SYNTEX (U.S.A.) INC. - AMERICAN HOME PRODUCTS CORPORATION SUBLICENSE AND SUPPLY AGREEMENT DATED SEPTEMBER 1, 1993 RE: NICARDIPINE IV

 

SUBLICENSE AND SUPPLY AGREEMENT

 

This AGREEMENT is made to be effective as of September 1, 1993 (the “effective date”), by and between American Home Products Corporation (“AMPC”), a corporation organized and existing under the laws of the State of Delaware, acting by the through its Wyeth-Ayerst Laboratories Division (“Wyeth-Ayerst”), having a mailing address at P.O. Box 8299, Philadelphia, Pennsylvania 19101, and syntex (U.S.A.) Inc., a corporation organized and existing under the laws of the State of Delaware, having a business address at 3401 Hillview Avenue, Palo Alto, California 94304 (“Syntex”).

 

RECITALS

 

WHEREAS, Syntex, a wholly-owned subsidiary of Syntex Corporation, is the assignee of the rights of Syntex Corporation granted by Yamanouchi International Limited (“Yamanouchi”) pursuant to an Agreement dated December, 16, 1977 (the “License Agreement”) to make, have made, use and sell the compound nicardipine hydrochloride (USAN), which has the full chemical name 2, 6-dimethyl-4-(3-nitrophenyl)-1, 4-dinydro-pyridine-3, 5-dicarboxylic acid 3-[2-(N-benzyl-N-methylamino] ethyl ester 5-methyl ester hydrochloride, which is also known as YC-93 and RS-69216-003 (the “Agreement Compound”), in certain countries;

 

WHEREAS, Syntex and American Hospital Supply Corporation (“AHSC”), acting through its American Critical Care Division (“ACC”), entered into an Agreement (the “Agreement”) providing for the marketing by ACC of the intravenous form of the Agreement

 

 

Compound in the United States;

 

WHEREAS, E.I. du Pont de Nemours & Company (“du Pont”), a Delaware corporation, acquired certain assets relating to the critical care business of AHSC, and received an assignment, with the consent of Syntex, whereby du Pont succeeded to all of the rights and obligations of AHSC under the Agreement;

 

WHEREAS, Syntex and du Pont entered into an Amendment to the Agreement to substitute “du Pont” for “ACC” throughout the Agreement and to include Canada as part of the Territory covered by the Agreement;

 

WHEREAS, du Pont and Calgon Corporation, a Delaware corporation and a wholly-owned subsidiary of Merck & Co., a New Jersey corporation, entered into a partnership agreement establishing The Du Pont Merck Pharmaceutical Company (“Du Pont Merck”), a Delaware partnership;

 

WHEREAS, du Pont assigned, with the consent of Syntex, its rights under the Agreement (as amended) to Du Pont Merck;

 

WHEREAS, Du Pont Merck desired to be relieved of its obligation to market the Covered Product (as defined below) in the Territory and, in furtherance thereof, has assigned its rights under the Agreement (as amended) to Syntex in contemplation, and with the knowledge, that such rights might be granted to AHPC, acting through Wyeth-Ayerst;

 

WHEREAS, AHPC desires to market, and is capable of marketing

 

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through Wyeth-Ayerst, the intravenous form of the Agreement Compound in the United States;

 

WHEREAS, Syntex desires that AHPC through Wyeth-Ayerst market the intravenous form of the Agreement Compound in the United States and, in furtherance thereof, is willing to sell the Agreement Compound to AHPC in bulk form to be processed by or on behalf of AHPC into the finished intravenous form(s) of the Agreement Compound for distribution and marketing by Wyeth-Ayerst in the United States; and

 

WHEREAS, AHPC is willing to purchase the Agreement Compound from Syntex in bulk form to be processed by or on behalf of AHPC into the finished intravenous form(s) of the Agreement Compound and to have Wyeth-Ayerst distribute and market such finished intravenous form(s) in the United States.

 

NOW, THEREFORE in consideration of the foregoing and of the mutual promises herein contained, AHPC and Syntex do hereby agree as follows:

 

1.                Definitions

 

1.1                                  “Affiliate” of a party shall mean any corporation or any other business entity controlling, controlled by or under common control with such party. “Control” shall mean the direct or indirect ownership of more than fifty percent (50%) of the voting or income interest in such corporation or other business entity. Any reference to Syntex or AHPC shall, unless otherwise expressly

 

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indicated, include reference to Syntex’s or AHPC’s affiliates (as the case may be), as defined in this Section.

