AGREEMENT
by and between
ENTREMED, INC.
and
CELGENE CORPORATION
Omitted portions (indicated by asterisks*) have been separately filed with the
United States Securities and Exchange Commission pursuant to a request for
confidential treatment.
TABLE OF CONTENTS
1 - DEFINITIONS...................................................................................................2
1.1 AFFILIATE.......................................................................................2
1.2 CALENDAR QUARTER................................................................................2
1.3 CELGENE DEVELOPED INTELLECTUAL PROPERTY.........................................................2
1.4 CELGENE DEVELOPED PATENT RIGHTS ................................................................2
1.5 CELGENE DEVELOPED TECHNOLOGY RIGHTS ............................................................3
1.6 CELGENE EXISTING INTELLECTUAL PROPERTY..........................................................3
1.7 CELGENE EXISTING PATENT RIGHTS..................................................................3
1.8 CELGENE EXISTING TECHNOLOGY RIGHTS .............................................................3
1.9 CMCC AGREEMENT .................................................................................3
1.10 ENTREMED DEVELOPED PATENT RIGHTS ...............................................................4
1.11 ENTREMED DEVELOPED TECHNOLOGY RIGHTS ...........................................................4
1.12 ENTREMED EXISTING PATENT RIGHTS.................................................................4
1.13 ENTREMED EXISTING TECHNOLOGY RIGHTS.............................................................4
1.14 ENTREMED INTELLECTUAL PROPERTY..................................................................5
1.15 FIELD ..........................................................................................5
1.16 FIRST COMMERCIAL SALE ..........................................................................5
1.17 NCI AGREEMENT...................................................................................5
1.18 NDA ............................................................................................6
1.19 NET SALES ......................................................................................6
1.20 PATENT RIGHT(s) ................................................................................7
1.21 PRODUCT.........................................................................................7
1.22 SUBLICENSEE.....................................................................................8
1.23 TECHNOLOGY RIGHTS...............................................................................8
1.24 TERRITORY ......................................................................................8
1.25 THALIDOMIDE ....................................................................................8
1.26 THIRD PARTY(IES) ...............................................................................8
1.27 VALID CLAIM ....................................................................................8
2 - GRANT.........................................................................................................9
2.1 Grant of ENTREMED EXISTING PATENT RIGHTS and ENTREMED EXISTING TECHNOLOGY RIGHTS................9
2.2 Grant of ENTREMED DEVELOPED PATENT RIGHTS and ENTREMED DEVELOPED TECHNOLOGY RIGHTS..............9
2.3 CELGENE'S Right To Sublicense..................................................................10
2.4 Assignment Of Investigational New Drug and
Orphan Drug Status Applications................................................................10
2.5 Assignment Of Agreements.......................................................................11
2.6 Technology Transfer............................................................................11
2.7 Understanding Regarding CMCC AGREEMENT. .......................................................12
3 - DUE DILIGENCE................................................................................................13
3.1 In the United States...........................................................................13
3.2 Outside the United States......................................................................15
3.3 For PRODUCTS For Use In Animals................................................................17
3.4 No Other ENTREMED Rights.......................................................................17
3.5 Co-Promotion By CELGENE And ENTREMED...........................................................17
3.6 Establishment Of A Scientific Committee........................................................19
4 - ROYALTIES....................................................................................................21
4.1 Royalty Payments...............................................................................21
4.2 Sublicensing Payments and Royalties. .........................................................22
4.3 Later-Issued VALID CLAIM.......................................................................23
4.4 No Multiple Royalties..........................................................................24
4.5 THIRD PARTY Sales..............................................................................24
4.6 Recordkeeping..................................................................................25
4.7 Quarterly Payments and Reports.................................................................25
4.8 Accounting Reports.............................................................................26
5 - CONFIDENTIALITY..............................................................................................26
5.1 Confidential Information. .....................................................................26
5.2 Non-Confidential Information...................................................................27
5.3 Disclosure To THIRD PARTIES. ..................................................................28
5.4 Disclosure To Sublicensees. ...................................................................28
5.5 Public Statements..............................................................................28
6 - ADVERSE MEDICAL EXPERIENCES..................................................................................29
6.1 Adverse Medical Experience Reporting. .........................................................29
7 - PATENTS......................................................................................................29
7.1 Patent Prosecution.............................................................................29
7.2 Cooperation In Prosecution.....................................................................29
7.3 Infringement and Declaratory Judgment Actions..................................................30
8 - REPRESENTATIONS AND WARRANTIES...............................................................................32
8.1 By Both Parties................................................................................32
8.2 By ENTREMED....................................................................................32
9 - INDEMNIFICATION AND INSURANCE................................................................................34
9.1 By CELGENE. ...................................................................................34
9.2 By ENTREMED. .................................................................................35
9.3 Conditions to Indemnification. ................................................................36
10 - ASSIGNMENT AND SUCCESSORS...................................................................................37
10.1 By Either Party................................................................................37
10.2 By CELGENE.....................................................................................37
10.3 CELGENE As Guarantor...........................................................................37
10.4 Binding Effect.................................................................................37
11 - FORCE MAJEURE...............................................................................................38
12 - TERMINATION.................................................................................................38
12.1 Term. ........................................................................................38
12.2 By Reason Of FDA Action........................................................................38
12.3 Termination Of Royalty Obligations. ..........................................................38
12.4 Breach.........................................................................................39
12.5 Insolvency. ..................................................................................41
12.6 Work-In-Progress. .............................................................................41
12.7 Survival.......................................................................................41
12.8 Reversion of Rights............................................................................41
13 - GENERAL PROVISIONS..........................................................................................42
AGREEMENT
This Agreement is effective this 9th day of December, 1998 (the
"EFFECTIVE DATE") by and between CELGENE CORPORATION, a Delaware corporation
located at 6 Powder Horn Drive, Warren, New Jersey 07059 ("CELGENE"), and
ENTREMED, INC., a Delaware Corporation located at 9610 Medical Center Drive,
Rockville, Maryland 20850 ("ENTREMED").
WHEREAS, CELGENE is a company that develops, manufactures, markets and
sells pharmaceutical products for healthcare, and that has developed and owns
certain patents, patent applications, proprietary technology, know-how, and
United States Food and Drug Administration ("FDA") filings relating to PRODUCTS,
as hereinafter defined; and
WHEREAS, ENTREMED is the owner or exclusive licensee of certain PATENT
RIGHTS as hereinafter defined, TECHNOLOGY RIGHTS, as hereinafter defined, and
FDA filings related to PRODUCTS, and has certain rights and obligations relating
to PRODUCTS pursuant to agreements with THIRD PARTIES, as hereinafter defined;
and
WHEREAS, CELGENE desires to obtain assignments and/or exclusive rights
in the TERRITORY in and to all of ENTREMED's PATENT RIGHTS, TECHNOLOGY RIGHTS,
rights by agreement, and FDA filings, whether presently existing or subsequently
developed, for the commercial development, use, and sale of PRODUCTS; and
WHEREAS, ENTREMED is willing to grant the assignments and/or exclusive
rights desired by CELGENE, as set forth herein, in order to transfer its entire
present and future right, title and interest in PRODUCTS to CELGENE.
NOW, THEREFORE, in consideration of the mutual promises and other good
and valuable
consideration, the parties agree as follows:
SECTION 1 - DEFINITIONS
The terms used in this Agreement have the following meaning:
1.1 The term "AFFILIATE" as applied to either party shall mean any
company or other legal entity other than the party in question
in whatever country organized, controlling controlled by or
under common control with that party. The term "control" means
ownership or control, directly or indirectly, of at least
fifty percent (50%) of the outstanding stock or voting rights
entitled to elect directors.
1.2 The term "CALENDAR QUARTER" shall mean the period of three
(3) consecutive calendar months ending on March 31, June
30, September 30 or December 31, as the case may be.
1.3 The term "CELGENE DEVELOPED INTELLECTUAL PROPERTY" shall mean
CELGENE DEVELOPED PATENT RIGHTS and CELGENE DEVELOPED
TECHNOLOGY RIGHTS.
1.4 The term "CELGENE DEVELOPED PATENT RIGHTS" shall mean any
United States or foreign patents or patent applications filed
by CELGENE, or an AFFILIATE, successor or assign thereof at
any time subsequent to the EFFECTIVE DATE, in which CELGENE
has a transferrable interest, relating to a modification of a
PRODUCT described in any ENTREMED INTELLECTUAL PROPERTY or a
method of using such PRODUCT, which modification is (a)
necessary for the manufacture, use, or sale of such PRODUCT,
and (b) then currently in use by CELGENE at the time ENTREMED
exercises its rights under Section 0(b), for the manufacture,
use, or sale of such PRODUCT.
1.5 The term "CELGENE DEVELOPED TECHNOLOGY RIGHTS" shall mean any
TECHNOLOGY RIGHTS developed, obtained, or acquired by CELGENE
or an AFFILIATE, successor or assign thereof at any time
subsequent to the EFFECTIVE DATE, in which CELGENE has a
transferrable interest, relating to a modification of a
PRODUCT described in any ENTREMED INTELLECTUAL PROPERTY or a
method of using or use of such PRODUCT, which modification is
(a) necessary for the manufacture, use, or sale of such
PRODUCT, and (b) then currently in use by CELGENE at the time
ENTREMED exercises its rights under Section 0(b), for the
manufacture, use, or sale of such PRODUCT.
1.6 The term "CELGENE EXISTING INTELLECTUAL PROPERTY" shall mean
CELGENE EXISTING PATENT RIGHTS and CELGENE EXISTING TECHNOLOGY
RIGHTS.
