[*] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS
AMENDED.
Exhibit 10.14
RESEARCH AGREEMENT
AND EXCLUSIVE LICENSE
Effective as of December 29, 0000, XXXXXXXXXX XXXXXXXXXX, a not-for-
profit corporation of the District of Columbia, having a principal address of
00xx & "X" Xxxxxxx, X.X., Xxxxxxxxxx, X.X. 00000 ("LICENSOR"), and ZEBRA
PHARMACEUTICALS, a Massachusetts corporation, having a principal place of
business at 00 Xxxxxxx Xxxx, Xxxxxx, Xxxxxxxxxxxxx 00000 ("LICENSEE") agree as
follows:
1. BACKGROUND
1.1 -- LICENSOR is the owner by assignment of inventions directed
generally to cocaine analogs, and specifically piperidine analogs thereof (the
"Invention(s)").
1.2 -- LICENSOR wishes to have the Invention(s) and related technologies
perfected and marketed at the earliest possible time in order that products
resulting therefrom may be available for public use and benefit.
1.3 -- LICENSEE wishes to acquire a license under said Invention(s) and
Licensed Patent(s), for the purpose of undertaking development, to manufacture,
use, and sell Licensed Produce(s) in the Licensed Field of Use.
2. DEFINITIONS
2.1 -- "Patent Rights" refers to LICENSOR's rights arising from
Provisional U.S. Patent Application Serial No. 60/042,775, filed April 7, 1997,
entitled "Analogs of Cocaine" and naming as inventors Xxxx X. Xxxxxxxxxx and
Gian Xxxx Xxxxxx, including the information contained in said application with
respect to the Invention(s), any foreign patent applications corresponding
thereto, any divisions, continuations, reissues, or reexaminations thereof, and
any patent(s) issuing or granted therefrom. Such patent application(s) are the
"Licensed Application(s)" and any resulting issued patents are the "Licensed
Patent(s)."
2.2 -- "Technology" means any existing technical data and information
provided to LICENSEE by LICENSOR or its employees or contractors relating to
Invention(s), including, without limitation, any biochemical, preclinical,
clinical, manufacturing, formulation, and scientific research information of a
confidential nature.
1
2.3 -- "Licensed Product(s)" means any compound, product or part thereof
in the Licensed Field of Use, the manufacture, use, or sale of which:
(a) is covered by a valid claim of an issued, unexpired Licensed Patent(s)
directed to the Invention(s). A claim of an issued, unexpired Licensed Patent(s)
shall be presumed to be valid unless and until it has been held to be invalid by
a final judgment of a court of competent jurisdiction from which no appeal can
be or is taken;
(b) is covered by any claim being prosecuted in Licensed Application(s).
2.4 -- "Net Sales" means the gross revenue of the Licensed Product(s) in
the form in which it is sold or used, whether or not assembled (and without
excluding therefrom any components or subassemblies thereof, whatever their
origin and whether or not patent impacted) less the following items:
(a) Import, export, excise, value added and sales taxes, plus custom
duties;
(b) Costs of insurance, packing, and transportation from the place of
manufacture to the customer's premises or point of installation;
(c) Normal and customary quantity and cash discounts, and
(d) Credit for returns, allowances, or trades actually given.
2.5 -- "Licensed Field of Use" means therapeutic and diagnostic uses of
transporters for neurotransmitters, including dopamine, serotonin and
norepinephrine, for substance abuse, obesity, depression, Xxxxxxxxx'x disease,
and related neuro psychological conditions or diseases.
2.6 -- "Exclusive" means LICENSOR has not granted and shall not grant
further licenses in the Licensed Field of Use, so long as this Agreement is
fully operative.
2.7 -- "Regulatory Approval" means any approval or clearance by any
governmental agency or agencies having authority to regulate the use or sale of
any Licensed Product(s) in the pertinent jurisdiction or territory.