 

1.2                                  “Average Net Selling Price” shall mean (a) the aggregate proceeds invoiced by Wyeth-Ayerst for sales of Covered Product (as herein defined) to non-Affiliated purchasers during the Quarter (as herein defined) in question, less (i) trade and cash discounts actually allowed and taken with respect to the Covered Product, (ii) credits or allowances actually allowed and taken for damaged, outdated, returned or recalled Covered Product, (iii) transportation or shipping charges invoiced to such purchasers, (iv) sales taxes imposed directly on such sales of the Covered Product by Wyeth-Ayerst, (v) volume or formulary or other positioning discount amounts paid or credited by AHPC to a wholesaler, purchaser, third party payor or other contractee as a result of a contractual arrangement specific to the Covered Product, (vi) rebates paid or credited by AHPC to any governmental agency (or branch thereof) or to any third party payor, administrator or contractee with respect to sales of the Covered Product, and (vii) discounts paid or credited by AHPC that are mandated by, or granted in response to, applicable federal or state law with respect to sales of the Covered Product, divided by (b) the aggregate number of grams of Agreement Compound contained in the quantities of Covered Product (according to package content as stated on the Covered Product label) invoiced during such Quarter.

 

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1.3                                  “Bulk Product” shall mean the Agreement Compound in unfinished form, having the specifications set forth in Schedule A to this Agreement.

 

1.4                                  “Covered Product” shall mean the Agreement Compound packaged (in other than oral dosage form) for use as an intravenous solution, the specifications of which shall be consistent with and shall conform to the requirements of the United States Food and Drug Administration (“FDA”).

 

1.5                                  “Indications” shall mean use of the Covered Product in the (a) short-term treatment of hypertension when oral therapy is not feasible or not desirable (b) such other indications for the Covered Product as may be approved by the FDA, and (c) use of the Covered Product in such other indications supported by clinical data.

 

1.6                                  “Licensed Patents” shall mean United States Patents Nos. 3,985,758, 4,880,823 and 5,164,405.

 

1.7                                  “Quarter” shall mean each calendar quarter, which shall begin each January 1st, April 1st, July 1st and October 1st during the term of this Agreement, or the portion of a calendar quarter just prior to termination or expiration hereof (as the case may be)

 

1.8                                  “Trademark” shall mean the product mark or marks, whether registered or not, designated by Syntex and owned by Syntex in the Territory for the Covered Product, and shall be the same product

 

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mark or marks used by Syntex in the Territory for its oral dosage forms of the Agreement Compound, which currently is “CARDENE” ^® .

 

1.9                                  “Territory” shall mean the United States of America and any of its territories or possessions, including the Commonwealth of Puerto Rico.

 

2.                Grant of Licenses

 

2.1                                  The grant of licenses are as follows:

 

(a)                                   Syntex grants to AHPC an exclusive sublicense under the License Agreement, including United States Patents Nos. 3,985,758 and 4,880,823, to (i) carry out the processing (including pharmaceutical formulation) and packaging of the Bulk Product into the Covered Product on its own or by a third party manufacturer approved by Syntex in accordance herewith and (ii) have Wyeth-Ayerst market, distribute, promote and sell the Covered Product in the Territory for use in the treatment of the Indications. Syntex represents and warrants that it has the right to grant such a sublicense under the License Agreement and the Licensed Patents listed above in this Section 2.1(a) and that such sublicense will not violate the rights of any party not a party hereto, including, without limitation, Yamanouchi, AHSC, du Pont and Du Pont Merck. In the event Syntex loses that right, this Agreement shall be terminated forthwith, but Syntex shall attempt, in good faith, to secure from Yamanouchi AHPC’s right to continue to manufacture, market, distribute, promote and sell the Covered Product in the

 

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Territory for use in the treatment of the Indications upon terms and conditions comparable to those set forth herein.

 

(b)                                  Syntex grants to AHPC an exclusive license under United States Patent No. 5,164,405 to (i) carry out the processing (including pharmaceutical formulation) and packaging of the Bulk Product into the Covered Product and (ii) have Wyeth-Ayerst market, distribute, promote and sell the Covered Product in the Territory for use in the treatment of the Indications. Syntex represents and warrants that it has the right to grant such a license under United States Patent No. 5,164,405.

