Exhibit 10.3

 

EXECUTION VERSION (02-08-08)

 

CONFIDENTIAL TREATMENT REQUESTED

UNDER 17 C.F.R §§ 200.80(b)4, AND 240.24b-2

 

VLA4 PARTNER SUPPORT AGREEMENT

 

BY AND BETWEEN

 

ISIS PHARMACEUTICALS, INC.

 

AND

 

TEVA PHARMACEUTICAL INDUSTRIES LTD.

 

FEBRUARY 8, 2008

 

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This VLA4 PARTNER SUPPORT AGREEMENT (the “Agreement”), entered into as of
February 8, 2008 (the “Effective Date”), is made by and between ISIS
Pharmaceuticals, Inc., a Delaware corporation with a principal place of business
at 1896 Rutherford Road, Carlsbad, CA  92008 (“ISIS”) and TEVA Pharmaceutical
Industries Ltd., a limited liability company organized under the laws of Israel
with its principal place of business at Petah Tiqva 49131, Israel (“TEVA”).

 

BACKGROUND

 

A.            ISIS and ATL entered into that certain collaboration and license
agreement, dated October 30, 2001, which agreement was amended and restated on
February 8, 2008 (the “Amended and Restated ISIS/ATL Agreement”).

 

B.            ATL and TEVA have agreed to enter into a license agreement dated
as of even date hereof (the “ATL/TEVA Agreement”).

 

C.            In order to, among other things, induce TEVA to enter into the
ATL/TEVA Agreement and to undertake its obligations thereunder, ISIS agrees to
provide TEVA, in ISIS’ capacity as licensor under the Amended and Restated
ISIS/ATL Agreement, with:

 

(i)            certain limited assurances and agreements supporting the
assurances and agreements made by ISIS to ATL under the Amended and Restated
ISIS/ATL Agreement and the assurances and agreements made by ATL to TEVA under
the ATL/TEVA Agreement, and

 

(ii)           support services in connection with the development of Products,
as more fully described herein.

 

NOW, THEREFORE, for and in consideration of the representations, warranties and
covenants hereinafter set forth, and for other good and valuable consideration,
the receipt and sufficiency of which are hereby acknowledged; it is agreed by
and between the parties as follows:

 

1.                                      DEFINITIONS

 

1.1          ALL CAPITALIZED TERMS USED BUT NOT DEFINED HEREIN WILL HAVE THE
MEANING ASCRIBED TO SUCH TERMS IN THE AMENDED AND RESTATED ISIS/ATL AGREEMENT.

 

1.2          OTHER DEFINED TERMS.  THE FOLLOWING DEFINED TERMS HAVE THE MEANINGS
SET FORTH IN THE RESPECTIVE SECTIONS REFERRED TO BELOW:

 

Defined Term

 

Section

VLA4 Compounds/Products

 

2.1

ISIS/TEVA Meeting

 

3.1

 

 

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ISIS Indemnitees

 

7.1(a)

Claims

 

7.1(a)

TEVA Indemnitees

 

7.1(b)

Indemnified Party

 

7.2

Indemnity Claim

 

7.2

Liaisons

 

10.3

Executives

 

10.12(a)

ICC

 

10.12(b)

 

1.3          INTERPRETATION.  THE SECTION, PARAGRAPH AND OTHER HEADINGS
CONTAINED IN THIS AGREEMENT ARE FOR REFERENCE PURPOSES ONLY AND WILL NOT AFFECT
THE MEANING OR INTERPRETATION OF THIS AGREEMENT.  ALL REFERENCES IN THIS
AGREEMENT TO A SECTION OR PARAGRAPH WILL REFER TO A SECTION OR PARAGRAPH IN OR
TO THIS AGREEMENT, UNLESS OTHERWISE STATED. ALL REFERENCES TO A “PARTY” IS TO A
PARTY TO THIS AGREEMENT ANY REFERENCE TO ANY FEDERAL, NATIONAL, STATE, LOCAL, OR
FOREIGN STATUTE OR LAW WILL BE DEEMED ALSO TO REFER TO ALL RULES AND REGULATIONS
PROMULGATED THEREUNDER, UNLESS THE CONTEXT REQUIRES OTHERWISE.  THE WORD
“INCLUDING” AND SIMILAR WORDS MEAN “INCLUDING WITHOUT LIMITATION.” THE WORDS
“HEREIN,” “HEREOF’ AND “HEREUNDER” AND OTHER WORDS OF SIMILAR IMPORT REFER TO
THIS AGREEMENT AS A WHOLE AND NOT TO ANY PARTICULAR SECTION, PARAGRAPH OR OTHER
SUBDIVISION.  REFERENCES IN THIS AGREEMENT TO “PROVISIONS OF THIS AGREEMENT”
REFER TO THE REPRESENTATIONS, WARRANTIES AND COVENANTS CONTAINED IN THIS
AGREEMENT TAKEN AS A WHOLE.  ALL REFERENCES TO DAYS, MONTHS, QUARTERS OR
YEARS/ANNUAL ARE REFERENCES TO BUSINESS DAYS, CALENDAR MONTHS, CALENDAR
QUARTERS, OR CALENDAR YEARS, RESPECTIVELY.  REFERENCES TO THE SINGULAR INCLUDE
THE PLURAL.

 

2.                                      ASSURANCES REGARDING AMENDED AND
RESTATED ISIS/ATL AGREEMENT

 

2.1          NO CONFLICT.  FOR THE PURPOSE OF ASSURING AND CONFIRMING TO TEVA
THE RIGHTS AND LICENSES GRANTED TO ATL IN THE AMENDED AND RESTATED ISIS/ATL
AGREEMENT, ISIS WILL NOT ENTER INTO ANY AGREEMENT, WITHOUT TEVA’S PRIOR WRITTEN
CONSENT, WHICH WOULD IMPAIR OR CONFLICT WITH OR ADVERSELY IMPACT THE RIGHTS AND
LICENSES GRANTED BY ISIS TO ATL UNDER THE AMENDED AND RESTATED ISIS/ATL
AGREEMENT WITH RESPECT TO ATL 1102, VLA4 COMPOUNDS OR OTHER VLA4 COMPOUNDS AND
VLA4 PRODUCTS (COLLECTIVELY, THE “VLA4 COMPOUNDS/PRODUCTS”).

 

2.2          FURTHER AMENDMENT OF THE AMENDED AND RESTATED ISIS/ATL AGREEMENT. 
WITHOUT THE PRIOR WRITTEN CONSENT OF TEVA, ISIS WILL NOT AMEND, MODIFY OR WAIVE
ANY PROVISION OF THE AMENDED AND RESTATED ISIS/ATL AGREEMENT (INCLUDING BUT NOT
LIMITED TO THE ASSIGNMENT PROVISION THEREOF) IN ANY MANNER THAT WOULD
(A) DIMINISH ANY RIGHTS OF ATL UNDER THE AMENDED

 

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and Restated ISIS/ATL Agreement that would result in any direct or indirect
diminution of TEVA’s rights under the ATL/TEVA Agreement, (b) diminish any
rights expressly conferred upon TEVA under the Amended and Restated ISIS/ATL
Agreement or under this Agreement, or (c) directly or indirectly impose any
additional financial or other obligations upon TEVA beyond those specified in
this Agreement and the ATL/TEVA Agreement.

 

2.3          MATERIAL DEFAULT UNDER THE AMENDED AND RESTATED ISIS/ATL AGREEMENT.

 

(A)         IN THE EVENT OF A DEFAULT BY ATL UNDER THE AMENDED AND RESTATED
ISIS/ATL AGREEMENT THAT RELATES TO VLA4 COMPOUNDS/PRODUCTS (INCLUDING, WITHOUT
LIMITATION, ANY FUNDAMENTAL BREACH OF THE AMENDED AND RESTATED ISIS/ATL
AGREEMENT BY ATL WITH RESPECT TO WHICH ISIS PROVIDES WRITTEN NOTICE TO ATL UNDER
SECTION 12.2 THEREOF), ISIS WILL PROMPTLY INFORM TEVA IN WRITING, AND THE
PARTIES AGREE THAT TEVA WILL HAVE THE RIGHT TO CURE SUCH DEFAULT ON ATL’S
BEHALF.

 

(B)        ISIS ACKNOWLEDGES AND AGREES THAT: (I) ISIS DOES NOT HAVE THE RIGHT
TO TERMINATE THE AMENDED AND RESTATED ISIS/ATL AGREEMENT EXCEPT IN THE EVENT ATL
IS IN FUNDAMENTAL BREACH OF ITS OBLIGATIONS THEREUNDER (I.E., A BREACH WHICH
GOES TO THE HEART OF THE AMENDED AND RESTATED ISIS/ATL AGREEMENT) AND NEITHER
ATL NOR TEVA HAS CURED SUCH BREACH WITHIN THE PERIOD SPECIFIED IN
SECTION 12.2(A) OF THE AMENDED AND RESTATED ISIS/ATL AGREEMENT; AND (II) A
MATERIAL BREACH OF THE AMENDED AND RESTATED ISIS/ATL AGREEMENT BY ATL THAT IS
NOT FUNDAMENTAL GIVES RISE SOLELY TO A RIGHT OF DAMAGES BUT NOT A RIGHT TO
TERMINATE THE AMENDED AND RESTATED ISIS/ATL AGREEMENT.