2.8 -- "LICENSEE" is understood to include all of its Affiliates. An
Affiliate of LICENSEE shall mean any corporation or other business entity
controlled by, controlling, or under common control with LICENSEE as of the date
of this Agreement. For this purpose, "control" means direct or indirect
beneficial ownership:
(a) Of at least fifty percent (50%) of the voting stock; or
(b) Of at least fifty percent (50%) interest in the income of such
corporation or other business.
2
[*] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS
AMENDED.
3. RESEARCH AGREEMENT
3.1 -- LICENSOR shall perform pre-clinical pharmacology and new compound
synthesis sufficient to identify, if feasible, a lead compound suitable for
development into a Licensed Product. (see attached Statement of Work and Budget)
3.2 -- Within two months of execution of this agreement, LICENSEE agrees
to pay to LICENSOR its costs, including overhead, incurred to-date in connection
with the preparation, filing and prosecution of the Licensed Applications, which
costs have been estimated by LICENSOR to be $2,500.
3.3 -- LICENSEE shall fund the LICENSOR's research as follows:
(a) LICENSEE shall pay to LICENSOR, upon execution of this
Agreement, an initial amount of $[******], which shall fund LICENSOR's initial
year of research.
(b) On the first day of both the 12th and 24th full calendar months
after the execution of this Agreement, LICENSEE shall pay to LICENSOR $[*****]
to fund an additional year of research, unless LICENSOR and LICENSEE agree that
such additional research is not necessary.
(c) If at any time LICENSOR shall determine that any of the above
sums are inadequate to fund the research or other work necessary to permit the
development of a Licensed Product, it shall notify LICENSEE of the amount that
LICENSOR reasonably believes will be necessary to fund the remaining research.
LICENSEE shall then have 60 days to notify LICENSOR, in writing, whether it is
willing to agree to provide such additional amounts. If LICENSEE does not agree
to provide such amounts, then either party may terminate this Agreement by
written notice to the other. Such termination will not apply to any previously
developed Licensed Products.
3.4 -- LICENSEE shall perform all toxicological, Phase I, Phase II or
other tests or studies necessary to obtain approval of a NDA and shall prepare,
prosecute and file any IND or NDA necessary to secure approval of all feasible
Licensed Products based on the Invention(s), Patent Rights or Technology in the
Licensed Field of Use. Upon notification from LICENSOR, as to any prospective
product, that LICENSOR has completed its research pursuant to paragraph 3.1,
LICENSEE shall promptly begin such studies and tests and diligently proceed with
them until approval has been obtained for all feasible Licensed Products.
LICENSEE shall thereafter use its best efforts to market, promote, manufacture
and sell any Licensed Products developed pursuant to this Agreement. If LICENSEE
determines that a potential Licensed product is not feasible, it
3
[*] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS
AMENDED.
shall notify LICENSOR. Such notification shall relinquish any rights of LICENSEE
in said Licensed Product. Any dispute between the parties as to the feasibility
of a Licensed Product shall be resolved pursuant to Article 16 below.
3.5 -- LICENSEE shall provide to LICENSOR, at least semi-annually, a
written report comprehensively describing its progress toward fulfillment of its
obligations pursuant to paragraph 3.4. If LICENSEE fails to make continuous and
reasonable progress toward the development of each feasible Licensed Product,
LICENSOR may notify LICENSEE of its dissatisfaction. In such event, LICENSOR and
LICENSEE shall negotiate in good faith in an attempt to resolve the basis for
such dissatisfaction. Should LICENSOR remain dissatisfied 30 days after such
notification, LICENSOR may, in its sole discretion, terminate this Agreement.
4. GRANT
4.1 -- LICENSOR hereby grants and LICENSEE hereby accepts a worldwide
license in the Licensed Field of Use to make, have made, use, and sell Licensed
Product(s).
4.2 -- Said license, which includes the right to sublicense, shall be
Exclusive in the Licensed Field of Use.