 

(c)                                   Subject to Syntex’s right to detail and promote the Covered Product as set forth in Section 6.6 below, the licenses granted to AHPC in Sections 2.1(a) and 2.1(b) above are exclusive even as against Syntex.

 

(d)                                  Syntex grants to Wyeth-Ayerst a license to use the Trademark only with respect to the marketing, distribution, promotion and sale of the Covered Product in the Territory during the term of this Agreement, subject to the terms and conditions set forth herein.

 

2.2                                  (a)                                   AHPC, on behalf of itself and Wyeth-Ayerst, hereby accepts the rights granted in Section 2.1 above and agrees to endeavor in good faith to process (including pharmaceutical formulation), package, market, distribute, promote and sell the Covered Product in the Territory at its own expense under the

 

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Trademark for any and all of the Indications, using generally the same channels and methods, exercising the same diligence and adhering to the same standards that Wyeth-Ayerst employs in processing (including pharmaceutical formulation), packaging, marketing, distributing, promoting and selling its own pharmaceutical products in the Territory. Wyeth-Ayerst shall, in its sole discretion, determine its prices and other terms and conditions for sales of the Covered Product to third parties.

 

2.2                                  (b)                                  In view of the fact that the FDA has approved the marketing of the Covered Product in the United States for the treatment of hypertension, AHPC and Syntex agree that it would be to the benefit of both parties, and the consuming public, if the Covered Product is launched in the Territory for that Indication as soon as is possible. Accordingly, the parties agree that:

 

(i)                                      AHPC and Wyeth-Ayerst shall endeavor in good faith to have One Hundred Thousand ampoules of non-shortdated, saleable (i.e., released) Covered Product in inventory by November 1, 1993; and

 

(ii)                                   AHPC, Wyeth-Ayerst and Syntex shall work together and endeavor in good faith to (x) review and submit promotional launch materials to the FDA as soon as possible and (y) assist the FDA in its review of such materials, including meeting with the FDA to seek and obtain FDA approval of such materials by November 1, 1993.

 

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If both (i) and (ii) above occur, then Wyeth-Ayerst shall launch the Covered Product in the Territory for that Indication by November 1, 1993. If (i) above is not achieved, after good faith pharmaceutical manufacturing efforts by AHPC and Wyeth-Ayerst (in conjunction with Berk (U.K.) to do so, launch may be delayed by Wyeth-Ayerst until December 1, 1993, but not beyond that date without the prior written approval of Syntax, which shall not unreasonably be withheld. If the FDA approval contemplated by (ii) above has not been obtained, after good faith efforts to obtain such approval, then launch may be delayed until such materials have been approved by the FDA.

 

2.3                                  Only Wyeth-Ayerst and not any Affiliate (s) thereof, shall market, distribute, promote (subject to Syntex’s right to detail and co-promote as set forth in Section 6.6 below) and sell the Covered Product in the Territory, unless Syntex agrees in writing to such activities being conducted by an Affiliate of Wyeth-Ayerst, such agreement by Syntex not to be unreasonably withheld.

 

3.                Supply of Bulk Product

 

3.1                                  Syntex shall supply, and AHPC shall purchase, all quantities of Bulk Product that AHPC requires to process, package, market, distribute, promote and sell the Covered Product in Territory, such supply and purchase to be in accordance with the following provisions of this Agreement. AHPC shall use all Bulk

 

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Product supplied by Syntex only to manufacture Covered Product for use or sale in the Territory for the Indications or for research purposes in support of such use or sale.

 

3.2                                  (a)                                   Syntex agrees that all quantities of Bulk Product supplied hereunder shall meet the specifications set forth in Schedule A attached hereto and made a part hereof, which shall conform to or be amended to conform to all applicable governmental requirements (whether or not contained in governmental regulatory approvals) in the Territory. In addition, Schedule A may be amended from time to time by written agreement of the parties. Syntex, with each quantity of Bulk Product supplied hereunder, shall provide AHPC with a Certificate of Analysis documenting that such Bulk Product complies with the specifications therefor as set forth in Schedule A hereto as determined according to the methods of analysis referenced in such specifications.

