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EXHIBIT 4.8
AMENDED AND RESTATED LICENSE AND SUPPLY AGREEMENT
This AMENDED AND RESTATED LICENSE AND SUPPLY AGREEMENT (this "Agreement"), made
the 29th day of March, 2002 ("Effective Date") by and between ▇▇▇ ▇▇▇▇▇ and
Company, an Indiana corporation located at Lilly Corporate Center, Indianapolis,
Indiana (hereinafter referred to as "Lilly"), and Amarin Corporation, plc, a
British corporation located at ▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇, ▇▇▇▇▇▇ ▇▇▇ ▇▇▇, ▇▇▇▇▇▇ ▇▇▇▇▇▇▇
(hereinafter referred to as "Amarin").
WHEREAS, Lilly has certain intellectual property rights in a pharmaceutical
product called Permax(R) (pergolide mesylate), useful in the management of the
signs and symptoms of ▇▇▇▇▇▇▇▇▇'▇ disease, and own and/or controls certain
patent rights, trademarks and Know-How (as hereinafter defined) relating
thereto;
WHEREAS, Lilly granted Athena Neurosciences, Inc., a Delaware corporation then
located at ▇▇▇ ▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇, ▇▇▇▇▇ ▇▇▇ ▇▇▇▇▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇ ("Athena")
an exclusive license to market Permax(R) in the Territory (as hereinafter
defined) and agreed to supply Athena with Permax(R) (collectively, "License and
Supply Rights") on the terms and conditions set forth in that certain License
and Supply Agreement between Lilly and Athena, dated April 16, 1993 ("Original
License Agreement");
WHEREAS, Athena agreed to pay Lilly $36,000,000.00 and to comply with certain
terms and conditions of the Original License Agreement in consideration of the
License and Supply Rights;
WHEREAS, Athena paid Lilly the $36,000,000.00 under the terms of the Original
License Agreement and the letter amendment between Lilly and Athena, dated
CERTAIN PORTIONS OF THIS EXHIBIT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR
CONFIDENTIAL TREATMENT. SUCH PORTIONS HAVE BEEN MARKED AS [*] IN THE TEXT OF
THIS EXHIBIT. THE OMITTED CONFIDENTIAL INFORMATION HAS BEEN FILED SEPARATELY
WITH THE US SECURITIES AND EXCHANGE COMMISSION.
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March 24, 1994 ("First Amendment"), which amended the Original License
Agreement;
WHEREAS, Lilly and Athena agreed to further amend the terms and conditions of
the Original Agreement and First Amendment, under the terms and conditions of
that certain Second Amendment To License And Supply Agreement between Lilly and
Athena, dated as of May 31, 1995 ("Second Amendment"), and the terms and
conditions of that certain Amendment To License And Supply Agreement between
Lilly and Athena, effective March 23, 1998 ("Third Amendment", which together
with the Original License Agreement, the First Amendment, the Second Amendment,
and the Third Amendment, shall hereinafter be collectively referred to as the
"Athena License Agreement");
WHEREAS, effective January 1, 1999, under the terms and conditions of an asset
transfer agreement, Athena assigned all of its rights, obligations, and interest
in the Athena License Agreement to Elan Pharmaceuticals, Inc., a Delaware
corporation located at ▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇, ▇▇▇▇▇ ▇▇▇ ▇▇▇▇▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇
(hereinafter referred to as "Elan"), and Elan assumed all of Athena's rights,
obligations, and interest in the Athena License Agreement;
WHEREAS, Elan granted Amarin an option to secure all of Elan's rights,
obligations, and interest under the Athena License Agreement, and appointed
Amarin as Elan's exclusive distributor for Permax(R), all pursuant to a
Distribution, Marketing, and Option Agreement between Elan and Amarin, dated May
17, 2001, as amended on September 30, 2001 ("Option Agreement");
WHEREAS, Lilly consented to the Option Agreement and further amended the Athena
License Agreement, pursuant to and under the terms and conditions of that
certain Written Consent and Amendment of License Agreement between Lilly and
Elan, effective June 30, 2001 ("Fourth Amendment", which together with
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the Athena License Agreement shall hereinafter be collectively referred to as
the "Elan License Agreement");
WHEREAS, NOW, Amarin desires to exercise its right under the Option Agreement to
secure and assume all of Elan's rights, obligations and interest in the Elan
License Agreement, except for the Elan Retained Rights ("Option"); and
WHEREAS, NOW, Lilly is willing to consent to the exercise by Amarin of the
Option conditioned upon Amarin executing and entering into this Agreement (which
by its terms and upon execution will amend and restate the Elan License
Agreement in its entirety relative to the rights and obligations assigned to
Amarin), and Elan, simultaneously, executing and entering into and that Consent
to Assignment and Limited Guaranty (under which Elan guarantees, for a limited
time period, Amarin's performance under this Agreement, and Elan affirms certain
of its obligations (e.g. continuing confidentiality obligation)) ("Guaranty"):
NOW, THEREFORE, in consideration of the mutual covenants herein contained, the
parties hereto mutually agree as follows:
ARTICLE 1
INCORPORATION OF RECITALS AND DEFINITIONS
1.-- The recitals, hereinabove, are incorporated into this Agreement by
reference.
1.01 "Affiliate" shall mean any company or entity controlled by, controlling or
under common control with a party to this Agreement and shall include, without
limitations (i) any company more than fifty percent (50%) of whose voting stock
or other ownership interest is owned or controlled, directly or indirectly, by
either party; (ii) any company that own or controls, directly or indirectly,
more than fifty percent (50%) of the voting stock of either party; and (iii) any
company the
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majority ownership of which is directly or indirectly common to the ownership of
either party.
1.02 "ANDA" shall mean an abbreviated new drug application for Permax(R) filed
with the FDA pursuant to the Code of Federal Regulations.
1.03 "Bulk Substance" shall mean the bulk active ingredient with the generic
name pergolide mesylate.
1.04 "Bulk Tablets" shall mean Bulk Substance formulated into finished tablets.
1.05 "Development Agreement" means that certain Development and Marketing
Agreement dated May 23, 1998, by and between Lilly and Athena, under which Lilly
and Athena agreed to develop and market a Permax Patch, which was terminated by
Lilly on June 9, 1999. Through an assignment, Elan became a
successor-in-interest to Athena's rights and obligations under the Development
Agreement.
1.06 "Elan Retained Rights" shall mean Lilly's Know-How and Patent Rights to the
extent the foregoing is reasonably required or necessary for the research,
development, manufacture and/or commercialization of the Permax Patch, as such
Know-How and Patent Rights were licensed or otherwise transferred to Elan under
the Elan License Agreement and/or the Development Agreement.
1.07 "Effective Date" shall have the meaning ascribed to such term in the
Recitals.
1.08 "FDA" means the United States Food and Drug Administration or any successor
thereof.
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1.09 "Formulate" means the process by which Bulk Substance is converted into
Bulk Tablets.
1.10 "Improvements" means inventions and discoveries related specifically to
Permax(R) including but not limited to: new/additional dosage forms,
formulations, salts, delivery systems, pro-drugs, analogues, process
improvements and clinical indications, whether or not patentable, developed or
acquired by a party and/or its Affiliates and sublicensees prior to or during
the term of this Agreement.
1.11 "Know-How" means all data, instructions, processes, formulae, expert
opinions, and information (and manufacturing, formulation or packaging, as
appropriate, if licenses for such activities are granted pursuant to this
Agreement) not generally known and reasonably necessary for the use and/or sale
of Permax(R) by Amarin in the possession of Lilly. Know-How shall include,
without limitation, marketing costs and marketing expense data, sales
information, distribution information, biological, chemical, pharmacological,
toxicological, pharmaceutical, physical and analytical, safety, quality control,
clinical data, and trade secrets. Notwithstanding, Know-How shall exclude
Retained Know-How, until the Elan Retained Rights are assigned to Amarin under a
separate assignment agreement between Amarin and Elan.
1.12 "Margin" when referring to Amarin's or Elan's Margin shall mean, with
respect to any Year, a percentage equal to (i) Amarin's or Elan's combined Net
Sales of all Pack presentations less the combined Supply Price for these Net
Sales divided by (ii) Amarin's or Elan's combined Net Sales of all Pack
presentations and when referring to Lilly's Margin shall mean, with respect to
any Year, a percentage equal to (i) the combined Supply Price for the Permax(R)
sold to Amarin hereunder less Lilly's combined cost of manufacturing such
Permax(R) divided by the combined Supply Price for the Permax(R) sold to Amarin.
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1.13 "NDA" means a new Drug Application as filed with the FDA pursuant to the
Code of Federal Regulations.
1.14 "Net Sales" shall mean the aggregate gross sales of Permax(R) by a party
and its Affiliates (other than sales among a party and its Affiliates)
determined in accordance with Generally Accepted Accounting Principles,
consistently applied, provided that Net Sales for purposes of Amarin shall be
reduced by the difference between the aggregate sales made directly to patients
through any mail order retail pharmacy owned, controlled by or Affiliated with
Amarin and the equivalent Net Wholesale Price of these sales, less: cash, trade
or quantity discounts; sales, use, tariff, or other excise taxes imposed upon
particular sales; transportation charges; and other credits or allowances,
including those granted on account of prices, adjustments, returns of rebates,
if any are incurred or granted.