5. ROYALTIES
5.1 -- (a) LICENSEE shall pay LICENSOR $[******] upon execution of this
Agreement;
(b) LICENSEE shall pay to LICENSOR benchmark royalties relating to each
Licensed Product as follows:
(1) $[*******] within 30 days after the IND approval;
(2) $[*******] within 30 days after commencement of Phase I tests;
(3) $[*******] within 30 days after commencement of Phase II tests;
(4)$[*******] upon filing and an additional $[*******] upon approval
of the NDA.
LICENSEE may investigate more than one Licensed Product through Phase II
tests, without paying more than one set of benchmark royalties. If LICENSEE
should choose to submit multiple NDAs or an NDA covering more than one Licensed
Product, then the benchmark royalties relating to additional Licensed Products
shall be reduced by [**]%. If, after obtaining approval of an NDA, LICENSEE
attempts to develop additional
4
Licensed Products, benchmark royalties relating to such products will by reduced
by 50%.
5.2 -- In addition, LICENSEE shall pay LICENSOR earned royalties on Net
Sales by LICENSEE of [*****] percent ([*]%). LICENSEE shall pay to LICENSOR, as
royalties relating to any sublicense, the greater of (a) [*]% of Net Sales by
such sublicensee or (b) [*************************] percent ([****]%) of any
compensation LICENSEE receives from the sublicensee. If the Licensed Product is
solely for diagnostic use in the Licensed Field of Use, LICENSEE shall pay
LICENSOR earned royalties on Net Sales by LICENSEE or any sublicensee of [***]
percent ([*]%).
5.3 -- The royalty on sales in currencies other than U.S. Dollars shall be
calculated using the appropriate foreign exchange rate for such currency quoted
by the Wall Street Journal, on the close of business on the last banking day of
each calendar quarter. Royalty payments to LICENSOR shall be in U.S. Dollars.
5.4 -- In the event that the Patent Rights relating to a particular
Licensed Product are finally determined or adjudged by the Patent and Trademark
Office or a court of competent jurisdiction to be unpatentable or invalid, or
upon the expiration of the last patent covering such Licensed Product, LICENSEE
shall be entitled to a [**]% reduction in all royalties related to such Licensed
Product accruing pursuant to this Article 5, commencing on the effective date of
such determination, judgment or expiration.
6. REPORTS, PAYMENTS, AND ACCOUNTING
6.1 -- Quarterly Royalty Payment and Report --LICENSEE shall make written
reports and royalty payments to LICENSOR within ninety (90) days after the end
of each calendar quarter following the first commercial sale. This report shall
state the number, description, and aggregate Net Sales of Licensed Produce(s)
during such completed calendar quarter, and resulting calculation of earned
royalty payment due LICENSOR for such completed calendar quarter. Concurrent
with the making of each such report, LICENSEE shall include payment due LICENSOR
of royalties for the calendar quarter covered by such report.
6.2 -- Accounting -- LICENSEE agrees to keep records for a period of
two (2) years showing the manufacturing, sales, use, and other disposition of
products sold or otherwise disposed of under the license herein granted in
sufficient detail to enable the royalties payable hereunder by LICENSEE to be
determined, and further agrees to permit its books and records to be examined by
LICENSOR from time to time to the extent necessary to verify reports provided
for in Paragraph 5.1. Such examination is to be
5
made by LICENSOR, at its expense. If LICENSOR determines that LICENSEE has, for
any reason, failed to pay adequate royalties, LICENSEE shall immediately upon
notice thereof pay to LICENSOR any owed royalties plus interest at the rate of
eleven percent (11% per annum, compounded daily, calculated from the date upon
which such royalties should have been paid to the date of actual payment of
LICENSOR).
7. WARRANTY
LICENSOR represents and warrants that it has not granted the Patent Rights
or any rights in any Licensed Product(s) to any third party, except for United
States government rights which may have been required by law. LICENSOR also
represents and warrants that, to the best of LICENSOR'S knowledge, information
and belief, the Invention(s) are novel.
