
- ------------------------------------------------------------------------------------------------------------------------------------
Hirschberg, Raimund The Harbor-UCLA Research & Education MTA 3/27/00 Renal: The role of BMP's in renal interstitial
Institute fibrosis
- ------------------------------------------------------------------------------------------------------------------------------------
Bhatia, Mick The John P. Robarts Research MTA 10/19/98 Morphogens; Hematopoiesis: the role of BMP's in
Institute hematopoiesis
- ------------------------------------------------------------------------------------------------------------------------------------
Bhatia, Mick The John P. Robarts Research MTA 2/16/98 Morphogens; Hematopoiesis: the role of BMP's in
Institute hematopoiesis
- ------------------------------------------------------------------------------------------------------------------------------------
Rutherford, Bruce The Regents of the University of MTA 4/16/02 OP-1 in an assay of the Osteoblastic conversion of
Michigan fibroblasts in response to secreted OP-1
- ------------------------------------------------------------------------------------------------------------------------------------
Choe, Senyon The Salk Institute MTA 4/27/00 BMP-7: To ascertain the structure of BMP-7
associated with Type II receptors.
- ------------------------------------------------------------------------------------------------------------------------------------
Page 14 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Johnson, Mary The University of Arizona MTA 1/18/99 The study of the ability of OP-1 to reverse the
effect of ethanol, nicotine and barbituates on
dendritic branching
- ------------------------------------------------------------------------------------------------------------------------------------
Sharma, Kumar Thomas Jefferson University MTA 10/15/98 Morphogens; Renal: role of BMPs in diabetic kidney
disease
- ------------------------------------------------------------------------------------------------------------------------------------
Ohtaka, Akihiko Tohoku University School of MTA 7/23/98 Renal: the role of OP-1 in tubulogenesis of
Medicine metanephric mesenchyme and glomerulogenesis in
animal models of nephritis
- ------------------------------------------------------------------------------------------------------------------------------------
Nifuji, Akira Tokyo Medical and Dental MTA 8/19/98 Morphogens: Patterning in development
Institute
- ------------------------------------------------------------------------------------------------------------------------------------
Asahina, Izumi Tokyo Medical/Dental MTA 12/27/93 Osteogenesis: OP-1 induced endochondral
University osteogenesis model system in vitro
- ------------------------------------------------------------------------------------------------------------------------------------
Noda, Masaki Tokyo Medical/Dental MTA 8/26/93 Osteoporosis: effects of OP-1 on bone metabolism
University
- ------------------------------------------------------------------------------------------------------------------------------------
Noda, Masaki Tokyo Medical/Dental MTA 7/8/98 Osteoporosis: Differentiation & Determination of
University Skeletal Tissue Using Mouse Cells & Chicken Embryo
- ------------------------------------------------------------------------------------------------------------------------------------
Albertini, David Tufts University School of MTA 8/2/99 Morphogen: reproduction: The role of morphogens in
Medicine ovarian function
- ------------------------------------------------------------------------------------------------------------------------------------
Libby, Peter Tufts University School of MTA 1/5/88 Morphogens; Cardiovascular: PDGH
Medicine
- ------------------------------------------------------------------------------------------------------------------------------------
Hata, Akiko Tufts University School of MTA 2/14/01 Studies of regulation of BMP target genes through
Medicine OAZ protein involved in the BMP-4 dependent gene
expression.
- ------------------------------------------------------------------------------------------------------------------------------------
Hata, Akiko Tufts University School of MTA-Amendment 3/18/02 Studies of regulation of BMP target genes through
Medicine OAZ protein involved in the BMP-4 dependent gene
expression.
