EXHIBIT NO. 10.8
CONFIDENTIAL MATERIALS OMITTED AND FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION. ASTERISKS DENOTE OMISSIONS.
RESEARCH AND LICENSE AGREEMENT
This Agreement is effective June 1, 1993 ("the EFFECTIVE DATE") by and
between the Trustees of Boston University ("UNIVERSITY"), having an address at
▇▇ ▇. ▇▇▇▇▇▇▇ ▇▇▇▇▇▇, ▇▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇, and NitroMed, Inc., a
Delaware Corporation having offices at ▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇, ▇▇▇▇. ▇▇▇, ▇▇▇▇▇▇▇▇▇,
▇▇▇▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇ ("NITROMED").
WHEREAS, the research program contemplated by this agreement is of mutual
interest and benefit to UNIVERSITY and NITROMED and will further the
instructional and research objectives of the UNIVERSITY in a manner consistent
with its status as a non-profit, tax-exempt, educational institution;
WHEREAS, NITROMED desires to fund certain work to be performed at
UNIVERSITY in exchange for exclusive licenses in and to certain patents,
technology, materials and information; and
WHEREAS, UNIVERSITY 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.
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, solely or jointly by at least one
INVESTIGATOR during the period in which his/her Sponsored Research Program is in
effect, which either is in the FIELD OF RESEARCH, or which results from the
performance of any research funded in whole or in part by NITROMED pursuant to
this Agreement.
1.4 The term "BACKGROUND INVENTION" shall mean any process, use, article
of manufacture, composition of matter conceived or reduced to practice by a
PRINCIPAL INVESTIGATOR (alone or with others) prior to the effective date of a
RESEARCH PROPOSAL for such PRINCIPAL INVESTIGATOR, which is within the FIELD OF
RESEARCH and which is owned by UNIVERSITY and in and to which UNIVERSITY has
transferable rights.
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 UNIVERSITY Professional Staff, graduate student, undergraduate
student, or
-2-
employee of UNIVERSITY who shall perform or shall work on SPONSORED RESEARCH
PROGRAM during the period in which the SPONSORED RESEARCH PROGRAM is in effect.
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.
1.8 The term "BACKGROUND MATERIAL" shall mean any material or substance
which is in the FIELD OF RESEARCH and is in the possession of UNIVERSITY through
the PRINCIPAL INVESTIGATOR or the PRINCIPAL INVESTIGATOR prior to the effective
date of a RESEARCH PROPOSAL for such PRINCIPAL INVESTIGATOR and in and to which
UNIVERSITY and/or PRINCIPAL INVESTIGATOR has a transferable right.
1.9 The term "RESEARCH MATERIAL" shall mean any material or substance
which is discovered, produced or derived solely or jointly by at least one
INVESTIGATOR during the period in which his/her Sponsored Research Program is in
effect, which either is in the FIELD OF RESEARCH or which results from any
research funded in whole or in part by NITROMED pursuant to this Agreement, and
in and to which the UNIVERSITY and/or PRINCIPAL INVESTIGATOR has a transferable
right.
1.10 "UNIVERSITY 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,
rebates and disallowed reimbursements and allowances and credit on account of
rejection or return of PRODUCT.
-3-
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, which is owned by UNIVERSITY insofar as
it contains one or more claims to a BACKGROUND INVENTION, BACKGROUND
INFORMATION, or BACKGROUND MATERIAL. The BACKGROUND PATENT RIGHTS are and/or
shall be tabulated in Appendix B hereto.
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. The
RESEARCH PATENT RIGHTS shall be tabulated in Appendix B hereto.
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 each and every
PRINCIPAL INVESTIGATOR named in a RESEARCH PROPOSAL.
1.16 The term "PRODUCT" shall mean any article, composition, apparatus,
substance, chemical, material, method or service which is or which incorporates
or utilizes an INVENTION, INFORMATION, and/or UNIVERSITY MATERIAL, or the
manufacture, import, sale or use of which is covered by PATENT RIGHTS.
-4-
1.17 The term "PROCESS" shall mean any 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 UNIVERSITY through PRINCIPAL INVESTIGATOR or the PRINCIPAL INVESTIGATOR
prior to the effective date of a RESEARCH PROPOSAL for such PRINCIPAL
INVESTIGATOR and in and to which UNIVERSITY and/or PRINCIPAL INVESTIGATOR has a
transferable right.
1.19 "RESEARCH INFORMATION" shall mean any data, formulas, process
information or other information produced solely or jointly by at least one
INVESTIGATOR during the period in which his/her Sponsored Research Program is in
effect, which either is in the FIELD OF RESEARCH or which results from any
research funded in whole or in part by NITROMED pursuant to this Agreement, and
in and to which the UNIVERSITY and/or PRINCIPAL INVESTIGATOR has a transferable
right.
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 a
SPONSORED RESEARCH PROGRAM, which is or shall be attached hereto as part of
Appendix A executed by duly authorized representatives of both parties,
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.
1.22 The term "SPONSORED RESEARCH PROGRAM" shall mean research described
in each RESEARCH PROPOSAL.
-5-
1.23 "VALID CLAIM" shall mean (i) a claim of a pending patent application
pending for no more than seven (7) years from the date of filing or from the
date an election has been made to pursue separate claims (but only with respect
to such claims) and (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 the field of research set forth in the
RESEARCH PROPOSAL for each SPONSORED RESEARCH PROGRAM.
1.25 "AGREEMENT YEAR" shall mean for each SPONSORED RESEARCH PROGRAM the
twelve month period beginning on the effective commencement date thereof as
specified in the Research Proposal ("COMMENCEMENT DATE"), and each subsequent
twelve (12) month period thereafter.
1.26 "LICENSED TERRITORY" shall mean all countries of the world.
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 a SPONSORED RESEARCH
PROGRAM by UNIVERSITY, during the period in which SPONSORED RESEARCH PROGRAM is
being conducted:
(i) NITROMED shall make annual research grants to UNIVERSITY for the
support of each SPONSORED RESEARCH PROGRAM in accordance with its
RESEARCH PROPOSAL, so long as such RESEARCH PROPOSAL remains in
effect and has not been terminated pursuant to Section 13 hereof.
-6-
(ii) each annual research grant shall be paid in four equal quarterly
payments in advance, commencing on the COMMENCEMENT DATE. In
addition, NITROMED shall provide Equipment Funding as provided in
any RESEARCH PROPOSAL;
(iii) Payments will be made in the name of "Trustees of Boston
University", and will be sent to Boston University School of
Medicine, Grant Accounting, ▇▇ ▇▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇, ▇▇▇▇▇▇,
▇▇▇▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇. UNIVERSITY shall retain title to all equipment
purchased and/or fabricated by it with funds provided by NITROMED
under this Agreement.
(iv) 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, for
any SPONSORED RESEARCH PROGRAM which is more than one year, UNIVERSITY 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 UNIVERSITY's plan and budget. Such approved plan and budget shall be
attached and made a part of a RESEARCH PROPOSAL attached hereto as part of
Appendix A
(C) within sixty (60) days after the end of an AGREEMENT YEAR,
UNIVERSITY shall provide NITROMED with an accounting of the expenditure of
research funds for such AGREEMENT YEAR for each SPONSORED RESEARCH PROGRAM in
accordance with UNIVERSITY standard procedures for such accounting. With respect
to any SPONSORED RESEARCH PROGRAM, the amount of research funds not expended in
an AGREEMENT
-7-
YEAR shall be applied to reduce NITROMED's funding obligation for such SPONSORED
RESEARCH PROGRAM for the following AGREEMENT YEAR, and if there is no funding
obligation for the next year, such amount shall be refunded to NITROMED.
2.2 Either party may propose in writing additional research not
previously described in a 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 UNIVERSITY and NITROMED, it
shall be appended hereto as a RESEARCH PROPOSAL and shall be subject to the
terms and conditions of this Agreement, and the SPONSORED RESEARCH PROGRAM
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.
2.3 During the period during which NITROMED is funding a SPONSORED
RESEARCH PROGRAM under this Agreement, an INVESTIGATOR, during such time as he
or she is working under such SPONSORED RESEARCH PROGRAM, may not seek or accept
funding from a commercial sponsor in the FIELD of RESEARCH for such SPONSORED
RESEARCH PROGRAM without the prior written consent of NITROMED.
SECTION 3: WORK OF UNIVERSITY.
3.1 During the thirty (30) days next following the effective date for
each SPONSORED RESEARCH PROGRAM, UNIVERSITY, through the PRINCIPAL INVESTIGATOR,
shall disclose to NITROMED such BACKGROUND INFORMATION and BACKGROUND MATERIAL
which shall be known to PRINCIPAL INVESTIGATOR on the EFFECTIVE DATE.
-8-
3.2 Beginning on the EFFECTIVE DATE and thereafter unless sooner
terminated, with respect to each SPONSORED RESEARCH PROGRAM, UNIVERSITY shall:
(a) through the PRINCIPAL INVESTIGATOR conduct each SPONSORED RESEARCH
PROGRAM, and apply the funds paid by NITROMED pursuant to Paragraph
2.1 to support the expenses of each SPONSORED RESEARCH PROGRAM in
accordance with its RESEARCH PROPOSAL and shall use reasonable
efforts and diligence consistent with UNIVERSITY's professional
standards to achieve the goals set forth in such RESEARCH PROPOSAL.
NITROMED understands that UNIVERSITY's primary mission is education
and advancement of knowledge and that each SPONSORED RESEARCH
PROGRAM will be performed consistent with the RESEARCH PROGRAM in a
manner best suited to carry out that mission. The manner of
performance of the SPONSORED RESEARCH PROGRAM shall be determined
solely by the PRINCIPAL INVESTIGATOR, and UNIVERSITY does not
guarantee specific results;
(b) On a regular basis and in a timely manner disclose to NITROMED,
INFORMATION, INVENTIONS and UNIVERSITY MATERIAL, and NITROMED shall
be entitled to use such INFORMATION, INVENTIONS and UNIVERSITY
MATERIAL for research purposes and pursuant to the terms of this
Research and License Agreement;
(c) for the purpose of facilitating disclosure to NITROMED of RESEARCH
INFORMATION, INVENTIONS, and UNIVERSITY MATERIAL, permit duly
authorized employees of or representatives of NITROMED to visit the
-9-
PRINCIPAL INVESTIGATOR'S laboratories at UNIVERSITY or other
UNIVERSITY facilities where each SPONSORED RESEARCH PROGRAM is
conducted at reasonable times and with reasonable notice; and
(d) at NITROMED's request and through the PRINCIPAL INVESTIGATOR,
provide NITROMED with UNIVERSITY MATERIALS.
3.3 UNIVERSITY shall, on a continuing basis, advise NITROMED of the
results of each SPONSORED RESEARCH PROGRAM and at least once every three (3)
months provide NITROMED with written progress reports concerning each SPONSORED
RESEARCH PROGRAM. A final written report setting forth in detail the results
achieved under and pursuant to each SPONSORED RESEARCH PROGRAM shall be
submitted by UNIVERSITY to NITROMED within ninety (90) days of termination of
each SPONSORED RESEARCH PROGRAM. 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 PROGRAM; and (iii) detailed
experimental protocols of the assays performed in the course of the SPONSORED
RESEARCH PROGRAM.
SECTION 4: UNIVERSITY MATERIALS.
4.1 (a) During the period in which NITROMED holds a license,
UNIVERSITY and INVESTIGATORS shall make reasonable efforts to ensure that they
will not, without NITROMED's prior written approval, distribute or knowingly
allow RESEARCH 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.
(b) UNIVERSITY and PRINCIPAL INVESTIGATOR shall have the right to
transfer UNIVERSITY MATERIALS to not-for-profit entities or persons known to be
affiliated
-10-
therewith provided that such entities or persons sign the Material Transfer
Agreement attached hereto as Appendix C or any other Agreement consented to by
the parties.
(c) Prior to any such distribution of any such UNIVERSITY MATERIAL,
UNIVERSITY shall provide notice and a sample of such material to NITROMED and
UNIVERSITY and NITROMED shall use reasonable efforts to consider the
patentability of such UNIVERSITY MATERIALS and cooperate to file, where
appropriate, PATENT RIGHTS protecting such UNIVERSITY MATERIALS prior to their
distribution, provided that UNIVERSITY shall not be required to delay
distribution to non-profit entities or persons affiliated therewith for more
than sixty (60) days after notice to NITROMED.
4.2 Notwithstanding anything else to the contrary, UNIVERSITY and
INVESTIGATOR will be free to publish the results of research under this
Agreement provided that they agree not to publish or disclose to third parties
any RESEARCH INVENTION or RESEARCH INFORMATION without supplying NITROMED with a
copy of the material to be disclosed or to be submitted for publication to third
parties at least forty-five (45) days prior to such publication, submission or
disclosure so that NITROMED may evaluate such material to determine whether the
material contains patentable subject matter relating to a RESEARCH 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 thirty (30) days of submission to NITROMED. At NITROMED's request,
UNIVERSITY initially may 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
-11-
NITROMED CONFIDENTIAL INFORMATION AND MATERIAL the inclusion of which would
contravene Paragraphs 6.1 hereof.
4.3 Title to and the right to determine the disposition of any
copyrights or copyrightable material first produced or composed in the
performance of a SPONSORED RESEARCH PROGRAM, shall remain with UNIVERSITY;
provided, however, that UNIVERSITY shall grant to NITROMED an irrevocable,
royalty-free, non-transferable, nonexclusive right to reproduce, translate and
use all such copyrightable material; except that such right with respect to
computer software and its programming documentation is applicable only to
computer software and its programming documentation specified to be developed
and delivered under the SPONSORED RESEARCH PROGRAM.
SECTION 5: GRANTS.
5.1 (a) UNIVERSITY hereby grants to NITROMED and NITROMED hereby
accepts from UNIVERSITY a sole and exclusive royalty bearing right and license
for the LICENSED TERRITORY under PATENT RIGHTS, INFORMATION and INVENTION to
make, have made, use and sell or have sold on its behalf PRODUCT or PROCESS,
including the right to sublicense third parties. NITROMED shall have the right
to extend such license to its AFFILIATES. Such license shall be subject to the
provisions of Paragraph 4.2 hereunder.
(b) In the event that PATENT RIGHTS and INVENTIONS are co-owned by
UNIVERSITY and a third party, the license granted in Paragraph 5.1(a) shall only
apply to UNIVERSITY'S interest in such PATENT RIGHTS and INVENTIONS. For PATENT
RIGHTS or INVENTIONS owned jointly by UNIVERSITY and a third party, pursuant to
Paragraph 7.1(a) of this Agreement, UNIVERSITY shall attempt to obtain an
agreement granting on behalf of all of the owners thereof a sole and exclusive
right and license to NITROMED. If
-12-
terms agreeable to all of the parties (including such third party assignees) can
not be reached or, at NITROMED's request, UNIVERSITY will be relieved from its
obligations under Paragraph 7.1(a) of this Agreement and only UNIVERSITY'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 UNIVERSITY a copy of any and all fully
executed sublicense agreements, and further agrees to forward to UNIVERSITY
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 UNIVERSITY under said sublicense
agreements.
5.3 The above licenses to sell any PRODUCT for which a royalty has been
paid under this Agreement 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 without payment of any further royalty hereunder.
5.4 Any license granted to NITROMED pursuant to paragraph 5.1 shall be
subject to the Boston University Medical Center Patent Policy. Additionally, the
license is subject to the following: (i) for UNIVERSITY and its affiliate,
University Hospital, Inc., to retain a non-exclusive license for noncommercial
research purposes only and if and to the extent applicable to the licensed
invention, that the rights of the United States of America as set forth in
Public Laws 96-517 and 98-620 (codified at 35 U.S.C. 200 ET SEQ.) are
specifically reserved, and that NITROMED shall comply with the provisions of
said laws and specifically with 35 U.S.C. 204, as amended from time to time.
5.5 UNIVERSITY agrees not to use or to acquire materials for use in any
SPONSORED RESEARCH PROGRAM under terms that will prevent UNIVERSITY from
-13-
granting NITROMED exclusive rights to PATENT RIGHTS, INFORMATION and INVENTION
as provided in this Section 5 without the prior written consent of NITROMED.
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
best efforts under the circumstances to research, develop and then commercialize
such selected PRODUCT. The efforts of a SUBLICENSEE and/or an AFFILIATE and/or
the RESEARCH PROGRAM shall be considered as efforts of NITROMED.
(b) In the event that UNIVERSITY reasonably believes that NITROMED is
not making best efforts under the circumstances to research, develop and then
commercialize a selected PRODUCT by NITROMED pursuant to Paragraph 5.6(a) then
UNIVERSITY shall provide written notice to NITROMED which specifies UNIVERSITY's
basis for such belief and what additional efforts UNIVERSITY believes should be
made by NITROMED. Upon receipt of such written notice, UNIVERSITY 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 ninety (90) 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.
(c) If NITROMED fails to exert the efforts determined by the parties or
in such arbitration, UNIVERSITY'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 without
the right to sublicense to take effect sixty (60) days after prior written
notice unless NITROMED cures such failure. Pursuant to Paragraph 13.5 existing
-14-
SUBLICENSEES can elect to obtain a direct license from UNIVERSITY.
Notwithstanding the foregoing, NITROMED shall retain the right to grant
sublicenses in conjunction with the granting of a license to all or a portion of
NITROMED's technology (not acquired from University) where such sublicense
grants rights used with or in, or for such NITROMED technology.