 

3.3                                  (b)                                  All Bulk product received by AHPC shall be deemed accepted, unless AHPC shall give written notice to Syntex within thirty (30) days after receipt of such Bulk Product specifying the manner in which the Bulk Product does not conform to the specifications therefor. Such notice shall be accompanied by written reports of any testing performed by AHPC on the Bulk Product. Upon receipt of such notice, Syntex may request AHPC to return the non-accepted Bulk Product, or samples thereof, for further testing by Syntex. AHPC’s test results shall be conclusive

 

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unless Syntex notifies AHPC within thirty (30) days after receipt by Syntex of the non-accepted Bulk Product, or samples thereof, that it disagrees with such test results. In the event of such notice of Syntex, (i) AHPC, to the extent necessary or required, shall conduct an investigation to determine if there are legally sufficient grounds upon which to invalidate its test results that suggested non-conformance of such Bulk Product with the specifications therefor, and (ii) the Bulk Product, or samples thereof, shall be submitted to a mutually acceptable independent laboratory for analysis. The results of the independent testing laboratory shall be binding upon AHPC and Syntex for the purposes of acceptance of, and the obligation to pay for, such Bulk Product. The costs of the independent testing laboratory shall be paid by the party against whom the discrepancy is resolved. In the event any Bulk Product not accepted by AHPC does not meet the specifications therefor as determined in accordance with this Section 3.2, Syntex will give AHPC full credit for such Bulk Product at the price invoiced by Syntex or paid by AHPC and will replace such Bulk Product with conforming Bulk Product to be invoiced at the original invoice price per gram. All transportation, shipping and insurance cost, and other fees incident to the shipping of such replacement (to the extent previously paid by AHPC with respect to the non-conforming Bulk Product) will be paid for by Syntex. Such replacement shall be

 

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made immediately upon written request by AHPC (so as to be able to maintain scheduled pharmaceutical manufacturing dates) or, if no such request is made, then within sixty (60) days after it is determined by the independent laboratory or agreed by both parties hereto that the Bulk Product was non-conforming unless the parties agree in writing to another delivery date.

 

3.2                                  (c)                                   Wyeth-Ayerst and Syntex agree that Syntex shall prepare and file, with the assistance and cooperation of Wyeth-Ayerst, the necessary documentation with the FDA to substitute Syntex’s Quality Control Method-QC-1203 (Limulus Amebocyte Lysate (LAL) gel clot test for bacterial endotoxins) as the NDA specification for pyrogens in place of the USP (151) rabbit test, which is less preferable to both parties.

 

3.2                                  (d)                                  Wyeth-Ayerst and Syntex agree that Syntex shall prepare, with the assistance and cooperation of Wyeth-Ayerst, and file with the FDA a U.S.P. monograph referencing the best analytical methods for the Covered Product (selected from the USP methods referenced in the attachment to Schedule A hereto, Syntex’s Quality Control methods for the Bulk Product, and the LAL method referred to in Section 3.2(c)), such filing being done for the purpose of establishing new methods of analysis (acceptable to the FDA) for the Bulk Product to be supplied by Syntex, and purchased by AHPC or Wyeth-Ayerst, hereunder.

 

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3.3                                  (a)                                   In connection with AHPC’s first purchase of Bulk Product, AHPC shall give Syntex written notice of the amount of such initial order prior to the execution and delivery hereof by the parties hereto. In connection with each subsequent order, AHPC shall provide Syntex with a written estimate during the first month of each Quarter as to the amount that it desires for delivery during the next succeeding Quarter. AHPC agrees to submit its firm order for the Bulk Product at least sixty (60) days prior to the desired delivery date and Syntex agrees to ship the Bulk Product to AHPC within sixty (60) days after receipt of AHPC’s firm order. Syntex will fill AHPC’s firm orders up to twice the amount specified in the Quarterly estimate applicable thereto (in five (5) kilogram pack increments, unless otherwise agreed to in writing by the parties), and will, in good faith, attempt to fill the balance (if any) as soon as possible, due consideration being given to Syntex’s own needs and the needs of the other parties to which it supplies the Bulk Product.