1.7 The term "CELGENE EXISTING PATENT RIGHTS" shall mean the
United States and foreign patents and patent applications
relating to PRODUCTS in which CELGENE has an interest, jointly
or solely, as owner, assignee, or licensee, whether exclusive
or nonexclusive, as of the EFFECTIVE DATE.
1.8 The term "CELGENE EXISTING TECHNOLOGY RIGHTS" shall mean any
TECHNOLOGY RIGHTS developed, obtained, or acquired, solely or
jointly, exclusively or non-exclusively, by CELGENE or an
AFFILIATE, successor or assign thereof as of the EFFECTIVE
DATE.
1.9 The term "CMCC AGREEMENT" shall mean that certain License
Agreement entered into by and between ENTREMED and Children's
Medical Center Corporation ("CMCC"), dated May 26, 1994, as
amended to the date hereof, attached hereto as Exhibit A.
1.10 The term "ENTREMED DEVELOPED PATENT RIGHTS" shall mean any
United
States or foreign patent applications relating to PRODUCTS
assigned to, licensed to or filed, solely or jointly, by
ENTREMED, or an AFFILIATE, successor or assign thereof at
any time subsequent to the EFFECTIVE DATE, including any
United States or foreign patent applications filed pursuant
to the CMCC AGREEMENT or NCI AGREEMENT, and the patents
issuing therefrom, which patent applications and patents
shall be added to Appendix A and shall be included in this
Agreement as PATENT RIGHTS and licensed to CELGENE in
accordance with Section 2 of this Agreement.
1.11 The term "ENTREMED DEVELOPED TECHNOLOGY RIGHTS" shall mean any
TECHNOLOGY RIGHTS developed, obtained, or acquired, solely or
jointly, exclusively or non-exclusively, by ENTREMED, or an
AFFILIATE, successor or assign thereof at any time subsequent
to the EFFECTIVE DATE, including any TECHNOLOGY RIGHTS
developed or obtained pursuant to the CMCC AGREEMENT or NCI
AGREEMENT, which TECHNOLOGY RIGHTS shall be included in this
Agreement and licensed to CELGENE in accordance with Section 2
of this Agreement.
1.12 The term "ENTREMED EXISTING PATENT RIGHTS" shall mean the
PATENT RIGHTS in which ENTREMED has an interest, jointly or
solely, as owner, assignee, or licensee, whether exclusive or
nonexclusive, as of the EFFECTIVE DATE.
1.13 The term "ENTREMED EXISTING TECHNOLOGY RIGHTS" shall mean any
TECHNOLOGY RIGHTS developed, obtained, or acquired, solely or
jointly, exclusively or non-exclusively, by ENTREMED, or an
AFFILIATE, successor or assign thereof as of the EFFECTIVE
DATE, including without limitation any TECHNOLOGY RIGHTS
developed or obtained pursuant to the CMCC AGREEMENT or NCI
AGREEMENT. ENTREMED EXISTING TECHNOLOGY RIGHTS expressly
includes any regulatory data and filings,
including without limitation all FDA Investigational New
Drug and Orphan Drug Status applications, as set forth in
Appendix C.
1.14 The term "ENTREMED INTELLECTUAL PROPERTY" shall mean and
include ENTREMED DEVELOPED PATENT RIGHTS, ENTREMED DEVELOPED
TECHNOLOGY RIGHTS, ENTREMED EXISTING PATENT RIGHTS, and
ENTREMED EXISTING TECHNOLOGY RIGHTS.
1.15 The term "FIELD" shall mean the use of THALIDOMIDE in humans
and animals, including without limitation any and all
diagnostic, prophylactic, therapeutic, and research and
development uses.
1.16 The term "FIRST COMMERCIAL SALE" shall mean, in each country
of the TERRITORY, the first sale after the EFFECTIVE DATE in
such country to a THIRD PARTY in connection with the
nationwide introduction of any PRODUCT by CELGENE, its
AFFILIATES or SUBLICENSEES following marketing and/or pricing
approval by the appropriate governmental agency for the
country in which the sale is to be made and, when governmental
approval is not required, the first sale in that country in
connection with the nationwide introduction of a PRODUCT in
that country.
1.17 The term "NCI AGREEMENT" shall mean that certain Agreement by
and between the Division of Cancer Treatment at the National
Cancer Institute ("NCI") and ENTREMED, dated November 16,
1994, and executed on behalf of ENTREMED on November 23, 1994,
and on behalf of NCI on November 18, 1994, attached hereto as
Exhibit B.
1.18 The term "NDA" shall mean a New Drug Application filed with
the United States Food and Drug Administration.
1.19 The term "NET SALES" means the gross amount received by
CELGENE or its AFFILIATES or SUBLICENSEES for sale of PRODUCT
to THIRD PARTIES, less: (i) cost of freight, postage, and
freight insurance, (if paid by seller); (ii) sales taxes,
value added taxes, excise taxes, and customs duties; (iii)
cost of export licenses and any taxes, fees or other charges
associated with the exportation or importation of PRODUCTS;
(iv) rebates accrued, incurred or paid to Federal Medicaid and
State Medicare and any other price reductions required by a
governmental agency; (v) rejected shipments, returns, and
retroactive deductions; (vi) the amount received for sales
which become the subject of a subsequent temporary or partial
recall by a regulatory agency for safety or efficacy reasons
outside the control of CELGENE; and (vii) customary cash,
quantity, and trade discounts; provided, however, that a sale
or transfer to an AFFILIATE or SUBLICENSEE for re-sale by such
AFFILIATE or SUBLICENSEE shall not be considered a sale for
the purpose of this provision but the resale by such AFFILIATE
or SUBLICENSEE shall be a sale for such purposes. A "sale"
shall also include a transfer or other disposition for
consideration, but not such transfers or dispositions, without
consideration, for pre-clinical, clinical, regulatory or
governmental purposes prior to receiving marketing approval
for the specific indication for which such transfer is made.
In the event that consideration in addition to or in lieu of
money is received for PRODUCT, such consideration shall be
added to the NET SALES as valued on the day of receipt thereof
by CELGENE. To the extent that a PRODUCT is sold in other than
an arms length transaction, NET SALES shall be the fair market
value of such PRODUCT if sold in an arms length transaction,
less the costs identified in subsections (i)-(vi) of this
Section 1.19. PRODUCT shall be considered "sold" at the
earlier of (a) the transfer of title in such PRODUCT to a
person other than an AFFILIATE or SUBLICENSEE of CELGENE or
(b) the shipment of such PRODUCT from the manufacturing or
warehouse facilities of CELGENE or its AFFILIATE or
SUBLICENSEE to a THIRD PARTY.
1.20 The term "PATENT RIGHT(s)" shall mean:
(a) the United States patent applications and patents
listed in Appendix A;
(b) the United States and foreign patents issued
from applications listed in Appendix A and from
divisionals and continuations of such
applications;
(c) claims of United States continuation-in-part
applications and of equivalent foreign
applications, and of the resulting
patent(s), that are directed to subject
matter described in the United States and
foreign applications listed in Appendix A;
(d) claims of all later-filed foreign patent
applications, and of the resulting patents,
that are directed to subject matter
described in the United States patents
and/or patent applications described in the
foregoing subsections of this Section 1.20;
(e) any reissues, re-examinations or extension
of United States patents described in the
foregoing subsections of this Section 1.20; and
(f) ENTREMED DEVELOPED PATENT RIGHTS, when
assigned to, licensed to or filed, solely or
jointly, by ENTREMED, or an AFFILIATE,
successor or assign thereof, pursuant to
Section 1.10 of this Agreement.
1.21 The term "PRODUCT" shall mean any article of manufacture,
substance, material, chemical, formulation or composition for
use in the FIELD which is or includes THALIDOMIDE as an active
ingredient, including, without limitation, a composition that
comprises THALIDOMIDE and a non-steroidal anti-inflammatory
compound(s). PRODUCT expressly excludes THALIDOMIDE analogs.
1.22 The term "SUBLICENSEE" shall mean any THIRD PARTY licensed by
CELGENE to make, have made, use, offer to sell, sell
or import any PRODUCT.
1.23 The term "TECHNOLOGY RIGHTS" shall mean any information
relating to PRODUCTS that is not covered by a patent or patent
application, including without limitation technical and
non-technical information, know-how, methods, processes,
procedures, compositions, devices, formulae, protocols,
techniques, software, designs, drawings, plans, diagrams,
specifications, data, the results of tests or assays, and all
other information relating to PRODUCTS.
1.24 The term "TERRITORY" shall mean all countries of the world.
1.25 The term "THALIDOMIDE" shall mean a compound with the chemical
structure described as
2-(2,6-Dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione, or as
otherwise defined in the Merck Index, entry 9390, 12th ed.,
and pharmaceutically acceptable salts thereof.
1.26 The term "THIRD PARTY(IES)" shall mean a person or entity
who or which is neither a party hereto nor an AFFILIATE of
a party hereto.
1.27 The term "VALID CLAIM" shall mean an issued claim of an
unexpired patent ("ISSUED VALID CLAIM") or a claim of a
pending patent application, which shall not have been
withdrawn, canceled or disclaimed, or held invalid or
unenforceable by a court of competent jurisdiction in an
unappealed or unappealable decision. Notwithstanding the
foregoing to the contrary, a claim of a pending patent
application, divisional application or continuation-in-part
shall cease to be a VALID CLAIM if no patent has issued on
such claim on or prior to the fifth (5th) anniversary of the
EFFECTIVE DATE of this Agreement, provided that such claim
shall once again become a VALID CLAIM on the issue date of a
patent that subsequently issues and covers such claim.
1.28 The use herein of the plural shall include the singular, and
the use of the masculine shall include the feminine.
