CLOPIDOGREL INTELLECTUAL PROPERTY LICENSE AND SUPPLY AGREEMENT

Exhibit 10.8

* CONFIDENTIAL TREATMENT REQUESTED. CONFIDENTIAL PORTION HAS BEEN FILED

SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION

 

CLOPIDOGREL

INTELLECTUAL PROPERTY LICENSE

AND

SUPPLY AGREEMENT

between

SANOFI

and

SANOFI PHARMA BRISTOL-MYERS SQUIBB

dated as of January 1, 1997

 

 

TABLE OF CONTENTS

 

 

* CONFIDENTIAL TREATMENT REQUESTED. CONFIDENTIAL PORTION HAS BEEN FILED

SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION

ii

 

 

* CONFIDENTIAL TREATMENT REQUESTED. CONFIDENTIAL PORTION HAS BEEN FILED

SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION

iii

 

 

 

* CONFIDENTIAL TREATMENT REQUESTED. CONFIDENTIAL PORTION HAS BEEN FILED

SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION

This CLOPIDOGREL INTELLECTUAL PROPERTY LICENSE AND SUPPLY AGREEMENT (this “ Agreement ”) dated as of January 1, 1997 is hereby made by and between:

Sanofi, a socièté anonyme organized and existing under the laws of the French Republic (“Licensor”); and

Sanofi Pharma Bristol-Myers Squibb, a socièté en nom collectif organized and existing under the laws of the French Republic (the “ SNC Partnership ” and, together with Licensor, the “ Parties ” and, individually, each a “ Party ”).

W I T N E S S E T H :

WHEREAS, Licensor has discovered and patented a new chemical entity known as SR 25990C with the international non-proprietary name Clopidogrel Hydrogenosulphate (“Clopidogrel”), with potential ethical pharmaceutical applications in the cardiovascular therapeutic field;

WHEREAS, Licensor, Bristol-Myers Squibb Company, a Delaware corporation (“SMS”), and Sterling Winthrop, Inc., a Delaware corporation (“ Sterling ”) entered into a Development Agreement dated July 29, 1993 (the “ Development Agreement ”) for, among other things, the development of Clopidogrel;

WHEREAS, pursuant to an Amended and Restated Asset Purchase Agreement dated as of September 30, 1994 among Eastman Kodak Company, Licensor and Sterling, Licensor acquired certain assets, and assumed certain obligations, of the ethical pharmaceutical business of Sterling, including the rights and obligations of Sterling under the Development Agreement;

WHEREAS, Licensor and BMS have entered into a Territory A Alliance Support Agreement dated as of the date hereof (the “ Alliance Support Agreement ”) and have formed through their indirect wholly owned subsidiaries the SNC Partnership pursuant to the statuts to be amended and restated as of June 6, 1997 (the “ SNC By-Laws ”) for, among other things, the commercialization of Clopidogrel Products in Territory A (as such terms are defined herein);

WHEREAS, Licensor, BMS and the SNC Partnership have entered into a Product Know-How License Agreement for Territory A dated as of the date hereof (the “Know-How License Agreement”), pursuant to which Licensor and BMS have granted to the SNC Partnership a license to use certain know-how for the commercialization of Clopidogrel Products and which was developed by Licensor and BMS under the Development Agreement;

 

* CONFIDENTIAL TREATMENT REQUESTED. CONFIDENTIAL PORTION HAS BEEN FILED

SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION

2

 

WHEREAS, Licensor owns or has acquired independent of BMS certain intellectual property, including certain patents, trademarks and know-how, for the commercialization of Clopidogrel Products in Territory A;

WHEREAS, Licensor is willing to grant to the SNC Partnership, and the SNC Partnership is willing to accept, a license under such intellectual property for the commercialization of Clopidogrel Products in Territory A on the terms and conditions set forth herein;

WHEREAS, Licensor and its Affiliates have the exclusive right, subject to the terms and conditions set forth in this Agreement, to provide the active substance chemical bulk containing Clopidogrel (the “ Clopidogrel Bulk ”) that is required for the development, clinical testing and manufacturing of Clopidogrel Products in Territory A; and

WHEREAS, Licensor, either directly or through its Affiliates, is willing to sell to the SNC Partnership, and the SNC Partnership is willing to purchase on an exclusive basis from Licensor or its Affiliates, the Clopidogrel Bulk on the terms and conditions set forth in this Agreement