 

(C)         IF ATL COMMITS A FUNDAMENTAL BREACH OF THE AMENDED AND RESTATED
ISIS/ATL AGREEMENT RELATING TO VLA4 COMPOUNDS/PRODUCTS, AND ISIS PROVIDES
WRITTEN NOTICE OF SUCH FUNDAMENTAL BREACH TO ATL UNDER SECTION 12.2(A) OF THE
AMENDED AND RESTATED ISIS/ATL AGREEMENT, ISIS WILL CONCURRENTLY PROVIDE A COPY
OF SUCH NOTICE TO TEVA, AND TEVA WILL HAVE THE RIGHT TO CURE SUCH BREACH ON
ATL’S BEHALF WITHIN THE APPLICABLE TIME PERIOD SPECIFIED IN SUCH
SECTION 12.2(A).  IF ATL CURES SUCH BREACH, OR TEVA CURES SUCH BREACH ON ATL’S
BEHALF, WITHIN THE APPLICABLE TIME PERIOD SPECIFIED IN SECTION 12.2(A), ISIS
WILL NOT HAVE THE RIGHT TO TERMINATE THE AMENDED AND RESTATED ISIS/ATL AGREEMENT
ON THE BASIS OF SUCH FUNDAMENTAL BREACH.

 

(D)        IF ATL COMMITS A FUNDAMENTAL BREACH OF THE AMENDED AND RESTATED
ISIS/ATL AGREEMENT UNRELATED TO VLA4 COMPOUNDS/PRODUCTS, AND ISIS PROVIDES
WRITTEN NOTICE OF SUCH FUNDAMENTAL BREACH TO ATL UNDER SECTION 12.2(A) OF THE
AMENDED AND RESTATED ISIS/ATL AGREEMENT, ISIS WILL CONCURRENTLY PROVIDE A COPY
OF SUCH NOTICE TO TEVA.  NOTWITHSTANDING ANY FAILURE BY ATL TO CURE SAID
FUNDAMENTAL BREACH WITHIN THE APPLICABLE TIME PERIOD SPECIFIED IN SUCH
SECTION 12.2(A), ISIS ACKNOWLEDGES AND AGREES THAT SUCH UNCURED FUNDAMENTAL
BREACH WILL NOT GIVE ISIS THE RIGHT TO TERMINATE THE AMENDED AND RESTATED
ISIS/ATL AGREEMENT IN ITS ENTIRETY, AND THAT IN SUCH EVENT, THE AMENDED AND
RESTATED ISIS/ATL AGREEMENT WILL: (A) TERMINATE AS IT

 

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RELATES TO RESEARCH TARGETS OTHER THAN CD49D AND COLLABORATION COMPOUNDS OTHER
THAN VLA4 COMPOUNDS/PRODUCTS; AND (B) REMAIN IN FULL FORCE AND EFFECT IN
ACCORDANCE WITH ITS TERMS (INCLUDING, WITHOUT LIMITATION, SUCH SECTION 12.2) AS
IT RELATES TO CD49D AND VLA4 COMPOUNDS/PRODUCTS.

 

2.4          OTHER TERMINATION OF THE AMENDED AND RESTATED ISIS/ATL AGREEMENT.
EXCEPT AS EXPRESSLY SET FORTH IN SECTION 2.3 ABOVE OR IN SECTION 2.5 BELOW, ISIS
WILL NOT TERMINATE THE AMENDED AND RESTATED ISIS/ATL AGREEMENT PRIOR TO ITS
EXPIRATION.  HOWEVER, IF IN FACT THE AMENDED AND RESTATED ISIS/ATL AGREEMENT IS
TERMINATED FOR ANY REASON WITH RESPECT TO VLA4 COMPOUNDS/PRODUCTS RESULTING IN
THE TERMINATION OF THE ATL/TEVA AGREEMENT, THEN ISIS AND TEVA SHALL ENTER INTO A
ISIS/TEVA LICENSE AGREEMENT AS PROVIDED IN SECTION 2.5 BELOW.

 

2.5          EFFECT OF TEVA’S CURING OF A FUNDAMENTAL BREACH BY ATL AND THE
EFFECT OF ATL’S BANKRUPTCY.  IN THE EVENT THAT (I) UNDER SECTION 2.3 OF THIS
AGREEMENT TEVA CURES MORE THAN ONE FUNDAMENTAL BREACH RELATING TO VLA4
COMPOUNDS/PRODUCTS BY ATL OF THE AMENDED AND RESTATED ISIS/ATL AGREEMENT OR IN
THE EVENT THAT ATL COMMITS A FUNDAMENTAL BREACH RELATING TO VLA4
COMPOUNDS/PRODUCTS OF THE AMENDED AND RESTATED ISIS/ATL AGREEMENT THAT IS NOT
CAPABLE OF BEING CURED BY TEVA (E.G., A BREACH THAT IS NOT MONETARY AND MAY BE
PERFORMED ONLY BY ATL), OR (II) TEVA EXERCISES ITS RIGHT TO TERMINATE THE
ATL/TEVA AGREEMENT UNDER SECTION 21.2(C) THEREOF, THEN ISIS SHALL TERMINATE THE
AMENDED AND RESTATED ISIS/ATL AGREEMENT AS IT RELATES TO VLA4 COMPOUNDS/PRODUCTS
AND TEVA SHALL TERMINATE THE ATL/TEVA AGREEMENT.  IN SUCH EVENT, ISIS AND TEVA
SHALL ON AN URGENT BASIS NEGOTIATE IN GOOD FAITH AND ENTER INTO AN AGREEMENT (AN
“ISIS/TEVA LICENSE AGREEMENT”) SUBSTANTIALLY ON THE SAME NON-FINANCIAL TERMS AND
CONDITIONS (BUT ON THE EXACT SAME FINANCIAL TERMS AND CONDITIONS) AS SET FORTH
IN THE AMENDED AND RESTATED ISIS/ATL AGREEMENT AS IT RELATES TO VLA4
COMPOUNDS/PRODUCTS, IN EFFECT SUBSTITUTING TEVA FOR ATL UNDER THOSE PROVISIONS
OF THE AMENDED AND RESTATED ISIS/ATL AGREEMENT RELATING TO VLA4
COMPOUNDS/PRODUCTS.  FOR THE AVOIDANCE OF DOUBT, SO AS NOT TO INTERRUPT THE
EXPLOITATION BY TEVA OF THE LICENSED RIGHTS WITH RESPECT TO VLA4
COMPOUNDS/PRODUCTS DURING ANY PERIOD OF NEGOTIATION AND DRAFTING OF AN ISIS/TEVA
LICENSE AGREEMENT, ISIS AND TEVA SHALL CONDUCT THEMSELVES AS IF THE ATL/TEVA
AGREEMENT IS IN FULL FORCE AND EFFECT, EXCEPT THAT REFERENCES TO “ATL” IN THE
THOSE PORTIONS OF THE AMENDED AND RESTATED ISIS/ATL AGREEMENT THAT RELATE TO
VLA4 COMPOUNDS/PRODUCTS SHALL BE DEEMED REFERENCES TO “TEVA” AS IF THE AMENDED
AND RESTATED ISIS/ATL AGREEMENT (AS IT RELATES TO VLA4 COMPOUNDS/PRODUCTS) WERE
BETWEEN ISIS AND TEVA.  BY ITS SIGNATURE BELOW, ATL (X) ACKNOWLEDGES AND AGREES
THAT THE GOAL OF ALLOWING TEVA TO EXPLOIT VLA4 COMPOUNDS/PRODUCTS AS
CONTEMPLATED IN THE ATL/TEVA AGREEMENT AND ALLOWING ISIS TO RECEIVE ROYALTIES
AND OTHER PAYMENTS UNDER THE AMENDED AND RESTATED ISIS/ATL AGREEMENT IS OF SUCH
FUNDAMENTAL IMPORTANCE TO TEVA AND ISIS THAT ANY SUCH TERMINATION OF THE AMENDED
AND RESTATED ISIS/ATL AGREEMENT AND THE ATL/TEVA AGREEMENT IS FAIR, (Y) CONSENTS
TO THE PROVISIONS OF THIS SECTION 2.5 AND (Z) AGREES THAT IT SHALL HAVE NO
CLAIMS AGAINST (A) TEVA OR ITS AFFILIATES, AGENTS, EMPLOYEES, OFFICERS OR
DIRECTORS ARISING FROM OR IN CONNECTION WITH ANY SUCH TERMINATION BY TEVA OF THE
ATL/TEVA AGREEMENT OR ITS ENTERING INTO AN ISIS/TEVA LICENSE AGREEMENT (EXCEPT
THAT TEVA AND ITS AFFILIATES, AGENTS, EMPLOYEES, OFFICERS AND DIRECTORS SHALL
NOT HAVE THE BENEFIT OF THIS CLAUSE (Z) IN THE EVENT THAT TEVA WRONGFULLY
EXERCISES ITS TERMINATION RIGHT IN CONTRAVENTION OF SECTION 21.2(C) OF THE
ATL/TEVA AGREEMENT), OR AGAINST (B) ISIS OR ITS AFFILIATES, AGENTS, EMPLOYEES,
OFFICERS OR DIRECTORS ARISING FROM OR IN CONNECTION

 

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WITH ANY SUCH TERMINATION BY ISIS OF THE AMENDED AND RESTATED ISIS/ATL AGREEMENT
OR ITS ENTERING INTO AN ISIS/TEVA LICENSE AGREEMENT (EXCEPT THAT ISIS AND ITS
AFFILIATES, AGENTS, EMPLOYEES, OFFICERS AND DIRECTORS SHALL NOT HAVE THE BENEFIT
OF THIS CLAUSE (Z) IN THE EVENT THAT ISIS WRONGFULLY EXERCISES ITS TERMINATION
RIGHT IN CONTRAVENTION OF THE AMENDED AND RESTATED ISIS/ATL AGREEMENT).