 

3.3                                  (b)                                  With respect to Covered Product that is pharmaceutically formulated outside the Territory, title to any quantities of Bulk Product sold by Syntex to AHPC for use in such formulation shall pass to AHPC upon delivery by Syntex to AHPC at Syntex’s European depot (currently Antwerp, Belgium) or such other Syntex facility as may be agreed to in writing by the parties. With respect to Covered Product that is pharmaceutically formulated

 

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in the Territory, title to any quantities of Bulk Product sold by Syntex to AHPC for use in such formulation shall pass to AHPC upon delivery by Syntex to AHPC at any Syntex warehouse in the United States (currently Columbus, Ohio). AHPC shall select the common carrier and determine the method of transportation and routing for all shipments of Bulk Product and shall pay (and be responsible for) all freight and insurance costs therefor.

 

3.4                                  (a)                                   The price of Bulk Product shall be, on a per gram basis for Bulk Product supplied by Syntex hereunder, [*] percent ([*]%) of the Average Net Selling Price (as defined in Section 1.2 above) in the Territory during the Quarter in which such Bulk Product is shipped times the number of grams of Bulk Product so shipped by Syntex.

 

3.4                                  (b)                                  An initial price per gram shall be invoiced by Syntex and paid by AHPC, which shall be equal to the actual price per gram calculated as above for the most recently reported Quarter (due to inherent time lag in the filing of Quarterly reports hereunder, the actual price for any given Quarter will become the estimated or invoice price for the second quarter thereafter, subject, or course, to the retroactive adjustment set forth in Section 3.4(c) below). The initial price per gram for orders for commercial quantities shipped to AHPC during the Quarter or Quarters immediately prior to commercial launch of the Covered Product in the Territory shall be [*] percent ([*]%) of

 

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Wyeth-Ayerst’s estimated initial ex-factory price of Covered Product, set by Wyeth-Ayerst in good faith.

 

3.4                                  (c)                                   Within sixty (60) days after the end of each Quarter, AHPC shall calculate the actual price due Syntex hereunder and shall give Syntex written notice thereof. Such notice shall specify all information on which the calculation is based as well as stating the actual price due. If the initial price paid by AHPC was less than the price actually due Syntex, AHPC shall remit to Syntex the difference together with its notice. If the initial price was greater than the price actually due Syntex, Syntex shall apply such difference as a credit against future purchases of Bulk Product hereunder, and upon termination or expiration of this Agreement, Syntex shall remit to AHPC within forty-five (45) days after receipt to such notice any credit(s) that have not been exhausted by subsequent purchases of Bulk product.

 

3.4                                  (d)                                  In the event there is a verifiable rejection of all or a substantial portion of a batch of Covered Product during the manufacture thereof and the loss associated with such rejection is not covered by insurance, Syntex shall replace the quantity of Bulk Product included within the rejected Covered Product for an additional price, on a per gram basis for each gram of Bulk Product supplied under this Section 3.4(d), of [*] percent ([*]%) of the price paid or to be paid by AHPC with respect thereto pursuant to Sections 3.4(a) or 3.4(b) above (i.e., [*] percent ([*]%) of

 

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[*] percent ([*]%), which is equal to [*] percent ([*]%) of the Average Net Selling Price, on a per gram basis).

 

3.4                                  (e)                                   Payment for each purchase of Bulk Product hereunder plus any other charges due Syntex shall be paid by AHPC forty-five (45) days after the date of Syntex’s invoice for each such purchase and shall be paid by AHPC in United States Dollars.

 

3.4                                  (f)                                     AHPC shall be responsible for and pay any and all customs duties, brokerage fees, excise, sales or use taxes, and other governmentally-imposed taxes (if any) incurred directly with respect to the shipment of Bulk Product supplied by Syntex hereunder of Covered Product shipped by AHPC of Wyeth-Ayerst hereunder, and shall pay or reimburse Syntex upon demand for customs duties, brokerage fees, excise, sales or use taxes or other governmentally-imposed taxes (if any) imposed directly by any taxing authority with respect to the sale of the Covered Product.

 

3.5                                  (a)                                   For each [*] grams of Bulk Product purchased by AHPC at the [*] percent ([*]%) price set forth in Section 3.4 above through June 30, 1995, Syntex shall provide [*] grams of Bulk Product free of any charge under Section 3.4(a) above (AHPC shall, however, be responsible for all freight, insurance, customs duties, brokerage fees, excise, sales or use taxes and other governmentally-imposed taxes (if any) referred to in Section 3.3(b) and 3.4(f) above). This material is

 

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provided by Syntex to assist AHPC with estimated yield losses of [*] percent ([*]%) during pharmaceutical formulation of the Bulk Product into the Covered Product.