5.7 UNIVERSITY 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, provided that this Paragraph does not diminish
NITROMED's obligations under Paragraph 5.6.
5.8 Subject to Section 5.6, NITROMED shall have sole discretion for
making all decisions relating to the commercialization and marketing of PRODUCT
5.9 Within sixty (60) days after the end of each calendar year, NITROMED
shall report in writing to UNIVERSITY 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 NITROMED
will disclose and/or provide to UNIVERSITY and PRINCIPAL INVESTIGATOR (i)
proprietary and confidential technology, inventions, technical information,
business information, biological materials and the like which are owned or
controlled by NITROMED or which NITROMED is obligated to maintain in confidence
(collectively "NITROMED CONFIDENTIAL INFORMATION AND MATERIAL"). UNIVERSITY
shall have the right to refuse to accept NITROMED CONFIDENTIAL INFORMATION AND
MATERIAL. NITROMED shall ▇▇▇▇
-15-
any written material as confidential. UNIVERSITY and PRINCIPAL INVESTIGATOR
agree to make reasonable efforts to retain such NITROMED CONFIDENTIAL
INFORMATION AND MATERIAL in confidence and not to disclose any such NITROMED
CONFIDENTIAL INFORMATION AND MATERIAL to a third party without the prior written
consent of NITROMED and to use such NITROMED CONFIDENTIAL INFORMATION AND
MATERIAL only with respect to a SPONSORED RESEARCH PROGRAM.
6.2 The obligations of confidentiality will not apply to NITROMED
CONFIDENTIAL INFORMATION AND MATERIAL which:
(i) was known to UNIVERSITY or PRINCIPAL INVESTIGATOR 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 UNIVERSITY or INVESTIGATOR by a third
party having a lawful right to make such disclosure;
(iv) is disclosed to obtain regulatory approval for PRODUCT, provided
that UNIVERSITY 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 the UNIVERSITY takes all reasonable steps to restrict and
maintain confidentiality of such disclosure and provides reasonable
notice to NITROMED; or
(vi) is approved for release by the parties.
-16-
SECTION 7: PATENTS.
7.1 (a) Each INVESTIGATOR who shall make an INVENTION, solely or
jointly, ("UNIVERSITY INVENTOR") shall promptly report such INVENTION to
UNIVERSITY. Each UNIVERSITY INVENTOR shall assign all of his rights, title and
interest in an INVENTION and PATENT RIGHTS relating thereto to UNIVERSITY
pursuant to the patent policy of the UNIVERSITY. 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 UNIVERSITY and NITROMED. UNIVERSITY
and NITROMED agree that for each PATENT RIGHT jointly owned by UNIVERSITY and
NITROMED, NITROMED and UNIVERSITY each own a one-half undivided interest in such
PATENT RIGHT in each country in which it is filed and UNIVERSITY'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
are not affiliated with either UNIVERSITY or NITROMED ("Unaffiliated
Collaborator(s)"), UNIVERSITY 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) UNIVERSITY shall promptly advise NITROMED in writing of each
INVENTION disclosed to UNIVERSITY. Representatives of UNIVERSITY 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
-17-
patent applications claiming an INVENTION filed after the EFFECTIVE DATE by
mutual agreement of UNIVERSITY and NITROMED shall be listed in Appendix B and
shall become PATENT RIGHTS.
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 UNIVERSITY 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 UNIVERSITY sufficiently prior to the filing of such application,
response or request to allow for review and comment by UNIVERSITY. UNIVERSITY
shall have the right to take any action that in its judgment is necessary to
preserve such PATENT RIGHTS.
SECTION 8: ROYALTIES.
8.1 (A) On all sales of PRODUCTS anywhere in the world by NITROMED,
its AFFILIATES or SUBLICENSEES, following the FIRST COMMERCIAL SALE in such
country by NITROMED its AFFILIATES or SUBLICENSEES, NITROMED shall pay
UNIVERSITY 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
-18-
AFFILIATES and SUBLICENSEES, NITROMED shall pay to UNIVERSITY 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)
[**] 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) [**] of the NET SALES
PRICE of PRODUCT which are diagnostic products or diagnostic services sold
or distributed by SUBLICENSEES in a country, whenever, in
-19-
each case, the PRODUCT, its manufacture, use or sale shall be subject to a
VALID CLAIM of only such PATENT RIGHTS which are licensed nonexclusively to
NITROMED in the country in question (the term non-exclusive license
includes a license in which UNIVERSITY 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).
(B) If a PRODUCT sold by NITROMED in a country is not subject to a VALID
CLAIM of any PATENT RIGHT licensed to NITROMED herein but the manufacture or use
of such PRODUCT incorporates or employs (i) any MATERIAL and/or (ii) any
INVENTION or INFORMATION not generally known, not used or not in the public
domain at the time of filing of a patent application with respect thereto,
NITROMED shall pay UNIVERSITY royalties equal to [**] of the NET SALES PRICE of
such PRODUCT sold by NITROMED or its AFFILIATES or [**] of the NET SALES PRICE
of such PRODUCT sold by SUBLICENSEES in such country for a period of seven (7)
years from FIRST COMMERCIAL SALE in such country; provided that such royalty
rate shall be reduced by [**]% in the event that competitive sales of products
employing similar technology amount to [**]% or more of NITROMED's sales of
PRODUCTS in the market as evidenced by documentation provided by NITROMED to
UNIVERSITY.
The provisions, terms, and conditions of Paragraph 8.1(A) are subject to
any future financing of the Center for Advanced Biomedical Research in which the
funding is obtained, all or in part, with tax-exempt bonds. In the event that,
at any time hereafter, (i) the UNIVERSITY enters into an agreement to receive
tax-exempt bond financing ("Financing Agreement") covering the building in which
the SPONSORED RESEARCH PROGRAM is conducted, and
-20-
(ii) the royalty rate stated herein is not competitive as defined below, the
license, except any license of an identified INVENTION on which a patent
application has been filed and tabulated in Appendix B prior to the date of the
Financing Agreement, shall be deemed to be granted at the lowest royalty rate
which is competitive at the time that the licensed INVENTION, INFORMATION,
MATERIAL or PATENT RIGHT is disclosed to NITROMED by UNIVERSITY as evidenced by
written disclosure. A royalty rate is "competitive" if it is either within the
range that UNIVERSITY would charge in an arms length transaction with a licensee
who was not a sponsor of research at UNIVERSITY or within the range of royalty
rates which would generally be charged by a not-for-profit entity to a person
who was not a sponsor of research at such not-for-profit entity. If the parties
are unable to agree on a rate that is "competitive" within one hundred eighty
(180) days after disclosure by the UNIVERSITY to NITROMED, then the parties
agree to submit the matter to arbitration pursuant to Paragraph 14.2 to
determine a competitive royalty rate.
(C) In the event that a PRODUCT includes both component(s) on which
royalties are payable pursuant to Paragraphs 8.1(A) and (B) hereof ("Licensed
Component(s)") and a component which is diagnostically usable or therapeutically
active alone or in a combination which does not require the Licensed
Component(s) and such component is not subject to royalties under Paragraph
8.1(A) or (B) hereof ("Unlicensed 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 Licensed Component(s) in an
arm's length transaction with an unaffiliated third party. If the Licensed
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
-21-
producing the Licensed Component(s) 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 which infringes the patent
rights of said party and also for which royalties are also due to UNIVERSITY
pursuant to Section 8.1 (such royalties to such party are hereinafter "Other
Royalties"), then the royalties to be paid to UNIVERSITY by NITROMED pursuant to
Section 8.1 shall be reduced by [**] of the amount of such other Royalties, but
in no event shall any royalties under Section 8.1 be reduced by more than [**]
percent ([**]%).
(b) In addition to Paragraph 8.2(a), in the event that a royalty paid to
UNIVERSITY 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, as evidenced by documentation provided by NITROMED to UNIVERSITY, then
the royalty paid to UNIVERSITY shall be reasonably reduced as to each affected
PRODUCT for the period during which such market condition exists. Factors
determining the size of a reasonable reduction will include profit margin on
PRODUCT and on analogous products, prices of competitive products, and
NITROMED's expenditures in PRODUCT development. In no event, however, shall the
reduction in royalties of 8.2(a) and this 8.2(b) exceed, in the aggregate, [**]
percent ([**]%).
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 UNIVERSITY. 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
-22-
pertain be open for inspection by UNIVERSITY or its designee upon reasonable
notice during normal business hours at UNIVERSITY'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 information 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 UNIVERSITY
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 and SUBLICENSEES;
(b) Total receipts for each PRODUCT subject to royalty (by country);
(c) Total royalties payable to UNIVERSITY, including the amounts claimed
as deductions against royalties;
(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
-23-
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 UNIVERSITY or its nominee in any
commercial bank or trust company located in that country, prompt notice of which
shall be given to UNIVERSITY. UNIVERSITY 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 UNIVERSITY, shall be promptly paid by
NITROMED for and on behalf of UNIVERSITY to the appropriate governmental
authority, and NITROMED shall use its best efforts to furnish UNIVERSITY with
proof of payment of such tax. Any such tax actually paid on UNIVERSITY's behalf
shall be deducted from royalty payments due UNIVERSITY.
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.
8.9 [**] percent ([**]%) of the amount paid by NITROMED pursuant to
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 8.9 by more than [**]%.
-24-
SECTION 9: INFRINGEMENT
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 UNIVERSITY and/or in the name of
NITROMED, and to join UNIVERSITY as a party plaintiff if required. NITROMED
shall promptly notify UNIVERSITY of any such infringement and shall keep
UNIVERSITY 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
UNIVERSITY, 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 [**]
percent ([**]%) of the royalties otherwise thereafter due UNIVERSITY 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 UNIVERSITY for any royalties withheld and applied pursuant to
this Section 9. The balance remaining from any such recovery shall be divided
between NITROMED and UNIVERSITY, as follows (i) for that portion, if any, based
on lost profits, UNIVERSITY shall recover the royalty UNIVERSITY would have
received under this Agreement if such sales had been made by NITROMED; and (ii)
for any other recovery, UNIVERSITY shall receive [**]percent ([**]%) of the
remaining amount.
9.2 In the event that NITROMED elects not to pursue an action for
infringement, upon written notice to UNIVERSITY by NITROMED that an unlicensed
third party is an
-25-
infringer of a VALID CLAIM of PATENT RIGHTS licensed to NITROMED, UNIVERSITY
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 UNIVERSITY in writing thereof.
NITROMED's costs as to any such defense shall be creditable against any and all
payments due and payable to UNIVERSITY under Paragraph 8.1 of this Agreement
but, subject to Paragraph 8.2(a) no royalty payment after taking into
consideration any such credit under this Paragraph 9.3 shall be reduced by more
than [**]%.
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 UNIVERSITY 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. However,
subject to Paragraphs 8.2(a) the royalty payment after taking into consideration
any such reduction under this Paragraph 9.4 shall not 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
-26-
testify when requested and make available relevant records, papers, information,
samples, specimens, and the like. All reasonable out-of-pocket costs of
UNIVERSITY incurred in connection with rendering cooperation requested by
NITROMED shall be paid by NITROMED.
SECTION 10: WARRANTIES.
10.1 Each of UNIVERSITY 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 UNIVERSITY warrants and represents that the named inventors have
assigned the PATENT RIGHTS tabulated in Appendix B to UNIVERSITY, 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 PROGRAM will be obligated to assign
to UNIVERSITY, the ownership of INVENTIONS and corresponding PATENT RIGHTS.
SECTION 11: INDEMNIFICATION, INSURANCE, AND LIABILITY.
11.1 UNIVERSITY shall promptly notify NITROMED of any claim or threatened
claim under this Paragraph 11.1, NITROMED shall defend, indemnify and hold
harmless UNIVERSITY, and its trustees, officers, employees, agents, and students
and their respective successors, heirs and assigns (the "Indemnitees"), against
any and all liability, damage, loss or
-27-
expense (including reasonable attorneys' fees and expenses of litigation) that
may be incurred by or imposed upon the indemnitees, or any of them, in
connection with any third party, claim, suit, demand, action or judgment arising
out of the following:
(a) the design, production, manufacture, sale, use in commerce, lease,
or promotion by NITROMED or by an AFFILIATE or SUBLICENSEES of
NITROMED of any product, process or service relating to or developed
pursuant to this Agreement; or
(b) any other activities to be carried out pursuant to this Agreement.
NITROMED's indemnity under (b) shall not apply to any liability, damage, loss or
expense to the extent that it is attributable to the negligence or willful
misconduct of the Indemnitees. NITROMED shall have full right and authority to
control the defense, compromise, or settlement of any such claim and UNIVERSITY
shall fully cooperate with all reasonable requests of NITROMED with respect
thereto.
NITROMED agrees at its own expense, to provide attorneys reasonably
acceptable to the UNIVERSITY 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. NITROMED
shall have the right to control the defense, settlement or compromise of any
such action.
UNIVERSITY 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.
This Paragraph 11.1 shall survive expiration or termination of this
agreement.
-28-
11.2 UNIVERSITY MAKES NO WARRANTIES, EXPRESS OR IMPLIED, AS TO ANY MATTER
WHATSOEVER, INCLUDING, WITHOUT LIMITATION, THE CONDITION OF THE RESEARCH OR ANY
INVENTION(S) OR PRODUCT(S), WHETHER TANGIBLE, CONCEIVED, DISCOVERED, OR
DEVELOPED UNDER THIS AGREEMENT, OR THE MERCHANTABILITY OR FITNESS FOR A
PARTICULAR PURPOSE OF THE RESEARCH OR ANY SUCH INVENTION OR PRODUCT.
11.3 At such time as any product, process or service 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, its
AFFILIATES or SUBLICENSEES, NITROMED shall at its sole expense, procure and
maintain for itself (or, in the alternative for UNIVERSITY) policies of
comprehensive general liability insurance in amounts not less than $2, 000, 000
per incident and $2, 000, 000 in the annual aggregate and naming the Indemnitees
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 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 UNIVERSITY's Risk Management
Office. The minimum amounts of insurance coverage required under this section
shall not be construed to create a limit of NITROMED's liability with respect to
its indemnification hereunder. NITROMED shall provide UNIVERSITY with written
evidence of such insurance upon request of UNIVERSITY. NITROMED shall provide
UNIVERSITY with written notice at least fifteen (15) days prior to the
cancellation, non-renewal or material change in such insurance; if NITROMED does
not obtain replacement insurance providing comparable
-29-
coverage within such fifteen (15) day period, UNIVERSITY shall have the right to
terminate this Agreement effective at the end of such fifteen (15) day period
without notice or any additional waiting periods. NITROMED shall maintain such
comprehensive general liability insurance beyond the expiration or termination
of this Agreement during the period that any product, process or service
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, its AFFILIATES or licensees, and for a reasonable period
of not less than fifteen (15) years after it has ceased commercial distribution
or sale of any such product, process or service.
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 UNIVERSITY
may assign this Agreement to an AFFILIATE or to a successor in interest or
transferee of all or substantially all of the portion of the business to which
this Agreement relates.
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 UNIVERSITY. 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.
-30-
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.
13.2 Except as qualified by Paragraph 13.7, NITROMED shall have the right
to terminate any or all licenses under one or more PATENT RIGHTS in one or more
countries upon sixty (60) days prior written notice.
13.3 Except as provided in Paragraph 5.6, upon material breach of any
material provisions of this Agreement other than by reason of Force Majeure, by
either party to this Agreement (including, but not limited to, the non-payment
of royalties), 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 or any affected RESEARCH PROPOSAL or affected license hereunder,
provided that such other party is not then in material breach of this Agreement.
In the event a party's breach affects only a SPONSORED RESEARCH PROGRAM or
license hereunder, the termination shall be limited to such affected RESEARCH
PROPOSAL or license, and the parties' obligations with respect thereto, and such
termination will not affect the rights and obligations of the parties under
other RESEARCH PROPOSALS or licenses granted herein.
13.4 Upon any termination of this Agreement or any license under this
Agreement NITROMED, at its option, shall be entitled, as a licensee under this
Agreement, to finish any work-in-progress which is completed within six (6)
months of such termination 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 UNIVERSITY the royalties
-31-
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 and/or the rights and licenses
granted under this Agreement to NITROMED are terminated, any sublicense granted
under this Agreement shall remain in full force and effect as a direct license
between UNIVERSITY and the SUBLICENSEE under the terms and conditions of the
sublicense agreement, subject to the SUBLICENSEE agreeing to be bound to
UNIVERSITY under such terms and conditions within thirty (30) days after
UNIVERSITY provides written notice to the SUBLICENSEE of the termination of
NITROMED's rights and licenses under this Agreement.
13.6 The obligations of Sections 6 and 11 and of Par. 13.1, 13.4, 13.5,
13.6 and 13.8 of this Agreement shall survive any termination of this Agreement.
13.7 Unless otherwise agreed to in a RESEARCH PROPOSAL, NITROMED may
terminate funding of any SPONSORED RESEARCH PROGRAM effective at any time on or
after the first anniversary thereof by giving UNIVERSITY three (3) months' prior
written notice of NITROMED's election to terminate.