NOW, THEREFORE, in consideration of the mutual covenants and the terms and conditions set forth herein, the Parties hereby agree as follows:

ARTICLE 1

DEFINITIONS

1.1 Defined Terms. As used in this Agreement, the following terms shall have the following meanings:

“ Adverse Event ” means any negative symptom experienced at the time of or after the taking of any Clopidogrel Product of which any Party or any of its Affiliates becomes aware, whether or not considered drug, related, including, without limitation, any side effects, injury, toxicity or sensitivity reaction, or significant failure of expected pharmacological action, as well as instances of symptomatic overdose, abuse or withdrawal reactions.

“ Affiliate ”, when used with reference to any Person, means any other Person controlling, controlled by, or under common control with, such Person; provided, however , that, with respect to Licensor, the definition of Affiliate shall exclude Elf Aquitaine and any Person not controlled by Licensor that would be an Affiliate of Licensor solely by reason of its being controlled by Elf Aquitaine. For the purposes of this definition, “ control ” shall refer to (a) the possession, directly or indirectly, of the power to direct the management or policies of a Person or to veto any material decision relating to the management of policies of a Person in each case whether through the ownership of voting securities, by contract or otherwise, (b) the beneficial ownership, directly or indirectly, of securities (excluding general partnership interests) representing at least 40% of the voting power of all outstanding voting securities of a Person or (c) the beneficial ownership of at least 50% of the partnership interests of a general partnership. The Parties

 

* CONFIDENTIAL TREATMENT REQUESTED. CONFIDENTIAL PORTION HAS BEEN FILED

SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION

3

 

confirm that each Co-Promotion Entity (as defined in the Alliance Support Agreement) in Territory A shall be considered to be an Affiliate of Licensor.

“ Alliance Agreements ” has the meaning set forth in the Alliance Support Agreement.

“ Alliance Strategic Committee ” has the meaning set forth in the Alliance Support Agreement.

“ BMS Partner ” means BMS Investco S.A.S., a partner in the SNC Partnership.

“ Clopidogrel Intellectual Property ” means the Clopidogrel Know-How and that part of the Licensed Patents relating to Clopidogrel.

“ Clopidogrel Know-How ” means any and all technical data, information, material and other know-how that relate to the manufacturing and purification of the Clopidogrel Bulk, including, without limitation, any analytical methodology, chemical, procedures, protocols, techniques and results of experimentation and testing, solely owned, developed or acquired by Licensor and its Affiliates as of the date hereof.

“ Clopidogrel Product ” means the product or products having as an active ingredient Clopidogrel or any salt, ester, metabolite or pro-drug thereof.

“ Competing Product ” means any product that [*], but which is not [*] set forth in Schedule [*]or selected for [*] by [*].

“ Cost of Bulk ” means (i) during the Exclusive Supply Period, [*] of the Clopidogrel Bulk used in the manufacture of Clopidogrel Products, as more fully described in Schedule 1A attached hereto, and (ii) following the Exclusive Supply Period, [*] for the supply of the Clopidogrel Bulk after the Manufacturing and Sourcing Committee shall have assured the supply of such Clopidogrel Bulk.

“ Development Committee ” has the meaning set forth in the Know-How License Agreement.

“ Exclusive Supply Period ” means the period of time during which Licensor, either directly or through its Affiliates, is the exclusive supplier of the Clopidogrel Bulk to the SNC Partnership.

“ Finance Committee ” has the meaning set forth in the Alliance Support Agreement.

“ Functional Committee ” means any Alliance Functional Committee (as such term is defined in the Alliance Support Agreement) or any License Functional Committee (as such term is defined in the Know-How License Agreement).

 

* CONFIDENTIAL TREATMENT REQUESTED. CONFIDENTIAL PORTION HAS BEEN FILED

SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION

4

 

“ Governmental Authority ” means any federal, state or local or any foreign or supranational government, governmental, regulatory or administrative authority, agency or commission or any court, tribunal or judicial or arbitral body.

“ License Steering Committee ” has the meaning set forth in the Know-How License Agreement

“ Licensed Intellectual Property ” means the Clopidogrel Intellectual Property and the Product Intellectual Property.

“ Licensed Know-How ” means the Clopidogrel Know-How and the Product Know-How.