- ------------------------------------------------------------------------------------------------------------------------------------
Bermek, Engin Turkish Sci Tech Res Institute MTA 10/5/93 Morphogens: mice embryos
- ------------------------------------------------------------------------------------------------------------------------------------
Maxian, Suzanne UMD, New Jersey MTA 4/11/94 Formulations: evaluate resorbable hydroxyapatite
coatings in osteointegration studies
- ------------------------------------------------------------------------------------------------------------------------------------
Zeevalk, Gail UMDNJ-Robert Wood Johnson MTA 2/7/00 Neuro: the effects of BMPs on the metabolic
Med. School processes and phenotype in cultured dopaminergic
ventral midbrain neurons (relating to Parkinson's
Disease)
- ------------------------------------------------------------------------------------------------------------------------------------
Boitani, Carla Universita di Roma "La MTA 7/13/98 Morphogens: Role of BMPs on Sertoli cell and
Sapienza" spermatogonial cell proliferation and
differentiation
- ------------------------------------------------------------------------------------------------------------------------------------
Luyten, Frank Universitaire Ziekenhuizen MTA 8/17/98 Osteoporosis: the role of OP-1 and related BMP's
Leuven in osteoporosis
- ------------------------------------------------------------------------------------------------------------------------------------
Ambrosio, Santiago Universitat de Barcelona MTA 4/25/96 Neuro: role of OP-1 in promoting survival of
fetal mesencephalic cells
- ------------------------------------------------------------------------------------------------------------------------------------
Page 15 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Reiriz, Julia Universitat de Barcelona MTA 7/2/98 Neuro: Effect of BMPs as protective agents against
excitotoxicity in primary neuronal cultures
- ------------------------------------------------------------------------------------------------------------------------------------
Ventura, Francesc Universitat de Barcelona MTA 1/18/99 Small Molecule: studies on the effect of BMPs on the
transcriptional regulation of the junB and TIEG
promoters differentiation of C2C12 cells
- ------------------------------------------------------------------------------------------------------------------------------------
Thomsen, G.H. University at Stony Brook MTA 3/24/95 Morphogens: role of OP-1 in Xenopus development
- ------------------------------------------------------------------------------------------------------------------------------------
Shepard, Pierre University Clinic of Cologne MTA 7/26/00 Research pertaining to research on wound healing in
the skin using mice as a model, focusing on the
expression of BMPs and their receptors during the
healing process
- ------------------------------------------------------------------------------------------------------------------------------------
Murphy, Madeline University College of Dublin MTA 1/8/01 Examine the ability of BMP-7 to modulate gremlin
function in primary human mesangial and primary human
renal proximal tubular cells, for studying
pathological mechanisms in diabetic neuropathy
- ------------------------------------------------------------------------------------------------------------------------------------
Hurle, Juan University de Cantabria, MTA 6/28/95 Morphogens: analyzing mechanisms accounting for
Facultad de Med Avda., establishment of interdigital spaces in the chick leg
bud
- ------------------------------------------------------------------------------------------------------------------------------------
Hurle, Juan University de Cantabria, MTA 9/17/98 Morphogens: role of BMPs in chick limb skeletogenesis
Facultad de Med Avda.,
- ------------------------------------------------------------------------------------------------------------------------------------
Johnson, Mary University of Arizona MTA 2/10/99 Neuro: study of the ability of OP-1 to reverse the
effects of ethanol, nicotine and barbituates on
dendritic branding
- ------------------------------------------------------------------------------------------------------------------------------------
Szivek, John University of Arizona MTA 11/17/93 Morphogens: techniques for attaching strain gauges
- ------------------------------------------------------------------------------------------------------------------------------------
Szivek, John University of Arizona Health MTA 11/17/93 Osteoporosis: techniques for attaching strain gauges
Sciences Ctr.
- ------------------------------------------------------------------------------------------------------------------------------------
Gaddy-Kurten, Dana University of Arkansas MTA 12/16/96 Morphogens: Role of OP-1 in bone cell differentiation
- ------------------------------------------------------------------------------------------------------------------------------------
Higgins, Dennis University of Buffalo, State MTA 12/16/93 Neuro: role of OP-1 in sympathetic neurons
University of New York
- ------------------------------------------------------------------------------------------------------------------------------------
Szabo, Sandor University of CA-Irvine MTA 2/3/95
- ------------------------------------------------------------------------------------------------------------------------------------
Cross, James University of Calgary MTA 2/26/01 Research pertaining to the testing of OP-1 effects in
vitro sing murine and human placental trophoblast
cell and tissue culture systems
- ------------------------------------------------------------------------------------------------------------------------------------
Reddi, A.H. University of California, Davis MTA 9/8/98 Morphogens: tissue regeneration & morphogenesis
- ------------------------------------------------------------------------------------------------------------------------------------
Horie, Kuniko University of California, MTA 4/17/98 Morphogens: role of OP-1 in C2C12 myoblasts
San Diego
- ------------------------------------------------------------------------------------------------------------------------------------
Shimasaki, Shunichi University of California, MTA 11/5/98 Morphogens: the effect of OP-1 on the control of
San Diego ovarian follicle growth