8. INFRINGEMENT
8.1 -- LICENSEE shall notify LICENSOR of any suspected infringement of the
Patent Rights by a third party.
8.2 -- In the event that information becomes known to or is brought to the
attention of LICENSEE that others without license are unlawfully infringing upon
rights granted to LICENSEE pursuant to this Agreement, LICENSEE shall diligently
prosecute any infringer at LICENSEE's cost and expense. LICENSEE arid LICENSOR
acknowledge and agree that, although LICENSOR shall have the right at LICENSOR'S
option to prosecute infringers, LICENSOR is not desirous of being a party to any
such infringement suit. LICENSEE shall not join LICENSOR as a party-plaintiff to
any suit which LICENSEE may institute unless necessary for the maintenance of
said suit, and then only with the prior knowledge and written consent of
LICENSOR. In such event, LICENSOR shall not be chargeable for any costs or
expenses. LICENSOR shall execute all documents necessary for the prosecution of
any infringement suit brought by LICENSEE and provide other such support as
LICENSEE may require, all however at the expense, with respect to travel and the
like, of LICENSEE. LICENSEE is under no obligation to defend an action brought
by a third party alleging that the Patent Rights infringe an issued U.S. patent
or to defend a declaratory judgment action brought by a third party asserting
that the Patent Rights are invalid as anticipated by, or obvious over, prior
art.
6
8.3 -- In the event that LICENSOR decides to institute suit, it shall
notify LICENSEE in writing. LICENSEE's failure to notify LICENSOR in writing,
within thirty (30) days after the date of notice, that it will join in enforcing
the patent pursuant to the provisions hereof, shall be deemed conclusively to be
LICENSEE's assignment to LICENSOR of all rights, causes of actions, and damages
resulting from any such alleged infringement, and LICENSOR shall be entitled to
retain the entire amount of any recovery or settlement. Furthermore, at its
option, LICENSOR may join LICENSEE as plaintiff.
8.4 -- LICENSOR shall be entitled to the percentage of any recovery
obtained in any infringement suit brought by LICENSEE equal to the amount to
which LICENSOR would be entitled under the sublicensee royalty provision of this
Agreement had said recovery been paid to LICENSEE as sublicense royalties by the
defendant in said infringement suit. LICENSEE may deduct its reasonable costs
and attorneys fees incurred in prosecuting such suit, to the extent such costs
and fees are not otherwise recovered, prior to calculating the share owing to
LICENSOR pursuant to this provision.
8.5 -- Should either LICENSOR or LICENSEE commence a suit under the
provisions of Paragraphs 8.2 or 8.3 and thereafter elect to abandon the same,
it shall give timely notice to the other party which may, if it so desires,
continue prosecution of such suit; provided, however, that the sharing of
expenses and any recovery in such suit shall be agreed upon between LICENSOR and
LICENSEE.
9. PROSECUTION OF LICENSED PATENTS
9.1 -- LICENSEE agrees to accept liaison and financial responsibilities,
as hereinafter set forth, for the prosecution, by a patent lawyer in independent
practice, who shall be nominated by LICENSEE and approved by GEORGETOWN, of the
Licensed Applications. Said financial responsibilities shall not only include
the costs of prosecution but also the payment of maintenance fees, where
required, to maintain said patent applications and patents, if issued, in force
and effect for as long as possible. It is further agreed that the patent lawyer
selected by LICENSEE and approved by GEORGETOWN shall be required, if so desired
by GEORGETOWN, to keep a patent lawyer selected by GEORGETOWN informed of all
steps in the prosecution and maintenance of said Patent Rights. Written approval
will be required from GEORGETOWN to the patent lawyer selected by LICENSEE for
actions concerning this patent.
7
9.2 -- Within two (2) weeks of notification to GEORGETOWN by LICENSEE of
the identity of the patent lawyer, GEORGETOWN will furnish to the patent lawyer
nominated in accordance with paragraph 9.1 above:
(a) Complete file histories of all of the patent applications constituting
said Licensed Applications; and
(b) An executed power of attorney or powers of attorney appointing such
patent lawyer as attorney of record in connection with all of said Licensed
Applications.