13.8 In the event PRINCIPAL INVESTIGATOR is no longer available or able
to continue direction of a SPONSORED RESEARCH PROGRAM, UNIVERSITY shall promptly
notify NITROMED and may nominate a replacement; if UNIVERSITY does not nominate
a replacement within sixty (60) days or if that replacement is unsatisfactory to
NITROMED, NITROMED may immediately terminate funding of such SPONSORED RESEARCH
PROGRAM. For a period of six (6) months, NITROMED shall continue funding of such
SPONSORED RESEARCH PROGRAM in accordance with the RESEARCH PROPOSAL
-32-
therefor to the extent required to fund any non-terminable and non-reducible
funded amounts thereunder.
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. Except as otherwise provided in
any RESEARCH PROPOSAL, upon any termination, UNIVERSITY shall be entitled,
without limitating any rights of the UNIVERSITY provided elsewhere herein, to be
compensated for all reasonable expenses and uncancellable commitments incurred
as of the effective date of termination, not to exceed the total contract amount
stated in the applicable RESEARCH PROPOSAL(S).
SECTION 14: GENERAL PROVISIONS.
14.1 The relationship between UNIVERSITY and NITROMED is that of
independent contractors. UNIVERSITY 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. UNIVERSITY
shall have no power to bind or obligate NITROMED in any manner. Likewise,
NITROMED shall have no power to bind or obligate UNIVERSITY in any manner.
14.2 Any matter or disagreement under Paragraph 5.6 or Paragraph 8.1
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.
-33-
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.
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 to have been given and 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) on the day when sent by
facsimile as confirmed by certified or registered mail. Notices shall be
delivered to the respective parties as indicated:
-34-
To NitroMed: NitroMed, Inc.
One ▇▇▇▇▇▇▇ Square
Bldg. 100
Cambridge, Mass. 02139
Attn: ▇▇. ▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇▇
Copy to: Carella, Byrne, Bain, Gilfillan,
▇▇▇▇▇▇, ▇▇▇▇▇▇▇ & ▇▇▇▇▇▇▇
▇ ▇▇▇▇▇▇ ▇▇▇▇ ▇▇▇▇
▇▇▇▇▇▇▇▇, ▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇
Fax no. (▇▇▇) ▇▇▇-▇▇▇▇
Attn: ▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇▇, Esq.
To University:
Regarding a Sponsored Research Program:
Office of Sponsored Programs
Boston University School of Medicine
▇▇ ▇▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇, ▇▇▇▇. ▇▇▇▇▇
Attn: ▇▇▇▇ ▇▇▇▇▇▇▇▇▇▇▇
Regarding Licensing:
Office of Patent and Technology Administration
Boston University School of Medicine
▇▇ ▇▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇, ▇▇▇▇ ▇▇▇▇▇
Attn: ▇▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇
14.8 Neither party shall use the name of the other party or of any
investigator in any advertising or promotional material without the prior
written approval of the other. NITROMED may utilize the name of UNIVERSITY
and/or PRINCIPAL INVESTIGATOR without prior written approval in connection with
a disclosure in a financing or an offering of securities, provided, however,
that NITROMED shall advise UNIVERSITY of such use. NITROMED may and UNIVERSITY
shall, however, acknowledge NITROMED's support for the investigations being
pursued under this Agreement. In any public statements or disclosures, the
relationship of the parties shall be accurately and appropriately described.
-35-
14.9 To the extent of any conflict in terms, the provisions of any
RESEARCH PROPOSAL incorporated herein as part of Appendix A shall supersede the
provisions of this Agreement.
-36-
IN WITNESS WHEREOF, the parties have executed this Agreement as of the date
set forth above.
NITROMED, INC. TRUSTEES OF BOSTON UNIVERSITY
By: /s/ ▇▇▇▇▇▇ ▇▇▇▇▇▇ By: /s/ ▇▇▇▇▇ ▇▇▇▇▇▇▇
-------------------------- --------------------------------------
Name: ▇▇▇▇▇▇ ▇▇▇▇▇ Name: ▇▇▇▇▇ ▇▇▇▇▇▇▇
------------------------- ------------------------------------
Title: President & CEO Title: Executive Director of Financial Affairs
------------------------ ---------------------------------------
By: /s/ ▇▇▇▇ ▇▇▇▇▇▇▇▇▇
--------------------------------------
Name: ▇▇▇▇ ▇. ▇▇▇▇▇▇▇▇▇
------------------------------------
Title: ▇▇▇▇, School of Medicine
-----------------------------------
Name: ▇▇▇▇▇▇▇ ▇▇▇▇▇
------------------------------------
Title: Vice President, for Administrative
----------------------------------
Services
--------
By: /s/ ▇▇▇▇ ▇. ▇▇▇▇▇▇▇, ▇▇.
-------------------------------------
Name: ▇▇▇▇ ▇. ▇▇▇▇▇▇▇, ▇▇.
------------------------------------
Title: Assistant Treasurer
-----------------------------------
-37-
APPENDIX A
to
RESEARCH AND LICENSE AGREEMENT
Dated June 1, 1993
between
TRUSTEES OF BOSTON UNIVERSITY
and
NITROMED, INC.
RESEARCH PROPOSAL
PRINCIPAL INVESTIGATOR: ▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇, M.D.
FIELD OF RESEARCH:
Cardiovascular, gastrointestinal, and pulmonary research, and research
relating to erectile dysfunction and ureteral relaxation, utilizing nitric
oxide compounds, nitrosothiols, nitrosoproteins, other nitrosylated
compounds and/or agonists and antagonists thereof, and other compounds
which mediate nitric oxide.
SPONSORED RESEARCH PROGRAM:
The SPONSORED RESEARCH PROGRAM is described in Exhibit 1 attached to this
RESEARCH PROPOSAL.
TERM OF RESEARCH PROPOSAL:
This RESEARCH PROPOSAL shall commence on January 1, 1994 ("COMMENCEMENT
DATE") and shall continue in effect until the expiration of the "EQUIPMENT
LEASE" as defined below, unless sooner terminated by either party as
provided in Section 13 of the Research and License Agreement.
FUNDING OF RESEARCH PROPOSAL:
1. ANNUAL RESEARCH GRANT (EXCLUSIVE OF LEASED EQUIPMENT FUNDING): The
annual research grant to be provided by NITROMED for the first AGREEMENT
YEAR (12-month period commencing on the COMMENCEMENT DATE) shall be in a
total amount of [**] dollars ($[**]) as provided in the Budget attached to
this RESEARCH PROPOSAL as Exhibit 2. Budgets for subsequent years shall be
determined and approved by the parties in accordance with Section 2 of the
Research and License Agreement and shall thereupon be attached and
incorporated into Exhibit 2 hereto.
2. EQUIPMENT FUNDING: Funding for the equipment ("EQUIPMENT") listed in
the Equipment List appended hereto as part of Exhibit 3 shall be provided
by NITROMED under the terms of the Lease Agreement and BancBoston Leasing
Co. Proposal Letter between the UNIVERSITY and BancBoston Leasing Co.
attached hereto as part of Exhibit 3 and the Equipment Schedules which
shall be executed between the UNIVERSITY and BancBoston Leasing Co.
pursuant thereto ("EQUIPMENT LEASE") as follows:
NITROMED shall be responsible for funding the UNIVERSITY's total costs of
leasing the EQUIPMENT on the terms and conditions (including a 36-month
term for each Equipment Schedule) set forth in the EQUIPMENT LEASE.
NITROMED shall pay to the UNIVERSITY the amounts payable by the UNIVERSITY
as lessee under the EQUIPMENT LEASE. A monthly payment from NITROMED to the
UNIVERSITY shall be due and payable ten (10) days in advance of the first
day of each month in which payment is required to be made by the UNIVERSITY
as specified in the EQUIPMENT LEASE. The UNIVERSITY will provide NITROMED
with a copy of each Equipment Schedule when executed under the EQUIPMENT
LEASE, evidencing the date and amount of payment due from the UNIVERSITY to
BancBoston Leasing Co. thereunder.
Payments shall be made by wire transfer to State Street Bank and Trust
Company, Trustees of Boston University Concentration Account #▇▇▇▇-▇▇▇-▇,
Reference: NitroMed lease, ABA # ▇▇▇-▇▇▇▇-▇▇.
In the event that this RESEARCH PROPOSAL, the SPONSORED RESEARCH PROGRAM or
funding for the SPONSORED RESEARCH PROGRAM shall be terminated as provided
in the Research and License Agreement by either party prior to the end of
the EQUIPMENT LEASE, then, at the option of the UNIVERSITY, which shall be
exercised by written notice to NITROMED within thirty (30) days after such
termination, either
(i) the UNIVERSITY shall fund the remainder of the EQUIPMENT LEASE and
shall own the EQUIPMENT at the end of the LEASE, and NITROMED shall
have no further obligation under this RESEARCH PROPOSAL with respect
to the EQUIPMENT,
or
(ii) NITROMED shall fund the remainder of the EQUIPMENT LEASE in
accordance with the terms of this RESEARCH PROPOSAL, and at the end
of the LEASE, the UNIVERSITY shall transfer to NITROMED its title to
the EQUIPMENT. Under this option, the UNIVERSITY, during the
remainder of the LEASE term, shall retain possession of and may use
the EQUIPMENT, shall use best efforts to maintain the EQUIPMENT in
good working condition, and the UNIVERSITY shall relinquish
possession to NITROMED, at its request, at the end of the LEASE
term. THE UNIVERSITY HEREBY DISCLAIMS ALL WARRANTIES WHATSOEVER,
EXPRESS OF IMPLIED, WITH RESPECT TO THE EQUIPMENT, WHICH WOULD BE
TRANSFERRED UNDER THIS
-39-
OPTION "AS IS - WHERE IS" NITROMED would be solely responsible for
the removal of the EQUIPMENT from the UNIVERSITY'S premises.
Further, the UNIVERSITY may exercise option (1) above with respect to
selected items of EQUIPMENT and option (ii) with respect to other selected
items of EQUIPMENT. In the event that the UNIVERSITY so opts to allocate
EQUIPMENT items between options (i) and (ii), then the costs of leasing the
items of EQUIPMENT shall be allocated between options (1) and (ii), PRO
RATA, based on the aggregate cost (at time of the lessor's purchase) of the
items of EQUIPMENT allocated by the UNIVERSITY to each option, such values
being as specified in the Equipment Schedules in Exhibit 3.
If, as a result of any failure by NITROMED to make timely payment of
EQUIPMENT funding hereunder, the UNIVERSITY defaults in any of its
obligations under the EQUIPMENT LEASE, then NITROMED shall indemnify, hold
harmless and defend the UNIVERSITY from any liability or expense resulting
from any such default by the UNIVERSITY under the EQUIPMENT LEASE.
In the event that the UNIVERSITY should default under the lease, and such
default should not be caused by a default by NITROMED, then NITROMED shall
have no obligation to make any payment which may become duo and payable
under the LEASE as a result of such default by the UNIVERSITY.
IN WITNESS WHEREOF, the parties have executed this RESEARCH PROPOSAL as of the
COMMENCEMENT DATE set forth above.
NITROMED, INC. TRUSTEES OF BOSTON UNIVERSITY
By: /s/ ▇▇▇▇▇▇ ▇▇▇▇▇▇ By: /s/ ▇▇▇▇▇ ▇▇▇▇▇▇▇
-------------------------- --------------------------------------
Name: ▇▇▇▇▇▇ ▇▇▇▇▇▇, MD Name: ▇▇▇▇▇ ▇▇▇▇▇▇▇
------------------------- ------------------------------------
Title: President, CEO Title: Executive Director of Financial Affairs
------------------------ ---------------------------------------
By: /s/ ▇▇▇▇ ▇. ▇▇▇▇▇▇▇▇▇
--------------------------------------
▇▇▇▇ ▇. ▇▇▇▇▇▇▇▇▇
▇▇▇▇, School of Medicine
By: /s/ ▇▇▇▇▇▇▇ ▇▇▇▇▇
--------------------------------------
▇▇▇▇▇▇▇ ▇▇▇▇▇, Vice President
for Administrative Services
By: /s/▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇
--------------------------------------
▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇, M.D.
Principal Investigator
-40-
EXHIBIT 1
In the cardiovascular arena, we plan to:
--evaluate the effects of [**]--evaluate the effects of [**]; and
--evaluate the effects of [**].
In the gastrointestinal arena, we plan to:
--evaluate the effects of [**]; and
--evaluate the effects of [**].
In the pulmonary arena, we plan to:
--evaluate the effects of [**]; and
--evaluate the effects of [**].
-41-
EXHIBIT 2
▇▇▇▇▇▇▇▇-NITROMED BUDGET
Cardiovascular
Personnel
Technician (1) [**]
Postdoc (1) [**]
Supplies [**]
Animals [**]
Total Direct Costs [**]
Total Indirect Costs ([**]%) [**]
TOTAL [**]
Gastrointestinal
Personnel
Postdoc (1) [**]
Technician (1) [**]
Supplies [**]
Animals (for hepatocytes) [**]
Total Direct Costs [**]
Total Indirect Costs ([**]%) [**]
TOTAL [**]
Pulmonary
Personnel
Technician (1) [**]
Supplies [**]
Animals [**]
Total Direct Costs [**]
Total Indirect Costs [**]
TOTAL [**]
GRAND TOTAL $[**]
-42-
EXHIBIT 3
EQUIPMENT LIST AND EQUIPMENT LEASE
▇▇▇▇▇▇▇▇ PROJECT - CABR - ITEMIZED LIST OF PURCHASE ORDERS
VENDOR
P.O. NUMBER DESCRIPTION AMOUNT DELIVERY
------------------ ------------------------- ---------------- ---------------------
MC113853XDB ▇▇▇▇▇▇ Scientific $ 2050.66 10 day delivery
Circulating Bath
MC113833XDB Grass Instrument $ 8875.00 60 day delivery
Benchtop polygraph
MC113844NDB Pie Medical Systems $ 27,133.00 overseas shipment*
License and software
MC113821XDB ▇▇▇▇ Zeiss Inc. Microscopy $ 19,845.00 6 week delivery
system
MC113822XDB Applied Biosystems $ 11,447.50 2 week delivery
Geneamp PCR system
MC113823XDB Pharmacia Biotech Smart $ 89,054.00 3 week delivery
system/Microtech
MC113825XDB Perimed Inc. $ 19,500.00 2 week delivery
PF4 Master
MC113826XDB PO-NE-MAH Inc. $ 29,184.00 60 day delivery
Eight channel digital
system
MC113726XDB PO-NE-MAH Inc. $ 25,179.00 60 day delivery
Eight channel digital
system
MC113836XDB ▇▇▇▇-▇▇▇▇▇▇ Co. $ 1,598.00 5 day delivery
Digital fluid pump
MC113838XDB Merck Research Lab $ 40,000.00 Immed. delivery**
Cardiometrics Floamp
MC113839XDB ▇▇▇▇▇ Electronics $ 41,326.00 60 day delivery
8 channel thermal pen
MC11384XDB Texas A & M Univ. $ 6,770.00 12 week delivery
Velocimeter
MC113841XDB Vista Electronics $ 6,550.00 120 day delivery
Image shearing device
MC113842XDB ALS Computer $ 8,102.45 1 week delivery
ALS 486DX2 system
MC113843XDB ALS Computer $ 17,008.00 1 week delivery
▇▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇▇▇▇▇▇ CVIS $ 90,000.00 30 day delivery
Insight system
MC113824XDB Sony Electronics $ 26,500.00 2 week delivery
Cinc Video System
*Vendor located in Holland exact charges and delivery time not available
**J. Vita already using equipment
Note: All purchase order amounts include estimated freight charges
-43-
BancBoston Leasing
January 19, 1994
▇▇. ▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇
Vice President Financial Affairs
Boston University
▇▇▇ ▇▇▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇
Dear ▇▇▇▇▇:
BancBoston Leasing Inc., an affiliate of The First National Bank of Boston, is
pleased to present the following outlined description of a proposed lease
purchase structure:
LESSEE: Trustees of ▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇▇
▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇
LESSOR: BancBoston Leasing Inc.
▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇
EQUIPMENT: Medical Research Equipment (▇▇▇▇▇▇▇▇ Project)
EQUIPMENT COST: Approximately $500,000
EQUIPMENT LOCATION: Lessee address (or as specified)
DELIVERY AND ACCEPTANCE: The equipment will be delivered and accepted for
lease no earlier than finalization of lease
documentation and no later than December 31, 1994.
MINIMUM TAKEDOWN: $25,000 of equipment cost.
LEASE TERM: Three (3) years.
LEASE PAYMENTS: Thirty-six (36) consecutive monthly payments payable
monthly in advance, at a rate to be established at
time of takedown, 200 basis points above our cost of
funds. Based upon our present cost of funds of
4.23%, the rate would be 6.23%, resulting in a
monthly factor of $30.37 per $1,000 of equipment
cost.
-44-
TYPE OF LEASE: Net lease transaction whereby Lessee shall be
responsible for the payment of taxes (other than
Lessor's income taxes), insurance and maintenance
and all other costs in connection with the equipment
and its operation. Taxes are invoiced by the Lessor
at the time they are due and payable. Lessee shall
provide evidence of physical damage and liability
insurance with endorsements in amount acceptable to
the Lessor prior to the delivery of the equipment.
DISPOSITION OF Upon expiration of the term of the lease, Lessor
EQUIPMENT: shall transfer title to the equipment to the Lessee,
provided that the total rent has been paid and the
Lessee is not otherwise in default.
