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EXHIBIT NO. 10.6
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Confidential Materials Omitted
and filed separately with the
Securities and Exchange Commission.
Asterisks denote ommissions.
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RESEARCH AND LICENSE AGREEMENT
This Agreement is effective August 1, 1992 ("the EFFECTIVE DATE") by
and between The Brigham and Women's Hospital, Inc. ("HOSPITAL"), having an
address at 75 Francis Street, Boston, Massachusetts 02115, and NitroMed, Inc., a
Delaware Corporation having offices at c/o Healthcare Investment Corp., 379
Thornall Street, Edison, New Jersey 08837 ("NITROMED").
WHEREAS, NITROMED desires to fund certain work to be performed at
HOSPITAL in exchange for exclusive licenses in and to certain Patents,
technology, materials and information; and
WHEREAS, HOSPITAL desires to receive such funding and is willing to
grant the exclusive licenses desired by NITROMED.
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 NITROMED shall mean any company or other
legal entity other than NITROMED in whatever country organized, controlling,
controlled by or under common control with NITROMED. The term "control" means
possession, of the power to direct or cause the direction of the management and
policies whether through the ownership of voting securities, by contract or
otherwise.
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1.2 The term "FIRST COMMERCIAL SALE" shall mean in each country the first
sale of any PRODUCT by NITROMED, its AFFILIATES or SUBLICENSEES, following
approval of its marketing 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.
1.3 The term "RESEARCH INVENTION" shall mean any process, use, article of
manufacture, composition of matter conceived or first actually or constructively
reduced to practice in the performance of SPONSORED RESEARCH and/or any other
research funded in whole or in part by NITROMED pursuant to this Agreement
solely or jointly by at least one INVESTIGATOR, whether or not in the FIELD OF
RESEARCH.
1.4 The term "BACKGROUND INVENTION" shall mean any process, use, article of
manufacture, composition of matter conceived or reduced to practice by PRINCIPAL
INVESTIGATOR (alone or with others) prior to the EFFECTIVE DATE, which is within
the FIELD OF RESEARCH.
1.5 "INVENTION" shall mean individually and collectively RESEARCH INVENTION
and BACKGROUND INVENTION.
1.6 The term "INVESTIGATOR" means PRINCIPAL INVESTIGATOR, any other member
of the HOSPITAL Professional Staff, graduate student, undergraduate student, or
employee of HOSPITAL who shall perform SPONSORED RESEARCH.
1.7 The term "SUBLICENSEE" shall mean any non-AFFILIATE third party
licensed by NITROMED to make, have made, import, use or sell any PRODUCT or use
any PROCESS under PATENT RIGHTS.
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1.8 The term "BACKGROUND MATERIAL" shall mean any material or substance
which relates to the FIELD OF RESEARCH and is in the possession of HOSPITAL
through the PRINCIPAL INVESTIGATOR or the PRINCIPAL INVESTIGATOR on the
EFFECTIVE DATE.
1.9 The term "RESEARCH MATERIAL" shall mean any material or substance which
is discovered, produced or derived by an INVESTIGATOR in the performance of
SPONSORED RESEARCH and/or any other research funded in whole or in part by
NITROMED pursuant to this Agreement.
1.10 "HOSPITAL MATERIAL" shall mean individually and collectively
BACKGROUND MATERIAL and RESEARCH MATERIAL.
1.11 "NET SALES PRICE" means the total amount received by NITROMED or
its AFFILIATES or SUBLICENSEE from sale of PRODUCT, less transportation
charges and insurance, sales taxes, use taxes, excise taxes, value added
taxes, customs duties or other imposts, normal and customary quantity and
cash discounts, and allowances and credit on account of rejection or return
of PRODUCT.
PRODUCT shall be considered "sold" when billed out or invoiced.
1.12 The term "BACKGROUND PATENT RIGHT(s)" shall mean any United States
patent application, including any division, continuation, or
continuation-in-part thereof and any foreign patent application or equivalent
corresponding thereto and any Letters Patent or the equivalent thereof issuing
thereon or reissue or extension thereof, insofar as it contains one or more
claims to a BACKGROUND INVENTION, BACKGROUND INFORMATION, or BACKGROUND
MATERIAL. The BACKGROUND PATENT RIGHTS are tabulated in Appendix B.
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1.13 The term "RESEARCH PATENT RIGHT(S)" shall mean any United States
patent application, including any division, continuation, or
continuation-in-part thereof and any foreign patent application or equivalent
corresponding thereto and any Letters Patent or the equivalent thereof issuing
thereon or reissue or extension thereof, insofar as it contains one or more
claims to a RESEARCH INVENTION, RESEARCH INFORMATION, or RESEARCH MATERIAL.
1.14 "PATENT RIGHT(S)" shall mean individually and collectively BACKGROUND
PATENT RIGHTS and RESEARCH PATENT RIGHTS.
1.15 The term "PRINCIPAL INVESTIGATOR" shall mean either or both Dr.
Joseph Loscalzo and Dr. Jonathan Stamler.
1.16 The term "PRODUCT" shall mean any article, composition, apparatus,
substance, chemical, material, method or service which is an HOSPITAL
MATERIAL, or which is, incorporates or utilizes an INVENTION and/or
INFORMATION, or the manufacture, import, sale or use of which is covered by
PATENT RIGHTS.
1.17 The term "PROCESS" shall mean any process or method for the
production, manufacture or use of any PRODUCT.
1.18 The term "BACKGROUND INFORMATION" shall mean any data, formulas,
process information or other information pertaining to the FIELD OF RESEARCH
known to HOSPITAL through PRINCIPAL INVESTIGATOR or the PRINCIPAL
INVESTIGATOR on the EFFECTIVE DATE.
1.19 "RESEARCH INFORMATION" shall mean any data, formulas, process
information or other information produced by an INVESTIGATOR in the performance
of SPONSORED RESEARCH and/or any other research funded in whole or in part by
NITROMED pursuant to this Agreement.
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1.20 "INFORMATION" shall mean individually and collectively RESEARCH
INFORMATION and BACKGROUND INFORMATION.
1.21 The term "RESEARCH PROPOSAL" shall mean the written description of
SPONSORED RESEARCH attached hereto as Appendix A, including a budget that
details the equipment, materials and the personnel to be provided by use of
the funds to be supplied by NITROMED to support the research described in
such proposal or any other written description of research attached hereto by
Agreement of the parties pursuant to Paragraph 2.2.
1.22 The term "SPONSORED RESEARCH" shall mean described in the RESEARCH
PROPOSAL.
1.23 VALID CLAIM shall mean (i) a claim of a pending patent Application
which has been pending for no more than seven (7) years from the filing date
of the original subject matter covered by the claim or, (ii) a claim of an
issued patent which has not lapsed or become abandoned or been declared
invalid or unenforceable by a court of competent jurisdiction or an
administrative agency from which no appeal can be or is taken.
1.24 "FIELD OF RESEARCH" means (i) nitric oxide compounds, nitrosothiol
compounds, nitroso protein compounds and nitrosylated compounds, and/or
compounds related to the above and/or (ii) uses for such compounds including but
not limited to diagnostic, therapeutic and prophylactic and/or (iii) agonists
and antagonists thereof.
1.25 "AGREEMENT YEAR" shall mean the twelve month period beginning on
the EFFECTIVE DATE, and each subsequent twelve (12) month period thereafter.
1.26 "LICENSED TERRITORY" shall mean all countries of the world.
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1.27 The use herein of the plural shall include the singular, and the use
of the masculine shall include the feminine.
SECTION 2 - FUNDING.
2.1 (A) In consideration of the undertaking of SPONSORED RESEARCH by
HOSPITAL, during the period in which SPONSORED RESEARCH is being conducted:
(i) subject to Paragraph 13.1, NITROMED shall make annual research grants
to HOSPITAL for the support of SPONSORED RESEARCH as follows:
<Table>
<Caption>
AGREEMENT RESEARCH
YEAR GRANT PER YEAR
---- --------------
1 $[**]
======
2 $[**]
======
3 through 10 $[**]
======
</Table>
(ii) each annual grant shall be paid in four equal quarterly payments. The
first payment shall be paid within thirty (30) days of the execution
of this Agreement by NITROMED;
(iii) the funding shall include direct and/or indirect expenses as set
forth in the RESEARCH PROPOSAL;
(B) at least sixty (60) days prior to the end of an AGREEMENT YEAR,
HOSPITAL shall submit to NITROMED for its approval a plan and budget
for use of the funding for the following AGREEMENT YEAR, which
approval shall not be unreasonably denied. NITROMED shall provide such
approval or disapproval within thirty (30) days from receipt of
HOSPITAL's plan and budget. Such approved-plan and budget shall be
attached and made a part hereof. The approved plan and budget for the
first AGREEMENT YEAR is attached hereto as Appendix C.