- ------------------------------------------------------------------------------------------------------------------------------------
Page 16 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Shanahan, Catherine University of Cambridge MTA 12/11/98 Morphogens: BMP expression in vascular
smooth muscle cells
- ------------------------------------------------------------------------------------------------------------------------------------
Roberts, Veronica University of CA-SD MTA 4/23/97 Small molecule: pax-6 expression in
immortalized immature pituitary cell
lines
- ------------------------------------------------------------------------------------------------------------------------------------
Mobley, William University of CA-SF MTA 11/19/97 Neuro: in vitro/in vivo studies
- ------------------------------------------------------------------------------------------------------------------------------------
Kelly, Katrina University of Cincinnati MTA 7/31/96 Renal: role of OP-1 in kidney disease
- ------------------------------------------------------------------------------------------------------------------------------------
Hoffer, Barry University of Colorado MTA 10/5/94 Neuro: role of OP-1 in spinal cord
injury
- ------------------------------------------------------------------------------------------------------------------------------------
Hoffman, Stephen University of Colorado MTA 10/8/93 Morphogens: effects of OP-1 on
melanoma cells and keratinocytes
- ------------------------------------------------------------------------------------------------------------------------------------
Fouty, Brian University of Colorado Health MTA 12/19/00 Studies involve proliferation of
pulmonary artery smooth muscle cells
in response to hypoxia and mitogens,
and the effects of BMP-7 on smooth
muscle cell proliferation in the
pulmonary circulation
- ------------------------------------------------------------------------------------------------------------------------------------
Bickford, Paula University of Colorado Health Science Center MTA 9/24/97 Neuro: Parkinson's Disease
- ------------------------------------------------------------------------------------------------------------------------------------
Granholm-Bentley, University of Colorado Health Science Center MTA 9/23/97 Neuro: effects of OP-1 on motoneurons
Ann-Charlotte
- ------------------------------------------------------------------------------------------------------------------------------------
Rutherford, Bruce University of Conn. Health Center. MTA 12/20/90 Dental: effect of OP-1 on ROS,
periodontal ligament fibroblast and
pulp fibroblast cell cultures
- ------------------------------------------------------------------------------------------------------------------------------------
Maxwell, Gerald University of Connecticut MTA 4/27/93 Neuro: the mechanism of precursor
cells development
- ------------------------------------------------------------------------------------------------------------------------------------
Brandi, Maria University of Florence MTA 8/16/91 Morphogens: effect of OP-1 on growth
and differentiation of bone
endothelial cells
- ------------------------------------------------------------------------------------------------------------------------------------
Brandt, Roland University of Heidelberg MTA 6/3/98 Neuro: mechanisms of dendritic
sprouting in cultured human neurons
- ------------------------------------------------------------------------------------------------------------------------------------
Solursh, Michael University of Iowa MTA 7/6/90 Morphogens: cellular responses of
cultured mesenchymal cells to OP-1
- ------------------------------------------------------------------------------------------------------------------------------------
Maenpaa, P. University of Kuopio MTA 11/26/92 Morphogens: regulation of osteocalcin
synthesis in cultured human
osteosarcoma cells by steroid hormones
and related vitamins
- ------------------------------------------------------------------------------------------------------------------------------------
Ferguson, Mark University of Manchester MTA 8/20/96 Morphogens: role of OP-1 and related
proteins to augment wound repair in
fetus and post-fetal life
- ------------------------------------------------------------------------------------------------------------------------------------
Greenberger, Joel University of Massachusetts Medical Center MTA 7/1/91 Morphogens: effect of OP-1 on bone
marrow cell differentiation in vitro
- ------------------------------------------------------------------------------------------------------------------------------------
Rusckowski, Mary University of Massachusetts Medical Center MTA 2/4/98 Morphogens: Biodistribution of Tc-OP-1
in normal mice
- ------------------------------------------------------------------------------------------------------------------------------------
Page 17 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Dietrich, W.D. University of Miami MTA 8/11/98 Neuro: traumatic brain
injury models
- ------------------------------------------------------------------------------------------------------------------------------------
Dietrich, W.D. University of Miami MTA 3/4/97 Neuro: traumatic brain
injury models
- ------------------------------------------------------------------------------------------------------------------------------------
Paredes, Ana University of Miami MTA 11/30/94 Renal: role of OP-1 in renal
models
- ------------------------------------------------------------------------------------------------------------------------------------
Franceschi, Renny University of Michigan MTA 5/18/00
- ------------------------------------------------------------------------------------------------------------------------------------
Franceschi, Renny University of Michigan MTA 5/29/92
- ------------------------------------------------------------------------------------------------------------------------------------
Franceschi, Renny University of Michigan MTA 9/28/93 Osteoporosis: expresssion of
osteoblast phenotypes in
vitro
- ------------------------------------------------------------------------------------------------------------------------------------
Oegema, Theodore University of Minnesota MTA 11/18/88 Morphogens: herniated disk
model of osteogenesis
- ------------------------------------------------------------------------------------------------------------------------------------