COVENANTS: The credit approval and acceptance of the terms
outlined in this proposal may be contingent upon
covenants including various financial covenants
required by the Lessor's credit committee. Any
required covenants will be included in documentation
mutually acceptable to Lessor and Lessee.
COMMITMENT The credit approval and acceptance of the terms
PERIOD: outlined in this proposal, if granted, shall remain
in effect for the period specified under Delivery
and Acceptance, but in no event, not longer than one
(1) year from the date of this proposal and subject
to no material adverse change in the financial
condition of the Lessee.
PROPOSAL This lease proposal outlined herein shall remain in
EXPIRATION DATE: effect for fifteen (15) days from the date of this
proposal.
This proposal is not an agreement or commitment to provide a lease purchase. The
Lessor's obligation to provide the proposed lease purchase is subject to an
agreement between Lessor and Lessee and other material terms of the proposed
lease purchase, the obtaining of all prior approvals by Lessor, including credit
committee approval, and the execution of documentation mutually acceptable to
Lessor and Lessee.
If the above terms and conditions are acceptable, please acknowledge your
acceptance below and return this letter.
Thank you for the opportunity to present our proposal and we look forward to a
long and mutually beneficial relationship.
Sincerely,
BANCBOSTON LEASING INC.
/s/ ▇▇▇▇▇▇▇ ▇▇▇▇
▇▇▇▇▇▇▇ ▇. ▇▇▇▇
Assistant Vice President
-45-
AWARD ACKNOWLEDGMENT
This proposal is acceptable to us,
and this financing is awarded to
BancBoston Leasing Inc.
By: /s/ ▇▇▇▇▇▇ ▇▇▇▇▇▇
-----------------------------------
Assistant Treasurer
Date: 1/28/94
---------------------------------
cc: ▇▇▇▇▇▇ ▇▇▇▇▇
-46-
LEASE AGREEMENT NO. BU/90M1
This Lease Agreement is made as of the 30th day of November, 1990, between
TRUSTEES OF BOSTON UNIVERSITY, a
Massachusetts corporation, with its principal
financial office located at ▇▇▇ ▇▇▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇▇, ▇▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇
(the "Lessee"), and BANCBOSTON LEASING INC., a
Massachusetts corporation, with
its principal office located at ▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇, ▇▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇
(the "Lessor"). The parties hereto agree as follows:
1. Lease:
Lessor agrees to lease to Lessee, and Lessee agrees to lease from Lessor,
the Equipment (the "Equipment") described in Equipment Schedule(s) attached
hereto. Any reference to "Lease" shall mean this Lease Agreement, the Equipment
Schedule(s) and Rider(s) thereto, if any.
2. Definitions:
(a) The "Installation Date" means the date determined in
accordance with the applicable Equipment Schedule.
(b) The "Commencement Date" means as to the Equipment designated
on any Equipment Schedule where the Installation Date for such Equipment falls
on the first day of the month, that date, or in any other case the first day of
the month following the month in which such Installation Date falls.
(c) The "Daily Rental" means 1/30th of the amount set forth as the
monthly rental in the applicable Equipment Schedule.
3. Term of Lease:
The term of this Lease, as to all Equipment designated on any Equipment
Schedule, shall commence on the Installation Date for such Equipment, and shall
continue for an initial period ending that number of months from the
Commencement Date as is specified on the applicable Equipment Schedule (the
"Initial Term").
4. Rental:
The monthly rental payable hereunder is as set forth in the Equipment
Schedule(s). Rental shall begin to accrue on the Installation Date and shall be
due and payable by Lessee monthly and in advance on the first day of each month.
If the Installation Date does not fall on the first day of a month, the rental
for that period of time from the Installation Date until the Commencement Date
shall be an amount equal to the Daily Rental multiplied by the number of days
from (and including) the Installation Date to (but not including) the
Commencement Date and shall be due and payable on the Installation Date. In
addition to the monthly rental set forth in the Equipment Schedule(s), Lessee
shall pay to Lessor an amount equal to all taxes paid, payable or required to be
collected by Lessor, however designated, which are levied or based on the
rental, on the Lease or on the Equipment or on its purchase for lease hereunder,
or on its use,
-47-
lease, operation, control or value (including, without limitation, state and
local privilege or excise taxes based on gross revenue), any penalties or
interest in connection therewith (if such penalties or interest arise by reason
of a delay in payment attributable to Lessee and not to Lessor) or taxes or
amounts in lieu thereof paid or payable by Lessor in respect of the foregoing,
but excluding taxes based on Lessor's net income. Personal property taxes
assessed on the Equipment during the term hereof shall be paid by Lessee. Lessee
agrees to file, on behalf of Lessor, all required property tax returns and
reports concerning the Equipment with all appropriate governmental agencies,
and, within not more than 30 days after the due date of such filing to send
Lessor confirmation of such filing.
Notwithstanding the provisions of this Section, but subject to the next
succeeding sentence, Lessee shall have no obligations with respect to the
payment of taxes so long as Lessee maintains its status as a tax-exempt entity
with respect to such taxes. Notwithstanding the preceding sentence, Lessee shall
be responsible for any and all taxes which are imposed on this Lease or on the
Equipment (a) without regard to Lessee's status as a tax-exempt entity or (b) by
any state which does not recognize Lessee's tax-exempt status or the tax-exempt
status of this Lease or the Equipment.
5. Installation, Use and Quiet Possession of Equipment:
(a) Lessee shall be entitled to unlimited usage of the Equipment
without extra charge by Lessor.
(b) Lessee will at all times keep the Equipment in its sole
possession and control. The Equipment shall not be moved from the location
stated in the applicable Equipment Schedule without the prior written consent of
Lessor (said consent not to be unreasonably withheld).
(c) After prior notice to Lessor, Lessee may make, or cause to be
made on its behalf, at its own expense, any improvement, modification or
addition to the Equipment unless such modification or addition decreases the
value of the Equipment and provided, however, that any such improvement,
modification or addition is readily removable without causing damage to or
impairment of the functional effectiveness of the Equipment. To the extent that
such improvement, modification or addition is not so removable, it shall
immediately become the property of Lessor and thereupon shall be considered
Equipment for all purposes of this Lease Agreement.
(d) So long as Lessee is not in default hereunder, Lessor shall
not interfere with Lessee's use or possession of the Equipment during the term
of this Lease.
(e) Lessee shall, during the term of this Lease, at its expense,
keep the Equipment in good working order and condition and make all necessary
adjustments, repairs and replacements and shall not use or permit the Equipment
to be used in any manner or for any purpose for which, in the opinion of the
Manufacturer, the Equipment is not designed or reasonably suitable.
(f) Upon the expiration of the Lease Term and provided that no
Event of Default as defined in Section 9 below, has occurred or is continuing,
Lessor shall transfer title to
-48-
the Equipment to Lessee "AS IS," "WITH ALL FAULTS," and WITH NO WARRANTIES
WHATSOEVER (except as to title), EITHER EXPRESS OR IMPLIED, INCLUDING WITHOUT
LIMITATION, ANY WARRANTIES OF MEACHANTAB1LITY OR FITNESS FOR USE OR FOR
PARTICULAR PURPOSE. Lessor shall deliver to Lessee a ▇▇▇▇ of sale and other
documents as may be required to transfer title to the Equipment free and clear
of any liens, claims, encumbrances restrictions or title defects arising through
Lessor.
6. Leasehold Rights and Inspection:
(a) The Equipment shall remain personalty regardless of the manner
in which it may be installed or attached. Lessee shall, at Lessor's request,
affix to the Equipment, tags, decals or plates furnished by Lessor, indicating
Lessor's ownership and Lessee shall not permit their removal or concealment.
(b) Lessee shall keep the Equipment free and clear of all liens
and encumbrances except for liens or encumbrances arising through the actions or
omissions of Lessor or any person or entity claiming through or under Lessor.
Lessee shall not assign or otherwise encumber this Lease or any of its rights
hereunder or sublease the Equipment without the prior written consent of Lessor
(said consent not to be unreasonably withheld) except that Lessee may assign
this Lease or sublease the Equipment to its parent or any subsidiary corporation
or to a corporation which shall have acquired all or substantially all of the
property of Lessee by merger, consolidation or purchase. No permitted assignment
or sublease shall relieve Lessee of any of its obligations hereunder.
(c) Lessor or its agents shall have free access to the Equipment
at all reasonable times for the purpose of inspection and for any other purpose
contemplated in this Lease.
(d) Lessee shall immediately notify Lessor of all details
concerning any damage to, or loss of, the Equipment arising out of any event or
occurrence whatsoever, including but not limited to, the alleged or apparent
improper manufacture, functioning or operation of the Equipment.
7. No Warranties By Lessor:
Lessee represents that, at the Installation Date thereof. It shall have (a)
thoroughly inspected the Equipment; (b) determined for itself that all items of
Equipment are of a size, design, capacity and manufacture selected by it; and
(c) satisfied itself that the Equipment is suitable for Lessee's purposes.
LESSOR SUPPLIES THE EQUIPMENT AS IS AND NOT BEING THE MANUFACTURER OF THE
EQUIPMENT, THE MANUFACTURER'S AGENT OR THE SELLER'S AGENT, MAKES NO WARRANTY OR
REPRESENTATION, EITHER EXPRESS OR IMPLIED AS TO THE EQUIPMENT'S MERCHANTABILITY,
FITNESS FOR A PARTICULAR PURPOSE, DESIGN, CONDITION, QUALITY, CAPACITY, MATERIAL
OR WORKMANSHIP OR AS TO PATENT INFRINGEMENT OR THE LIKE, it being agreed that
all such risks, as between Lessor and Lessee, are to be borne by Lessee. Lessee
agrees to look solely to the Manufacturer or to suppliers of the Equipment for
any and all warranty claims. Any and all warranties and indemnities made by the
Manufacturer
-49-
or the supplier of Lessor are) to the extent to which the same may be
assignable, hereby assigned to Lessee for the term of the applicable Equipment
Schedule. Lessee agrees that Lessor shall not be responsible for the delivery,
installation, maintenance, operation or service of the Equipment or for delay or
inadequacy of any or all of the foregoing. Lessor shall not be responsible for
any direct or consequential loss or damage resulting from the installation,
operation or use of the Equipment.
8. Indemnities; Payment of Taxes:
8.1 Lessee hereby agrees to indemnify, defend and hold harmless Lessor,
its agents, employees, successors an assigns from and against any and all
claims, actions, suits proceedings, costs, expenses, damages and liabilities
whatsoever arising out of or in connection with the manufacture, ordering,
selection, specifications, availability, delivery, titling, registration,
rejection, installation, possession, maintenance, ownership, use, operation or
return of the Equipment including, but not limited to, any claim or demand based
upon any STRICT OR ABSOLUTE LIABILITY IN TORT and upon any infringement or
alleged infringement or any patent, trademark, trade secret, license, copyright
or otherwise, except to the extent any of the foregoing arises out of or in
connection with any negligent or wrongful act or omission of Lessor, or any of
its directors, officers, agents, employees, successors or assigns. All costs and
expenses incurred by Lessor in connection with any of the foregoing (but subject
to the foregoing exceptions) including, not limited to, reasonable legal fees,
shall be paid by Lessee on demand.
8.2 Lessee hereby agrees to indemnify, defend and hold Lessor harmless
against all Federal, state and local taxes, assessments, licenses, withholdings,
levies, imposts, duties, assessments, excise taxes, registration fees and other
governmental fees and charges whatsoever, which are imposed, assessed or levied
on or with respect to the Equipment or its use or related in any way to this
Lease Agreement ("Tax Assessments"), except for taxes on or measured by the net
income of Lessor. Lessee shall file all returns, reports or other such documents
required in connection with the Tax Assessments and shall provide Lessor with
copies thereof. If, under local law or custom, Lessee is not authorized to make
the filings required by a taxing authority, Lessee shall notify Lessor in
writing and Lessor shall thereupon file such returns, reports or documents and
upon Lessee's written request shall provide Lessee with copies thereof. Without
limiting any of the foregoing, Lessee shall indemnify, defend and hold Lessor
harmless from all penalties, fines, interest payments, claims and expenses
including, but not limited to, reasonable legal fees, arising from any failure
of Lessee to comply with the requirements of this Section 8.2 Notwithstanding
anything in this Lease to the contrary, Lessee shall have no obligations under
this Section 8.2 with respect to any Tax Assessments, including but not limited
to any penalties, fines, interest payments, claims and expenses, to the extent
that such Tax Assessments arise solely out of or in connection with any
negligent or wrongful act or omission of Lessor, or any of its directors,
officers, agents, employees, successors or assigns.
8.3 Notwithstanding anything in this Lease to the contrary, Lessor
hereby agrees to indemnify, defend and hold harmless Lessee, its trustees,
employees, successors and assigns from and against any and all claims, actions,
suits proceedings, costs, expenses, damages and liabilities to the extent
arising solely out of or in connection with the negligent or wrongful act or
-50-
omission of Lessor or any of its directors, officers, agents, employees,
successors or assigns with respect to the Equipment or this Lease Agreement.
8.4 Notwithstanding anything to the contrary, Lessee's obligations under
Section 8.2 above are subject to the last paragraph of Section 4 of the Lease,
and Lessee's obligations under Section 8.1 and 8.2 above are subject to the
following conditions: (a) Lessee shall have received timely written notice of
and (b) Lessee shall have the right to control the defense, including but not
limited to the settlement of any claim, demand, action, suit, proceeding, cost,
expense, damage or liability pursuant to Sections 8.1 and 8.2
8.5 Notwithstanding anything to the contrary, Lessor's obligations under
Section 8.3 above are subject to the following conditions: (a) Lessor shall have
received timely written notice of and (b) Lessor shall have the right to control
the defense, including but not limited to the settlement of any claim, demand,
action, suit, proceeding, cost, expense damage or liability pursuant to Section
8.3.
8.6 The obligations and indemnities of Lessee and Lessor under this
Section 8 for events occurring or arising during the Initial Term or any
Extended Term shall continue in full force and effect, notwithstanding the
expiration or other termination of this Lease Agreement.
9. Risk of Loss on Lessee:
(a) Beginning on the Installation Date thereof and continuing
until the end of the Initial Term. Lessee relieves Lessor of responsibility for
all risks of physical damage to or loss or destruction of the Equipment,
howsoever caused. During the term of this Lease as to any Equipment Schedule,
Lessee shall, at its own expense, keep in effect all risk and public liability
insurance policies covering the Equipment designated in each Equipment Schedule.
The public liability insurance policy shall be in such amount as is reasonably
acceptable to Lessor. The all risk insurance policy shall be for an amount not
less than the replacement cost of the Equipment. Lessor, its direct or indirect
successors and assigns and/or such other party as may be designated by any
thereof to Lessee, who shall have an equity interest or security interest in
this Lease Agreement. Equipment Schedule(s) or the Equipment, shall be named as
additional insureds on such policies, which shall be written by an insurance
company of recognized responsibility which is reasonably acceptable to Lessor.
Evidence of such insurance coverage shall be furnished to Lessor no later than
the Installation Date set forth in the Equipment Schedule(s) and, from time to
time, thereafter as Lessor may request. Such policies shall provide that no less
than ten days written notice shall be given Lessor prior to cancellation of such
policies for any reason.
(b) If any item of Equipment is rendered unusable as a result of
any physical damage to, or destruction of, the Equipment or for any other
reason, Lessee shall give to Lessor immediate notice thereof and this Lease
shall continue in full force and effect without any abatement of rental unless
and until it is terminated as provided herein. Lessee shall determine, within
twenty (20) days after the date of occurrence of such damage or destruction,
whether such item of Equipment can repaired. In the event Lessee determines that
the item of Equipment cannot be repaired, Lessee at its expense shall prompt
replace such item of Equipment and convey title to such replacement to Lessor
free and clear of all liens and encumbrances and this Lease shall continue in
full force and effect as though such damage or destruction had not
-51-
occurred. Subject to the rights of any insurer, Lessee shall have title to any
item of Equipment that has been replaced. In the event Lessee determines that
such item of Equipment can be repaired, Lessee shall cause such item of
Equipment to be promptly repaired. All proceeds of insurance received by Lessor,
the designated loss payee, or Lessee under the policy referred to in the
preceding paragraph of this Section shall be given to Lessee following the
receipt by Lessor of either evidence that the Equipment has been satisfactorily
repaired or replaced or the Termination Value (as hereinafter defined) and so
long as Lessee shall not be in default of its obligations hereunder. In lieu of
repairing or replacing the item(s) of Equipment, Lessee shall have the right,
upon notice to Lessor, to purchase any item(s) of Equipment and terminate the
Equipment Schedule, in whole or in part as the case may be, as of the first day
of the month following such notice in accordance with and subject to the
conditions (other than the notice period) set forth in Section 13 of the Lease.
10. Events of Default and Remedies:
The occurrence of any one of the following shall constitute an Event of
Default hereunder:
(a) Lessee fails to pay any installment of rent within seven (7)
days the same becomes due and payable.
(b) Lessee attempts to remove, sell, transfer, encumber, sublet or
part with possession of the Equipment or any items thereof, except as expressly
permitted herein.
(c) Lessee shall fail to observe or perform any of the other
obligations required to be observed or performed by Lessee hereunder and such
failure shall continue uncured for thirty (30) days after written notice thereof
to Lessee by Lessor or the then assignee hereof.
