exv10w28






Exhibit 10.28




*** Text
Omitted and Filed Separately to the Commission

Confidential Treatment Requested




DEVELOPMENT AND LICENSE AGREEMENT




          This Development and License Agreement (“Agreement”) is entered into effective as of May 15,
2000 (the “Effective Date”) between Alkermes Controlled Therapeutics Inc. II (“ACTII”) and
Amylin Pharmaceuticals, Inc. (“Amylin”).



RECITALS




          WHEREAS, ACTII owns or has licensed from third parties certain intellectual property rights
relating to injectable, sustained release formulation systems, including the Medisorb® microsphere
system (the “System,” as defined below);



          WHEREAS, Amylin owns or has licensed from third parties certain intellectual property rights
relating to Field Products (as defined below);



          WHEREAS, ACTII and Amylin previously entered into a Feasibility Study Agreement dated as of
June 24, 1999 between ACTII and Amylin, as extended pursuant to the Feasibility Study Extension
Agreement dated February 15, 2000 (collectively, the “Feasibility Agreement”);



          WHEREAS, based upon the results to date of the study performed pursuant to the Feasibility
Agreement, the Parties have determined that the use of ACTII’s System formulations for AC2993 shows
sufficient promise to justify further development pursuant to this Agreement; and,



          WHEREAS, ACTII and Amylin wish to enter into this Agreement, in accordance with the terms set
forth herein.



          NOW THEREFORE, in consideration of the mutual covenants and promises contained herein, the
parties hereto, intending to be legally bound hereby, agree as follows:



          1.    Definitions. The following terms shall have the following meanings:



                       1.1      “AC2993” means synthetic exendin-4.



                       1.2      “ACTII Know-How” means any and all confidential information, data and knowledge
related to the subject matter of ACTII Patents including, without limitation, any know-how, trade
secrets, techniques, strategies, methods, processes, practices, skills, experience, documents,
apparatus, devices, assays, screens, databases, database structures and data analysis methods.
ACTII Know-How does not include ACTII Patents.



                       1.3      “ACTII Patents” means all patents and patent applications owned or controlled by
ACTII relating to the System that are necessary or useful in the manufacture or use of products in
the Field, including those patents and patent applications listed on Exhibit A hereto,
together with any patents resulting therefrom, including divisionals, continuations,
continuations-in-part, continued prosecution applications, reissues, re-examinations, extensions of
term, substitutions, revalidations, renewals, supplemental protection certificates, registrations



 









 




and confirmations thereof, and any other patent or patent application that covers an Invention
which is owned (either jointly or solely by ACTII) or controlled by ACTII. ACTII Patents does not
include ACTII Know How.




                       1.4      “Affiliate” means any entity controlled by, controlling or under common control of
any entity. For purposes of this Section 1.4, “control” denotes the ownership of fifty per cent
(50%) or more of the voting stock or voting equity interests.



                       1.5      “Amylin Patents and Proprietary Information” means (i) the patents and patent
applications necessary or useful in the development of a product in the Field under this Agreement,
initially AC2993, together with any patents resulting therefrom, including divisionals,
continuations, continuations-in-part, continued prosecution applications, reissues,
re-examinations, extensions of term, substitutions, revalidations, renewals, supplemental
protection certificates, registrations and confirmations thereof, and (ii) the proprietary
information, including data, results, knowledge, materials, compositions, formulas, specifications,
designs, devices, methods, processes and techniques, whether patentable or not, developed,
conceived, discovered, synthesized or acquired by Amylin, and/or its Affiliates, necessary or
useful in the development of a product in the Field under this Agreement, initially AC2993.



                       1.6      “Average 20-Day Trailing Price” means, on any day, the average of the closing
prices, as reported on the Nasdaq National Market, for Amylin’s common stock for the 20 trading
days immediately preceding such day.



                       1.7      “Clinical Trial” means a human clinical trial conducted in normal volunteers or
patients and designed to evaluate safety, efficacy or required dosage regimen of a Product.



                       1.8      “Co-Marketer” means any co-marketer, co-detailer, marketing partner, distributor,
wholesaler, consignee or other person or entity acting under an arrangement that is the functional
equivalent of a license or sublicense, but excluding distribution, wholesaling and consignment
arrangements where the distributor, wholesaler or consignee is not obligated, in addition to
selling a Product, to undertake any significant promotional or similar marketing efforts with
respect to the Product.



                       1.9      “Commercially Reasonable Efforts” means a Party’s efforts to develop, market, or
distribute a Product, as applicable, depending on such Product’s stage of development or
commercialization, at a level consistent with the efforts that are devoted (or would be devoted) by
that Party to other products of comparable commercial potential at a similar stage of development
or commercialization.



                       1.10      “Confidential Information”means information relating to the subject matter of
this Agreement, provided by the Disclosing Party to the Receiving Party and identified as
“Confidential”; provided, however, that Confidential Information shall not include any such
information that:



                                      (a) was known to the Receiving Party at the time of disclosure by the Disclosing Party (other
than through receipt from the Disclosing Party or its Affiliates), as can be established by written
documentation; or



 









 





                                      (b) was generally available to the public or was otherwise part of the public domain at the
time of such disclosure or became generally available to the public or otherwise part of the public
domain after such disclosure other than through any act or omission of the Receiving Party in
breach of this Agreement; or



                                      (c) became known to the Receiving Party after disclosure by the Disclosing Party through a
non-confidential disclosure from a source that had a lawful right to disclose such information to
others; or



                                      (d) was independently developed by the Receiving Party where such independent development can
be established by written documentation.



                       1.11      “Disclosing Party” means a Party that discloses its Confidential Information to
the other Party.



                       1.12      “FDA” means the U.S. Food and Drug Administration.



                       1.13      “Field” means System formulations of Field Products.



                       1.14      “Field Products” means [***]



                       1.15      “FTE Hourly Rate” means [***]



                       1.16      “Inventions” means any inventions or discoveries, whether or not patentable,
conceived pursuant to the Product Development Plan during the term of this Agreement or within
three (3) months thereafter.



                       1.17      “Joint Inventions” has the meaning given to it in Section 10.2 (a).



                       1.18      “Major European Market Country” means each of France, Germany, Italy, Spain and
the United Kingdom.



                       1.19      “Major Market Country” means each of France, Germany, Italy, Spain, the United
Kingdom, the United States and Japan.



                       1.20      “NDA” means a New Drug Application filed with the FDA.



                       1.21      “Net Sales” means [***]



          If ACTII is receiving royalties under this Agreement from any Product sold in a form
containing Product and at least one other ingredient, product or component which is Therapeutically
Active, Net Sales for such combination Product will be calculated by multiplying actual Net Sales
of such combination Product by the fraction A/(A+B) where A is the invoice price of the Product if
sold separately, and B is the invoice price of any other ingredient which is Therapeutically Active
in the combination, if sold separately. If, on a country-by-country basis, the other ingredient
which is Therapeutically Active in the combination is not sold separately in said country, Net
Sales for the purpose of determining royalties of the combination Product shall be calculated by
multiplying actual Net Sales of such



 









 




combination Product by the fraction A/C where A is the invoice
price of the Product, if sold separately, and C is the invoice price of the combination Product.
If, on a country-by-country basis, neither the Product nor the other ingredient which is
Therapeutically Active of the combination Product is sold separately in said country, Net Sales for
the purpose of determining royalties of the combination Product shall be determined by the Parties
in good faith. In general, the Parties agree to negotiate in good faith for an equitable
determination of Net Sales of Product, on a country-by-country basis, in the event that Amylin or
its Affiliates, sublicensees or Co-Marketers sell Product in such a manner that gross sales of the
same are not readily identifiable.




                       1.22      “Party” means each of ACTII and Amylin.



                       1.23      “Phase III Clinical Trial” means a large-scale human clinical trial conducted in
patients and designed to indicate a statistically significant level of efficacy for a Product in
the treatment of the disease state being studied and required to obtain clinical registration of
the Product with health regulatory authorities such as the FDA.



                       1.24      “Product” means any Field Product the manufacture, use, sale, offer for sale, or
import of which, but for the licenses granted in this Agreement, would infringe a Valid Claim of
any of the ACTII Patents.



                       1.25      “Product Development Plan” has the meaning given to it in Section 4.3(d)(i).



                       1.26      “Project Working Team” means the working team formed pursuant to Section 4.3(a).



                       1.27      “Receiving Party” means a Party that receives Confidential Information from the
Disclosing Party.



                       1.28      “Regulatory Approval” means approval of an NDA by the FDA or approval of a
comparable application or set of applications by a comparable regulatory authority in a country
other than the United States, together with satisfaction of any related regulatory and notification
requirements of the FDA or such other regulatory authority.



                       1.29      “Steering Committee” means the committee formed pursuant to Section 4.2(a).



                       1.30      “System” refers to methods for preparing microspheres/microparticles by combining
two phases by mixing or other means of blending to form an emulsion, which is then subjected to one
or more extraction steps to remove drug/polymer solvents and complete the formation of
microspheres/microparticles, and to the microspheres/microparticles prepared thereby. The first
phase comprises active ingredient, polymer, and polymer and/or drug solvents. The second phase
comprises water and an emulsifying agent. By way of further clarification, the emulsion could
comprise two phases (e.g., oil in water) or multiple phases (e.g., water in oil in water),
depending on the choice of solvents for the drug and polymer.



 









 





                       1.31      “Therapeutically Active” means biologically active but shall not
include diluents, vehicles or specific adjuvants or
any other ingredient (other than a Product) which does not have any, or only incidental,
therapeutic properties when present alone.



                       1.32      “Valid Claim” means a claim of an issued patent which claim has not lapsed, been
canceled or become abandoned and has not been declared invalid or unenforceable by an unreversed
and unappealable decision or judgment of a court or other appropriate body of competent
jurisdiction, and that has not been admitted to be invalid through disclaimer or found to be
unenforceable through reissue.



                       1.33      “Warrant” means a warrant for one share of the common stock of Amylin,
exercisable at any time on or after the date on which the warrant is issued. [***]



          2.    License Grants.



                       2.1      Grants.



                                 (a) Subject to the limitations, terms and conditions set forth in this Agreement, ACTII hereby
grants to Amylin an exclusive (even as to ACTII, except as provided in Section 2.1(b), below),
worldwide license in the Field under ACTII Patents and ACTII Know-How, together with the right to
grant sublicenses, to make, have made, use, import, offer to sell, sell and have sold Products.



                                 (b) Subject to the limitations, terms and conditions set forth in this Agreement, Amylin
hereby grants to ACTII a non-exclusive, non-transferable, worldwide, royalty-free license, without
the right to grant sublicenses, under the Amylin Patents and Proprietary Information to carry out
its duties and obligations with respect to Field Products under this Agreement.



                       2.2      Commercialization by Amylin. Amylin shall use Commercially Reasonable Efforts to
develop Products for marketing or distribution in all Major Market Countries and to take such other
actions as are necessary to obtain government approvals to market the Products in such markets
throughout the world as Amylin believes appropriate, and thereafter to use Commercially Reasonable
Efforts to market or distribute such Products in such markets.



          3.    Payments to ACTII.



                       3.1      Feasibility Study Completion Milestone. At [***] Amylin shall pay to ACTII [***]
and shall issue to ACTII [***] Warrants exercisable at a purchase price equal to the Average 20-Day
Trailing Price on the Effective Date of this Agreement. If Amylin does not make the payment and
issue the Warrants as provided in
the Section 3.1 as set forth above, the Agreement shall automatically terminate and neither
Party shall have any obligation to the other.



                       3.2      Development Funding.According to Section 4, Amylin will pay to ACTII the FTE
Hourly Rate for all work performed by ACTII under the Product Development Plan.



 









 




                       3.3      Milestones.The following milestone payments shall be paid in accordance with the
following schedule for the first Product to reach each milestone in the Field, said milestone
payments to be made within thirty (30) days of the milestone date:



	 	 	 	 	 	 
	 	Milestone	 	 	Milestone Payment	 
	 	 
	 	 	 	 
	 	 	 	 	 	 
	 	[***]

	 	 	[***]	 
	 	 
	 	 	 	 
	 	 	 	 	 	 
	 	Enrollment of first patient in a Phase III Clinical Trial
	 	 	$5,000,000 	 
	 	 
	 	 	 	 
	 	 	 	 	 	 
	 	First commercial sale of a Product in the United States

	 	 	$7,000,000 	 
	 	 
	 	 	 	 
	 	 	 	 	 	 
	 	First commercial sale of a Product in a Major European
Market Country

	 	 	$7,000,000 	 
	 	 
	 	 	 	 
	 	 	 	 	 	 




All milestone payments are non-refundable and non-creditable.




                       3.4      Payment for Products Manufactured by ACTII. According to Section 6, Amylin will
pay to ACTII a transfer price based on Net Sales of all Products manufactured by ACTII.


                       3.5      Royalties on Products Not Manufactured by ACTII. For all Products that are not
manufactured by ACTII and are instead manufactured by a third party pursuant to Section 6.2
(“Failure to Supply”), below, Amylin shall pay to ACTII a royalty on Net Sales at the rate of
[***]. For all Products that are not manufactured by ACTII and are instead manufactured by a third
party pursuant to Section 6.3 (“Second Source”), below, Amylin shall pay to ACTII a royalty on Net
Sales at the rate of [***]. The royalty payable under this Section 3.5 will be payable only once
with respect to a particular sale of a Product regardless of there being more than one patent or
Valid Claim applicable to such Product.


                       3.6      Transfer Price and Royalty Terms.
This Section 3.6 shall apply to both the transfer price payable under Section 3.4 and the
royalty payable under Section 3.5.


                                 (a)      [***]


                                 (b)      Mode of Payment. Royalty and transfer price payments shall be made within thirty
(30) days after the end of the calendar quarter for all Net Sales invoiced by Amylin, its
Affiliates, sublicensees and Co-Marketers in such calendar quarter. Each royalty and transfer
price payment shall be accompanied by a detailed statement that shall include for each country in
which sales of Products occurred: (a) the gross sales and Net Sales in such country’s currency or
in the Euro, if applicable; (b) the applicable exchange rate for converting such currency to United
States Dollars and gross sales and Net Sales in United States Dollars; (c) an accounting of all
deductions taken in the calculation of Net Sales; (d) a separate accounting for all combination
Products sold and the formulas used in the calculation of the royalty owed thereon; and (e) the
royalty payable in United States Dollars. Such statement shall


 








 




be deemed Confidential Information
of Amylin. The rate of exchange to be used in any currency conversion to United States Dollars
shall be the rate reported in the Wall Street Journal for the purchase of United States Dollars
with such currency on the last business day in Geneva, Switzerland for the quarter for which the
report is being prepared. All royalty and transfer price payments hereunder shall be made to ACTII
in United States Dollars by bank wire transfer in immediately available funds to a bank account
designated by ACTII. All payments hereunder shall be made net of any withholding taxes, duties,
levies, fees or charges required to be withheld under the law on behalf of ACTII. Amylin shall
make any withholding payment due on behalf of ACTII and shall promptly provide ACTII with written
documentation of any such payment.




