LICENSE AGREEMENT

1.1

“Agreement” shall mean the License Agreement entered into by and among BTG, Duke and MVP on August 12, 1998.

1.3

“Amendment Date” shall mean November 12, 2001.

3.1

This amendment is conditioned upon the payment to MVP by BTG (by wire transfer) of $[**], (consisting of $[**] allocated to Milestone No. 4 and $[**] allocated to Milestone No. 5), as an advance payment in partial satisfaction of the payments due under Milestone Nos. 4 and 5.

3.2

Except as expressly modified in this Amendment, the Agreement shall remain in full force and effect according to its terms.

BlO-TECHNOLOGY GENERAL CORP.
 

By:  

/s/ Norman Barton  

Name:  

Norman Barton 

Title:  

Chief Medical Officer 

DUKE UNIVERSITY
 

By:  

/s/ Robert L. Taber  

Name:  

Robert L. Taber, Ph.D. 

Title:  

Vice Chancellor. Science & Tech. Dev. 

MOUNTAIN VIEW PHARMACEUTICALS, INC.
 

By:  

/s/ Mark Saifer  

Name:  

Mark Saifer 

Title:  Vice President

2.1

“AFFILIATES” of a person or an entity shall mean any individual, sole proprietorship, firm, partnership, corporation, trust, joint venture or other entity, whether de jure or de facto, which, directly or indirectly, controls, is controlled by or is under common control with such person or entity. As used in this definition, “control” means the possession, directly or indirectly, of the power to direct or cause the direction of the policies and management of a person or entity, whether by the ownership of stock, by contract or otherwise.

2.3

“BIRD” shall mean the U.S.-Israel Binational Industrial Research and Development Foundation.

2.5

“DUKE” shall mean Duke University, a North Carolina not-for-profit corporation, having its principal office at Durham, North Carolina 27710, and its AFFILIATES.

2.6

“DUKE TECHNOLOGY” shall mean technologies conceived, reduced to practice, developed, or acquired, by or for DUKE, or licensed to DUKE, or developed jointly with MVP, relating to mammalian urate oxidase (mammalian uricase), including the know-how and other information described in detail in Exhibit A attached hereto and made a part hereof, as of the EFFECT1VE DATE, and including any improvement made by DUKE thereon during the TERM of this AGREEMENT, for use in the FIELD; provided, however, that with respect to such improvements DUKE shall promptly disclose each such improvement to BTG and it shall be included in the license only if, within six (6) months after disclosure, BTG elects to incorporate the improvement into LICENSED PRODUCTS or the manufacturing process thereof.

2.8

“FIELD” shall mean the treatment of humans.

2.10

“IMPUTED NET SALES” shall have the meaning ascribed to it in Section 2.17(a).

2.12

“LICENSED PRODUCTS” shall mean any products (including all dosage forms, strengths, and package sizes) that utilize TECHNOLOGY in whole or in part.

2.14

“LICENSOR” shall mean MVP, DUKE or both of them, depending on the context.

2.16

“MVP TECHNOLOGY” shall mean technologies conceived, reduced to practice, developed, or acquired, by or for MVP, or licensed to MVP, or developed jointly with DUKE, relating to mammalian urate oxidase (mammalian uricase) and non- mammalian urate oxidase (non-mammalian uricase) and PEG conjugates of both mammalian uricase and non-mammalian uricase, including the know-how and other information described in detail in Exhibit B attached hereto and made a part hereof, as of the EFFECTIVE DATE, including any improvements made by MVP thereon during the TERM of this AGREEMENT, for use in the FIELD; provided, however, that with respect to such improvements, MVP shall promptly disclose each such improvement to BTG and it shall be included in the license only if, within six (6) months after disclosure, BTG elects to incorporate the improvement into LICENSED PRODUCTS or the manufacturing process thereof.

(a)

In the event that the LICENSED PRODUCTS are distributed by LICENSEE at no cost to the recipient for revenue-producing activities, these shall be deemed to be NET SALES (“IMPUTED NET SALES”) for purposes of computing royalty

2.18

“NIH” shall mean the US. National Institutes of Health.

2.19

“PATENT RIGHTS” shall mean rights to any claims directed to any aspect of the TECHNOLOGY in all United States and foreign patent applications filed and any patents now issued or hereinafter issuing from such patent applications, substitutes, continuations, continuations-in-part, divisional applications, reexaminations or reissues thereof, which contain at least one claim directed to any aspect of the TECHNOLOGY, a current listing of which appears in Exhibit C attached hereto and made a part hereof, as amended from time to time during the TERM of this AGREEMENT.