“ Licenced Patents ” means the patents and patent applications of Licensor and its Affiliates existing on the date hereof relating to Clopidogrel and Clopidogrel Products, including, without limitation, those listed on Schedule 1B attached hereto and all reissues, renewals, divisions, continuations, continuations-in-part, reexaminations, patent term restorations, patents of additions and extensions thereof.

“ Licensed Trademarks ” means the trademarks and registered trademarks and applications for registered trademarks listed on Schedule 1C attached hereto, and the trademarks, the registered trademarks and applications for registered trademarks selected by the Marketing Working Group.

“ Line Extension ” has the meaning set forth in the Know-How License Agreement.

“Loss of Exclusivity” means the loss of exclusivity in any country in Territory A upon the occurrence of all of the three following conditions: (i) a Clopidogrel Product shall have lost its marketing exclusivity (whether by virtue of compulsory license under, or expiration, invalidity or unenforceability of, the patents covering such Clopidogrel Product, loss or expiration of any exclusivity conferred de facto or de jure by any statutory marketing or data exclusivity or any other cause), (ii) one or more Competing Products shall have been legally marketed in such country by one or more Third Parties and (iii) Net Sales of such Clopidogrel Product in such country over any period of [*] (after the conditions set forth in sub-clauses (i) and (ii) above shall have been satisfied) shall have [*] the level of Net Sales of such Clopidogrel Product in such country over the immediately preceding period of [*].

“ MAA ” means any marketing authorizations, licenses, approvals, registrations, certificates and exemptions submitted to or granted by or pending with any Governmental Authority for the purpose of allowing the manufacture, production, supply, marketing, distribution or sale of any Clopidogrel Product in a particular country.

“ Manufacturing and Sourcing Committee ” has the meaning set forth in the Alliance Support Agreement.

 

* CONFIDENTIAL TREATMENT REQUESTED. CONFIDENTIAL PORTION HAS BEEN FILED

SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION

5

 

“ Market Penetration ” means, with respect to one or more Competing Products in any given country in Territory A, the number of units of such Competing Products sold in such country, expressed as a percentage of the sum of (i) the [*]with respect to which [*]constitute [*] and (ii) the [*], in each case over a period of [*], as reported by [*].

“ Marketing Entity ” has the meaning set forth under the definition of Entilé de Marketing in the Règlement Intérieur.

“ Marketing Working Group ” has the meaning set forth in the Know-How License Agreement.

“ Net Sales ” means for any given period and with respect to any Clopidogrel Product, the gross amount invoiced in respect thereof by the Marketing Entities to any Person (excluding any transfers between any Party and its Affiliates solely for purposes of resale, promotional use or clinical trials), less (i) quantity and/or cash discounts, allowances and/or rebates actually allowed or given, (ii) freight, postage and shipping insurance expenses (if separately identified in such invoice), (iii) sales taxes directly related to the sale to the extent included in the gross invoice price (but not including taxes assessed against the income derived from such sale) and (iv) amounts repaid or credited on account of rejections, outdating or the return of such Clopidogrel Product.

“New Drug Application” means the application required to be filed with the relevant Governmental Authority in any country in order to obtain approval to market commercially any Clopidogrel Product in such country.

“ New Indication ” has the meaning set forth in the Know-How License Agreement.

“ Person ” means any individual, partnership, firm, corporation, Société anonyme, Société en nom collectif, Société en participation, limited liability company, joint venture, association, trust or other entity or any government or any agency or political subdivision thereof, as well as any syndicate or group that would be deemed to be a person under Section 13(d)(3) of the U.S. Securities Exchange Act of 1934, as amended.

“ Product Intellectual Property ” means the Product Know-How, the Licensed Trademarks and that part of the Licensed Patents relating to Clopidogrel Products.

“ Product Know-How ” means any and all technical data, information, material and other know-how that relate to the formulation of Clopidogrel Products, including, without limitation, any analytical methodology, chemical, toxicological, pharmacological and clinical data, formulae, procedures, protocols, techniques and results of experimentation and testing, solely owned, developed or acquired by Licensor as of the date hereof.

 

* CONFIDENTIAL TREATMENT REQUESTED. CONFIDENTIAL PORTION HAS BEEN FILED

SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION

6

 

“ Réglement Intérieur ” means the réglement int é rieur to be entered into between the Sanofi Partner and the BMS Partner with effect as of the date hereof.