1.15 "Net Wholesale Price" shall mean the price for Permax(R) offered by Lilly
or Amarin, as applicable, to authorized wholesalers in the Territory.
1.16 "Pack" shall mean a package containing a number of Permax(R) tablets in
final packaging form ready for supply to wholesalers, retailers or customers.
1.17 "Package" or "Packaging" shall mean the conversion of Bulk Tablets into
finished Packs for sale.
1.18 "Patent Rights" shall mean any and all patent applications heretofore filed
or having legal force in the Territory owned by or licensed to Lilly as set
forth in EXHIBIT A or to which Lilly otherwise acquired rights, which pertain to
the manufacture, use or sale of Permax(R) in the Territory, together with any
and all patents that have issued or in the future issue therefrom, including
certificates of inventions and any and all divisions, continuations,
continuations-in-part, extensions, reissues or additions to any of the aforesaid
patents and patent
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applications. Notwithstanding, Patent Rights shall exclude Retained Patent
Rights, until Elan Retained Rights are assigned to Amarin under a separate
assignment agreement between Amarin and Elan.
1.19 "Permax(R)" shall mean any pharmaceutical formulation containing pergolide
mesylate, chemically designated as 8a-[ (Methylthio)methyl] -6-propylergoline
monomethanesulfonate, currently sold under the registered trademark Permax(R) or
subsequently introduced and sold in the Territory. Notwithstanding, Permax(R)
shall exclude any rights to or interest in the Permax Patch, until such rights
and interest are assigned to Amarin under a separate assignment agreement
between Amarin and Elan.
1.20 "Permax Patch" shall mean any transdermal patch used for the delivery of a
formulation of the human pharmaceutical product in which the active ingredient
is pergolide mesylate.
1.21 "Programs" shall mean Amarin's indigent supply program and Amarin's
physician courtesy supply program, as each is in effect from time to time In
Amarin's sole discretion.
1.22 "Retained Know-How" shall mean Know-How to the extent the foregoing is
reasonably required or necessary for the research, development, manufacture
and/or commercialization of the Permax Patch.
1.23 "Retained Patent Rights" shall mean Patent Rights to the extent the
foregoing is reasonably required or necessary for the research, development,
manufacture and/or commercialization of the Permax Patch.
1.24 "Samples" shall mean 30 count 0.05 mg strength and 30 count 0.25 mg
strength Packaged Bulk Tablets (or other presentations of Packaged Bulk Tablets
as may be agreed by Amarin and Lilly) for sampling to physicians.
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1.25 "Specifications" shall mean the manufacturing specifications for Permax(R)
as set forth in Exhibit B and in Lilly's NDA for Permax(R). If Amarin obtains
its ANDA, the Specifications shall be the manufacturing specifications for
Permax(R) as set forth in Amarin's ANDA, provided that such specifications are
not different than the Specifications in effect immediately prior to Amarin
obtaining its ANDA unless Lilly has given its prior written consent to such
change.
1.26 "Supply Price" shall mean the price which Lilly charges Amarin for Packs,
Bulk Tablets, Bulk Substance or Samples determined in accordance with Section
6.1 and 6.4.
1.27 "Territory" shall mean the United States of America, its territories and
possessions, including Puerto Rico.
1.28 "Year" shall mean any calendar year during the term of this Agreement
except that the first calendar year of this Agreement shall be pro-rated from
the Effective Date through December 31, 2002.
ARTICLE 2
LICENSE AND KNOW-HOW TRANSFER
2.1 Lilly hereby grants to Amarin and Amarin hereby accepts an exclusive paid-up
license, with the right to sublicense, under the Patent Rights and Lilly's
Know-How, to use, promote, market and sell Permax(R) (excluding only the Elan
Retained Rights) in the Territory in accordance with the terms and conditions
set forth in this Agreement, provided that such right to sublicense is effective
only after Amarin has its own ANDA approved by FDA or equivalent regulatory
authorization in the Territory. Lilly also hereby grants to Amarin and Amarin
hereby accepts a paid-up sole license to exclusively distribute Permax(R)
(excluding only the Elan Retained Rights) in the Territory in accordance with
the
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terms and conditions set forth in this Agreement, except for Lilly's right to
distribute Permax(R) for its sales to Amarin and its own sales outside the
Territory; provided, however, that Amarin shall also have the right to
sublicense after it has its own ANDA approved by FDA or equivalent regulatory
authorization in the Territory. If Amarin exercises its right to acquire Bulk
Substance or Bulk Tablets as provided in Section 5.3, Lilly shall grant to
Amarin a paid-up sole license, with a right to sublicense, under the Patent
Rights and Lilly's Know-How to Formulate the Bulk Substance into Bulk Tablets
and/or to Package the Bulk Tablets, as appropriate, to allow Amarin to exercise
its rights in accordance with the terms and conditions set forth in this
Agreement. Notwithstanding any other provision of this Agreement, if Elan
assigns all of its rights to and interest in the Elan Retained Rights to Amarin
and causes all persons to whom Elan has transferred any right or interest in the
Elan Retained Rights to assign all of such rights and interests to Amarin, then
the licenses described in the prior sentences shall include the Elan Retained
Rights.
2.2 Lilly is the owner of United States trademark registration No. 1382020 for
the ▇▇▇▇ Permax(R) (the "▇▇▇▇"). Subject to the terms and conditions of this
Agreement, Lilly hereby grants to Amarin an exclusive license to use the ▇▇▇▇ in
the Territory during the term of this Agreement. Provided this Agreement is not
terminated by Amarin pursuant to Section 14.2 or by Lilly pursuant to Section
14.3, Amarin's license to use the ▇▇▇▇ shall survive the termination of this
Agreement for a period of five (5) years. Thereafter, Lilly shall assign to
Amarin all United States rights, title and interest in the ▇▇▇▇, provided Amarin
did not terminate this Agreement pursuant to Section 14.2 or Lilly did not
terminate this Agreement pursuant to Section 14.3. The foregoing shall not
convey any rights to Amarin to use the ▇▇▇▇ outside the Territory and shall not
limit Lilly's use of the ▇▇▇▇ outside the Territory. Amarin agrees to use the
▇▇▇▇ in accordance with applicable state and federal laws and regulations and
reasonable quality standards established by Lilly and provided to Amarin.
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2.3 Amarin understands and acknowledges that Elan is retaining the Elan Retained
Rights under the terms and conditions of the Elan License Agreement. Amarin also
acknowledges that Elan and Amarin are currently negotiating in good faith for
Elan (and/or any person to whom Elan has transferred any interest in the Elan
Retained Rights) to assign all of the Elan Retained Rights to Amarin under the
terms and conditions of a separate assignment agreement. Amarin agrees that if
Elan or any other person (including, without limitation, Elan Affiliates or
joint ventures in which Elan owns any interest) assigns to Amarin Retained
Know-How and/or Retained Patent Rights, such Retained Know-How and Retained
Patent Rights shall be deemed Know-How and Patent Rights, respectively, as
defined in this Agreement, and subject to the terms and conditions of this
Agreement, and Lilly hereby consents to such assignment.
2.4 Lilly shall make available to Amarin, promptly upon Amarin's request, the
Know-How not provided to Athena or Elan prior to the Effective Date, as
necessary to exercise its rights and comply with its responsibilities under this
Agreement.
ARTICLE 3
MARKETING
3.1 During the term of this Agreement and for a period of five (5) years after
its termination, Amarin agrees that it will not sell pergolide outside the
Territory. Lilly agrees that it will not sell pergolide in the Territory during
the term of this Agreement and for a period of five (5) years thereafter, other
than sales to Amarin and except to the extent such sales are intended as part of
Lilly's distribution outside the Territory. These obligations are specifically
intended to survive any expiration or termination of this Agreement.
3.2 Amarin shall submit to Lilly's Regulatory Affairs group an annual marketing
plan by October 1st for the coming Year which will include Amarin's plans for
the
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promotion, marketing and sale of Permax(R) in the Territory so that Lilly may
review such plan to ensure coordination of regulatory compliance. Lilly shall
have thirty (30) days to review such marketing plan and provide Amarin with its
comments on same. Amarin shall give good faith consideration to Lilly's
comments, however, Lilly shall not have the right to approve such plan and
Amarin shall be free to implement its annual marketing plan regardless of
Lilly's approval of same. Disagreements regarding Amarin's annual marketing plan
shall be discussed in good faith between a Lilly nominee and Amarin's Vice
President of Marketing. Amarin shall, moreover, provide any written changes to
such marketing plan to Lilly as quickly as possible after such changes occur and
Lilly shall then have the opportunity to review and provide Amarin with its
comments on such changes, which comments Amarin shall consider in good faith.
3.3 Amarin shall have exclusive control over the pricing of Permax(R) for its
sales in the Territory, to the extent legally permissible.