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(C) within sixty (60) days after the end of an AGREEMENT YEAR, HOSPITAL
shall provide NITROMED with an accounting of the expenditure of
research funds for such AGREEMENT YEAR in accordance with HOSPITAL
standard procedures for such accounting.
(D) NITROMED shall pay the costs of leasing those items of equipment
listed or to be listed in Appendix D which are selected by PRINCIPAL
INVESTIGATOR and leased by HOSPITAL and which have an aggregate fair
market value not exceeding $[**] in the first AGREEMENT YEAR, and
$[**] in each of the subsequent AGREEMENT YEARS, all of such
equipment shall be owned by HOSPITAL upon completion of the term of
the relevant lease. All such leases shall have terms at least as long
as the initial term of the RESEARCH PROPOSAL for the research in
which the equipment is to be used. NITROMED shall pay HOSPITAL the
amounts owed under each lease at least thirty (30) days prior to the
date on which payments are due to the lessor.
2.2 During the period during which NITROMED is funding SPONSORED RESEARCH
under this Agreement, either party may propose in writing additional research
not previously described in the RESEARCH PROPOSAL appended hereto as Appendix A.
Each such proposal shall include a description of the additional research
proposed and a budget of the costs to be funded by NITROMED and a schedule of
payment of such costs. When and if such proposal is accepted by HOSPITAL and
NITROMED, it shall be appended hereto as a RESEARCH PROPOSAL and shall be
subject to the terms and conditions of this Agreement unless otherwise
specified, and the SPONSORED RESEARCH described therein shall commence and
additional budgeted amounts shall be paid as set forth in the proposal or as
otherwise agreed by the parties in writing. When and if such proposal is
rejected by NITROMED, subject to Paragraph 2.3 below, HOSPITAL may seek funding
from another commercial sponsor.
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2.3 During the period during which NITROMED is funding SPONSORED RESEARCH
under this Agreement, an INVESTIGATOR may not seek funding from another
commercial sponsor for an additional research proposal in the FIELD of RESEARCH
until such proposal has been submitted to NITROMED in accordance with the
foregoing Paragraph 2.2 and the parties have not agreed to append such proposal
hereto as a RESEARCH PROPOSAL. In the event of such failure to agree, an
INVESTIGATOR shall be free to seek and accept funding from another commercial
sponsor for such research proposal, provided, that the subject.
In the event an INVESTIGATOR is permitted to seek funding from another
commercial sponsor under this Paragraph 2.3, INVESTIGATOR shall discuss with
NITROMED potential commercial sponsors from whom INVESTIGATOR intends to seek
such funding.
2.4 The Hospital shall have the right to choose one or more outside
observers to make an independent scientific review of the research conducted
hereunder by the Hospital and to report to the Hospital on an annual basis. The
costs and expenses of the review, not to exceed $[**] per year, shall be paid
by NITROMED. It is expected that the annual cost will generally be no more than
$[**] per year.
SECTION 3 - WORK OF HOSPITAL.
3.1 During the thirty (30) days next following the EFFECTIVE DATE,
HOSPITAL, through the PRINCIPAL INVESTIGATOR, shall disclose to NITROMED such
BACKGROUND INFORMATION and BACKGROUND MATERIAL which shall be known to HOSPITAL
and PRINCIPAL INVESTIGATOR on the EFFECTIVE DATE.
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3.2 Beginning on the EFFECTIVE DATE and thereafter unless sooner
terminated, HOSPITAL shall:
(a) through the PRINCIPAL INVESTIGATOR conduct SPONSORED RESEARCH, and
apply the funds paid by NITROMED pursuant to Paragraph 2.1 or 2.2 to
support the expenses of SPONSORED RESEARCH in accordance with the
RESEARCH PROPOSAL and shall use reasonable efforts and diligence
consistent with HOSPITAL's professional standards to achieve the goals
set forth in such RESEARCH PROPOSAL.
(b) promptly and systematically disclose to NITROMED, INFORMATION,
INVENTIONS and HOSPITAL MATERIAL, and NITROMED shall be entitled to
use such INFORMATION, INVENTIONS and HOSPITAL MATERIAL as provided
herein.
(c) for the purpose of facilitating disclosure to NITROMED of RESEARCH
INFORMATION, INVENTIONS, and HOSPITAL MATERIAL, permit duly authorized
employees of or representatives of NITROMED to visit the PRINCIPAL
INVESTIGATOR'S laboratories at HOSPITAL or other HOSPITAL facilities
where SPONSORED RESEARCH is conducted at reasonable times and with
reasonable notice;
(d) promptly advise NITROMED of any INVENTION and adequate advance notice
of the intent to file, filing, allowance and issuance of any PATENT
RIGHT; and
(e) at NITROMED's request provide NITROMED with HOSPITAL MATERIALS.
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3.3 HOSPITAL shall, on a continuing basis, advise NITROMED of the results
of the SPONSORED RESEARCH and at least once every six (6) months provide
NITROMED with written progress reports concerning the SPONSORED RESEARCH. A
final written report setting forth in detail the results achieved under and
pursuant to the SPONSORED RESEARCH shall be submitted by HOSPITAL to NITROMED
within ninety (90) days of termination of the SPONSORED RESEARCH. Such final
report shall include: (i) a complete summary of the research carried out; (ii) a
scientific assessment by the PRINCIPAL INVESTIGATOR of the SPONSORED RESEARCH;
and (iii) detailed experimental protocols of the assays performed in the course
of the SPONSORED RESEARCH.
SECTION 4 - HOSPITAL MATERIALS.
4.1 (a) During the period in which the SPONSORED RESEARCH is being
conducted, and in which NITROMED holds a license, HOSPITAL and INVESTIGATORS
shall not, without NITROMED's prior written approval, distribute or knowingly
allow HOSPITAL MATERIALS to be distributed to for-profit entities or persons
known to be employed thereby or consulting or performing research therefor other
than under a license permitted under this Agreement.
(a) HOSPITAL and PRINCIPAL INVESTIGATOR shall have the right to transfer
HOSPITAL MATERIALS to not-for-profit entities or persons known to be affiliated
therewith provided that such entities or persons sign the Material Transfer
Agreement attached hereto as Appendix E or any other Agreement consented to by
the parties.
(b) Prior to any such distribution of any such HOSPITAL MATERIAL, HOSPITAL
and NITROMED shall use reasonable efforts to consider the patentability of such
HOSPITAL MATERIALS and cooperate to file, where appropriate, PATENT RIGHTS
protecting such HOSPITAL MATERIALS prior to their distribution.
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4.2 Notwithstanding anything else to the contrary, HOSPITAL and
INVESTIGATOR agree not to publish or disclose to third parties the identity of
new compounds, or new methods of synthesis, conceived or developed as part of
the performance of the SPONSORED RESEARCH without supplying NITROMED with a copy
of the material to be disclosed or published to third parties at least sixty
(60) days prior notice of such publication or disclosure so that NITROMED may
evaluate such material to determine whether the material contains patentable
subject matter relating to an INVENTION on which a patent application should be
filed or contains NITROMED Confidential Information as defined in Paragraph 6.1.
NITROMED shall review the material within fifteen (15) days of submission to
NITROMED. At NITROMED's request, HOSPITAL initially will delay submission of the
manuscript for an additional thirty (30) days in order to enable the preparation
and filing of a patent application on any such patentable subject matter and
will cooperate with NITROMED in deleting from any such manuscript NITROMED
Confidential Information the inclusion of which would contravene Paragraphs 6.1
and 6.3 hereof. Notwithstanding anything to the contrary HOSPITAL will not be
required to withhold submission of such material for a period which is more than
ninety (90) days after NITROMED is first provided with the material to be
disclosed or published.
SECTION 5 - GRANTS.
5.1 (a) HOSPITAL hereby grants to NITROMED and NITROMED hereby accepts from
HOSPITAL a sole and exclusive royalty bearing right and license for the LICENSED
TERRITORY under PATENT RIGHTS and INVENTION to make, have made, use and sell or
have sold on its behalf PRODUCT or LICENSED PROCESS, including the right to
sublicense third parties. NITROMED shall have the right to extend such license
to its AFFILIATES.
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(b) In the event that PATENT RIGHTS and INVENTIONS are co-owned by HOSPITAL
and a third party, the license granted in Paragraph 5.1(a) shall only apply to
HOSPITAL'S interest in such PATENT RIGHTS and INVENTIONS. For PATENT RIGHTS or
INVENTIONS owned jointly by HOSPITAL and at least one third party, HOSPITAL
shall pursuant to Paragraph 7.1(a) of this Agreement attempt to obtain an
agreement granting on behalf of all of the owners thereof a sole and exclusive
right and license to NITROMED. If terms agreeable to all of the parties
(including such third party assignees) can not be reached or, at NITROMED's
request, HOSPITAL will be relieved from its obligations under Paragraph 7.1(a)
of this Agreement and only HOSPITAL'S interest in such PATENT RIGHTS and
INVENTION shall be licensed to NITROMED under Paragraph 5.1(a) of this
Agreement.