2.20

“PARTY” or “PARTIES” shall mean LICENSEE on the one hand and DUKE and/or MVP on the other hand, or all three, depending on the context.

2.21

“PBC URICASE” shall mean [**].

2.22

“PEG” shall mean poly(ethylene glycol) or poly(ethylene oxide).

2.23

“SALES AND REVENUE REPORTS” shall have the meaning ascribed to it in Section 6.9.

2.24

“STTR” shall mean the Small Business Technology Transfer Research program.

2.25

“SUBLICENSE REVENUES” shall mean all revenues or other consideration received by LICENSEE from sublicensees, including, without limitation, sublicense issue fees, other sublicense fees, royalties, and milestone payments.

2.26

“TECHNOLOGY” shall mean the DUKE TECHNOLOGY and the MVP TECHNOLOGY.

2.27

“TERM” shall have the meaning ascribed to it in Section 10.1.

2.28

“TERRITORY” shall mean each and every country of the world, including, with respect to each country, its territories and possessions.

2.29

“TOP [**] MARKETS” shall mean the [**] countries with the greatest dollar volume of sales of allopurinol during the twelve (12) months preceding any particular date, based on monthly data compiled by IMS America.

2.30

“TOTAL REVENUES” shall mean the sum of NET SALES plus SUBLICENSE REVENUES.

2.31

“TOTAL SALES” shall mean the cumulative sum of NET SALES of LICENSED PRODUCTS by LICENSEE plus net sales of LICENSED PRODUCTS by its sublicensees from the EFFECTIVE DATE.

2.32

“USPTO” shall mean the United States Patent and Trademark Office.

3.2

LICENSEE agrees to provide not less than $[**] to DUKE and $[**] to MVP (less any amounts received by MVP from BIRD) for sponsored research during the first twenty-four (24) months following the EFFECTIVE DATE.

3.4

The funding for sponsored research at DUKE is to support research at DUKE by Dr. [**], and it is understood that if for any reason, Dr. [**] should no longer be affiliated with DUKE during the period for which the funding is provided, then DUKE will transfer the funding to another institution with which Dr. [**] may affiliate, upon his departure from DUKE.

4.2

Within sixty (60) days after the execution of this AGREEMENT:

4.3

MVP hereby grants to LICENSEE the exclusive, royalty-free, right and license in the TERRITORY and in the FIELD to use such rights as MVP may possess in the trademark, PURICASE ^TM , the registration of which has been published in the Official Gazette of the USPTO (Volume 1211, Number 2, page TM 100) and is pending in the European Community (Application No. 716019).

(a)

LICENSEE may use whichever trademark or trademarks it may elect, in its sole discretion, in connection with the marketing of LICENSED PRODUCTS, and shall be under no obligation to use the trademark, PURICASE ^TM .

(b)

If LICENSEE elects not to use the trademark PURICASE ^TM or otherwise fails to use such trademark by one (1) year after the first sale of any LICENSED PRODUCT, MVP shall retain all rights to its use.

(a)

LICENSORS recognize that the currently projected market for LICENSED PRODUCTS does not justify a second manufacturing facility, and that LICENSEE currently has a manufacturing facility in Israel, and, therefore, LICENSORS and LICENSEE agree to cooperate and use their best efforts to promptly obtain a waiver of the U.S. manufacturing requirement.

(b)

DUKE represents that PBC URICASE was constructed at DUKE prior to its receipt of the GRANT and that U.S. Government funds did not support its development; and represents further that subject to review and determination by DUKE, other uricases may also have been constructed at DUKE prior to its receipt of the GRANT, developed without the support of U.S. Government funds, and that DUKE shall promptly identify any such uricases for LICENSEE.

(a)

LICENSEE agrees to be responsible for any obligations assumed hereunder by its sublicensees.

(b)

LICENSEE further agrees that all sublicense agreements will provide that if LICENSORS terminate this AGREEMENT pursuant to Section 10.3 or 10.6 prior to the end of the TERM in one or more countries, or if LICENSEE terminates this AGREEMENT pursuant to Section 10.2, all such sublicenses in those countries shall be assigned directly to LICENSORS; provided, however, that LICENSORS first agree, in writing, to assume all of LICENSEE’s obligations under such sublicenses and to hold LICENSEE harmless with respect to any claims made by such sublicensees as a result of such termination; provided, however, that LICENSORS shall not be liable for any claims against LICENSEE arising out of LICENSEE’s negligence or willful wrongdoing, or claims arising from LICENSEE’s breach, prior to termination, of its obligations under a sublicense.