Sanders, Michel University of Minnesota MTA 12/15/98 Morphogens: examining the
differential expression of
OP-1 in diverse tissues in
the chicken
- ------------------------------------------------------------------------------------------------------------------------------------
McKee, Marc University of Montreal MTA 7/29/93 Morphogens: role of OP-1 in
bone cell differentiation
- ------------------------------------------------------------------------------------------------------------------------------------
Nanci, Antonio University of Montreal MTA 7/29/93 Morphogens: role of OP-1
- ------------------------------------------------------------------------------------------------------------------------------------
Echevarria, Diego University of Murcia MTA 4/30/99 Neuro: the role of morphogens
in the early regionalization
of the forebrain
- ------------------------------------------------------------------------------------------------------------------------------------
Cooper, Lyndon University of N. Carolina MTA 4/8/94 Morphogens: OP-1 in
osteoblastic cells for wound
healing
- ------------------------------------------------------------------------------------------------------------------------------------
Sartor, R. Balfour University of North Carolina at Chapel Hill MTA 3/29/99 Morphogens; Gastro: role of
BMP-6 and morphogenic
proteins in the treatment of
inflammatory bowel disease -
amendment to expand Sample
- ------------------------------------------------------------------------------------------------------------------------------------
Sartor, R. Balfour University of North Carolina at Chapel Hill MTA 12/11/98 Morphogens; Gastro: effects
of OP-1 on intestinal
epithelial cell proliferation
- ------------------------------------------------------------------------------------------------------------------------------------
Sartor, R. Balfour University of North Carolina at Chapel Hill MTA 1/29/99 Morphogens; Gastro: role of
BMP-6 and morphogenic
proteins in the treatment of
inflammatory bowel disease -
amendment
- ------------------------------------------------------------------------------------------------------------------------------------
Langille, Robert University of Ottawa MTA 8/15/95 Morphogens: role of OP-1 in
mandibular development
- ------------------------------------------------------------------------------------------------------------------------------------
Vaananen, Kalvervo University of Oulu MTA 11/2/90 morphogens: effect of OP-1 in
osteoclast mediated bone
resorption
- ------------------------------------------------------------------------------------------------------------------------------------
Emerson, Charles University of Pennsylvania MTA 12/15/95 Morphogens: Cell culture
model for study of MyoD
regulation
- ------------------------------------------------------------------------------------------------------------------------------------
Leboy, Phoebe University of Pennsylvania MTA 8/16/91 Osteoporosis: Osteoblast
differentiation: effect of
OP-1 on rat stromal cell
cultures
- ------------------------------------------------------------------------------------------------------------------------------------
Fabisiak, James University of Pittsburg MTA 1/30/92 Morphogens: ability of OP-1
to protect the lung after
oxidant-induced injury in rat
model
- ------------------------------------------------------------------------------------------------------------------------------------
Patel, Ketan University of Reading MTA 7/30/99 Molecular Therapeutics: role
of BMPs in the development
and positioning of the muscle
masses during chick limb and
thorax development
- ------------------------------------------------------------------------------------------------------------------------------------
O'Keefe, Regis University of Rochester MTA 3/11/99 Small Moleucle: the role of
BMPs in limb patterning
signaling
- ------------------------------------------------------------------------------------------------------------------------------------
Lee, Amy University of S. California MTA 3/12/92 Production: GRP78 producing
CHO cell line
- ------------------------------------------------------------------------------------------------------------------------------------
Page 18 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Wuthier, Roy University of S. Carolina MTA 7/18/91 Cartilage: effect of OP-1 on avian growth plate
chondrocytes in vitro
- ------------------------------------------------------------------------------------------------------------------------------------
Andrews, Peter University of Sheffield MTA 2/24/93 Morphogens: cancer: role of OP-1 in the
de-differentiation of human transformed cells
- ------------------------------------------------------------------------------------------------------------------------------------
Nishimoto, S. Ken University of Tennessee MTA 11/11/92 Morphogens: effects of OP-1 on the regulation of MGP
synthesis in chondrosarcoma, chondrocytes, osteoblasts
and kidney cells
- ------------------------------------------------------------------------------------------------------------------------------------
Raghow, Rajendra University of Tennessee MTA 3/15/91 Renal: effect of OP-1 and BMP-2A on type I collagen gene
expression in synovial, dermal & pulmonary mesenchymal
cells in vitro
- ------------------------------------------------------------------------------------------------------------------------------------
Abboud, Hanna University of Texas MTA 11/20/94 Renal: role of OP-1 in kidney function
- ------------------------------------------------------------------------------------------------------------------------------------
D'Souza, Rena University of Texas MTA 3/15/94 Morphogens: recombinant OP-1, monoclonal and polyclonal
antibodies, cDNA probes to hard tissue repair
- ------------------------------------------------------------------------------------------------------------------------------------
Olson, Merle (cbm University of Texas MTA 7/8/96 Renal: role of OP-1 in kidney
refusd)
- ------------------------------------------------------------------------------------------------------------------------------------
Talpaz, Moshe University of Texas MTA 5/3/93 Cancer: de-differentiation of transformed cells
- ------------------------------------------------------------------------------------------------------------------------------------