3.4 During the term of this Agreement, an employee of Lilly will be designated
as a liaison to Amarin and shall be available at reasonable times to consult
with Amarin regarding regulatory and clinical matters and the supply, promotion,
distribution and sale of Permax(R) in the Territory, as reasonably requested by
Amarin. Lilly shall have no obligation to provide any other training or
materials to Amarin.
3.5 Amarin will develop, prepare and pay for all product promotional materials,
selling aids, journal ads and other items used to promote Permax(R) in the
Territory. Throughout the term of this Agreement, Lilly shall provide Amarin,
free of charge, with reasonable information regarding Lilly's worldwide sales
efforts for Permax(R) as Amarin and Lilly may deem useful for developing sales
in the Territory, including, but not limited to market research, promotional
materials and
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forecasts prepared by Lilly, as is normally done by Lilly as part of its
communications among Affiliates.
3.6 Amarin shall use reasonable efforts consistent with generally accepted
business practices and legal requirements to promote and market Permax(R) in the
Territory, which efforts shall in no event be less than the efforts customarily
given to the promotion of Amarin's other prescription products, and which shall
be in accordance with the marketing plan(s) as provided in Section 3.2.
3.7 Amarin will have responsibility for all correspondence with physicians in
the Territory related to Permax(R) and Lilly will refer questions related to
Permax(R) raised by such physicians to Amarin for its response. However, the
foregoing is not intended to restrict Lilly from responding directly to such
physicians to the extent required by applicable law or regulation. If Lilly
believes that it is appropriate for it to correspond directly with physicians in
the Territory related to Permax(R) but is not required by applicable law or
regulation, Lilly may do so with the prior written consent of Amarin, such
consent to not be unreasonable withheld. Lilly and Amarin will each provide the
other with copies of any responses it sends to physicians in the Territory.
3.8 Amarin and Lilly shall each have publication rights with respect to the
other party's data regarding Permax(R), provided that the other party gives its
prior approval.
ARTICLE 4
REGULATORY COMPLIANCE AND CLINICAL AFFAIRS
4.1 (a) Lilly will retain the ownership of its Permax(R) NDA (except as set
forth in Section 4.1(b)) and shall file all required filings (except
for those set forth in Section 4.2). All communications to the FDA
relating to Lilly's Permax(R) NDA, except for those set forth below in
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Section 4.2, shall come from Lilly. Amarin may if it so desires,
apply for its own ANDA and Lilly will provide Amarin authorization to
allow the FDA to review information in Lilly's Permax(R) NDA for
purposes of approving Amarin's ANDA.
(b) Lilly, upon written notice to Amarin, has the right but not the
obligation during the term of this Agreement to assign and transfer to
Amarin all of Lilly's rights, title, and interest in and to the United
▇▇▇▇▇▇ ▇▇▇ ▇▇▇▇ ▇▇▇▇▇▇▇▇▇▇▇ ▇▇-▇▇▇, ▇▇▇▇▇▇ ▇▇▇▇▇▇ Investigational Drug
Application [*] (LY127809, Dopamine Agonist), United States
Investigational Drug Application [*] (LY127809, Dopamine Agonist in
[*] and [*] without [*]), United States Investigational Drug
Application [*] (LY127809, Dopamine Agonist in [*] with [*] ), and all
amendments and supplements to such documents (the "U.S. Permax(R)
Regulatory Documents"). Such assignment and transfer will be
effective, subject to any prior notice required by law to be given to
the Food and Drug Administration ("FDA") by the Parties, forty-five
(45) days after Amarin's receipt of Lilly's written notice. Lilly,
upon written notice to Amarin, also has the right but not the
obligation during the term of this Agreement to assign and transfer to
Amarin all of Lilly's rights, title, and interest in and to the U.S.
trademark registration 1382020 for the ▇▇▇▇ Permax(R) (the "▇▇▇▇").
Such assignment and transfer will be effective, subject to any notice
required by law to be given to the United States Patent and Trademark
Office ("USPTO") by the Parties, forty-five (45) days after Amarin's
receipt of Lilly's written notice. Lilly will be allowed to retain
copies of all assigned and transferred documents for its legal
records. If Lilly assigns and transfers the U.S. Permax(R) Regulatory
Documents to Amarin, Lilly will retain (and/or Amarin will ▇▇▇▇▇
▇▇▇▇▇) a paid-up right to reference the U.S. Permax(R) Regulatory
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Documents after such assignment and transfer for purposes of obtaining
or maintaining its Permax(R) marketing authorizations outside the
United States. Within the forty-five (45) days after Lilly's written
notice to Amarin that Lilly is exercising either of its rights to
assign and transfer hereunder, Lilly and Amarin will negotiate and
execute in good faith a written instrument memorializing the
assignment(s) so that the assignment(s) may be properly recorded with
the FDA and USPTO, as applicable, and shall negotiate in good faith a
procedure to coordinate the transfer of information (e.g. adverse
event reports) necessary to maintain such transferred item. Lilly
shall not charge Amarin for the assignment and transfer of the items
described in this Section. If Lilly assigns to Amarin the U.S.
Permax(R) Regulatory Documents and/or the ▇▇▇▇, as described above,
Amarin agrees to assume full responsibility for the assigned rights
and obligations (i.e. legal, financial and otherwise) from the
effective date of such transfer, which shall include, without
limitation, making all filings, and reports required by to local,
state and federal law. Such assignment will not affect Lilly's rights
and obligations under the U.S. Regulatory Documents and/or the ▇▇▇▇
▇▇▇▇▇ to the effective date of such transfer. If appropriate, the
parties will negotiate in good faith a procedure, separate agreement,
and/or amendment to this Agreement, necessary or reasonably useful to
coordinate the transfer of items and/or information described in this
Section.
4.2 (a) To the extent permitted by the FDA, Amarin shall be responsible for
(i) reviewing promotional materials and advertising compliance with
applicable local, state and federal laws and regulations and (ii)
filing in accordance with applicable regulations all promotional
materials and advertising with FDA, or other appropriate regulatory
bodies, as may be required by FDA or such bodies. Lilly will cooperate
with
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Amarin to coordinate direct access between FDA (DDMAC) and promotional
materials and advertising, to the extent such direct access is
permitted by FDA. Amarin shall establish standard operating procedures
for internal review of promotional materials and advertising, the
current version of which is attached as ATTACHMENT A. Amarin shall
comply in all material respects with such procedures during the term
of this Agreement. Amarin shall submit all proposed amendments to the
procedures in Attachment A to Lilly thirty (30) days prior to
implementation. Lilly may review and comment on such amendments and
Amarin shall consider such comments in good faith.
(b) Amarin shall submit advance copies of all proposed promotional
materials and advertising for Permax(R) for Lilly's review at least
thirty (30) days before submission to the FDA. Amarin will discuss
with Lilly in good faith any concerns and comments Lilly might have on
Amarin's promotional materials and advertising, however, Lilly will
have no veto rights over such materials and advertising nor any right
to delay or prevent implementation, distribution or use, except as
specifically provided in Section 4.2(c), below.
(c) In the event of a regulatory action related to Amarin's promotional
activities (including, without limitation, a notice of violation) for
Permax(R) (defined as a written notice of an alleged violation of law
or regulation, whether titled or not, by a governmental agency) and
Lilly will have the option to re-assume the review and approval of all
of Amarin's promotional materials and advertising for Permax(R) for
compliance with applicable local, state and federal laws and
regulations for a period of six (6) months or such shorter time as in
Lilly's discretion may be necessary to ensure to Lilly's reasonable
satisfaction that compliance will be assured and no further issues
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remain. In the event of two (2) or more regulatory actions concerning
Amarin's promotional activities for Permax(R), Lilly shall have the
right in its discretion to reassume permanently such review and
approval responsibilities.
(d) Should Lilly elect to exercise its right of review and approval set
forth in subsection (c), it shall discuss such exercise in good faith
with Amarin prior to notifying Amarin, in writing, of such exercise
and Amarin shall submit all Amarin advertising for Permax(R) for
Lilly's review and approval at least thirty (30) days before the date
of the intended use. Amarin will not use any such material without
Lilly's approval and Lilly agrees to use reasonable efforts to
complete its review and respond to Amarin within thirty (30) days of
receipt. If Amarin does not receive a response from Lilly within
thirty (30) days, Amarin may thereafter send written notice to Lilly
that it intends to use such material and Amarin is permitted to use
any such material if Amarin does not receive a response from Lilly
within ten (10) days of Lilly's receipt of the written notice. At the
request of Amarin, Lilly shall discuss with Amarin its reasons for
objecting to any item of such written material. Amarin shall provide
Lilly a copy of such material immediately prior to use (to allow Lilly
to submit it to the FDA).
(e) Notwithstanding any other provision in this Agreement to the contrary,
Amarin shall have no right to modify the package inserts or labeling
for Permax(R) cartons and containers without the prior written consent
of Lilly, not to be unreasonably withheld.
Finally, to the extent Amarin is not permitted to file promotional
materials or advertising with the FDA or other appropriate regulatory body,
Amarin shall provide Lilly with a copy of such material sufficiently in advance
of its use to allow
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Lilly to submit it to the FDA or other appropriate body.