SECTION 2 - GRANT
2.1 Grant of ENTREMED EXISTING PATENT RIGHTS and ENTREMED EXISTING
TECHNOLOGY RIGHTS. ENTREMED hereby grants to CELGENE and
CELGENE hereby accepts from ENTREMED an exclusive, royalty
bearing right and license or sublicense, as the case may be,
under the ENTREMED EXISTING PATENT RIGHTS and the ENTREMED
EXISTING TECHNOLOGY RIGHTS to make, have made, use, offer to
sell, sell, and import PRODUCTS in the TERRITORY.
2.2 Grant of ENTREMED DEVELOPED PATENT RIGHTS and ENTREMED
DEVELOPED TECHNOLOGY RIGHTS. ENTREMED hereby grants to
CELGENE, to the extent not prohibited by the United States
Government or by prior contractual obligations to any THIRD
PARTY, and CELGENE hereby accepts from ENTREMED:
(a) an exclusive, royalty bearing right and license
under the ENTREMED DEVELOPED PATENT RIGHTS and the
ENTREMED DEVELOPED TECHNOLOGY RIGHTS to make, have
made, use, offer to sell, sell, and import PRODUCTS
in the TERRITORY; and
(b) to the extent an exclusive license is not available
to CELGENE in a country under a particular ENTREMED
DEVELOPED PATENT RIGHT or ENTREMED DEVELOPED
TECHNOLOGY RIGHT, but a non-exclusive license would
be available, ENTREMED hereby grants CELGENE a
nonexclusive, royalty bearing right and license under
such ENTREMED DEVELOPED PATENT RIGHT(s) and ENTREMED
DEVELOPED TECHNOLOGY RIGHT(s) to make, have made,
use, offer to sell, sell, and
import PRODUCTS in the TERRITORY.
2.3 CELGENE'S Right To Sublicense.
(a) In the United States. ENTREMED hereby grants to
CELGENE the right to sublicense ENTREMED INTELLECTUAL
PROPERTY in the United States with the consent of
ENTREMED, to be exercised in ENTREMED's sole
discretion.
(b) Outside the United States. ENTREMED hereby grants to
CELGENE the right to sublicense ENTREMED INTELLECTUAL
PROPERTY outside the United States with the written
consent of ENTREMED, which consent shall not be
unreasonably withheld. Outside the United States,
CELGENE shall use reasonable efforts to negotiate
sublicensing agreements that are commercially
reasonable according to contemporaneous prevailing
standards within the pharmaceutical industry.
2.4 Assignment Of Investigational New Drug and Orphan Drug Status
Applications. Within ten (10) days of the EFFECTIVE DATE,
ENTREMED and CELGENE shall notify the Food and Drug
Administration ("FDA") of the transfer of ENTREMED's rights in
PRODUCTS to CELGENE by submitting to the FDA letters
substantially in the form attached hereto as Exhibit C, and
ENTREMED shall notify CELGENE of its compliance with this
Section 0 by copies of such letters. ENTREMED shall take all
further steps necessary or helpful to assign to CELGENE all
Orphan Drug Status and Investigational New Drug applications
filed by ENTREMED as of the EFFECTIVE DATE, as set forth in
Appendix C. If the FDA declines to allow the assignment of any
of ENTREMED's Investigational New Drug and/or Orphan Drug
Status application(s) to CELGENE, for whatever reason, then
ENTREMED's rights under such application(s) will be included
in this Agreement as ENTREMED EXISTING TECHNOLOGY RIGHTS and
will be licensed to CELGENE in accordance with Section 2 of
this Agreement.
2.5 Assignment Of Agreements. Within ten (10) days of the
EFFECTIVE DATE, ENTREMED shall notify CMCC and NCI of the
sublicense and transfer, respectively, of its rights in
PRODUCTS to CELGENE, and shall take all steps necessary or
helpful to assign to CELGENE the NCI AGREEMENT, including
without limitation requesting consent to assign ENTREMED's
obligations and entire right, title, and interest, under such
agreement to CELGENE, and upon receipt of the consent of NCI
to assign the NCI AGREEMENT, CELGENE will expressly assume all
of ENTREMED's duties and obligations thereunder. In the event
that ENTREMED is not permitted to assign its rights under the
NCI AGREEMENT to CELGENE, ENTREMED's rights in any PATENT
RIGHTS or TECHNOLOGY RIGHTS resulting from the NCI AGREEMENT
will be included in this Agreement as ENTREMED DEVELOPED
PATENT RIGHTS and ENTREMED DEVELOPED TECHNOLOGY RIGHTS,
respectively, and will be licensed to CELGENE in accordance
with Section 0 of this Agreement.
2.6 Technology Transfer. As soon as reasonably possible following
the EFFECTIVE DATE, but in no event later than one (1) month
after such date, ENTREMED shall transfer to CELGENE all
ENTREMED EXISTING TECHNOLOGY RIGHTS and ENTREMED DEVELOPED
TECHNOLOGY RIGHTS not already in CELGENE's possession.
ENTREMED agrees to disclose and transfer all ENTREMED
DEVELOPED TECHNOLOGY RIGHTS to CELGENE promptly, as they are
obtained or developed. ENTREMED also agrees to provide, upon
reasonable notice from CELGENE, any technical, scientific,
statistical, and/or regulatory support necessary or useful to
CELGENE's understanding and/or use of ENTREMED EXISTING
TECHNOLOGY RIGHTS and ENTREMED DEVELOPED TECHNOLOGY RIGHTS.
2.7 Understanding Regarding CMCC AGREEMENT. To the extent
TECHNOLOGY RIGHTS and/or PATENT RIGHTS licensed to CELGENE
under this Agreement
are rights which ENTREMED has licensed from CMCC under the
CMCC AGREEMENT, CELGENE and ENTREMED understand and agree as
follows:
(a) The rights licensed to CELGENE by ENTREMED are
subject to the terms, limitations, restrictions and
obligations of the CMCC AGREEMENT.
(b) CELGENE will comply with the terms, obligations,
limitations and restrictions of sublicensees under
Articles II, V, VII, VIII, IX, X, XII, XIII, and XV
of the CMCC AGREEMENT.
(c) ENTREMED will, at its own expense, timely pay the
milestone payment of *******************************
due to CMCC upon completion of a Phase II clinical
trial for any indication, pursuant to Section 4.1.3
of the CMCC AGREEMENT. ENTREMED shall promptly
provide written notice to CELGENE of such payment.
(d) CELGENE will, at its own expense, timely pay the
milestone payment of *******************************
due to CMCC upon completion of a Product License
Application for any indication, pursuant to
Section 4.1.4 of the CMCC AGREEMENT, which payment
shall be made to ENTREMED and timely forwarded by
ENTREMED to CMCC; provided, however, that if (i)
such payment becomes due prior to January 1, 2000,
and (ii) CELGENE's annual sales in the year such
payment becomes due are less than
********************, CELGENE may notify ENTREMED,
in writing, that it wishes ENTREMED to pay such
amount to CMCC directly, which ENTREMED hereby
agrees to do, and, by June 30, 2000 CELGENE shall
reimburse ENTREMED the amount paid to CMCC, plus
interest calculated at the annual rate of the sum
of ************ plus the prime interest rate quoted
by Citibank, N.A. on the date said payment is due.
ENTREMED shall promptly provide written notice to
CELGENE of all
payments under this Section 2.7(d).
(e) ENTREMED will comply with the terms, obligations,
limitations and restrictions of the CMCC AGREEMENT,
including, without limitation, any provisions
relating to due diligence, notification with respect
to sublicenses, and milestone payments, subject to
Sections 2.7(c) and (d) of this Agreement.
(f) The CMCC AGREEMENT and ENTREMED's rights thereunder
shall remain in full force and effect for the life of
the last to expire patent issued under the Patent
Rights, as defined therein, unless earlier terminated
pursuant to Article XIII of the CMCC AGREEMENT.
SECTION 3 - DUE DILIGENCE
3.1 In the United States.
(a) CELGENE shall initiate and diligently use reasonable
efforts to develop, or to file for regulatory
approval of or register, and to market and sell
PRODUCTS in the United States. Reasonable efforts
with respect to the development and/or pursuit of
regulatory approval or registration for PRODUCTS
in the United States shall be demonstrated by
CELGENE (i) developing and pursuing regulatory
approval for PRODUCTS for those uses CELGENE, in
good faith, determines to be commercially and
scientifically reasonable, including but not
limited to (a) one (1)**************, (b) one (1)
****************, and (c) one (1)
****************; and (ii) funding and conducting
clinical trials for PRODUCTS for other uses in
order to enhance scientific knowledge with regard
to such PRODUCTS, including for the publication of
data and results in scientific journals, whether
or not such clinical trials result in or
facilitate the pursuit of regulatory approval.
(b) ENTREMED agrees that, subject to Section 3.6 of this
Agreement, (i) the decision regarding which uses to
pursue regulatory approval of PRODUCTS for, and/or to
fund and conduct clinical trials of PRODUCTS for,
pursuant to Section 3.1(a) of this Agreement, shall
be made by and in the sole discretion of CELGENE; and
(ii) with respect to the manner in which regulatory
approval is sought and/or clinical trials are funded
and conducted, CELGENE shall have sole discretion,
including, without limitation, complete control over
all regulatory submissions of PRODUCTS to the
appropriate regulatory agencies worldwide, including
whether, when, and how to file, maintain, withdraw,
or abandon an application for regulatory approval of
PRODUCTS.
(c) Within 90 days after the EFFECTIVE DATE, CELGENE
shall draft a Development Plan outlining CELGENE'S
development objectives for PRODUCTS, in accordance
with Sections 3.1(a)(i) and (b) of this Agreement.