 

3.5                                  (b)                                  Syntex will also provide such assistance to AHPC for the first six (6) months of pharmaceutical formulation of the Bulk Product into the Covered Product by AHPC (or Wyeth-Ayerst) in its own facilities even if such assistance extends beyond June 30, 1995, but such assistance by Syntex for all or any portion of such six (6)-month period after June 30, 1995 will only be applicable to that Bulk Product purchased by AHPC for pharmaceutical formulation in its (or Wyeth-Ayerst’s) facilities, unless otherwise agreed to in writing by Syntex.

 

3.5                                  (c)                                   During the Quarter ending June 30, 1995, and after completion of six (6) months in-house production experience by AHPC (or Wyeth-Ayerst) (if later), AHPC (or Wyeth-Ayerst) and Syntex shall meet to discuss what level of yield loss assistance Syntex, in its sole discretion, considers appropriate under the circumstances (given the formulating experience by or on behalf of AHPC to that time) and will thereafter make available to AHPC (or Wyeth-Ayerst).

 

3.6                                  (a)                                   For each [*] grams of Bulk Product purchased by AHPC at the [*] percent ([*]%) price set forth in Section 3.4 above, Syntex shall provide [*] grams of Bulk Product free of any charge under Section 3.4(a) above (AHPC

 

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shall, however, be responsible for all freight, insurance, customs duties, brokerage fees, excise, sales or use taxes and other governmentally-imposed taxes (if any) referred to in Sections 3.3(b) and 3.4(f) above), which free material shall be in support of AHPC’s (or Wyeth-Ayerst’s) importation, packaging, marketing, distributing, promoting (including sampling) and selling of the Covered Product. This support shall only apply for that period of time when the Covered Product is pharmaceutically formulated outside the United States and a duty on the formulated Covered Product must be paid upon importation thereof into the United States. Thereafter, the support of Syntex under this Section 3.6 shall be limited to [*] grams per each [*] grams of Bulk Product purchased by AHPC at the [*] percent ([*]%) price set forth in Section 3.4 above

 

3.6                                  (b)                                  AHPC shall provide written documentation showing duties paid by AHPC upon important of the Covered Product into the United States for so long as the Covered Product is pharmaceutically formulated outside the United States, duties are paid upon the importation thereof into the United States, and support is sought by AHPC under Section 3.6(a) above for such duties.

 

4.                Development Work and Regulatory Approvals

 

4.1                                  Upon execution of this Agreement and periodically thereafter, Syntex shall provide AHPC, subject to the provisions of

 

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Section 11 below, relevant information and data developed by it with respect to the agreement Compound, the Bulk Product and/or the Covered Product. Syntex shall continue to provide such information and data that is relevant to additional development work to be undertaken by AHPC with respect to the Covered Product during the term of this agreement. Syntex shall provide written consent directly to the FDA to permit AHPC to refer to Syntex’s Notice of Claimed Investigational Exemption for New Drug and New Drug Application (“NDA”) for the Agreement Compound, and all information relating to the manufacture and control of the Bulk Product, with respect to development work that is conducted by AHPC in accordance with this agreement.

 

4.2                                  (a)                                   Syntex shall make available to AHPC all information received from Du Pont Merck that Du Pont Merck has developed for a subarachnoid hemorrhage indication for the Covered Product (the “SAH Indication”). AHPC shall promptly review such information and determine, in good faith, if in AHPC’s judgment the development of the SAH Indication is appropriate or desirable.

 

4.2                                  (b)                                  If the development of the SAH Indication is considered appropriate or desirable by AHPC, then AHPC shall conduct all clinical tests and develop all technical data reasonably necessary to seek FDA approval for the SAH Indication. The NDA for the SAH Indication to be submitted to the FDA shall be reviewed and approved by Syntex in writing in advance of submission

 

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to the FDA. In addition, AHPC shall provide Syntex fifteen (15) working days to review all data, including all technical and clinical data (including summaries thereof), to be submitted by Syntex to the FDA. All such data, and the back-up data pertaining thereto, shall be available for inspection and review by Syntex at any reasonable time, and copies thereof shall be promptly provided to Syntex upon Syntex’s written request therefor. AHPC shall use reasonable efforts to complete the SAH studies (but may terminate its efforts at any time in its sole discretion) and shall file, in Syntex’s name, NDA or a supplemental NDA for the SAH Indication. All technical and clinical data developed by AHPC in support of the SAH Indication shall be and remain the property of AHPC. Syntex shall, however, own any resulting registration and AHPC shall ensure that any such registration (including all right, title and interest thereto) is issued in Syntex’s name.