9.3 -- GEORGETOWN shall have the right at any time, by notice in writing
and sent to LICENSEE by registered mail, to assume and continue at its own
expense, direction of the prosecution of any of said Licensed Applications. Upon
receipt by LICENSEE of any such notice from GEORGETOWN, LICENSEE and the patent
lawyer nominated in accordance herewith shall provide in two weeks from the time
of notice an executed power of attorney and all the file histories of the patent
applications constituting said Licensed Applications. Upon receipt of this
documentation, LICENSEE and the patent attorney nominated by LICENSEE shall be
relieved of all future responsibilities to prosecute the Licensed Applications
to which the notice is directed. If, for any reason, prosecution is to be
abandoned by LICENSEE, GEORGETOWN will be notified in sufficient time to assume
prosecution. LICENSEE shall bear all cost to maintain the patent prosecution
until such time that Georgetown can assume patent prosecution.
10. TERMINATION
10.1 -- LICENSOR may terminate this Agreement:
(a) if LICENSEE is in default in payment of royalties or providing
of reports; or
(b) if LICENSEE is in material breach of any provision hereof; and
LICENSEE fails to remedy any such default or breach within thirty (30) days
after written notice thereof by LICENSOR;
(c) pursuant to paragraph 3.3 or 3.5; or
(d) if LICENSEE is unable to provide adequate assurance of future
performance within sixty (60) days of written notice of LICENSOR's reasonable
belief that LICENSEE may not be able to perform its future obligations under
this Agreement, whether such belief is due to LICENSEE's financial circumstances
or other factors.
10.2 -- Surviving any termination are:
(a) LICENSEE's obligation to pay royalties accrued or accruable;
8
(b) Any cause of action or claim of LICENSEE or LICENSOR, accrued or
to accrue, because of any breach or default by the other party; and
(c) The provisions of Articles 6 and 8.
10.3 -- In the event of termination of this Agreement for any reason, any
and all rights granted LICENSEE hereunder, including any rights granted by
LICENSEE to any sublicensee, shall cease and terminate, and all such rights
shall revert to LICENSOR. LICENSEE shall diligently thereafter return to
LICENSOR, or to LICENSOR's designated attorneys, any files or other documents in
its possession or in the possession of its attorneys, agents or sublicensees,
relating to pending or issued Licensed Patent(s), and shall execute any and all
documents necessary to return control of said Licensed Patent(s) until such time
as control has properly been transferred to LICENSOR. Further, LICENSEE shall
immediately return to LICENSOR all research data, biological and other material
(including but not limited to licensed cell lines), prototypes, process
information, clinical data, and the like of LICENSOR in its possession or in the
possession of its sublicensees.
11. CONFIDENTIALITY
11.1 -- LICENSEE agrees not to disclose or transfer any technical reports,
data and information provided to the LICENSEE by LICENSOR, including the
contents of Licensed Applications to any person other than its employees and
consultants, without prior written approval of LICENSOR. Should LICENSEE wish to
disclose any such information to a third party, it shall provide LICENSOR with
the identity of such party, the purpose of the disclosure, the text of the
proposed disclosure and a proposed confidentiality agreement to be executed by
the third party prior to disclosure of the confidential information. LICENSOR
shall respond within ten working days of any such request for consent to
disclosure, which consent will not be unreasonably withheld.
11.2 -- LICENSEE shall not utilize any Invention, Patent Rights or
Technology in connection with any research or product development in which it
may engage except pursuant to this Agreement. Upon request, LICENSEE shall
permit LICENSOR access to its records and facilities sufficient to confirm
whether such use is occurring.
11.3 -- LICENSEE shall not use LICENSOR's name or refer to LICENSOR in any
promotion, marketing or solicitations without providing LICENSOR a copy of any
such proposed use or reference and obtaining LICENSOR's prior approval in
writing.