CELGENE shall consult with ENTREMED concerning the
Development Plan. The Development Plan shall include
suitable clinical milestones which are reasonably
intended to lead to regulatory approval of PRODUCTS,
in accordance with Sections 3.1(a)(i) and (b) of this
Agreement.
(d) CELGENE shall provide a written summary report to
ENTREMED within thirty (30) days after June 30th and
December 31st of each calendar year concerning the
efforts being made in accordance with this Section
3.1 with respect to PRODUCTS. CELGENE shall provide
ENTREMED with any additional information reasonably
requested by ENTREMED in this respect.
(e) At ENTREMED'S reasonable request, CELGENE shall
provide ENTREMED access to all clinical trial data
for PRODUCTS conducted by
CELGENE in accordance with the Development Plan
set forth in this Section 3.1. In the event that
rights are returned to ENTREMED under Section
3.1(f) of this Agreement, ENTREMED shall have the
right to review and use the clinical trial data in
its own clinical program.
(f) In the event that CELGENE fails to meet any of its
obligations under this Section 3.1 with respect to
PRODUCTS in the United States, and such failure is
not cured within sixty (60) days after written notice
thereof is received by CELGENE from ENTREMED, then
ENTREMED shall have the right and option to terminate
the license granted in this Agreement and this
Agreement by giving CELGENE sixty (60) days prior
written notice thereof.
3.2 Outside the United States.
(a) Diligence. CELGENE shall initiate and diligently use
reasonable efforts to develop, or to file for
regulatory approval of or register, and to market
and sell PRODUCTS in Europe, in Canada, and in the
Pacific Rim, Japan, and Australia (collectively,
the "PACIFIC RIM"). Reasonable efforts with
respect to the development and/or pursuit of
regulatory approval or registration for PRODUCTS
in Europe, Canada, and the PACIFIC RIM shall be
demonstrated by CELGENE, or a sublicensee thereof,
pursuing regulatory approval for PRODUCTS (i) in
Italy, France, the United Kingdom, and Germany (in
the case of Europe), and in Japan and one other
country of the PACIFIC RIM (in the case of the
PACIFIC RIM), within ************ from the date of
the first FDA approval of a PRODUCT for an
oncology indication or Crohn's disease, whichever
occurs earlier; and (ii) in Canada, within one (1)
year from the date of the first FDA approval of a
PRODUCT for an oncology indication or Crohn's
disease, whichever occurs earlier.
(b) CELGENE's Discretion. ENTREMED agrees that, subject
to Section 3.6 of this Agreement, (i) the decision
regarding which uses to pursue regulatory approval
of PRODUCTS for, and/or to fund and conduct
clinical trials of PRODUCTS for, pursuant to
Section 3.2(a) of this Agreement, shall be made by
and in the sole discretion of CELGENE; and (ii)
with respect to the manner in which regulatory
approval is sought and/or clinical trials are
funded and conducted, CELGENE shall have sole
discretion, including, without limitation,
complete control over all regulatory submissions
of PRODUCTS to the appropriate regulatory agencies
worldwide, including whether, when, and how to
file, maintain, withdraw, or abandon an
application for regulatory approval of PRODUCTS.
(c) Cooperation. If CELGENE fails to use reasonable
efforts in Europe, Canada, or the PACIFIC RIM, as set
forth in Section 3.2(a) of this Agreement, or to
sublicense its rights to a THIRD PARTY, then ENTREMED
shall have the right and option to either (i)
terminate the licenses granted in the region where
such failure has occurred, i.e., Europe, Canada, or
the PACIFIC RIM, respectively, by giving CELGENE
sixty (60) days prior written notice thereof, or (ii)
cooperate with CELGENE to find an appropriate
SUBLICENSEE for such rights.
3.3 For PRODUCTS For Use In Animals.
(a) Diligence. CELGENE shall initiate and diligently use
reasonable efforts to develop, or to file for
regulatory approval of or register, and to market and
sell PRODUCTS for use in animals. Such reasonable
efforts shall be demonstrated by CELGENE obtaining
regulatory approval for the sale of a PRODUCT for use
in animals within four (4) years of the EFFECTIVE
DATE in the United States and, outside the United
States, in one of the following countries: Italy,
France, the United Kingdom, or Germany.
(b) Cooperation. If CELGENE fails to use reasonable
efforts either in the
United States or outside the United States, as set
forth in Section 3.3(a) of this Agreement, or to
sublicense its rights in such regions to a THIRD
PARTY, then ENTREMED shall have the right and
option to either (i) terminate CELGENE's rights in
the region where such failure has occurred, i.e.,
in the United States or outside the United States,
respectively, in and to such PRODUCTS for use in
animals by giving CELGENE sixty (60) days prior
written notice thereof, or (ii) cooperate with
CELGENE to find an appropriate SUBLICENSEE for
such rights.
3.4 No Other ENTREMED Rights. Except as otherwise expressly
provided in this Agreement, ENTREMED agrees that it has not
retained any rights under ENTREMED INTELLECTUAL PROPERTY to
PRODUCTS, and that is shall not (i) make, use, offer to sell,
sell, or import PRODUCTS in the TERRITORY, or (ii)
collaborate, negotiate, or deal with THIRD PARTIES with
respect to PRODUCTS.
3.5 Co-Promotion By CELGENE And ENTREMED.
(a) With Regard To PRODUCTS. If CELGENE, in its sole
discretion, decides to co-promote any PRODUCT or to
seek sales assistance in promoting any PRODUCT,
including, but not limited to, sales assistance for
indications not then promoted by CELGENE sales
personnel, CELGENE shall, in good faith, consider
ENTREMED for the opportunity to co-promote such
PRODUCT(S) for such indications in the United States.
(i) CELGENE will give ENTREMED due consideration
for the opportunity to co-promote such
PRODUCT(S) as set forth herein, provided
that ENTREMED has a sales force capable of
providing the required details to the
targeted physician audience, or is capable
of assembling such a sales force within six
(6) months, and agrees to do so. If and only
if ENTREMED either has a sales force capable
of providing the required details to the
targeted physician audience, or commits to
assembling such a sales force within six (6)
months, the
decision to offer ENTREMED the opportunity
to co-promote such PRODUCT(s) for such
indications in the United States shall be
made, in good faith, by CELGENE, and CELGENE
shall notify ENTREMED of its decision in
writing.
(ii) If CELGENE offers ENTREMED the opportunity
to co-promote, pursuant to Section 3.5(a)(i)
of this Agreement, ENTREMED shall have
thirty (30) days to accept such offer by
written notice to CELGENE. If ENTREMED
accepts such offer to co-promote PRODUCTS,
then the parties will negotiate, in good
faith, a co-promotion agreement setting
forth the substance of this Section 3.5 and
other normal and customary conditions within
six (6) months of CELGENE's receipt of
ENTREMED's acceptance pursuant to this
Section 3.5(a)(ii).
(iii) ENTREMED's co-promotion efforts will focus
on detailing (product presentations) the
PRODUCT to the targeted physician audience.
In such case, ENTREMED's sales
representatives will also have the
opportunity, from time to time, to
participate in seminars, in-service
training, group presentations, and other
educational and promotional activities
initiated by CELGENE in consultations with
ENTREMED. In addition, ENTREMED will assign
a product manager to participate with the
CELGENE marketing team to provide input as
appropriate and to be the operational
liaison between CELGENE and ENTREMED's sales
force.
(b) With Regard To Anti-angiogenic Compounds. If
ENTREMED, in its sole discretion, decides to
co-promote an anti-angiogenic compound or a
composition containing, as an active ingredient,
such a compound, or to seek sales assistance in
promoting any such anti-angiogenic compound or
composition, including, but not limited to, sales
assistance for indications not then promoted by
ENTREMED sales personnel, ENTREMED shall, in good
faith, consider CELGENE for the opportunity to
co-promote such anti-
angiogenic compounds and/or compositions. The
decision to offer CELGENE the opportunity to
co-promote such anti-angiogenic compounds and/or
compositions shall be made in the sole discretion of
ENTREMED, and be subject, mutatis mutandis, to the
terms and conditions set forth in Sections
3.5(a)(ii) and (iii) of this Agreement.
3.6 Establishment Of A Scientific Committee. CELGENE agrees to
conduct and fund a development program designed to obtain
approval to market PRODUCTS, in accordance with its
obligations under Section 3.1(a)(i) and 3.1(b) of this
Agreement (the "PROGRAM"). To ensure the continued
participation of ENTREMED in these development activities, the
PROGRAM will be monitored by a Scientific Committee as
described herein (the "COMMITTEE").
(a) Members. Within ten (10) days of the date hereof,
ENTREMED and CELGENE shall each appoint two (2)
persons to serve on the COMMITTEE. Each party will
have the right to change its representation on the
COMMITTEE upon written notice to the other.
(b) Chairperson. The COMMITTEE will be chaired by one
representative of CELGENE, who shall be chosen in the
sole discretion of CELGENE.
(c) Responsibilities. The COMMITTEE will have authority
to:
(i) act in an advisory role and provide
information, including without limitation
technical and regulatory information and
marketing and sales information, helpful in
connection with the PROGRAM;
(ii) make recommendations regarding the
performance of the PROGRAM and the conduct
of the work pursuant thereto, and monitor
performance thereunder;
(iii) propose modifications to the PROGRAM;
(iv) review any and all proposed publication(s)
relating to the PROGRAM and the results
therefrom; and
(v) review all information and data resulting
from the PROGRAM.
(d) Meetings. The COMMITTEE will meet not less than four
(4) times a year
during the term of the PROGRAM, at such dates and
times as agreed to by the parties. The COMMITTEE
will prepare written minutes of each meeting and a
written record of all decisions whether made at a
formal meeting or not. All decisions made and
actions taken by the COMMITTEE will be made or taken
in the sole discretion of CELGENE after good faith
consideration of the position or opinion of the
ENTREMED members.