 

4.2                                  (c)                                   At least semi-annually, AHPC shall provide to Syntex a written report on any development undertaken by AHPC of the SAH Indication.

 

4.2                                  (d)                                  In addition to any reports provided to Syntex by AHPC under Section 4.2(c) above, SAH Indication review meetings shall be held at least annually at locations to be agreed on until the NDA or supplemental NDA for the SAH Indication is approved. At such meetings, AHPC shall report on its progress in the development of the SAH Indication for the Covered Product. Each party hereby

 

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designates the person listed in Schedule B as its clinical co-ordinator to receive and respond to inquiries during the regulatory phase concerning the SAH Indication and to make arrangements for the joint review meetings.

 

4.3                                  (a)                                   Syntex shall have and retain ownership of the NDA for the Covered Product. Syntex shall inform the FDA in writing that AHPC, acting through Wyeth-Ayerst, has become Syntex’s exclusive sub-licensee of the Covered Product in the Territory and will have the right, in conjunction with Syntex, to interact with the FDA with respect to the NDA pertaining thereto, subject to the terms and conditions hereof.

 

4.3                                  (b)                                  Each party shall promptly provide to the other copies of all correspondence received from the FDA concerning the Covered Product, and shall advise each other within ten (10) working days of any oral communications that it receives from the FDA concerning the Covered Product.

 

4.3                                  (c)                                   Unless otherwise required by law, or required by the FDA in written correspondence with Wyeth-Ayerst, or by this agreement, Wyeth-Ayerst shall provide Syntex fifteen (15) working days to review and approve correspondence to the submitted by Wyeth-Ayerst to the FDA with respect to the Covered Product (if the FDA requires that the correspondence be submitted to the FDA in less than fifteen (15) days, then Wyeth-Ayerst shall provide Syntex at least two (2) full working days to review and approve such

 

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correspondence). Wyeth-Ayerst shall not submit any such correspondence that is objected to by Syntex in good faith, unless required by law or the FDA in writing. Syntax agrees to make all necessary filings to the FDA with respect to the NDA for the Agreement Compound, including Annual Reports (21 C.F.R. 314.80(c) (2)) and promotional submissions (21 C.F.R. 314.81(b) (3) (i), as are (i) prepared by Wyeth-Ayerst, provided on a timely basis by Wyeth-Ayerst to Syntex, and reviewed and approved by Syntex in accordance with the provisions of this Agreement, or (ii) prepared by Syntex (e.g., periodic or increased frequency adverse drug event reports (21 C.F.R. 314.81(b) (2) and provided by Syntex to Wyeth-Ayerst for comment prior to any such filing.

 

4.3                                  (d)                                  Each party shall inform the other party of any meetings scheduled with the FDA concerning the Covered Product and shall provide the other party the opportunity to review and approve any submissions (including promotional materials and labeling) to be sent to, reviewed by, or any presentations to be made to, the FDA with respect to the Covered Product and to have representatives present at any meetings pertaining to the Covered Product; provided, however, that Syntex, by virtue of its ownership of the NDA for the Covered Product, shall be the primary contact with the FDA, unless the parties agree otherwise in writing.

 

4.3                                  (e)                                   Syntex’s approval under this Section 4.3 shall not be unreasonably withheld, but may be withheld, in Syntex’s sole

 

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discretion, if Syntex considers, in good faith, that any Wyeth-Ayerst correspondence or presentation will have an adverse impact on the other dosage forms of the Agreement Compound that are being marketed in, or being developed for, the Territory by or on behalf of Syntex.

 

4.3                                  (f)                                     Syntex agrees, subject to the review and approval procedures set forth in this Agreement, to submit to the FDA Supplementary data supplied to Syntex by AHPC or Wyeth-Ayerst to permit AHPC or Wyeth-Ayerst to manufacture and test the Covered Product in its facilities, and to substitute supplementary or alternative packaging designs or Covered Product presentations that Wyeth-Ayerst desires. Subject to the terms and conditions of this agreement, all data developed by AHPC or Wyeth-Ayerst in support of such submissions to the FDA shall be and remain the property of AHPC or Wyeth-Ayerst.