Venkatachalam, M. A. University of Texas MTA 1/6/97 Small Molecule: expression of pax-2
- ------------------------------------------------------------------------------------------------------------------------------------
Yoneda, Toshiyuki University of Texas MTA 10/24/95 Morphogens; Cancer: role of OP-1 on cancer metastasis
- ------------------------------------------------------------------------------------------------------------------------------------
Jester, James University of Texas MTA 7/8/99 Morphogens: Role of morphogens on corneal keratocyte
Southwestern Medical Center differentiation and growth in in vitro models of corneal
wound healing
- ------------------------------------------------------------------------------------------------------------------------------------
Karsenty, Gerard University of Texas, MD MTA 10/26/94 Morphogens: BMP's in development
Anderson Cancer Center
- ------------------------------------------------------------------------------------------------------------------------------------
Nagarajan, Lalitha University of Texas, MD MTA 12/8/98 Small Molecule: Smad5 response to BMPs
Anderson Cancer Center
- ------------------------------------------------------------------------------------------------------------------------------------
Noji, Sumihare University of Tokushima MTA 10/18/95 Morphogens: function of OP-1 in limb bud formation, role
of shh
- ------------------------------------------------------------------------------------------------------------------------------------
Asashima, Makoto University of Tokyo MTA 11/27/97 Renal: tissue differentiation
- ------------------------------------------------------------------------------------------------------------------------------------
Kurabayashi, Masahiko University of Tokyo MTA 3/3/97 Morphogens: Cardiovascular
- ------------------------------------------------------------------------------------------------------------------------------------
Yamashita, Hidetoshi University of Tokyo MTA 11/25/94 Morphogens; Ocular: effects of OP-1 on ocular tissue
- ------------------------------------------------------------------------------------------------------------------------------------
Sodek, Jaro University of Toronto MTA 11/13/92 Osteoporosis: in vivo induction of bone formation
- ------------------------------------------------------------------------------------------------------------------------------------
Page 19 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
EFFECTIVE
DATE OF
PRINCIPAL TYPE OF ORIGINAL
INVESTIGATOR INSTITUTE AGREEMENT AGREEMENT FIELD OF AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Sodek, Jaro University of Toronto MTA 10/15/98 Osteoporosis: in vivo induction of bone formation -
amendment
- ------------------------------------------------------------------------------------------------------------------------------------
Harkonen, Pirkko University of Turku MTA 11/23/93 Morphogens; Cancer: effects and expression of OP-1 in
human breast and prostate cancer cell lines
- ------------------------------------------------------------------------------------------------------------------------------------
Rao, Mahendra University of Utah Medical MTA 5/12/99 Neuro: stem cell differentiation in the nervous system
Center
- ------------------------------------------------------------------------------------------------------------------------------------
Erlacher, Ludwig University of Vienna MTA 5/5/98 Cartilage: Postnatal human articular chondrocytes &
other in vitro cell-based assays
- ------------------------------------------------------------------------------------------------------------------------------------
Balian, Gary University of Virginia MTA 3/13/91 Osteoporosis: effect of OP-1 on clonal bone marrow
stromal cell lines
- ------------------------------------------------------------------------------------------------------------------------------------
Banker, Gary University of Virginia MTA 8/18/95 Neuro: role of OP-1 on Dendritic outgrowth
- ------------------------------------------------------------------------------------------------------------------------------------
Phillips, Aled University of Wales College of MTA 1/2/00 Renal: studies on renal mechanism of action
Medicine
- ------------------------------------------------------------------------------------------------------------------------------------
Hauschka, Stephen University of Washington MTA 7/28/93 Morphogens: role of OP-1 in muscle differentiation and
regeneration
- ------------------------------------------------------------------------------------------------------------------------------------
Reh, T.A. University of Washington MTA 11/19/98 Morphogens; Ocular: role of BMPs in auditory function
- ------------------------------------------------------------------------------------------------------------------------------------
Reh, T.A. University of Washington MTA 7/23/97 Morphogens; Ocular: role of BMP's in formation of
vertebrate eye during embryonic development
- ------------------------------------------------------------------------------------------------------------------------------------
Stone, Jennifer University of Washington MTA 2/25/98 Morphogens; Auditory: OP-1 in regeneration of sensory
tissues in the ear
- ------------------------------------------------------------------------------------------------------------------------------------
Stone, Jennifer University of Washington MTA 5/25/99 Morphogens; Auditory: OP-1 in regeneration of sensory
tissues in the ear (amended to expand Sample)
- ------------------------------------------------------------------------------------------------------------------------------------
Thomas, Regi University of Washington MTA 2/10/98 Morphogens; Cancer: Role of OP-1 in prostate cancer
- ------------------------------------------------------------------------------------------------------------------------------------
D'Souza, Sudhir University of Western Ontario MTA 4/7/00 Renal: To examine the role of BMP-7 in an in vitro
model of proximal tubule injury
- ------------------------------------------------------------------------------------------------------------------------------------
Hoffmann, Michael University of Wisconsin MTA 1/17/94 Morphogens: role of dpp/BMP family in Drosophila
development
- ------------------------------------------------------------------------------------------------------------------------------------