                                 (c)      Records Retention; Audit. Amylin agrees to keep for at least five (5) years
records of all sales of Products in sufficient detail to permit ACTII to confirm the accuracy of
Amylin’s royalty calculations. At ACTII’s request upon at least forty-five (45) days’ prior
written notice, and at the expense of ACTII, Amylin shall permit a nationally recognized
independent certified public accountant appointed by ACTII, and reasonably acceptable to Amylin, to
examine these records solely to the extent necessary to verify such calculations, provided that
such accountant has entered into a confidentiality agreement with Amylin or ACTII substantially
similar to the confidentiality provisions of this Agreement, limiting the use and disclosure of
such information to those comparable of a royalty statement provided pursuant to Section 3.6(b)
hereof. Such examination may occur only once in each calendar year and may apply only to records
pertaining to the preceding five (5) calendar years. Results of any such examination shall be made
available to ACTII and to Amylin. If such examination reveals an uncontested underpayment of
royalties by five percent (5%) or more, Amylin shall pay all costs of such examination. In the
event such accountant concludes that additional royalties are owed, the additional royalties shall
be paid within thirty (30) days after the date Amylin receives the accountant’s written report
reflecting such conclusion. Amylin shall either (i) keep for at least five (5) years copies of
records of its Affiliates, sublicensees and Co-Marketers sufficient for auditing purposes under
this Section 3.5(c) or (ii) secure the right for ACTII to conduct an audit of the records of
Amylin’s Affiliates, sublicensees and Co-Marketers under this Section 3.6(c) including records
pertaining to gross sales and all deductions taken in the calculation of Net Sales. This
Section 3.6(c) shall survive any termination of this Agreement for two (2) years.



                                 (d)      Termination of Obligation to Pay Royalties. Notwithstanding anything in this
Agreement to the contrary, Amylin’s obligation to pay royalties on Net Sales of a Product shall
cease on a country-by-country basis upon the later of (i) ten (10) years from first commercial sale
of Product, and (ii) the expiration or invalidation of the last Valid Claim of all patents within
the ACTII Patents covering Product in such country.



                                 (e)      Late Payments. Any payment due pursuant to Sections 3, 4 or 6 which is not made
by the date it is due will accrue simple interest from that date to the date of actual payment at a
rate of [***] per annum, computed for the number of days actually elapsed and a year of 365 days.



          4.    Product Development Program.



 









 





                       4.1      Scope. ACTII shall have principal responsibility for the formulation and
non-clinical development of a Product for use in the Field, including formulation, development and
optimization, stability testing, manufacturing of clinical supplies, process scale-up and process
validation. Amylin shall have principal responsibility for toxicological and clinical development
of a Product through Regulatory Approval and sole responsibility for commercialization of a
Product. Each Party shall use Commercially Reasonable Efforts in performing its functions under
the Product Development Plan.



                       4.2      Steering Committee.



                                 (a) Within thirty (30) days after the date of this Agreement, the Parties shall form a
Steering Committee consisting of an equal number of representatives of each Party. The Steering
Committee shall have general authority over the strategic direction and overall management of the
Product Development Plan and shall operate and have the further authority described in this
Section 4.2.



                                 (b) ACTII and Amylin shall each appoint three (3) representatives as their representatives to
serve on the Steering Committee. A Party may change its representatives from time to time by
giving written notice to the other Party.



                                 (c) The Steering Committee shall generally meet at such times as it may decide and at least
once per calendar quarter. The location of Steering Committee meetings shall alternate between
ACTII’s offices and Amylin’s offices unless otherwise agreed by the Parties, with the first meeting
being held at Amylin’s office. Minutes of a meeting setting forth decisions of the Steering
Committee shall be prepared by the Party hosting the meeting. Minutes will become official when
agreed to by all members of the Steering Committee. Each Party will bear all expenses associated
with attendance of its representatives at meetings. If the Steering Committee members all agree, a
meeting may be held by telephone.



                                 (d) Decisions of the Steering Committee shall be made by unanimous vote, with each member
having one vote. If the Steering Committee is unable to reach a unanimous vote on any issue, the
issue shall be referred to the President of ACTII (or successor position), and the Vice President
of Corporate Development of Amylin (or successor position)
for resolution. These individuals shall, as soon as practicable, attempt in good faith to
decide the issue. If the issue is not decided within fifteen (15) days after it has been referred
to such individuals, it shall be referred to Amylin’s Chief Executive Officer (or successor
position), who shall make the final decision regarding such issue.



                                 (e) Within fifteen (15) days after the receipt of the proposed Product Development Plan or any
amendments thereto from the Project Working Team or any appeals of decisions of the Project Working
Team, the Steering Committee shall meet to consider approval of such plan or amendments, or appeal
of such decision, as applicable. The Steering Committee shall periodically review the Product
Development Plan from a strategic perspective, the status of efforts to implement it and to make
any changes to it that it deems necessary to accomplish the purpose of this Agreement. The
Steering Committee shall also settle any disputes among the Project Working Team.



 









 





                       4.3      Project Working Team.



                                 (a) Within thirty (30) days after the date of this Agreement, the Parties shall form a Project
Working Team, which shall consist of representatives of each Party. Either party may change its
representatives on the Project Working Team at any time by giving written notice to the other
Party. The Project Working Team shall be responsible for the preparation, modification (if
appropriate) and implementation of the Product Development Plan. Although each Party has been
given principal responsibility for certain activities, all significant decisions with respect to
such activities (other than those relating to commercialization of Product which shall be the sole
responsibility of Amylin) shall be made by the Project Working Team. The Project Working Team
shall operate under the terms of and shall carry out the further responsibilities described in this
Section 4.3.



                                 (b) The Project Working Team shall meet as frequently as necessary to accomplish the
objectives of the Product Development Plan but at least once every calendar quarter. It is
anticipated that meetings will occur monthly at the commencement of the work and will be needed
less frequently as the collaboration progresses. The location of the meetings will alternate
between the offices of ACTII and Amylin, unless the Parties agree otherwise. Meetings of the
Project Working Team can be conducted by telephone by decision of the Project Working Team. Each
Party will bear all expenses associated with attendance of its representatives at meetings of the
Project Working Team.



                                 (c) Except as provided in the succeeding sentence of this paragraph, decisions of the Project
Working Team shall be made by consensus when possible, and otherwise by majority vote, subject to
the right of either Party to appeal any decision of the Project Working Team to the Steering
Committee. Amylin’s representatives on the Project Working Team shall have the sole right to
determine how to proceed with respect to any commercialization activity related to a Product. No
vote of the Project Working Team shall be taken unless a majority of the members of the Project
Working Team are present, including at least one (1) representative of each Party. The Project
Working Team shall keep minutes of any meeting at which a decision is to be reached and shall
circulate such minutes to all members of the Project Working Team and the Steering Committee.
Responsibility for the preparation of the minutes shall rest with the hosting party. Minutes shall
be deemed approved unless any member
of the Project Working Team objects to the accuracy of such minutes within five (5) days of
receipt. A Party desiring to appeal a decision of the Project Working Team to the Steering
Committee shall make its appeal in writing to all Steering Committee members within five (5) days
of receipt of the minutes for the meeting at which the decision was made. Action pursuant to any
decision appealed to the Steering Committee shall be suspended pending a determination by the
Steering Committee to accept, reject or modify the decision of the Project Working Team. A Party
may at any time request reconsideration of any issue if it in good faith believes that substantial
changes in circumstances have occurred that necessitate such reconsideration.



                                 (d) (i) The Project Working Team shall develop, and present to the Steering Committee for
consideration, a detailed development plan to address fully, consistent with the terms of this
Agreement, the key elements reasonably necessary for the research, development, formulation, and
manufacture of Products through Regulatory Approval and the budgeted FTEs and other expenses
related to all work to be conducted under the development



 









 




plan (“Product Development Plan”). The
Product Development Plan shall be based on an initial product development plan, a first draft of
which is attached as      Exhibit B to this Agreement. The Product Development Plan shall be
completed to the satisfaction of the Parties prior to the time set forth in Section 3.1 above. and
prior to the time that Amylin elects to make the payment and issue the Warrants as provided
therein. The product to be the subject of the initial product development plan shall be AC2993.
Should Amylin determine at any time during the course of this Agreement that it wishes to develop
and commercialize an additional Field Product, or that it wishes to discontinue development and
commercialization of AC2993 and instead develop and commercialize a different Field Product, the
Parties will negotiate in good faith whether to develop such additional or different Field Product
and, if so, any appropriate alterations or additions to the provisions of this Agreement, including
but not limited to its financial provisions. In the event that Amylin discontinues the development
and commercialization of AC2993 and the Parties are unable to agree upon the development of a
different Field Product within 180 days of such discontinuation, then this Agreement shall
terminate as if Amylin had terminated this Agreement under Section 9.2(b). The Project Working
Team shall be responsible for implementing the Product Development Plan, addressing fully the
appropriate strategy for development and Regulatory Approval of Product, developing the
responsibilities and procedures for handling any and all regulatory issues related to a Product and
for addressing all issues that develop during the course of implementing the Product Development
Plan. Such implementation efforts shall include: (A) establishing comprehensive and detailed
plans designed to accomplish the goals of the Product Development Plan, including a plan pursuant
to which ACTII will perform technical and scientific work under this Agreement, (B) allocating
tasks and coordinating activities required to carry out the objectives of the Product Development
Plan, (C) monitoring progress of the Product Development Plan, (D) monitor the FTEs worked and
expenditures made under the Product Development Plan and (E) discharging such other obligations as
are assigned to the Project Working Team under this Agreement or by the Steering Committee.




                                        (ii) The Project Working Team may propose modifications to the Product Development Plan to the
Steering Committee for its approval. No modification may be implemented unless approved by the
Steering Committee.



                       4.4      Quarterly Reports.
Within 30 days following the end of each calendar quarter each Party shall provide the
Steering Committee and the Project Working Team with quarterly status reports summarizing its
research and development efforts under the Product Development Plan during such quarter. This
report shall include a general summary of important events and milestones achieved, personnel
changes, learning points and such other matters as the Party believes are relevant or that the
Steering Committee may request.



                       4.5      Governance Following Product Launch. As soon as practicable following launch of
the Product in a Major Market Country, the Parties shall meet to review whether it is appropriate
to continue the Product Development Plan under the day-to-day management of the Project Working
Team, or whether the objectives of the Project Working Team have been substantially achieved and it
is appropriate to disband or reorganize the Project Working Team. Regardless of whether the
Parties elect to disband or reorganize the Project Working Team, the Steering Committee shall
continue to provide overall direction to development of Product.



 









 





                       4.6      Other Working Teams. The Steering Committee and Project Working Team, with the
approval of the Steering Committee, may appoint one or more other working teams (“Working Teams”)
to perform such functions as the Steering Committee or Project Working Team, as applicable, may
determine. Unless a Party elects not to participate on a particular Working Team, all Working
Teams shall have at least one representative of each Party. Working Teams may provide advice and
make recommendations to the Project Working Team, but shall have no authority to bind the Project
Working Team or either Party.



                       4.7      Development Funding to ACTII. In order to facilitate Amylin’s accomplishment of
the development program, ACTII shall employ such ACTII FTEs as the Project Working Team reasonably
deems appropriate in accordance with the Product Development Plan and subject to the following
provisions:



                                 (a)      ACTII Development Funding and Reimbursement of Third Person Costs. Amylin shall
pay ACTII for work performed by it under the Product Development Plan according to the FTE Hourly
Rate. In the event that third persons are utilized by ACTII to perform services for the Product
Development Plan, Amylin shall only reimburse ACTII’s actual costs incurred in connection with such
third persons, as opposed to reimbursement through the FTE Hourly Rate.



                                 (b)      Quarterly Report/Invoice. Within thirty (30) days following the end of each
calendar quarter, ACTII shall provide Amylin with a report detailing third person costs incurred as
described in Section 4.7(a), together with the actual time spent by ACTII personnel (including a
breakdown of the names of the employees working on the development program and the number of hours
billed under the Product Development Plan by each employee during such calendar quarter). Amylin,
or its representatives, shall have the right to audit (with
financial and scientific representatives) ACTII records with respect to such reports, in
accordance with Section 4.7(d).



                                 (c)      Payments. Amylin shall make the payments due under this Section 4.7 on a calendar
quarter basis to ACTII net thirty (30) days after Amylin’s receipt of the invoice as described in
Section 4.7(b).



                                 (d)      Records Retention; Audit. ACTII agrees to keep for at least five (5) years all
records of time spent by ACTII personnel working on the development program and in sufficient
detail to permit Amylin to confirm the accuracy of ACTII’s invoices under Section 4.7(b). At
Amylin’s request upon at least forty-five (45) days’ prior written notice, and at the expense of
Amylin, ACTII shall permit a nationally recognized independent certified public accountant or
independent scientific expert, in both cases, appointed by Amylin and reasonably acceptable to
ACTII, to examine these records solely to the extent necessary to verify such invoices, provided
that such accountant or scientific expert has entered into a confidentiality agreement with ACTII
substantially similar to the confidentiality provisions of this Agreement, limiting the use and
disclosure of such information to those comparable of an invoice statement provided pursuant to
Section 4.7(b) hereof. Such examination may occur only once in each calendar year and may apply
only to records pertaining to the preceding five (5) calendar years. Results of any such
examination shall be made available to Amylin and to ACTII. If such examination reveals an
uncontested overpayment under Section 4.7 by five percent (5%) or



 









 




more, ACTII shall pay all costs
of such examination. In the event such accountant or scientific expert concludes that an
overpayment was made by Amylin under Section 4.7, ACTII will credit such overpayment amount against
future amount owed by Amylin to ACTII. This Section 4.7(d) shall survive any termination of this
Agreement for two (2) years.