5.2 NITROMED agrees to forward to HOSPITAL a copy of any and all fully
executed sublicense agreements, and further agrees to forward to HOSPITAL
annually a copy of such reports received by NITROMED from its SUBLICENSEES
during the preceding twelve (12) month period under the sublicensees as shall be
pertinent to a royalty accounting to HOSPITAL under said sublicense agreements.
5.3 The above licenses to sell any PRODUCT includes the right of NITROMED,
its AFFILIATES, and SUBLICENSEES to grant to the purchaser thereof the right to
use and/or resell such purchased PRODUCT.
5.4 All licenses pursuant to Paragraphs 5.2 and 5.3 above to PATENT RIGHTS
conceived or first actually reduced to practice during the course of research
funded by a U.S. federal agency are subject to the rights, conditions and
limitations imposed by U.S. law. The words "sole and exclusive license" as used
herein shall mean sole and exclusive except for the royalty free non-exclusive
license granted to the U.S. government by HOSPITAL pursuant to 35 USC Section
202(c)(4) for any PATENT RIGHTS claiming any INVENTION subject to 35 USC Section
201 and any other federal laws and applicable regulations.
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5.5 HOSPITAL agrees not to enter into an agreement with a third party to
acquire materials for use in SPONSORED RESEARCH under terms that will prevent
HOSPITAL from granting NITROMED exclusive rights to PATENT RIGHTS and INVENTION.
5.6 (a) Taking into account the complexity, and stage of development of the
PRODUCT and the science related thereto, NITROMED shall select and use
reasonable efforts and diligence under the circumstances to research, develop
and then commercialize a selected PRODUCT. The efforts of a SUBLICENSEE and/or
an AFFILIATE and the SPONSORED RESEARCH shall be considered as efforts of
NITROMED.
(b) In the event that HOSPITAL reasonably believes that NITROMED is not
making reasonable efforts under the circumstances to research, develop and then
commercialize a selected PRODUCT by NITROMED pursuant to Paragraph 5.6(a) then
HOSPITAL shall provide written notice to NITROMED which specifies HOSPITAL's
basis for such belief and what additional efforts HOSPITAL believes should be
made by NITROMED. Upon receipt of such written notice, HOSPITAL and NITROMED
shall enter into good faith negotiations in order to reach mutual agreement as
to what efforts by NITROMED shall satisfy the requirements of this Paragraph
5.6, and if such mutual agreement is not reached within [**] days after
receipt of such written notice, then the parties agree to submit to
arbitration pursuant to Paragraph 14.2 to determine the efforts which should
be exerted by NITROMED. Thereafter, NITROMED shall exert the efforts
determined by the parties or in such arbitration.
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(c) If NITROMED fails to exert the efforts determined by the parties or in
such arbitration, HOSPITAL's sole and exclusive remedy for NITROMED's failure to
meet such efforts is for the licenses granted hereunder to be converted from an
exclusive right and license to a non-exclusive license, provided that NITROMED
has initiated and continues to expend a minimum of [**] dollars ($[**]) per
year on the research and development of a selected PRODUCT until the FIRST
COMMERCIAL SALE of a PRODUCT. If NITROMED does not initiate and continue the
research and development of a selected PRODUCT as specified in this Paragraph
5.6(c), HOSPITAL's sole and exclusive remedy is for the such non-exclusive
license to be terminated.
5.7 HOSPITAL acknowledges that NITROMED is in the business of developing,
manufacturing and selling of medical processes and products and nothing in this
Agreement shall be construed as restricting such business or imposing on
NITROMED the duty to market, and/or sell and exploit PRODUCT for which royalties
are due hereunder to the exclusion of or in preference to any other product or
process.
5.8 Subject to Section 5.6, NITROMED shall have sole discretion for making
all decisions relating to the commercialization and marketing of PRODUCT, and
will bear the cost of preparing such PRODUCT for market and for obtaining
governmental approvals where required.
5.9 Within sixty (60) days after the end of each calendar year, NITROMED
shall report in writing to HOSPITAL on the progress of its efforts under
Paragraph 5.6.
SECTION 6 - CONFIDENTIALITY.
6.1 During the term of this Agreement, it is contemplated that each party
will disclose to the other proprietary and confidential technology, inventions,
technical information, 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 shall have the right to refuse to accept the other party's Confidential
Information. Each party agrees to retain such Confidential Information in
confidence and not to disclose any such Confidential Information to a third
party without the prior written consent of the party providing such information
and to use such Confidential Information only for the purposes of this
Agreement.
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6.2 The obligations of confidentiality will not apply to Confidential
Information which:
(i) was known to the receiving party or generally known to the public
prior to its disclosure hereunder; or
(ii) 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;
(iii) is subsequently disclosed to the receiving party by a third party
having a lawful right to make such disclosure;
(iv) is disclosed to obtain regulatory approval for PRODUCT, provided that
the disclosing party takes all reasonable steps to restrict and
maintain the confidentiality of the disclosure ;
(v) is required by law or BONA FIDE legal process to be disclosed,
provided that the disclosing party takes all reasonable steps to
restrict and maintain confidentiality of such disclosure and provides
reasonable notice to the non-disclosing party; or
(vi) is approved for release by the parties.
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SECTION 7 - PATENTS.
7.1 (a) Each INVESTIGATOR who during the course of SPONSORED RESEARCH shall
make an INVENTION, solely or jointly, ("HOSPITAL INVENTOR") shall promptly
report such INVENTION to HOSPITAL. Each HOSPITAL INVENTOR shall assign all of
his rights, title and interest in an INVENTION and PATENT RIGHTS relating
thereto to HOSPITAL. Each employee of NITROMED who makes an INVENTION jointly
with an INVESTIGATOR, shall report such INVENTION to NITROMED and shall assign
all his rights, title and interest in such INVENTION and PATENT RIGHTS relating
thereto to NITROMED. INVENTIONS made jointly by one or more INVESTIGATORS and
one or more NITROMED employees and PATENT RIGHTS relating thereto shall be
jointly owned by HOSPITAL and NITROMED. HOSPITAL and NITROMED agree that for
each PATENT RIGHT jointly owned by HOSPITAL and NITROMED, NITROMED and HOSPITAL
each own a one-half undivided interest in such PATENT RIGHT in each country in
which it is filed and HOSPITAL's interest therein is subject to the rights
granted to NITROMED under this Agreement.
In the event any INVENTION results from collaboration with personnel who
is not affiliated with either HOSPITAL or NITROMED ("Unaffiliated
Collaborator(s)"), HOSPITAL shall attempt to obtain the relevant rights from
the institution of such Unaffiliated Collaborators and include same in the
aforesaid rights granted to NITROMED under Section 5 of this Agreement.
(b) HOSPITAL shall promptly advise NITROMED in writing of each INVENTION
disclosed to HOSPITAL. Representatives of HOSPITAL and NITROMED shall then
discuss whether a patent application or applications pertaining to such
INVENTION should be filed and in which countries. The titles, serial numbers and
other identifying data of patent applications claiming an INVENTION filed after
the EFFECTIVE DATE by mutual agreement of HOSPITAL and NITROMED shall be listed
in Appendix B and shall become PATENT RIGHTS.
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NITROMED shall file, prosecute and maintain patent applications and
patents directed to INVENTIONS through patent counsel selected by NITROMED who
shall consult with and keep HOSPITAL advised with respect thereto.
After the EFFECTIVE DATE of this Agreement, NITROMED shall bear the
cost and expense for the filing, prosecution and maintenance of PATENT RIGHTS in
the United States, European Patent Office, Canada, Japan and any other foreign
countries designated by NITROMED.
7.2 With respect to any PATENT RIGHTS, each patent application, office
action, response to office action, request for terminal disclaimer, and request
for reissue or reexamination of any patent issuing from such application shall
be provided to HOSPITAL sufficiently prior to the filing of such application,
response or request to allow for review and comment by HOSPITAL. HOSPITAL shall
have the right to take any action that in its judgment is necessary to preserve
such PATENT RIGHTS.
7.3 [**] percent ([**]%) of the amount paid by NITROMED pursuant to
this Section 7 expended by NITROMED to secure or maintain any PATENT RIGHTS
shall be fully creditable against royalties due under Section 8, but no royalty
payment, after taking into consideration any deduction pursuant to Section 8.2,
shall be reduced under this Paragraph 7.3 by more than [**]%.
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SECTION 8 - ROYALTIES AND EQUITY.