(d) Lessee ceases doing business as a going concern, makes an
assignment for the benefit of creditors, admits in writing its inability to pay
its debts as they become due, files a voluntary petition in bankruptcy, is
adjudicated a bankrupt or an insolvent, files a petition seeking for itself any
reorganization, arrangement, composition, readjustment, liquidation, dissolution
or similar arrangement under any present or future statute, law or regulation or
files an answer admitting the material allegations of the petition filed against
it in any such proceeding, consents to or acquiesces in the appointment of a
trustee, receiver, or liquidator of it or of all or any substantial part of its
assets or properties, or if it or its shareholders shall take any action looking
to its dissolution or liquidation.
(e) Within 30 days after the commencement of any proceedings
against Lessee seeking reorganization, arrangement, readjustment, liquidation,
dissolution or similar relief under any present or future statute, law or
regulation, such proceedings shall not have been dismissed, or if within 30 days
after the appointment without Lessee s consent or acquiescence of any trustee,
receiver or liquidator of it or of all or any substantial part of its assets and
properties, such appointment shall not be vacated.
Upon the occurrence of an Event of Default, Lessor may at its option do any
of the following provided there is no duplication of recovery, (i) by notice to
Lessee terminate this
-52-
Lease as to any or all Equipment Schedules; (ii) whether or not this Lease is
terminated as to any or all Equipment Schedules, take possession of any or all
of the Equipment listed on any or all Equipment Schedules, wherever situated,
and for such purpose, enter upon any premises without liability for so doing or
Lessor may cause Lessee and Lessee hereby agrees, to return said Equipment to
Lessor as provided in this Lease; (iii) recover from Lessee, as liquidated
damages for loss of a bargain and not as a penalty, an amount equal to the
present value of all monies to be paid by Lessee during the remaining Initial
Term or any successive period then in effect, calculated by discounting at the
rate set forth on the applicable Equipment Schedule as the discount rate annum
compounded monthly, which payment shall become immediately due and payable; and
(iv) after reasonable written notice to Lessee, sell, dispose of, hold, use or
lease the Equipment in a commercially reasonable manner, however, Lessor shall
not be obligated to give preference to the sale, lease or other disposition of
the Equipment over the sale, lease or other disposition of similar equipment
owned or leased by Lessor.
In the event that Lessee shall have first paid to Lessor or its assigns the
liquidated damages referred to in (iii) above, the party having received such
liquidated damages shall pay to Lessee, promptly after receipt thereof, all
rentals or proceeds received from any sale, disposition or reletting of the
Equipment during the balance of the Initial Term (after deduction of all
expenses incurred in connection therewith) said amount never to exceed the
amount of the liquidated damages paid by Lessee. Lessor shall use reasonable
efforts in connection with any sale, disposition or retetting of the Equipment.
Lessee shall in any event remain fully liable for reasonable damages as provided
by law and for all costs and expenses incurred by Lessor or its assigns on
account of such default including but not limited to all court costs and
reasonably attorney's fees. Lessee hereby agrees that, in any event, it will be
liable for any deficiency after any sale, lease or other disposition of the
Equipment. The rights afforded Lessor hereunder shall not be deemed to be
exclusive, but shall be in addition to any rights or remedies provided by law.
11. Net Lease:
Except as otherwise specifically provided in this Lease, it is understood
and agreed that this is a net lease, and that, as between Lessor and Lessee,
Lessee shall be responsible for all costs and expenses of every nature
whatsoever arising out of or in connection with or related to this Lease or the
Equipment (including, but not limited to, transportation in and out, rigging,
drayage, packing, installation and disconnect charges). Lessee hereby agrees
that, in the event that Lessee fails to pay or perform any obligation under this
Lease, Lessor may, at its option, pay or perform said obligation and any payment
made or expense incurred by Lessor in connection therewith shall become
additional rent which shall be due and payable by Lessee upon demand.
12. Assignment:
Lessee agrees that Lessor may transfer or assign all or any part of
Lessor's right, title and interest in, under or to the Equipment and this Lease
and any or all sums due or to become due pursuant to any of the above, to any
third party (the "Assignee") for any reason and that the Assignee may so
re-assign and transfer. Lessee agrees that upon receipt of written notice from
Lessor or Assignee of such assignment. Lessee shall perform all of its
obligations hereunder for the benefit of Assignee and any successor assignee
and, if so directed, shall pay all sums due or to become due hereunder directly
to the Assignee or to any other party designated by the
-53-
Assignee. Lessee hereby covenants, represents and warrants as follows and agrees
that the Assignee and any successor assignee shall be entitled to rely on and
shall be considered a third party beneficiary of the following covenants,
representations and warranties: (i) Lessee's obligations hereunder are absolute
and unconditional and are not subject to any abatement, reduction, recoupment,
defense, offset or counterclaim available to Lessee for any reason whatsoever
including operation of law, defect in the Equipment, failure of Lessor or
Assignee to perform any of its obligations hereunder or for any other cause or
reason whatsoever, whether similar or dissimilar to the foregoing except that
Lessee hereby expressly reserves all rights of independent recourse against
Lessor or Assignee, or any other third Party for any loss, damage, or liability
for which Lessor, Assignee or such other third party may be responsible; (ii)
Lessee shall not look to Assignee or any successor assignee to perform any of
Lessor's obligations hereunder; (iii) Lessee will not amend or modify this
Agreement without the prior written consent of the Assignee and any successor
assignee; and (iv) Lessee will send a copy to Assignee and any successor
assignee of each notice which Lessee sends to Lessor.
Upon receipt of notice of any such assignment, Lessee agrees to execute and
deliver to Lessor such documentation as Assignee or any successor assignee may
require, including but not limited to (i) an acknowledgment of, or consent to,
assignment which may require Lessee to make certain representations or
reaffirmations as to some of the basic terms and covenants contained in this
Lease; and (ii) a Certificate of Delivery and Acceptance. Nothing contained in
such documentation required by Assignee shall be in derogation of any of the
rights granted to Lessee hereunder. Notwithstanding such assignment: (i) Lessor
shall not be relieved of any of its obligations hereunder, and (ii) the rights
of Lessee hereunder shall not be impaired.
13. Lessee Option to Terminate:
Lessee shall have the option, upon four months prior written notice to
Lessor, to terminate the above referenced Equipment Schedule(s) and take title
to the Equipment on the first day of the month following expiration of the
notice period (the "Termination Date") subject to the following conditions:
(a) no Event of Default shall be continuing and no event which,
but for the passing of time or the giving of notice or both, would have been an
Event of Default, shall have occurred and be continuing on the Termination Date;
(b) Lessor or the then assignee (if any) of said Schedule(s) shall
receive the Termination Value (as defined herein), on the Termination Date.
(c) In addition to the payment of the Termination Value, Lessee
shall also pay to Lessor, upon demand, a dollar amount, if such amount is
greater than zero, computed pursuant to the formula set forth below.
L = (R-T) X TV X D
--------------
360
L = amount payable to Lessor for loss.
-54-
R = the effective fixed rate of interest quoted by the Treasury Division
of The First National Bank of Boston ("Treasury") to Lessor on the
Commencement Date applicable to the Equipment for funds in the
amount of the Acquisition Cost of the Equipment and for a term equal
to the Initial Term of lease for such Equipment.
T = the effective fixed rate of interest quoted on the Termination Date
by Treasury for funds in the outstanding amount of the Termination
Value and maturing on the last day of the Initial Term of the lease
for the Equipment.
TV = the amount of the Termination Value for the Equipment applicable to
the Termination Date.
D = the number of days remaining from, but excluding, the Termination
Date to, and including, the last day of the Initial Term of lease
for the Equipment.
In the event Lessee shall exercise the option aforesaid, Lessee shall pay
to Lessor or the then assignee (if any) of said Schedule(s) on the Termination
Date, a termination value ("Termination Value") as defined in Exhibit A which is
attached to each Equipment Schedule, for the Termination Date.
After the Termination Date and upon payment of the Termination Payment and
the payment as set forth in subsection (c) above, if any, Lessee shall be
released and discharged from all obligations with respect to said Equipment
Schedule(s) which shall be required to be performed by Lessee after, but not
before, the Termination Date, and title to the Equipment shall then pass to
Lessee on an As-is, Where-is basis, free and clear of all liens and encumbrances
arising by or through Lessor. Lessor shall deliver to Lessee a ▇▇▇▇ of sale and
such other instruments as may be required to transfer and deliver to Lessee,
good and marketable title to the Equipment, free and clear of all liens, claims,
encumbrances, restrictions and title defects arising by or through Lessor.
14. Miscellaneous:
(a) No consent or approval provided for herein shall be binding
upon Lessor unless signed on its behalf by an officer of Lessor. This agreement
shall be deemed to have been made in the Commonwealth of
Massachusetts and shall
be governed in all respects by the laws of such Commonwealth.
(b) This Lease constitutes the entire agreement between Lessee and
Lessor with respect to the Equipment, and no covenant, condition or other term
or provision hereof may be waived or modified orally.
(c) All notices to Lessor shall be in writing and shall be
delivered in person or sent by registered or certified mail, postage prepaid, to
the address of the Lessor as set forth herein or to such other address as such
party shall have designated by proper notice. All notices
-55-
to Lessee shall be in writing and shall be delivered in person or sent by
registered or certified mail, postage prepaid, to the address of the Lessee as
set forth in the applicable Equipment Schedule or to such other address as
Lessee shall have designated by proper notice.
(d) This Lease shall be binding upon and inure to the benefit of
Lessor and Lessee and their respective successors and assigns (including any
subsequent assignee of Assignee).
(e) No waiver of any of the terms and conditions hereof shall be
effective unless in writing and signed by the party against whom such waiver is
sought to be enforced. Any waiver of the terms hereof shall be effective only in
the specific instance and for the specific purpose given.
(f) Lessor is hereby authorized by Lessee to cause this Lease or
other instruments, including Uniform Commercial Code Financing Statements, to be
filed or recorded for the purpose of showing Lessor's interest in the Equipment
and Lessee agrees to execute such Instruments.
(g) In the event of any conflict between the terms and conditions
of this Lease Agreement and the terms and conditions of any Equipment
Schedule(s) or Rider(s) thereto, the terms and conditions of such Equipment
Schedule(s) or Rider(s) shall prevail.
(h) Each year during the term of this Lease, Lessee hereby agrees
to deliver to Lessor or Assignee and any successor assignee a copy of Lessee's
annual audited financial statements within a reasonable time after said
statements are available.
(i) The obligations which Lessee is required to perform during the
term of this Lease shall survive the expiration or other termination of this
Lease.
(j) Lessor agrees that to the extent of the performance by the
Initial User or any other permitted sublessee of Lessee's obligations hereunder,
such obligations of Lessee shall be deemed performed and satisfied hereunder.
Lessee: TRUSTEES OF BOSTON UNIVERSITY
By: /s/ ▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇
-----------------------------------
Title: Assistant Treasurer
--------------------------------
Lessor: BANCBOSTON LEASING INC.
By: /s/
-----------------------------------
Title: Vice President
--------------------------------
-56-
RIDER NO. 1
TO
LEASE AGREEMENT NO. BU/90M1
This Rider No. 1 (the "Rider") is entered into between BancBoston Leasing
Inc. ("Lessor") and Trustees of Boston University ("Lessee"), and is
contemporaneous with and amends that certain Lease Agreement No. BU/90M1 dated
as of November 30, 1990, including any riders thereto (together the "Lease
Agreement") between Lessor and Lessee. It is the intention of Lessor and Lessee
that, upon execution, this Rider shall constitute a part of the Lease Agreement.
IN CONSIDERATION OF the mutual covenants and promises as hereinafter set
forth, Lessor and Lessee hereby agree as follows:
1. The second sentence of Section 1 of the Lease Agreement is deleted,
and the following is substituted therefor:
"Any reference to "Lease" shall mean this Lease Agreement,
all Riders thereto (if any), the relevant Equipment
Schedule, and all Riders thereto (if any). Each Equipment
Schedule and Riders thereto (if any) together with this
Lease Agreement and Riders thereto (if any) shall
constitute a separate Lease."
2. In the third line of Section 4 of the Lease Agreement after the word
"month" the following is inserted:
", but no earlier than thirty (30) days after Lessee's
receipt of a monthly invoice for such rental;"
3. In the first line of Section 5(d) of the Lease Agreement the words
"Lessor shall not" are deleted, and the following is substituted therefor:
"neither Lessor nor any person or entity claiming under or
through Lessor shall"
4. Notwithstanding anything to the contrary in the Lease Agreement, if
Lessee commits an Event of Default under Section 10(a) of the Lease Agreement
with respect to any Equipment Schedule to the Lease Agreement, and if Lessee has
not cured such Event of Default within fifteen (15) days after written notice
thereof from Lessor, then all Equipment Schedules executed under the Lease
Agreement shall be in default.
5. In the third line of Section 12 of the Lease Agreement after the
word "reason" the following is inserted:
"(provided, in each case, that the Assignee agrees that,
by accepting such assignment or transfer, neither it nor
any person or
-57-
entity claiming under or through it shall interfere with
Lessee's use or possession of the Equipment so long as
Lessee is not in default under the Lease),"
6. In the tenth line of Section 12 of the Lease Agreement before the
word "Lessee's" the following is inserted:
"provided that Lessee's right to the use or possession of
the Equipment has not been impaired by Lessor or any
person or entity claiming under or through Lessor,"
7. All capitalized terms used in this Rider shall, unless otherwise
defined, have the meanings set forth in the Lease Agreement. The terms and
conditions of this Rider shall prevail where there may be conflicts or
inconsistencies with the terms and conditions of the Lease Agreement.
IN WITNESS WHEREOF, Lessor and Lessee, by their duly authorized
representatives, have executed and delivered this Rider which is intended to
take effect as a sealed instrument as of the date of the Lease Agreement.
BANCBOSTON LEASING INC. TRUSTEES OF BOSTON UNIVERSITY
By: /s/ By: /s/ ▇▇▇▇▇▇ ▇▇▇▇▇▇
------------------------------- -------------------------------
Title: Assistant Vice President Title: Assistant Treasurer
---------------------------- -----------------------------
-58-
INVESTIGATOR'S STATEMENT OF AGREEMENT
The undersigned investigator, _______________________________________
("Investigator") declares that he or she has read and is familiar with the
provisions of the
Research and License Agreement ("AGREEMENT") dated June 1,
1993 between NITROMED, INC. ("SPONSOR") and TRUSTEES OF BOSTON UNIVERSITY
("UNIVERSITY"), and hereby agrees with the UNIVERSITY to be bound by the terms
and conditions thereof with respect to the Research Proposal of Dr. ▇▇▇▇▇▇
▇▇▇▇▇▇▇▇. Further, Investigator specifically acknowledges and agrees as follows:
1. MAINTAINING CONFIDENTIALITY OF NITROMED CONFIDENTIAL INFORMATION AND
MATERIAL: Investigator shall comply with his or her obligations to maintain the
confidentiality of NITROMED CONFIDENTIAL INFORMATION AND MATERIALS, disclosed or
provided by NITROMED to Investigator or UNIVERSITY, as defined in Section 6 of
the AGREEMENT.
2. SEEKING RESEARCH FUNDING FROM OTHER COMMERCIAL SPONSORS IN THE FIELD
OF RESEARCH - NITROMED WRITTEN APPROVAL REQUIRED: Investigator shall comply with
his or her obligations under Section 2.3 of the AGREEMENT which requires that
the Investigator obtain the written consent of NITROMED prior to seeking or
accepting any funding from a commercial sponsor in the Field of Research. The
Investigator will consult with the Medical Campus Office of Sponsored Programs
regarding such prior written consent, before applying for any such funding in
the Field of Research, which is defined in the Research Proposal in Appendix A
to the AGREEMENT, as follows:
Cardiovascular, gastrointestinal, and pulmonary research,
and research relating to erectile dysfunction and ureteral
relaxation, utilizing nitric oxide compounds,
nitrosothiols, nitrosoproteins, other nitrosylated
compounds and/or agonists and antagonists thereof, and
other compounds which mediate nitric oxide.
3. USING OR ACQUIRING MATERIALS FOR USE IN THE RESEARCH - MATERIALS
MUST BE ACQUIRED ON TERMS CONSISTENT WITH NITROMED'S RIGHTS UNDER THE AGREEMENT:
In accordance with Section 5.5 of the AGREEMENT, Investigator shall not use or
acquire any biological or chemical materials for use in the sponsored research
under terms that will prevent UNIVERSITY from granting to NITROMED exclusive
rights in technology developed while using such materials in the sponsored
research. Investigator will consult with the Medical Campus Office of Sponsored
Programs regarding any agreement with a third party for transfer of materials to
the Investigator for use in the sponsored research or in the Field of Research.
4. DISCLOSING ALL INVENTIONS, INFORMATION AND MATERIALS DEVELOPED IN
THE FIELD OF RESEARCH DURING THE RESEARCH PROGRAM: Investigator acknowledges his
or her obligation to disclose to the UNIVERSITY all inventions, information and
materials as defined in the AGREEMENT developed in the Field of Research during
the research program. Ownership of all such technology shall vest in the
UNIVERSITY and be licensed to NITROMED in accordance with the terms of the
AGREEMENT. Further, Investigator acknowledges that he or she has signed the
Boston University Medical Center Patent Policy and Agreement, a signed
-59-
copy of which is attached hereto, pursuant to which Investigator shall share in
net royalties received by the UNIVERSITY as provided therein.