Lilly agrees that it will file such items with the FDA or other appropriate body
as promptly as reasonably possible and, in no event, later than thirty-five (35)
days after receipt of same from Amarin. In such instance, Amarin shall abstain
from use of such promotional materials or advertising until it receives
confirmation that such items have been submitted to the FDA or such other
appropriate body. Furthermore, Lilly shall have an annual audit right for all
promotional material and/or advertising prepared by Amarin for Permax(R) in
order to ensure that (i) Lilly has a copy of all filings and correspondence
between Amarin and the FDA with respect to such items; (ii) Amarin has followed
its standard operating procedures for internal review of these items in all
material respects; and (iii) Amarin has not received a regulatory action related
to its promotional activities for Permax(R).
4.3 Each party shall endeavor to provide the other with information necessary to
comply with their respective regulatory obligations.
(a) While Lilly is supplying Permax(R) to Amarin under Lilly's NDA, Amarin
shall submit to Lilly in a timely fashion or at Lilly's request such
information as necessary to allow Lilly to comply with the regulatory
requirements applicable to the Permax(R) NDA (e.g., adverse drug
experience reporting, annual reporting, filing supplements to NDA).
Such information to be provided by Amarin to Lilly shall include, by
way of illustration but not limitation, information on Permax(R) from
any studies, as well as adverse drug experience reports from clinical
trials and marketed commercial experience with Permax(R).
(b) During the term of this Agreement, Lilly shall provide to Amarin on a
semi-annual basis, for informational purposes only, copies of
significant communications with any governmental agency throughout the
world concerning Permax(R) that may have an impact
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on the distribution and sale of Permax(R) in the Territory, including
but not limited to communications relating to the issues that could be
reportable to the FDA. Lilly shall be allowed to exclude confidential
or proprietary information which has not been licensed to Amarin.
(c) During the term of this Agreement, Lilly shall promptly notify Amarin
if any regulatory action may impact Lilly's supply obligations under
this Agreement. Notwithstanding the above, Lilly shall be allowed to
exclude confidential or proprietary information which has not been
licensed to Amarin.
(d) If reasonably practicable, Lilly shall consult with Amarin prior to
any communication with the FDA concerning any information described in
Sections 4.3 (a)-(c) above.
(e) During the term of this Agreement, each party shall provide the other
with copies of significant communications with any governmental agency
in the Territory concerning Permax(R) that may have an impact on the
distribution and sale of Permax(R) in the Territory, including but not
limited to communications relating to issues that could be reportable
to the FDA as well as all filings with the FDA. Such communications
shall be provided to the other party contemporaneously or, at the very
latest, within fifteen (15) days of filing with or receipt of same
from the governmental agency. Either party shall be allowed to exclude
confidential or proprietary information which has not been licensed to
the other.
(f) During the term of this Agreement, Amarin shall promptly notify Lilly
of any regulatory action related to Amarin's promotional activities
for Permax(R).
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4.4 Specific details regarding the management of adverse event information for
Permax(R) will be delineated in a separate document. The pharmacovigilance
representatives of the parties will develop within thirty (30) days of the
Effective Date a document that identifies which safety information, if any, that
will be exchanged; when this information will be exchanged; which party has
regulatory reporting responsibilities; who will manage the global safety
database; who obtains follow-up information on incomplete safety reports; who
reviews the literature for safety report information; who prepares any required
periodic safety updates; and the identification of any other details required to
appropriately manage safety information for Permax(R). It is understood and
agreed that unless and until the NDA for Permax is transferred to Amarin, Lilly,
as holder of the NDA, will have the responsibility for reporting adverse events
to FDA and otherwise complying with 21 C.F.R. Section 314.80.
4.5 Each party will have the right to conduct its own clinical trials related to
Permax(R) in the Territory with the other party's prior consent and approval,
which shall not be unreasonably withheld. The party proposing to conduct the
clinical trial shall be responsible for updating the Clinical Investigator's
Brochure ("CIB") and shall submit the updated CIB to the other party for
approval, which shall not be unreasonably withheld, prior to sending it to
proposed investigators.
4.6 Each party shall keep the other apprised of the status and results of
clinical trials involving pergolide that are conducted by or on behalf of each
party, its Affiliates and sublicensees, as the case may be, within or outside of
the Territory. The party conducting the trial shall be responsible for making
all required reports to the FDA. If Amarin wishes to conduct a clinical trial
prior to obtaining its ANDA, the parties shall, prior to commencement of the
clinical trial, agree on an acceptable arrangement for submitting reports to the
FDA.
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4.7 In the event (i) any government authority issues a request, directive or
order that Permax(R) be recalled, (ii) a court of competent jurisdiction orders
that Permax(R) be recalled or (iii) Lilly or Amarin reasonably determine, after
mutual consultation, that Permax(R) should be recalled, the parties shall take
all appropriate corrective actions. In the event such recall results from the
breach of Lilly's obligations or warranties under this Agreement or other fault
of ▇▇▇▇▇, ▇▇▇▇▇ shall be responsible for the expenses of the recall. In the
event such recall results from the breach of Amarin's obligations or warranties
under this Agreement, the sale or marketing of Permax in the Territory by Amarin
or its permitted sublicensees after the Effective Date of this Agreement, or
other fault of Amarin, Amarin shall be responsible for the expenses of the
recall. For purposes of this Agreement, the expenses of recall shall be the
expenses of notification and return or destruction of the recalled Permax(R),
the costs of Permax(R) recalled and any costs directly associated with the
distribution of replacement Permax(R). Lilly and Amarin shall cooperate fully
with one another in conducting any recall.
ARTICLE 5
MANUFACTURE AND SUPPLY OF PERMAX(R)
5.1 Lilly will manufacture, package and label for Amarin and Amarin will
purchase from Lilly, except as provided in Sections 5.3, 14.5 and 14.6, all of
Amarin's requirements for Permax(R) through April 1, 2008, including Bulk
Substance and Packs. The parties will agree to the appropriate labeling and
trade dress for Permax(R) that recognizes the house-style of Amarin and the
respective responsibilities of the parties and such labeling and trade dress
shall be implemented as soon as all applicable regulatory requirements have been
met with respect to such labeling and trade dress. Lilly will not be required to
re-label or modify the trade dress of any of the Permax(R) product. The parties
contemplate that Amarin's name shall appear as the exclusive distributor of
Permax(R) in the Territory and Lilly shall appear as the manufacturer of
Permax(R).
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5.2 Subject to Sections 5.3, 14.5 and 14.6, Lilly will supply finished, packaged
and labeled Packs to Amarin in the quantities of the various dosage forms
requested by Amarin and meeting the Specifications applicable at the time of
manufacture. The determination of whether a given lot of Permax(R) meets the
Specifications and can be released by Lilly to Amarin will be made solely by
Lilly. Lilly will manufacture Permax(R) supplied to Amarin hereunder at a site
meeting FDA current Good Manufacturing Practices ("cGMP"). Subject to Section 7,
Lilly shall use reasonable efforts to ensure that sufficient stock of Permax(R)
will be available in its inventory to promptly fill Amarin's orders and that it
will have a cGMP manufacturing facility which can produce amounts of Permax(R)
during the term of this Agreement to meet Amarin's requirements for sales of
Permax(R).
5.3 In the event Lilly decides to subcontract the right to Formulate Bulk
Substance or Package Bulk Tablets to a third party, Amarin shall have the right
but not the obligation to acquire Bulk Substance or Bulk Tablets from Lilly so
that Amarin or a subcontractor to Amarin can complete the Formulation and/or
Packaging for Amarin's requirements for Permax(R), provided that applicable
regulatory requirements permit Amarin or its subcontractors to do the
Formulation and/or Packaging. Amarin desires to exercise its right to Formulate
or Package Permax(R), Amarin shall notify Lilly of such determination within
ninety (90) days of the date Amarin receives notice from Lilly expressing
Lilly's desire to subcontract such right.
5.4 Provided Amarin has the right under Section 5.3 to Formulate and/or Package,
Lilly shall assist and transfer to Amarin or its subcontractor all Know-How and
licenses necessary to allow Amarin or its subcontractor to Formulate and/or
Package. Once Amarin assumes the Formulating and/or the Packaging, Lilly shall
be relieved of its obligations under this Agreement related to such activities.
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5.5 If Amarin exercises its right to Formulate and/or Package under Section 5.3,
Lilly agrees to grant Amarin reasonable wastage allowances comparable to Lilly's
experience in its Formulation and Packaging activities related to Permax(R). In
addition, Lilly shall supply such quantities of Bulk Substance and/or Bulk
Tablets as reasonable required to initiate Amarin's Formulation and Packaging
activities, including initial runs and stability needs, at a price not to exceed
one-third (1/3) of the applicable Supply Price that would then be in effect
assuming that Section 6.1(b) is never applicable, provided such material
supplied hereunder will not be sold by Amarin.