                       4.8      Supply for Development. Amylin shall supply ACTII, without cost to ACTII, with
sufficient quantities of Field Products for ACTII to conduct all the activities described in the
Product Development Plan.



          5.    Clinical Studies; Supply of Field Products and Product. Amylin shall be
responsible for all clinical trials or studies at its own cost, as shall be provided in the
Development Plan. Amylin will supply ACTII, without cost to ACTII, with sufficient quantities of
Field Products necessary for ACTII to produce and provide to Amylin the Products needed for such
studies, and Amylin will compensate ACTII for technical and scientific time devoted to the
production of such Products at the FTE Hourly Rate. Payments to ACTII under this Section 5 shall
be made within thirty (30) days after receipt of invoices therefor, and the provisions of Section
4.7(d) regarding retention of records and audits by Amylin shall apply with regard to payments
under this Section 5.



          6.    Manufacturing Rights; Transfer Price.



                       6.1      Manufacturing Agreement.
For a period of five (5) years after the first commercial sale in a Major Market Country of a
System formulation of AC2993 developed pursuant to a Product Development Plan, ACTII will be the
exclusive manufacturer of such Product, and as such shall exclusively manufacture and supply such
Product, in the amounts and at such delivery times as required by Amylin, its Affiliates,
sublicensees and Co-Marketers. Upon commencement of Phase III Clinical Trials for a System
formulation of AC2993 developed pursuant to a Product Development Plan, or sooner if agreed by
Amylin and ACTII, the Parties shall negotiate in good faith and enter into a manufacturing and
supply agreement (the “Manufacturing Agreement”) on the terms provided in this Section 6 and such
other terms to be mutually agreed upon, including but not limited to, provisions dealing with
forecasting of Amylin’s requirements for Product, delivery times and terms, rejection of Product,
recall of Product, inspection of ACTII’s manufacturing facilities, indemnification, Amylin’s and
ACTII’s responsibilities with respect to compliance with global governmental regulations and force
majeure. The agreement shall provide that Amylin will supply sufficient quantities of Field
Products for use in the manufacture of Products for commercialization at no cost to ACTII. Under
the agreement Amylin shall pay ACTII a transfer price equal to the greater of (a) [***] Net Sales
of such Product and (b) [***] for each monthly dose of such product. Such [***] price shall be
adjusted annually by ACTII in accordance with the annual percentage change in the Consumer Price
Index (U.S. Bureau of Labor Statistics for all urban consumers, U.S.
City Average – all items less
food and energy (October 1999 equals 178.3 (Reference CUUR0000 SAOL1E)). The Parties shall also
negotiate in good faith provisions for inclusion in the agreement regarding payment by Amylin to
ACTII of some portion of the transfer price at the time of shipment of Product and quarterly
reconciliation of the balance of the transfer price owed on Net Sales of Products. In the event
that the Product is not approved as a monthly dose, the Parties shall negotiate in good faith the
appropriate minimum payment per dose to be paid by


 








 




Amylin to ACTII. The agreement shall also
include provisions regarding the manufacturing options provided to Amylin in Sections 6.2 and 6.3
below.




                       6.2      Failure to Supply. Should ACTII ever fail to supply any or all of Amylin’s (as
well as any Affiliate, sublicensee or Co-Marketer of Amylin’s) needs for Products to the extent
Amylin has forecasted such needs, ACTII shall have the first right to secure a third party to
manufacture that amount of Product which ACTII has failed or anticipates failing to supply. Such
third party shall be approved by Amylin, which approval may not be unreasonably withheld. In the
event that ACTII is unable to secure a third party manufacturer, or ACTII continues to fail to
supply all of Amylin’s (as well as any Affiliate, sublicensee or Co-Marketer of Amylin’s) needs for
Products for more than three (3) months, Amylin may do any of the following: (i) elect to make
nonexclusive the license grant to ACTII granted in accordance with Section 6.1, above, (ii)
terminate the Manufacturing Agreement with ACTII for ACTII’s breach (should said breach be
material), and (iii) either by itself and/or by utilizing the services of a third party,
manufacture and supply Products or components thereof (without an obligation to pay to ACTII any
transfer price payments on Products manufactured by Amylin or such third party). Any Products sold
by Amylin, its Affiliates, sublicensees or Co-Marketers under this Section 6.2 shall be subject to
the applicable royalty payment provided in Section 3.5, above.



                       6.3      Second Source.
After the expiration of ACTII’s manufacturing exclusivity period of five (5) years, as
described in Section 6.1, above, Amylin may do any of the following: (i) elect to make
nonexclusive the license grant to ACTII granted in accordance with Section 6.1, above, (ii) either
by itself and/or by utilizing the services of a third party, manufacture and supply Products or
components thereof (without an obligation to pay to ACTII any transfer price payments on Products
manufactured by Amylin or such third party). Any Products sold by Amylin, its Affiliates,
sublicensees or Co-Marketers under this Section 6.3 shall be subject to the applicable royalty
payment provided in Section 3.5, above.



                       6.4      ACTII Cooperation. In the event Amylin exercises its rights pursuant to
Sections 6.2 or 6.3, above, to provide for manufacture of Product not by ACTII, ACTII shall
transfer to Amylin or a third party, as appropriate, any ACTII Know-How required to enable Amylin
or such third party to manufacture Product and provide such assistance as is reasonably necessary
to assist such manufacture and supply. Amylin shall pay ACTII the FTE Hourly Rate for time spent
by ACTII personnel in such technology transfer.



          7.    Representations and Warranties.



                       7.1      Representations and Warranties of ACTII. ACTII hereby represents and warrants
that:



                                 (a)      ACTII Patents and ACTII Know-How. ACTII is the owner or exclusive licensee of
ACTII Patents and ACTII Know-How. ACTII has the legal right and authority to license ACTII Patents
and ACTII Know-How to Amylin as contemplated by this Agreement. To ACTII’s knowledge, none of the
ACTII Patents is subject to any invalidity proceedings in front of, or has been found to be invalid
by, a court of competent jurisdiction, and that none of the subject matter of the ACTII Patents is
subject to any proceedings alleging infringement of third party rights in front of, or has been
found to infringe third party rights by, a



 









 




court of competent jurisdiction. To ACTII’s knowledge,
none of the ACTII Know-How is subject to any proceedings alleging misappropriation of any of said
ACTII Know-How from a third party. ACTII agrees that, at a time not later than the time Amylin
elects to make the payment and issue the Warrants provided in Section 3.1 above, it will agree to
amend this Agreement to include its further representation and warranty that at least one Valid
Claim, or at least one claim of a pending patent application within ACTII Patents, in each Major
Market Country will cover a System formulation of AC2993 to be developed and commercialized under
this Agreement.




                                 (b)      Corporate Power. ACTII is duly organized and validly existing under the laws of
the state of its incorporation and has the full right and corporate authority to execute and
deliver this Agreement and to carry out the provisions hereof, without the consent or approval of
any third party.



                                 (c)      No Conflicts. ACTII’s obligations and duties hereunder are not contrary to, or in
conflict with, any of its obligations and duties to third parties.



                                 (d)      Binding Agreement. This Agreement is a legal and valid obligation binding upon
ACTII and is enforceable against ACTII in accordance with its terms, subject to the effect of
bankruptcy, insolvency, reorganization, receivership, moratorium and other similar laws of general
application relating to or affecting creditors’ rights, and as may be limited by general principles
of equity. The execution, delivery and performance of this Agreement by ACTII do not conflict with
any agreement, instrument or understanding, oral or written, to which it is a party or to which it
may be bound, nor do the execution, delivery and performance of this Agreement by ACTII violate any
law or regulation of any court, governmental body or administrative or other agency having
authority over it.



                                 (e)      Investment Representations. ACTII is aware of Amylin’s business affairs and
financial condition and has acquired sufficient information about Amylin to reach an informed and
knowledgeable decision to acquire any Warrants pursuant to this Agreement. ACTII will acquire each
Warrant, if issued, for investment for ACTII’s own account only and not with a view to, or for
resale in connection with, any “distribution” thereof within the meaning of the Securities Act of
1933, as amended (the “Act”). ACTII understands that neither the Warrants issuable pursuant to
this Agreement nor the shares of Common Stock issuable upon exercise of such Warrants (the “Warrant
Shares”) have been or will be registered under the Act by reason of a specific exemption therefrom,
which exemption depends upon, among other things, the bona fide nature of ACTII’s investment intent
as expressed herein. ACTII further acknowledges and understands that (i) the Warrants and the
Warrant Shares must be held indefinitely unless the Warrants or the Warrant Shares, as the case may
be, are subsequently registered under the Act or an exemption from such registration is available,
and (ii) that the certificates evidencing the Warrants and the Warrant Shares will be imprinted
with a legend which prohibits the transfer of the Warrants and the Warrant Shares unless the
Warrants or the Warrant Shares, as the case may be, are registered or such registration is not
required in the opinion of counsel for Amylin. ACTII further warrants and represents it has the
capacity to protect its own interests in connection with the purchase of the Warrants and the
Warrant Shares by virtue of the business or financial expertise of its officers and directors or of
professional



 









 




advisors to ACTII who are unaffiliated with and who are not compensated by Amylin or
any of its affiliates, directly or indirectly.




                       7.2      Representations and Warranties of Amylin. Amylin hereby represents and warrants
that:



                                 (a)      Amylin Patents. Amylin is the owner or exclusive licensee of Amylin Patents.
Amylin has the legal right and authority to license Amylin Patents to ACTII as contemplated by
this Agreement. To Amylin’s knowledge, none of the Amylin Patents is subject to any invalidity
proceedings in front of, or has been found to be invalid by, a court of competent jurisdiction, and
none of the Amylin Patents is subject to any proceedings alleging infringement of third party
rights in front of, or has been found to infringe third party rights by, a court of competent
jurisdiction. To Amylin’s knowledge, none of the Amylin Proprietary Information is subject to any
proceedings alleging misappropriation of any of said Amylin Proprietary Information from a third
party.



                                 (b)      Corporate Power. Amylin is duly organized and validly existing under the laws of
the jurisdiction of its incorporation and has the full right and corporate authority to execute and
deliver this Agreement and to carry out the provisions hereof, without the consent or approval of
any third party.



                                 (c)      No Conflicts. Amylin’s obligations and duties hereunder are not contrary to, or
in conflict with, any of its obligations and duties to third parties.



                                 (d)      Binding Agreement. This Agreement is a legal and valid obligation binding upon
Amylin and is enforceable against Amylin in accordance with its terms, subject to the effect of
bankruptcy, insolvency, reorganization, receivership, moratorium and other similar laws of general
application relating to or affecting creditors’ rights, and as may be limited by general principles
of equity. The execution, delivery and performance of this Agreement by Amylin do not conflict
with any agreement, instrument or understanding, oral or written, to which it is a party or to
which it may be bound, nor do the execution, delivery and performance of this Agreement by Amylin
violate any law or regulation of any court, governmental body or administrative or other agency
having authority over it.



                       7.3      Disclaimer of Additional Warranties. EXCEPT AS OTHERWISE PROVIDED IN THIS
AGREEMENT, EACH PARTY DISCLAIMS ANY AND ALL WARRANTIES, EXPRESS OR IMPLIED, INCLUDING WITHOUT
LIMITATION, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, NON-INFRINGEMENT OF
THIRD PARTY RIGHTS, AND TITLE.



          8.    Use of Materials and Information.



                       8.1      Use of Materials. ACTII agrees not to use any materials provided by Amylin, and
Amylin agrees not to use any materials provided by ACTII, except as contemplated by this Agreement.



                       8.2      Protection of Confidential Information. Each Party, as a Receiving Party, agrees
that it will exercise reasonable care, including not less than the same steps it takes to



 









 




protect
its own proprietary and confidential information, to protect the confidentiality of the Disclosing
Party’s Confidential Information. Each Receiving Party shall protect and keep confidential and
shall not use, publish or otherwise disclose to any third party, except as contemplated by this
Agreement or with the Disclosing Party’s written consent, the Disclosing Party’s Confidential
Information for a period of five (5) years following the termination of this Agreement. Joint
Inventions shall constitute Confidential Information.




                       8.3      Exceptions.



                                 (a)      Use. Notwithstanding any provision of this Section 8 to the contrary and subject
to the disclosure and publication limitations set forth in this Section 8, both Parties shall be
entitled to research, develop and commercialize Inventions jointly owned by the
Parties; provided, however, that, except pursuant to Section 2.1 hereof, ACTII shall have no
right to research, develop or commercialize Products before termination of this Agreement.
Provided further, however, that nothing in this Section shall constitute or be construed as
constituting or granting to a Party any license in or to any patents or other intellectual property
of the other Party.



                                 (b)      Disclosure. Each Receiving Party shall also be entitled to disclose to
consultants and other third parties if necessary for any purpose contemplated by or related
directly to this Agreement the Disclosing Party’s Confidential Information; provided that the third
party recipient of any Confidential Information shall first execute a confidentiality undertaking
containing provisions at least as protective as those set forth in this Section 8, and provided
further that ACTII may not disclose in conjunction with any disclosure of Inventions jointly owned
by the Parties, either explicitly or implicitly, the identity of Amylin or the identity or
structure of AC2993 or the identity of the indication without the prior consent of Amylin. Amylin
shall also be entitled to disclose ACTII’s Confidential Information to regulatory and other
government authorities for the purpose of seeking Regulatory Approval and other necessary or
appropriate regulatory or government review or approvals of the Product pursuant to this Agreement,
and both Parties shall be entitled to disclose Inventions jointly developed by personnel of both
Parties to regulatory and other government authorities for the purpose of seeking Regulatory
Approval and other necessary or appropriate regulatory or government review or approvals of
products pursuant to their rights set forth in this Section 8. Amylin shall also be entitled to
disclose the results of the Feasibility Study to third parties, provided that the results are
disclosed only to third parties who are bound by written agreement to maintain the confidentiality
of such results and that such results be used for the sole purpose of business development.