5. RESTRICTIONS ON DISCLOSURE OF RESEARCH RESULTS: In order to protect
NITROMED's rights in inventions, information and materials developed in the
Field of Research, the Investigator will comply with the following provisions of
the AGREEMENT:
a. PUBLICATION DELAYS: Investigator agrees to comply
with the requirements of Section 4.2 of the AGREEMENT.
Investigator will ensure that he or she submits to NITROMED a
copy of any material to be disclosed to a third party or
submitted for publication at least 45 days prior to such
publication, submission or disclosure,
b. RESTRICTION ON TRANSFER OF BIOLOGICAL OR CHEMICAL
MATERIALS: Investigator agrees to comply with the requirements of
Section 4.1 of the AGREEMENT. Investigator will ensure that
research materials are not transferred to any for-profit entity
or person known to be an employee or consultant of such entity.
Investigator will ensure that materials are not transferred to a
non-profit entity or person affiliated therewith except under the
terms of a signed Material Transfer Agreement ("MTA") in the form
attached as Appendix C to the AGREEMENT or as otherwise approved
by NITROMED and UNIVERSITY. Investigator will consult with the
Medical Campus Office of Sponsored Research regarding any such
MTA and will provide a copy thereof to that Office.
/s/ ▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇
------------------------------------- ---------------------------------------
Signature of Investigator/Date Name of Investigator (typed)
WITNESSED BY:
/s/ ▇▇▇▇ der ▇▇▇▇▇▇▇▇ ▇▇▇▇ der ▇▇▇▇▇▇▇▇
------------------------------------- ---------------------------------------
Signature of Witness/Date Name of Witness (typed)
-▇▇-
▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇▇ MEDICAL CENTER CAMPUS
PATENT POLICY AND AGREEMENT
PREAMBLE
The patent policy outlined herein is the policy of the Boston University Medical
Center, whose constituent members are Boston University School of Medicine,
▇▇▇▇▇▇▇ School of Graduate Dentistry and University Hospital. The Medical Center
recognizes that patentable inventions may be made in the course of research
sponsored by the Medical Center and/or by others through the Medical Center. It
is the desire of the Medical Center to maximize the benefit to the individual
who makes such a patentable invention, the Medical Center and the general
public, and to stimulate initiative in the faculty, staff, and employees of the
Medical Center. The Medical Center recognizes that this may best be accomplished
through patenting and licensing such inventions in a manner consistent with the
public interest and for such purpose the Medical Center hereby establishes the
patent policy set forth herein. This policy supersedes the policy as issued
March 1, 1963.
1. PATENT POLICY
A. In order to protect the public good and the general character of the
Medical Center and its members, and in order to fulfill obligations to research
sponsors, the Medical Center shall claim on behalf of its constituent members
equity in all discoveries and its right to acquire the title and control to such
discoveries where the discoveries are made by faculty, staff, employees or
students (including all types of trainees or postgraduate residents or fellows)
working on or arising from programs supported in whole or in part by funds,
space, personnel, or facilities provided by the Medical Center or any of its
members.
B. Where a discovery is made by an inventor outside of any program
conducted by the Medical Center or any constituent member of the Medical Center
with which the inventor is connected, and where the Medical Center or any
constituent member did not provide or administer significant funds, space,
personnel, or facilities for work leading to the discovery, the discovery shall
remain the exclusive property of the inventor or his sponsor. The Medical Center
and its constituent members shall not ordinarily consider provision of office,
classroom, or library facilities as constituting significant use of Medical
Center funds, space, personnel or facilities.
C. When necessary, the Medical Center Committee on Inventions and
Discoveries shall decide whether an invention or discovery should be classified
under 1A or 1B. The decision of the Committee is appealable to the Director of
the Medical Center, who shall consult with the President of Boston University
and the President of University Hospital. The Director shall recommend final
action to the Trustee Council, whose decision shall be final.
2. ROYALTIES
Where the Medical Center claims equity in a discovery, the inventor will
ordinarily receive at least 15 percent but not more than 30 percent of the net
royalties accruing therefrom. The exact share shall be determined, promptly
after the disclosure by the Deans of the Medical and Dental Schools and the
Administrator of University Hospital. In determining the exact share, the Deans
-61-
and the Administrator shall take into account but not be limited to the state of
development of the discovery, the ease of licensing and marketing, the scope of
patent protection and the degree of novelty of the discovery. The Community
Technology Foundation of Boston University, when it acts as agent for the
administration of patents or discoveries made within the Medical Center, shall
receive 20 percent of the net royalties (see Paragraph 4). The remaining
royalties from and equities in the invention shall be divided among the
constituent members of the Medical Center, including any shares to be allocated
to the inventor's department or division, in proportions determined by the Deans
of the Medical and Dental Schools and the Administrator of University Hospital.
In case the Deans and the Administrator cannot reach a consensus, the Director
of the Medical Center shall decide.
3. DISCLOSURES
Because the securing of rights in discoveries and inventions depends on prompt
and efficient patent application and administration, all faculty, staff,
students, and employees of the Medical Center who make inventions or discoveries
shall immediately disclose said inventions or discoveries to the Medical Center
Patent Office, which, upon approval of the Medical Center Committee on
Inventions and Discoveries, shall forward such disclosures of inventions and
discoveries covered under Paragraph 1A to the Community Technology Foundation,
Patent Administrator. This disclosure obligation shall apply to all inventions
and discoveries whether they fall under Paragraph 1A or 1B above.
4. PATENT ADMINISTRATION
Unless otherwise determined in specific instances by the Medical Center
Committee on Inventions and Discoveries, the Community Technology Foundation of
Boston University ordinarily shall be the agent of the Medical Center for the
administration of inventions and discoveries covered under Paragraph 1A made
within the Medical Center, subject to the terms herein. The Community Technology
Foundation Patent Administrator shall present the disclosures to the Medical
Center Committee on Inventions and Discoveries. The membership of that Committee
shall consist of an equal number of representatives from each of Boston
University and University Hospital, all designated by the Director of the
Medical Center. The Chairman of the Committee shall be designated by the
Director of the Medical Center after consultation with the President of Boston
University and the President of University Hospital. It shall be the Committee's
responsibility to determine whether an invention or discovery is worth further
development, and how to proceed with the development, including such delegation
to the Community Technology Foundation Patent Administrator of duties and
authority with respect to the development as the Committee shall determine.
Community Technology Foundation shall render a written semiannual report to the
Director of the Medical Center and the Committee on the disposition and status
of all inventions and discoveries submitted. If the Committee determined that
Community Technology Foundation has not filed a patent application within one
year after it has received a disclosure, the Committee, in consultation with the
inventor, shall determine what other dispositions, if any, shall be made of the
invention or its discovery and its development.
-62-
5. COVERAGE
This policy shall cover only discoveries and inventions that are patentable as
the term is defined in the United States Code, as amended, or the laws of other
countries where applications are filed.
6. TRUSTEE REVIEW
Any disputes that arise under this policy shall be referred to the Director of
the Medical Center, who, after consultation with the President of Boston
University and the President of University Hospital, shall recommend final
action to the Trustee Council of the Medical Center whose decision shall be
final.
7. EMPLOYMENT AGREEMENT
An appropriate form shall be signed by all faculty, staff, employees and
students working at the Medical Center providing for specific acceptance of the
terms of this policy. Rights and obligations under this agreement shall survive
any termination of enrollment or employment at the Medical Center.
Nothing herein contained is intended to grant or dispose of any right, title,
and interest to any disclosure, idea, improvement, or invention, whether
patentable or not, which has been supported or funded by outside parties who
acquire rights to such disclosure, idea, improvement and invention.
8. ADOPTION
The above policy is adopted by the Medical Center and its constituent members by
vote of the Trustees of Boston University, Trustees of University Hospital and
Trustee Council of the Medical Center.
9. EFFECTIVE DATE AND TERM
This policy shall be effective as of the date first written below and shall
continue in effect until termination by any of the members by written notice to
the other members. The policy shall cover any and all inventions and discoveries
which are disclosed or occur after said effective date and which are disclosed
prior to said termination.
DATE November 23, 1981
UNIVERSITY HOSPITAL, INC. TRUSTEES OF BOSTON UNIVERSITY
By: /s/ ▇▇▇▇ ▇. ▇▇▇▇▇, ▇▇. By: /s/ ▇▇▇▇ ▇. ▇▇▇▇▇▇
---------------------------------- ------------------------------------
▇▇▇▇ ▇. ▇▇▇▇▇, ▇▇. ▇▇▇▇ ▇. ▇▇▇▇▇▇
President President
-63-
PATENT AGREEMENT
I affirm that I have received and have read the Boston University Patent
Policy/Medical Center Campus.
For and in consideration of the provisions by Boston University Medical Center
of support in the form of funds, space, personnel, facilities, instruction,
supervision or other assistance. I hereby accept and will abide by, and fully
comply with the aforesaid Patent Policy as determinative of my rights and
obligations in relation to any discoveries or patentable inventions.
/s/ ▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇ 2/18/94
--------------------------------------------------------------------------------
SIGNATURE DATE
▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇
--------------------------------------------------------------------------------
NAME (please type or print) DEPARTMENT
--------------------------------------------------------------------------------
INSTITUTION
Keep one copy for your files and return signed copy in enclosed envelope.
-64-
APPENDIX A
TO
RESEARCH AND LICENSE AGREEMENT
DATED JUNE 1, ▇▇▇▇
▇▇▇▇▇▇▇
▇▇▇▇▇▇▇▇ ▇▇ ▇▇▇▇▇▇ UNIVERSITY
AND
NITROMED, INC.
RESEARCH PROPOSAL
PRINCIPAL INVESTIGATOR: ▇▇▇▇▇ ▇▇▇▇▇ ▇▇ ▇▇▇▇▇▇, M.D.
FIELD OF RESEARCH:
Research relating to erectile dysfunction and ureteral relaxation,
utilizing nitric oxide compounds, nitrosothiols, nitrosoproteins, other
nitrosylated compounds and/or agonists and antagonists thereof, and other
compounds which mediate nitric oxide.
SPONSORED RESEARCH PROGRAM:
The SPONSORED RESEARCH PROGRAM is described on Exhibit 1 attached
to this RESEARCH PROPOSAL.
TERM OF RESEARCH PROPOSAL
This RESEARCH PROPOSAL shall commence on June 1, 1993 ("COMMENCEMENT DATE")
and shall continue in effect until May 31, 1994, unless sooner terminated
by either party as provided in Section 13 of the
Research and License
Agreement.
FUNDING OF RESEARCH PROPOSAL
The annual research grant to be provided by NITROMED for the first
AGREEMENT YEAR (12-month period commencing on the START DATE) shall be in a
total amount of [**] dollars ($[**]) as provided in the Budget attached to
this RESEARCH PROPOSAL as Exhibit 2. Budgets for subsequent years, if any,
shall be determined and approved by the parties in accordance with Section
2 of the
Research and License Agreement and shall thereupon be attached and
incorporated into Exhibit 2 hereto.
IN WITNESS WHEREOF, the parties have executed this RESEARCH PROPOSAL as of the
COMMENCEMENT DATE of the SPONSORED RESEARCH PROGRAM set forth above.
-65-
NITROMED, INC. TRUSTEES OF BOSTON UNIVERSITY
By: /s/ ▇▇▇▇▇▇ ▇▇▇▇▇▇ By: /s/ ▇▇▇▇▇ ▇▇▇▇▇▇▇
-------------------------- --------------------------------
Name: ▇▇▇▇▇▇ ▇▇▇▇▇▇ Name: ▇▇▇▇▇ ▇▇▇▇▇▇▇
------------------------ ------------------------------
Title: President & CEO Title: Executive Director of Financial Affairs
----------------------- -----------------------------------------
/s/ ▇▇▇▇▇ ▇▇▇▇▇ ▇▇ ▇▇▇▇▇▇
------------------------------------
▇▇▇▇▇ ▇▇▇▇▇ ▇▇ ▇▇▇▇▇▇, M.D.
Principal Investigator
-66-
EXHIBIT 1
A) Design and evaluation for NO donors for the treatment of impotence. Because
of the realization that nitric oxide exerts such an important role as a
physiological mediator of penile erection, the possibility of using NO as a
therapeutic agent for impotence is proposed. NO, a free radical, is too unstable
and short lived to allow its use as a pharmacological agent, however, it can by
stabilized by reaction with carrier molecules that prolong its half life and
preserve its biological activity [▇▇▇▇▇▇▇ et al. PNAS. 89: 7674-7677, 1992;
▇▇▇▇▇▇▇ et al. PNAS. 89: 444-448, 1992]. A group of molecules that contain
reduced sulfhydryl functional groups subserve this role as NO carriers due to
the rapid reaction of free thiol with oxides of nitrogen with the formation of
S-nitrosothiols. These molecules are more stable than NO and are potent
vasodilators [▇▇▇▇▇▇▇ et. al; PNAS. 89: 7674-7677, 1992; ▇▇▇▇▇▇▇ et al. PNAS.89
444-448, 1992.] Utilizing this approach, in collaboration with Drs. ▇▇▇▇▇▇▇▇ and
▇▇▇▇▇▇▇, we are currently developing NO donors for the purpose of treating
impotence. Our overall goal is to identify molecules with biological activity
that facilitate or induce relaxation of smooth muscle and that, in their
molecule, have a free thiol group susceptible to S-nitrosylation. These
molecules in addition to their own biological activity would also be NO donors
with a potential for a synergism of action (relaxation) on penile smooth muscle.
We have performed preliminary studies with two molecules: S-nitroso-captopril
and S-nitroso-VIP. Rationale for S-nitroso-captopril. Captopril, an angiotensin
converting enzyme inhibitor has been shown to improve endothelium-dependent
relaxation in vascular disease. The converting enzyme not only catalyzes the
formation of angiotensin II (a potent vasoconstrictor) from its precursor
angiotensin I, but also participates in the inactivation of the potent
endogenous vasodilator bradykinin. This substance has been shown to be a potent
endothelium-dependent dilator of human corpus cavernosum smooth muscle. In
addition, although the role of angiotensin II as a constrictor of corpus
cavernosum remains elusive, pulsatile release of angiotensin I and II has been
demonstrated in this tissue. Our preliminary studies show that captopril (I uM)
causes a significant shift to the left of the concentration-dependent relaxation
of trabecular smooth muscle by bradykinin. Captopril has a free thiol on its
molecule susceptible to S-nitrosylation. Lozcalzo et al. [J Pharmacol Exp Ther.
249: 726-734, 1989.] and ▇▇▇▇▇▇▇ et al. [J Pharmacol Exp Ther. 256: 704-709,
1991.], have demonstrated the potent vasodilator effects of S-nitroso-captopril
in blood vessels. In addition, they have demonstrated that S-nitroso-captopril
maintains its full activity as an angiotensin converting enzyme inhibitor.
Preliminary studies in our laboratory have demonstrated that S-nitroso-captopril
is also a potent dilator of human and rabbit corpus cavernosum tissue. Unlike
the dilator effects of NO, S-nitroso-captopril causes a more sustained
relaxation of corpus cavernosum smooth muscle which is probably due to the
increased stability of NO in this compound. These potent NO dependent relaxant
effects, together with the potentiation of endothelium-dependent relaxation
described above, make S-nitroso-captopril, a potentially useful agent for the
treatment of impotence. Experiments are herein proposed to continue the
evaluation of S-nitroso-captopril as a potential drug for the treatment of
impotence.
Rationale for S-nitroso-VIP. Intracellular accumulation of either CAMP or cGMP
lead to a reduction in intracellular calcium concentration, causing myosin
dephosphorylation and relaxation. Strong evidence suggests that activation of
cGMP-dependent protein kinase mechanisms is a critical step for the actions of
both cyclic nucleotides. Also both, NO and VIP, can induce vascular smooth
muscle relaxation through cyclic nucleotide-independent mechanisms, including
hyperpolarization and the activation of ATP-sensitive K+ channels. The
-67-
combined actions of the two potent vasodilators, and their mediation via
multiple pathways, offer the advantages of making relaxation failure less likely
than if only one transmitter or mechanism were in place (Sami Said, Trends in
Physiological Sciences). With this rationale and with the goal of combining the
effects of VIP and NO we have designed a VIP-NO-donor. Because VIP does not have
a free thiol susceptible to nitrosylation we have designed a VIP analog.
(VIP-glycine-cystene-NH2) that in the added cysteine presents a free thiol
functional group. Preliminary experiments show that VIP-G-C maintains the
biological activity of VIP and that the free thiol in cysteine can be
nitrosylated, making S-nitroso-VIP a NO donor. Experiments are proposed herein
to continue the characterization of S-nitroso-VIP as a potential drug for the
treatment of impotence.
The following experiments are planned:
1) S-nitroso-captopril. Since the synthesis of this compound has been
demonstrated, and its potent dilator effects on human and rabbit corpus
cavernosum smooth muscle established, our next step with this compound will be
to evaluate its effects in vivo in an animal model. Unfortunately, the rabbit
animal model is not valid for this purpose, since rabbit corpus cavernosum
responds very poorly to bradykinin. Thus, the possible synergism between the
potentiation of bradykinin responses by captopril and the dilator effects of NO
can not be evaluated in the rabbit. For this reason we plan to perform these
experiments in the dog model. These experiments will be done in collaboration
with Dr. Michael Stroky, in the Urology Research Laboratory at the Boston VA
Medical Center. This laboratory is fully equipped for in vivo studies in
animals. ▇▇. ▇▇▇▇▇▇ has published extensively on a dog model to examine the
hemodynamics of penile erection. While the animal is under deep anesthesia,
intracavernosal pressure, systemic blood pressure and blood flow to the penis
will be monitored. S-nitroso-captopril (0.5 ml solutions of 10 TO THE POWER OF
6 - 10 TO THE POWER OF 3 M) will be delivered by intracavernosal injection while
monitoring these parameters. The response to vehicle, captopril, and acidified
NaNO2 will be studied as controls.
2) S-nitroso-VIP-G-C. Preliminary data shows that S-nitroso-VIP is a potent
dilator of human and rabbit corpus cavernosum. Optimization of conditions for
deprotection of the sulfhydryl group of cysteine (removal of the acetamidomethyl
group) and nitrosylation of the peptide with a maximum yield are underway in the
laboratory of ▇▇. ▇▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇ at the ▇▇▇▇▇▇▇ and Women's Hospital. The
following experiments are planned.
WHAT IS THE POTENCY, AS A DILATOR, OF VIP-G-C COMPARED TO VIP? Studies will be
done on human and rabbit corpus cavernosum tissue in organ ▇▇▇▇▇▇▇▇. Tissues
from the same animal or patient will be contracted (phenylephrine, 3-6 X 10 TO
THE POWER OF -7 M) and exposed to cumulative concentrations of either VIP or
VIP-GC. The duration of the effects will be assessed by measuring the time of
maximal relaxation after the last maximum effective does is given. If VIP-G-C
has a dilator potency comparable to VIP, subsequent studies will focus on the
comparison of VIP-G-C to S-nitro-VIP-G-C.
WHAT IS THE POTENCY, AS A DILATOR, OF S-NITOSO-VIP-G-C COMPARED TO VIP-G-C? In a
similar protocol as that described above, the relative potency of the peptides
will be compared in human and rabbit corpus cavernosum tissue. Potency of the
peptides will be evaluated by measuring the maximal relaxation attained,
defining the ED50 and ED max for each peptide, and determining
-68-
the duration of the effect by measuring the time of maximal relaxation after the
last maximum effective dose is given.
WHAT IS THE MECHANISM OF S-NITROSO-VIP-G-C INDUCED RELAXATION? Tissues and human
corpus cavernosum smooth muscle cells (HCC-SMC) will be exposed to either VIP,
VIP-G-C or S-nitroso-VIP-G-C and the accumulation of cyclic nucleotides
measured. These experiments will be done in the presence and absence of
phosphodiesterase inhibitors.
DOES INTRACAVERNOSAL S-NITORSO-VIP-G-C ELICIT PENILE ERECTION IN VIVO? Once the
in vitro characterization of the peptide has been completed the potency of this
molecule to induce penile erection in vivo will be assessed. These experiments
will be done in ▇▇. ▇▇▇▇▇▇'▇ laboratory with a similar protocol as that
described for S-nitroso-captopril. The effects of vehicle, VIP, VIP-G-C and
S-nitroso-VIP will be compared. The dog animal model is again chosen because it
will allow comparison of the effects of S-nitro-captopril to those of
S-nitroso-VIP-G.C.
Evaluation of the effects of NO donors on ureteral contractility Rationale. A
variety of diseased of the kidney and ureter make the endoiscopic exploration of
the ureter (ureteroscopy) necessary. One of the most significant difficulties in
performing this technique is overcoming the ureteral spasm that makes
cannulation of the ureter very difficult. Overcoming this spasm by mechanical
means (e.g. use of dilators) is frequently associated with considerable
morbidity due to rupture of the ureter. For this reason, the development of
pharmacological agents capable of relaxing the spastic smooth muscle, would
represent a very useful tool as an adjunct therapy in ureteroscopy.
We have developed a pressurized pig ureter in vitro model that allows the
evaluation of the effects of pharmacological agents on ureteral smooth muscle
tone. With this model, pharmacological agents can be delivered inside the
ureteral lumen, which would be the route of delivery in vivo. Preliminary
experiments with this model show that S-nitroso-N-acetyl-cysteine (10 TO THE
POWER OF -4 - 10 TO THE POWER OF -3 M) inhibits ureteral contraction elicited by
either electrical stimulation or norepinephrine.
It is our plan to continue the characterization of NO donors in this model; the
following molecules will be tested:
1) Continue the characterization of the effects of S-nitroso-N-acetyl-cysteine
2) Evaluation of the effects of S-nitroso-glutathione
3) Design and evaluation of more lypophilic NO donors (better penetration of the
ureteral epithelium), to inhibit ureteral smooth muscle contraction.
-69-
EXHIBIT 2
▇▇▇▇▇▇-NITROMED BUDGET
NitroMed Budget - ▇▇▇▇▇▇
------------------------------------------------------------ ------------------ ------------------- ------------------
Boston University Portion:
------------------------------------------------------------ ------------------ ------------------- ------------------
Budget A
------------------------------------------------------------ ------------------ ------------------- ------------------
Salaries $[**]
------------------------------------------------------------ ------------------ ------------------- ------------------
Fringe Benefits $[**]
------------------------------------------------------------ ------------------ ------------------- ------------------
------------------------------------------------------------ ------------------ ------------------- ------------------
Supplies:
--------------------- -------------------------------------- ------------------ ------------------- ------------------
Rabbits $[**]
--------------------- -------------------------------------- ------------------ ------------------- ------------------
Other Supplies $[**]
--------------------- -------------------------------------- ------------------ ------------------- ------------------
Equipment: $[**] $[**]
--------------------- -------------------------------------- ------------------ ------------------- ------------------
--------------------- -------------------------------------- ------------------ ------------------- ------------------
Budget B Supplies and Other $[**] $[**]
--------------------- -------------------------------------- ------------------ ------------------- ------------------
Tot.D.C. $[**]
--------------------- -------------------------------------- ------------------ ------------------- ------------------
--------------------- -------------------------------------- ------------------ ------------------- ------------------
Indirect Costs @ [**]% $[**] $[**]
--------------------- -------------------------------------- ------------------ ------------------- ------------------
Total BU Portion of Budget $[**]
------------------------------------------------------------ ------------------ ------------------- ------------------
VA Subcontract
--------------------- -------------------------------------- ------------------ ------------------- ------------------
Salaries $[**]
--------------------- -------------------------------------- ------------------ ------------------- ------------------
Supplies $[**]
--------------------- -------------------------------------- ------------------ ------------------- ------------------
Other $[**]
--------------------- -------------------------------------- ------------------ ------------------- ------------------
Tot.D.C. $[**]
--------------------- -------------------------------------- ------------------ ------------------- ------------------
Ind.Cost @ [**]% $[**] $[**]
--------------------- -------------------------------------- ------------------ ------------------- ------------------
--------------------- -------------------------------------- ------------------ ------------------- ------------------
Total VA Budget Portion $[**]
--------------------- -------------------------------------- ------------------ ------------------- ------------------
--------------------- -------------------------------------- ------------------ ------------------- ------------------
------------------------------------------------------------ ------------------ ------------------- ------------------
Total Budget All components $[**]
------------------------------------------------------------ ------------------ ------------------- ------------------
------------------------------------------------------------ ------------------ ------------------- ------------------
------------------------------------------------------------ ------------------ ------------------- ------------------
------------------------------------------------------------ ------------------ ------------------- ------------------
adh 1/11/93
------------------------------------------------------------ ------------------ ------------------- ------------------
-70-
INVESTIGATOR'S STATEMENT OF AGREEMENT
The undersigned investigator, /s/ ▇▇▇▇▇ ▇▇▇▇▇ ▇▇ ▇▇▇▇▇▇ ("Investigator")
declares that he or she has read and is familiar with the provisions of the
Research and License Agreement ("AGREEMENT") dated June 1, 1993 between
NITROMED, INC. ("SPONSOR") and TRUSTEES OF BOSTON UNIVERSITY ("UNIVERSITY"), and
hereby agrees with the UNIVERSITY to be bound by the terms and conditions
thereof with respect to the Research Proposal of ▇▇. ▇▇▇▇▇ ▇▇▇▇▇ ▇▇ ▇▇▇▇▇▇ .
Further, Investigator specifically acknowledges and agrees as follows:
1. MAINTAINING CONFIDENTIALITY OF NITROMED CONFIDENTIAL INFORMATION AND
MATERIAL: Investigator shall comply with his or her obligations to maintain the
confidentiality of NITROMED CONFIDENTIAL INFORMATION AND MATERIALS, disclosed or
provided by NITROMED to Investigator or UNIVERSITY, as defined in Section 6 of
the AGREEMENT.
2. SEEKING RESEARCH FUNDING FROM OTHER COMMERCIAL SPONSORS IN THE FIELD
OF RESEARCH - NITROMED WRITTEN APPROVAL REQUIRED: Investigator shall comply with
his or her obligations under Section 2.3 of the AGREEMENT which requires that
the Investigator obtain the written consent of NITROMED prior to seeking or
accepting any funding from a commercial sponsor in the Field of Research. The
Investigator will consult with the Medical Campus Office of Sponsored Programs
regarding such prior written consent, before applying for any such funding in
the Field of Research, which is defined in the Research Proposal in Appendix A
to the AGREEMENT, as follows:
Research relating to erectile dysfunction and ureteral
relaxation, utilizing nitric oxide compounds, nitrosothiols,
nitrosoproteins, other nitrosylated compounds and/or
agonists and antagonists thereof, and other compounds which
mediate nitric oxide.
3. USING OR ACQUIRING MATERIALS FOR USE IN THE RESEARCH - MATERIALS
MUST BE ACQUIRED ON TERMS CONSISTENT WITH NITROMED'S RIGHTS UNDER THE AGREEMENT:
In accordance with Section 5.5 of the AGREEMENT, Investigator shall not use or
acquire any biological or chemical materials for use in the sponsored research
under terms that will prevent UNIVERSITY from granting to NITROMED exclusive
rights in technology developed while using such materials in the sponsored
research. Investigator will consult with the Medical Campus Office of Sponsored
Programs regarding any agreement with a third party for transfer of materials to
the Investigator for use in the sponsored research or in the Field of Research.
4. DISCLOSING ALL INVENTIONS, INFORMATION AND MATERIALS DEVELOPED IN
THE FIELD OF RESEARCH DURING THE RESEARCH PROGRAM: Investigator acknowledges his
or her obligation to disclose to the UNIVERSITY all inventions, information and
materials as defined in the AGREEMENT developed in the Field of Research during
the research program. Ownership of all such technology shall vest in the
UNIVERSITY and be licensed to NITROMED in accordance with the terms of the
AGREEMENT. Further, Investigator acknowledges that he or she has signed the
Boston University Medical Center Patent Policy and Agreement, a signed copy of
which is attached hereto, pursuant to which Investigator shall share in net
royalties received by the UNIVERSITY as provided therein.
-71-
5. RESTRICTIONS ON DISCLOSURE OF RESEARCH RESULTS: In order to protect
NITROMED's rights in inventions, information and materials developed in the
Field of Research, the Investigator will comply with the following provisions of
the AGREEMENT:
a. PUBLICATION DELAYS: Investigator agrees to comply with the
requirements of Section 4.2 of the AGREEMENT. Investigator will
ensure that he or she submits to NITROMED a copy of any material
to be disclosed to a third party or submitted for publication at
least [**] days prior to such publication, submission or
disclosure,
b. RESTRICTION ON TRANSFER OF BIOLOGICAL OR CHEMICAL MATERIALS:
Investigator agrees to comply with the requirements of Section 4.1
of the AGREEMENT. Investigator will ensure that research
materials are not transferred to any for-profit entity or person
known to be an employee or consultant of such entity.
Investigator will ensure that materials are not transferred to a
non-profit entity or person affiliated therewith except under the
terms of a signed Material Transfer Agreement ("MTA") in the form
attached as Appendix C to the AGREEMENT or as otherwise approved
by NITROMED and UNIVERSITY. Investigator will consult with the
Medical Campus Office of Sponsored Research regarding any such
MTA and will provide a copy thereof to that Office.
/s/ ▇▇▇▇▇ ▇▇▇▇▇ ▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇ ▇▇▇▇▇ ▇▇ ▇▇▇▇▇▇
------------------------------------ -----------------------------------
Signature of Investigator/Date Name of Investigator (typed)
WITNESSED BY:
/s/ ▇▇▇▇ Der ▇▇▇▇▇▇▇▇ ▇▇▇▇ Der ▇▇▇▇▇▇▇▇
------------------------------------ -----------------------------------
Signature of Witness/Date Name of Witness (typed)
-▇▇-
▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇▇ MEDICAL CENTER CAMPUS
PATENT POLICY AND AGREEMENT
PREAMBLE
The patent policy outlined herein is the policy of the Boston University Medical
Center, whose constituent members are Boston University School of Medicine,
▇▇▇▇▇▇▇ School of Graduate Dentistry and University Hospital. The Medical Center
recognizes that patentable inventions may be made in the course of research
sponsored by the Medical Center and/or by others through the Medical Center. It
is the desire of the Medical Center to maximize the benefit to the individual
who makes such a patentable invention, the Medical Center and the general
public, and to stimulate initiative in the faculty, staff, and employees of the
Medical Center. The Medical Center recognizes that this may best be accomplished
through patenting and licensing such inventions in a manner consistent with the
public interest and for such purpose the Medical Center hereby establishes the
patent policy set forth herein. This policy supersedes the policy as issued
March 1, 1963.
1. PATENT POLICY
A. In order to protect the public good and the general character of the
Medical Center and its members, and in order to fulfill obligations to research
sponsors, the Medical Center shall claim on behalf of its constituent members
equity in all discoveries and its right to acquire the title and control to such
discoveries where the discoveries are made by faculty, staff, employees or
students (including all types of trainees or postgraduate residents or fellows)
working on or arising from programs supported in whole or in part by funds,
space, personnel, or facilities provided by the Medical Center or any of its
members.
B. Where a discovery is made by an inventor outside of any program
conducted by the Medical Center or any constituent member of the Medical Center
with which the inventor is connected, and where the Medical Center or any
constituent member did not provide or administer significant funds, space,
personnel, or facilities for work leading to the discovery, the discovery shall
remain the exclusive property of the inventor or his sponsor. The Medical Center
and its constituent members shall not ordinarily consider provision of office,
classroom, or library facilities as constituting significant use of Medical
Center funds, space, personnel or facilities.
C. When necessary, the Medical Center Committee on Inventions and
Discoveries shall decide whether an invention or discovery should be classified
under 1A or 1B. The decision of the Committee is appealable to the Director of
the Medical Center, who shall consult with the President of Boston University
and the President of University Hospital. The Director shall recommend final
action to the Trustee Council, whose decision shall be final.
2. ROYALTIES
Where the Medical Center claims equity in a discovery, the inventor will
ordinarily receive at least 15 percent but not more than 30 percent of the net
royalties accruing therefrom. The exact share shall be determined, promptly
after the disclosure by the Deans of the Medical and Dental Schools and the
Administrator of University Hospital. In determining the exact share, the Deans
-73-
and the Administrator shall take into account but not be limited to the state of
development of the discovery, the ease of licensing and marketing, the scope of
patent protection and the degree of novelty of the discovery. The Community
Technology Foundation of Boston University, when it acts as agent for the
administration of patents or discoveries made within the Medical Center, shall
receive 20 percent of the net royalties (see Paragraph 4). The remaining
royalties from and equities in the invention shall be divided among the
constituent members of the Medical Center, including any shares to be allocated
to the inventor's department or division, in proportions determined by the Deans
of the Medical and Dental Schools and the Administrator of University Hospital.
In case the Deans and the Administrator cannot reach a consensus, the Director
of the Medical Center shall decide.
3. DISCLOSURES
Because the securing of rights in discoveries and inventions depends on prompt
and efficient patent application and administration, all faculty, staff,
students, and employees of the Medical Center who make inventions or discoveries
shall immediately disclose said inventions or discoveries to the Medical Center
Patent Office, which, upon approval of the Medical Center Committee on
Inventions and Discoveries, shall forward such disclosures of inventions and
discoveries covered under Paragraph 1A to the Community Technology Foundation,
Patent Administrator. This disclosure obligation shall apply to all inventions
and discoveries whether they fall under Paragraph 1A or 1B above.
4. PATENT ADMINISTRATION
Unless otherwise determined in specific instances by the Medical Center
Committee on Inventions and Discoveries, the Community Technology Foundation of
Boston University ordinarily shall be the agent of the Medical Center for the
administration of inventions and discoveries covered under Paragraph 1A made
within the Medical Center, subject to the terms herein. The Community Technology
Foundation Patent Administrator shall present the disclosures to the Medical
Center Committee on Inventions and Discoveries. The membership of that Committee
shall consist of an equal number of representatives from each of Boston
University and University Hospitals, all designated by the Director of the
Medical Center. The Chairman of the Committee shall be designated by the
Director of the Medical Center after consultation with the President of Boston
University and the President of University Hospital. It shall be the Committee's
responsibility to determine whether an invention or discovery is worth further
development, and how to proceed with the development, including such delegation
to the Community Technology Foundation Patent Administrator of duties and
authority with respect to the development as the Committee shall determine.