ARTICLE 6
COSTS OF PRODUCT
6.1 Amarin shall pay Lilly for the supply of Permax(R) as follows:
(a) The initial Supply Price per Pack presentation, Bulk Tablet, Bulk
Substance as of the Effective Date shall be as follows:
$[*] per Pack containing 30 Permax(R) tablets of 0.05 mg strength
($[*]per 1000 tablets for 0.05 mg strength Bulk Tablets)
$[*] per Pack containing 30 Permax(R) tablets of 0.25 mg strength
($[*]per 1000 tablets 0.25 mg strength Bulk Tablets)
$[*] per Pack containing 100 Permax(R) tablets of 0.25 mg strength
($[*]per 1000 tablets for 0.25 mg strength Bulk Tablets)
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$[*] per Pack containing 100 Permax(R) tablets of 1.0 mg strength
($[*]per 1000 tablets for 1.00 mg strength Bulk Tablets)
$[*] per gram of Bulk Substance
The Supply Price for any Pack containing a different tablet number or
strength shall be agreed upon by Lilly and Amarin generally in a manner
consistent with that used to establish the initial Supply Prices above.
(b) Beginning May 1, 2002, and every anniversary thereafter, the Supply Price
set forth in Section 6.1(a) shall be increased in percentage terms by the
greater of (i) two thirds (2/3) of the percentage change in [*]or (ii) one third
(1/3) of the percentage change in the [*], that has been experienced or reported
in the preceding twelve (12) month period ending March 31st. For purposes of the
first increase, the parties shall utilize Elan's Net Wholesale Price for any
portion of the twelve-month period ending March 31, 2002 in which Elan was the
distributor of Permax in the Territory.
(c) If any law or regulation becomes effective after the Effective Date, or
if Amarin encounters generic competition (other than from an Affiliate of Amarin
or any other Amarin partner in the area of adjunctive therapy or monotherapy for
the treatment of ▇▇▇▇▇▇▇▇▇'▇ disease), which significantly restricts or lowers
Amarin's [*] of Permax(R) and Amarin determines that its Margin has fallen below
[*] percent ([*]%), Amarin will notify Lilly of such determination and Amarin
shall allow Lilly or Lilly's independent auditors access to such financial
records of Amarin's Margin determination. Within sixty (60) days of such notice,
Amarin and Lilly will agree to an adjustment to the future Supply Price for
Permax(R) or such other rebates or allowances so that Amarin
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and Lilly share proportionally in the reduction of their respective Margins;
provided, however, that in no event will the Supply Price be reduced below [*]
percent ([*]%) of the Supply Price on the Effective Date of the Third Amendment,
increased by any appropriate factor equivalent to the increase in the [*]
(with August, 1997 as the baseline measurement date (i.e. 2.2)) from that
Effective Date, to the extent this Section 6.1(c) is triggered by Amarin.
Notwithstanding the above, in the event Amarin in its reasonable business
judgment recommends to Lilly that Amarin's Net Wholesale Price be voluntarily
reduced due to competitive or other market circumstances, Lilly agrees to
negotiate in good faith a reduction in Supply Price.
(d) Notwithstanding the foregoing, the Supply Price for Permax shall remain
at the Supply Price in effect as of September 30, 200[*] until Amarin's Margin
is improved by [*]% over Elan's Margin as of September 30, 200[*] (i.e. when
Amarin's Margin increases to [*]%). Thereafter, Supply Price adjustments shall
be determined by Section 6.1(b) and (c), without retroactive adjustment to
account for the time period between October 1, 200[*] and the date the Margin
improvement described above occurs.
6.2 Payments shall be made by Amarin to Lilly in United States dollars on a
shipment-by-shipment basis based on Lilly's invoice. So long as the Guaranty
between Lilly and Elan is effective, payments shall be made on a net 60-day
basis after the date of invoice, which date shall be no earlier than the
requested date of delivery. After the expiration or earlier termination of the
Guaranty, Amarin acknowledges that Lilly will establish a credit line for Amarin
to facilitate its purchases of Permax(R) and that Lilly may periodically review
and adjust this credit line as it deems appropriate, in accordance with Lilly's
credit approval
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guidelines then in place for customers of equivalent size, history,
creditworthiness and purchase volume, and any other reasonable factors typically
taken into account by Lilly under such guidelines . In consideration for
providing this credit line, Amarin agrees to provide Lilly, upon request, the
financial information reasonably necessary for Lilly to perform credit reviews;
provided, however, that if Amarin does not provide such information, or if
Lilly's analysis of that information does not meet Lilly's standard credit
approval guidelines, then Lilly will have the right to require a letter of
credit (containing terms and conditions reasonably acceptable to Lilly) drawn on
an internationally recognized bank in advance of shipment. Lilly also reserves
the right to ask for cash in advance of shipment should Amarin experience a
condition of insolvency, or if notice of intent to terminate has been issued
pursuant to Section 14. All payments will be made by means of an electronic
funds transfer, as reasonably requested by Lilly to an account designated by
Lilly, except as provided in the prior paragraph.
6.3 Amarin will pay all sales, use, property or similar taxes relating to
Amarin's sales of Permax(R) in the Territory and shall pay all sales, use,
property or similar taxes relating to sales of Permax(R) by Lilly to Amarin
hereunder. Lilly shall pay all sales, use, property of similar taxes relating to
its sale of Permax outside of the Territory. Amarin will be responsible for the
payment of any deductions from gross sales to calculate Net Sales.
6.4 Lilly will provide Bulk Tablets to Amarin for Samples at a price equal to
[*] ([*]) of the Supply Price that would then be in effect for Bulk Tablets
assuming that Section 6.1(c) is never applicable. If Amarin requests Lilly to
Package
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Samples (or if Amarin is unable to comply with all applicable regulatory
requirements to allow Lilly to ship Bulk Tablets to Amarin), Lilly will supply
packaged Samples to Amarin at a price equal to [*] ([*]) of the Supply Price
that would then be in effect for Permax(R) assuming that Section 6.1(c) is never
applicable. In addition to the Supply Pricing for Samples described above, Lilly
shall include a reasonable, mutually agreed up-charge for packaging Samples in
multi-container packaging, which the parties may change from time to time by
mutual agreement.
6.5 Lilly will from the Effective Date provide Amarin with reasonable quantities
of Permax(R) for distribution by Amarin pursuant to the Programs; provided that
such quantities of the 1 mg tablets do not exceed [*] percent ([*] %) of
Amarin's sales of such tablets in any given calendar year. Amarin will
separately account for all strengths and quantities of Permax(R) distributed
under the Programs. Amarin's cost for Permax(R) distributed through the Programs
shall be [*] ([*]) of the then-current Supply Price for Bulk Tablets or Pack
presentation, as the case may be, of the same strength. The quantities of
Permax(R) purchased by Amarin for the Programs shall be separately accounted for
by Amarin at the prices provided for in the previous sentence and aggregated for
each calendar quarter in which Program shipments occur (the "Program Credit").
Program Credit amounts shall be identified as such and applied by Amarin as a
credit against open invoices in any successive quarter, on an ongoing basis,
until all outstanding Program Credits are exhausted.
Lilly and Amarin shall each have the right to inspect the other's
records pertaining to shipments, invoices and payments under the Programs for
the purpose of verifying compliance with this Section 6.5. Such inspections may
occur at reasonable times during normal business hours, upon advance written
request, but no more frequently than once per calendar quarter. Any errors in
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calculation of applicable prices and payments for Program shipments shall be
promptly corrected by payment from the appropriate party.
6.6 Payments due and unpaid under this Agreement shall bear interest from the
date payment is due at an interest rate equal to two percent (2%) above the
average prime rate for the thirty (30) days prior to the date payment is due and
as reported in the Money Rates section of the Wall Street Journal, or similar
reputable source, calculated daily on the basis of a three-hundred sixty (360)
day year.
ARTICLE 7
ORDERING PROCEDURE
7.1 Within thirty (30) days after the Effective Date, Amarin will provide Lilly
with a non-binding five-year forecast of its projected requirements per Pack
strength during each Year. Thereafter, Amarin shall provide a rolling five-year
forecast to Lilly by October 31st of each Year.
7.2 Commencing ninety (90) days prior to the commencement of the second full
calendar quarter after the Effective Date, and ninety (90) days prior to the
beginning of each calendar quarter thereafter, Amarin shall provide Lilly with a
written forecast of its estimated purchase requirements per Pack strength (or
for Bulk Substance or Bulk Tablets, as the case may be) for each quarter in the
ensuing 24-month period. Each first quarter projection in such 24-month forecast
shall be that quarter's "Purchase Requirement". The Purchase Requirement for the
first partial and the first full calendar quarter shall be based upon the last
24-month forecast submitted to Lilly by Amarin or Elan prior to the Effective
Date. Amarin's orders and purchases and Lilly's obligations to supply Permax(R)
shall be subject to the following:
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(a) Each quarter Amarin must purchase at least ninety percent (90%) of
that quarter's Purchase Requirements.
(b) Lilly shall not be obligated to supply in any quarter more than
one-hundred twenty percent (120%) of that quarter's Purchase
Requirement.
(c) Actual orders are to be issued by Amarin to Lilly at least ninety (90)
days in advance of requested delivery dates.