“ Safety Problem ” has the meaning set forth in the Alliance Support Agreement.

“ Sanofi Partner ” means Sanofi Participations, a partner in the SNC Partnership.

“ Serious Adverse Event ” means any Adverse Event that is life-threatening in that such Adverse Event places the patient at risk of dying, requires hospitalization, prolongs existing hospitalization or results in permanent disability, birth defect, cancer or death.

“ Territory A ” means the countries and geographic areas described and listed in Schedule 1D attached hereto,

“ Third Party ” means a Person who or which is neither a Party nor an Affiliate of a Party.

1.2 Additional Defined Terms. The following additional defined terms shall have the meanings set forth in the sections of this Agreement listed below:

 

 

* CONFIDENTIAL TREATMENT REQUESTED. CONFIDENTIAL PORTION HAS BEEN FILED

SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION

7

 

ARTICLE 2

GRANT OF LICENSE

2.1 License Grant . Subject to the terms and conditions of this Agreement, Licensor hereby grants to the SNC Partnership, and the SNC Partnership hereby accepts:

 

(i)

an exclusive license for the term hereof under the Product Intellectual Property (a) to make, have made, sell, offer for sale and import Clopidogrel Products in Territory A, (b) to develop Clopidogrel Products for Territory A, including, without limitation, New Indications and Line Extensions thereof, and (c) with the prior approval of the Manufacturing and Sourcing Committee, to make, have made and export the Clopidogrel Products outside of Territory A; provided, however, that such exclusivity shall not apply to Sanofi and BMS with respect to the Ongoing Studies (as such term is defined in the Know-How License Agreement), which are being conducted by Sanofi and BMS under the Development Agreement; and

 

(ii)

after the Exclusive Supply Period, an exclusive license for the term hereof under the Clopidogrel Intellectual Property solely for the purpose of making and having Clopidogrel made to produce Clopidogrel Products for Territory A by the entity(ies) approved by Licensor (which approval shall not be unreasonably withheld), which shall include the entity(ies) selected by the Manufacturing and Sourcing Committee.

2.2 No Transfer . The SNC Partnership hereby acknowledges and agrees that this Agreement does not, and shall not be deemed to, transfer any proprietary ownership interest whatsoever to the SNC Partnership in or to the Licensed Intellectual Property. Nothing herein shall give the SNC Partnership any right, title or interest in or to any of the Licensed Intellectual Property, except the rights granted pursuant to this Agreement.

2.3 No Implicit Rights . All of the rights granted hereunder are explicitly stated herein and nothing in this Agreement shall be construed to grant any implied rights whatsoever to the SNC Partnership in or to the Licensed Intellectual Property.

2.4 Goodwill . The SNC Partnership hereby acknowledges that all goodwill connected with the Licensed Trademarks shall inure to the benefit of Licensor, and the SNC Partnership shall not take any action that may be detrimental to such goodwill.

2.5 Improvements . Any new or useful invention, process or improvement, patentable or unpatentable, relating to the formulation of any Clopidogrel Product under the Clopidogrel Intellectual Property developed or acquired by the SNC Partnership during the term hereof shall be the property of the SNC Partnership, which shall have all ownership rights thereto.

 

* CONFIDENTIAL TREATMENT REQUESTED. CONFIDENTIAL PORTION HAS BEEN FILED

SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION

8

 

ARTICLE 3

SUPPLY OF ACTIVE SUBSTANCE CHEMICAL BULK

3.1 Supply during the Exclusive Supply Period. During the Exclusive Supply Period, Licensor shall supply, or shall cause one or more of its Affiliates to supply, as exclusive supplier to the SNC Partnership, the Clopidogrel Bulk required for the development, clinical testing and manufacturing of Clopidogrel Products for Territory A. The price to be paid by the SNC Partnership for the Clopidogrel Bulk shall be based on the Cost of Bulk and shall be paid to Licensor pursuant to Article 6 hereof.