8.1 (A) On all sales of PRODUCTS anywhere in the world by NITROMED, its
AFFILIATES or SUBLICENSEE, following the FIRST COMMERCIAL SALE in such country
by NITROMED its AFFILIATES or SUBLICENSEES, NITROMED shall pay HOSPITAL
royalties in accordance with the following schedule, such undertaking and
schedule having been agreed to for the purpose of reflecting and advancing the
mutual convenience of the parties. For each PRODUCT sold or distributed by
NITROMED or its AFFILIATES and SUBLICENSEES NITROMED shall pay to HOSPITAL one
of the following:
(1) (i) [**] percent ([**]%) of the NET SALES PRICE of PRODUCTS (other
than PRODUCTS which are a diagnostic product or service) sold or
distributed by NITROMED or its AFFILIATES in a country and (ii) [**]
percent ([**]%) of the NET SALES PRICE of PRODUCT (other than PRODUCTS
which are a diagnostic product or service) sold or distributed by
SUBLICENSEES in a country (iii) [**] percent ([**]%) of the NET SALES
PRICE of PRODUCTS which are diagnostic products or diagnostic services
sold or distributed by NITROMED or its AFFILIATES in a country and
(iv) [**] ([**]%) of the NET SALES PRICE of PRODUCT which are
diagnostic products or diagnostic services sold or distributed by
SUBLICENSEES in a country so long as in each case the PRODUCT, its
manufacture, use or sale in the country in question shall be subject
to a VALID CLAIM of any PATENT RIGHT which is licensed exclusively to
NITROMED In such country, or
(2) (i) [**] percent ([**]%) of the NET SALES PRICE of PRODUCTS (other
than PRODUCTS which are diagnostic products or diagnostic services)
sold or distributed by NITROMED or its AFFILIATES in a country and
(ii) [**]percent ([**]%) of the NET SALES PRICE of PRODUCT (other
than PRODUCTS which are diagnostic products or diagnostic services)
sold or distributed by SUBLICENSEES in a country (iii) [**] percent
([**]%) of the NET SALES PRICE of PRODUCTS which are diagnostic
products or diagnostic services sold or distributed by NITROMED or its
AFFILIATES and (iv) [**] percent ([**]%) of the NET SALES PRICE
of PRODUCT which are diagnostic products or diagnostic services sold
or distributed by SUBLICENSEES in a country, whenever, in each case,
the PRODUCT, its manufacture, use or sale shall be subject to a VALID
CLAIM of only such PATENT RIGHTS which are licensed non-exclusively to
NITROMED in the country in question (the term non-exclusive license
includes a license in which HOSPITAL co-owns the applicable PATENT
RIGHTS with a third party(ies) and NITROMED does not receive an
exclusive license under this Agreement from all of the owners), or
18
<Page>
(3) (a) For each PRODUCT sold by NITROMED in which a competing product
employing similar technology is not available, (i) [**] percent
([**]%) of the NET SALES PRICE of PRODUCTS sold or distributed by
NITROMED or its AFFILIATES and (ii) [**] percent ([**]%) of the NET
SALES PRICE of PRODUCT sold or distributed by SUBLICENSEES (1) for
ten (10) years next following the FIRST COMMERCIAL SALE of any
PRODUCT whose manufacture, use or sale shall employ or incorporate
any HOSPITAL MATERIAL where such HOSPITAL MATERIALS are not subject
to one or more VALID CLAIMS of any PATENT RIGHT licensed to NITROMED
in such country or (2) for the ten (10) years next following the FIRST
COMMERCIAL SALE of any PRODUCT whose manufacture, use or sale shall
employ as a significant part thereof INFORMATION which is not subject
to any VALID CLAIM of a PATENT RIGHT licensed to NITROMED in such
country;
(B) In the event that a PRODUCT includes both component(s) covered by a
VALID CLAIM of a PATENT RIGHT ("Patented Component(s)") and a component which is
diagnostically useable or therapeutically active alone or in a combination which
does not require the Patented Component and such component is not covered by a
VALID CLAIM of a PATENT RIGHT ("Unpatented Component(s)") (such PRODUCT being a
"Combined Product"), then NET SALES PRICE shall be the amount which is normally
received by NITROMED or its AFFILIATES from a sale of the Patented Component(s)
in an arm's length transaction with an unaffiliated third party. If the Patented
Component(s) are not sold separately, then NET SALES PRICE upon which a royalty
is paid shall be the NET SALES PRICE of the Combined Product multiplied by a
fraction, the numerator of which is the cost for producing the Patented
Components and the denominator of which is the cost for producing the Combined
Product.
8.2 (a) In the event that royalties are to be paid by NITROMED to a party
who is not an AFFILIATE of NITROMED for PRODUCT for which royalties are also due
to HOSPITAL pursuant to Paragraph 8.1 ("Other Royalties"), then the royalties to
be paid to HOSPITAL by NITROMED pursuant to Paragraph 8.1 shall be reduced by
[**] of the amount of such Other Royalties, but in no event shall any
royalties under Paragraph 8.1 be reduced by more than [**] percent ([**]%).
(b) In addition to Paragraph 8.2(a), in the event that the royalty paid to
HOSPITAL is a significant factor in the return realized by NITROMED so as to
diminish NITROMED's capability to respond to competitive pressures in the
market, HOSPITAL agrees to consider a reasonable reduction in the royalty paid
to HOSPITAL as to each such PRODUCT for the period during which such market
condition exists. Factors determining the size of the reduction will include
profit margin on PRODUCT and on analogous products, prices of competitive
products, and NITROMED's expenditures in PRODUCT development.
19
<Page>
8.3 NITROMED shall keep, and shall cause each of its AFFILIATES and
SUBLICENSEES to keep, full and accurate books of account containing all
particulars that may be necessary for the purpose of calculating all royalties
payable to HOSPITAL. 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 HOSPITAL or its designee upon reasonable
notice during normal business hours at HOSPITAL's expense for the sole purpose
of verifying royalty statements or compliance with this Agreement, but in no
event more than once in each calendar year. All information and data offered
shall be used only for the purpose of verifying royalties and shall be treated
as NITROMED Confidential Information subject to the obligations of this
Agreement. In the event that such inspection shall indicate that in any calendar
year that the royalties which should have been paid by NITROMED are at least
five percent (5%) greater than those which were actually paid by NITROMED, then
NITROMED shall pay the cost of such inspection.
8.4 With each semi-annual payment, NITROMED shall deliver to HOSPITAL a
full and accurate accounting to include at least the following information:
(a) Quantity of each PRODUCT subject to royalty sold (by country) by
NITROMED, and its AFFILIATES;
(b) Total receipts for each PRODUCT subject to royalty (by country);
(c) Total royalties payable to HOSPITAL;
20
<Page>
(d) Royalties received from SUBLICENSEES.
8.5 In each year the amount of royalty due shall be calculated
semi-annually as of June 30 and December 31 (each as being the last day of an
"ACCOUNTING PERIOD") and shall be paid semi-annually within the sixty days next
following such date, every such payment shall be supported by the accounting
prescribed in Paragraph 8.4 and shall be made in United States currency.
Whenever for the purpose of calculating royalties conversion from any foreign
currency shall be required, such conversion shall be at the rate of exchange
thereafter published in the Wall Street Journal for the business day closest to
the applicable ACCOUNTING PERIOD, as the case may be.
8.6 If the transfer of or the conversion into United States Dollar
Equivalent of any remittance due hereunder is not lawful or possible in any
country, such remittance shall be made by the deposit thereof in the currency of
the country to the credit and account of HOSPITAL or its nominee in any
commercial bank or trust company located in that country, prompt notice of which
shall be given to HOSPITAL. HOSPITAL shall be advised in writing in advance by
NITROMED and provide to NITROMED a nominee, if so desired.
8.7 Any tax required to be withheld by NITROMED under the laws of any
foreign country for the account of HOSPITAL, shall be promptly paid by NITROMED
for and on behalf of HOSPITAL to the appropriate governmental authority, and
NITROMED shall use its best efforts to furnish HOSPITAL with proof of payment of
such tax. Any such tax actually paid on HOSPITAL's behalf shall be deducted from
royalty payments due HOSPITAL.
8.8 Only one royalty shall be due and payable for the manufacture, use and
sale of a PRODUCT irrespective of the number of patents or claims thereof which
cover the manufacture, use and sale of such PRODUCT.
21
<Page>
8.9 NITROMED shall sell to HOSPITAL common shares of NITROMED in accordance
with a Restricted Stock Purchase Agreement which incorporates the following
terms.
(a) Upon each issuance of stock by NITROMED, up until and including
issuances pursuant to which the aggregate gross proceeds, from the
capitalization of NITROMED, (other than proceeds from sales to HOSPITAL) shall
equal $3,500,000.00, HOSPITAL shall have the option to purchase a number of
shares of common stock of NITROMED as may be required in order that HOSPITAL'S
pro rata share of the equity of NITROMED on a fully diluted converted basis
immediately after the exercise of such option shall equal fifteen percent (15%).
The price per share is $.01 per share. In the event that the Research and
License Agreement by and between NITROMED and HOSPITAL is terminated for any
reason whatsoever, prior to the noted anniversaries, NITROMED shall have the
right to repurchase from HOSPITAL at a price of $.01 per share the following
percentage of the common shares of stock purchased pursuant to this paragraph.