 

2.6          NOTICE UNDER THE AMENDED AND RESTATED ISIS/ATL AGREEMENT.  ISIS
AGREES THAT ALL NOTICES TO ATL UNDER THE AMENDED AND RESTATED ISIS/ATL AGREEMENT
(OTHER THAN NOTICES REGARDING MATTERS THAT ARE UNRELATED TO THE VLA4
COMPOUNDS/PRODUCTS AND IN ISIS’ GOOD FAITH JUDGMENT WOULD NOT REASONABLY BE
EXPECTED TO HAVE AN ADVERSE IMPACT ON THE DEVELOPMENT OR COMMERCIALIZATION OF
VLA4 COMPOUNDS/PRODUCTS) WILL BE COPIED TO TEVA AT THE ADDRESS SET FORTH IN
SECTION 10.6 HEREOF.

 

3.                                      FURTHER ASSURANCES AND SUPPORT

 

3.1          [***] EDUCATION AND SUPPORT.  ISIS WILL PROVIDE, [***] TO TEVA,
ASSISTANCE, EDUCATION AND SUPPORT REASONABLY REQUESTED BY TEVA FOR UP TO
(A) [***] HOURS PER [***] FOR THE PERIOD ENDING [***] FOLLOWING THE EFFECTIVE
DATE AND (B) [***] HOURS PER [***] FOR EACH [***] THEREAFTER UNTIL TEVA FILES AN
NDA (OR FOREIGN EQUIVALENT IN A MAJOR MARKET) FOR A PRODUCT; PROVIDED, HOWEVER,
THAT HOURS NOT USED IN A [***] DO NOT CARRY OVER TO THE NEXT [***] (I.E., NO
BANKING OF HOURS NOT USED IN A [***]).  ISIS WILL ALSO HOST, AT [***] TEVA, AN
EDUCATIONAL MEETING FOR TEVA PERSONNEL (THE “ISIS/TEVA MEETING”) FOR UP TO
[***], AT A MUTUALLY AGREEABLE TIME, AFTER THE EFFECTIVE DATE.  THE ISIS/TEVA
MEETING WILL BE IN ADDITION TO THE [***] SUPPORT TO BE PROVIDED BY ISIS FOR THE
MONTH IN WHICH THE MEETING OCCURS.  IN ADDITION, ISIS WILL PROVIDE TO TEVA
COPIES OF EXISTING REPORTS OR OTHER EXISTING INFORMATION RELATING TO VLA4
COMPOUNDS/PRODUCTS THAT ARE IN ISIS’ POSSESSION AND CONTROL THAT TEVA MAY
REASONABLY REQUEST, INCLUDING ANY SUCH REPORTS RELATED TO CLASS EFFECT.  SUCH
REPORTS WILL BE PROVIDED AT NO COST TO TEVA, EXCEPT THAT TEVA WILL REIMBURSE
ISIS’ OUT-OF-POCKET COSTS INCURRED IN PROVIDING THE SAME.

 

3.2          [***] EDUCATION AND SUPPORT.  IN ADDITION TO THE ASSISTANCE,
EDUCATION AND SUPPORT REFERENCED IN SECTION 3.1, ISIS WILL PROVIDE ADDITIONAL
ASSISTANCE, EDUCATION AND SUPPORT AS REASONABLY REQUESTED BY TEVA FROM TIME TO
TIME HEREAFTER, AT [***] COST AND EXPENSE, IN ACCORDANCE WITH A PLAN MUTUALLY
AGREED UPON BY THE PARTIES IN WRITING (WHICH AGREEMENT WILL NOT BE UNREASONABLY
WITHHELD), FOR (A) THE REGULATORY ASPECTS OF [***] WITH RESPECT TO VLA4
COMPOUNDS/PRODUCTS, (B) [***] WITH RESPECT TO VLA4 COMPOUNDS/PRODUCTS, INCLUDING
THE [***], (C) [***] ISSUES/ACTIVITIES WITH RESPECT TO VLA4 COMPOUNDS/PRODUCTS,
INCLUDING RESPONDING TO QUERIES SUBMITTED BY TEVA WITH RESPECT TO THE [***]
BUILT BY ISIS WITH RESPECT TO VLA4 COMPOUNDS/PRODUCTS IN ORDER FOR TEVA TO GAIN
THE BENEFIT OF THE INFORMATION CONTAINED THEREIN, AND (D) SUCH OTHER MATTERS
RELATED TO VLA4 COMPOUNDS/PRODUCTS AS THE PARTIES MAY MUTUALLY AGREE IN WRITING.

 

3.3          VLA4 RESTRICTIVE COVENANT. IN ORDER TO ALLOW TEVA TO FULLY EXPLOIT
ITS RIGHTS UNDER THE ATL/TEVA AGREEMENT AND AS A MATERIAL INDUCEMENT FOR TEVA TO
ENTER INTO THE ATL/TEVA AGREEMENT, ISIS COVENANTS AND AGREES THAT, DURING THE
TERM OF THIS AGREEMENT, ISIS WILL [***] OF THIS AGREEMENT AND THE AMENDED AND
RESTATED ISIS/ATL AGREEMENT [***] WITH RESPECT TO [***] WITH RESPECT TO ANY
[***]; PROVIDED, HOWEVER, THAT IF A VLA4 PRODUCT HAS NOT

 

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been [***] (or such later date as is mutually agreed by the parties), then the
provisions of this Section 3.3 shall terminate as of such date.

 

3.4          CERTAIN FUTURE INVENTIONS AND INTELLECTUAL PROPERTY.  PURSUANT TO
SECTION 4.2(C)(I)(A) OF THE AMENDED AND RESTATED ISIS/ATL AGREEMENT, ISIS HAS
GRANTED TO ATL RIGHTS TO CERTAIN FUTURE INVENTIONS.

 

4.                                      ADDITIONAL TECHNOLOGY

 

4.1          OTHER VLA4 COMPOUNDS OR NEXT GENERATION VLA4 COMPOUNDS.  ISIS WILL
HAVE NO OBLIGATION TO GENERATE FOR TEVA ANY OTHER VLA4 COMPOUNDS OR NEXT
GENERATION VLA4 COMPOUNDS, UNLESS AND UNTIL:

 

(A)         TEVA AND ISIS MUTUALLY AGREE IN WRITING UPON A RESEARCH PLAN, WHICH
AGREEMENT SHALL NOT BE UNREASONABLY WITHHELD, SPECIFICALLY DESCRIBING THE
ACTIVITIES TO BE UNDERTAKEN BY ISIS, INCLUDING THE AMOUNTS TO BE REIMBURSED BY
TEVA TO ISIS FOR PERFORMING SUCH ACTIVITIES; AND

 

(B)        WITH RESPECT TO NEXT GENERATION VLA4 COMPOUNDS, TEVA AND ISIS
MUTUALLY AGREE IN WRITING UPON LICENSE TERMS (INCLUDING, WITHOUT LIMITATION,
MILESTONES AND ROYALTIES PAYABLE TO ISIS) WITH RESPECT TO PRODUCTS DEVELOPED
UTILIZING SUCH NEXT GENERATION VLA4 COMPOUNDS.

 

4.2          ACCESS TO ADDITIONAL TECHNOLOGY.  IF, AFTER THE EFFECTIVE DATE AND
DURING THE TERM OF THIS AGREEMENT, ISIS CREATES, DEVELOPS, COMES TO OWN, OR
ACQUIRES A LICENSE WITH THE RIGHT TO GRANT SUBLICENSES THEREUNDER, ANY NEW OR
ADDITIONAL ISIS CORE TECHNOLOGY PATENT RIGHTS OR MANUFACTURING PATENT RIGHTS, OR
ANY NEW OR ADDITIONAL TECHNOLOGY THAT BOTH (I) IS NECESSARY OR USEFUL FOR THE
DEVELOPMENT, MANUFACTURE OR COMMERCIALIZATION OF VLA4 COMPOUNDS/PRODUCTS AND
(II) IS OR HAS BEEN [***] AND TEVA DESIRES ACCESS TO ANY OF THE FOREGOING RIGHTS
FOR THE PURPOSE OF DEVELOPMENT, MANUFACTURE OR COMMERCIALIZATION OF VLA4
COMPOUNDS/PRODUCTS, ISIS AGREES TO NEGOTIATE IN GOOD FAITH WITH ATL AND TEVA
REGARDING SUCH ACCESS, PROVIDED THAT ANY LICENSES OR SUBLICENSES FROM ISIS TO
ATL OR TEVA UNDER SUCH PATENTS AND/OR TECHNOLOGY ARE CONDITIONED ON ATL’S OR
TEVA’S (AS APPLICABLE) AGREEMENT (A) TO [***]; AND (B) TO ABIDE BY ALL TERMS OF
THE AGREEMENT UNDER WHICH A THIRD PARTY LICENSE IS GRANTED TO ISIS. 
NOTWITHSTANDING THE FOREGOING, ISIS AGREES TO PROVIDE TO TEVA, [***], (I) ANY
[***] THAT ARE USED IN ISIS’ [***], AND/OR (II) SUCH ISIS TECHNOLOGY THAT (A) IS
REQUIRED FOR TEVA TO BE ABLE TO [***] AND (B) ISIS IS [***] FOR SUCH REQUIRED
TECHNOLOGY.