                                 (c)      Publications. Each Party shall consult with the other Party prior to any oral
presentation or the submission of any manuscript for publication or presentation if the
presentation or manuscript relates to injectable, sustained release formulations of [***]. Such
consultation shall include providing a copy of a summary of the oral presentation and draft of any
related abstract or the proposed manuscript to the reviewing Party at least thirty (30) days prior
to the proposed date of presentation or submission to a publisher, incorporating appropriate
changes as are reasonably proposed by the reviewing Party into the presentation or manuscript, and
deleting Confidential Information that the reviewing Party does not agree should be published or
presented. If the reviewing Party does not respond within thirty (30) days of such



 









 




initial
consultation or notice of intention to publish, then the requesting Party shall be free to publish
as proposed. This Section 8.4 does not control the filing of any patent application or other
patent-related filing; instead, Section 10.2 shall control the parties’ obligations with regard to
prior notification, consultation, disclosure and publication when filing any patent application or
other patent-related filing which incorporates any Confidential Information.




                       8.4      Required Disclosures. In the event that a Receiving Party is required by
applicable statute or regulation or by judicial or administrative process to disclose any part of
the Disclosing Party’s Confidential Information, the Receiving Party shall (a) promptly notify the
Disclosing Party of each such requirement and identify the documents so required thereby, so that
the Disclosing Party may
seek an appropriate protective order or other remedy and/or waive compliance by the Receiving
Party with the provisions of this Agreement; and (b) consult with the Disclosing Party on the
advisability of taking legally available steps to resist or narrow the scope of such requirement.
If, in the absence of such a protective order or such a waiver by the Disclosing Party of the
provisions of this Agreement, the Receiving Party is nonetheless required by mandatory applicable
law to disclose any part of such Confidential Information, the Receiving Party may disclose such
Confidential Information without liability under this Agreement, except that the Receiving Party
shall (i) furnish only that portion of such Confidential Information which is legally required and
(ii) use its best efforts to obtain an order or other reliable assurance that confidential
treatment shall be accorded to the portion of such Confidential Information so required to be
disclosed.



                       8.5      Return of Confidential Information. In the event of termination of this
Agreement, at any time thereafter upon the request of the Disclosing Party, the Receiving Party
shall promptly return to the Disclosing Party or destroy (at the Disclosing Party’s option) any of
the Disclosing Party’s Confidential Information responsive to such request, including all copies
thereof, except that the Receiving Party may retain one copy of the Confidential Information to be
used solely to determine the scope of its obligations under this Agreement. The return and/or
destruction of such Confidential Information as provided above shall not relieve the Receiving
Party of its other obligations under this Agreement.



          9.    Term; Termination.



                       9.1      Term; Expiration at Full Term. This Agreement shall commence as of the Effective
Date hereof and, unless terminated in accordance with this Section 9, will continue until and
expire upon the later of (i) ten (10) years from the first commercial sale of Product or (ii) the
expiration or invalidation of the last Valid Claim of all patents within the ACTII Patents. Upon
expiration of this Agreement under this Section 9.1, all licenses granted pursuant to this
Agreement shall become non-exclusive, worldwide, fully paid-up licenses.



                       9.2      Unilateral Termination by Amylin.



                                 (a)      Termination Prior to Satisfactory Completion of Feasibility Study. Amylin may
terminate this Agreement at any time prior to giving notice that the results of the studies
completed by ACTII under the Feasibility Agreements are satisfactory to Amylin, in Amylin’s sole
discretion. Upon termination by Amylin under this Section 9.2(a), Amylin shall have no further
obligation under this Agreement.



 









 






                                 (b)      General Termination. Amylin may terminate this Agreement at any time prior to the
filing of an NDA for Product by giving ninety (90) days prior written notice to ACTII. After the
filing of an NDA for Product, Amylin may terminate this Agreement at any time by giving one hundred
eighty (180) days prior written notice to ACTII. Upon termination by Amylin under this
Section 9.2(b), Amylin shall be obligated to reimburse ACTII within thirty
(30) days after receipt of an invoice therefor for any expenses incurred by ACTII prior to or
in connection with such termination of this Agreement.



                                 (c)      Licenses Terminated. Upon termination by Amylin under this Section 9.2, all
license rights granted under this Agreement shall automatically terminate and revert in their
entirety back to the granting party.



                       9.3      Breach. Any material breach by either Party of its material obligations contained
in this Agreement shall entitle the other Party (the      “Non-Defaulting Party”) to give to the
Party in default (the “Defaulting Party”) written notice specifying the nature of the
default and requiring it to cure such default. If such default is not cured within sixty (60) days
after the receipt of such notice, the Non-Defaulting Party shall be entitled, without prejudice to
any of its other rights conferred on it by this Agreement, by law or in equity, immediately to
terminate this Agreement by giving written notice to the Defaulting Party. Any dispute between the
Parties to be resolved under this agreement as to whether a product is covered by a Valid Claim of
any ACTII Patent shall not be grounds for termination. If ACTII terminates this Agreement under
this Section 9.3 due to Amylin’s breach, all license rights granted by ACTII under this Agreement
shall automatically terminate and revert in their entirety back to ACTII. If Amylin terminates
this Agreement under this Section 9.3 due to ACTII’s breach, then Amylin’s licenses granted
pursuant to Section 2.1(a) shall survive and Amylin shall owe ACTII [***] of the royalty
on Net Sales of Products that would have otherwise been owed under this Agreement pursuant to
Section 3.5, above.



                       9.4      Insolvency or Bankruptcy. ACTII may, in addition to any other remedies available
to it by law or in equity, terminate this Agreement, by written notice to Amylin in the event
Amylin shall have become insolvent or bankrupt, or shall have made an assignment for the benefit of
its creditors, or there shall have been appointed a trustee or receiver of Amylin for all or a
substantial part of its property, or any case or proceeding shall have been commenced or other
action taken by or against Amylin in bankruptcy or seeking reorganization, liquidation,
dissolution, winding-up, arrangement, composition or readjustment of its debts or any other relief
under any bankruptcy, insolvency, reorganization or other similar act or law of any jurisdiction
now or hereafter in effect, or there shall have been issued a warrant of attachment, execution,
distraint or similar process against any substantial part of the property of Amylin, and any such
event shall have continued for sixty (60) days undismissed, unbonded and undischarged.



                       9.5      No Termination upon ACTII’s Bankruptcy. All rights and licenses granted under or
pursuant to this Agreement by ACTII to Amylin are, and shall otherwise be deemed to be, for
purposes of Section 365(n) of the United States Bankruptcy Code, as amended from time to time (the
“Bankruptcy Code”), licenses of rights to “intellectual property” as defined under Section 101(35A)
of the Bankruptcy Code. The Parties agree that Amylin, as a licensee of such rights under this
Agreement, shall retain and may fully exercise all of its rights



 









 




and elections under the Bankruptcy
Code. The Parties further agree that, in the event of the commencement of a bankruptcy proceeding
by or against ACTII under the Bankruptcy Code that is not dismissed within sixty (60) days after it
is filed, Amylin shall be
entitled to a complete duplicate of (or complete access to, as appropriate) any such
intellectual property and all embodiments of such intellectual property, including without
limitation all intellectual property necessary or useful to give Amylin the capability of
manufacturing Products, and the same, if not already in its possession, shall be promptly delivered
to Amylin (i) upon any such commencement of a bankruptcy proceeding upon written request therefor
by Amylin, unless ACTII elects to continue to perform all of its obligations under this Agreement,
or (ii) if not delivered under (i) above, upon the rejection of this Agreement by or on behalf of
ACTII, upon written request therefor by Amylin.


                       9.6      Accrued Rights; Survival. Termination of this Agreement for any reason shall be
without prejudice to any rights which shall have accrued to the benefit of either Party prior to
such termination. Such termination shall not relieve either Party from obligations including those
under the following provisions which shall survive termination of this Agreement, Sections 3.6(b),
(c), and (e), 4.7(d) 8, 9, 10.1, 11, 12.1, 12.8 and 12.17, or any other obligations which are
expressly indicated to survive termination of this Agreement.


                       9.7      Selling Rights Upon Termination. Upon any termination of this Agreement, Amylin
shall have the right to sell its inventory of Products for a period of six (6) months from the date
of termination provided that Amylin complies with the provisions of Sections 3.4 through 3.6 and
Section 6.1 hereof.


          10.    Rights to Intellectual Property.


                       10.1
     Ownership of Inventions. Any and all Inventions, whether made solely by personnel of a Party or
jointly by personnel of the Parties, shall be the property of the Parties as follows:


                                      (a)      Amylin Ownership.
[***]


                                      (b)      ACTII Ownership. [***]


                                      (c)      All Other Inventions. The United States laws of inventorship shall govern the
ownership of all other Inventions that are neither assigned to Amylin nor ACTII pursuant to the
ownership provisions of Sections 10.1(a) and (b).


          Each Party shall cooperate with the other in completing any patent applications relating to
both solely and jointly developed Inventions that will be owned by the other Party. Each Party
shall also cooperate with the other in executing and delivering any instrument required to assign,
convey or transfer to such other Party its interest should such assignment, conveyance or transfer
be required by the terms of this Agreement.


          Furthermore, upon the discovery, generation or development of a particular Invention, the
Party so discovering, generating or developing shall promptly disclose to the other Party the
particular Invention at issue and in no event shall a Party file a patent on such particular


 








 




Invention until ownership as described in this Section 10.1 is determined by the Parties after
such Parties have had a reasonable opportunity to review and discuss the particular Invention at
issue.


                       10.2      Prosecution and Maintenance of Patents.


                                    (a)      ACTII’s Obligations to Prosecute. ACTII shall file and control prosecution and
maintenance of patent applications for all ACTII Patents, including ACTII Patents claiming
Inventions owned by ACTII, and, subject to the consultation rights granted to Amylin in
Section 10.2(b) below, patents claiming Inventions owned jointly by ACTII and Amylin (“Joint
Inventions”) and be responsible for related interference proceedings in accordance with reasonable
commercial standards and reasonable principles of intellectual property protection, all at ACTII’s
expense. ACTII shall endeavor to ensure that all ACTII Patents, and patents claiming Joint
Inventions are filed before any public disclosure of the inventions claimed therein to maximize the
scope of protection of such patents filed outside the United States. ACTII shall furnish Amylin
with copies of all substantive communications between ACTII and applicable patent offices regarding
patents and patent applications claiming Inventions.


                                    (b)      Consultation; No Disclosure by Amylin. ACTII and Amylin shall discuss and
evaluate Joint Inventions and confer with each other regarding the advisability of filing patent
applications in the United States and in foreign countries to cover Joint Inventions. ACTII shall
provide to Amylin (i) draft patent applications, and (ii) draft official correspondence to national
or international patent authorities which purports to amend the scope of the claims presented in
the originally filed application, each to be provided sufficiently in advance of filing for Amylin
to have the opportunity to comment thereon, and at least 30 days prior to the contemplated filing
date whenever possible. Any reasonable requests made by Amylin pertaining to such drafts shall be
reflected in such drafts, provided that Amylin provides such input to ACTII sufficiently in advance
of such proposed submission date to permit inclusion therein. Amylin shall endeavor to delay any
public disclosure of the subject matter of any patent application filed or to be filed by ACTII
under this Agreement until after filing by ACTII of such patent application.


                                    (c)      Amylin’s Standby Filing Rights. If ACTII elects not to seek or maintain patent
protection for any Invention at all or in any particular country, ACTII shall provide Amylin prompt
notice of such election, and Amylin may file and control the prosecution and maintenance of patent
applications, at its expense, with respect to Inventions everywhere or in particular countries, as
the case may be. In the event Amylin elects to file or maintain such a patent application, ACTII
will grant any necessary authority to Amylin to do so everywhere or in such particular country, as
appropriate, and will cooperate as is reasonable, at Amylin’s expense, with Amylin’s prosecution
and maintenance efforts. ACTII shall delay any public disclosure of the subject matter of such
patent application until after filing by Amylin of such patent application.


                       10.3      Infringement by Third Parties.


                                    (a)      Notice. Any Party learning of any activities of a third party which are believed
to infringe or misappropriate the ACTII Patents or patents that claim Joint


 








 




Inventions in the Field
or any claim of a third party that any of the ACTII Patents are invalid or unenforceable shall
promptly notify the other Party of such activities or such claim.




                                      (b)      Prosecution of Actions Involving Product.



                                                (i) Amylin shall have the primary right, but not the obligation, to institute, prosecute and
control any action or proceeding with respect to any infringement/misappropriation of any of the
ACTII Patents or patents claiming Joint Inventions arising from the use thereof and involving
Product, by counsel of its own choice. ACTII shall cooperate with Amylin at Amylin’s request in
the prosecution of such action or proceeding. If Amylin reasonably determines that ACTII is an
indispensable party to the action, ACTII hereby consents to be joined. In such event, ACTII shall
have the right to be represented in that action by counsel of its own choice and at ACTII’s
expense.



                                                (ii) If Amylin fails to bring an action or proceeding within a period of ninety (90) days
after receiving written notice from ACTII or otherwise having knowledge of that
infringement/misappropriation of ACTII Patents or patents claiming Joint Inventions involving
Products, as described in Section 10.3(b)(i), ACTII shall have the right to bring and control any
such action by counsel of its own choice and expense. IF ACTII reasonably determines that Amylin
is an indispensable party to the action, Amylin hereby consents to be joined. In such event,
Amylin shall have the right to be represented in that action by counsel of its own choice and at
Amylin’s expense.



                                                (iii) No settlement, consent judgment or other voluntary final disposition of a suit under
this Section 10.3(b) may be entered into without the joint consent of Amylin and ACTII (which
consent shall not be unreasonably withheld).



                                                (iv) If Amylin brings action, any damages or other monetary awards recovered by Amylin
attributable to sales of Products, shall be applied pro-rata to defray the reasonable costs and
expenses incurred in the action by both Parties. Any remaining recovery shall be used to reimburse
Amylin for lost profits, to the extent the recovery or settlement is calculated on the basis of
lost profits, and ACTII for lost royalties or transfer price payments on account of lost sales.
Any remaining recovery shall be allocated to Amylin.



                                                (v) If Amylin fails to bring action and ACTII brings action, any damages or other monetary
awards recovered by ACTII attributable to sales of Product derived therefrom, shall be applied
pro-rata to defray the reasonable costs and expenses incurred in the action by both Parties. If
any balance remains it shall be allocated to ACTII.