(d) Lilly agrees to maintain in inventory a supply of Permax(R) (either in
Bulk Substance, Bulk Tablets or finished product) equal to the lesser
of ten (10) kg of Bulk Material or an amount sufficient to meet
Amarin's forecast for the two (2) quarters following the most recent
quarter, except to the extent the forecast for such quarters
significantly exceeds prior forecasts. In addition, Lilly also agrees
to maintain in inventory for the Territory an amount equal to the
lesser of ten (10) kg of Bulk Substance or an amount sufficient to
meet Amarin's forecast for the two (2) quarters following the most
recent quarter in inventory for the Territory. The maintenance of the
foregoing inventory levels shall not be required during the period
between the time Lilly depletes its existing Permax(R) inventory and
the time Lilly restocks its inventory with Permax(R) with Amarin's
labeling and trade dress.
On a calendar quarter basis, Lilly shall report to Amarin the total inventory of
Permax(R) held in inventory for the Territory, including Bulk Substance and Bulk
Tablets.
7.3 Lilly will ship the product to Amarin in accordance with Amarin's reasonable
shipping instructions. All shipments will be on an FOB Lilly's U.S. production
facility/distribution center basis. Amarin will pay all costs associated
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with shipping (transportation, insurance, taxes, tariffs, etc.). Title and risk
of loss shall pass to Amarin upon delivery to the carrier.
7.4 Amarin will examine and inspect the product within sixty (60) days of
receipt. Any claims by Amarin for refunds or returns for defective product must
be raised within the inspection period. Lilly's obligation to Amarin for
defective product will be limited to replacing defective product with conforming
product. In no event will Lilly's liability to Amarin exceed the Supply Price
for such product.
ARTICLE 8
CONFIDENTIALITY
8.1 Each party shall use all reasonable efforts to prevent the disclosure of any
Know-How, Improvements or any other information disclosed to it by the other
party under this Agreement without the other party's prior written consent.
Neither party shall use such information for its own benefit or for the benefit
of third parties except for the purpose of performing its rights and obligations
under the Agreement, without the other party's prior written consent.
8.2 This restriction shall not apply to any information which the disclosing or
using party can establish:
(a) is, at the time of use or disclosure, in the public domain
without fault of the disclosing or using party;
(b) was in its possession at the time of receipt and was not
acquired, directly or indirectly, from the other party or an
Affiliate subject to confidentiality relative to the disclosed
information;
(c) was obtained from a third party without restriction as to use or
disclosure, provided, however, that such information was not
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obtained by such third party, directly or indirectly, from the
disclosing or using party; and
(d) has been developed independently of information received from the
other party.
8.3 Nothing in this Section 8 shall prevent the disclosure of information (i) to
those proper governmental agencies or others as part of an initial submission or
to the extent required by law or governmental regulation; and/or (ii) to
consultants, subcontractors and others who have signed an agreement not to use
such information and to keep the information confidential no less restrictive
than as set forth herein.
8.4 The obligations in this Section 8 shall survive the Agreement for five (5)
years as and from the date of termination or expiration of the entire Agreement.
ARTICLE 9
REPRESENTATIONS AND WARRANTIES; CERTAIN COVENANTS
9.1 Lilly warrants that it has the right to grant Amarin the licenses set forth
in this Agreement, except as limited by Athena's or Elan's rights in the ▇▇▇▇ or
Permax(R). Lilly warrants that there is no impediment to Lilly's granting such
licenses or entering into this Agreement, except as limited by Athena's or
Elan's rights in the ▇▇▇▇ or Permax(R). Furthermore, Lilly represents and
warrants to Amarin that:
(a) there is no other patent or other proprietary technology other
than the Know-How, Patent Rights and the ▇▇▇▇ licensed to Amarin
hereunder for which a license would be required for the
manufacture, promotion, distribution and sale by Amarin of
Permax(R) as contemplated by this Agreement;
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(b) Lilly has not granted rights or licenses in derogation of this
Agreement and the Agreement will not be in conflict with any
other material existing agreements to which it is a party;
(c) it knows of no patent or trade secret rights which are owned by a
third party which would be infringed by the practice of the
Patent Rights to manufacture, promote, distribute and sell
Permax(R) in the Territory;
(d) EXHIBIT A contains a complete and accurate listing, with dates of
filing and dates of issuance, of the Patent Rights;
(e) Lilly has not received any communication, and is not aware that
any party had made claim, which challenges or is inconsistent
with any of the statements contained in this Section 9.1;
(f) Lilly is the sole owner of the entire right, title and interest
in and to the Patent Rights listed on EXHIBIT A hereto and the
inventors named in the Patent Rights listed in EXHIBIT A have
assigned such Patent Rights to Lilly.
9.2 Lilly agrees that it shall not enter into any other agreements that conflict
with rights or obligations provided hereunder, including any rights and
obligations that survive termination hereof.
9.3 Lilly covenants that for so long as Amarin has a license to use the ▇▇▇▇
under Section 2.2 and thereafter if the ▇▇▇▇ is assigned to Amarin, neither
Lilly nor Lilly's Affiliates will use the ▇▇▇▇ or any trademark, trade name or
service ▇▇▇▇ confusingly similar to the ▇▇▇▇ within the Territory.
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9.4 Lilly warrants that its manufacture and quality assurance of Permax(R) will
comply to the Specifications and cGMP requirements applicable at the time of
manufacture. Prior to Amarin obtaining its ANDA, Lilly will not make any changes
in the Specifications that will affect Permax(R) to be supplied by Lilly to
Amarin without Amarin's consent, which consent shall not be unreasonably
withheld. After Amarin obtains its ANDA, Amarin will not make any changes in the
Specifications that will affect Lilly's manufacture or Permax(R) for Amarin
without Lilly's consent, which consent shall not be unreasonably withheld.
9.5 Lilly warrants that the products comprising each shipment or other delivery
made by Lilly to Amarin, as of the date of such shipment or delivery, shall be
neither misbranded, nor adulterated within the meaning of the Federal Food, Drug
and Cosmetic Act, or introduced in interstate commerce in violation of Section
505 (New Drug Provisions) of the Act as a result of Lilly's actions.
9.6 Amarin represents and warrants to Lilly that it will comply with the
requirements of the Prescription Drug Marketing Act of 1987 (PDMA) and any
regulations promulgated thereunder. Amarin will comply with written procedures
developed by Amarin. Amarin will forward to Lilly copies of any notices sent to
governmental agencies under the PDMA. Amarin will provide Lilly with copies of
all records required to be maintained under the PDMA on a periodic basis upon
request. Lilly will have the right, upon prior notice and at a mutually
convenient time, to conduct periodic audits of Amarin's records, procedures and
facilities to ensure compliance with the PDMA. Amarin will defend and indemnify
Lilly from and against any claims, actions or liability arising under the PDMA
as a result of Amarin's distribution of Permax(R) samples.
9.7 Lilly and Amarin both represent and certify to the other that they are not
debarred and that they have not and will not use in any capacity the services of
any person who has been debarred under subsections 306(a) or (b) of the Generic
Drug Enforcement Act of 1992 at the time such services are performed.
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9.8 Amarin represents, warrants and covenants to Lilly that:
(a) it has not entered into a material agreement that would conflict
with any of its obligations under this Agreement and Amarin
agrees that it shall not enter into any other agreements that
conflict with rights and obligations provided hereunder,
including any rights and obligation that survive termination
hereof;
(b) it had reasonable access to all information regarding Permax(R)
as deemed necessary by Amarin; and
(c) it shall comply with all applicable local, state and federal laws
and regulations applicable to its activities related to
Permax(R).
ARTICLE 10
INDEMNIFICATION AND INSURANCE
10.1 Amarin shall indemnify and hold Lilly, its officers, directors, employees
and agents harmless from and against any and all liabilities, claims, suits,
damages, losses, costs or expenses (including reasonable attorneys' fees)
(collectively "Claims") incurred by or rendered against Lilly, its officers,
directors, employees and agents to the extent such Claims are caused by (or are
alleged to have been caused by) Amarin's: (i) negligence, gross negligence,
recklessness or willful misconduct, (ii) manufacturing, packaging, testing, use,
labeling, storage, handling, promotion, distribution and sale of Permax, (iii)
breach of any representations, warranty, or covenant under this Agreement, or
(iv) actions in connection with any aspect of Amarin's marketing activity for
Permax(R) (including activity with any third party) (collectively, "Amarin
Activities"). Such indemnification shall not apply to the extent that such
Claims are caused by (or are alleged to have been caused by) Lilly's: (i)
negligence, gross negligence,
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recklessness or willful misconduct, (ii) manufacturing, packaging, testing, use,
labeling, storage, handling, promotion, distribution and sale of Permax(R)
outside the Territory or prior to the date of execution of this Agreement within
the Territory or prior to the date of execution of this Agreement within the
Territory, or (iii) breach of any representations, warranty or covenant under
this Agreement (collectively, "Lilly Activities").
10.2 Lilly shall indemnify and hold Amarin, its officers, directors, employees
and agents harmless from and against any and all Claims incurred by or rendered
against Amarin, its officers, directors, employees and agents to the extent such
Claims are caused by Lilly Activities. Such indemnification shall not apply to
the extent that such Claims are caused by (or alleged to have been caused by)
Amarin Activities.