 

4.3          UPDATES.  NO MORE THAN ONCE PER CALENDAR YEAR AT ISIS’ FACILITY IN
CARLSBAD, CALIFORNIA (OR SUCH OTHER LOCATION AS IS AGREED UPON BY THE PARTIES),
UPON THE WRITTEN REQUEST OF, BUT AT NO COST TO, TEVA, ISIS WILL PRESENT AN
UPDATE TO A REASONABLE NUMBER OF TEVA STAFF SCIENTISTS ON [***] AND ANY [***]
FOR VLA4 COMPOUNDS/PRODUCTS (PROVIDED THAT TEVA WILL BE RESPONSIBLE FOR THE
EXPENSES INCURRED BY TEVA PERSONNEL IN ATTENDING SUCH UPDATE).  IN ADDITION,
UPON TEVA’S WRITTEN REQUEST NO MORE THAN ONCE PER YEAR, AND AT NO COST TO TEVA,
ISIS WILL UPDATE EXHIBIT 1.39 TO THE AMENDED AND RESTATED ISIS/ATL AGREEMENT AND
PROVIDE SUCH UPDATED EXHIBIT TO TEVA.

 

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5.                                      REPRESENTATIONS, COVENANTS AND
WARRANTIES.

 

5.1          MUTUAL WARRANTIES.  EACH OF ISIS AND TEVA HEREBY REPRESENTS AND
WARRANTS TO THE OTHER  AS OF THE EFFECTIVE DATE AS FOLLOWS:

 

(A)         IT IS DULY ORGANIZED AND VALIDLY EXISTING UNDER THE LAWS OF THE
JURISDICTION OF ITS INCORPORATION.  IT HAS THE REQUISITE LEGAL AND COMPANY POWER
AND AUTHORITY TO CONDUCT ITS BUSINESS AS PRESENTLY BEING CONDUCTED AND AS
PROPOSED TO BE CONDUCTED BY IT  AND IS DULY QUALIFIED TO DO BUSINESS IN THOSE
JURISDICTIONS WHERE ITS OWNERSHIP OF PROPERTY OR THE CONDUCT OF ITS BUSINESS
REQUIRES, IN EACH CASE THE FAILURE TO HAVE SUCH POWER, AUTHORITY OR
QUALIFICATION WOULD HAVE A MATERIAL ADVERSE IMPACT UPON THE RESPECTIVE RIGHTS
AND OBLIGATIONS OF THE PARTIES UNDER THIS AGREEMENT.

 

(B)        IT HAS ALL REQUISITE LEGAL AND COMPANY POWER AND AUTHORITY TO ENTER
INTO THIS AGREEMENT AND TO PERFORM ITS OBLIGATIONS CONTEMPLATED HEREUNDER.  ALL
COMPANY ACTIONS ON ITS PART, ITS BOARDS OF DIRECTORS OR MANAGERS, OR SIMILAR
GOVERNING BODY AND ITS EQUITY HOLDERS NECESSARY FOR (A) THE AUTHORIZATION,
EXECUTION, DELIVERY AND PERFORMANCE BY IT OF THIS AGREEMENT, AND (B) THE
CONSUMMATION OF THE TRANSACTIONS CONTEMPLATED HEREBY, HAVE BEEN DULY TAKEN.

 

(C)         THIS AGREEMENT IS A LEGALLY VALID AND BINDING OBLIGATION OF IT,
ENFORCEABLE AGAINST IT IN ACCORDANCE WITH ITS TERMS.

 

(D)        NONE OF THE EXECUTION AND DELIVERY OF THIS AGREEMENT, THE
CONSUMMATION OF THE TRANSACTIONS PROVIDED FOR HEREIN OR CONTEMPLATED HEREBY, OR
THE FULFILLMENT BY IT OF THE TERMS HEREOF OR THEREOF, WILL (WITH OR WITHOUT
NOTICE OR PASSAGE OF TIME OR BOTH) (A) CONFLICT WITH OR RESULT IN A BREACH OF
ANY PROVISION OF THE CERTIFICATE OR ARTICLES OF INCORPORATION OR FORMATION,
BY-LAWS, STATUTES, OPERATING AGREEMENT OR OTHER GOVERNING DOCUMENTS OF IT,
(B) RESULT IN A DEFAULT, CONSTITUTE A DEFAULT UNDER, GIVE RISE TO ANY RIGHT OF
TERMINATION, CANCELLATION OR ACCELERATION, OR REQUIRE ANY CONSENT OR APPROVAL
(OTHER THAN APPROVALS THAT HAVE HERETOFORE BEEN OBTAINED) OF ANY GOVERNMENTAL
AUTHORITY OR UNDER ANY OF THE TERMS, CONDITIONS OR PROVISIONS OF ANY MATERIAL
NOTE, BOND, MORTGAGE, INDENTURE, LOAN, ARRANGEMENT, LICENSE, AGREEMENT, LEASE OR
OTHER INSTRUMENT OR OBLIGATION TO WHICH IT IS A PARTY OR BY WHICH ITS ASSETS MAY
BE BOUND, OR (C) VIOLATE ANY RULE OR REGULATION OF ANY STOCK EXCHANGE ON WHICH
SUCH PARTY’S SECURITIES ARE LISTED APPLICABLE TO IT.

 

5.2          ADDITIONAL REPRESENTATIONS AND WARRANTIES OF ISIS.  ISIS HEREBY
FURTHER REPRESENTS AND WARRANTS TO TEVA, REGARDLESS OF ANY INVESTIGATION BY
TEVA, THAT AS OF THE EFFECTIVE DATE:

 

(A)         ISIS HAS ASSIGNED TO ATL, FREE AND CLEAR OF ALL LIENS, CLAIMS AND
ENCUMBRANCES OF EVERY KIND OR NATURE, ALL RIGHTS, TITLE AND INTERESTS IN AND TO
THE VLA4 COMPOUND PATENT RIGHTS;

 

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(B)        TO THE BEST OF ISIS’ KNOWLEDGE AS OF THE EFFECTIVE DATE, THE VLA4
COMPOUND PATENT RIGHTS ARE VALID AND ENFORCEABLE AND ARE NOT SUBJECT TO ANY
PENDING OR THREATENED RE-EXAMINATION, OPPOSITION, INTERFERENCE OR LITIGATION
PROCEEDINGS, AND ALL ASSIGNMENTS AND MAINTENANCE FEES HAVE BEEN TIMELY FILED AND
PAID WITH RESPECT TO THE VLA4 COMPOUND PATENT RIGHTS;

 

(C)         TO THE BEST OF ISIS’S KNOWLEDGE AS OF THE EFFECTIVE DATE, THE
PRACTICE OF THE ISIS CORE TECHNOLOGY PATENT RIGHTS, AND THE MANUFACTURING
TECHNOLOGY TO MANUFACTURE VLA4 COMPOUNDS, AS CURRENTLY MANUFACTURED BY ISIS AS
OF THE EFFECTIVE DATE, DOES NOT INFRINGE ON ANY THIRD PARTY PATENTS;

 

(D)        TO THE BEST OF ISIS’ KNOWLEDGE AS OF THE EFFECTIVE DATE, WITHOUT
REFERENCE TO A SPECIFIC DEVELOPMENT PLAN AND WITHOUT ANY INVESTIGATION, THE ISIS
CORE TECHNOLOGY PATENT RIGHTS, ISIS FORMULATION PATENT RIGHTS, MANUFACTURING
PATENT RIGHTS AND VLA4 COMPOUND PATENT RIGHTS, CONSIDERED TOGETHER, CONSTITUTE
ALL OF THE PATENTS CONTROLLED BY ISIS (AS OF IMMEDIATELY PRIOR TO THE EFFECTIVE
DATE) THAT ARE NECESSARY FOR THE DEVELOPMENT AND COMMERCIALIZATION OF THE
ATL1102 COMPOUND AND VLA4 COMPOUNDS USING THE ISIS STANDARD CHEMISTRY;

 

(E)         ISIS HAS NOT GRANTED, DIRECTLY OR INDIRECTLY, ANY LICENSES OR OTHER
RIGHTS UNDER THE VLA4 COMPOUND PATENT RIGHTS TO ANY PERSON OTHER THAN ATL AND
ITS AFFILIATES;

 

(F)         THE AMENDED AND RESTATED ISIS/ATL AGREEMENT IS IN FULL FORCE AND
EFFECT AND HAS NOT BEEN MODIFIED OR AMENDED; AND

 

(G)        TO THE BEST OF ISIS’ KNOWLEDGE AS OF THE EFFECTIVE DATE, NEITHER ISIS
NOR ATL IS IN MATERIAL DEFAULT UNDER, AND NEITHER PARTY CLAIMS OR HAS GROUNDS
UPON WHICH TO CLAIM THE OTHER PARTY IS IN MATERIAL DEFAULT UNDER, THE AMENDED
AND RESTATED ISIS/ATL AGREEMENT.

 

5.3          NOTICE OF PATENT INFRINGEMENT.  ISIS WILL PROMPTLY ADVISE TEVA IF
IT BECOMES AWARE OF ANY SUSPECTED OR ACTUAL INFRINGEMENT OF THE VLA4 COMPOUND
PATENT RIGHTS BY ANY PERSON OR OF ANY SUSPECTED OR ACTUAL INFRINGEMENT BY THE
VLA4 COMPOUND PATENT RIGHTS OF ANY RIGHTS OF ANY PERSON.  IN ADDITION, ISIS WILL
NOTIFY TEVA OF ANY FINAL DETERMINATION OF ANY LEGAL ACTION OF ISIS OR KNOWN TO
ISIS INVOLVING THE ISIS CORE TECHNOLOGY PATENT RIGHTS AND/OR THE MANUFACTURING
PATENT RIGHTS THAT, IN EACH CASE, CLAIM INVENTIONS USED IN THE MANUFACTURE OF
VLA4 COMPOUNDS/PRODUCTS THEN UNDER DEVELOPMENT OR BEING COMMERCIALIZED BY OR ON
BEHALF OF TEVA.