Baas, Peter University of Wisconsin, MTA 7/26/96
Madison School of Medicine
- ------------------------------------------------------------------------------------------------------------------------------------
Fallon, John University of Wisconsin-Madison MTA 4/14/99 Morphogens: the role of BMPs in the pattern formation
- ------------------------------------------------------------------------------------------------------------------------------------
Ripamonti, Ugo University of Witwatersrand MTA 7/22/94 Stryker: craniofacial reconstruction
- ------------------------------------------------------------------------------------------------------------------------------------
Vukicevic, Slobodan University of Zagreb MTA 2/5/98 Renal/Stryker/Cartilage/Osteoporosis/Morphogens: Role
of BMP's in the regulation of bone mass
- ------------------------------------------------------------------------------------------------------------------------------------
Page 20 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Vukicevic, Slobodan University of Zagreb MTA 7/22/91 Renal/Stryker/Cartilage/Osteoporosis/Morphogens:
Localization of OP-1 and related BMPs on human fetal
sections and the induction of second messengers in
chondrocytes and osteoblasts in vitro
- ------------------------------------------------------------------------------------------------------------------------------------
Vukicevic, Slobodan University of Zagreb MTA 4/20/98 Renal/Stryker/Cartilage/Osteoporosis/Morphogens:
Role of BMP-3 in inductin of mesonephric mesenchyme
and the development of fetal lungs
- ------------------------------------------------------------------------------------------------------------------------------------
Vukicevic, Slobodan University of Zagreb MTA 7/14/98 Renal/Stryker/Cartilage/Osteoporosis/Morphogens:
Role of BMP-6 in kidney development and repair
- ------------------------------------------------------------------------------------------------------------------------------------
Vukicevic, Slobodan University of Zagreb MTA 7/14/98 Renal/Stryker/Cartilage/Osteoporosis/Morphogens:
The role of morphogens and growth factors in the
prevention/repair or gastro-intestinal disorders
- ------------------------------------------------------------------------------------------------------------------------------------
Mohler, Hanns University of Zurich/ MTA 8/15/98 Neuro: to the role of OP-1 in enhancing the
Institute of Pharmacology regenerative plasticity of epileptogenic tissue in
vivo
- ------------------------------------------------------------------------------------------------------------------------------------
Wong, Sui-Lam University Technologies MTA 9/14/92 Morphogens: WB600 strain; THEIRS
International Inc.
- ------------------------------------------------------------------------------------------------------------------------------------
Ebendal, Ted Uppsala Universitet MTA 12/9/96 Neuro: neuro/ocular: role of OP-1 in retinal neurons
- ------------------------------------------------------------------------------------------------------------------------------------
Nimni, Marcel USC/Children's Hospital-LA MTA 12/9/93 Osteoporosis: mineralization and maturation process
of resobable porous hydroxyapatite in rats;
capability of DBM carrier to stimulate bone marrow
derived cells to transform osteoblasts
- ------------------------------------------------------------------------------------------------------------------------------------
Fu, Y.H. Florence V.A. Medical Center MTA 10/29/92 Cartilage: chondrocyte differentiation
- ------------------------------------------------------------------------------------------------------------------------------------
Szabo, Sandor V.A. Medical Center MTA 2/3/95 Morphogens: Gastroinstestinal
- ------------------------------------------------------------------------------------------------------------------------------------
Conger, John V.A. Medical Center (MTA/CA), Denver MTA 5/22/96 Renal: Effects of OP-1 in Acute Renal Failure
Research Institute (SRA)
- ------------------------------------------------------------------------------------------------------------------------------------
Frantz, Frazier VA Commonwealth University MTA 5/31/91 Morphogens: role of OP-1 in fetal healing
- ------------------------------------------------------------------------------------------------------------------------------------
Hogan, Brigid Vanderbilt University MTA 10/30/90 Morphogens: embryogenesis
- ------------------------------------------------------------------------------------------------------------------------------------
Pang, Roy Verax Corp MTA 2/22/93 Osteoporosis: study the effect of OP-1 & other
growth factors on bone marrow culture
- ------------------------------------------------------------------------------------------------------------------------------------
Wang, Tongwen Virginia Mason Research Center MTA 7/28/00
- ------------------------------------------------------------------------------------------------------------------------------------
Charness, Michael W. Roxbury VA Medical Center MTA 8/31/92 Neuro: NCAM expression
- ------------------------------------------------------------------------------------------------------------------------------------
Page 21 of 25
SCHEDULE F
Research and Development Agreements
- -----------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- -----------------------------------------------------------------------------------------------------------------------------------
Perides, George W. Roxbury VA Medical Center MTA 6/30/92 Neuro: NCAM regulation by BMPs
- ------------------------------------------------------------------------------------------------------------------------------------
Khouri, Roger WA University School MTA 9/25/92 Cartilage: repair of bone and cartilage
of Medicine
- ------------------------------------------------------------------------------------------------------------------------------------
Weeks, Paul WA University School of Medicine MTA 12/21/90 Cartilage: effect of growth factors on rate & quality
of tendon healing in vivo
- ------------------------------------------------------------------------------------------------------------------------------------
Liapis, Helen Washington University School MTA 3/3/00 Renal: The role of BMP-7 in animal models of
of Medicine obstructive nephropathy in the newborn.