10.3 Lilly shall promptly notify Amarin of any Claim brought against Lilly for
which Lilly seeks indemnification and shall permit Amarin, at Amarin's cost and
expense, to respond to and control the defense of such Claim. Lilly shall have
the right to participate in any defense to the extent that in its judgment,
Lilly will be prejudiced thereby. In any Claim in which Lilly seeks
indemnification by Amarin, Lilly shall not settle, offer to settle or admit
liability or damages in any such Claim without the consent of Amarin, which
consent shall not be unreasonably withheld.
10.4 Should Amarin seek indemnification from Lilly, Section 10.3 shall apply
reciprocally.
10.5 Each party shall maintain levels of product liability insurance coverage
consistent with general industry standards with respect to its activities as
contemplated by this Agreement. Notwithstanding the foregoing, Lilly may choose
to self-insure and Amarin may self-insure with Lilly's consent, which will not
be unreasonably withheld.
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10.6 In the event of a regulatory action or a private action in connection with
any aspect of Amarin's marketing activity for Permax(R) (including activity with
any third party), Amarin will, in addition to the indemnification obligations
set forth in Section 10.1, above, do the following: (i) act in full cooperating
with Lilly to resolve the action in an expeditious manner; and (ii) reimburse
Lilly for any reasonable internal costs incurred by Lilly in defending,
negotiating or settling the situation with the appropriate government body or
private party. Lilly shall not settle any regulatory or private action without
Amarin's prior written consent, not to be unreasonably withheld.
10.7 The obligations in this Section 10 shall survive termination of this
Agreement.
ARTICLE 11
IMPROVEMENTS
11.1 Improvements made by either party and/or its Affiliates or sublicenses
shall be the property of the party making such Improvements. Both parties will
cooperate as reasonably necessary to perfect title to such Improvements in the
name of the party entitled to same. Each party shall promptly disclose to the
other party the general nature of any Improvements made by it, its Affiliates
and/or sublicensees along with sufficient detail to enable the other to reach a
decision as to whether it desires to commercially develop such Improvements
itself or share the costs of such development based on the relative value of the
Improvements. The parties agree to negotiate in good faith a separate agreement
relating to such development and granting licenses to the other party as set
forth in Section 11.2. No party may initiate any clinical studies on indications
for Permax(R) other than for the management of the signs and symptoms of
▇▇▇▇▇▇▇▇▇'▇ disease as described in Section 4.5 without the other party's
written consent, which shall not be unreasonably withheld.
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11.2 To the extent Lilly is legally free to do so, the separate development
agreement shall grant Amarin a sole license, with a right of sublicense, free of
charge in the Territory to make, use and exclusively sell such Improvements, as
appropriate, pursuant to the terms of this Agreement, except for Lilly's right
to manufacture and distribute such Improvement for its sales to Amarin and its
own sales outside the Territory. To the extent Amarin is legally free to do so,
the separate development agreement shall ▇▇▇▇▇ ▇▇▇▇▇ an exclusive license, with
right of sublicense, free of charge to make, use and sell outside the Territory
any Improvements made by Amarin, its Affiliates and/or sublicensees hereunder
for use only with products containing pergolide.
11.3 After expiration of this Agreement, other than pursuant to Section 14.2
with respect to Improvements made by Lilly or Section 14.3 with respect to
Improvements made by the terminating party, either party shall be entitled to
continue to use and/or develop Improvements made by the other party as provided
in the separate development agreement.
ARTICLE 12
PATENTS AND TRADEMARK INFRINGEMENT
Amarin shall advise Lilly promptly upon Amarin's becoming aware of any
infringement by a third party of the Patent Rights or the ▇▇▇▇. ▇▇▇▇▇ shall
advise Amarin promptly upon Lilly's becoming aware of any infringement by a
third party of the Patent Rights or the ▇▇▇▇ in the Territory. If warranted in
the opinion of ▇▇▇▇▇, ▇▇▇▇▇ shall promptly take such legal action as ▇▇▇▇▇ ▇▇▇▇▇
appropriate to restrain such infringement. Amarin may be represented by counsel
or professional advisors of its own selection at its own expense in any suit or
proceeding brought to restrain such infringement, but Lilly shall have the right
to control the suit or proceeding brought by Lilly. In the event Lilly chooses
not to take legal action to restrain any infringement, it will promptly inform
Amarin of its
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decision not to do so, in which event Amarin shall have the right, at Amarin's
expense, to control any suit or proceeding brought to restrain such
infringement. Each party will cooperate fully with the other in any attempt to
restrain an infringement. Any recovery from a suit or proceeding brought to
restrain infringement in the Territory shall be shared first in proportion to
the costs reasonably incurred by each party in bringing such action or
proceeding and in cooperating in any such action or proceeding, and then once
such costs are paid, shall be shared forty percent (40%) by Lilly and sixty
percent (60%) by Amarin.
ARTICLE 13
FORCE MAJEURE
Neither party shall be responsible to the other for any failure or delay in
performing any of its obligations under this Agreement or for other
non-performance hereof (except for obligations to make payments), provided that
such delay or non-performance is occasioned by a cause beyond the reasonable
control and without fault or negligence of such party, including, but not
limited to act of God, fire, flood, explosion, sabotage, riot, or accident;
delays by suppliers of fuel, power, raw materials, containers, or
transportation; breakage or failure of machinery or equipment, strikes or labor
trouble; or court order or governmental restriction or interference, and
provided that such party promptly informs the other party and that it will again
commence to perform its obligations as soon as possible after the relevant cause
has ceased its effect.
ARTICLE 14
TERM AND TERMINATION
14.1 This Agreement shall become effective on the Effective Date. Unless
extended in writing on mutually agreeable terms and conditions, this Agreement
will expire on April 1, 2008.
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14.2 Notwithstanding the foregoing, Amarin may terminate this Agreement at any
time upon ninety (90) days notice to Lilly, provided that upon the effective
date of such termination, Amarin shall immediately cease all use, promotion,
marketing and sales of Permax(R) and shall immediately assign to ▇▇▇▇▇ ▇▇▇▇▇▇'▇
ANDA and any other regulatory approvals applicable to Permax(R) or Improvements.
Notwithstanding the foregoing, in the event of the termination of this Agreement
by Amarin under this Section 14.2, Amarin shall promptly purchase from Lilly all
inventory held by Lilly with Amarin's labeling and trade dress and Amarin shall
promptly make an accounting to Lilly of Permax(R) as of the date of such
termination and Amarin shall have the right to promote, market and sell its
stock for a reasonable period after the date of such termination sufficient to
sell all inventory, provided, Lilly or a third party designated by Lilly shall
have the right to repurchase the inventory at the Supply Price charged to Amarin
for such inventory.
14.3 Either party may terminate this Agreement immediately by written notice of
termination to the other in the event:
(a) the other party (the "Breaching Party") shall commit a material
breach of any of the provisions of this Agreement and shall not,
within forty-five (45) days (fifteen (15) days for payments that
are past due) of request or written notice of breach by the
non-breaching party remedy such breach. The right of either party
to take this action with respect to breach shall not be affected
in any way by its waiver of or failure to take any action with
respect to any previous breach.
(b) The other party (the "Troubled Party") becomes generally unable
to pay its debts when due or makes an assignment for the benefit
of creditors, has instituted on its behalf or against it
proceedings in voluntary or involuntary bankruptcy (and fails to
aggressively
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defend such involuntary bankruptcy proceeding within ninety (90)
days), or is dissolved, wound up or confiscated, sequestered or
in any other way transferred into state ownership, or has a
receiver or trustee of its property appointed, provided the
non-Troubled Party gives ten (10) days written notice to the
Troubled Party.
14.4 Except as specifically provided in this Agreement, in the event this
Agreement is terminated under Sections 14.2, 14.3 or 14.4, all licenses and
rights granted hereunder to the terminating, Breaching or Troubled Party, as the
case may be, including without limitation any licenses and rights to
Improvements, shall revert to the granting party and all confidential
information and documents containing Know-How held by the other, terminating,
Breaching or Troubled Party shall be returned to the granting party upon its
request, except that one (1) copy of each document may be retained in legal
files for record purposes. In addition, if Amarin is the Breaching or Troubled
Party, Amarin shall immediately, upon such termination, assign to ▇▇▇▇▇ ▇▇▇▇▇▇'▇
ANDA and any other regulatory approvals applicable to Permax(R) or Improvements.
14.5 Lilly may terminate its manufacturing and supply obligations under this
Agreement for any reason at any time upon three (3) years prior notice to
Amarin. Upon such notice of termination, Lilly shall grant to Amarin a sole
license to exclusively manufacture Permax(R) in the Territory, with the right to
sublicense, under the Patent Rights and Know-How, except for Lilly's right to
manufacture Permax(R) for its sales outside the Territory. Within eighteen (18)
months of such termination, Lilly shall provide to Amarin all Know-How
reasonably necessary or desirable for the efficient manufacture of Permax(R)
provided that sales of Permax(R) manufactured by Amarin shall not commence
before such termination without the prior written consent of Lilly.