11.4 -- LICENSOR shall have the right to distribute information relating
to the Invention(s) to (i) academic investigators at not-for-profit institutions
for non-commercial
9
research purposes, and (ii) third parties for the purpose of obtaining chemical,
physical, or biological analysis or characterization of any information
necessary for furtherance of LICENSOR's academic research. Nothing in this
Paragraph shall limit the right of LICENSOR to disclose any information which,
through no fault of LICENSOR, becomes generally available to the public.
11.5 -- Nothing in this Agreement shall limit in any way LICENSOR's
ability to undertake (i) the filing of any report required by any public
authority, or (ii) the non-public disclosure and discussion of information
between investigators and their academic colleagues.
12. PUBLICATION RIGHTS
12.1 -- LICENSOR shall have the right to publish, disclose and disseminate
("Right to Publish") in whole or in part, any data and information related to
the Invention(s). LICENSEE agrees that it shall not under any circumstances use
the name or names of the LICENSOR or of its employees or contractors, or any
adaptation thereof, (i) in any advertising, promotional, or sales literature,
securities prospectus, press release or other publicity relating to any
invention, discovery or other commercially exploitable product or process, (ii)
on any invention, discovery or other commercially exploitable product or
process, or (iii) generally on any matter arising out of this Agreement, without
prior written consent of LICENSOR.
13. ASSIGNMENT
LICENSEE may not assign any right or delegate any obligation under this
Agreement without the prior written consent of LICENSOR. Consent of the LICENSOR
shall not be unreasonably withheld with respect to publicly traded companies.
Any change in the ownership interests in LICENSEE that exceeds 50% within a
one-year period shall be deemed an assignment.
14. INDEMNIFICATION
14.1 -- LICENSEE agrees that during the term of this Agreement and
thereafter, it will indemnify, defend and hold GEORGETOWN, its trustees,
officers, employees and affiliates, harmless against all claims and expenses,
including legal expenses and attorneys' fees, arising out of the death of or
injury to any person or persons, or out of any damage to property, and against
any other claim, proceeding, demand, expense and
10
liability of any kind whatsoever resulting from the production, manufacture,
sales, use, consumption or advertisement of Licensed Products by LICENSEE.
15. NOTICES
All notices under this Agreement shall be deemed to have been fully given
when done in writing and deposited in the United States mail, registered or
certified, and addressed as follows:
To LICENSOR: To LICENSEE:
GEORGETOWN UNIVERSITY ZEBRA PHARMACEUTICALS
Director Attn: Xxxxx Xxxxxxx
Office of Technology Transfer 00 Xxxxxxx Xxxx
0000 Xxxxxxxxx Xxxxxx, X.X. Xxxxxx, XX 00000
Xxxxx 000
Xxxxxxxxxx, X.X. 00000
Either party may change its address upon notice to the other party as
provided herein.
16. DISPUTE RESOLUTION
Should the parties hereafter have any dispute as to their obligations
pursuant to this Agreement, they shall first attempt to resolve such dispute
among themselves. If such efforts are not successful, the exclusive method for
resolving such a dispute shall be arbitration as described herein.
Either party may elect to submit the issue to arbitration by giving
written notice to the other party and naming an arbitrator. The other party will
then have 30 days to select its own arbitrator. Once both arbitrators have been
selected they shall meet within 30 days of the appointment of the second
arbitrator and select a third arbitrator mutually agreeable to them.
If the dispute relates to the scope of the Patent Rights, Field of Use or
Technology or the feasibility of a Licensed Product, then all arbitrators
selected pursuant to this provision shall have adequate scientific
qualifications, including an advanced degree in a field related to biochemistry
and significant research experience.