 

5.4          ADDITIONAL COVENANT OF THE PARTIES.  EACH OF THE PARTIES WILL NOT
INSIST UPON, CLAIM, PLEAD, OR TAKE ANY BENEFIT UNDER ANY LOCAL LAWS OF ANY
JURISDICTION, OTHER THAN THE INTERNAL LAWS OF THE UNITED STATES AND THE STATE OF
NEW YORK, THAT MAY BE AVAILABLE TO IT, IN ORDER TO PREVENT, DELAY, HINDER OR
OTHERWISE FRUSTRATE THE ENFORCEMENT BY THE OTHER OF ANY OF THE PROVISIONS OF
THIS AGREEMENT.  IN FURTHERANCE OF THE FOREGOING, EACH OF THE PARTIES WAIVES ANY
RIGHTS OR BENEFITS THAT MAY BE AVAILABLE UNDER ANY LOCAL LAWS OF ANY
JURISDICTION (OTHER THAN THE

 

8

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internal laws of the United States and New York) that are contrary to any
provision of this Agreement.

 

5.5          DISCLAIMER.  THE PARTIES EXPRESSLY DISCLAIM ALL WARRANTIES, EXPRESS
OR IMPLIED, INCLUDING WITHOUT LIMITATION WARRANTIES OF MERCHANTABILITY, FITNESS
FOR A PARTICULAR PURPOSE, OR NON-INFRINGEMENT OF THIRD PARTY RIGHTS, UNLESS
OTHERWISE EXPRESSLY PROVIDED IN THIS AGREEMENT.

 

6.                                      CONFIDENTIALITY AND NONDISCLOSURE

 

6.1          NONDISCLOSURE AGREEMENT.  THE NON-DISCLOSURE AGREEMENT ENTERED INTO
BY AND BETWEEN THE PARTIES ON JULY 23, 2007 IS HEREBY INCORPORATED HEREIN AS IF
SET FORTH IN FULL, AND THE TERMS THEREOF WILL BE DEEMED TO APPLY TO ALL
INFORMATION AS MAY BE DISCLOSED BY EACH OF THE PARTIES DURING THE TERM OF THIS
AGREEMENT.

 

6.2          PUBLICATIONS.  TEVA WILL HAVE THE RIGHT TO REVIEW ANY PAPER
PROPOSED FOR PUBLICATION BY OR WITH THE AUTHORIZATION OF ISIS THAT DISCUSSES
VLA4 COMPOUNDS/PRODUCTS, INCLUDING ORAL PRESENTATIONS AND ABSTRACTS, REGARDLESS
OF WHETHER SUCH PAPER OR PRESENTATION INCLUDES ANY CONFIDENTIAL INFORMATION. 
ISIS WILL DELIVER A COMPLETE COPY TO TEVA AT LEAST [***] DAYS PRIOR TO
SUBMITTING THE PAPER TO A PUBLISHER.  TEVA WILL REVIEW ANY SUCH PAPER AND GIVE
ITS COMMENTS TO ISIS WITHIN [***] DAYS OF THE DELIVERY OF SUCH PAPER TO TEVA. 
ISIS WILL CONSIDER IN GOOD FAITH ANY TEVA REQUEST TO DELETE REFERENCES TO ANY
RIGHTS SPECIFIED HEREIN AND COMPLY WITH ANY TEVA REQUEST TO DELETE REFERENCES TO
ANY TEVA CONFIDENTIAL INFORMATION IN ANY SUCH PAPER AND AGREES TO WITHHOLD
PUBLICATION OF SAME FOR AN ADDITIONAL [***] DAYS IN ORDER TO PERMIT THE PARTIES
TO OBTAIN PATENT PROTECTION, IF TEVA DEEMS IT NECESSARY, IN ACCORDANCE WITH THE
TERMS OF THIS AGREEMENT.  TO THE EXTENT THAT ANY APPROVAL OF TEVA IS NOT
FORTHCOMING WITHIN THE TIME PERIODS SET FORTH HEREIN, THE ISIS LIAISON WITH
CONFER WITH THE TEVA LIAISON REGARDING TEVA’S APPROVAL.  NOTWITHSTANDING THE
FOREGOING, ISIS WILL NOT HAVE THE RIGHT TO PUBLISH OR PRESENT ANY CLINICAL TRIAL
RESULTS FROM TRIALS OF VLA4 COMPOUNDS/PRODUCTS WITHOUT THE PRIOR WRITTEN CONSENT
OF TEVA.

 

6.3          PUBLIC ANNOUNCEMENTS.  IF THE PARTIES MUTUALLY AGREE, THEY WILL
ISSUE A JOINT PRESS RELEASE REGARDING THE EXECUTION OF THIS AGREEMENT. EXCEPT AS
OTHERWISE SPECIFIED IN THIS AGREEMENT OR REQUIRED BY LAW, NEITHER PARTY WILL
ORIGINATE ANY NEWS RELEASE OR OTHER PUBLIC ANNOUNCEMENT, WRITTEN OR ORAL,
WHETHER IN THE PUBLIC PRESS, OR STOCKHOLDERS’ REPORTS, OR OTHERWISE, RELATING TO
THIS AGREEMENT, AND NEITHER PARTY WILL USE THE NAME, TRADEMARK, TRADE NAME, LOGO
OR LIKENESS OF THE OTHER PARTY OR ITS EMPLOYEES IN ANY PUBLICITY, NEWS RELEASE
OR DISCLOSURE RELATING TO THIS AGREEMENT, OR ITS SUBJECT MATTER, WITHOUT THE
PRIOR EXPRESS WRITTEN PERMISSION OF THE OTHER PARTY. THE FOREGOING PROHIBITION
AGAINST NEWS RELEASE OR OTHER PUBLIC ANNOUNCEMENT WILL NOT APPLY WHERE SUCH
PUBLICATION, PRESENTATION OR OTHER PUBLIC ANNOUNCEMENT IS REQUIRED BY LAW OR THE
RULES OF ANY RELEVANT STOCK EXCHANGE, AS INSTRUCTED BY THE PARTY’S OUTSIDE LEGAL
COUNSEL; PROVIDED, HOWEVER, THAT IN ANY SUCH CASE THE DISCLOSING PARTY WILL
PROVIDE NOTICE THEREOF TO THE OTHER PARTY WITH SUFFICIENT OPPORTUNITY TO RESPOND
AND, TO THE EXTENT FEASIBLE, TO PREVENT OR LIMIT ANY SUCH DISCLOSURE OR TO
REQUEST CONFIDENTIAL TREATMENT THEREOF, AND THE RECEIVING PARTY WILL GIVE
REASONABLE ASSISTANCE TO THE DISCLOSING PARTY TO PRESERVE THE INFORMATION

 

9

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as confidential.  The Liaisons will be the contact persons for the exchange of
the proposed public disclosures for party review.

 

7.                                      INDEMNIFICATION

 

7.1          INDEMNIFICATION.

 

(A)         TEVA WILL INDEMNIFY, DEFEND AND HOLD ISIS AND ITS AGENTS, EMPLOYEES,
OFFICERS AND DIRECTORS (THE “ISIS INDEMNITEES”) HARMLESS FROM AND AGAINST ANY
AND ALL LIABILITY, DAMAGE, LOSS, COST OR EXPENSE (INCLUDING REASONABLE
ATTORNEYS’ FEES) ARISING OUT OF THIRD PARTY CLAIMS OR SUITS (COLLECTIVELY,
“CLAIMS”) RELATED TO (I) BREACH BY TEVA OF ITS REPRESENTATIONS, WARRANTIES OR
COVENANTS SET FORTH IN THIS AGREEMENT; OR (II) THE DEVELOPMENT, MANUFACTURE,
USE, HANDLING, STORAGE, SALE OR OTHER DISPOSITION OF ANY VLA4 COMPOUNDS/PRODUCTS
BY TEVA OR ANY OF ITS AFFILIATES, CONTRACTORS OR SUBLICENSEES; PROVIDED,
HOWEVER, THAT TEVA’S OBLIGATIONS PURSUANT TO THIS SECTION 6.1(A) WILL NOT APPLY
TO THE EXTENT SUCH CLAIMS RESULT FROM (A) THE GROSS NEGLIGENCE OR WILLFUL
MISCONDUCT OF ANY OF THE ISIS INDEMNITEES OR (B) A BREACH BY ISIS OF ITS
REPRESENTATIONS AND WARRANTIES SET FORTH IN THIS AGREEMENT.

 

(B)        ISIS WILL INDEMNIFY, DEFEND AND HOLD TEVA AND ITS AFFILIATES AND EACH
OF THEIR RESPECTIVE AGENTS, EMPLOYEES, OFFICERS AND DIRECTORS (THE “TEVA
INDEMNITEES”) HARMLESS FROM AND AGAINST ANY AND ALL CLAIMS RELATED TO BREACH BY
ISIS OF ITS REPRESENTATIONS, WARRANTIES OR COVENANTS SET FORTH IN THIS
AGREEMENT; PROVIDED HOWEVER, THAT ISIS’ OBLIGATIONS PURSUANT TO THIS
SECTION 6.1(B) WILL NOT APPLY TO THE EXTENT THAT SUCH CLAIMS RESULT FROM (A) THE
GROSS NEGLIGENCE OR WILLFUL MISCONDUCT OF ANY OF THE TEVA INDEMNITEES; (B) A
BREACH BY TEVA OF ITS REPRESENTATIONS AND WARRANTIES SET FORTH IN THIS
AGREEMENT, OR (C) ISIS’ PERFORMANCE OF DEVELOPMENT OR OTHER ACTIVITIES WITH
RESPECT TO VLA4 COMPOUNDS/PRODUCTS ON BEHALF OF TEVA IN ACCORDANCE WITH TEVA’S
WRITTEN INSTRUCTIONS AND SPECIFICATIONS.