First Anniversary 80%
Second Anniversary 40%
Third Anniversary 20%
(b) Prior to an IPO, in any venture capital round of financing, HOSPITAL
has the right to purchase a number of shares offered in such round at the per
share price of such round to maintain the HOSPITAL's percent ownership interest
in NITROMED which exists prior thereto under the same terms provided to
participating venture capital investors.
(c) Prior to an IPO, HOSPITAL can not sell its purchased shares to a third
party without first offering such shares to NITROMED on terms proposed by
HOSPITAL. If NITROMED elects not to purchase, for a period of six months after
such election by NITROMED, HOSPITAL can sell such shares to a third party on
terms no more favorable than those offered NITROMED. NITROMED has the right to
assign its right as set forth in this subparagraph 8.9(c) to any one or more of
its shareholders.
22
<Page>
(d) HOSPITAL is hereby granted "piggy-back" registration rights subject to
underwriter cut-back, on a pro-rata basis with other selling shareholders under
"piggy-back" rights. NITROMED will provide and pay for counsel for HOSPITAL for
such registration, which counsel shall be the same as the counsel for other
sellers in such round. The "piggy back" rights of this Paragraph, 8.9(d) shall
also be applicable to demand registrations.
(e) HOSPITAL agrees to be bound by any "lock-up" requirements of an
underwriter, provided that they are no more stringent then those imposed on the
venture capital shareholders.
SECTION 9 - INFRINGEMENT AND NONASSERTION.
9.1 (a) If any of the PATENT RIGHTS under which NITROMED is the licensee is
infringed by a third party, NITROMED shall have the right and option but not the
obligation to bring an action for infringement, at its sole expense, against
such third party in the name of HOSPITAL and/or in the name of NITROMED, and to
join HOSPITAL as a party plaintiff if required. NITROMED shall promptly notify
HOSPITAL of any such infringement and shall keep HOSPITAL informed as to the
prosecution of any action for such infringement. No settlement, consent judgment
or other voluntary final disposition of the suit which adversely affects PATENT
RIGHTS may be entered into without the consent of HOSPITAL, which consent shall
not unreasonably be withheld.
(b) In the event that NITROMED shall undertake the enforcement and/or
defense of the PATENT RIGHTS by litigation, NITROMED may withhold up to fifty
percent (50%) of the royalties otherwise thereafter due HOSPITAL hereunder and
apply the same toward reimbursement of its expenses, including reasonable
attorneys' fees, in connection therewith. Any recovery of damages by NITROMED
for any such suit shall be applied first in satisfaction of any unreimbursed
expenses and legal fees of NITROMED relating to the suit, and next toward
reimbursement of HOSPITAL for any royalties withheld and applied pursuant to
this Section 9. The balance remaining from any such recovery shall be divided
between NITROMED and HOSPITAL, as follows (i) for that portion, if any, based on
lost profits, HOSPITAL shall recover the royalty HOSPITAL "would have received
under this Agreement if such sales had been made by NITROMED; and (ii) for any
other recovery, HOSPITAL shall receive thirty percent (30%) of the remaining
amount.
23
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9.2 In the event that NITROMED elects not to pursue an action for
infringement, upon written notice to HOSPITAL by NITROMED that an unlicensed
third party is an infringer of a VALID CLAIM of PATENT RIGHTS licensed to
NITROMED, HOSPITAL 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.
9.3 In the event that litigation against NITROMED is initiated by a
third-party charging NITROMED with infringement of a patent of the third party
as a result of the manufacture, use or sale by NITROMED of PRODUCT covered by
PATENT RIGHTS, NITROMED shall promptly notify HOSPITAL in writing thereof.
NITROMED's costs as to any such defense shall be creditable against any and all
payments due and payable to HOSPITAL under Paragraph 8.1 of this Agreement but
no royalty payment after taking into consideration any such credit under this
Paragraph 9.3 shall be reduced by more than [**]%.
24
<Page>
9.4 In the event of a judgment in any suit in which a court of competent
jurisdiction rules that the manufacture, use or sale by NITROMED of PRODUCT
covered by a PATENT RIGHT has infringed on a third-party's patent requiring
NITROMED to pay damages or a royalty to said third party, or in the event of a
settlement of such suit requiring damages or royalty payments to be made,
payments due to HOSPITAL under Paragraph 8.1 of this Agreement arising from the
applicable PRODUCT shall be correspondingly reduced by the amounts due under the
requirement of such judgment or under the terms of such settlement. In no case,
however, shall the royalty payment after taking into consideration any such
reduction under this Paragraph 9.4 be reduced by more than [**]%.
9.5 In any infringement suit either party may institute to enforce 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 of HOSPITAL incurred in connection with rendering
cooperation requested by NITROMED shall be paid by NITROMED.
SECTION 10 - WARRANTIES.
10.1 Each of HOSPITAL and NITROMED warrants and represents to the other
that it has the full right and authority to enter into this Agreement, and that
it is not aware of any impediment which would inhibit its ability to perform the
terms and conditions imposed on it by this Agreement.
10.2 HOSPITAL warrants and represents that the named inventors have
assigned the PATENT RIGHTS tabulated in Appendix B to HOSPITAL, that it has not
licensed or assigned any right or interest in or to INVENTIONS and PATENT RIGHTS
to any third party; it has the right to grant the rights granted hereunder; that
the granting of such rights does not require the consent of a third party; that
there are and will be no outstanding agreements, assignments or encumbrances
inconsistent with the provisions of this Agreement, and that all INVESTIGATORS
performing SPONSORED RESEARCH will be obligated to assign to HOSPITAL, in
accordance with the Patent Policy of HOSPITAL, the ownership of INVENTIONS and
corresponding PATENT RIGHTS developed during SPONSORED RESEARCH.
25
<Page>
10.3 HOSPITAL covenants, warrants and represents that no other patents or
patent applications in the FIELD of RESEARCH naming the PRINCIPAL INVESTIGATORS
exists other than the PATENT RIGHTS tabulated in Appendix B.
10.4 HOSPITAL covenants, warrants, represents that (i) HOSPITAL has not
received any information with respect to any challenge by another as to the
validity of the BACKGROUND PATENT RIGHTS tabulated in Appendix B and (ii) the
HOSPITAL has not received any information that any of these BACKGROUND PATENT
RIGHTS is involved in an interference action.
SECTION 11 - INDEMNIFICATION.
11.1 (a) Each party shall notify the other of any claim, lawsuit or other
proceeding related to PRODUCT. Subject to the preceding sentence, NITROMED shall
indemnify, defend and hold harmless HOSPITAL and its trustees, officers, medical
and professional staff, employees and agents and their respective successors,
heirs and assigns (the "Indemnitees"), against any liability, damage, loss or
expense (including 'reasonable attorneys' fees and expenses of litigation)
incurred by or imposed upon the Indemnitees or any one of them in connection
with: (i) claims, suits, actions, demands or judgments arising out of any theory
of product liability (including, but not limited to, actions in the form of
tort, warranty or strict liability) concerning any product, process or service
relating to, or developed pursuant to this Agreement, or (ii) any third party
claims, suits, actions, demands or judgments arising out of any activities to be
carried out by Indemnitees pursuant to this Agreement.
26
<Page>
(b) NITROMED's indemnification under (a) shall not apply to any liability,
damage, loss or expense to the extent that it is directly attributable to the
negligent activities or intentional misconduct of the Indemnitees.
(c) NITROMED agrees at its own expense, to provide attorneys reasonably
acceptable to the HOSPITAL to defend against any actions brought or filed
against any party indemnified hereunder with respect to the subject of indemnity
contained herein, whether or not such actions are rightfully brought.
(d) HOSPITAL shall notify NITROMED promptly of any claim or threatened
claim under this Paragraph 11.1 and shall fully cooperate with all reasonable
requests of NITROMED with respect thereto.
(e) This Paragraph 11.1 shall survive expiration or termination of this
agreement.
11.2 (a) At such time as any PRODUCT or PROCESS relating to, or developed
pursuant to, this Agreement is being commercially distributed or sold (other
than for the purpose of obtaining regulatory approvals) by NITROMED or by a
licensee, AFFILIATE or agent of NITROMED, NITROMED shall, at its sole cost and
expense, procure and maintain comprehensive general liability insurance in
amounts not less than two million dollars ($2,000,000) per accident and two
million dollars ($2,000,000) annual aggregate and naming the Indemnities as
additional insureds. Such comprehensive general liability insurance shall
provide (i) product liability coverage and (ii) broad form contractual liability
coverage for NITROMED's indemnification under Paragraph 11.1 of this Agreement.