(e) Term and Termination. The PROGRAM will continue until
there are no longer any ongoing activities in
pursuit of regulatory approval, or any pending
applications for regulatory approval, for PRODUCTS,
pursuant to Sections 3.1(a)(i) and (b) of this
Agreement. Once all such activities have been
completed and all such regulatory approvals have
been obtained, CELGENE may, in its sole discretion,
extend the term of the PROGRAM to include PRODUCTS
in clinical trials for other uses, as set forth in
Sections 3.1(a)(ii) and (b) of this Agreement, in
which case the PROGRAM will continue until such
clinical trials have been completed or otherwise
terminated or, if applicable, until regulatory
approval has been obtained, unless the PROGRAM is
sooner terminated by CELGENE.
SECTION 4 - ROYALTIES
4.1 Royalty Payments.
(a) First Twelve Years. CELGENE shall pay to ENTREMED the
following royalties on the NET SALES of PRODUCTS sold by
CELGENE or its AFFILIATES in each country of the TERRITORY (i)
for the first consecutive twelve (12) years from the date of
the FIRST COMMERCIAL SALE of a PRODUCT in each country of the
TERRITORY, and, separately and independently, (ii) for the
first consecutive twelve (12) years from the date of the FIRST
COMMERCIAL SALE of each PRODUCT that contains, as a second
active ingredient, a compound other than THALIDOMIDE, in each
country of the TERRITORY:
(i) **************of NET SALES up to ************* of such
sales;
(ii) ************** of NET SALES between **********
and ************ of such sales;
(iii) *************of NET SALES between **************and
**************dollars of such sales; and
(iv) ***************of NET SALES over **************** of
such sales.
(b) After Twelve Years. For each PRODUCT in each country in the
TERRITORY in which the twelve (12) year period provided for in
Section 4.1(a) of this Agreement shall have terminated,
CELGENE shall pay to ENTREMED the following royalties on the
NET SALES of such PRODUCT covered by an ISSUED VALID CLAIM of
the PATENT RIGHTS that are sold by CELGENE or its AFFILIATES
in such country:
(i) ************of NET SALES up to **************of such
sales;
(ii) ************of NET SALES between *************and
********************of such sales;
(iii) *************of NET SALES between **************and
******************dollars of such sales; and
(iv) **************of NET SALES over ************* of such
sales;
and such royalties under this Section 4.1(b) shall be payable
until the last to expire PATENT RIGHT containing an ISSUED
VALID CLAIM covering such PRODUCT sold by CELGENE or its
AFFILIATES in such country.
4.2 Sublicensing Payments and Royalties.
(a) Under CELGENE's Rights. If CELGENE grants a
sublicense of its exclusive rights under this
Agreement, pursuant to Section 2.3 of this Agreement,
in any country(ies) of the TERRITORY, CELGENE shall
pay to ENTREMED (i) ***************of any non-royalty
consideration, including but not limited to any
sublicensing and/or milestone payments received by
CELGENE pursuant to such sublicense and (ii)
*************of the royalty income paid by
SUBLICENSEES to CELGENE on NET SALES of PRODUCTS.
(b) CELGENE-ENTREMED Cooperation. If CELGENE grants
a sublicense of any of its rights under this
Agreement in any area of the FIELD or any country of
the TERRITORY with respect to which ENTREMED and
CELGENE are cooperating pursuant to Sections 3.2 or
3.3 of this Agreement, CELGENE shall pay to ENTREMED
************** of any non-royalty consideration,
including but not limited to any sublicensing and/or
milestone payments received by CELGENE pursuant to
such sublicense. CELGENE shall also pay to ENTREMED,
as applicable, the following: (i) if CELGENE and
ENTREMED are cooperating in any country(ies)
pursuant to Section 3.2 of this Agreement,
*************of the royalty income paid by
SUBLICENSEES to CELGENE on NET SALES, in such
country(ies), of PRODUCTS; and (ii) if CELGENE and
ENTREMED are cooperating in any country(ies) with
regard to PRODUCTS for use in animals pursuant to
Section 3.3 of this Agreement, **************of the
royalty income paid by SUBLICENSEES to CELGENE on
NET SALES in such country(ies) of such PRODUCTS.
4.3 Later-Issued VALID CLAIM. In the event that there is no ISSUED
VALID CLAIM of a PATENT RIGHT in a country within the
TERRITORY on the date the twelve (12) year period provided for
in Section 4.1(a) of this Agreement expires, no royalties
shall be owed by CELGENE to ENTREMED under Sections 4.1(b) and
4.2 of this Agreement on PRODUCTS sold by CELGENE or its
AFFILIATES in such country, provided, however, that if a VALID
CLAIM of a PATENT RIGHT thereafter issues in such country,
CELGENE shall pay ENTREMED royalties on the NET SALES in such
country of PRODUCTS covered by an ISSUED VALID CLAIM of the
PATENT RIGHTS that are sold by CELGENE or its AFFILIATES,
according to the royalty rates set forth in Sections 4.1(b)
and 4.2 of this Agreement, and such royalties under this
Section 4.3 shall be payable until the last to expire PATENT
RIGHT containing an ISSUED VALID CLAIM covering the PRODUCTS
sold by CELGENE, its AFFILIATES or SUBLICENSEE in such
country.
4.4 No Multiple Royalties. No multiple royalties shall be payable
because any PRODUCT, its manufacture, use, importation, lease,
or sale is or shall be covered by more than one PATENT RIGHT.
4.5 THIRD PARTY Sales. In any country where sales by a THIRD PARTY
of a PRODUCT(s) for a similar dosage form and/or route of
administration:
(a) are equal to or greater than ************of the
dollar market share for such PRODUCT in such country
("MARKET SHARE"), but less than ************of the
MARKET SHARE, then the royalty payable to ENTREMED
pursuant to Sections 4.1 and 4.3 of this Agreement
shall be reduced by ***********;
(b) are equal to or greater than **************of the
MARKET SHARE, but less than ************of the MARKET
SHARE, then the royalty payable to ENTREMED pursuant
to Sections 4.1 and 4.3 of this Agreement shall be
reduced by**************;
(c) are equal to or greater than ************of the
MARKET SHARE, but less than ***************of the
MARKET SHARE, then the royalty payable to ENTREMED
pursuant to set Sections 4.1 and 4.3 of this
Agreement shall be reduced by***********; and
(d) are equal to or greater than *************of the
MARKET SHARE, then the royalty payable to ENTREMED
pursuant to Sections 4.1 and 4.3 of this Agreement
shall be reduced by************;
provided that royalties payable to ENTREMED shall never be
reduced below ************of NET SALES in each royalty
bracket. For purposes of this Section 4.5, oral dosage forms
shall include, without limitation, all capsule, caplet,
tablet, and liquid formulations for oral administration.
4.6 Recordkeeping. CELGENE shall keep, and shall cause each of its
AFFILIATES and SUBLICENSEES to keep, full and accurate books
of account containing all particulars relevant to its sales of
PRODUCTS that may be necessary for the purpose of calculating
all royalties payable to ENTREMED. Such books of account shall
be kept at their principal place of business and, with all
necessary supporting data shall, for the three (3) years next
following the end of the calendar year to which each shall
pertain, be open for inspection by an independent certified
public accountant reasonably acceptable to CELGENE, upon
reasonable notice during normal business hours at ENTREMED'S
expense for the sole purpose of verifying royalty statements
or compliance with this Agreement. In the event the inspection
determines that royalties due ENTREMED for any period have
been underpaid by ***********or more, then CELGENE shall pay
for all costs of the inspection. In all cases, CELGENE shall
pay to ENTREMED any underpaid royalties promptly and with
interest at the prime rate available to ENTREMED from its bank
plus**********. All information and data reviewed in the
inspection shall be used only for the purpose of verifying
royalties and shall be treated as CELGENE CONFIDENTIAL
INFORMATION subject to the obligations of this Agreement. No
audit by an agent of ENTREMED shall occur more frequently than
once during
any twelve (12) month period.
4.7 Quarterly Payments and Reports. In each year the amount of
royalty due shall be calculated quarterly as of the end of
each CALENDAR QUARTER and shall be paid quarterly within the
forty-five (45) days next following such date. Every such
payment shall be supported by the accounting described in
Section 4.8 of this Agreement. All royalties due ENTREMED are
payable in United States dollars. When PRODUCTS are sold for
currency other than United States dollars, the earned
royalties will first be determined in the foreign currency of
the country in which such PRODUCTS were sold and then
converted into equivalent United States funds. The exchange
rate will be that rate quoted in the Wall Street Journal on
the last business day of the CALENDAR QUARTER in which such
sales were made.
4.8 Accounting Reports. With each quarterly payment, CELGENE shall
deliver to ENTREMED a full and accurate accounting to include
at least the following information:
(a) Quantity of PRODUCT subject to royalty sold, by
country, by CELGENE, its AFFILIATES or SUBLICENSEES;
(b) Total receipts for each PRODUCT subject to royalty,
by country and, to the extent used in any royalty
calculations during such quarter, the exchange rate
set forth in Section 4.7 of this Agreement;
(c) Compensation on PRODUCTS received from SUBLICENSEES
pursuant to a sublicense of CELGENE's rights under
this Agreement; and
(c) Total royalties and/or compensation payable to
ENTREMED.
SECTION 5 - CONFIDENTIALITY
5.1 Confidential Information. During the term of this Agreement,
it is contemplated that each party may disclose to the other,
proprietary and confidential technology, inventions, technical
information, material, reagents, biological materials and the
like which are owned or controlled by the party providing such
information or which that party is obligated to maintain in
confidence and which is designated by the party providing such
information as confidential ("CONFIDENTIAL INFORMATION"). Each
party agrees not to disclose the CONFIDENTIAL INFORMATION and
to maintain the CONFIDENTIAL INFORMATION in strict confidence,
to cause all of its agents, representatives and employees to
maintain the disclosing party's CONFIDENTIAL INFORMATION in
confidence and not to disclose any such CONFIDENTIAL
INFORMATION to a THIRD PARTY without the prior written consent
of the disclosing party, and not to use such CONFIDENTIAL
INFORMATION for any purpose other than as provided under this
Agreement. The secrecy obligations of the parties with respect
to CONFIDENTIAL INFORMATION shall continue for a period ending
ten (10) years from the termination of this Agreement.
5.2 Non-Confidential Information. The obligations of
confidentiality will not apply to information that:
(a) was known to the receiving party or generally known
to the public prior to its disclosure hereunder
through no fault of the disclosing party or any
agent, representative or employee thereof; or
(b) subsequently becomes known to the public by some
means other than a breach of this Agreement,
including publication and/or laying open to
inspection of any patent applications or patents;
(c) is subsequently disclosed to the receiving party by a
THIRD PARTY having
a lawful right to make such disclosure and who is
not under an obligation of confidentiality to the
disclosing party;
(d) is required by law, rule, regulation or bona fide
legal process to be disclosed, provided that the
disclosing party takes all reasonable stem to
restrict and maintain confidentiality of such
disclosure and provides reasonable notice to the
non-disclosing party; or
(e) is approved for release by the parties.
5.3 Disclosure To THIRD PARTIES. The obligations of Section 5.1
notwithstanding, CELGENE or ENTREMED, as the case may be, may
disclose the CONFIDENTIAL INFORMATION licensed hereunder to
THIRD PARTIES
(a) who need to know the same in order to obtain
regulatory approval for a PRODUCT under this
Agreement, provided that the actions of such THIRD
PARTY are not in conflict with CELGENE's rights under
this Agreement,
(b) who need to know the same in order to work towards
the commercial development of PRODUCT on behalf of
CELGENE, or
(c) for whom the non-disclosing party, ENTREMED or
CELGENE, as the case may be, has given prior written
approval
provided that such THIRD PARTIES are bound by obligations of
confidentiality and non-use at least as stringent as those set
forth herein.
5.4 Disclosure To Sublicensees. CELGENE may disclose ENTREMED's
CONFIDENTIAL INFORMATION to a SUBLICENSEE without ENTREMED's
approval, provided that such SUBLICENSEES are bound by
obligations of confidentiality and non-use at least as
stringent as those set forth herein.
5.5 Public Statements. Neither CELGENE nor ENTREMED may issue a
public statement, including without limitation a press
release, with regard to this Agreement without the prior
written consent of the other party, which consent shall not be
unreasonably withheld. In accordance with the rules and
regulations promulgated by the Securities and Exchange
Commission, the parties will request that this Agreement be
treated as confidential.
SECTION 6 - ADVERSE MEDICAL EXPERIENCES
6.1 Adverse Medical Experience Reporting. CELGENE shall comply
fully with all applicable medical/adverse experience reporting
requirements in all countries where CELGENE intends to carry
out clinical trials and/or market PRODUCT.
SECTION 7 - PATENTS
7.1 Patent Prosecution.
(a) ENTREMED shall use reasonable efforts to prepare,
file, prosecute and maintain patent applications and
patents directed to PATENT RIGHTS and PRODUCTS
through patent counsel selected by ENTREMED and
reasonably acceptable to CELGENE, who shall consult
with and keep CELGENE advised with respect thereto.
(b) CELGENE shall reimburse ENTREMED for all reasonable
costs and expenses incurred after the EFFECTIVE DATE
for the filing, prosecution and maintenance of PATENT
RIGHTS.
7.2 Cooperation In Prosecution.
(a) With respect to any PATENT RIGHTS, each patent
application, office
action, response to office action, request for
terminal disclaimer, petition, and request for
reissue or reexamination of any patent issuing from
such application shall be provided to CELGENE
sufficiently prior to the filing of such
application, response, petition, or request to allow
for review and comment by CELGENE. ENTREMED shall
have the right to take any action that, in its
judgement, is necessary to preserve such PATENT
RIGHTS.
(b) Within a reasonable time from the EFFECTIVE DATE,
CELGENE and ENTREMED will discuss each party's patent
portfolio with regard to PRODUCTS, in accordance with
prior obligations of confidentiality owed by each
party to any THIRD PARTY, and will use reasonable
efforts to coordinate their respective patent
portfolio, to the extent possible, so as to maximize
the patent protection for PRODUCTS.
7.3 Infringement and Declaratory Judgment Actions.
(a) Notification. In the event that either party learns
of the infringement of any PATENT RIGHT, or the
filing of a Declaratory Judgement action alleging the
invalidity, unenforceability, or noninfringement of
any PATENT RIGHT ("DJ ACTION"), that party must
promptly notify the other party of the infringement
or DJ ACTION, as the case may be, in writing, and
must provide reasonable evidence of the infringement.
Neither party will notify a THIRD PARTY of the
infringement of any PATENT RIGHT or of the filing of
a DJ ACTION directed to any PATENT RIGHT without
first obtaining consent of the other party, which
consent shall not be unreasonably withheld.
(b) CELGENE's Right To File Infringement Actions. To the
extent ENTREMED has the right to bring a suit or
action to compel the termination
of infringement of the PATENT RIGHTS, including to
the extent provided in Article 7 of the CMCC
AGREEMENT, ENTREMED hereby grants CELGENE the right
and option, but not the obligation, to bring an
action for infringement or to defend against a DJ
action, at its sole expense, in the name of ENTREMED
and/or in the name of CELGENE, and to join ENTREMED
as a party plaintiff if required. No settlement,
consent judgment or other voluntary final
disposition of a suit that adversely affects PATENT
RIGHTS may be entered into without the consent of
ENTREMED, which consent shall not be unreasonably
withheld.
(c) CELGENE's Right To Defend DJ ACTIONS. In the event
that a DJ ACTION is brought naming CELGENE as a
defendant, CELGENE shall have the right to proceed
with the litigation or settle such action provided,
however, that no settlement, consent judgment or
other voluntary final disposition of a suit that
adversely affects PATENT RIGHTS may be entered into
without the consent of ENTREMED, which consent shall
not be unreasonably withheld.
(d) CELGENE's Recovery. In the event that CELGENE shall
undertake the enforcement and/or defense of the
PATENT RIGHTS by litigation, any recovery of damages
by CELGENE for any such litigation shall be applied
first in satisfaction of any unreimbursed expenses
and legal fees of CELGENE relating to the suit. The
balance remaining from any such recovery shall, after
ENTREMED receives its royalties from lost sales,
belong to CELGENE.
(e) ENTREMED's Right To Litigate. In the event that
CELGENE elects not to pursue an action for
infringement or to defend against a DJ action, as the
case may be, CELGENE shall notify ENTREMED in writing
of such election and ENTREMED shall have the right
and option, but not the
obligation, at its cost and expense, to initiate
infringement litigation and to retain any recovered
damages.
(f) Cooperation. In any infringement suit either party
may institute to enforce or defend the PATENT RIGHTS
pursuant to this Agreement, the other party hereto
shall, at the request of the party initiating such
suit, cooperate in all respects and, to the extent
possible, have its employees testify when requested
and make available relevant records, papers,
information, samples, specimens, and the like. All
reasonable out-of-pocket costs incurred in connection
with rendering cooperation requested hereunder shall
be paid by the party requesting cooperation.
(g) THIRD PARTY Royalty Reduction. In the event that an
infringement action is brought by a THIRD PARTY
against CELGENE alleging that CELGENE's making,
using, offering to sell, selling, or importing of
PRODUCTS under the PATENT RIGHTS infringes a THIRD
PARTY patent, and results in a judgment or
settlement requiring royalties to be paid by CELGENE
to such THIRD PARTY, the royalties owed by CELGENE
to ENTREMED under Section 4 of this Agreement shall
be reduced by an amount equal to ****************of
the royalties owed to such THIRD PARTY, provided
that the royalties owed to ENTREMED shall not be
reduced under this Section 7.3(f) to less than
************of NET SALES, nor shall any specific
royalty payment be reduced under this Section 7.3(g)
by more than**********.
SECTION 8 - REPRESENTATIONS AND WARRANTIES.
8.1 By Both Parties. Each party hereby represents and warrants
that each has the full right and authority to enter into this
Agreement and that the entry into this Agreement does not
require the consent of a THIRD PARTY whose consent has not
been obtained.
8.2 By ENTREMED. ENTREMED represents and warrants as follows:
(a) that ENTREMED has not received any notice of
infringement of THIRD PARTY patents or notice of
interfering subject matter; that, without having made
any special investigation, ENTREMED is not aware of
any THIRD PARTY patents or patent applications that
contain any interfering subject matter, or any issued
THIRD PARTY patents that would be infringed by the
making, using, selling, offering for sale, or
importing by CELGENE of PRODUCTS covered by the
ENTREMED EXISTING PATENT RIGHTS or the ENTREMED
EXISTING TECHNOLOGY RIGHTS in any country in the
TERRITORY, or by the exercise by CELGENE of any right
granted to it under this Agreement, aside from those
set forth in Appendix D;
(b) that the PATENT RIGHTS set forth in Appendix A and
the TECHNOLOGY RIGHTS transferred to CELGENE under
this Agreement, constitute the entirety of ENTREMED
EXISTING PATENT RIGHTS and ENTREMED EXISTING
TECHNOLOGY RIGHTS;
(c) that ENTREMED presently has no rights in PRODUCTS,
nor any option in or expectation of any rights in
PRODUCTS, apart from those identified in this
Agreement and set forth in the agreements listed in
Appendix B, and that ENTREMED is not in material
breach or default of any of the agreements set forth
in Appendix B, and that if ENTREMED acquires any such
rights after the EFFECTIVE DATE, the agreements
setting forth those rights, including all licenses
and assignments for ENTREMED DEVELOPED PATENT RIGHTS
and ENTREMED DEVELOPED TECHNOLOGY RIGHTS, shall be
redacted to the extent they do not relate to
CELGENE's rights under this Agreement, and attached
hereto as independent Exhibits and incorporated
herein;
(d) that, with regard to PRODUCTS, ENTREMED has no
applications filed or pending with the FDA as of the
EFFECTIVE DATE, including without
limitation any Investigational New Drug or Orphan
Drug Status applications, apart from those set forth
in Appendix C;
(e) that ENTREMED will comply with all obligations and
duties with regard to PRODUCTS under the CMCC
AGREEMENT and, unless and until it is assigned to
CELGENE pursuant to Section 2.5 of this Agreement,
the NCI AGREEMENT, including, without limitation, any
notification provisions necessary to maintain in
effect this Agreement or preserve CELGENE's exclusive
or non-exclusive rights under this Agreement,
including without limitation the preservation of
CELGENE's rights hereunder in the event that ENTREMED
shall breach or default on its obligations under the
CMCC AGREEMENT or the NCI AGREEMENT;
(f) that ENTREMED understands and agrees that it has not
retained any rights under the ENTREMED INTELLECTUAL
PROPERTY to PRODUCTS in the TERRITORY, and that the
licenses and assignments granted in Sections 0, 0, 0,
and 0 of this Agreement are exclusive of any
continuing right of ENTREMED, except as otherwise
provided herein; and
(g) that ENTREMED will not collaborate, negotiate, or
deal with THIRD PARTIES with respect to PRODUCTS,
except as expressly provided herein.
8.3 EXCEPT AS OTHERWISE EXPRESSLY SET FORTH HEREIN, ENTREMED MAKES
NO REPRESENTATIONS OR EXTENDS ANY WARRANTIES OF ANY KIND
EITHER EXPRESS OR IMPLIED, INCLUDING, BUT NOT LIMITED TO,
WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR
PURPOSE, NON-INFRINGEMENT OR VALIDITY OF ANY ENTREMED PATENT
OR OTHER INTELLECTUAL PROPERTY RIGHTS.
SECTION 9 - INDEMNIFICATION AND INSURANCE
9.1 By CELGENE. CELGENE will defend, indemnify and hold harmless
ENTREMED, its successors, AFFILIATES and licensors and their
employees,
agents, officers, trustees, shareholders and directors and
each of them (the "ENTREMED Indemnified Parties") from and
against any and all THIRD PARTY claims, causes of action and
costs (including reasonable attorney's fees) of any nature
made or lawsuits or other proceedings filed or otherwise
instituted against the ENTREMED Indemnified Parties in
connection with any claims, suits or judgments arising out of
any theory of product liability concerning the development,
testing, manufacture, sale or use of any PRODUCT by CELGENE,
its AFFILIATES or its SUBLICENSEES.
9.1.1 CELGENE's indemnification under this Section
9.1 shall not apply to any liability,
damage, loss or expense to the extent that
it is directly attributable to the negligent
activity, reckless misconduct or intentional
misconduct of ENTREMED.
9.1.2 Commencing not later than the date of FIRST
COMMERCIAL SALE of a PRODUCT, CELGENE shall
obtain and carry in full force and effect
product liability insurance against any
claims, judgments, liabilities and expenses
for which it is obligated to indemnify
ENTREMED and others under Section 9.1 of
this Agreement, in such amounts and with
such deductibles as are customary at the
time for companies engaged in a similar
business, and shall provide ENTREMED with
written evidence of such insurance upon
request.
9.2 By ENTREMED. ENTREMED will defend, indemnify and hold harmless
CELGENE, its successors, AFFILIATES and licensors and their
employees, agents, officers, trustees, shareholders and
directors and each of them (the "CELGENE Indemnified Parties")
from and against any and all THIRD PARTY claims, causes of
action and costs (including reasonable attorney's fees) of any
nature made or lawsuits or other proceedings filed or
otherwise instituted against the CELGENE
Indemnified Parties in connection with any claims, suits or
judgments arising out of any theory of product liability
concerning the development, testing, manufacture, sale or use
of any PRODUCT by ENTREMED, its AFFILIATES or its SUBLICENSEES
prior to the EFFECTIVE DATE.
9.2.1 ENTREMED's represents and warrants that it
presently carries, in full force and effect,
and will continue to carry, product
liability insurance against any claims,
judgments, liabilities and expenses incurred
in connection with the use of THALIDOMIDE in
clinical trials by or on behalf of ENTREMED,
and shall provide CELGENE with written
evidence of such insurance upon request.
9.3 Conditions to Indemnification. A person or entity that intends
to claim indemnification under this Section 9 (the
"Indemnitee") shall promptly notify the party from whom
indemnification is sought (the "Indemnitor"), of any loss,
claim, damage, liability or action in respect of which the
Indemnitee intends to claim such indemnification, and the
Indemnitor shall assume the defense thereof with counsel
mutually satisfactory to the Indemnitee whether or not such
claim is rightfully brought; provided, however, that an
Indemnitee shall have the right to retain its own counsel,
with the fees and expenses to be paid by the Indemnitor if
Indemnitor does not assume the defense, or if representation
of such Indemnitee by the counsel retained by the Indemnitor
would be inappropriate due to actual or potential differing
interests between such Indemnitee and any other person
represented by such counsel in such proceedings. The failure
to deliver notice to the Indemnitor within a reasonable time
after the commencement of any such action, only if prejudicial
to its ability to defend such action, shall relieve such
Indemnitor of any liability to the Indemnitee under this
Section 9, but the omission so to deliver notice to the
Indemnitor will not relieve it of any liability that it may
have to any Indemnitee otherwise than under this Section 9.
The Indemnitee under this Section 9, its employees and agents,
shall cooperate fully with the Indemnitor and its legal
representatives in the investigations of any action, claim or
liability covered by this
indemnification.
SECTION 10 - ASSIGNMENT AND SUCCESSORS
10.1 By Either Party. This Agreement shall not be assignable by
either party without the written consent of the other party,
except that either party may assign this Agreement to an
AFFILIATE, successor in interest or transferee of all or
substantially all of the portion of the business to which this
Agreement relates without the consent of the other party.
10.2 By CELGENE. If CELGENE assigns or licenses its rights under
this Agreement to a SUBLICENSEE or an AFFILIATE, such
SUBLICENSEE or AFFILIATE shall be bound by the terms and
conditions of this Agreement. CELGENE shall advise ENTREMED of
any such assignment or license and provide ENTREMED with a
copy of any sublicense within thirty (30) days of execution of
such sublicense.
10.3 CELGENE As Guarantor. CELGENE shall guarantee and be
responsible for the payment of all royalties due and the
making of reports under this Agreement by reason of the
development and sales of any PRODUCTS by CELGENE, its
AFFILIATES and SUBLICENSEES and their compliance with all
applicable terms of this Agreement. Performance or
satisfaction of any obligations of CELGENE under this
Agreement by any of its AFFILIATES or SUBLICENSEES shall be
deemed performance or satisfaction of such obligation by
CELGENE.
10.4 Binding Effect. This agreement shall be binding upon and inure
to the benefit of said successors in interest and assignees to
the parties. Any such successor or assignee of a party's
interest shall expressly assume in writing the performance of
all the terms and conditions of this Agreement to be performed
by said party and such Assignment shall not relieve the
Assignor of any of its obligations under this Agreement.
SECTION 11 - FORCE MAJEURE
11.1 Neither party shall be liable to the other party for damages
or loss occasioned by failure of performance by the defaulting
party if the failure is occasioned by war, fire, explosion,
flood, strike or lockout, embargo, or any similar cause beyond
the control of the defaulting party, provided that the party
claiming this exception has exerted all reasonable efforts to
avoid or remedy such event and provided such event does not
extend for more than six (6) months.
SECTION 12 - TERMINATION
12.1 Term. Unless earlier terminated as hereinafter provided, this
Agreement shall remain in full force and effect until
CELGENE's obligations to pay royalties or other compensation
under Section 4 of this Agreement, either directly or pursuant
to a sublicense, terminate.
12.2 By Reason Of FDA Action. If the FDA withdraws or recalls
THALIDOMIDE from the market permanently, or in any other way
revokes or terminates CELGENE's regulatory approval to market
and sell THALIDOMIDE and/or PRODUCTS, CELGENE shall promptly
notify ENTREMED in writing, and this Agreement and all of
CELGENE's and ENTREMED's rights and obligations hereunder
shall terminate upon receipt by ENTREMED of such notice.
12.3 Termination Of Royalty Obligations. Upon termination of
CELGENE's obligation to pay royalties and other compensation
hereunder with respect to a specific country and specific
PRODUCT as to which CELGENE's license is then in effect, the
license granted to CELGENE with respect to such country and
such PRODUCT pursuant to Section 2 shall be deemed to be fully
paid and CELGENE shall thereafter have a royalty free,
exclusive right to use the PATENT RIGHTS to make,
have made, use, offer to sell, sell and import such PRODUCT
in such country.
12.4 Breach.
(a) By Either Party. This Agreement shall be terminable
upon the material breach or default of either party.
In the event of a material breach or default by a
party ("Defaulting Party"), the other party
("Non-Defaulting Party") shall give the Defaulting
Party written notice of the default. The Defaulting
Party will then have sixty (60) days to cure the
breach. If cure has not been affected within said
sixty (60) days, the Non-Defaulting Party shall have
the right to terminate this Agreement.
(b)
By CELGENE.
(i) Payments. If and only if CELGENE materially
breaches this Agreement by failure to pay
royalties and/or sublicensing or milestone
payments due under Section 4 of this
Agreement, and fails to cure such material
breach within sixty (60) days of receiving
written notice thereof pursuant to Section
12.4(a) of this Agreement then:
a) CELGENE's rights under this
Agreement to ENTREMED INTELLECTUAL
PROPERTY shall terminate; and
b) CELGENE shall grant to ENTREMED, to
the extent not prohibited by the
United States Government or by prior
contractual obligations to any THIRD
PARTY, an exclusive, worldwide,
royalty-free license, with the right
to sublicense, under CELGENE
DEVELOPED INTELLECTUAL PROPERTY to
make, use, offer to sell, sell, and
import PRODUCTS in the TERRITORY.
(ii) Diligence. If and only if ENTREMED exercises
its right and option to terminate the
license granted to CELGENE in the entire
TERRITORY, pursuant to Section 3.1(f) of
this Agreement, or
ENTREMED exercises its right and option to
terminate the license granted to CELGENE in
Europe, Canada, or the PACIFIC RIM, pursuant
to Section 3.2(c)(i) of this Agreement,
then, either in the entire TERRITORY or in
the region in which such termination has
occurred, i.e., Europe, Canada, or the
PACIFIC RIM, as applicable:
a) CELGENE's rights under this
Agreement to ENTREMED INTELLECTUAL
PROPERTY shall terminate; and
b) CELGENE shall grant to ENTREMED, to
the extent not prohibited by the
United States Government or by prior
contractual obligations to any THIRD
PARTY, an exclusive, worldwide,
royalty-free license, with the right
to sublicense, under CELGENE
DEVELOPED INTELLECTUAL PROPERTY to
make, use, offer to sell, sell, and
import PRODUCTS.
The grant of rights by CELGENE to ENTREMED under this
Section 12.4 expressly excludes rights in any CELGENE
EXISTING INTELLECTUAL PROPERTY.
(c) Termination under this Section 12.4 will be effective
upon the date specified in the written notice. All
termination rights shall be in addition to and not in
substitution for any other remedies that may be
available to the Non-Defaulting Party. Termination
pursuant to this Section 12.4 shall not relieve the
Defaulting Party from liability and damages to the
Non-Defaulting Party for default. Waiver by either
party of a single default or a succession of defaults
shall not deprive such party of any right to
terminate or convert this Agreement arising by reason
of any subsequent default.
12.5 Insolvency. Either party to this Agreement may terminate this
Agreement upon receipt of notice that the other party has
become insolvent or has suspended business in all material
respects hereof, or has consented to an involuntary petition
purporting
to be pursuant to any reorganization or insolvency law of any
jurisdiction, or has made an assignment for the benefit of
creditors or has applied for or consented to the appointment
of a receiver or trustee for a substantial part of its
property, by giving written notice to the other party, and
termination of this Agreement will be effective upon receipt
of such notice.
12.6 Work-In-Progress. Upon termination of this Agreement, CELGENE
shall be entitled to, but shall not be obligated to finish any
work-in-progress at the time of termination and sell the same
as well as all completed inventory of PRODUCTS which remains
on hand as of the date of the termination, so long as CELGENE
pays to ENTREMED the royalties applicable to said subsequent
sales in accordance with the same terms and conditions as set
forth in this Agreement.
12.7 Survival. The obligations of Sections 5 and 9, as well as
Sections 12.6, 12.7, 12.8, and 13.3, shall survive any
termination of this Agreement.
12.8 Reversion of Rights. Upon termination of this Agreement or of
the rights and licenses granted to CELGENE in any country of
the TERRITORY, CELGENE agrees not to use the TECHNOLOGY RIGHTS
or PATENT RIGHTS or information or technology derived
therefrom for the manufacture, use or sale of PRODUCTS in any
country other than those countries in which CELGENE retains a
license under this Agreement. In addition, all rights to the
TECHNOLOGY RIGHTS and PATENT RIGHTS in such country shall
revert to ENTREMED and may be used by ENTREMED without
restriction in any country other than those countries in which
CELGENE retains a license under this Agreement.
SECTION 13 - GENERAL PROVISIONS
13.1 Relationship of Parties. The relationship between ENTREMED and
CELGENE is that of independent contractors. ENTREMED and
CELGENE are not joint venturers, partners, principal and
agent, master and servant, employer or employee, and have no
relationship other than as independent contracting parties.
ENTREMED shall have no power to bind or obligate CELGENE in
any manner. Likewise, CELGENE shall have no power to bind or
obligate ENTREMED in any manner.
13.2 Entire Understanding. This Agreement sets forth the entire
agreement and understanding between the parties as to the
subject matter thereof and supersedes all prior agreements in
this respect. There shall be no amendments or modifications to
these Agreements, except by a written document which is signed
by both parties.
13.3 Governing Law. This Agreement shall be construed and enforced
in accordance with the laws of the State of Delaware,
U.S.A. without reference to its choice of law principles.
13.4 Headings. The headings in this Agreement have been inserted
for the convenience of reference only and are not intended to
limit or expand on the meaning of the language contained in
the particular or section or paragraph.
13.5 No Waiver. Any delay in enforcing a party's rights under this
Agreement or any waiver as to a particular default or other
matter shall not constitute a waiver of a party's right to the
future enforcement of its rights under this Agreement,
excepting only as to an expressed written and signed waiver as
to a particular matter for a particular period of time.
13.6 Export Controls. In conducting any activities under this
Agreement or in connection with the manufacture use or sale of
PRODUCT, CELGENE shall comply with all
applicable laws and regulations including, but not limited to,
all Export Administration Regulations of the United States
Department of Commerce.
13.7 Notices. Any notices given pursuant to this Agreement shall be
in writing and shall be deemed delivered upon the earlier of
(i) when received at the address set forth below, or (ii)
three (3) business days after mailed by certified or
registered mail postage prepaid and properly addressed, with
return receipt requested, or (iii) when sent, if sent by
facsimile, as confirmed by certified or registered mail.
Notices shall be delivered to the respective parties as
indicated below:
If To ENTREMED EntreMed, Inc.
9610 Medical Center Drive
Rockville, MD 20850
Attn: CEO
Fax: (301) 217-9594
If To CELGENE: Celgene Corporation
6 Powder Horn Drive
Warren, NJ 07059
Attn: President
Fax: (732) 805-3931
13.8 Original Counterparts. This Agreement may be executed in any
number of separate counterpart, each of which shall be deemed
to be an original, but which together shall constitute one and
the same instrument.
IN WITNESS WHEREOF, the parties have executed this Agreement
as of the date set forth above.
ENTREMED, INC. CELGENE CORPORATION
By:____________________________ By:____________________________
Name:__________________________ Name:__________________________
Title:_________________________ Title:_________________________
IN WITNESS WHEREOF, the parties have executed this Agreement as of the
date set forth above.
ENTREMED, INC. CELGENE CORPORATION
By: /s/ Edward R. Gubish By: /s/ John W. Jackson
------------------------------- -------------------------------
Name: Edward R. Gubish Name: John W. Jackson
---------------------------- ----------------------------
Title: Sr. V.P. R & D Title: Chairman & CEO
--------------------------- ----------------------------
APPENDIX A
United States Patent No. 5,629,327
United States Patent No. 5,593,990
United States Patent Application Serial No. 08/025,046
United States Patent Application Serial No. 08/168,817
United States Patent Application Serial No. 08/371,987
United States Patent Application Serial No. 08/468,792
United States Patent Application Serial No. 08/918,610
United States Patent Application Serial No. 08/955,638
United States Patent Provisional Application Serial No. 60/028,708
United States Patent Application Serial No. 08/963,058
United States Patent Application Serial No. 09/107,578
United States Patent Application Serial No. 09/126,542
APPENDIX B
1. That certain License Agreement entered into by and between ENTREMED and
Children's Medical Center Corporation ("CMCC"), dated May 26, 1994, as
amended to the date hereof, attached as Exhibit A to this Agreement.
2. That certain Agreement by and between the Division of Cancer Treatment
at the National Cancer Institute ("NCI") and ENTREMED, dated November
16, 1994, and executed on behalf of ENTREMED on November 23, 1994, and
on behalf of NCI on November 18, 1994, attached as Exhibit C to this
Agreement.
APPENDIX C
Orphan Drug Designation Application (ODA) 97-1011 Primary Brain Malignancies
Orphan Drug Designation Application (ODA) 98-1149 Kaposis Sarcoma
Orphan Drug Designation Application (ODA) 98-1143 Prostate Cancer
Investigational New Drug Application 46,591 Ophthalmology
Investigational New Drug Application 55,966 Oncology
APPENDIX D
United States Patent No. 5,605,684 to Piacquadio
United States Patent No. 5,443,824 to Piacquadio
United States Patent No. 5,731,325 to Andrulis, Jr. et al.
United States Patent No. 5,654,312 to Andrulis, Jr. et al.
United States Patent No. 5,643,915 to Andrulis, Jr. et al.
United States Patent No. 5,434,170 to Andrulis, Jr.
EXHIBIT A
CMCC AGREEMENT
EXHIBIT B
NCI AGREEMENT
EXHIBIT C
LETTER TO FDA INDICATING TRANSFER OF
RIGHTS IN INVESTIGATIONAL NEW DRUG
AND ORPHAN DRUG APPLICATIONS TO CELGENE