 

7.2          PROCEDURE.  A PARTY WILL GIVE THE OTHER PARTY NOTICE OF ANY CLAIM
UPON WHICH SUCH PARTY (THE “INDEMNIFIED PARTY”) INTENDS TO BASE AN
INDEMNIFICATION CLAIM (AN “INDEMNITY CLAIM”).  THE INDEMNIFYING PARTY HAS THE
RIGHT TO CONTROL THE DEFENSE, SETTLEMENT OR DISPOSITION OF ANY INDEMNITY CLAIM
USING COUNSEL OF ITS CHOICE AND ON TERMS THAT IT DEEMS ARE APPROPRIATE, EXCEPT
THAT INDEMNIFIED PARTY MAY, AT ITS OWN EXPENSE, PARTICIPATE IN THAT DEFENSE,
SETTLEMENT OR DISPOSITION USING COUNSEL OF ITS OWN CHOICE.  WITH RESPECT TO THE
DEFENSE, SETTLEMENT OR DISPOSITION OF AN INDEMNIFIED CLAIM, THE INDEMNIFIED
PARTY WILL PROVIDE THE INDEMNIFYING PARTY, UPON ITS REQUEST, WITH REASONABLE
ASSISTANCE AND COOPERATION WITH RESPECT TO THE INDEMNIFIED CLAIM.  WITHOUT
LIMITING THE GENERALITY OF THE FOREGOING, INDEMNIFYING PARTY MAY NOT CEASE TO
DEFEND, SETTLE OR OTHERWISE DISPOSE OF ANY INDEMNITY CLAIM WITHOUT THE
INDEMNIFIED PARTY’S PRIOR WRITTEN CONSENT, WHICH CONSENT MAY BE UNREASONABLY
WITHHELD, IF, AS A RESULT THEREOF, THE INDEMNIFIED PARTY WOULD BECOME SUBJECT TO
INJUNCTIVE OR OTHER EQUITABLE RELIEF.

 

7.3          LIMITATION OF LIABILITY.  NOTWITHSTANDING ANY OTHER PROVISION OF
THIS AGREEMENT TO THE CONTRARY, IN NO EVENT WILL ISIS’ TOTAL LIABILITY UNDER
THIS AGREEMENT (INCLUDING, BUT NOT

 

10

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limited to, liability under Section 7.1) exceed [***]; provided, however, that
the foregoing limitation shall not apply in the case of (a) any knowing
misrepresentation by ISIS under this Agreement, or (b) any knowing and
intentional breach of any covenant made by ISIS under this Agreement.

 

8.                                      TERM AND TERMINATION.

 

8.1          TERM.  THIS AGREEMENT WILL EXPIRE UPON THE EXPIRATION OR
TERMINATION OF BOTH THE AMENDED AND RESTATED ISIS/ATL AGREEMENT AND THE ATL/TEVA
AGREEMENT.

 

8.2          INSOLVENCY OR BANKRUPTCY.  ALL RIGHTS AND LICENSES GRANTED UNDER OR
PURSUANT TO THIS AGREEMENT BY ISIS OR TEVA ARE, AND WILL OTHERWISE BE DEEMED TO
BE, FOR PURPOSES OF SECTION 365(N) OF THE U.S. BANKRUPTCY CODE, LICENSES OF
RIGHT TO “INTELLECTUAL PROPERTY” AS DEFINED UNDER SECTION 101 OF THE U.S.
BANKRUPTCY CODE.  THE PARTIES AGREE THAT THE PARTIES, AS LICENSEES OF SUCH
RIGHTS UNDER THIS AGREEMENT, WILL RETAIN AND MAY FULLY EXERCISE ALL OF THEIR
RIGHTS AND ELECTIONS UNDER THE U.S. BANKRUPTCY CODE.  THE PARTIES FURTHER AGREE
THAT, IN THE EVENT OF THE COMMENCEMENT OF A BANKRUPTCY PROCEEDING BY OR AGAINST
EITHER PARTY UNDER THE U.S. BANKRUPTCY CODE, THE PARTY HERETO WHICH IS NOT A
PARTY TO SUCH PROCEEDING WILL BE ENTITLED TO A COMPLETE DUPLICATE OF (OR
COMPLETE ACCESS TO, AS APPROPRIATE) ANY SUCH INTELLECTUAL PROPERTY AND ALL
EMBODIMENTS OF SUCH INTELLECTUAL PROPERTY, AND SAME, IF NOT ALREADY IN THEIR
POSSESSION, WILL BE PROMPTLY DELIVERED TO THEM (I) UPON ANY SUCH COMMENCEMENT OF
A BANKRUPTCY PROCEEDING UPON THEIR WRITTEN REQUEST THEREFOR, UNLESS THE PARTY
SUBJECT TO SUCH PROCEEDING ELECTS TO CONTINUE TO PERFORM ALL OF ITS OBLIGATIONS
UNDER THIS AGREEMENT, OR (II) IF NOT DELIVERED UNDER (I) ABOVE, FOLLOWING THE
REJECTION OF THIS AGREEMENT BY OR ON BEHALF OF THE PARTY SUBJECT TO SUCH
PROCEEDING UPON WRITTEN REQUEST THEREFOR BY THE NON-SUBJECT PARTY.

 

8.3          SURVIVAL.  EXPIRATION OR TERMINATION OF THIS AGREEMENT WILL NOT
RELIEVE THE PARTIES OF ANY OBLIGATION ACCRUING PRIOR TO SUCH EXPIRATION OR
TERMINATION.  SECTIONS 5.4 AND 5.5, THIS SECTION 8.3 AND ARTICLE 10 WILL SURVIVE
EXPIRATION OR TERMINATION OF THIS AGREEMENT.  ANY EXPIRATION OR EARLY
TERMINATION OF THIS AGREEMENT WILL BE WITHOUT PREJUDICE TO THE RIGHTS OF EITHER
PARTY AGAINST THE OTHER ACCRUED OR ACCRUING UNDER THIS AGREEMENT PRIOR TO
TERMINATION, INCLUDING THE OBLIGATIONS TO MAKE ANY PAYMENTS THAT WERE DUE OR HAD
ACCRUED IMMEDIATELY PRIOR THE EFFECTIVE DATE OF SUCH TERMINATION.

 

9.                                      CHANGE OF CONTROL

 

9.1          CHANGE OF CONTROL OF ISIS.  ISIS ACKNOWLEDGES AND AGREES THAT IN
THE EVENT OF A CHANGE OF CONTROL OF ISIS IN WHICH THE THIRD PARTY ACQUIRING
CONTROL OF ISIS OR ITS ASSETS RELATING TO VLA4 COMPOUNDS/PRODUCTS IS [***],
THEN: (A) ISIS (OR THE SUCCESSOR ENTITY) WILL NOT BE ALLOWED TO [***]; AND
(B) ATL WILL BE PROHIBITED FROM PROVIDING ISIS (OR THE SUCCESSOR ENTITY) WITH
[***], OTHER THAN (A) REPORTS AND INFORMATION REQUIRED TO BE MADE AVAILABLE
UNDER SECTIONS 5.6 AND 5.8 OF THE AMENDED AND RESTATED ISIS/ATL AGREEMENT AND
(B) SUMMARY ANNUAL REPORTS REGARDING TEVA’S DEVELOPMENT AND COMMERCIALIZATION
ACTIVITIES WITH RESPECT TO VLA4 COMPOUNDS/PRODUCTS IN SUFFICIENT DETAIL TO ALLOW
ISIS TO ASCERTAIN ATL’S COMPLIANCE WITH ITS DILIGENCE OBLIGATIONS UNDER THE
AMENDED AND RESTATED ISIS/ATL AGREEMENT.

 

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9.2          CHANGE OF CONTROL OF ATL.  IN THE EVENT OF A CHANGE OF CONTROL OF
ATL IN WHICH THE THIRD PARTY ACQUIRING CONTROL OF ATL OR ITS ASSETS RELATING TO
VLA4 COMPOUNDS/PRODUCTS IS [***], THEN TEVA AGREES THAT IT WILL CONTINUE TO
PROVIDE TO ISIS ALL REPORTS RELATING TO THE DEVELOPMENT OR COMMERCIALIZATION OF
VLA4 COMPOUNDS/PRODUCTS THAT WOULD HAVE BEEN DELIVERED TO ATL BUT FOR SUCH
CHANGE OF CONTROL OF ATL.  ISIS AGREES THAT IT WILL HOLD ALL SUCH REPORTS AND
THE INFORMATION CONTAINED THEREIN CONFIDENTIAL TO THE SAME EXTENT THAT ISIS
WOULD BE REQUIRED TO HOLD SUCH REPORTS AND INFORMATION CONFIDENTIAL PURSUANT TO
THE AMENDED AND RESTATED ISIS/ATL AGREEMENT IF RECEIVED FROM ATL.

 

10.                               MISCELLANEOUS.

 

10.1        PAYMENT RELATED TO [***].  WITHIN FIVE (5) BUSINESS DAYS AFTER ISIS’
RECEIPT OF NOTICE FROM ATL THAT ATL HAS [***], ON OR BEFORE [***].