If NITROMED elects to self-insure all or part of the limits described above
(including deductibles or retentions which are in excess of $250,000 annual
aggregate) such self-insurance program must be acceptable to the HOSPITAL and
the Risk Management Foundation of the Harvard Medical Institutions, Inc. The
minimum amounts of insurance coverage required under this Paragraph 11.2 shall
not be construed to create a limit of NITROMED's liability with respect to its
indemnification under Paragraph 11.2 of this Agreement. At such time NITROMED
can request that HOSPITAL ascertain whether Risk Management Foundation has in
effect Uniform Indemnification and Insurance Provisions more favorable than
those of this Agreement, in which event NITROMED and HOSPITAL shall amend this
Agreement to include such more favorable insurance provisions.
27
<Page>
(b) NITROMED shall provide HOSPITAL with written evidence of such insurance
upon request of HOSPITAL. NITROMED shall provide HOSPITAL with written notice at
least fifteen (15) days prior to the cancellation, non-renewal or material
change in such insurance.
(c) NITROMED shall maintain such comprehensive general liability insurance
during (i) the period that any PRODUCT or PROCESS relating to, or developed
pursuant to this Agreement is being commercially distributed to sold (other than
that for the purpose of obtaining regulatory approvals) by NITROMED or by a
licensee, AFFILIATE or agent of NITROMED and (ii) a reasonable period after the
period referred to in (c)(i) above, which in no event shall be less than fifteen
(15) years. The obligations of (c)(ii) above can be satisfied by the purchase of
insurance by NITROMED or third party which covers claims made during such period
of (c)(ii) above for PRODUCT or PROCESS commercially distributed or sold by
NITROMED during the period referred in (c)(i) above.
(d) This Paragraph 11.2 shall survive expiration or termination of this
Agreement.
SECTION 12 - ASSIGNMENT; SUCCESSORS.
12.1 This Agreement shall not be assignable by either of the parties
without the prior written consent of the other party (which consent shall not be
unreasonably withheld), except that NITROMED without the consent of HOSPITAL may
assign this Agreement to an AFFILIATE or to a successor in interest of all or
substantially all of the portion of the business to which this Agreement relates
and HOSPITAL without the consent of NITROMED may assign this Agreement to THE
BRIGHAM MEDICAL CENTER, INC. or any wholly owned subsidiary thereof.
12.2 Subject to the limitations on assignment herein, this Agreement shall
be binding upon and inure to the benefit of said successors in interest and
assigns of NITROMED and HOSPITAL. 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 13 - TERMINATION.
13.1 Except as otherwise specifically provided herein and unless sooner
terminated pursuant to Paragraph 13.2 or 13.3 of this Agreement, this Agreement
and the licenses and rights granted thereunder shall remain in full force and
effect until the expiration of the last to expire PATENT RIGHT, at which time
NITROMED shall have a fully paid-up license.
28
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13.2 Except as qualified by Paragraph 13.7, NITROMED shall have the right
to terminate this Agreement or any or all licenses under one or more PATENT
RIGHTS in one or more countries upon sixty (60) days prior written notice.
13.3 Upon material breach of any material provisions of this Agreement by
either party to this Agreement, in the event the breach is not cured within
sixty (60) days after written notice to the breaching party by the other party,
in addition to any other remedy it may have, the other party at its sole option
may terminate this Agreement, provided that such other party is not then in
breach of this Agreement.
13.4 Upon any termination of this Agreement NITROMED shall be entitled to
finish any work-in-progress which is completed within six (6) months of
termination of this Agreement and to sell any completed inventory of a PRODUCT
covered by this Agreement which remains on hand as of the date of the
termination, so long as NITROMED pays to HOSPITAL the royalties applicable to
said subsequent sales in accordance with the same terms and conditions as set
forth in this Agreement.
13.5 In the event that this Agreement is terminated any SUBLICENSEE shall
have the right to become a direct license of HOSPITAL under PATENT RIGHTS and
INVENTION, to the extent such SUBLICENSEE was previously licensed by NITROMED,
provided that such SUBLICENSEE by written notice to HOSPITAL accepts the
licensing term and conditions of this Agreement within thirty (30) days after
such SUBLICENSEE receives notice that this Agreement has been terminated. Upon
HOSPITAL'S receipt of such notice from SUBLICENSEE, SUBLICENSEE shall be
automatically licensed under the licensing terms and conditions of this
Agreement.
29
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13.6 The obligations of Section 6 shall survive any termination of this
Agreement. Further, the obligations of Section 11 shall perpetually survive any
termination of this Agreement.
13.7 NITROMED may terminate funding of SPONSORED RESEARCH under Paragraph
2.1(A) and lease payments under Paragraph 2.1(D) under this Agreement on the
twenty-fourth (24th) month from the EFFECTIVE DATE of this Agreement, or any day
thereafter by giving HOSPITAL six (6) months prior written notice of its
election to terminate. If such funding is so terminated, NITROMED shall pay
HOSPITAL any reasonable costs and expenses which HOSPITAL has committed to pay
directly related to performance of the SPONSORED RESEARCH which cannot be
eliminated or reduced.
13.8 In the event PRINCIPAL INVESTIGATOR is no longer available or able to
continue direction of SPONSORED RESEARCH, HOSPITAL shall promptly notify
NITROMED and may nominate a replacement; if HOSPITAL does not nominate a
replacement within thirty (30) days or if that replacement is unsatisfactory to
NITROMED, NITROMED may immediately terminate funding of SPONSORED RESEARCH. If
such funding is so terminated, NITROMED shall pay HOSPITAL any reasonable costs
and expenses which HOSPITAL has committed to pay directly related to performance
of the SPONSORED RESEARCH which cannot be eliminated or reduced.
13.9 Upon termination of this Agreement for any reason, nothing herein
shall be construed to release either party from any obligation that matured
prior to the effective date of such termination.
30
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SECTION 14 - GENERAL PROVISIONS.
14.1 The relationship between HOSPITAL and NITROMED is that of independent
contractors. HOSPITAL and NITROMED are not joint venturers, partners, principal
and agent, master and servant, employer or employee, and have no relationship
other than as independent contracting parties. HOSPITAL shall have no power to
bind or obligate NITROMED in any manner. Likewise, NITROMED shall have no power
to bind or obligate HOSPITAL in any manner.
14.2 Any matter or disagreement under Paragraph 2.3 or 5.6 which this
Agreement specifically specifies is to be resolved by arbitration shall be
submitted to a mutually selected single arbitrator to so decide any such matter
or disagreement. The arbitrator shall conduct the arbitration in accordance with
the Rules of the American Arbitration Association, unless the parties agree
otherwise. If the parties are unable to mutually select an arbitrator, the
arbitrator shall be selected in accordance with the procedures of the American
Arbitration Association. The decision and award rendered by the arbitrator shall
be final and binding. Judgment upon the award may be entered in any court having
jurisdiction thereof. Any arbitration pursuant to this section shall be held in
Boston, MA, or such other place as may be mutually agreed upon in writing by the
parties.
14.3 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
this Agreement, except by a written document which is signed by both parties.
14.4 This Agreement shall be construed and enforced in accordance with the
laws of the Commonwealth of Massachusetts without reference to its choice of law
principles.
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14.5 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 article or section.
14.6 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.
14.7 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) by facsimile as confirmed by certified or registered
mail. Notices shall be delivered to the respective parties as indicated:
To NITROMED: NitroMed, Inc.
c/o Healthcare Investments Corp.
379 Thornall Street
Edison, NJ 08837
Attn: CEO
Copy to: Carella, Byrne, Bain, Gilfillan,
Cecchi & Stewart
6 Becker Farm Road
Roseland, New Jersey 07068
Fax no. (201)994-1744
Attn: Elliot M. Olstein, Esq.
To HOSPITAL: The Brigham and Women's Hospital, Inc.
75 Francis Street
Boston, Massachusetts 02115
Attn: Maria I. Marmarinos
Assistant Vice President/Ventures
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Copy to: Brigham and Women's Medical
Center, Inc.
10 Vining Street
Boston, MA 02115
Attn: Office of General Counsel
14.8 NITROMED shall not use the name of the HOSPITAL or of any HOSPITAL
staff member, employee or student or any adaptation thereof in any advertising,
promotional or sales literature without the prior written approval of HOSPITAL.
Except that NITROMED shall be permitted to use the name of the HOSPITAL
or any HOSPITAL staff member, employee or student for the following
(i) as required to obtain regulatory approval for PRODUCT;
(ii) as required by law or BONA FIDE legal process; and
(iii) in connection with a financing or offering of securities provided
that HOSPITAL is permitted to review such material to determine the
correctness thereof prior to release of the material to the general
public.
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IN WITNESS WHEREOF, the parties have executed this Agreement as of the date
set forth above.
NITROMED, INC. THE BRIGHAM AND WOMEN'S
HOSPITAL, INC.