3.2 Supply after the Exclusive Supply Period . (a) The Exclusive Supply Period shall end sixty (60) days following the earlier of:

 

(x)

Licensor shall have given the SNC Partnership and BMS written notice that Licensor’s or its Affiliates’ [*] in Territory A (or in such other geographic area as [*] may identify from time to time) represents or appears likely to represent [*] in Territory A (or in such other geographic area), computed over the [*] immediately preceding the date of such notice; or

 

(y)

Competing Products shall have reached, in the aggregate, [*] in Territory A as determined by the [*] (computed over the [*] immediately preceding the date of such determination).

(b) Promptly after delivery of the notice or determination described in subclause (a) above, the Manufacturing and Sourcing Committee shall ensure the supply of the Clopidogrel Bulk from Licensor, BMS, their respective Affiliates and/or qualified Third Parties and, for the period after the Exclusive Supply Period, shall award, to the extent practicable, the right to supply the Clopidogrel Bulk to the Person(s) that will supply the Clopidogrel Bulk (i) for the lowest price, (ii) in substantially identical quality and quantity to the Clopidogrel Bulk previously supplied by Licensor or its Affiliates and (iii) pursuant to a supply commitment of at least [*]. Notwithstanding the foregoing, upon and after the occurrence of the event described in sub-clause (y) above, Licensor shall continue to be the exclusive supplier thereof for so long as Licensor offers to supply the Clopidogrel Bulk, either directly or through its Affiliates, at a price that is [*]with respect thereto.

3.3 Terms and Conditions of Supply . The Parties shall agree on the other terms and conditions for the supply of the Clopidogrel Bulk during the Exclusive Supply Period, including, without limitation, the payment mechanism thereof.

3.4 Samples. Clopidogrel Products and the Clopidogrel Bulk used as promotional samples shall be sold on a basis to be determined by the Finance Committee.

 

* CONFIDENTIAL TREATMENT REQUESTED. CONFIDENTIAL PORTION HAS BEEN FILED

SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION

9

 

3.5 Manufacturing Improvements . (a) For so long as Licensor, directly or through its Affiliates, is the exclusive supplier of the Clopidogrel Bulk pursuant to Section 3.1 hereof, BMS shall notify Licensor of any proposal to improve the manufacturing process used for the Clopidogrel Bulk and shall offer Licensor, by written notice, the right to participate in the development of such improvement by financing [*] of all development costs incurred after the receipt of such notice.

(b) If Licensor elects to participate in the development of such improvement within ninety (90) days after receipt of such notice and such development results in the issuance of a process patent, (i) the Parties and BMS shall amend and restate this Agreement so that BMS and Licensor shall share equally the economic benefit resulting from such patent and (ii) such patent shall be registered in the name of (x) BMS (who shall grant a license to Licensor with respect to such patent), if the patented process has applications other than in the manufacture of the Clopidogrel Bulk or (y) Licensor, if the patented process has applications only in the manufacture of the Clopidogrel Bulk.

(c) If Licensor does not elect to participate in such development within ninety (90) days after receipt of such notice and the proposed process has applications only in the manufacture of the Clopidogrel Bulk, then BMS shall not undertake any development work on such manufacturing process (whether directly, by licensing, or by transferring its know-how to, a Third Party) until termination of the Exclusive Supply Period.

ARTICLE 4

SUB-LICENSE

4.1 General Sub-License . Except as permitted under Section 4.2 hereof, the SNC Partnership shall not, without the prior written consent of Licensor, sub-license any of its rights and obligations under this Agreement; provided, however, that if the representatives of Licensor on any Functional Committee, the Alliance Strategic Committee or the License Steering Committee consensually agree to sub-license any of the SNC Partnership’s rights or obligations hereunder, such agreement shall be deemed to be Licensor’s consent for the purposes of this Section 4.1. No such sub-license shall relieve the SNC Partnership of its obligations hereunder.

4.2 Sub-License for Alliance Agreements . The SNC Partnership shall sub-license those of its rights and obligations under this Agreement, to any Affiliate of Licensor or BMS that is a party to any Alliance Agreement, solely for the purposes of permitting such Affiliate to perform its obligations under such Alliance Agreement.

4.3 Termination of Sub-License . Licensor shall have the right to require the SNC Partnership to terminate any sub-license hereunder in the event that the sub-licensee fails to comply in any material respect with, or takes any action contrary to, the terms of such sub-license or any decision made by any Functional Committee, the Alliance Strategic Committee or the License Steering Committee, and such sub-licensee has failed to remedy such non-compliance within thirty (30) days from its receipt of written notice thereof