                                      (c)      Infringement of ACTII Patents or Patents Claiming Joint Inventions Outside Field.
In the event that any ACTII Patents or patents claiming Join Inventions that have application
outside the Field are infringed outside the Field by a third person, the Party first having
knowledge of such infringement shall notify the other as set forth above and the Parties shall
consult with each other as to how they should proceed, but each Party shall be free to pursue or
protect its own respective interests to the extent it is legally entitled to
do so. ACTII hereby agrees to use commercially reasonable efforts to diligently enforce such
ACTII Patents or patents claiming Joint Inventions that have application outside the Field.



 









 




                       10.4      Infringement of Third Parties.


                                    (a)      Notice. If either Party believes that patent rights held by a third party may be
necessary or useful to make, have made, use, sell, supply or import Products or learns of a third
party who has filed suit or has threatened to file suit because of a claim that a Product may be
infringing such third party’s rights, they shall promptly notify the other Party in writing. The
Parties shall then meet to discuss in good faith whether or not both Parties agree that such third
party rights may be necessary or useful to make, have made, use, sell, supply or import a Product
and whether such possible infringement, or the claims in such infringement suit or threatened suit
are based on an allegation that any of the Field Products (but not the Product incorporating such
Field Product), infringes such third party patents. In the event the Parties are unable to so
agree, the matter will be decided in accordance with the dispute resolution provisions of
Section 12.17.


                                    (b)      Defense, Settlement or Securing Third Party Rights.


                                               (i)      By ACTII. If it is determined, either by mutual agreement or as a result of the
dispute resolution procedures that such third party’s rights are necessary and not based on
allegations related to infringement of third party rights by any of the Field Products (excluding
the Product incorporating such Field Product), then ACTII shall be responsible to defend any suit
alleging infringement of a third party, seek to settle any suit or threatened suit, or secure the
rights of such third party for use in the Field. ACTII shall not settle or secure such third party
rights without Amylin’s prior approval, which shall not be unreasonably withheld. The Parties
shall share equally any payments or royalties owed to the third party for settling such suit or for
securing such third party rights.


                                               (ii)      By Amylin. If it is determined, either by mutual agreement or as a result of the
dispute resolution procedures that such third party’s rights are necessary and are based on
allegations related to related to infringement of third party rights by any of the Field Products
(excluding the Product incorporating such Field Product), then Amylin shall be responsible to
defend any suit alleging infringement of a third party, seek to settle any suit or threatened suit,
or secure the rights of such third party for use in the Field. Amylin shall be solely responsible
for any payments or royalties owed to the third party for settling such suit or for securing such
third party rights.



                                                (iii)      Amylin Standby Right to Secure Third Party Rights. In the event that ACTII is
unable to secure the rights of a third party under Section 10.4(b)(i), unless ACTII is diligently
defending such infringement action, Amylin may secure such rights from the third party, after
obtaining ACTII’s prior approval, which shall not be unreasonably withheld.


          11.    Indemnification.


                       11.1      Indemnification by Amylin.
Amylin hereby agrees to indemnify and hold harmless ACTII and its Affiliates and each of their
respective agents, employees, officers and directors (the “ACTII Indemnitees”) from and
against any and all suits, claims, actions, demands, liabilities, expenses and/or losses, including
reasonable investigation expenses, legal expenses and attorneys’ fees (“Losses”) resulting
directly from (a) any material breach of this


 








 




Agreement by Amylin, (b) the marketing, packaging,
testing, labeling, manufacture, use or sale of Field Products or Products or (c) the performance of
the Product Development Plan by Amylin (except that Amylin shall not indemnify ACTII for Losses
resulting from the Product Development Plan or flaws or omissions in the Product Development Plan
itself) except to the extent such Losses are required to be indemnified by ACTII pursuant to
Section 11.2 hereof, and except to the extent such Losses are attributable to the gross negligence
or willful misconduct of any ACTII Indemnitee.




                       11.2      Indemnification by ACTII. ACTII hereby agrees to indemnify and hold harmless
Amylin and its Affiliates and each of their respective agents, employees, officers and directors
(the “Amylin Indemnitees”) from and against any and all Losses resulting directly from (a)
any material breach of this Agreement by ACTII, (b) the manufacture and supply of Product by ACTII
under this Agreement or (c) the performance of the Product Development Plan by ACTII (except that
ACTII shall not indemnify Amylin for Losses resulting from the Product Development Plan or flaws or
omissions in the Product Development Plan itself), except to the extent such Losses are
attributable to the gross negligence or willful misconduct of any Amylin Indemnitee.



                       11.3      Notification of Claims; Condition to Indemnification Obligations. As a condition
to a Party’s right to receive indemnification under this Section 11, it shall (a) notify the other
Party as soon as it becomes aware of a claim or Action for which indemnification may be sought
pursuant hereto, (b) cooperate with the indemnifying Party in the defense of such claim or suit,
and (c) permit the indemnifying Party to control the defense of such claim or suit, including
without limitation the right to select defense counsel. In no event, however, may the indemnifying
Party compromise or settle any claim or suit in a manner which admits fault or negligence on the
part of the indemnified party or includes injunctive relief without the prior written consent of
the indemnified party. The indemnifying Party shall have no liability under this Section 11 with
respect to claims or suits settled or compromised without its prior written consent.



                       11.4      Limitation on Liability. ACTII does not represent, warrant or guarantee that its
efforts under the Product Development Plan will produce any particular results or that any Product
resulting therefrom will be merchantable or satisfactory for any particular purpose. Amylin does
not represent, warrant or guarantee that its efforts under the Product Development Plan will
produce any particular results or that any Product resulting therefrom will be merchantable or
satisfactory for any particular purpose. Except pursuant to their indemnification and hold
harmless obligations set forth in this Section 11, neither Party shall be responsible or liable in
contract or in tort to the other Party for any special, indirect, incidental or consequential
damages, including but not
limited to loss of product, profits or revenues, damage or loss from operation or
non-operation of plant.



                       11.5      Insurance. Each Party shall maintain and keep in force for the term of this
Agreement comprehensive general liability insurance including products/completed operations,
contractual and broad form property damage covering its indemnification obligations hereunder with
a minimum limit of [***] per annum combined single limit for bodily injury and property damage. It
is understood that such insurance shall not be construed to limit a Party’s liability with respect
to such indemnification obligations. Such insurance shall be placed with a first



 









 




class insurance carrier with at least a BBB rating by Standard & Poors. Promptly after execution and delivery of
this Agreement, each Party shall furnish a certificate of insurance to the other Party evidencing
the foregoing endorsements, coverage and limits, and providing that such insurance shall not expire
or be canceled or modified without at least thirty (30) days prior notice to the other Party.


                   11.6
     Survival. This Section 11 shall survive termination or expiration of this
Agreement for two (2) years.


          12.    Miscellaneous Provisions.


                   12.1
     Acts and Omissions. Each Party assumes any and all risks of personal injury and
property damage attributable to the acts or omissions of it and its officers, employees and agents
in the performance of this Agreement.


                   12.2
     Compliance with Law. The parties shall perform all Actions under this Agreement
in accordance with all applicable laws, rules and regulations.


                   12.3
     Notices. All notices and other communications required or permitted hereunder
shall be effective upon receipt and shall be in writing and may be delivered in person, by
facsimile, overnight delivery service or United States mail, in which event it may be mailed by
first-class, certified or registered, postage prepaid, addressed to the parties as follows:


If to Amylin:


General Counsel

Amylin Pharmaceuticals, Inc.

9373 Towne Centre Drive

San Diego, CA 92121

Fax: 858-552-1936


If to ACTII:


President

Alkermes Controlled Therapeutics Inc. II

64 Sidney Street

Cambridge, MA 02139

Fax: 617-494-9263


or to such other addresses as may from time to time be given in writing by either Party to the
other pursuant to the terms hereof.


                   12.4      No Third-Party Beneficiaries. Nothing in this Agreement is intended to confer on
any person other than the Parties or their permitted assigns, any benefits, rights or remedies.


                   12.5      Independent Contractors. The parties hereto shall be independent contractors
with respect to each other, and neither shall be deemed to be the agent, principal,


 








 




employee,
servant, joint venturer or partner of the other for any purpose which could impose liability upon
one Party for the act or failure to act of the other Party.




                       12.6      Entire Agreement. This Agreement and the Exhibits attached hereto, together with
the Feasibility Agreement, constitute the entire agreement between the parties concerning the
subject matter hereof and supersede all prior understandings and agreements, whether written or
oral.



                       12.7      Severability. Any of the provisions of this Agreement which are determined to be
invalid or unenforceable in any jurisdiction shall be ineffective to the extent of such invalidity
or unenforceability in such jurisdiction, without rendering invalid or unenforceable the remaining
provisions hereof or affecting the validity or enforceability of any of the terms of this Agreement
in any other jurisdiction.



                       12.8      Governing Law. This Agreement shall be governed by and construed in accordance
with the laws of the State of Delaware, without giving effect to the principles of conflict of
laws.



                       12.9      Assignment. Neither Party shall assign any of its rights or delegate any of its
obligations hereunder without the other Party’s prior written consent except pursuant to:
(i) a merger, consolidation or reorganization of the assigning Party or the sale of substantially
all of the assets of the assigning
Party; (ii) with respect to Amylin, as incident to the establishment of a corporate
partnership arrangement with respect to any of the Field Products; or (iii) an assignment to any
Affiliate of the assigning Party if the assigning Party remains liable and responsible for the
performance and observance of all the Affiliate’s duties and obligations hereunder.



                       12.10      No Waiver. A waiver by either Party of a breach or violation of any provision
of this Agreement will not constitute or be construed as a waiver of any subsequent breach or
violation of that provision or as a waiver of any breach or violation of any other provision of
this Agreement.



                       12.11      Amendments. This Agreement may not be amended, supplemented or otherwise
modified except by an instrument in writing signed by both parties.



                       12.12      Headings. Any headings and captions included herein are for convenience of
reference only and shall not be used to construe this Agreement.



                       12.13      Counterparts. This Agreement shall become binding when any one or more
counterparts hereof, individually or taken together, shall bear the signature of each of the
parties hereto. This Agreement may be executed in counterparts, each of which shall be an original
as against any Party whose signature appears thereon, but all of which together shall constitute
but one and the same instrument.



                       12.14      Publicity. The Parties shall each have the right, upon its election, to issue a
press release containing, and publicly disclose, some or all of the information included in
Exhibit C and such further information as the Parties shall mutually approve in each
Party’s sole discretion. Except as set forth in the immediately preceding sentence, each Party
agrees not to



 









 




make any disclosure or written dissemination with respect to this Agreement or its
terms without giving the other Party a reasonable opportunity to comment thereon and obtaining the
other Party’s prior written consent, which consent will not be unreasonably withheld, provided that
such opportunity and such consent will not be required where such disclosure or dissemination (a)
is required by law; or (b) is reasonably necessary in connection with any potential transaction
referred to in Section 12.9 or contemplated by this Agreement.


                       12.15      Adverse Event Reports. In order to comply with adverse event reporting
regulations of the FDA (as provided in Title 21 of the Code of Federal Regulations) and other
international regulatory agencies, each Party acknowledges that once the parties hereunder are
selling and/or clinically testing in
humans any Product they must report promptly to each other the occurrence of adverse events
regarding Products for timely reporting to the FDA and other reporting agencies.


                       12.16      No Trademark Rights. Except as otherwise provided herein, no right, express or
implied, is granted by this Agreement to use in any manner the marks “Amylin,” “Medisorb®,” or any
other trade name or trademark of Alkermes, ACTII or Amylin, in connection with the performance of
this Agreement.


                       12.17      Dispute Resolution. Except as otherwise provided in Section 4, the Parties
agree that any claim or controversy arising pursuant to this Agreement, or the rights or
obligations of the Parties hereunder shall be resolved solely by application of the procedures set
forth in this Section 12.17. These procedures, however, may be modified by written agreement of
the Parties with respect to any particular dispute.


                                      (a)      Settlement Meeting. In the event any such claim or controversy arises, the
Parties shall first attempt to settle their differences amicably between themselves. Either Party
may initiate such informal dispute resolution by sending written notice of the dispute to the other
Party, and within twenty (20) days after receipt of such notice appropriate representatives of the
Parties, each with full authority from the chief executive officer of the Party to settle the
dispute, shall meet for attempted resolution of the claim or controversy by good faith
negotiations. If the representative of either Party intends to be accompanied at the settlement
meeting by counsel, the other Party shall be given at least seven (7) days notice of such intention
and may also be accompanied by counsel. All negotiations pursuant to this Section 12.17 shall be
confidential and treated as compromise and settlement negotiations and shall not be admissible in
any arbitration or other proceeding


                                      (b)      Arbitration. If such representatives are unable to resolve such dispute within
thirty (30) days following the day of the settlement meeting, either Party may demand arbitration
by sending written notice to the other Party. Such arbitration shall be administered by the
American Arbitration Association (“AAA”) in accordance with its Commercial Arbitration
Rules. The arbitration proceedings shall be conducted before one arbitrator in Denver, Colorado or
any other place selected by mutual agreement of the Parties. The arbitrator shall apply the
governing law set forth in Section 13.8 hereof. If the Parties are unable to agree upon a single
arbitrator within sixty (60) days after arbitration is demanded, three (3) arbitrators shall be
used, one selected by each Party within ten (10) days after the conclusion of the sixty (60) day
period and a third selected by the first two within ten (10) days thereafter.


 








 




The arbitrator or
arbitrators shall be accredited by the AAA and shall be individuals with knowledge of and
experience with the pharmaceutical industry.




                                      (c)      Award. The arbitrator(s) shall have authority to award any remedy or relief that
a Colorado court could order or grant, including, without limitation, specific performance of any
obligation created under this Agreement, the issuance of an injunction or the imposition of
sanctions for abuse or frustration of the arbitration process as well as to allocate
between the Parties the costs of arbitration in such equitable manner as they determine. The
arbitrator(s) may not make any ruling, finding or award that does not conform to the terms and
conditions of this Agreement. Pending the issuance of the decision of the arbitrator(s), the
Parties shall continue to operate under this Agreement as it existed on the date the arbitration
was initiated; provided, however, that the decision of the arbitrator(s) shall be retroactive to
such date. The Parties hereby exclude any right of appeal to any court on the merits of the
dispute. Subject to the previous sentence, the arbitral award (i) shall be final and binding upon
the Parties; and (ii) may be entered in any court of competent jurisdiction.