11
Once the patent of arbitrators have been chosen, they shall conduct an
arbitration on the disputed issue or issues in accordance with the Commercial
Arbitration Rules of the American Arbitration Association. The third arbitrator
shall serve as the presiding arbitrator, although, in the event of dispute among
the arbitrators, the majority decision of the arbitration panel shall be
binding. The decision of the arbitrators shall be final and either party may
apply to a court located in the District of Columbia to enter judgment based on
the arbitrator's decision. All costs of the arbitrators and the arbitration,
other than the respective parties' attorneys' fees and costs, shall be borne
equally by the parties.
17. WAIVER
None of the terms, covenants, and conditions of this Agreement can be
waived except by the written consent of the party waiving compliance.
18. APPLICABLE LAW
This Agreement shall be construed, interpreted, and applied in accordance
with the laws of the District of Columbia and applicable federal laws.
19. ENTIRE AGREEMENT
This writing constitutes the entire agreement of the parties and there are
no promises, understandings, or agreements of any kind pertaining to this
agreement other than those written in this agreement.
[Signatures follow on page 13]
12
IN WITNESS WHEREOF the parties thereto have executed this Agreement in
duplicate originals by their duly authorized officers or representatives.
Date 12-5-97 Date 12/18/97
For GEORGETOWN UNIVERSITY For XEBRA PHARMACEUTICALS
By : /s/ Xxxxxxx X. Xxxxxxx By : /s/ Xxxxx Xxxxxxx
---------------------- -----------------------
Xxxxxxx X. Xxxxxxx Xxxxx Xxxxxxx, Ph.D.
Acting Chief Operating Officer President
/s/ Xxxxxx Xxxxxx
--------------------------------------
Xxxxxx Xxxxxx, Ph.D.
Acting Associate Xxxx for Research Operations
/s/ Wm. Xxxx Xxxxxxx
--------------------------------------
Wm. Xxxx Xxxxxxx
Director of Research Grants and Contracts
/s/ Xxxxx Xxxxx Xxxx
--------------------------------------
Xxxxx Xxxxx Xxxx, Esq.
Director, Office of Technology Transfer
13
STATEMENT OF WORK CONCERNING THE RESEARCH
CONTRACT BETWEEN GU AND ZEBRA PHARMACEUTICALS.
PREPARED BY XXXXXXXXX XXXXXXXXXX, GU MEDICAL CENTER
Immediate therapies are needed for the treatment of cocaine abuse
worldwide. In this direction, we have recently identified a piperidine-based
analog of cocaine (specifically, the trans isomer of 1-methyl
-4-(4-chlorophenyl)piperidine-3-carboxylic acid methyl ester) that binds to the
cocaine recognition site with comparable affinity to cocaine; additionally, this
compound acts as an inhibitor of dopamine uptake. In spite of the compound's
potency, it has been observed that in discrimination studies in rats, the
compound exhibits only weak cocaine- and amphetamine-like effects. Unlike
cocaine, this compound has weak motor stimulant effects and is not
self-administered by rats. These results appear to be promising from the
standpoint of discovering a possible medication for drug abuse treatment. In
order to properly follow up on these encouraging preliminary results, it is our
plan to conduct further chemical analog synthesis, in vitro pharmacological
studies, and in vivo animal experiments on the 4-phenylpiperidine analogs with
the objective to improve upon the biological profile of this compound.
Within the context of the research contract with Zebra Pharmaceuticals, it
is our intention to pursue the following specific aim:
To conduct additional structure-activity relationship studies in this
piperidine series in order to establish that we are advancing the best compound
as a possible medication. These studies would include preparation of the lead
structure in larger amounts in optically pure form, and the design and synthesis
of related analogs embodying the following structural changes: a) modification
of the nature and position of the substituent borne by the
[*] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS
AMENDED.
Phenyl ring; b) replacement of the N-methyl group by other alkyl groups and
sulfonyl groups, as well as isosteric replacement of NMe by CH(2) and O; c)
replacement of the ester group by alkyl and alkenyl groups.
A budget that reflects how the initial one year budget of $[******] will
be spent is attached.
AMENDMENT TO RESEARCH AGREEMENT AND EXCLUSIVE LICENSE
Dated October 27, 2005
Between Molecular Insight Pharmaceuticals, Inc. (formerly designated in the
above referenced Agreement as Zebra Pharmaceuticals) and Georgetown University.
This Amendment serves to modify the Agreement entered into December 29,
1997 for Patent Rights and Technology related to US Patent Application Serial
No. 60/042,775 (filed April 7, 1997) entitled "Analogs of Cocaine", as well as
any foreign applications corresponding thereto, and any divisions,
continuations, or any reexaminations thereof, and will be enforceable on the
date of the last signature of this Second Amendment.
Molecular Insight Pharmaceuticals, Inc. and Georgetown University agree
that the following provisions in the above referenced agreement shall be
modified as follows:
PREAMBLE
The Agreement preamble formerly reciting:
Effective as of December 29, 0000, XXXXXXXXXX XXXXXXXXXX, a not-for-profit
corporation of the District of Columbia, having a principal address at 00xx & X
Xxxxxxx, X.X., Xxxxxxxxxx, X.X. 00000 ("LICENSOR") and ZEBRA PHARMACEUTICALS, a
Massachusetts corporation, having a principal place of business at 000 Xxxxxx
Xx., Xxxxxxxxx, Xxxxxxxxxxxxx 00000 ("LICENSEE"), agrees as follows:
Shall be replaced by:
Effective as of December 29, 0000, XXXXXXXXXX XXXXXXXXXX, a not-for-profit
corporation of the District of Columbia, having a principal address at 00xx & X
Xxxxxxx, X.X., Xxxxxxxxxx, X.X. 00000 ("LICENSOR") and MOLECULAR INSIGHT
PHARMACEUTICALS, a Massachusetts corporation, having a principal place of
business at 000 Xxxxxx Xx., Xxxxxxxxx, Xxxxxxxxxxxxx 00000 ("LICENSEE"), agree
as follows:
2. DEFINITIONS
Section 2.1 formerly reciting:
2.1 "Patent Rights" refers to LICENSOR's rights arising from U.S.
Provisional Patent Applications Serial No. 60/042,775, filed April 7, 1997
entitled "Analogs of Cocaine", and naming as inventors Xxxx X. Xxxxxxxxxx, and
Gian Xxxx Xxxxxx, including the information contained in said application with
respect to the Invention(s) any foreign patent applications corresponding
thereto, any United States divisions, continuations, reissues, or
reexaminations thereof, and any patent(s) issued or granted therefrom. Such
patent application(s) are the "Licensed Application(s)" and any resulting
patents are the "Licensed Patent(s)."
Shall be replaced by:
2.1 "Patent Rights" refers to LICENSOR's rights arising from U.S.
Provisional Patent Application Serial No. 60/042,775, filed April 7, 1997
entitled "Analogs of Cocaine", including the information contained in said
application with respect to the Invention(s) any foreign patent applications
corresponding thereto, any United States divisions, continuations, continuations
in-part to the extent the claims are directed to subject matter specifically
described in PCT/US98/07081, reissues, or reexaminations thereof, and any
patent(s) issued or granted therefrom, specifically, 6,180,648, 6,472,422 and
6,806,281, all to the extent owned or controlled by Georgetown. Such patent
application(s) are the "Licensed Application(s)" and any resulting patents are
the "Licensed Patents(s)."
In witness thereof, the parties have executed this Amendment on the dates
indicated.
MOLECULAR INSIGHT GEORGETOWN UNIVERSITY
PHARMACEUTICALS, INC.
By: By: /s/ Xxxxxx X. Xxxxxxx
-------------------------- --------------------------
Name: Xxxx X. Xxxxxx Name: Xxxxxx Xxxxxxx
Title: President and CSO Title: Vice President
Office of Technology Transfer
Date: Date: 11/1/05
------------------------- -------------------------
2