 

4.4                                  All data developed by AHPC or Wyeth-Ayerst for the United States NDA or supplemental NDA may be used by Syntex for filing applications for government registration in countries outside the Territory and in supporting FDA filings for other products containing the Agreement Compound. AHPC and Wyeth-Ayerst shall provide to Syntex without charge all data requested by Syntex for this purpose and hereby consents to Syntex’s use of such data for the sole purposes of obtaining foreign registrations in any and all countries outside the Territory and formulating, packaging,

 

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distributing, marketing, promoting and selling the products covered by such registrations pursuant thereto. Syntex agrees to keep all such data confidential in accordance with Article 11 hereof, and shall not use such data except as provided for herein. Neither AHPC nor Wyeth-Ayerst shall be required to develop data to be used solely for Syntex’s needs or desires outside the Territory, unless AHPC or Wyeth-Ayerst is willing to do so upon terms and conditions to be agreed upon in writing by the parties.

 

4.5                                  As an inducement for Syntex to continue to furnish information and data pertaining to the Agreement Compound and the Bulk Product, to cooperate in filing and obtaining approval of any NDA for the SAH Indication, to provide subsequent information (including trade secrets and other confidential information relating to the marketing of products containing the Agreement Compound), and to grant to AHPC the exclusive rights to the Covered Product in the Territory (as set forth herein), including with respect to the currently approved NDA for certain indications for the Covered Products, AHPC, on behalf of itself and Wyeth-Ayerst, agrees that it shall not manufacture or sell in the Territory, or apply for FDA approval to manufacture or sell in the Territory, any product containing the Agreement Compound except the Covered Product during the term of this agreement. This provision shall not preclude AHPC from manufacturing

 

Covered Product (a) in the Territory with Bulk Product purchased

 

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from Syntex hereunder for sale by Wyeth-Ayerst in accordance with this agreement or (b) for Syntex for countries outside the Territory pursuant to separate written agreements between the parties.

 

5.                Trademarks and Quality Control

 

5.1                                  The use of the Trademark by Wyeth-Ayerst shall be governed by the following provisions:

 

(a)                                   Syntex shall have equitable and legal ownership of the entire right, title and interest in and to the Trademark.

 

(b)                                  Syntex shall file and maintain registration of the Trademark in the Territory, and neither AHPC, Wyeth-Ayerst nor any of their respective Affiliates shall obtain any right, title of interest in the Trademark, except the right to use the Trademark on the Covered Product pursuant to this Agreement.

 

(c)                                   If AHPC or Wyeth-Ayerst becomes aware that a third party is infringing any of Syntex’s rights with respect to the use of the Trademark on the Covered Product, AHPC or Wyeth-Ayerst shall give notice to Syntex of such infringement. Syntex may, at its sole discretion, bring legal action to restrain such infringement and for damages, and AHPC and Wyeth-Ayerst agree to cooperate at their own expense in any such action involving the Covered Product. If within six (6) months after receipt of such notice, Syntex does not effect a cessation of such infringement or institute a legal action for infringement, then AHPC or Wyeth-Ayerst shall have the right,

 

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at their own expense, to bring suit against any such infringing party. If such a suit by AHPC or Wyeth-Ayerst is successful, AHPC or

Wyeth-Ayerst shall be entitled to any monetary recovery obtained. If AHPC or Wyeth-Ayerst elects to bring such action, it agrees to fully indemnify Syntex for any costs, expenses or losses incurred by Syntex as a result of any such action. Syntex reserves the right to intervene in any such action at its own expense. AHPC or Wyeth-Ayerst shall only have the right to bring a trademark infringement or related action in the Territory against a third party who uses the precise Trademark on the precise Covered Product, and nothing herein shall grant AHPC or Wyeth-Ayerst the right to otherwise enforce the Trademark. AHPC or Wyeth-Ayerst shall not settle any such suit without the prior written approval of Syntex.

 

(d)                                  Each Covered Product processed and distributed by Wyeth-Ayerst shall bear a Trademark and a label approved by Syntex featuring the Wyeth-Ayerst name and the Syntex name in a manner acceptable to the FDA and to both parties. Neither party, by virtue of this agreement, obtains any rights whatsoever in the