                                      (d)      Discovery. The arbitrator(s) shall have discretion to order a prehearing exchange
of information by the Parties, including, without limitation, production of directly relevant
documents, exchanges of testimony, summaries of proposed witnesses and depositions of the Parties.
All issues regarding compliance with discovery requests shall be decided by the arbitrator(s).



                                      (e)      Injunctive and Other Relief. Nothing contained in this Section 12.17 or any other
provisions of this Agreement shall be construed to limit or preclude a Party from bringing any
action in any court of competent jurisdiction for injunctive or other provisional relief to compel
the other Party to comply with its obligations hereunder before or during the pendency of
arbitration proceedings.



                       12.18      Electronic Documents. Upon either Party’s request in order to facilitate
compliance with the securities laws of the United States, the other Party shall provide an
electronic version of any document it has in such format that has previously been provided to the
requesting Party. The Parties agree to accommodate reasonable requests for confidential treatment
of documents filed with the SEC, such that no Confidential Information of either Party is publicly
disclosed by such filing.



[REMAINDER OF PAGE INTENTIONALLY LEFT BLANK]




 









 




          IN WITNESS WHEREOF, the parties have caused this Agreement to be executed by their respective
duly authorized officers as of the day and year first above written.



	 	 	 	 	 

	 	 	ALKERMES CONTROLLED
THERAPEUTICS INC. II
	 
	 	 	 	 
	 

	 	By:
	 	/s/ Michael Landine
	 	 	 	 	
	 
	 	 	 	 
	 

	 	Title:
	 	Vice President
	 	 	 	 	
	 
	 	 	 	 
	 
	 	 	 	 
	 	 	AMYLIN PHARMACEUTICALS, INC.
	 
	 	 	 	 
	 

	 	By:
	 	/s/ Daniel M. Bradbury
	 	 	 	 	
	 
	 	 	 	 
	 

	 	Title:
	 	Senior Vice President, Corporate
Development
	 	 	 	 	





 








 




     EXHIBIT A


     ACTII PATENTS


Exhibit A-1


MEDISORB PATENTS


1. “PREPARATION OF BIODEGRADABLE MICROPARTICLES CONTAINING A BIOLOGICALLY ACTIVE AGENT”


US:

US Patent No. 5,650,173; issued July 22, 1997 [***]

US Patent No. 5,654,008; issued August 5, 1997 [***]


Foreign: [***]



	2.	 	“PREPARATION OF EXTENDED SHELF-LIFE BIODEGRADABLE, BIOCOMPATIBLE
MICROPARTICLES CONTAINING A BIOLOGICALLY ACTIVE AGENT”






US:

US Patent No. 5,792,477; Issued August 11, 1998

US Patent No. 5,916,598; Issued June 29, 1999

[***]


Foreign: [***]



	3.	 	[***]








	4.	 	[***]








	5.	 	[***]







 








 




EXHIBIT B



The two pages of Exhibit B have been omitted entirely and have been

filed 
separately with the Secretary of the Commission. 


     PROGRAM DEVELOPMENT PLAN


Exhibit B-1


-DRAFT-





DEVELOPMENT
WORK PLAN

ALKERMES AC2993 SUSTAINED-RELEASE DEPOT


[***]


 








 





EXHIBIT C




PRE-APPROVED INFORMATION FOR PRESS RELEASE



CONTACT:

Alice P. Bahner

Amylin Pharmaceuticals, Inc.

Senior Director, Corporate Development

(858) 552-2200

www.amylin.com



Richard F. Pops

Alkermes, Inc.

Chief Executive Officer

(617) 494-0171

www.alkermes.com


FOR IMMEDIATE RELEASE


AMYLIN PHARMACEUTICALS AND ALKERMES SIGN AGREEMENT FOR

DEVELOPMENT OF LONG-ACTING FORMULATION OF AC2993

(SYNTHETIC EXENDIN-4)


     San
Diego, CA - May 15, 2000 - Amylin Pharmaceuticals, Inc. (Nasdaq: AMLN) and Alkermes, Inc.
(Nasdaq: ALKS) today announced that they have signed an agreement for the development, manufacture
and commercialization of an injectable long-acting formulation of AC2993 (synthetic exendin-4),
Amylin’s second diabetes drug candidate. The development program will utilize Alkermes’ patented
and proprietary Medisorb(R) injectable sustained release drug delivery technology. Based upon
results obtained to date from initial feasibility studies, the goal of the new Alkermes-Amylin
agreement is a formulation that would allow once a month administration of AC2993 for the treatment
of type 2 diabetes.


     “With this technology, we hope to develop and commercialize a more convenient delivery system
for AC2993,” said Joseph C. Cook, Jr., Chairman of the Board and Chief Executive Officer of Amylin
Pharmaceuticals. “We are encouraged by results of Phase 2 clinical studies of AC2993 in the
treatment of type 2 diabetes, and we plan to continue with development of AC2993 in its current
formulation in parallel with our work with Alkermes on a long-acting
formulation of AC2993.”


     Under the terms of the agreement, Alkermes has granted to Amylin an exclusive, worldwide
license to their formulation technology for the development and commercialization of injectable
sustained release formulations of exendins, such as AC2993, and other related compounds that Amylin
may develop. In exchange, Alkermes will receive funding for research and development


 








 




and milestone payments comprised of cash and warrants for Amylin common stock upon achieving
certain development and commercialization goals. Alkermes will also receive a
combination of royalty payments and manufacturing fees based on any future product sales. Alkermes
will initially be responsible for developing and testing several formulations, manufacturing any
products commercialized as a result of the agreement, and Amylin will be responsible for conducting
clinical trials, securing regulatory approvals and marketing on a worldwide basis.




     “This collaboration is an example of our interest in applying our drug delivery technologies
to exciting new product candidates earlier in the development process,” said Richard Pops, Chief
Executive Officer of Alkermes. “Our goal is to continue to leverage our experience in developing
advanced formulations of protein and peptide drugs.”



     Alkermes is a leader in the development of products based on sophisticated drug delivery
technologies. The Company has several areas of focus: (i) controlled, sustained release of
injectable drugs lasting several days to several weeks, utilizing its ProLease(R) and Medisorb (R)
technologies; (ii) the development of pharmaceutical products based on proprietary pulmonary
drug delivery technologies utilizing its AIR technology, (iii) oral delivery of drugs using the
RingCap(TM) and DST technologies, and (iv) the delivery of drugs into the brain past the
blood-brain barrier, utilizing its Cereport(R) technology. In addition to its Cambridge,
Massachusetts headquarters, research and manufacturing facilities, Alkermes operates research and
manufacturing facilities in Ohio and a medical affairs office in Cambridge, England.




     Amylin Pharmaceuticals is engaged in the discovery and development of potential drug
candidates for the treatment of metabolic disorders. The Company is developing SYMLIN for the
treatment of people with diabetes who use insulin. The Company has completed its Phase 3 clinical
trials for SYMLIN and is planning for a submission to the FDA for approval to market SYMLIN in the
US for the treatment of type 1 diabetes and insulin-using type 2 diabetes in the fourth quarter of
2000, with a submission for regulatory approval in Europe to follow later in 2000 or early in 2001.
Amylin Pharmaceuticals’ second diabetes drug candidate, AC2993, is in Phase 2 evaluation for the
treatment of type 2 diabetes. The Company’s third drug candidate, AC3056, is currently undergoing
preclinical evaluation as a potential treatment for metabolic disorders relating to cardiovascular
disease. The Company is considering a wide range of
commercialization options for SYMLIN, including some combination of (1) a worldwide distribution
arrangement with a major pharmaceutical company, (2) regional distribution and marketing
arrangements, and (3) performance of some commercialization activities by Amylin Pharmaceuticals.
The Company is also examining collaborative research, development and commercialization
opportunities for AC2993. Further information on Amylin Pharmaceuticals and its pipeline in
metabolism is available at www.amylin.com.




     This press release contains forward-looking statements about Alkermes’ and Amylin’s plans.
These forward-looking statements involve risks and uncertainties. The actual results could differ
materially from those discussed in this press release, due to risks and uncertainties including
those regarding the formulation and development of AC2993, the timing of submission of
applications for marketing approvals for SYMLIN and, if approvals are obtained, time to market
thereafter and the ability of Amylin to commercialize SYMLIN, the ability of Amylin to enter



 








 







into sales, distribution, marketing and/or corporate partnering agreements with respect to SYMLIN
and AC2993, and the results of Amylin’s preclinical and clinical studies of its product candidates,
including AC2993 and AC3056. Additional risks and uncertainties are described in Amylin’s most
recently filed SEC documents, such as its Annual Report on Form 10-K for
the fiscal year ended December 31, 1999 under the heading “Risk Factors,” and its subsequently
filed Quarterly Reports on Form 10-Q, and in Alkermes’ SEC filings, such as its Annual Report on
Form 10-K for the fiscal year ended March 31, 1999 under the heading “Risk Factors.”



 









 




*** Text
Omitted and Filed Separately to the Commission

Confidential Treatment Requested


AMENDMENT TO DEVELOPMENT AND LICENSE AGREEMENT


          THIS AMENDMENT TO DEVELOPMENT AND LICENSE AGREEMENT (the “Amendment”) is entered into as of
October 24, 2005 (the “Amendment Effective Date”) by and between AMYLIN PHARMACEUTICALS, INC., a
Delaware corporation (“Amylin”), and ALKERMES CONTROLLED THERAPEUTICS INC. II, a Pennsylvania
corporation (“ACTII”).


          WHEREAS, ACTII and Amylin are parties to that certain Development and License Agreement dated
May 15, 2000 (the “Agreement”); and


          WHEREAS, the Parties desire to amend the Agreement as set forth in this Amendment.


          NOW, THEREFORE, in consideration of the premises and the covenants herein contained, the
Parties hereby agree to amend the Agreement as follows:


1.          Definitions.


               1.1
     All capitalized terms used but not otherwise defined herein shall have the
meanings given to them in the Agreement.


               1.2     Section 1.16 of the Agreement is hereby amended and restated in its entirety
as follows:


                     “1.16     “Inventions” means any inventions or discoveries, whether or not
patentable, conceived pursuant to (i) the Product Development Plan during the term of this
Agreement or within three (3) months thereafter and (ii) the Project Plan or the provision of
Ongoing Technical Support during the term of the Tech Transfer Agreement or within three (3) months
thereafter.”


              1.3     Section 1.29
of the Agreement is hereby amended and restated in its entirety as follows:


                      “1.29     [INTENTIONALLY OMITTED]”


               1.4     The following new sections, beginning with Section 1.34, are hereby inserted
at the end of Section 1 of the Agreement:


                      “1.34     “API” shall have the meaning assigned to it in the Tech Transfer
Agreement.”


                      “1.35     “Core Oversight Group” means a group formed pursuant to Section 4.2.1(a).”


 








 




                    “1.36     “Executive Committee” means a committee formed pursuant to Section
4.2.2(a).”


                    “1.37     “Exenatide LAR” shall have the meaning assigned to it in the Tech Transfer
Agreement.”


                    “1.38     “First Commercial Sale” means, with respect to Exenatide LAR, the first
commercial sale of such product in a country after all Regulatory Approvals for such product have
been obtained in such country.”


                    “1.39     “Four-Week Exenatide LAR” means a Product that is a formulation of API and
that is designed to deliver API over a four-week period of time.”


                    “1.40      “Lilly” means Eli Lilly and Company.”


                    “1.41      “Ongoing Technical Support” shall have the meaning assigned to it in the
Tech Transfer Agreement.”


                    “1.42      “Project” shall have the meaning assigned to it in the Tech Transfer
Agreement.”


                    “1.43      “Project Plan” shall have the meaning assigned to it in the Tech Transfer
Agreement.”


                    “1.44     “RACI Task Analysis” means a list of the major tasks required to perform
the Product Development Plan to be agreed by the Parties, including for each task: the person or
Party that is responsible for final decision making; the person or Party that is required to
approve steps in the process; the person or Party that needs to be consulted for input and
direction, but not approve decisions; and the person or Party that needs to be updated or informed,
as such RACI Task Analysis may be amended from time to time as provided herein.”


                    “1.45     “Tech Transfer” shall have the meaning assigned to it in the Tech Transfer
Agreement.”


                    “1.46      “Tech Transfer Agreement” means the Technology Transfer and Construction
Management Agreement to be entered into between ACTII and Amylin concurrently herewith, as may be
amended in accordance with its terms.”


2.                      NON-SUIT


             2.1
     Section 2.1 of the Agreement is hereby amended by adding the following
provision:


                     “(c)     Amylin and its Affiliates, sublicensees and agents, agree, on a worldwide basis,
not to sue ACTII or its Affiliates, or any third party collaborating with ACTII


 








 




or its Affiliates, for developing, making, having made, using, selling, offering to sell or
importing a product outside the Field under patent rights held by Amylin or its Affiliates, or
either of their sublicenses or agents, that cover or are an improvement to the process for the
manufacture of Exenatide LAR transferred to Amylin by ACTII pursuant to the Tech Transfer
Agreement.”


3.                        PAYMENTS TO ACTII


          3.1      Section 3.4
of the Agreement is hereby amended and restated in its entirety as
follows:


                 “3.4     Payment for Four-Week Exenatide LAR. According to Section 6, Amylin
shall pay to ACTII a transfer price based on Net Sales of all Four-Week Exenatide LAR manufactured
by ACTII. For all Four-Week Exenatide LAR that is not manufactured by ACTII and is instead
manufactured by a third party pursuant to Section 6.2 (“Failure to Supply”), below, Amylin shall
pay to ACTII a royalty on Net Sales at the rate of [***] percent ([***]%). For all Four-Week
Exenatide LAR that is not manufactured by ACTII and is instead manufactured by a third party
pursuant to Section 6.3 (“Second Source”), below, Amylin shall pay to ACTII a royalty on Net Sales
at the rate of [***] percent ([***]%). The royalty payable under this Section 3.4 will be payable
only once with respect to a particular sale of Four-Week Exenatide LAR regardless of there being
more than one Valid Claim of an ACTII Patent applicable to such Product”


          3.2      Section 3.5 of the Agreement is hereby amended and restated in its entirety as
follows:


                 “3.5     Royalties on Products Not Manufactured by ACTII. Until December
31st of the tenth full calendar year following the year in which the First Commercial
Sale of Exenatide LAR occurs, Amylin shall pay to ACTII a royalty on Net Sales of Exenatide LAR at
the following rates: (i) eight percent (8%) of Net Sales of the first 40,000,000 units of
Exenatide LAR sold or commercially disposed of for value during any full calendar year, or portion
thereof, during such period and (ii) five and one-half percent (5.5%) of Net Sales of the remaining
units of Exenatide LAR sold or commercially disposed of for value during such full calendar year,
or portion thereof, during such period. Except as otherwise provided in this Agreement, Amylin
shall pay to ACTII a royalty on Net Sales of Products not manufactured by ACTII at the rate of five
and one-half percent (5.5%). The royalty payable under this Section 3.5 will be payable only once
with respect to a particular sale of a Product regardless of there being more than one Valid Claim
of an ACTII Patent applicable to such Product.”