- ------------------------------------------------------------------------------------------------------------------------------------
Jaenisch, Rudolf Whitehead Institute MTA 2/15/94 Renal: organ cultures
- ------------------------------------------------------------------------------------------------------------------------------------
Kreidberg, Jordan Whitehead Institute MTA 2/15/94 Renal: organ cultures
- ------------------------------------------------------------------------------------------------------------------------------------
Andrews, Peter Wistar Institute MTA 1/8/91 Morphogens; Cancer: carcinoma cells
- ------------------------------------------------------------------------------------------------------------------------------------
Levine, Elliot Wistar Institute MTA 5/21/98 Osteoporosis: Matrix formation and osteogenesis with
regards to osteoporosis in cultured human cells
- ------------------------------------------------------------------------------------------------------------------------------------
Levine, Elliot Wistar Institute MTA 8/6/98 Osteoporosis: Matrix formation and osteogenesis with
regards to osteoporosis in cultured human cells
- ------------------------------------------------------------------------------------------------------------------------------------
Lewis, Alan Wyeth-Ayerst MTA 6/11/91 Morphogens: animal models
- ------------------------------------------------------------------------------------------------------------------------------------
Baron, Roland Yale University MTA 9/10/90 Osteoporosis: effect of OP-1 on osteoclast-mediated
bone resorption
- ------------------------------------------------------------------------------------------------------------------------------------
Vignery, Agnes Yale University MTA 11/4/92 Morphogens: T-cell proliferation assays
- ------------------------------------------------------------------------------------------------------------------------------------
- ------------------------------------------------------------------------------------------------------------------------------------
SPONSORED RESEARCH AGREEMENTS
- -----------------------------------------------------------------------------------------------------------------------------------
Barnes Jewish Keith Hruska Research 5/8/98 The Role of OP-1 in Urinary Obstruction Models in Rat
Hospital Agreement +
Amendments
- ------------------------------------------------------------------------------------------------------------------------------------
Beth Israel Raghu Kalluri Research 2/20/98 The Role of OP-1 in Rat Kidney Fibrosis Model
Deaconess Agreement
- ------------------------------------------------------------------------------------------------------------------------------------
Beth Israel Raghu Kalluri Research 1/5/00 The role of BMP-7 in alpha 3 (type IV collagen) KO
Deaconess Agreement mice
- ------------------------------------------------------------------------------------------------------------------------------------
Beth Israel Vikas Suthatme Research 1/1/97 Evaluation of a gene therapy based approach for
Deaconess Agreement delivery of OP-1 and related genes in the area of
chronic renal disease/gene delivery of OP-1
- ------------------------------------------------------------------------------------------------------------------------------------
Beth Israel Larry Suva Research 3/16/94 Characterization of the CBFA1 Gene Promoter
Deaconess Agreement +
Amendment
- ------------------------------------------------------------------------------------------------------------------------------------
Page 22 of 25
SCHEDULE F
Research and Development Agreements
- -----------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- -----------------------------------------------------------------------------------------------------------------------------------
Boston Biomedical Walter F. Stafford Research 5/5/97 Efforts to Characterize the Physical State of
Research Institute Agreement OP-1 in Solution: Effects of pH, Protein, Buffer
Components
- -----------------------------------------------------------------------------------------------------------------------------------
Brandeis University William D. Carlson Research and 10/1/90 OP-1 Dimer Structure
License
Agreement
- -----------------------------------------------------------------------------------------------------------------------------------
Brandeis University William D. Carlson Research 12/20/95 OP-1 3D structures used in drug design for
Agreement bone disorders
- -----------------------------------------------------------------------------------------------------------------------------------
Harvard College Claire Doerschuk Research 9/15/98 OP-1 and its therapeutic potential in
Agreement Bleomycin-Induced Lung Injury
- -----------------------------------------------------------------------------------------------------------------------------------
Harvard College Malcolm Whitman Research 11/15/98 Identifying Genomic Targets for BMP and
Agreement + Smad1 Signals
Amendments
- -----------------------------------------------------------------------------------------------------------------------------------
Indiana University Bruce Molitoris Research 6/1/99 In vitro studies concerning the mechanism of
Agreement morphogen action in the kidney
- -----------------------------------------------------------------------------------------------------------------------------------
Johns Hopkins David Blake Research 5/2/94 Metabolic Fate of Systemic OP-1: Binding and
University Agreement Sequestration Administration
- -----------------------------------------------------------------------------------------------------------------------------------
Loma Linda Univrsity David J. Baylink Research 11/29/93 Effects of OP-1 in ischemia
Agreement
- -----------------------------------------------------------------------------------------------------------------------------------
Ludwig Institute for Dr. Kohei Miyazono Research 6/1/97 Type I receptors ALK-1, ALK-2, ALK-3 and ALK-6
Cancer Agreement antibodies with OP-1 for drug development or
Research/Japanese discovery
Foundation of
Cancer/CBMI
- -----------------------------------------------------------------------------------------------------------------------------------
Massachusetts Seth Finklestein Research 9/1/93 The Effects of OP-1 in ischemia
General Hospital Agreement
- -----------------------------------------------------------------------------------------------------------------------------------
Massachusetts Dr. Joseph V. Bonventre Research 8/1/95 OP-1 in recovery from Acute Renal Failure
General Hospital Agreement
- -----------------------------------------------------------------------------------------------------------------------------------
Massachusetts Robert H. Brown Research 12/15/98 OP-1 as a candidate therapeutic in ALS mice
General Hospital Agreement
- -----------------------------------------------------------------------------------------------------------------------------------
Miami Children's Ana Paredes Research 2/25/98 Effect of mOP-1: Time course of disease
Hospital Agreement progression in the rat remnant kidney model
- -----------------------------------------------------------------------------------------------------------------------------------
Sierra Biomedical Contract Research 1/18/99 Non-human primate toxicology studies
- -----------------------------------------------------------------------------------------------------------------------------------
Page 23 of 25
SCHEDULE F
Research and Development Agreements
- -----------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- -----------------------------------------------------------------------------------------------------------------------------------
The University of R. Bruce Rutherford Research 4/15/92 OP-1 to induce secondary dentin formation
Connecticut Health Agreement
Center
- -----------------------------------------------------------------------------------------------------------------------------------
University of Miami Ana Paredes Research 4/1/96 Effect of rbOsteogenic Protein-1
Agreement
- -----------------------------------------------------------------------------------------------------------------------------------
University of Miami W. Dalton Dietrich Research 9/12/97 Effects of OP-1 Administration following
Agreement severe traumatic brain injury in rats
- -----------------------------------------------------------------------------------------------------------------------------------
University of Miami W. Dalton Dietrich Research 4/27/98 Effects of OP-1 Administration following
Agreement middle cerebral artery occlusion in rats
- -----------------------------------------------------------------------------------------------------------------------------------
University of Miami W. Dalton Dietrich Research 9/4/98 Role of BMPs in neuronal development
Agreement
- -----------------------------------------------------------------------------------------------------------------------------------
University of NY at Dennis Higgins Research 4/1/98 OP-1 on dendritic growth in vivo,OP-1
Buffalo, SUNY Agreement transported by neurons in vivo, OP-1
mediates neurotrophi interactions in tissue culture
- -----------------------------------------------------------------------------------------------------------------------------------
University of NY at Dennis Higgins Amendment to 9/11/98 OP-1 on dendritic growth in vivo,OP-1 transported
Buffalo, SUNY Research by neurons in vivo, OP-1 mediates neurotrophi
Agreement dated interactions in tissue culture
April 1, 1998
- -----------------------------------------------------------------------------------------------------------------------------------
University of NY at Dennis Higgins Amendment to OP-1 on dendritic growth in vivo,OP-1 transported by
Buffalo, SUNY Research neurons in vivo, OP-1 mediates neurotrophi interactions
Agreement dated in tissue culture
April 1, 1998 and
September 11,1998
- -----------------------------------------------------------------------------------------------------------------------------------
University of F. Michael Hoffman Research 4/1/94 Structure-function Analysis of BMPs
Wisconsin-Madison Agreement
Medical School
- -----------------------------------------------------------------------------------------------------------------------------------
Uppsala University Ted Ebendal Collaboration 12/20/96 OP-1 effects in the nervous system
Agreement
- -----------------------------------------------------------------------------------------------------------------------------------
University of Thomas Reh Research 9/21/98 Role of BMPs in delaying or rescuing rod photoreceptors
Washington Agreement in animal models of retinal degenerative diseases
- -----------------------------------------------------------------------------------------------------------------------------------
Washington Ted Ebendal Research 1/15/00 BMP-7 on the progression of renal disease in a mouse
University Agreement model of Alport syndrome
- -----------------------------------------------------------------------------------------------------------------------------------
SBIR Grants
Page 24 of 25
SCHEDULE F
Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------
PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT
INVESTIGATOR AGREEMENT DATE OF
ORIGINAL
AGREEMENT
- ------------------------------------------------------------------------------------------------------------------------------------
Creative Biomolecules Dattatreyamurty Bosukonda SBIR Grant 1 R43 AR44140-01 12/12/96 OP-1 3D Structure Used in Drug
Design for Bone Disorders
- ------------------------------------------------------------------------------------------------------------------------------------
Creative Biomolecules Paul L. Kaplan SBIR Grant 1 R43 NS37970-01 8/1/98 OP-1 Treatment for Parkinson's
Disease
- ------------------------------------------------------------------------------------------------------------------------------------
Page 25 of 25
SCHEDULE G
Third Party Agreements
Company Date of Agreement
Stryker Corporation
Master Restructuring Agreement October 15, 1998
Creative Irrevocable License Agreement November 20, 1998
Stryker Irrevocable License Agreement November 20, 1998
First Amendment to Master Restructuring Agreement November 2, 2001
First Amendment to Stryker License Agreement November 2, 2001
First Amendment to Creative License Agreement November 2, 2001
Second Amendment to Master Restructuring Agreement October 1, 2002
Assignment October 1, 2002
Genetics Institute / Stryker Corporation
Cross-License Agreement July 15, 1996
Biogen Corporation
Research Collaboration and License Agreement December 9, 1996
Amendment Agreement December 30, 1998
Ludwig Institute for Cancer Research
Agreement June 1, 1997
34