 

10.2        FORCE MAJEURE.  NEITHER PARTY WILL BE RESPONSIBLE OR LIABLE IN ANY
WAY FOR FAILURE OR DELAY IN CARRYING OUT THE TERMS OF THIS AGREEMENT RESULTING
FROM ANY CAUSE OR CIRCUMSTANCE BEYOND ITS REASONABLE CONTROL, INCLUDING FIRE,
FLOOD, OTHER NATURAL DISASTERS, WAR, INTERRUPTION OF TRANSIT, ACCIDENT,
EXPLOSION, CIVIL COMMOTION, AND ACTS OF ANY GOVERNMENTAL AUTHORITY; PROVIDED,
THAT THE PARTY SO AFFECTED WILL GIVE PROMPT NOTICE THEREOF TO THE OTHER.  NO
SUCH FAILURE OR DELAY WILL TERMINATE THIS AGREEMENT, AND EACH PARTY WILL
COMPLETE ITS OBLIGATIONS HEREUNDER AS PROMPTLY AS REASONABLY PRACTICABLE
FOLLOWING CESSATION OF THE CAUSE OR CIRCUMSTANCES OF SUCH FAILURE OR DELAY.

 

10.3        LIAISONS.  FOR PURPOSES OF COORDINATING ACTIVITIES BETWEEN THE
PARTIES UNDER THE AGREEMENT, INCLUDING, WITHOUT LIMITATION, SHARING OF PRESS
RELEASES AND PUBLICATIONS FOR REVIEW, EACH PARTY WILL APPOINT AN INDIVIDUAL TO
ACT AS ITS LIAISON (EACH A “LIAISON” AND COLLECTIVELY, THE “LIAISONS”).  A PARTY
MAY CHANGE ITS LIAISON AT ANY TIME BY PROVIDING WRITTEN NOTICE TO THE OTHER
PARTY ALONG WITH CONTACT INFORMATION FOR THE ITS NEW LIAISON.

 

10.4        AGENCY.  NEITHER PARTY IS, NOR WILL BE DEEMED TO BE, AN EMPLOYEE,
AGENT OR LEGAL REPRESENTATIVE OF THE OTHER PARTY FOR ANY PURPOSE.  NEITHER PARTY
WILL BE ENTITLED TO ENTER INTO ANY CONTRACTS IN THE NAME OF, OR ON BEHALF OF THE
OTHER PARTY, NOR WILL A PARTY BE ENTITLED TO PLEDGE THE CREDIT OF THE OTHER
PARTY IN ANY WAY OR HOLD ITSELF OUT AS HAVING AUTHORITY TO DO SO.

 

10.5        CHOICE OF LAW.  THIS AGREEMENT WILL BE GOVERNED AND INTERPRETED, AND
ALL RIGHTS AND OBLIGATIONS OF THE PARTIES WILL BE DETERMINED, IN ACCORDANCE WITH
THE LAWS OF THE STATE OF NEW YORK (USA), WITHOUT REGARD TO ITS CONFLICT OF LAWS
RULES.

 

10.6        NOTICES.  ALL NOTICES, REQUESTS, DEMANDS, WAIVERS, CONSENTS,
APPROVALS OR OTHER COMMUNICATIONS TO ANY PARTY HEREUNDER WILL BE IN WRITING AND
WILL BE DEEMED TO HAVE BEEN DULY GIVEN IF DELIVERED PERSONALLY TO SUCH PARTY OR
SENT TO SUCH PARTY BY FACSIMILE TRANSMISSION OR BY REGISTERED OR CERTIFIED MAIL,
POSTAGE PREPAID, TO THE ADDRESSES LISTED BELOW, OR TO SUCH OTHER ADDRESS AS THE
ADDRESSEE MAY HAVE SPECIFIED IN NOTICE DULY GIVEN TO THE SENDER AS PROVIDED
HEREIN.

 

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If to TEVA:

 

with a copy to:

TEVA Pharmaceutical Industries Ltd.

 

TEVA’s General Counsel, Uzi Karniel,

5 Basel Street, P.O.  Box 3190

 

at the address of TEVA (Fax: 972-3-926-7429); and

Petah Tiqva 49131

 

Richard S. Egosi, Esq.

Israel

 

Senior Vice President and General

Attn: Vice President, Global Innovative Pipeline Management

 

Counsel

Fax: 972-3-926-7742

 

TEVA North America

 

 

1090 Horsham Road

 

 

North Wales, PA 19454-1090

 

 

Fax: (215) 591-8813

 

If to ISIS:

 

With a copy to:

Isis Pharmaceuticals, Inc.

 

Isis Pharmaceuticals, Inc.

1896 Rutherford Road

 

1896 Rutherford Road

Carlsbad, CA 92008

 

Carlsbad, CA 92008

USA

 

USA

Attention: Chief Operating Officer

 

Attention: General Counsel

Fax No.: +1 (760) 931-9639

 

Fax No.: +1 (760) 268-4922

 

 

 

 

Such notice, request, demand, waiver, consent, approval or other communications
will be deemed to have been given as of the date so delivered, if sent by
facsimile transmission, or five (5) days after so mailed.

 

10.7        SEVERABILITY.  SHOULD ONE OR MORE PROVISIONS OF THIS AGREEMENT BE
HELD UNENFORCEABLE OR IN CONFLICT WITH APPLICABLE LAW OR REGULATION, THE PARTIES
WILL SUBSTITUTE, BY MUTUAL CONSENT, VALID PROVISIONS FOR SUCH INVALID PROVISIONS
WHICH VALID PROVISIONS IN THEIR ECONOMIC EFFECT ARE SUFFICIENTLY SIMILAR TO THE
INVALID PROVISIONS THAT IT CAN BE REASONABLY ASSUMED THAT THE PARTIES WOULD HAVE
ENTERED INTO THIS AGREEMENT WITH SUCH VALID PROVISIONS.  IN CASE SUCH VALID
PROVISIONS CANNOT BE AGREED UPON, THE INVALIDITY OF ONE OR SEVERAL PROVISIONS OF
THIS AGREEMENT WILL NOT AFFECT THE VALIDITY OF THIS AGREEMENT AS A WHOLE, UNLESS
THE INVALID PROVISIONS ARE OF SUCH ESSENTIAL IMPORTANCE TO THIS AGREEMENT THAT
IT IS TO BE REASONABLY ASSUMED THAT THE PARTIES WOULD NOT HAVE ENTERED INTO THIS
AGREEMENT WITHOUT THE INVALID PROVISIONS.

 

10.8        ENTIRE AGREEMENT.  THIS AGREEMENT, ALONG WITH ANY AGREEMENTS
REFERENCED HEREIN AND THAT CERTAIN DRUG SUPPLY, MANUFACTURE AND TECHNOLOGY
TRANSFER AGREEMENT BETWEEN THE PARTIES DATED AS OF THE EFFECTIVE DATE, EACH AS
AMENDED FROM TIME TO TIME, STATES THE ENTIRE AGREEMENT REACHED BETWEEN THE
PARTIES WITH RESPECT TO THE TRANSACTIONS CONTEMPLATED HEREBY AND MAY NOT BE
AMENDED OR MODIFIED EXCEPT BY WRITTEN INSTRUMENT DULY EXECUTED BY THE PARTIES. 
THIS AGREEMENT REPLACES AND SUPERSEDES ANY AND ALL PREVIOUS AGREEMENTS AND
UNDERSTANDINGS BETWEEN THE PARTIES REGARDING THE SUBJECT MATTER HEREOF, WHETHER
WRITTEN OR ORAL (INCLUDING, WITHOUT LIMITATION, THAT CERTAIN LETTER OF
AGREEMENT, DATED AUGUST 8, 2007, BY AND AMONG ISIS, TEVA AND ATL).

 

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10.9        NO WAIVER.  THE FAILURE OF EITHER PARTY TO ENFORCE AT ANY TIME, OR
FOR ANY PERIOD OF TIME, ANY PROVISION OF THIS AGREEMENT WILL NOT BE CONSTRUED AS
A WAIVER OF SUCH PROVISION OR OF THE RIGHT OF SUCH PARTY THEREAFTER TO ENFORCE
EACH AND EVERY PROVISION.

 

10.10      ASSIGNMENT; BINDING EFFECT.  THIS AGREEMENT IS PERSONAL TO EACH PARTY
AND NEITHER PARTY MAY ASSIGN, DISPOSE OF, TRANSFER OR DELEGATE ANY OF ITS
RIGHTS, DUTIES OR OBLIGATIONS UNDER THIS AGREEMENT OR ANY INTEREST IN THIS
AGREEMENT WITHOUT THE OTHER PARTY’S PRIOR WRITTEN CONSENT, WHICH CONSENT MAY NOT
BE UNREASONABLY WITHHELD, EXCEPT THAT SUBJECT TO THE PROVISIONS OF THIS
SECTION 10.10, (A) EITHER PARTY MAY ASSIGN OR DELEGATE ANY OR ALL OF ITS RIGHTS
AND OBLIGATIONS UNDER THIS AGREEMENT TO ITS AFFILIATES WITHOUT THE OTHER PARTY’S
PRIOR WRITTEN CONSENT; PROVIDED, THAT THE ASSIGNING PARTY REMAINS PRIMARILY
LIABLE FOR THE PERFORMANCE AND NONPERFORMANCE OF ITS AFFILIATE’S DUTIES AND
OBLIGATIONS UNDER THIS AGREEMENT AND PROVIDED, FURTHER, THAT THE NON-ASSIGNING
PARTY DOES NOT INCUR OR SUFFER ANY ADVERSE TAX OR OTHER FINANCIAL CONSEQUENCES
AS A RESULT THEREOF, AND (B) EITHER PARTY MAY ASSIGN THIS AGREEMENT WITHOUT THE
OTHER PARTY’S PRIOR WRITTEN CONSENT TO ITS SUCCESSOR IN INTEREST IN CONNECTION
WITH A MERGER, ACQUISITION OR SALE OF ALL OR SUBSTANTIALLY ALL OF SUCH PARTY’S
ASSETS; AND (C) TEVA MAY ASSIGN THIS AGREEMENT WITHOUT THE PRIOR WRITTEN CONSENT
OF ISIS TO A SUCCESSOR IN INTEREST IN CONNECTION WITH THE SALE OF SUBSTANTIALLY
ALL OF THE ASSETS USED PRIMARILY IN ITS MULTIPLE SCLEROSIS BUSINESS OR  ANY
OTHER BUSINESS OF AN INDICATION BEING EXPLOITED HEREUNDER; PROVIDED, THAT IN ALL
SUCH CASES SUCH SUCCESSOR IN INTEREST AGREES IN WRITING TO BE BOUND BY ALL OF
SUCH PARTY’S OBLIGATIONS AS ASSIGNEE.   THIS AGREEMENT IS BINDING UPON,
ENFORCEABLE AGAINST, AND INURES TO THE BENEFIT OF THE PARTIES  AND THEIR
RESPECTIVE SUCCESSORS AND PERMITTED ASSIGNS.  ANY ATTEMPT BY EITHER PARTY TO
ASSIGN OR DELEGATE ANY OF THE DUTIES, RESPONSIBILITIES OR OTHER OBLIGATIONS OF
THIS AGREEMENT THAT IS NOT IN COMPLIANCE WITH THIS PARAGRAPH 8.8 WILL BE DEEMED
TO BE NULL AND VOID AB INITIO.