By: /s/ JOSEPH F.X. MCGUIRL By: /s/ WILLIAM TERRY
-------------------------- ------------------------
Name: Joseph F.X. McGuirl Name: William Terry
------------------------ ------------------------
Title: Chairman, NitroMed Inc. Title: Senior Vice President
----------------------- ----------------------
We, Drs. Joseph Loscalzo and Jonathan Stamler, named as PRINCIPAL
INVESTIGATORS in this Agreement, attest that we have read this Agreement in its
entirety; and that we consent to the terms herein.
PRINCIPAL INVESTIGATORS
By: /S/ JOSEPH LOSCALZO By: /S/ JONATHAN STAMLER
---------------------------- ---------------------------
Dr. Joseph Loscalzo Dr. Jonathan Stamler
34
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FIRST YEAR BUDGET AND OBJECTIVES
For
RESEARCH ON INTERMEDIARY NITRIC OXIDE METABOLISM:
NOVEL COMPOUNDS, DELIVERY SYSTEMS, AND CELL REGULATION
Joseph Loscalza, M.D., Ph.D.
Jonathan Stamler, M.D.
Brigham and Women's Hospital
Boston, Massachusetts
March, 1992
35
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CARDIOVASCULAR EFFECTS OF S-NO ADDUCTS
Personnel:
Technicians (2) [**]
======
Postdocs (2) [**]
======
Administrator (1) [**]
======
Secretary (1) [**]
======
Supplies: [**]
======
Animals: [**]
======
Total Direct Costs: [**]
======
Total Indirect Costs ([**]%) [**]
======
Grand Total: [**]
======
OBJECTIVES
-- synthesize and characterize [**] S-NO [**]
-- examine [**] S-NO [**]
-- [**] S-NO [**]
36
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BASIC LONG-TERM PROJECT OBJECTIVES
-- organic chemistry of [**]
[**]
-- cellular metabolism of [**]:
[**]
-- [**] of proteins
-- [**] states
* Over first five years; NOT dependent on milestones
39
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EQUIPMENT
EPR Spectrometer [**]
=======
Chemiluminescence Spectrometer [**]
=======
NMR Spectrometer [**]
=======
Capillary Zone Electrophoresis [**]
=======
w/ Indirect Fluorescence Detector
Infrared Spectrometer [**]
-======
CC/Mass Spectrometer System [**]
=======
Quantitative Angiography System [**]
=======
Intravascular Ultrasound System [**]
=======
Microvascular Vasomotor Apparatus [**]
=======
Microvascular Permeability Equipment [**]
=======
[**]
=======
37
<Page>
ANCILLARY PROJECTS AND BUDGETS
I. PULMONARY EFFECTS OF S-NO ADDUCTS
Personnel:
Technicians (2) [**]
======
Postdocs (2) [**]
======
Supplies: [**]
======
Animals: [**]
======
Total Direct Costs: [**]
======
Total Indirect Costs ([**]%) [**]
======
GRAND TOTAL [**]
======
OBJECTIVES
-- examine [**] S-NO [**]
[**] NO [**]
-- [**] NO [**] processes
II. [**] EFFECTS OF S-NO [**]
Personnel:
Technicians (2) [**]
======
Postdocs (2) [**]
======
Supplies: [**]
======
Animals: [**]
======
Total Direct Costs: [**]
======
Total Indirect Costs ([**]%) [**]
======
GRAND TOTAL [**]
======
38
<Page>
OBJECTIVES
-- evaluate effect of NO [**]
-- evaluate effect of NO [**]
-- assess effect of NO [**]
39
<Page>
<Table>
<Caption>
============================================================================================================================
Patent Applications or Invention Disclosures of Jonathan Stamler ET AL.
- ----------------------------------------------------------------------------------------------------------------------------
Docket No. Title Inventors Status
- ----------------------------------------------------------------------------------------------------------------------------
0627.2210000 Nitrosylation of Hortocysteine Jonathan Stamler Application consisting of claim and
As A Novel Antithrombotic Joseph Loscalzo abstract files April 10, 1991,
Mechanism Serial No. 07/683,415.
Application abandoned in favor of
continuation-in-part application,
Serial No. 07/339,188, filed
February 21, 1992, Docket No.
0627.2960004.
- ----------------------------------------------------------------------------------------------------------------------------
0627,2460000 Nitrosylation of Protein SH Jonathan Stamler Application filed November 14,
Groups And Amino Acid Residues Joseph Loscalzo 1991, Serial No. 07/791,668. Also
As A Therapeutic Modality Daniel Simon include the subject matter
David Siegel pertaining to nitrosation of
tyrosine and other amino acids
(invention disclosure; Docket No.
0627.290000).
Plan to review the application to
determine whether a continuation-in-part
application including no data pertaining
to ______ amino acids should be filed.
- ----------------------------------------------------------------------------------------------------------------------------
0627.2470000 S-Nitroso-N-Acetylcysteine As A Jonathan Stamler Application consisting of claim and
Treatment For Airway Obstruction Joseph Loscalzo abstract, filed March 29, 1991,
Robert Brown Serial No. 7/676,691.
Jeffrey Dazen
Application abandoned in favor of
continuation-in-part application,
Serial No. 07/804,665; filed
December 11, 1991; Docket No.
0627.2860004.
- ----------------------------------------------------------------------------------------------------------------------------
0627.2480000 S-Nitroso-N-Acetylcysteine As A Jonathan Stamler This subject matter was included in
Direct Biliary Smooth Muscle Adam Slivka the continuation-in-part
Relaxant (Invention disclosure) Joseph Loscalzo application (Docket No.
0627.2860004) filed on December 11,
1991.
Page 1
Revision Date: 05/22/92
<Page>
- ----------------------------------------------------------------------------------------------------------------------------
0627.2490000 Low Molecular Weight Thiols For Daniel Simon This subject matter was included in
Impotence (Invention disclosure) Jonathan Stamler the continuation-in-part
Joseph Loscalzo application (Docket No.
0627.2860004) filed on December 11,
1991.
- ----------------------------------------------------------------------------------------------------------------------------
0627.2560000 Novel Anionic-Iron Nitrosyl Jonathan Stamler No application to be filed at this
Complexes With Smooth Muscle David Siegel time. We will reconsider when
Relaxant And Antiplatelet Joseph Loscalzo additional information pertaining
Properties (Invention disclosure) Daniel Simon to synthesis and testing of
compounds becomes available.
- ----------------------------------------------------------------------------------------------------------------------------
0627.2900000 S-Nitrosothiols As Smooth Muscle Jonathan Stamler Continuation-in-part application,
Relaxants And Therapeutic Uses David Simon Serial No. 07/804,665, filed on
Thereof (CIP of 07/676,691, Joseph Loscalzo December 11, 1991.
Docket No. 0627.2470000) Robert Brown
Jeffrey Dazen Application was foreign filed in
Adam Slivka the PCT and Israel, on March 30,
1992.
- ----------------------------------------------------------------------------------------------------------------------------
0627.2860004 O-Nitrosylation of Tyrosine And Jonathan Stamler This subject matter was included in
Related Compounds (Invention Joseph Loscalzo CIP application 07/791,668
disclosure) (0627.2460000), which was filed on
November 14, 1991.
- ----------------------------------------------------------------------------------------------------------------------------
0627.2960004 Nitrosylation of Homocysteine As Jonathan Stamler Continuation-in-part application
a Novel Antithrombotic Mechanism Joseph Loscalzo No. 07/839,188, filed February 21,
CIP of 07/683,415, Docket No. 1992.
0627.2210000
Application was foreign filed in the
PCT and Israel on April 9, 1992
and April 10, 1992, respectively.
- ----------------------------------------------------------------------------------------------------------------------------
0627.3030000 Use of Guanylate Cyclase Jonathan Stamler Application filed April 8, 1992.
Inhibitors In The Treatment of Joseph Loscalzo
Shock
- ----------------------------------------------------------------------------------------------------------------------------
0627.3050000 The Use of Nitric Oxide Adducts Jonathan Stamler Preparation of application in
on Artificial Surfaces to Joseph Loscalzo progress. Anticipate filing in
Prevent Platlet Adherence and John Folts June 1992.
Thrombosis
- ----------------------------------------------------------------------------------------------------------------------------
Page 2
Revision Date: 05/22/92
<Page>
- ----------------------------------------------------------------------------------------------------------------------------
0627.3090000 The use of Nitric Oxide-Donating Jonathan Stamler Preparation of application in
Compounds as Antidotes To NO Joseph Loscalzo progress. Anticipate filing in
Synthetase Inhibitors June 1992.
- ----------------------------------------------------------------------------------------------------------------------------
0627.3100000 A Method For Detecting Nitric Jonathan Stamler Application filed April 22, 1992.
Oxide, Nitrososonian Joseph Loscalzo
Equivalents, S-Nitrosothiols and
S-Nitroso-Proteins in Biological
Systems
- ----------------------------------------------------------------------------------------------------------------------------
0627.3110000 The Use of Lipophilic Jonathan Stamler Preparation of patentability
Thionitrates And Other Joseph Loscalzo opinion.