4.                        PRODUCT DEVELOPMENT PROGRAM


          4.1      Section 4.1 of the Agreement is hereby amended and restated in its entirety
as follows:



                 “4.1      Scope. ACTII shall have principal responsibility for the formulation and
non-clinical development of a Product for use in the Field, including formulation,



 









 




development and optimization, stability testing, manufacturing of clinical supplies (except as
provided below), process scale-up, process validation and preparation of the chemistry,
manufacturing and controls (CMC) section of the NDA for Exenatide LAR. Amylin shall have principal
responsibility for toxicological and clinical development of a Product through Regulatory Approval
and sole responsibility for commercialization of a Product. Amylin and ACTII agree to use the RACI
Task Analysis as a tool to assign responsibilities for decision making and to ensure information
flow at the Project Working Team level with respect to performance by the Parties under the Product
Development Plan. The RACI Task Analysis with respect to the Product Development Plan may be
amended from time to time during the term of this Agreement upon mutual written agreement of ACTII
and Amylin. The Parties acknowledge that as a result of such amendment, responsibilities for
decision making may shift from one Party to another. Each Party shall use Commercially Reasonable
Efforts in performing its functions under the Product Development Plan. Subsequent to Tech
Transfer except as otherwise agreed by the Parties, Amylin shall be responsible for the manufacture
of any clinical supplies of Products other than pilot phase material to be used in clinical studies
prior to Phase III Clinical Trials. ACTII acknowledges that Lilly may collaborate with Amylin in
the development of a Product, as a potential sublicensee of certain of Amylin’s rights hereunder.”


          4.2     Section 4.2 of the Agreement is hereby amended and restated in its entirety as
follows:


                  “4.2     Governance.


                          4.2.1      Core Oversight Group.


                         (a)     The committee known as the Steering Committee that was initially formed by the
Parties under the Agreement shall after the Amendment Effective Date be known as the Core Oversight
Group. The Core Oversight Group shall operate and have the authority described in this Section
4.2, including the general authority over the management of the Product Development Plan and the
Project Working Team, and shall have the further authority over the management of the Project as
described in Article 3 of the Tech Transfer Agreement.


                         (b)     ACTII and Amylin shall each appoint three (3) representatives as their
representatives to serve on the Core Oversight Group. A Party may change its representatives from
time to time by giving written notice to the other Party.


                         (c)     The Core Oversight Group shall generally meet at such times as it may decide and
at least once per calendar quarter. The location of Core Oversight Group meetings shall alternate
between ACTII’s offices and Amylin’s offices unless otherwise agreed by the Parties. Minutes of a
meeting setting forth decisions of the Core Oversight Group shall be prepared by the Party hosting
the meeting. Minutes will become official when agreed to by all members of the Core Oversight
Group. Each Party will bear all expenses associated with attendance of its representatives at
meetings. If the Core Oversight Group members all agree, a meeting may be held by telephone.


 








 





                         (d)     Decisions of the Core Oversight Group shall be made by unanimous vote, with each
member having one vote. If the Core Oversight Group is unable to reach a unanimous vote on any
issue, the issue shall be referred to the Executive Committee for resolution.



                         (e)     Within fifteen (15) days after the receipt of a proposed Product Development
Plan or any amendments thereto from the Project Working Team or referral of any matter on which the
Project Working Team did not reach consensus, the Core Oversight Group shall meet to consider the
resolution of such matter or recommending approval of such proposed Product Development Plan or
amendments to the Executive Committee, as applicable. The Core Oversight Group shall also settle
any disputes among the Project Working Team.



                         4.2.2 Executive Committee.



                         (a)     Within thirty (30) days after the Amendment Effective Date, the Parties shall
form an Executive Committee. The Executive Committee shall operate and have the authority
described in this Section 4.2, including the general authority over the progress, budget and
strategic direction of the Product Development Plan, and shall have the further authority over the
progress, budget and strategic direction of the Project as described in Article 3 of the Tech
Transfer Agreement.



                         (b)     ACTII and Amylin shall each appoint two (2) representatives as their
representatives to serve on the Executive Committee. A Party may change its representatives from
time to time by giving written notice to the other Party.



                         (c)     The Executive Committee shall generally meet at such times as it may decide and
at least twice per calendar year. The location of Executive Committee meetings shall alternate
between ACTII’s offices and Amylin’s offices unless otherwise agreed by the Parties, with the first
meeting being held at Amylin’s office. Minutes of a meeting setting forth decisions of the
Executive Committee shall be prepared by the Party hosting the meeting. Minutes will become
official when agreed to by all members of the Executive Committee. Each Party will bear all
expenses associated with attendance of its representatives at meetings. If the Executive Committee
members all agree, a meeting may be held by telephone.



                         (d)     Decisions of the Executive Committee shall be made by unanimous vote, with each
member having one vote. Except as otherwise specifically set forth in Sections 3.3(a)(i) and (iii)
of the Tech Transfer Agreement, if the Executive Committee is unable to reach a unanimous vote on
any issue over which it has decision-making authority, the issue shall be referred to Amylin’s
Chief Executive Officer (or successor position), who shall make the final decision regarding such
issue.



                         (e)     Within fifteen (15) days after the receipt of a proposed Product Development
Plan or any amendments thereto from the Core Oversight Group or referral of any dispute by the Core
Oversight Group, the Executive Committee shall meet to consider approval of such plan or amendments
or resolution of such dispute. The Executive Committee, or the Core Oversight Group if and to the
extent so designated by the Executive Committee, shall



 









 




periodically review the Product Development Plan from a strategic perspective, the status of
efforts to implement it and shall make any changes to the Product Development Plan that it deems
necessary to accomplish the purpose of this Agreement.”


               4.3     Subsections (c) and (d) to Section 4.3 of the Agreement are hereby amended and
restated in their entirety as follows:


                       “(c)     As a general principle, the Project Working Team will use the RACI Task Analysis
to agree to responsibilities, approvals, consultations and information flow under the Product
Development Plan. Except as provided in the succeeding sentence of this paragraph, in the event
that the Project Working Team members do not reach consensus with respect to a matter that is
within the purview of the Project Working Team within fifteen (15) days after the meeting in which
they consider such matter, such matter may be referred by either Party to the Core Oversight Group
for resolution. Amylin’s representatives on the Project Working Team shall have the sole right to
determine how to proceed with respect to any commercialization activity related to a Product. No
vote of the Project Working Team shall be taken unless a majority of the members of the Project
Working Team are present, including at least one (1) representative of each Party. The Project
Working Team shall keep minutes of any meeting at which a decision is to be reached and shall
circulate such minutes to all members of the Project Working Team and the Core Oversight Group.
Responsibility for the preparation of the minutes shall rest with the hosting party. Minutes shall
be deemed approved unless any member of the Project Working Team objects to the accuracy of such
minutes within five (5) days of receipt. A Party desiring to refer a matter on which consensus has
not been reached by the Project Working Team to the Core Oversight Group shall make its referral in
writing to all Core Oversight Group members within twenty (20) days of the meeting at which the
matter was considered. Action pursuant to any matter referred to the Core Oversight Group shall be
suspended pending a determination by the Core Oversight Group or the referral of the matter to the
Executive Committee for resolution. A Party may at any time request reconsideration of any issue
if it in good faith believes that substantial changes in circumstances have occurred that
necessitate such reconsideration.



                         (d) (i)     The Project Working Team shall develop, and present to the Core Oversight Group
for consideration, a detailed development plan to address fully, consistent with the terms of this
Agreement, the key elements reasonably necessary for the research, development, formulation, and
manufacture of Products through Regulatory Approval and the budgeted FTEs and other expenses
related to all work to be conducted under the development plan (“Product Development Plan”). The
Product Development Plan shall be based on an initial product development plan, a first draft of
which is attached as Exhibit B to this Agreement. The product to be the subject of the
initial product development plan shall be Exenatide LAR. Should Amylin determine at any time
during the course of this Agreement that it wishes to develop and commercialize an additional Field
Product, or that it wishes to discontinue development and commercialization of Exenatide LAR and
instead develop and commercialize a different Field Product, the Parties will negotiate in good
faith whether to develop such additional or different Field Product and, if so, any appropriate
alterations or additions to the provisions of this Agreement, including but not limited to its
financial provisions. In the event that Amylin discontinues the development and commercialization
of Exenatide LAR and the



 









 




Parties are unable to agree upon the development of a different Field Product within 180 days
of such discontinuation, then this Agreement shall terminate as if Amylin had terminated this
Agreement under Section 9.2(b). The Project Working Team shall be responsible for implementing the
Product Development Plan, addressing fully the appropriate strategy for development and Regulatory
Approval of a Product, developing the responsibilities and procedures for handling any and all
regulatory issues related to a Product and for addressing all issues that develop during the course
of implementing the Product Development Plan. Such implementation efforts shall include: (A)
establishing comprehensive and detailed plans designed to accomplish the goals of the Product
Development Plan, including a plan pursuant to which ACTII will perform technical and scientific
work under this Agreement, (B) allocating tasks and coordinating activities required to carry out
the objectives of the Product Development Plan, (C) monitoring progress of the Product Development
Plan, (D) monitoring the FTEs worked and expenditures made under the Product Development Plan and
(E) discharging such other obligations as are assigned to the Project Working Team under this
Agreement or by the Core Oversight Group.


                               (ii)     The Project Working Team may propose modifications to the Product Development
Plan to the Core Oversight Group for its approval and recommendation to the Executive Committee.
No modification may be implemented unless approved by the Executive Committee or any authorized
designee.”


             4.4      Sections 4.4, 4.5 and 4.6 of the Agreement are hereby amended and restated in
their entirety as follows:


                     “4.4      Quarterly Reports. Within 30 days following the end of each calendar
quarter each Party shall provide the Core Oversight Group and the Project Working Team with
quarterly status reports summarizing its research and development efforts under the Product
Development Plan during such quarter. This report shall include a general summary of important
events and milestones achieved, personnel changes, learning points and such other matters as the
Party believes are relevant or that the Core Oversight Group may request.



                     4.5      Governance Following Product Launch. As soon as practicable following
launch of the Product in a Major Market Country, the Parties shall meet to review whether it is
appropriate to continue the Product Development Plan under the day-to-day management of the Project
Working Team, or whether the objectives of the Project Working Team have been substantially
achieved and it is appropriate to disband or reorganize the Project Working Team. Regardless of
whether the Parties elect to disband or reorganize the Project Working Team, the Executive
Committee shall continue to provide overall direction to development of Products.



                     4.6      Other Working Teams. The Core Oversight Group and Project Working Team,
with the approval of the Core Oversight Group, may appoint one or more other working teams
(“Working Teams”) to perform such functions as the Core Oversight Group or Project Working Team, as
applicable, may determine. Unless a Party elects not to participate on a particular Working Team,
all Working Teams shall have at least one representative of each



 









 







Party. Working Teams may provide advice and make recommendations to the Project Working Team,
but shall have no authority to bind the Project Working Team or either Party.”


5.                        FOUR-WEEK EXENATIDE LAR


          5.1     Section 6 of the Agreement is hereby amended and restated in its entirety as
follows:


         “6      Four-Week Exenatide LAR.


                  6.1     Manufacturing Agreement. In the event Amylin decides to proceed with
the development and commercialization of Four-Week Exenatide LAR, then Amylin and ACTII shall
proceed in accordance with Section 4.3(d)(i). If the Parties negotiate a Four-Week Exenatide LAR
Product Development Plan, then ACTII shall have the option to be the exclusive manufacturer of
Four-Week Exenatide LAR for a period of [***]
([***]) [***] after the first commercial sale in a Major Market
Country of Four-Week Exenatide LAR, and, if ACTII exercises this option, ACTII shall exclusively
manufacture and supply Four-Week Exenatide LAR, in the amounts and at such delivery times as
required by Amylin, its Affiliates, sublicensees and Co-Marketers. ACTII shall decide whether to
exercise this option prior to the commencement of Phase III Clinical Trials for Four-Week Exenatide
LAR. Upon ACTII’s exercise of this option and prior to the commencement of Phase III Clinical
Trials for Four-Week Exenatide LAR, or sooner if agreed by Amylin and ACTII, the Parties shall
negotiate in good faith and enter into a manufacturing and supply agreement (the “Manufacturing
Agreement”) on the terms provided in this Section 6 and such other terms to be mutually agreed
upon, including but not limited to, provisions dealing with ACTII’s responsibility to incur all
capital expenditures necessary to develop manufacturing capability for Four-Week Exenatide LAR
(subject to the last sentence of this Section 6.1), minimum purchase requirements for Four-Week
Exenatide LAR, forecasting of Amylin’s requirements for Four-Week Exenatide LAR, delivery times and
terms, rejection of Four-Week Exenatide LAR, recall of Four-Week Exenatide LAR, inspection of
ACTII’s manufacturing facilities, indemnification, and Amylin’s and ACTII’s responsibilities with
respect to compliance with global governmental regulations and force majeure. The agreement shall
provide that Amylin will supply sufficient quantities of API for use in the manufacture of
Four-Week Exenatide LAR for commercialization at no cost to ACTII. Under the agreement Amylin
shall pay ACTII a transfer price equal to the greater of (a) [***]% of Net Sales of Four-Week
Exenatide LAR and (b) [***] dollars ($[***]) for each dose of Four-Week Exenatide LAR. Such $[***]
price shall be adjusted annually by ACTII in accordance with the annual percentage change in the
Consumer Price Index (U.S. Bureau of Labor Statistics for all urban consumers, U.S. City Average —
all items less food and energy (October 1999 equals 178.3 (Reference CUUR0000 SAOL1E)). The
Parties shall also negotiate in good faith provisions for inclusion in the agreement regarding
payment by Amylin to ACTII of some portion of the transfer price at the time of shipment of
Four-Week Exenatide LAR and quarterly reconciliation of the balance of the transfer price owed on
Net Sales of Four-Week Exenatide LAR. The agreement shall also include provisions regarding the
manufacturing options provided to Amylin in Sections 6.2 and 6.3 below. In addition the agreement
shall include provisions regarding the reimbursement of ACTII by Amylin of any costs and expenses
ACTII has incurred to design, construct, commission or validate any manufacturing facility, or
portion thereof, including the


 








 




purchase of equipment, to permit the manufacture of Four-Week Exenatide LAR in the event that
Amylin does not develop Four-Week Exenatide LAR and commercialize it for a period of
 five (5) years  after its first commercial sale in a Major Market Country.