14.6 No later than three (3) years prior to expiration of this Agreement the
parties shall negotiate in good faith for the terms of a new agreement for the
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continued and uninterrupted supply of Permax(R) for Amarin by Lilly. In the
event the parties are unable to agree on the terms for such supply of Permax(R)
after six (6) months of negotiation, or longer if agreed by Amarin and Lilly,
then in that event Lilly shall, upon expiration of this Agreement, grant to
Amarin a sole license to exclusively manufacture Permax(R) in the Territory,
with the right to sublicense, under the Patent Rights and Know-How, except for
Lilly's right to manufacture Permax(R) for its sales outside the Territory.
Within eighteen (18) months of the expiration of this Agreement, Lilly shall
provide to Amarin all Know-How reasonably necessary or desirable for the
efficient manufacture of Permax(R) provided that sales of Permax(R) manufactured
by Amarin shall not commence before the expiration of this Agreement without the
prior written consent of Lilly.
14.7 Lilly agrees to treat Amarin or an Amarin subcontractor as if Amarin or the
Amarin subcontractor were a Lilly manufacturing facility for purposes of
transferring licenses and Know-How pursuant to Sections 14.5, 14.6 and 15(b).
14.8 Upon the termination of this Agreement for any reason each provision which
is specified to continue beyond such termination shall continue in force and
effect to the extent necessary to effectuate its purpose.
ARTICLE 15
LIABILITY
Notwithstanding anything else to the contrary contained in this Agreement:
(a) Should Amarin fail to comply with its obligations set forth in
Section 3.7, Lilly's sole remedy, after ninety (90) days written
notice to Amarin, should Amarin continue to fail to comply with
such obligations, shall be to convert the exclusive licenses
granted according to Section 2.1 into non-exclusive licenses.
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(b) In the event Lilly should commit a material breach of its
obligation to supply Amarin's requirements of Permax(R) in
accordance with Section 5 and 6.4 hereof and fails to cure such
breach during the period as set forth in Section 14.3(a), Lilly
shall grant to Amarin a license to manufacture Permax(R) in the
Territory, under the Patent Rights and Know-How, except for
Lilly's right to manufacture Permax for its sales outside the
Territory. Lilly shall promptly deliver to Amarin all Know-How
necessary or desirable for Amarin to manufacture or subcontract
the manufacture of Permax(R) and shall cooperate and assist
Amarin in the transfer or use of any License, registrations or
information reasonably required by Amarin to permit Amarin to
manufacture Permax(R).
ARTICLE 16
ASSIGNMENT; SUBCONTRACTING
16.1 Assignment. Except as provided in Section 16.2, neither party may assign
its rights or obligations under this Agreement (other than to Affiliates)
without prior written authorization from the other party, except that an
assignment may be made to a third party acquiring all or substantially all of
the business of Lilly or Amarin, as the case may be, or entering into a merger
with Lilly or Amarin, as the case may be.
16.2 Notwithstanding the foregoing, Lilly may subcontract or assign, in whole or
in part, its obligations to manufacture Permax(R) for Amarin hereunder to a
third-party, provided that such third-party manufacturer agrees to (i) not use
Permax(R) manufacturing Know-How or other information provided by Lilly relating
to Permax(R) other than for the supply of Permax(R) to Amarin or Lilly; and (ii)
such agreement does nor relieve Lilly of its obligations under this Agreement.
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ARTICLE 17
MISCELLANEOUS
17.1 Limitation of Liability. Neither party shall be liable to the other party
for indirect, incidental or consequential damages. Nothing in this Section 17.1
is intended to limit or restrict the rights or obligations of Amarin or Lilly
under Section 10.
17.2 Validity. Should one or several provisions of this Agreement be or become
invalid, then the parties hereto shall substitute such invalid provisions by
valid ones, which in their economic effect come so close to the invalid
provisions that it can be reasonably assumed that the parties would have
contracted this Agreement with those new provisions. In case such provisions
cannot be found, the invalidity of one of several provisions of the Agreement
shall not affect the validity of the Agreement as a whole, unless the invalid
provisions are of such essential importance for this Agreement that it is to be
reasonably assumed that the parties would not have contracted this Agreement
without the invalid provisions.
17.3 Applicable Law. This Agreement shall be construed and the rights of the
parties determined in accordance with the substantive laws of the State of
Delaware, without regard to Delaware choice of law provisions.
17.4 Notice. All notices which are required or may be given pursuant to this
Agreement shall be sufficient upon receipt, if given in writing and delivered by
hand, by electronic media or by registered or certified mail, postage prepaid
and addressed as follows:
If to Lilly, to Vice President, Manufacturing
▇▇▇ ▇▇▇▇▇ and Company
Lilly ▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇
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With a copy to General Counsel
▇▇▇ ▇▇▇▇▇ and Company
Lilly ▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇
If to Amarin Vice-President, Commercial Development
Amarin Corporation, plc
▇▇▇ ▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇, ▇▇▇▇▇ ▇▇▇
▇▇▇▇ ▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇
With a copy to General Counsel & Secretary
Amarin Corporation, plc
▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇ ▇▇▇ ▇▇▇ ▇▇
The address of either party set forth above may be changed from time to time by
written notice in the manner described herein from the party requesting the
change. All payments due under this Agreement shall be payable in United States
dollars at the addresses listed in this Section 17.4 or such other address as
set forth in Lilly's invoice to Amarin.
17.5 Entire Agreement. This Agreement contains the entire understanding of the
parties with respect to the subject matter hereof. No amendment or alteration of
this Agreement shall be valid unless agreed upon by both parties in writing. The
Exhibits to this Agreement shall be considered an integral part hereof.
17.6 Waiver. The waiver by either party hereto of any right hereunder of the
failure to perform or of a breach by the other party shall not be deemed a
waiver of any other right hereunder or of any other breach or failure by said
other party whether of a similar nature otherwise.
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17.7 Obligations. Termination of this Agreement shall not affect obligations
accrued prior to termination.
17.8 Performance by Affiliates. Any party hereto may satisfy any of its
obligations hereunder through any of its Affiliates, provided, however, that
each party guarantees the performance at all times of any such party's
obligations so delegated pursuant to this section.
17.9 Effect of this Amended and Restated License and Supply Agreement. This
Agreement amends and restates the Elan License Agreement. By its effect and upon
execution hereof by the parties, this Agreement shall supersede the Elan License
Agreement, and the Elan License Agreement shall have no further force or effect
as between the parties.
17.10 Media Relations/Public Disclosure. Each party shall provide the other with
as much advance notice as is practical of any proposed use of the other's name
in any written public disclosure or press release. If such a public disclosure
is required by law, rule or regulation, the disclosing party shall provide
copies of the disclosure reasonably in advance of such disclosure for the prior
review and comment by the nondisclosing party's external corporate
communications (public relations) department.
17.11 Survival. The provisions of this Section 17 (other than Section 17.10)
will survive termination or expiration of this Agreement.
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IN WITNESS WHEREOF, the parties hereto have executed this Agreement, in
duplicate originals, by their respective officers thereunto duly authorized, the
day and year herein written.
▇▇▇ ▇▇▇▇▇ AND COMPANY
By: /s/ ▇▇▇▇ ▇. ▇▇▇▇▇▇▇▇▇▇▇
-----------------------------
Title: Executive Vice President
--------------------------
Date: 5/30/02
---------------------------
AMARIN CORPORATION, PLC
By: /s/ ▇▇▇▇▇▇▇ ▇. Coffee
-----------------------------
Title: PRES. AND COO
--------------------------
Date: 6/3/02
---------------------------
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EXHIBIT A
PATENT RIGHTS
Filing Issue
Date Date
------ -------
A. Compound and ▇▇▇▇▇▇▇▇▇'▇ indications
U.S. Patent 4,166,182 2/8/78 8/28/79
U.S. Patent 4,180,582 2/8/78 12/25/79
B. Presently used stabilization method
U.S. Patent 5,114,948 10/19/89 5/19/92
C. Synthetic methods
U.S. Patent 4,782,152 8/16/85 11/1/88
U.S. Patent 5,463,060 5/21/92 10/31/95
D. Additional indications
U.S. Patent 5,416,090 12/8/92 5/16/95
U.S. Patent 5,063,234 4/5/91 11/5/91
E. Additional formulation methods
U.S. Patent 4,797,405 10/26/87 1/10/89
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EXHIBIT B
Permax(R) supplied by Lilly shall conform to the Specifications of Lilly's NDA
and Lilly will use its best efforts to assure that the Permax(R) has a minimum
thirteen (13) months' expiry dating remaining when delivered to Amarin. Should
stability lot production, lot manufacture scheduling problems, special testing
requirements or other factors result in Lilly delivering to Amarin quantities of
Permax(R) with less than thirteen (13) months' expiry dating remaining, Lilly
and Amarin agree to cooperate in arranging distribution of those quantities to
Amarin wholesalers who will accept the expiry dating remaining. If
notwithstanding that cooperation, the Permax(R) with less than thirteen (13)
months' expiry dating remaining when delivered to Amarin is not distributable by
Amarin to its wholesalers, Amarin may return that Permax(R) to Lilly on a full
credit basis.
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