Community Technology Foundation shall render a written semiannual report to the
Director of the Medical Center and the Committee on the disposition and status
of all inventions and discoveries submitted. If the Committee determined that
Community Technology Foundation has not filed a patent application within one
year after it has received a disclosure, the Committee, in consultation with the
inventor, shall determine what other dispositions, if any, shall be made of the
invention or its discovery and its development.
-74-
5. COVERAGE
This policy shall cover only discoveries and inventions that are patentable as
the term is defined in the United States Code, as amended, or the laws of other
countries where applications are filed.
6. TRUSTEE REVIEW
Any disputes that arise under this policy shall be referred to the Director of
the Medical Center, who, after consultation with the President of Boston
University and the President of University Hospital, shall recommend final
action to the Trustee Council of the Medical Center whose decision shall be
final.
7. EMPLOYMENT AGREEMENT
An appropriate form shall be signed by all faculty, staff, employees and
students working at the Medical Center providing for specific acceptance of the
terms of this policy. Rights and obligations under this agreement shall survive
any termination of enrollment or employment at the Medical Center.
Nothing herein contained is intended to grant or dispose of any right, title,
and interest to any disclosure, idea, improvement, or invention, whether
patentable or not, which has been supported or funded by outside parties who
acquire rights to such disclosure, idea, improvement and invention.
8. ADOPTION
The above policy is adopted by the Medical Center and its constituent members by
vote of the Trustees of Boston University, Trustees of University Hospital and
Trustee Council of the Medical Center.
9. EFFECTIVE DATE AND TERM
This policy shall be effective as of the date first written below and shall
continue in effect until termination by any of the members by written notice to
the other members. The policy shall cover any and all inventions and discoveries
which are disclosed or occur after said effective date and which are disclosed
prior to said termination.
DATE November 23, 1981
UNIVERSITY HOSPITAL, INC. TRUSTEES OF BOSTON UNIVERSITY
By: /s/ ▇▇▇▇ ▇. ▇▇▇▇▇, ▇▇. By: /s/ ▇▇▇▇ ▇. ▇▇▇▇▇▇
------------------------------ -----------------------------
▇▇▇▇ ▇. ▇▇▇▇▇, ▇▇. ▇▇▇▇ ▇. ▇▇▇▇▇▇
President President
-75-
PATENT AGREEMENT
I affirm that I have received and have read the Boston University Patent
Policy/Medical Center Campus.
For and in consideration of the provisions by Boston University Medical Center
of support in the form of funds, space, personnel, facilities, instruction,
supervision or other assistance. I hereby accept, and will abide by, and fully
comply with the aforesaid Patent Policy as determinative of my rights and
obligations in relation to any discoveries or patentable inventions.
--------------------------------------------------------------------------------
SIGNATURE DATE
--------------------------------------------------------------------------------
NAME (please type or print) DEPARTMENT
--------------------------------------------------------------------------------
INSTITUTION
Keep one copy for your files and return signed copy in enclosed envelope.
-76-
MODIFICATION #1 TO APPENDIX A
TO
RESEARCH AND LICENSE AGREEMENT
DATED JUNE 1, ▇▇▇▇
▇▇▇▇▇▇▇
▇▇▇▇▇▇▇▇ ▇▇ ▇▇▇▇▇▇ UNIVERSITY
AND
NITROMED, INC.
RESEARCH PROPOSAL
PRINCIPAL INVESTIGATOR: ▇▇▇▇▇ ▇▇▇▇▇ ▇▇ ▇▇▇▇▇▇, M.D.
FIELD OF RESEARCH:
Research relating to erectile dysfunction and ureteral relaxation,
utilizing nitric oxide compounds, nitrosothiols, nitrosoproteins, other
nitrosylated compounds and/or agonists and antagonists thereof, and other
compounds which mediate nitric oxide.
SPONSORED RESEARCH PROGRAM:
The SPONSORED RESEARCH PROGRAM is described on Exhibit 1 attached to the
original RESEARCH PROPOSAL.
TERM OF RESEARCH PROPOSAL:
This modification shall extend the termination date of the RESEARCH
PROPOSAL through May 31, 1995, unless sooner terminated by either party as
provided in Section 13 of the Research and License Agreement.
FUNDING OF RESEARCH PROPOSAL:
The research grant to be provided by NITROMED for the second AGREEMENT YEAR
(12-month period commencing on 6/1/94) shall be in a total amount of [**]
($[**]), as provided in the Budget attached to this modification # 1 of the
RESEARCH PROPOSAL as Exhibit 2. Budgets for subsequent years, if any, shall
be determined and approved by the parties in accordance with Section 2 of
the Research and License Agreement and shall thereupon be attached and
incorporated into Exhibit 2 hereto.
-77-
IN WITNESS WHEREOF, the parties have executed this RESEARCH PROPOSAL as of the
COMMENCEMENT DATE of the SPONSORED RESEARCH PROGRAM set forth above.
NITROMED, INC. TRUSTEES OF BOSTON UNIVERSITY
By: /s/ ▇▇▇▇▇▇ ▇▇▇▇▇▇ By: /s/ ▇▇▇▇▇ ▇▇▇▇▇▇▇
--------------------------------- --------------------------------
Name: ▇▇▇▇▇▇ ▇▇▇▇▇▇ Name: ▇▇▇▇▇ ▇▇▇▇▇▇▇
Title: President & CEO Title: Exec. Dir. for Financial Affairs
/s/ ▇▇▇▇▇ ▇▇▇▇▇ ▇▇ ▇▇▇▇▇▇
-----------------------------
▇▇▇▇▇ ▇▇▇▇▇ ▇▇ ▇▇▇▇▇▇, M.D.
-78-
▇▇▇▇▇▇-NITROMED BUDGET
Budget for Modification #1 to Appendix A
▇▇▇▇▇ ▇▇▇▇▇ ▇▇ ▇▇▇▇▇▇, M.D.
Period covered: 6/1/94-6/30/95
Salaries Technician $[**]
Fringe Benefits $[**]
Supplies: $[**]
Equipment: $[**]
Other: $[**]
Director Cost: $[**]
Indirect Cost @ [**]% $[**]
Total Budget [**]
--------
The above budget is for research studies related to the design and
characterization of nitric oxide donors for the treatment of impotence and
ureteral spasm. An exception to this would be if additional experiments are
required for the evaluation of new molecules, in vivo, at the VA Medical Center.
-▇▇-
▇▇▇▇▇▇▇▇ ▇
1. Boston University Disclosure Number: 93-20
Submitted to the Boston University Office of Patent and Technology
Administration on June 23, 1993
Title: S-Nitrosylation of VIP, VIP Family of Peptides and Synthetic Analogs
of These Peptides for the Treatment of Impotence
Boston University Investigator: ▇▇. ▇▇▇▇▇ ▇▇▇▇▇ ▇▇ ▇▇▇▇▇▇
-80-
APPENDIX C
Agreement dated ________________ by and among ________________________ (the
"Institution") and _______________________ (the "Investigator") and Boston
University ("University") with respect to the samples of a
In consideration of the receipt from University by the Institution and the
Investigator of the samples, the Institution and the Investigator agree to the
following conditions:
1. Those samples, their progeny and derivatives thereof (the "Materials")
remain the property of University.
2. The Investigator will use the Materials solely for academic noncommercial
research conducted by the Investigator at the Institution in the 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 University.
3. The Investigator will not give access to the Materials to any party not
connected with the Research Program without written permission from University.
4. 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 University and its
employees and agents for all claims and damages (including legal fees) arising
from the use, storage, or handling, of the Materials by the Institution and/or
the Investigator.
INSTITUTION: INVESTIGATOR:
By: By:
------------------------------ -------------------------
BOSTON UNIVERSITY
By:
------------------------------
-81-
AMENDMENT TO RESEARCH AND LICENSE AGREEMENT
WHEREAS, Trustees of Boston University, a
Massachusetts not-for-profit
corporation with offices at ▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇, ▇▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇ (the
"UNIVERSITY") and NitroMed, Inc., a Delaware corporation with its principal
office at ▇▇ ▇▇▇ ▇▇▇▇ ▇▇▇▇▇, ▇▇▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇ ("NITROMED"), entered
into a research and license agreement dated as of June 1, 1993, (the
"Agreement") for certain RESEARCH PROGRAMS to be sponsored by NITROMED and
performed by UNIVERSITY, which RESEARCH PROGRAMS are more particularly described
therein; and
WHEREAS, NITROMED desires to sponsor an additional RESEARCH PROGRAM at
UNIVERSITY and UNIVERSITY desires to perform said additional RESEARCH PROGRAM;
and
WHEREAS, UNIVERSITY and NITROMED mutually desire to amend said Agreement to
reflect the additional RESEARCH PROGRAM to be sponsored by NITROMED and to be
performed by UNIVERSITY;
NOW, THEREFORE, for good and valuable consideration, the receipt and
sufficiency of which are hereby acknowledged, UNIVERSITY and NITROMED hereby
agree to amend the Agreement by:
Adding the attached RESEARCH PROPOSAL to Appendix A of the Agreement, which
shall be a duly authorized SPONSORED RESEARCH PROGRAM as that term is defined in
the Agreement.
All terms not expressly defined herein, shall have the definition set forth
in the Agreement.
Except as expressly provided herein or in said Agreement, said Agreement as
originally executed is hereby ratified and confirmed.
EXECUTED as a sealed instrument as of the 1st day of July, 1997.
NITROMED, INC. TRUSTEES OF BOSTON UNIVERSITY
By:/s/▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇▇▇, ▇▇. By: /s/ ▇▇▇▇▇▇▇ ▇. ▇▇▇▇
-------------------------------------- ---------------------------
▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇▇, ▇▇. ▇▇▇▇▇▇▇ ▇. ▇▇▇▇, Executive
Its Vice President Hereunto Authorized Title: Director for Financial Affairs
RESEARCH PROPOSAL
-82-
NITROMED SPONSORED RESEARCH PROGRAM
ON RSNOS AND PLATELET FUNCTION
▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇, M.D., PH.▇.
▇▇▇▇▇▇▇▇ CARDIOVASCULAR INSTITUTE
BOSTON UNIVERSITY SCHOOL OF MEDICINE
-83-
SECTION 15: BACKGROUND
Platelets play an important role in primary hemostasis and in the
pathophysiology of thrombotic disorders. Nitric Oxide (NO) and S-nitrosothiols
(RSNOs) are potent antiplatelet agents that exert their effects through a
variety of mechanisms, including activation of guanylyl cyclase and modulation
of nonspecific cation channels in the platelet plasma membrane. Our laboratory
has played a central role in dissecting the role of NO and RSNOs in modulating
platelet function and in developing approaches to the pharmacological inhibition
of platelet activation utilizing RSNO-based approaches. In this proposal, we
present planned experiments that focus on 1) developing a novel S-NO-based
inhibitor of platelet adhesion and activation that can be used as an adjunct for
thrombolytic therapy, and 2) dissecting the molecular mechanism by which RSNOs
gain access to the cytosolic compartment of cells through a mechanism that
involves [**].
SECTION 16: TERM OF RESEARCH PROGRAM
The research program (the "Research Program") described herein shall be
conducted during the period from July 1, 1997 through June 30, 2000.
SECTION 17: RESEARCH PROPOSAL
17.1 We wish to develop a novel inhibitor of platelet adhesion and
activation based on a [**].
SECTION 18: COMPENSATION
In consideration of Boston University's agreement to undertake the Research
Program described herein, NitroMed will pay University a total of $[**]. The
program funds will be paid, in advance to Boston University in equal quarterly
installments with the first payment due on July 1, 1997. The annual budget
consists of:
-84-
Postdoctoral Fellow Salary and Fringe $[**]Supplies/Animal Costs
$[**]Institutional Overhead $[**]
Total $[**]We view these studies as of potentially
great interest, both to the overall area of platelet biology, but also to
the mission of NitroMed and to its focused interest in the effects of NO
and RSNOs on platelet function.
[**]
-85-
AMENDMENT TO RESEARCH AND LICENSE AGREEMENT
WHEREAS, Trustees of Boston University of
Massachusetts not-for-profit
corporation with offices at ▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇, ▇▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇ (the
"UNIVERSITY") and NitroMed, Inc., a Delaware corporation with its principal
office at ▇▇ ▇▇▇ ▇▇▇▇ ▇▇▇▇▇, ▇▇▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇ ("NITROMED "), entered
into a research and license agreement dated as of June 1, 1993, (the
"Agreement") for certain RESEARCH PROGRAMS to be sponsored by NITROMED and
performed by UNIVERSITY, which RESEARCH PROGRAMS are more particularly described
therein; and
WHEREAS, NITROMED desires to sponsor an additional RESEARCH PROGRAM at
UNIVERSITY and UNIVERSITY desires to perform said additional RESEARCH PROGRAM;
and
WHEREAS, UNIVERSITY and NITROMED mutually desire to amend said Agreement to
reflect the additional RESEARCH PROGRAM to be sponsored by NITROMED and to be
performed by UNIVERSITY;
NOW, THEREFORE, for good and valuable consideration, the receipt and
sufficiency of which are hereby acknowledge, UNIVERSITY and NITROMED hereby
agree to amend the Agreement by:
Adding the attached RESEARCH PROPOSAL entitled "Evaluation of
Antithrombotic Properties of Nitroso-Derivative of Recombinant Fragment of Von
Willebrand Factor Using In Vivo and Ex Vivo Guinea Pig Model" to Appendix A of
the Agreement, which shall be a duly authorized SPONSORED RESEARCH PROGRAM as
that term is defined in the Agreement.
All terms not expressly defined herein, shall have the definition set forth
in the Agreement.
Except as expressly provided herein or in said Agreement, said Agreement as
originally executed is hereby ratified and confirmed.
EXECUTED as a sealed instrument as of the 1st day of January, 1999.
NITROMED, INC. TRUSTEES OF BOSTON UNIVERSITY
By:/s/▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇▇▇, ▇▇. By: /s/ ▇▇▇▇▇▇▇ ▇. ▇▇▇▇
------------------------------- ----------------------------------
▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇▇, ▇▇. ▇▇▇▇▇▇▇ ▇. ▇▇▇▇, Executive
Its Vice President Hereunto Title: Director for Financial Affairs
Authorized
-▇▇-
▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇▇ 88 East ▇▇▇▇▇▇ Street ▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇, M.D., Ph.D.
SCHOOL ▇▇ ▇▇▇▇▇▇▇▇ ▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇-▇▇▇▇ ▇▇▇▇ PROFESSOR AND CHAIRMAN
Tel: ▇▇▇ ▇▇▇-▇▇▇▇ Department of Medicine
BOSTON MEDICAL CENTER Fax: ▇▇▇ ▇▇▇-▇▇▇▇ Boston University
▇▇▇▇▇▇▇▇@▇▇.▇▇▇ School of Medicine
March 26, 2003 ▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇ Medical Center
Boston, MA 02118-2544
▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇, Ph.D. Tel: ▇▇▇ ▇▇▇-▇▇▇▇ DIRECTOR
▇▇▇▇ ▇▇▇▇▇ ▇▇▇▇▇▇▇▇ ▇▇▇▇▇ Cardiovascular Institute
▇▇▇▇▇▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇
Dear ▇▇▇▇▇▇:
I am pleased to offer you a position in the Section of Molecular Medicine
of the Department of Medicine at Boston University School of Medicine. The
details of this position are as follows:
1. You will be proposed for appointment as Professor of Medicine.
2. Your salary will be $[**] per annum with the standard benefits package. We
expect that you will contribute to your salary support through grant
resources. To this end, NitroMed, Inc., will provide $[**] per annum (with
cost of living increases) for three years toward your salary. After year
three, I expect that you will generate [**]% of your salary from grants.
3. NitroMed, Inc., has agreed to purchase up to $[**] of equipment you
requested during your visit on February 5, 2003, as needed.
4. You will be given access for support for a postdoctoral fellow on the
Cardiovascular Training Grant for up to three years.
5. You will be provided access to a graduate student through the Graduate
Program in Molecular Medicine.
6. You will be given $[**] per annum for supplies for three years as
additional support from NitroMed, Inc.
7. You will be given 1,500 sq. ft. of space in the ▇▇▇▇▇ Biomedical Research
Center through the Boston University School of Medicine. This space will be
leased from Boston University by NitroMed, Inc., at $40 per sq. ft. for
three years.
8. We expect that you will work up to [**] days per week on NitroMed, Inc.
projects under the terms of the existing license agreement between
NitroMed, Inc. and the Trustees of Boston University. In addition, you will
be given a position on the Scientific Advisory Board of NitroMed, Inc.
We trust this letter details all the major issues we discussed, and meets
your projected needs adequately. We look forward with enthusiasm to your
joining us and to many years of gratifying academic productivity with us.
With best personal regards, we remain
Sincerely,
/s/ ▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇ /s/ ▇▇▇▇ ▇▇▇▇▇▇▇▇▇ /s/ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇
------------------- ------------------ ------------------
▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇, M.D., Ph.D. ▇▇▇▇ ▇▇▇▇▇▇▇▇▇, M.D. ▇▇▇▇▇▇▇ ▇▇▇▇▇▇, Ph.D.
Chairman, Department of Medicine ▇▇▇▇ and ▇▇▇▇▇▇▇ Chief Executive Officer
BU School of Medicine NitroMed, Inc.
I have read and accept the position as outlined above.
/s/▇▇▇▇▇▇ Feelish May 5, 2003
-----------------------------------------------
▇▇▇▇▇▇ Feelish, Ph.D. Date
-87-