Nitroso-Derivatives To Prevent Joseph Bonventura
Barnacle Attachment To Marine
Vessels
- ----------------------------------------------------------------------------------------------------------------------------
0627.3130000 Use of NO Synthetase Inhibitors Jonathan Stamler Preparation of patentability
As A Treatment for Thinitis Joseph Loscalzo opinion.
- ----------------------------------------------------------------------------------------------------------------------------
0627.3140000 Short Acting Thionitrites And Jonathan Stamler Prepare application.
Dithionitrites As Selective Joseph Loscalzo
Pulmonary Vasorelaxants
- ----------------------------------------------------------------------------------------------------------------------------
0627.3170000 A Method For Detection And Jonathan Stamler Preparation of application in
Separation of Thiols And Their Joseph Loscalzo progress. Anticipate filing in
S-nitrosated Derivatives In June 1992.
Biological Samples Using
Capillary Electrophoresis
- ----------------------------------------------------------------------------------------------------------------------------
0627.3200000 Novel Uses for NO Synthetase Jonathan Stamler Preparation of patentability
Inhibitors (includes uses Joseph Loscalzo opinion.
disclosed in the 0627.3130000
invention disclosure other than
for the treatment of rhinitis)
============================================================================================================================
Page 3
Revision Date: 05/22/92
<Page>
BRIGHAM
AND
WOMEN'S
H O S P I T A L
MATERIALS TRANSFER AGREEMENT
Agreement dated _____________ by and among _________________________
(the "Institution"), ___________________ (the "Investigator") and The Brigham
and Women's Hospital, Inc. ("Brigham") with respect to samples of a
In consideration of the receipt from Brigham by the Institution and the
Investigator of the samples, the Institution and the Investigator agree to the
following conditions:
1. These samples, their progeny and derivatives thereof (the "Materials")
remain the property of Brigham.
2. The Investigator will use the Materials solely for academic non-commercial
research conducted by the Investigator at the Institution a research
program described in Exhibit A hereto (the "Research Program"). Neither the
Investigator nor the Institution will use the results of the Research
Program, including inventions, directly or indirectly for profit-making
purposes without the consent of the Brigham
3. The Investigator and the Institution understand that Brigham has applied
for a patent on the and derivatives thereof.
4. The Investigator will not give access to the Materials to any party not
connected with the Research Program without written permission from
Brigham.
5. The Investigator and the Institution accept the Materials with the
knowledge that they are provided without warranty of merchantability of
fitness for a particular purpose or any other warranty, express or implied.
The Institution agrees to defend and indemnify and hold harmless Brigham
and its employees and agents from all claims and damages (including legal
fees) arising from the use, storage, handling, or direct sale of the
Materials by the Institution and/or the Investigator.
INSTITUTION: INVESTIGATOR:
By:_________________________________ ____________________________________
THE BRIGHAM AND WOMEN'S HOSPITAL, INC.
By:_________________________________
<Page>
AMENDMENT TO RESEARCH AND LICENSE AGREEMENT
This Amendment is effective as of November 22, 1996 by and between The
Brigham and Women's Hospital, Inc. ("HOSPITAL"), having an address at 75 Francis
Street, Boston, Massachusetts 02115, and NitroMed, Inc., a Delaware Corporation
having offices at 801 Albany Street, Boston, Massachusetts 02118 ("NITROMED").
WHEREAS, NITROMED and HOSPITAL entered into a RESEARCH AND LICENSE
AGREEMENT effective as of August 1, 1992; and
WHEREAS, HOSPITAL and NITROMED desire to amend such RESEARCH AND LICENSE
AGREEMENT.
NOW, THEREFORE, in consideration of the mutual promises and other good and
valuable consideration, the parties agree as follows:
1. All fully capitalized terms in this Amendment shall have the same meaning
as in the RESEARCH AND LICENSE AGREEMENT.
2. Section 8.1A of the RESEARCH AND LICENSE AGREEMENT is amended and rewritten
in its entirety to read as follows:
8.1 (A) On all sales of PRODUCTS anywhere in the world by NITROMED, its
AFFILIATES or SUBLICENSEE, following the FIRST COMMERCIAL SALE in such country
by NITROMED its AFFILIATES or SUBLICENSEES, NITROMED shall pay HOSPITAL
royalties in accordance with the following schedule, such undertaking and
schedule having been agreed to for the purpose of reflecting and advancing the
mutual convenience of the parties. For each PRODUCT sold or distributed by
NITROMED or its AFFILIATES and SUBLICENSEES, N1TROMED shall pay to HOSPITAL one
of the following:
<Page>
(1) (i) [**] percent ([**]%) of the NET SALES PRICE of PRODUCTS (other
than PRODUCTS which are a diagnostic product or service) sold or
distributed by NITROMED or its AFFILIATES in a country and or (ii)
[**] percent ([**]%) of the NET SALES PRICE of PRODUCTS which are
diagnostic products or diagnostic services sold or distributed by
NITROMED or its AFFILIATES in a country so long as in each case the
PRODUCT, its manufacture, use or sale in the country in question shall
be subject to a VALID CLAIM of any PATENT RIGHT which is licensed
exclusively to NITROMED in such country, or (2) (i) [**] percent
([**]%) of the NET SALES PRICE of PRODUCTS (other than PRODUCTS which
are diagnostic products or diagnostic services) sold or distributed by
NITROMED or its AFFILIATES in a country or (ii) [**] percent ([**]%)
of the NET SALES PRICE of PRODUCTS which are diagnostic products or
diagnostic services sold or distributed by NITROMED or its AFFILIATES,
whenever, in each case, the PRODUCT, its manufacture, use or sale
shall be subject to a VALID CLAIM of only such PATENT RIGHTS which are
licensed non-exclusively to NITROMED in the country is question (the
term non-exclusive license includes a license in which HOSPITAL
co-owns the applicable PATENT RIGHTS with a third party(ies) and
NITROMED does not receive an exclusive license under this Agreement
from all of the owners), or (3) the following percentage of royalties
received from a SUBLICENSEE for sale or distribution of a PRODUCT
whose manufacture, use or sale is subject to a VALID CLAIM of PATENT
RIGHTS:
(i) [**] percent ([**]%) where HOSPITAL owns all right and title in
and to such PATENT RIGHTS; or
(ii) [**] percent ([**]%) where HOSPITAL does not own all right and
title in and to such PATENT RIGHTS.
(4) (a) For each PRODUCT sold by NITROMED in which a competing product
employing similar technology is not available, (i) [**] percent
([**]%) of the NET' SALES PRICE of PRODUCTS sold or distributed by
NITROMED or its AFFILIATES and (ii) [**] percent ([**]%) of royalties
received from a SUBLICENSEE for salt or distribution of PRODUCT (1)
for ten (10) years next following the FIRST COMMERCIAL SALE of any
PRODUCT whose manufacture, use or sale shall employ or incorporate any
HOSPITAL MATERIAL where such HOSPITAL MATERIALS are not subject to one
or more VALID CLAIMS of any PATENT RIGHT licensed to NITROMED in such
country or (2) for the ten (10) years next following the FIRST
COMMERCIAL SALE of any PRODUCT whose manufacture, use or sale shall
employ as a significant part thereof INFORMATION which is not subject
to any VALID CLAIM of a PATENT RIGHT licensed to NITROMED in such
country;
<Page>
3. Section 8.2(a) of the RESEARCH AND LICENSE AGREEMENT is amended and
rewritten in its entirety to read as follows:
8.2 (a) In the event that royalties are to be paid by NITROMED to a party
who is not an AFFILIATE of NITROMED for PRODUCT for which royalties are also due
to HOSPITAL pursuant to Paragraph 8.1A(1), 8.1A(2), 8.IA(3)(i) or 8.1 A(4)
("Other Royalties"), then the royalties to be paid to HOSPITAL by NITROMED
pursuant to such Paragraphs shall be reduced by one-half of the amount of such
Other Royalties, but in no event shall any royalties under such Paragraphs be
reduced by more than [**] percent ([**]%).
4. The RESEARCH AND LICENSE AGREEMENT is hereby amended effective as of the
date first above written in accordance with Paragraph 14.3 thereof. Except as
amended herein or previously amended, the terms and conditions of the RESEARCH
AND LICENSE AGREEMENT remain in full force and effect as originally written.
<Page>
IN WITNESS WHEREOF, the parties have executed this Agreement as of the date
set forth above.
<Table>
NITROMED, INC. THE BRIGHAM AND WOMEN'S
HOSPITAL, INC.
By:/s/ MANUEL WORCEL By: /s/ SHELBY CALVERT MORSS
------------------------------------------- -----------------------------------------
Name: Manuel Worcel Name: Shelby Calvert Morss
------------------------------------ ----------------------------------------
Title: President and Chief Executive Officer Title: Vice President, Ventures Department
---------------------------------------- --------------------------------------
</Table>