 

10.11      COUNTERPARTS.  THIS AGREEMENT MAY BE EXECUTED IN ANY NUMBER OF
COUNTERPARTS EACH OF WHICH WILL BE DEEMED TO BE AN ORIGINAL AND ALL OF WHICH
TAKEN TOGETHER WILL CONSTITUTE ONE AND THE SAME INSTRUMENT.

 

10.12      DISPUTE RESOLUTION.

 

(A)         IT IS THE OBJECTIVE OF THE PARTIES TO SEEK TO RESOLVE ANY ISSUES OR
DISPUTES ARISING UNDER THIS AGREEMENT IN AN EXPEDIENT AND AMICABLE MANNER, IF AT
ALL POSSIBLE, AND TO THAT END THE PARTIES AGREE TO ABIDE BY THE FOLLOWING
PROCEDURES SET FORTH IN THIS SECTION 10.12 TO RESOLVE ANY SUCH ISSUES OR
DISPUTES.  THE PARTIES INITIALLY WILL ATTEMPT TO SETTLE ANY SUCH ISSUE OR
DISPUTE THROUGH GOOD FAITH NEGOTIATIONS IN THE SPIRIT OF MUTUAL COOPERATION
BETWEEN BUSINESS EXECUTIVES WITH AUTHORITY TO RESOLVE THE DISPUTE.  PRIOR TO
TAKING ACTION AS PROVIDED IN SECTION 10.12(B) OF THIS AGREEMENT, THE PARTIES
WILL FIRST SUBMIT SUCH DISPUTE TO THE EXECUTIVE VICE PRESIDENT AND CHIEF
FINANCIAL OFFICER OF ISIS AND THE GROUP VICE PRESIDENT OF GLOBAL INNOVATIVE
RESOURCES OF TEVA (COLLECTIVELY, THE “EXECUTIVES”) FOR RESOLUTION.  THE
EXECUTIVES WILL ATTEMPT TO RESOLVE THE DISPUTE THROUGH GOOD FAITH NEGOTIATIONS
OVER A REASONABLE PERIOD OF UP TO 60 CALENDAR DAYS, UNLESS THE EXECUTIVES
MUTUALLY AGREE IN WRITING TO EXTEND SUCH PERIOD OF NEGOTIATION.  SUCH
60-CALENDAR DAY PERIOD WILL BE DEEMED TO COMMENCE ON THE DATE THE DISPUTE WAS
SUBMITTED TO THE EXECUTIVES.  THE EXECUTIVES WILL, IF MUTUALLY AGREED BY THE
EXECUTIVES, SUBMIT THE DISPUTE TO

 

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VOLUNTARY MEDIATION AT SUCH PLACE AND FOLLOWING SUCH PROCEDURES AS THE PARTIES
WILL REASONABLY AGREE.  ALL NEGOTIATIONS PURSUANT TO THIS SECTION 10.12(A) WILL
BE CONFIDENTIAL, AND WILL BE TREATED AS COMPROMISE AND SETTLEMENT NEGOTIATIONS
FOR PURPOSES OF APPLICABLE RULES OF EVIDENCE.

 

(B)        ANY DISPUTE THAT IS NOT RESOLVED BY THE PARTIES BY NEGOTIATION AND/OR
MEDIATION PURSUANT TO SECTION 10.12(A) ABOVE WILL, UPON THE SUBMISSION OF A
WRITTEN REQUEST OF EITHER PARTY TO THE OTHER PARTY, BE SUBMITTED TO BINDING
ARBITRATION BEFORE A SINGLE ARBITRATOR IN ACCORDANCE WITH THE THEN PREVAILING
RULES OF THE INTERNATIONAL CHAMBER OF COMMERCE (“ICC”).

 

(C)         IF THE DISPUTE INVOLVES TECHNICAL ISSUES, THE ARBITRATOR WILL BE
QUALIFIED IN THE FIELD OF PHARMACEUTICALS RESEARCH AND DEVELOPMENT.  IF THE
PARTIES CANNOT AGREE ON AN ARBITRATOR WITHIN THIRTY (30) DAYS OF FILING WITH THE
ICC, THEN THE ICC WILL APPOINT ONE IN ACCORDANCE WITH ITS THEN PREVAILING RULES.

 

(D)        THE ARBITRATION WILL BE HELD IN NEW YORK, NEW YORK, USA.  THE
DECISION AND AWARD OF THE ARBITRATOR WILL BE FINAL AND BINDING AND THE AWARD SO
RENDERED MAY BE ENTERED IN ANY COURT HAVING JURISDICTION IN RELATION TO THE
AWARD, AS A JUDGMENT OF THE COURT.

 

(E)         EACH PARTY WILL PAY ONE HALF OF THE FEE CHARGED BY THE ARBITRATOR,
AND HALF OF ANY CHARGE PAYABLE IN RESPECT OF THE VENUE WHERE THE ARBITRATION IS
CONDUCTED; PROVIDED, HOWEVER, THAT IN RENDERING ITS DECISION THE ARBITRATOR HAS
THE DISCRETION TO REALLOCATE THE AFOREMENTIONED PAYMENTS. THE PARTIES WILL
OTHERWISE EACH BEAR THEIR OWN COSTS OF ARBITRATION.

 

(F)         THE DECISION OF THE ARBITRATOR MAY BE REDUCED TO A JUDGMENT BY ANY
COURT OF COMPETENT JURISDICTION.

 

(G)        NOTWITHSTANDING THE ABOVE, TO THE FULL EXTENT ALLOWED BY LAW, EITHER
PARTY MAY BRING AN ACTION IN ANY COURT OF COMPETENT JURISDICTION FOR INJUNCTIVE
RELIEF (OR ANY OTHER PROVISIONAL REMEDY) TO PROTECT THE PARTIES’ RIGHTS OR
ENFORCE THE PARTIES’ OBLIGATIONS UNDER THIS AGREEMENT PENDING FINAL RESOLUTION
OF ANY CLAIMS RELATED THERETO IN AN ARBITRATION PROCEEDING AS PROVIDED ABOVE. 
IN ADDITION, EITHER PARTY MAY BRING AN ACTION IN ANY COURT OF COMPETENT
JURISDICTION TO RESOLVE DISPUTES PERTAINING TO THE VALIDITY, CONSTRUCTION,
SCOPE, ENFORCEABILITY, INFRINGEMENT OR OTHER VIOLATIONS OF PATENTS OR OTHER
PROPRIETARY OR INTELLECTUAL PROPERTY RIGHTS.

 

10.13      NO CONSEQUENTIAL DAMAGES.  IN NO EVENT SHALL EITHER ISIS OR TEVA OR
THEIR AFFILIATES BE LIABLE FOR SPECIAL, INDIRECT, INCIDENTAL, PUNITIVE OR
CONSEQUENTIAL DAMAGES, WHETHER BASED ON CONTRACT, TORT OR ANY OTHER LEGAL
THEORY; PROVIDED, THAT THIS LIMITATION SHALL NOT LIMIT THE INDEMNIFICATION
OBLIGATION OF SUCH PARTY UNDER THE PROVISIONS OF SECTION 6 FOR SUCH DAMAGES
CLAIMED BY A THIRD PARTY.

 

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IN WITNESS WHEREOF, THE PARTIES HAVE CAUSED THIS AGREEMENT TO BE DULY EXECUTED
AND DELIVERED IN DUPLICATE ORIGINALS AS OF THE DATE FIRST ABOVE WRITTEN.

 

TEVA PHARMACEUTICAL INDUSTRIES, LTD.

 

 

By:

/s/ Ruth Levy, Ph.D

 

 

 

Its:

Vice President

 

 

 

ISIS PHARMACEUTICALS, INC.

 

 

By:

/s/ B. Lynne Parshall

 

 

 

Its:

COO & CFO

 

 

 

 

 

With respect to Section 2.5 and Section 10.1 only,

 

ANTISENSE THERAPEUTICS LTD.

 

 

By:

/s/ Mark Diamond

 

 

 

Its:

CEO

 

 

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