                  6.2     Failure to Supply. Should ACTII ever fail to supply any or all of
Amylin’s (as well as any Affiliate, sublicensee or Co-Marketer of Amylin’s) needs for Four-Week
Exenatide LAR to the extent Amylin has forecasted such needs, ACTII shall have the first right to
secure a third party to manufacture that amount of Four-Week Exenatide LAR which ACTII has failed
or anticipates failing to supply. Such third party shall be approved by Amylin, which approval may
not be unreasonably withheld. In the event that ACTII is unable to secure a third party
manufacturer, or ACTII continues to fail to supply all of Amylin’s (as well as any Affiliate,
sublicensee or Co-Marketer of Amylin’s) needs for Four-Week
Exenatide LAR for more than [***] ([***]) [***],
Amylin may do any of the following: (i) elect to make nonexclusive the license grant to ACTII with
respect to Four-Week Exenatide LAR granted in accordance with Section 6.1, above, (ii) terminate
the Manufacturing Agreement with ACTII for ACTII’s breach (should said breach be material), and
(iii) either by itself and/or by utilizing the services of a third party, manufacture and supply
Four-Week Exenatide LAR or components thereof (without an obligation to pay to ACTII any transfer
price payments on such Four-Week Exenatide LAR manufactured by Amylin or such third party). Any
Four-Week Exenatide LAR sold by Amylin, its Affiliates, sublicensees or Co-Marketers under this
Section 6.2 shall be subject to the applicable royalty payment provided in Section 3.4, above.


                  6.3      Second Source. After the expiration of ACTII’s manufacturing
exclusivity period of [***] ([***]) [***], as described in Section 6.1, above, Amylin may do any of the
following: (i) elect to make nonexclusive the license grant to ACTII with respect to Four-Week
Exenatide LAR granted in accordance with Section 6.1, above, or (ii) either by itself and/or by
utilizing the services of a third party, manufacture and supply Four-Week Exenatide LAR or
components thereof (without an obligation to pay to ACTII any transfer price payments on such
Four-Week Exenatide LAR manufactured by Amylin or such third party). Any Four-Week Exenatide LAR
sold by Amylin, its Affiliates, sublicensees or Co-Marketers under this Section 6.3 shall be
subject to the applicable royalty payment provided in Section 3.4, above.


                  6.4     ACTII Cooperation. In the event Amylin exercises its rights pursuant to
Sections 6.2 or 6.3, above, to provide for manufacture of Four-Week Exenatide LAR other than by
ACTII, ACTII shall transfer to Amylin or a third party, as appropriate, any ACTII Know-How required
to enable Amylin or such third party to manufacture Four-Week Exenatide LAR and provide such
assistance as is reasonably necessary to assist such manufacture and supply. Amylin shall pay
ACTII the FTE Hourly Rate for time spent by ACTII personnel in such technology transfer.”


6.                          USE OF MATERIALS AND INFORMATION


          6.1     The following new section is hereby inserted at the end of Section 8 of the
Agreement:


 








 




               “8.6     Disclosure to Collaboration Partner. Notwithstanding anything to the
contrary in this Agreement, Amylin may disclose the terms of this Agreement and Confidential
Information of ACTII to Lilly as necessary or appropriate for the research, development or
commercialization of Products; provided that Lilly is subject to obligations of confidentiality
comparable to those contained herein.”


7.                          PROSECUTION AND MAINTENANCE OF PATENTS


          7.1     Subsections (a) and (b) of Section 10.2 of the Agreement are hereby amended
and restated in their entirety as follows:


                 “(a)     ACTII’s Obligations to Prosecute. ACTII shall file and control
prosecution and maintenance of patent applications for all ACTII Patents, including ACTII Patents
claiming Inventions owned by ACTII, and, subject to consultation rights granted to Amylin in
Section 10.2(b) below, patents claiming Inventions owned jointly by ACTII and Amylin (“Joint
Inventions”) and be responsible for related interference proceedings in accordance with reasonable
commercial standards and reasonable principles of intellectual property protection, all at ACTII’s
expense. For prosecution and maintenance of patents and patent applications claiming Joint
Inventions, ACTII shall use external counsel of its choosing, subject to the consent of the General
Counsel of Amylin, which consent shall not unreasonably be withheld. ACTII shall endeavor to
ensure that all ACTII Patents, and patents claiming Joint Inventions are filed before any public
disclosure of the inventions claimed therein to maximize the scope of protection of such patents
filed outside the United States. ACTII shall furnish Amylin with copies of all substantive
communications between ACTII and applicable patent offices regarding patents and patent
applications claiming Inventions.


                 (b)     Consultation; No Disclosure by Amylin. ACTII and Amylin shall discuss
and evaluate Joint Inventions and confer with each other regarding the advisability of filing
patent applications in the United States and in foreign countries to cover Joint Inventions. ACTII
shall provide to Amylin (i) draft patent applications, and (ii) draft official correspondence to
national or international patent authorities which purports to amend the scope of the claims
presented in the originally filed application, each to be provided sufficiently in advance of
filing for Amylin to have the opportunity to comment thereon, and at least 30 days prior to the
contemplated filing date whenever possible. Any reasonable requests made by Amylin pertaining to
such drafts shall be reflected in such drafts, provided that Amylin provides such input to ACTII
sufficiently in advance of such proposed submission date to permit inclusion therein. Amylin shall
endeavor to delay any public disclosure of the subject matter of any patent application filed or to
be filed by ACTII under this Agreement until after filing by ACTII of such patent application.
Should the respective patent counsel of ACTII and Amylin be unable to agree, within thirty (30)
days (or earlier if such time period might affect patentability) of a set of claims being presented
by one Party to the other, as to the inventorship of any patent application claiming an Invention
in which each Party claims its employee or agent is an inventor, the Parties shall refer such
dispute to a neutral patent attorney or other appropriately qualified person mutually agreed upon
by the Parties. Such neutral third party shall be instructed to complete his/her determination as
to inventorship within thirty (30) days of referral of the dispute (or earlier if such time period
might affect patentability). Such neutral third party’s determination



 









 




regarding the referred issue shall be final and binding upon the Parties. The Party whose
position did not agree with the neutral third party’s determination will pay the fees associated
with such neutral third party decision, unless neither Party’s position prevails in which case the
Parties will share on a 50/50 basis the fees associated with such neutral third party’s decision.”


8.                           MISCELLANEOUS PROVISIONS


             8.1          Governing Law. This Amendment shall be governed by and construed in
accordance with the laws of the State of Delaware, without giving effect to the principles of
conflicts of laws.


             8.2          Entire Agreement. Except as specifically amended by this Amendment,
the Agreement shall remain in full force and effect. If there is any inconsistency or conflict
between any provision in this Amendment and any provision in the Agreement, the provision in this
Amendment shall control.


             8.3          Headings. Any headings and captions included herein are for
convenience of reference only and shall not be used to construe this Amendment.


             8.4          Counterparts; Facsimile. This Amendment shall become binding when
any one or more counterparts hereof, individually or taken together, shall bear the signature of
each of the Parties hereto. This Amendment may be executed in counterparts, each of which shall be
an original as against any Party whose signature appears thereon, but all of which together shall
constitute but one and the same instrument. This Amendment may be executed and delivered by
facsimile and upon such delivery the facsimile signature will be deemed to have the same effect as
if the original signature had been delivered to the other Party.


             IN WITNESS WHEREOF, the Parties have duly executed and delivered this AMENDMENT TO DEVELOPMENT
AND LICENSE AGREEMENT as of the Amendment Effective Date.



	 	 	 	 	 	 	 	 	 

	AMYLIN PHARMACEUTICALS, INC.	 	ALKERMES CONTROLLED THERAPEUTICS INC. II	 	 
	 
	 	 	 	 	 	 	 	 
	By:
	 	/s/ Daniel M. Bradbury
 
	 	By:	 	/s/ Michael Landine
 
	 	 
	 
	 	 	 	 	 	 	 	 
	Title: Chief Operating Officer	 	Title: Vice President, Corporate
	 	 
	 
	 	 	 	 	 	 Development	 	 
	 
	 	 
	 	 	 	 
	 	 





 








 





	 	 	 	 	 
	 
	 	Amylin Pharmaceuticals, Inc.	 	Tel (858) 552-2200
	 
	 	9360 Towne Centre Drive	 	Fax (858) 552-2212
	 
	 	San Diego, CA 92121 USA	 	www.amylin.com






July 13, 2006




Alkermes Controlled Therapeutics Inc. II

88 Sidney Street

Cambridge, MA 02139

Attn: Mike Landine




Dear Mr. Landine:



Amylin Pharmaceuticals, Inc. (“Amylin”) and Alkermes Controlled
Therapeutics Inc. II (“ACT II”) are parties to a Development and License
Agreement effective as of May 15, 2000, as amended (the “Development and
License Agreement”), pursuant to which the Parties are developing a synthetic
exendin-4 long-acting injectable product (“Exenatide LAR”) (capitalized
terms used but not defined herein shall have the meaning set forth in the
Development and License Agreement). The Parties now wish to amend the Development
and License Agreement to incorporate the following additional terms and
conditions set forth in this letter agreement (the “Letter Agreement”):



1.      In connection with the development of Exenatide LAR, Amylin and ACT II have
agreed to conduct a single species nonclinical carcinogenicity study, as
described in the March 16, 2006 meeting of the Core Oversight Group, which study
will have three arms - a diluent control arm, a placebo microsphere control arm
and an Exenatide LAR arm (the “Carcinogenicity Study”). In addition to
its existing obligations under the Development and License Agreement, ACT II has
agreed to supply Amylin solely for use in the Carcinogenicity Study and such
other studies as mutually agreed upon by both Parties, both placebo microspheres
(in the amount of either 240g or 1000g depending upon the final protocol(s) for
each of the Carcinogenicity Study and such other mutually agreed studies) and
diluent (in the amount of either 18.1L or 23.5L depending upon such final
protocol(s)). Amylin will compensate ACT II for the technical and scientific
time devoted to the production of these materials at the FTE Hourly Rate and
reimburse ACT II for any reasonable out-of-pocket expenses incurred in connection
with the supply of these materials. Payments to ACT II for the supply of these
materials shall be made within thirty days after receipt of invoices therefor,
and the provisions of Section 4.7(d) of the Development and License Agreement
regarding retention of records and audits by Amylin shall apply with regard to
payments under this Letter Agreement.



As additional consideration for ACT II’s supply of these materials, Amylin agrees
that ACT II will receive a separate report of any information, data and/or results
generated with respect to both the diluent control arm and the placebo microsphere
control arm of the Carcinogenicity Study as well as such other information, data
and/or results as may be mutually agreed upon by the Parties in connection with
any other studies mutually agreed upon by the Parties (the “Data”). Amylin
and ACT II agree that, subject to Section 8.3(c) of the Development and License
Agreement, ACT II has the right to use the Data for any and all purposes, except
the research, development and commercialization of a Product prior to the
termination of the Development and License Agreement. As used in the prior
sentence, the term “Product” means any Field Product the manufacture, use, sale,
offer for sale or import of which by a party, other than one who has a right or
license to the ACT II Patents, would infringe a Valid Claim of any of the ACT II
Patents. In addition Amylin agrees that ACT II will have the right to review the
final protocol for the Carcinogenicity Study, and Amylin agrees to consider in


 









 







good faith any comments suggested by ACT II with respect to such final protocol.
Amylin also agrees to furnish to ACT II copies of any proposed communications to
the FDA regarding the Carcinogenicity Study and to consider in good faith any
comments suggested by ACT II with respect thereto. Amylin will promptly inform
ACT II of any written or oral communications received from the FDA with respect
to the Carcinogenicity Study and provide to ACT II a copy of any such written
communications or notes of any such oral communications.



2.      Except as specifically amended herein, all provisions of the Development and
License Agreement shall remain in full force and effect in accordance with their
terms. In the event of a conflict between the provisions of the
Development and License Agreement and those of this Letter Agreement, this Letter
Agreement shall control. This Letter Agreement and the Development and License
Agreement constitute the entire agreement between the Parties regarding the subject
matter hereof, and supersede all prior understandings and agreements, whether
written or oral, regarding the subject matter hereof. No amendment or modification
of the terms and conditions of this Letter Agreement shall be binding on either
Party unless reduced to a writing referencing this Letter Agreement and signed by
an authorized officer of the Party to be bound.



3.      This Letter Agreement may be executed in two or more counterparts, each of
which shall be deemed an original for all purposes, but all of which together
shall constitute one and the same instrument. This Letter Agreement may be
executed and delivered by facsimile and upon such delivery the facsimile
signature will be deemed to have the same effect as if the original signature
had been delivered to the other Party.



4.      This Letter Agreement shall be governed by and construed in accordance with
the laws of the State of Delaware, without giving effect to the principles of
conflict of laws.



If this Letter Agreement correctly sets forth our understanding, please sign in
the space provided below and return a copy of this Letter Agreement to me.



Sincerely yours,



	 	 	 	 	 

	Amylin Pharmaceuticals, Inc.	 	 
	 
	 	 	 	 
	By:

	 	/s/ Lloyd A. Rowland
 

Lloyd A. Rowland

Vice President and General Counsel	 	 
	 
	 	 	 	 
	Accepted and Agreed:	 	 
	 
	 	 	 	 
	Alkermes Controlled Therapeutics Inc. II	 	 
	 
	 	 	 	 
	By:

	 	/s/ Michael Landine	 	 
	 
	 	 	 	 
	 
	 	 	 	 
	Printed Name: Michael Landine 	 	 
	 
	 	 	 	 
	Title: Vice President
 	 	 
	 
	 	 	 	 
	Date:7-17-06