(c)

LICENSORS shall promptly be provided a copy of each sublicense agreement, provided, however, that during the TERM of this AGREEMENT, LICENSORS shall maintain such agreements in confidence and shall not contact any such sublicensee without LICENSEE’s prior written consent.

4.6

Upon expiration of the TERM of this AGREEMENT with respect to each country as set forth in Article 10, the licenses granted in this Article 4 shall become fully paid-up, irrevocable and non-exclusive in each such country.

(a)

Payments 1) upon execution of this AGREEMENT.

(b)

Payments 2) not later than thirty (30) days after successful transfer of the technology for the production of PEG conjugates of uricase, as set forth in Section 5.10.

(c)

Payment 3) on the first anniversary of the EFFECTIVE DATE.

(d)

Payments 4) not later than thirty (30) days after the first filing of an application for an investigational new drug exemption for LICENSED PRODUCTS.

(e)

Payments 5) not later than thirty (30) days after enrolling the first patient in a Phase 2 clinical study of LICENSED PRODUCTS.

(f)

Payments 6) not later than thirty (30) days after filing an application to permit marketing of LICENSED PRODUCTS in any one of the [**].

(g)

Payments 7) not later than thirty (30) days after obtaining approval to market LICENSED PRODUCTS in any one of the [**].

(h)

Payments 8) not later than sixty (60) days after the end of the calendar quarter in which cumulative TOTAL REVENUES from LICENSED PRODUCTS exceed the equivalent of $[**].

(i)

Payments 9) not later than sixty (60) days after the end of the calendar quarter in which cumulative TOTAL REVENUES from LICENSED PRODUCTS exceed the equivalent of $[**].

5.4

All payments required by this AGREEMENT, if not paid when due, shall bear interest at the rate of one and one-half percent (1 ¹ / 2 %) per month or fraction thereof, or the maximum interest rate allowed by applicable law, whichever is less.

(a)

If upon such review subsequent to execution of this AGREEMENT, which LICENSEE shall complete within sixty (60) days after receipt of such application, LICENSEE determines in good faith that such application is inadequate (e.g., for lack of support in the specification or in view of the prior art), LICENSEE may elect, in its sole discretion, to terminate this AGREEMENT.

(b)

If LICENSEE does so elect to terminate, MVP and DUKE shall each refund to LICENSEE all payments made to them by LICENSEE as of the date of termination, and MVP shall be solely responsible for the repayment to BIRD, should such repayment be required, of any funds received by MVP from BIRD.

(a)

MVP and DUKE have been notified, in writing, by BTG following the review of their patent application as set forth in Section 5.5, either that such patent application is acceptable or, if unacceptable, that BTG nonetheless elects not to terminate the AGREEMENT, and that, therefore, the payments made by BTG to MVP and DUKE as of the date of such written notice are irrevocable;

(b)

BTG and MVP have selected a specific uricase and BTG has provided at least [**] from a single batch to MVP for each [**] of PEG conjugate to be prepared by MVP as part of the technology transfer; and

(c)

BTG has installed at its facility in Israel all of the necessary instruments, accessories, columns and other materials for assessing the activity of uricase, the purity of the PEG-uricase conjugates and the number of strands of PEG attached per uricase subunit according to MVP’s protocols. [**]

5.7

Such transfer shall commence as soon as practical after BTG has met all of the conditions in Section 5.6.

5.8

The technology transfer shall include the following steps: [**]

5.9

BTG and MVP shall use their best efforts to complete successful transfer of such technology as promptly as possible and each company shall therefore assign appropriately skilled personnel to this task.

5.10

The technology transfer shall be complete once Sections 5.8(c) and 5.8(d) have been completed and BTG shall notify LICENSORS in writing within thirty (30) days of such completion.

5.11

Failure to successfully transfer the technology within one (1) year after the transfer is initiated by MVP, unless such failure is caused by BTG’s failing to comply with Section 5.9, shall have the following consequences:

5.12

If the U.S. Government declines to waive the U.S. manufacturing requirement, MVP shall cooperate with LICENSEE to transfer such technology to a U.S. manufacturer selected by LICENSEE; provided, however: