<PAGE> 1
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
PURSUANT TO SECTION 13 OR 15(d) OF THE
SECURITIES EXCHANGE ACT OF 1934
Date of Report (Date of earliest event reported): AUGUST 31, 1999
ISIS PHARMACEUTICALS, INC.
(Exact name of registrant as specified in its charter)
DELAWARE
(State or other jurisdiction of incorporation)
0-19125 33-0336973
(Commission File No.) (IRS Employer Identification No.)
2292 FARADAY AVENUE
CARLSBAD, CALIFORNIA 92008
(Address of principal executive offices and zip code)
(760) 931-9200
(Registrant's telephone number, including area code)
<PAGE> 2
ITEM 5. OTHER EVENTS.
On July 18, 1995, Isis Pharmaceuticals, Inc. ("Isis") and Boehringer Ingelheim
International, GmbH ("BI") formed a collaboration to combine the clinical
development and research programs of both companies in the field of cell
adhesion. Effective August 31, 1999 Isis has reacquired control of the ISIS
2302 drug compound in order to redirect the commercialization of this product.
In connection with the collaboration, Isis and BI entered into a Stock Purchase
Agreement effective July 18, 1995. The Stock Purchase Agreement has been amended
effective August 31, 1999 in accordance with the attached Exhibit 10.2.
ITEM 7. FINANCIAL STATEMENTS AND EXHIBITS.
(a) Financial Statements of Businesses Acquired. Not applicable.
(b) Pro Forma Financial Information. Not applicable.
(c) Exhibits
Exhibit 10.1* Agreement dated August 31, 1999 between
Boehringer Ingelheim International GmbH and Isis
Pharmaceuticals, Inc.
Exhibit 10.2 Amendment to the Stock Purchase Agreement dated
August 31, 1999
*Confidential treatment has been requested with respect to certain portions of
this exhibit. Omitted portions have been filed separately with the Securities
and Exchange Commission.
<PAGE> 3
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the
registrant has duly caused this report to be signed on its behalf by the
undersigned hereunto duly authorized.
ISIS PHARMACEUTICALS, INC.
Dated: September 2, 1999 By: /S/ B. LYNNE PARSHALL
---------------------------------
B. Lynne Parshall
Executive Vice President
<PAGE> 1
EXHIBIT 10.1
*Confidential treatment has been requested with respect to certain portions of
this exhibit. Omitted portions have been filed separately with the Securities
and Exchange Commission.
AGREEMENT
This AGREEMENT, dated as of August 31, 1999 (the "Effective Date"), by and
between BOEHRINGER INGELHEIM INTERNATIONAL GmbH ("BI"), a company organized and
existing under the laws of the Federal Republic of Germany, with its principal
place of business at D-55216 Ingelheim/Rhein, Federal Republic of Germany, and
ISIS PHARMACEUTICALS, INC. ("Isis"), a Delaware corporation with its principal
place of business at 2292 Faraday Drive, Carlsbad, California 92008, U.S.A.,
W I T N E S S E T H :
WHEREAS, pursuant to the Collaborative Agreement, dated as of July 18,
1995, BI and Isis previously entered into collaborative research, development
and commercial relationship in the Field; and
WHEREAS, BI and Isis have mutually agreed to terminate the Collaborative
Agreement and to set forth in this Agreement, which shall supercede the
Collaborative Agreement as of the Effective Date, their mutual agreement with
respect to collaborative research in the Field
WHEREAS, BI and Isis have mutually agreed to continue their
collaboration with respect to research under the Research Plan through December
31, 1999, and to discontinue their collaboration with respect to development, in
each case, as provided herein,
NOW, THEREFORE, in consideration of the foregoing and the mutual
covenants and agreements herein contained, the Parties hereby agree as follows:
ARTICLE 1.
DEFINITIONS
For purposes of this Agreement, the capitalized terms defined in this Agreement
shall have the meanings specified in Appendix A attached hereto.
ARTICLE 2.
SCOPE AND STRUCTURE OF COLLABORATION
2.1 Termination of Collaborative Agreement. Pursuant to the Collaborative
Agreement, BI and Isis established a collaboration for the purpose of
identifying, developing and commercializing products in the Field. The
Parties hereby acknowledge and mutually agree that as of the Effective
Date the Collaborative Agreement shall be terminated. The Parties
further hereby agree that as of the Effective Date this Agreement shall
supercede the Collaborative Agreement and no agreement with respect to
the subject matter hereof shall exist between the Parties other than the
agreements expressly set forth herein. The Parties further agree that
they will continue their collaboration with respect to research under
the Research Plan and discontinue their collaboration with respect to
development, in each case, as provided herein.
2.2 ISIS 2302.
(a) The Parties hereby acknowledge and agree that BI has
abandoned its participation in the further development and
commercialization of ISIS 2302 in any and all formulations and
indications of every kind whatsoever. BI acknowledges and agrees that
Isis has full responsibility and authority to develop and commercialize
ISIS 2302.
-1-
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(b) As of the Effective Date, Isis shall pay BI a royalty, on a
country-by-country basis, on Net Sales of any formulation or indication
of ISIS 2302 occurring on or after the Effective Date as follows:
(i) With respect to all sales of any [***] of ISIS 2302
for [***], such royalty rate shall be [***] of Net Sales;
(ii) With respect to all sales of any [***] other than
for [***], such royalty rate shall be [***] of Net Sales;
(iii) With respect to sales of any [***] of ISIS 2302
for the indications of [***], such royalty rate shall be [***]
of Net Sales; and
(iv) With respect to all sales of ISIS 2302 not
specified in clause (i), (ii) or (iii) above, such royalty rate
shall be [***] of Net Sales.
(c) The obligations to pay royalties under this Section 2.2
shall continue, on a country-by-country basis, until the later of (i)
the [***], or (ii) [***] anniversary of the Effective Date.
2.3 Additional Compounds. The Parties further agree that, as of the
Effective Date, they shall have the respective rights and obligations
set forth in this Section 2.3 with respect to the Additional Compounds.
(a) BI shall have the sole right to develop, commercialize, sell
and license any of the compounds known as [***] or any compound from out
of the [***] series that had been synthesized as of the Effective Date.
If BI commercializes any of the compounds known as [***] or any compound
from out of the [***] series that had been synthesized as of the
Effective Date, either by itself or through a Third Party, BI shall pay
Isis a royalty, on a country-by-country basis, of [***] on any and all
Net Sales of [***] or any compound from out of the [***] series that had
been synthesized as of the Effective Date, as the case may be. Isis
hereby represents that during the term of the Collaborative Agreement it
did not discover any small-molecule compounds in the Field with the
exception of Isis's small molecule combinatorial libraries.
(b) Isis shall have the sole right to develop, commercialize,
sell and license any of the compounds known as [***]. If Isis
commercializes the compounds known as [***], either by itself or through
a Third Party, Isis shall pay BI a royalty, on a country-by-country
basis, of [***] on any and all Net Sales of [***], as the case may be.
BI hereby represents that during the term of the Collaborative Agreement
it did not discover any Antisense Molecules in the Field.
(c) Each Party shall have the right, in its sole discretion, to
in- and out-license and establish collaborations with Third Parties
within the Field without the approval of, and without any obligation to,
the other Party.
*CONFIDENTIAL TREATMENT REQUESTED
2
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(d) The obligations to pay royalties under Section 2.3(a) and
Section 2.3(b), respectively, shall continue, on a country-by-country
basis, until the later of (i) the [***], or (ii) the [***] anniversary
of the Effective Date.
2.4 Both Parties shall have the right to practice the Joint [***] Patent(s);
provided, however, that:
(i) Isis shall have the sole right to develop,
commercialize and sell Antisense Molecules covered by
any issued Joint [***] Patent(s), and Isis shall pay BI
a royalty, on a country-by-country basis, of [***] of
any and all Net Sales of such Antisense Molecules or
compounds containing such Antisense Molecules;
(ii) BI shall have the sole right to develop,
commercialize and sell small-molecule compounds covered
by any issued Joint [***] Patent(s), and BI shall pay
Isis a royalty, on a country-by-country basis, of [***]
of any and all Net Sales of such small-molecule
compounds or compounds containing such small-molecule
compounds; and
(iii) Either Party may develop, commercialize and sell
any compound that is not (a) an Antisense Molecule or
(b) a small-molecule compound, covered by an issued
Joint [***] Patent(s), so long as such Party has the
intellectual property right to develop, commercialize or
sell such compound, and such Party shall pay the other
Party a royalty, on a country-by-country basis, of [***]
of any and all Net Sales of such compound.
(b) The obligations to pay royalties under Section 2.4 shall
continue, on a country-by-country basis, until the later of (i) the
[***], or (ii) [***] anniversary of the Effective Date.
2.5 [***].
(a) As of the Effective Date, BI shall pay Isis a royalty, on a
country-by-country basis, of [***] on Net Sales of the [***] in the
indications of [***] occurring on or after the Effective Date.
(b) As of the Effective Date, BI shall pay Isis a royalty, on a
country-by-country basis, of [***] on Net Sales of any formulation or
indication of [***] occurring on or after the Effective Date.
(c) Isis acknowledges and agrees that BI has full responsibility
and authority to develop and commercialize [***].
*CONFIDENTIAL TREATMENT REQUESTED
3
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(d) The obligations to pay royalties under this Section 2.5
shall continue, on a country-by-country basis, until the later of (i)
the [***], as the case may be, or (ii) [***] anniversary of the
Effective Date.
2.6 Other Compounds. Any given compound in the Field, including without
limitation, compounds which have been part of the ongoing screening and
optimization of (i) Antisense Molecules and small-molecule compounds by
Isis and (ii) small-molecule compounds by BI, throughout the term of the
Collaborative Agreement, other than ISIS 2302, [***], the Additional
Compounds, and Antisense Molecules, small-molecule compounds and other
compounds covered by an issued Joint [***] Patent may be commercialized
and/or sold by the Party having the intellectual property right to
develop, commercialize or sell such compound without any obligation
whatsoever to the other Party under this Agreement.
ARTICLE 3.
RESEARCH PLAN
3.1 Research Plan. The Parties hereby agree to cooperate in carrying out the
Research Plan during the Research Period, as described in this Article
3.
3.2 Research Agreement. During the Research Period, BI and Isis hereby agree
to work cooperatively to fulfill the Research Plan.
3.3 Research Period. The Research Plan shall be undertaken by the Parties
during the Research Period.
3.4 Research Management Committee. An RMC composed of four (4)
representatives from each Party shall be appointed upon signing of this
Agreement. The RMC shall be responsible for managing day-to-day work
necessary to perform the Research Plan during the Research Period.
3.5 Research Expenses. BI shall make the payments with respect to the
funding of the Research Plan in the amounts and at the times described
in this Section 3.5:
(a) 1999 research expenses for Isis shall be [***].
(b) Other research expenses relating to the [***] and other
expenses approved by the RMC for Isis shall be [***].
(c) 1999 research expenses for BI shall be [***].
(d) With respect to the expenses described in paragraphs (a),
(b) and (c) above, BI shall pay Isis [***] on the 45th day after
December 31, 1999. Other than the payment expressly set forth in this
Section 3.5(d), there shall be no other costs or expenses of any kind
with respect to the Research Plan attributable to or payable by BI. Isis
shall not be responsible for any research expenses relating to [***]
that have not already been paid as of the Effective Date.
*CONFIDENTIAL TREATMENT REQUESTED
4
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ARTICLE 4.
COLLABORATIVE COSTS
4.1 Collaborative Costs for 1998. Notwithstanding the termination of the
Collaborative Agreement, the Parties hereby acknowledge and agree that
all costs associated with the Collaborative Agreement incurred for
calendar year 1998 shall be attributed and paid as provided in this
Section 4.1.
(a) Such 1998 collaborative costs in the amount of [***] shall
be attributed to Isis.
(b) Such 1998 collaborative costs in the amount of [***] shall
be attributed to BI.
(c) With respect to such 1998 collaborative costs, BI hereby
agrees to make a cash payment to Isis in the amount of [***] by wire
transfer in immediately available funds within ten (10) business days of
the Effective Date. Except as expressly provided in this Section 4.1(c),
there shall be no other research or development costs associated with
the Collaborative Agreement payable by either Party to the other Party
for calendar year 1998.
4.2 ISIS 2302 Development Costs in 1999. Notwithstanding the termination of
the Collaborative Agreement, the Parties hereby acknowledge and agree
that costs with respect to the development of ISIS 2302 in calendar year
1999 shall be attributed and paid as provided in this Section 4.2.
Except as expressly provided in this Section 4.2, there shall be no
other costs payable by either Party to the other Party for development
costs related to ISIS 2302 in calendar year 1999. With respect to such
development costs, BI hereby agrees to make a cash payment to Isis in
the amount of [***] within ten (10) business days of the Effective Date
and a cash payment to Isis in the amount of [***] on December 31, 1999,
in each case, by wire transfer in immediately available funds.
4.3 Future Development Costs of ISIS 2302. There shall be no other costs or
expenses of any kind with respect to the development of ISIS 2302
attributable to or payable by BI after December 31, 1999.
4.4 Other Costs. Except as expressly set forth in this Agreement, there
shall be no other costs or expenses of any kind with respect to the
research or development of any compound or product attributable to or
payable by either Party.
ARTICLE 5.
REPAYMENT OF ADVANCES
5.1 Credit Facility under the Collaborative Agreement. The Parties hereby
acknowledge and agree that BI has made Advances to Isis pursuant to
Article 7 of the Collaborative Agreement (each, an "Outstanding
Obligation"), in the aggregate amount of $22,576,405, as follows:
*CONFIDENTIAL TREATMENT REQUESTED
5
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<TABLE>
<CAPTION>
AMOUNT OF
OUTSTANDING CREDIT MATURITY INTEREST
DATE OF ADVANCE OBLIGATION DATE RATE
- --------------- ---------- ---- ----
<S> <C> <C> <C>
October 15, 1996 $8,300,000 October 15, 2003 8.46%
December 30, 1996 $7,900,000 December 30, 2003 8.36%
June 30, 1997 $6,376,405 June 30, 2004 8.45%
</TABLE>
5.2 Repayment of Outstanding Obligations; No Further Advances. Isis shall
repay the principal amount of each Outstanding Obligation to BI in full
prior to the respective Credit Maturity Date of each Outstanding
Obligation. The Parties expressly acknowledge and agree that BI and its
Affiliates have no obligation whatsoever under the Collaborative
Agreement or hereunder to make any additional Advances to Isis.
5.3 Interest Rate on Outstanding Obligations. Isis shall pay BI interest on
the unpaid principal amount of each Outstanding Obligation at the
respective interest rate specified in the column captioned "Interest
Rate" in the chart set forth in Section 5.1. Interest shall be due and
payable by Isis to BI two (2) times in each calendar year, on May 31st
and November 30th, or the first business day thereafter, if any such
date shall occur on a non-business day.
5.4 Prepayment of Principal.
(a) Optional Prepayment. Isis may prepay the outstanding
principal balance of any Outstanding Obligation, in whole or in part, at
any time without penalty or premium; provided, however, that the accrued
interest on such prepaid amounts of Outstanding Obligations shall be
included in the prepayment of principal on the date of such prepayment.
(b) Mandatory Prepayment. Notwithstanding anything to the
contrary set forth in this Agreement, for as long as any Outstanding
Obligation is outstanding:
(i) for each fiscal year in which commercial sales of [***] or
any compound from out of the [***] series that had been
synthesized as of the Effective Date, or any small-molecule
compounds covered by the Joint [***] Patent(s) occur, Isis shall
prepay the outstanding principal amount of the Outstanding
Obligations in an amount calculated for such year equal to [***]
of the total royalties received by Isis on such commercial sales
during such year as determined based upon the audited year-end
financial statements for such year;
(ii) prior to January 1, 2002, for each fiscal year in which
commercial sales of ISIS 2302 occur, Isis shall prepay the
outstanding principal amount of the Outstanding Obligations in
an amount calculated for such year equal to [***] of the net
royalties (total royalties received by Isis less the royalty
paid by Isis to BI) on such commercial sales during such year as
determined based upon the audited year-end financial statements
for such year; and
(iii) after January 1, 2002, for each fiscal year in which
commercial sales of ISIS 2302 occur, Isis shall prepay the
outstanding principal amount of the Outstanding Obligations in
an amount calculated for such year equal to [***] of the net
royalties (total royalties received by Isis less the royalty
paid by Isis to BI) on such commercial sales during such year,
as determined based upon the audited year-end financial
statements for such year.
*CONFIDENTIAL TREATMENT REQUESTED
6
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Each mandatory prepayment under this Section 5.4(b) shall be payable within 30
calendar days after completion of Isis' consolidated annual audited year-end
financial statements for such year.
5.5 Method of Payment.
(a) All interest on each Outstanding Obligation shall be paid in
cash and in U.S. dollars on the dates described in Section 5.3.
(b) All optional prepayments on Outstanding Obligations pursuant
to Section 5.4(a) shall be paid in cash in U.S. dollars.
(c) All mandatory prepayments on Outstanding Obligations
pursuant to Section 5.4(b) shall be made in cash in U.S. dollars.
(d) All regular repayments of principal on Outstanding
Obligations shall be made on the applicable Credit Maturity Date in cash
in U.S. dollars and/or, at the option of Isis, in shares of Isis Common
Stock, par value U.S.$.001 par share, at a price per share equal to
[***] of the average Fair Market Value (as such term is defined in the
Stock Purchase Agreement) over the [***] trading days preceding the
Credit Maturity Date.
(e) Bank Wire. All payments made to BI in immediately available
cash funds hereunder shall be addressed and wired to:
Boehringer Ingelheim International GmbH
Corporate Department Pharma Controlling
Citibank AG, Frankfurt/Main, F.R. Germany
Bank Account: 120/3497/004
ARTICLE 6.
RECORDS, REPORTS AND INFORMATION EXCHANGE
6.1 Record Keeping. Isis and BI shall each maintain records in sufficient
detail and in good scientific and commercial manner appropriate for
regulatory, patent, know how, trade secret, other intellectual property
and commercial purposes, including but not limited to the calculation of
Net Sales, and as shall properly reflect all work done, results achieved
and costs expended in the performance of each Party's respective
obligations hereunder and under the Collaborative Agreement. Isis and BI
shall each provide the other Party the right to inspect and make copies
(at such other Party's expense) of all such records to the extent
reasonably required for the performance of its obligations and the
exercise of its rights under this Agreement.
6.2 Technology and Information Transfer. The Parties shall exchange all Isis
Background Intellectual Property, BI Intellectual Property and Program
Intellectual Property, and shall provide reasonable technical assistance
and training to the other, as shall be necessary to carry out the
Research Plan. All information transferred, provided or exchanged under
this Section 6.2 shall be subject to the confidentiality requirements
set forth in Article 9 and may be used and disclosed only to carry out
the Research Plan hereunder.
6.3 Exchange Rate; Records of Net Sales. All payments with respect to
royalties under this Agreement shall be payable [***]. All royalty
payments to Isis shall be calculated in U.S. dollars on the last
business day of each quarter or such pro rata share thereof as is then
applicable, using the applicable exchange
*CONFIDENTIAL TREATMENT REQUESTED
7
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rates for such date published in the Wall Street Journal. All royalty
payments to BI shall be calculated in Deutsche Mark or Euros, at the
written request of BI prior to the date of calculation, on the last
business day of each quarter or such pro rata share thereof as is then
applicable, using the applicable exchange rates for such date published
in the Wall Street Journal. Both parties shall keep complete and
accurate records (including Net Sales information on a
country-by-country basis) in sufficient detail to enable the amounts
payable to be determined.
6.4 Right to Audit. Upon written request, each Party shall have the right to
have an independent audit of Net Sales by the other Party and its
Affiliates performed once after each calendar year on an aggregated
country-by-country basis and on a country-by-country basis for Major
Market Countries. As used in this Agreement, "Major Market Countries"
shall mean the United States, Germany, France, Italy, Japan and the
United Kingdom. Internal auditors or independent public accountants
selected by each Party and acceptable to the other shall conduct such
verification at the respective Party's expense and during regular
business hours. With respect to Net Sales by a Party's licensees
(including sub-licensees), the other Party shall have the right to
request an audit of the Net Sales by such licensees and/or
sub-licensees, at such requesting Party's expense, once after each
calendar year on an aggregated country-by-country basis and on a
country-by-country basis for Major Market Countries, in which case the
Party receiving such request to audit shall promptly cause an audit to
be undertaken of Net Sales made by its licensees and/or sub-licensees
and promptly deliver the results of such audit to the Party requesting
same. Any discrepancies of 5% or less shall not be considered material.
ARTICLE 7.
INTELLECTUAL PROPERTY RIGHTS
7.1 Ownership of Background Intellectual Property. The rights to BI
Background Intellectual Property and Isis Background Intellectual
Property shall remain the property of the respective Party which owned
such rights at the date of execution of this Agreement. Each Party
hereby acknowledges and agrees that it shall have no rights to the other
Party's Background Intellectual Property other than the licensed rights
specifically granted herein.
7.2 Ownership of Joint Intellectual Property. The rights to all Program
Intellectual Property that are discovered, made or conceived during and
as a result of the Research Plan solely by employees of one Party or by
others acting on behalf of the same Party shall be owned by that Party.
The rights to all Program Intellectual Property that is discovered, made
or conceived during and as a result of the Research Plan jointly by
employees of BI and Isis or others acting on their behalf shall be
jointly owned by BI and Isis. Each Party shall disclose to the other
Party the making, conception or reduction to practice of Program
Intellectual Property by employees or others acting on behalf of such
Party. Inventorship shall be determined in accordance with common
international practice.
7.3 Joint [***] Intellectual Property. The Parties acknowledge and agree
that the only joint intellectual property resulting from the Research
Program (as such term is defined in the Collaborative Agreement) was the
Joint [***] Patent(s) (as such term is defined herein). The Parties'
agreement with respect to royalties relating to the Joint [***]
Patent(s) are set forth in Section 2.4. The Parties' agreements with
respect to the filing and prosecution of the Joint [***] Patent(s) and
other matters are set forth in Article 13.
*CONFIDENTIAL TREATMENT REQUESTED
8
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ARTICLE 8.
GRANT OF LICENSES
8.1 Grant of License by BI to Isis. BI hereby agrees to grant and grants to
Isis a worldwide, royalty-free license to the BI Background Intellectual
Property and the Program Intellectual Property, owned or controlled by
BI solely for the purpose of allowing Isis to carry out the Research
Plan, as provided herein. Such license shall terminate upon the
termination of the Research Period.
8.2 Grant of License by Isis to BI. Isis hereby agrees to grant and grants
to BI a worldwide, royalty-free license to the Isis Background
Intellectual Property and the Program Intellectual Property, owned or
controlled by Isis solely for the purpose of allowing BI to carry out
the Research Plan, as provided herein. Such license shall terminate upon
the termination of the Research Period.
8.3 Characteristics of Licenses. The licenses granted under Sections 8.1 and
8.2 shall be exclusive for the purposes for which they are granted,
except as to the Party granting the license, which shall retain all
rights necessary to conduct the activities contemplated by this
Agreement and to use the intellectual property freely. Notwithstanding
the above, the Parties shall have the right to grant sublicenses to
Affiliates.
8.4 Non-Use of Intellectual Property. Each of BI and Isis hereby covenants
and agrees that it shall not, nor shall it cause its Affiliates to, use
directly or indirectly any Isis Background Intellectual Property (in the
case of BI) or BI Background Intellectual Property (in the case of Isis)
or Program Intellectual Property (in both cases) for any purpose other
than to conduct activities under this Agreement during the Research
Period.
ARTICLE 9.
CONFIDENTIALITY
9.1 Confidentiality. Each Party hereto shall maintain in confidence all
Confidential Information disclosed by the other Party hereto. Neither
Party shall use, disclose or grant use of such Confidential Information
except as expressly authorized by this Agreement and/or without the
prior written consent of the other Party. To the extent that disclosure
is authorized by this Agreement, the disclosing Party shall obtain prior
agreement from its employees, agents, consultants or clinical
investigators and designated permitted sublicensees to whom disclosure
is to be made to hold in confidence and not make use of such
Confidential Information for any purpose other than those permitted by
this Agreement. Each Party shall use at least the same standard of care
as it uses to protect its own trade secrets or proprietary information
to ensure that such employees, agents, consultants and clinical
investigators do not disclose or make any unauthorized use of such
Confidential Information. Each Party shall promptly notify the other
upon discovery of any unauthorized use or disclosure of the Confidential
Information.
9.2 Authorized Disclosure. Each Party may disclose the Confidential
Information to the extent such disclosure is reasonably necessary in
filing or prosecuting patent applications, prosecuting or defending
litigation or complying with applicable governmental regulations, or
achieving the purposes of this Agreement; provided that, if such Party
is required to make any such disclosure of the Confidential Information,
it shall to the extent practicable give reasonable advance notice to the
other Party of such disclosure requirement and, except to the extent
inappropriate in the case of patent applications, shall use reasonable
efforts to secure confidential treatment of such Confidential
Information required to be disclosed.
9
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ARTICLE 10.
TERM; TERMINATION
10.1 Term. This Agreement shall commence as of the Effective Date and, unless
sooner terminated, as provided hereunder, shall continue in effect until
such date as no royalties shall be payable to any Party hereunder.
10.2 Termination for Breach. In the event either Party breaches a material
obligation under this Agreement, and such breach is not cured within 90
days of written notice thereof, the non-breaching Party shall not have
the right to terminate this Agreement, but shall have the right only to
pursue an action for damages, arising as a result of such breach
pursuant to Article 15, and this Agreement shall continue in full force
and effect, including all licenses and funding obligations hereunder.
10.3 Accrued Rights, Surviving Obligations. Termination, relinquishment or
expiration of this Agreement or any part thereof for any reason shall be
without prejudice to any rights that shall have accrued to the benefit
of either Party prior to such termination, relinquishment or expiration,
including damages arising from any breach hereunder. Such termination,
relinquishment or expiration shall not relieve either Party from
obligations that are expressly indicated to survive termination or
expiration of this Agreement.
10.4 Survival. Section 2.2, Section 2.3, Section 2.4, Section 2.5, Section
3.4, Article 4, Article 5, Section 6.4, Article 7, Article 9, Article
13, Article 14 and Article 15 shall survive the termination of this
Agreement.
ARTICLE 11.
REPRESENTATIONS AND WARRANTIES
Each Party hereby represents and warrants to the other that:
11.1 Corporate Power. Such Party is duly organized and validly existing under
the laws of the jurisdiction of its incorporation and has full corporate
power and authority to enter into this Agreement and to carry out the
provisions hereof.
11.2 Due Authorization. Such Party is duly authorized to execute and deliver
this Agreement and to perform its obligations hereunder.
11.3 Binding Agreement. This Agreement is a legal and valid obligation
binding upon it and enforceable in accordance with its terms. The
execution, delivery and performance of this Agreement by such Party does
not conflict with any agreement, instrument or understanding, oral or
written, to which it is a Party or by which it may be bound, nor violate
any law or regulation of any court, governmental body or administrative
or other agency having jurisdiction over it.
11.4 No Conflict. Such Party has not granted any licenses or rights to any
other person which would restrict or conflict with or prevent such Party
from granting the rights granted to the other Party pursuant to this
Agreement.
10
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ARTICLE 12.
PUBLICATIONS
12.1 Publications
(a) During the term of this Agreement, Isis and BI each
acknowledge the other Party's interest in publishing certain of its
results to obtain recognition within the scientific community and to
advance the state of scientific knowledge. Accordingly, each Party shall
have the right to publish such results pertaining to its own products or
intellectual property without the prior review or consent of the other
Party; provided, however, that each Party hereby agrees to exercise good
scientific practice with respect to any publications involving joint
authorship and, in the case of joint authorship, to provide the other
Party with notice and a copy of such proposed publication sixty (60)
days prior to such publication.
(b) Notwithstanding paragraph (a) of this Section 12.1, with
respect to CS-11, an integrated clinical trial report shall be prepared
in accordance with the study protocol. BI and Isis shall each have the
right to review the final manuscript at least four (4) weeks prior to
submission for publication.
ARTICLE 13.
PATENTS
13.1 Filing, Prosecution and Maintenance of the Joint [***] Patent(s). With
respect to the Joint [***] Patent(s), Isis shall have the right, but not
the obligation, to file, prosecute and maintain the Joint [***]
Patent(s) and to pay the costs and expenses related thereto. If,
however, Isis fails to file, prosecute or maintain the Joint [***]
Patent(s) within a reasonable amount of time, then BI shall have the
right, but not the obligation, to file, prosecute and maintain the Joint
[***] Patent(s) and to pay the costs and expenses related thereto. Each
of the Parties hereto shall consult with the other Party as to the
filing, prosecution and maintenance of the Joint [***] Patent(s), shall
furnish to the other Party copies of documents relevant to any filing,
prosecution or maintenance sufficiently prior to filing such document or
making any payment due thereunder to allow for review and comment by the
other Party, and shall seriously consider all such comments.
13.2 Filings. With respect to any patent applications filed or to be filed
with respect to any intellectual property conceived, created or
developed either under the Collaborative Agreement or during and as part
of the Research Plan, (a) BI shall be responsible for filing and
prosecuting such application on such intellectual property owned solely
by BI (each, a "BI Application or Patent") and paying the costs and
expenses related thereto and (b) Isis shall be responsible for filing
and prosecuting such application on such intellectual property owned
solely by Isis (each, an "Isis Application and Patent") and paying the
costs and expenses related thereto. Except as provided in Section 13.1,
with respect to any such intellectual property jointly owned by BI and
Isis (each, a "Joint Application or Patent"), (X) for any Joint
Application or Patent relating or pertaining to small molecules, BI
shall be responsible for filing such Joint Application or Patent and
paying the costs and expenses related thereto; (Y) for any Joint
Application and Patent relating or pertaining to Antisense Molecules or
Ibis technology, Isis shall be responsible for filing and prosecuting
such Joint Application or Patent and paying the costs and expenses
related thereto; and (Z) for any Joint Application or Patent relating or
pertaining to both small molecules, on the one hand, and Antisense
Molecules or Ibis technology, on the other, or to none of small
molecules,
*CONFIDENTIAL TREATMENT REQUESTED
11
<PAGE> 12
Antisense Molecules or Ibis technology, the Parties shall negotiate on a
case-by-case basis which Party shall be responsible for filing and
prosecuting such application and paying the costs and expenses related
thereto.
13.3 Filing, Prosecution and Maintenance. The Party selected for filing a
given Joint Application or Patent pursuant to Section 13.2 shall have
the right, but not the obligation, to file, prosecute and maintain such
Joint Application or Patent and to pay the costs and expenses related
thereto. If, however, such Party fails to file, prosecute or maintain a
given Joint Application or Patent within a reasonable amount of time,
the other non-filing Party shall have the right, but not the obligation,
to file, prosecute and maintain such Joint Application or Patent and to
pay the costs and expenses related thereto. Each of the Parties hereto
shall consult with the other Party as to the filing, prosecution and
maintenance of each Joint Application or Patent, shall furnish to the
other Party copies of documents relevant to any filing, prosecution or
maintenance sufficiently prior to filing such document or making any
payment due thereunder to allow for review and comment by the other
Party, and shall seriously consider all such comments.
ARTICLE 14.
INDEMNIFICATION
14.1 Indemnification for Products. Unless otherwise provided herein, each
Party agrees to indemnify and hold the other Party harmless, from and
against all Third Party claims, demands, liabilities, damages and
expenses (including attorney's fee) arising out of such Party's, its
Affiliates or agents, research, development, manufacture, use, handling,
storage, commercialization or sale of ISIS 2302 or any Additional
Compound, but only to the extent such claims, demands and the like
result from the negligence of the indemnifying Party, its Affiliates or
agents and not to result from the negligence of the Party seeking to be
indemnified. The Party providing the indemnity shall have the right to
conduct the defense. Notwithstanding the foregoing, neither Party shall
be responsible for any Third Party claims, demands, liabilities, damages
and expenses (including attorney's fees) which may arise out of the use
by the other Party of any information and data received by the other
Party from it, its Affiliates and/or its licensees or sublicensees. In
the event either Party receives notice of a claim with respect to ISIS
2302 or any Additional Compound, such Party shall inform the other as
soon as reasonably practicable and the Parties shall confer in good
faith as to how best to handle the claim in an efficient and equitable
manner.
ARTICLE 15.
DISPUTE RESOLUTION; GOVERNING LAW
15.1 Dispute Resolution. In case of any possible disputes arising out of or
relating or pertaining to the Collaborative Agreement and/or this
Agreement, the Parties shall use their reasonable best efforts to try to
settle those disputes amicably and, if unsuccessful, shall submit the
matter for review under the Rules of Conciliation and Arbitration of the
International Chamber of Commerce by one or more arbitrators appointed
in accordance with said Rules. If resolution of such disputes
satisfactory to both Parties cannot be reached in this manner, then
either Party shall have the right to bring an action to resolve such
dispute before a court of jurisdiction where the Party being sued
maintains its principal executive offices.
15.2 Governing Law. This Agreement shall be governed and construed in
accordance with the laws of the State of New York.
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<PAGE> 13
ARTICLE 16.
MISCELLANEOUS
16.1 Taxes. In the event a Party paying a royalty hereunder is required to
withhold taxes imposed upon the Party receiving a royalty by virtue of
the statutes, laws, codes or governmental regulations of a given country
in which products subject to such royalties are sold, then such payments
shall be made by the royalty-paying Party on behalf of the other Party
by deducting them from the royalty payment due such other Party and
remitting such taxes to the proper authorities on a timely basis; and
the royalty payments provided for under this Agreement shall be adjusted
appropriately, provided that the royalty-paying Party supplies the other
Party with official documentation and/or tax receipts on such
withholdings supporting such taxes and such payments as may be required
by such other Party for its tax records.
16.2 Export. In order to comply with the United States Export Administration
Act of 1979, as amended from time to time (the "Export Act"), each Party
hereby certifies that no technology or information licensed from the
other, and no product thereof, shall be made available or re-exported,
directly or indirectly, to any areas outside the United States except in
compliance with all applicable laws and regulations of the Bureau of
Export Administration in accordance with the Export Act. BI shall give
Isis such written assurance against re-export as required by the Export
Act.
16.3 Force Majeure. Neither Party shall be held liable or responsible to the
other Party nor be deemed to have defaulted under or breached this
Agreement for failure or delay in fulfilling or performing any term of
this Agreement when such failure or delay is caused by or results from
causes beyond the reasonable control of the affected Party, including
but not limited to fire, floods, embargoes, war, act of war (whether war
be declared or not), insurrections, riots, civil commotions, strikes,
lockouts or other labor disturbances, acts of God or acts, omissions or
delays in acting by any governmental authority or the other Party;
provided, however, it is understood that this Section 16.3 is intended
only to suspend and not discharge a Party's obligations under this
Agreement and that when the causes of the failure or delay are removed
or alleviated, the affected Party shall resume performance of its
obligations hereunder.
16.4 Assignment. This Agreement may not be assigned or otherwise transferred
nor, except as expressly provided hereunder, may any right or
obligations hereunder be assigned or transferred, by either Party
without the written consent of the other Party; provided, however, that
either Isis or BI may, without such consent, assign this Agreement and
its rights and obligations thereunder to a wholly-owned subsidiary. Isis
and BI may elect to assign this Agreement (a) in connection with the
transfer or sale of all or substantially all of its business to which
this Research Plan is related, if such assets include substantially all
of the assets relating to its performance of its respective obligations
hereunder, or (b) in the event of its merger or consolidation with
another company at any time during the term of this Agreement. Each
Party shall promptly inform the other of the identity and location of
any permitted assignee. Any purported assignment in violation of the
preceding sentence shall be void. Any permitted assignee shall assume
all obligations of its assignor under this Agreement.
16.5 Severability. In case any provision contained in this Agreement shall be
held to be invalid, illegal or unenforceable in any respect, the
validity, legality and enforceability of the remaining provisions
contained herein shall not in any way be affected or impaired thereby.
13
<PAGE> 14
16.6 Notices. All notices, requests, consents and other communications
hereunder shall be in writing, shall be delivered personally, by
facsimile transmission or mailed by first-class registered or certified
airmail or by internationally recognized overnight express courier,
postage prepaid, and shall be deemed given upon personal delivery, upon
confirmation of receipt of such facsimile transmission or on the 10th
day following such mailing and shall be addressed as follows:
if to Isis, to:
Isis Pharmaceuticals, Inc.
2292 Faraday Drive
Carlsbad, California 92008
Attn.: Ms. B. Lynne Parshall
Executive Vice President
or to such other person at such other address as Isis shall
designate to BI in writing; and
if to BI, to:
Boehringer Ingelheim International GmbH
Postbox 200
D 55216 Ingelheim/Rhein
Federal Republic of Germany
Attn.: Corporate Division Pharma Business Development
Telephone: 49 61 32 77 2430
Telecopy: 49 61 32 77 3926
with copy to
Boehringer Ingelheim International GmbH
Postbox 200
D 55216 Ingelheim/Rhein
Federal Republic of Germany
Attn.: Head of Corporate Legal Department
Telephone: 49 61 32 77 2106
Telecopy: 49 61 32 77 4080
or to such other person(s) at such other address(es) as BI shall
designate to Isis in writing.
16.7 Entire Agreement. This Agreement constitutes the full and entire
understanding and agreement among the Parties with regard to the
subjects hereof and no Party shall be liable or bound to any other Party
in any manner by any representations, warranties, covenants, or
agreements except as specifically set forth herein or therein. Nothing
in this Agreement, expressed or implied, is intended to confer upon any
Party, other than the Parties hereto and their respective successors and
assigns, any rights, remedies, obligations, or liabilities under or by
reason of this Agreement, except as expressly provided herein.
16.8 Amendment and Waiver. Any term of this Agreement may be waived or
amended in a writing agreed to by Isis and BI.
16.9 Headings. The headings of the various sections of this Agreement have
been inserted for convenience of reference only and shall not be deemed
to be part of this Agreement.
14
<PAGE> 15
16.10 Independent Contractors. It is expressly agreed that Isis and BI shall
be independent contractors and that the relationship between the two
Parties shall not constitute a partnership or agency of any kind.
Neither Isis nor BI shall have the authority to make any statements,
representations or commitments of any kind, or to take any action, which
shall be binding on the other, without the prior written authorization
of the Party to do so.
16.11 Waiver. This waiver by either Party hereto of any right hereunder or the
failure to perform or of a breach by the other Party shall not be deemed
a waiver of any other right hereunder or of any other breach or failure
by said other Party whether of a similar nature or otherwise.
16.12 English language. The official text of this Agreement or any notices
given or accounts or statements required shall be in English.
16.13 Public Announcements. Isis and BI shall consult with each other before
issuing any press release or otherwise making any public statements or
disclosures with respect to the transactions contemplated by this
Agreement or by that certain Amendment to the Stock Purchase Agreement,
dated as of August 31, 1999, by and between Isis and BI, and shall not
issue any such press release or make any such public statement or
disclosure prior to such consultation, except as may be required by
applicable law.
15
<PAGE> 16
IN WITNESS WHEREOF, the Parties have executed this Agreement as of the
date first set forth above.
ISIS PHARMACEUTICALS, INC.
By: _____________________________________________
Name:
Title:
BOEHRINGER INGELHEIM INTERNATIONAL GmbH
By: _____________________________________________
Name:
Title:
By: _____________________________________________
Name:
Title:
16
<PAGE> 17
APPENDIX A
DEFINITIONS
- - "Additional Compounds" shall mean, collectively, the compounds known as
[***] and any compound from out of the [***] series that had been
synthesized as of the Effective Date, the compounds known as [***].
- - "Advance" shall have the meaning set forth in Article 7 of the
Collaborative Agreement.
- - "Affiliate" shall mean any corporation or other entity which controls,
is controlled by, or is under common control with a Party to this
Agreement. A corporation or other entity shall be regarded as in control
of another corporation or entity if it owns or directly or indirectly
controls more than fifty percent (50%) of the voting stock or other
ownership interest of the other corporation or entity, or if it
possesses, directly or indirectly, the power to direct or cause the
direction of the management and policies of the corporation or other
entity or the power to elect or appoint fifty percent (50%) or more of
the members of the governing body of the corporation or other entity.
- - "Agreement" shall mean this Agreement, dated as of August 31, 1999, by
and between BI and Isis, including all appendices, exhibits and
schedules attached hereto.
- - "Antisense Molecule" shall mean [***]. An "oligonucleotide" may include
[***].
- - "Bankruptcy" shall have the meaning set forth in the Stock Purchase
Agreement.
- - "BI Background Intellectual Property" shall mean all issued patents and
patent applications owned or controlled by BI or any of its Affiliates,
together with any reissues, reexamination certificates, divisions,
continuations or continuations-in-part and extensions (patent term
restoration, supplementary protection certificate, etc.) thereof and
know-how necessary or useful to carry out the Research Plan.
- - "Change in Control" shall have the meaning set forth in the Stock
Purchase Agreement.
- - "Collaborative Agreement" shall mean that certain Collaborative
Agreement, dated as of July 18, 1995, between Boehringer Ingelheim
International GmbH and its Affiliates and Isis and the appendices,
exhibits and schedules thereto, as amended.
- - "Confidential Information" means any confidential information, trade
secrets, know how and any other information relating to any research
project, work in process, future development, scientific engineering,
manufacturing, marketing, business plan, financial or personnel matter
relating to either Party, whether under the Collaborative Agreement or
this Agreement, such Party's present or future products, sales
suppliers, customers, employees, investors or business, whether in oral,
written, graphic or electronic form. Confidential Information shall not
include:
*CONFIDENTIAL TREATMENT REQUESTED
17
<PAGE> 18
(a) information already known to the receiving Party, other than under
an obligation of confidentiality, at the time of disclosure by the other
Party;
(b) information generally available to the public or otherwise part of
the public domain at the time of its disclosure to the other Party,
(c) information that became generally available to the public or
otherwise part of the public domain after its disclosure and other than
through any act or omission of the receiving Party in breach of this
Agreement;
(d) information disclosed to the receiving Party, other than under in
obligation of confidentiality, by a Third Party who had no obligation to
the other Party not to disclose such information to others.
The Parties agree that the material financial terms of this Agreement
shall also be considered Confidential Information of both Parties. The
ownership and control of all Confidential Information relating or
pertaining to Antisense Molecules shall be deemed to have been
transferred to Isis hereunder and the ownership and control of all
Confidential Information relating or pertaining to small molecules shall
be deemed to have been transferred to BI hereunder in a manner
consistent with the treatment of Additional Compounds pursuant to
Section 2.3.
- - "Credit Maturity Date" means, as to each Advance, the date seven (7)
years after the date upon which such Advance was made pursuant to the
Collaborative Agreement.
- - "Field" shall mean the identification, optimization and development of
molecules which interfere with the normal process of leucocyte adhesion
to cellular and extracellular substrates to be used in the treatment of
immune and non-immune based inflammatory diseases. Specifically included
within the Field are (a) Antisense Molecules which directly inhibit the
expression of ICAMs, VCAM-1, PECAM-1, selectins and(beta)2 integrins,
(b) compounds which modulate the interaction of leucocyte integrins,
with their respective binding ligands and the interaction of selectins
with their binding structures, (c) non-antisense compounds which
modulate the expression of ICAMs, VCAM-1, PECAM-1, selectins and
leucocyte integrins by interfering with in intracellular process, and
(d) compounds which inhibit the shedding of selectins, ICAMs, VCAM-1,
and PECAM-1 from the cell surface.
- - "Isis Background Intellectual Property" shall mean all issued patents
and patent applications owned or controlled by Isis or any of its
Affiliates, together with any reissues, reexamination certificates,
divisions, continuations or continuations-in-part and extensions (patent
term restoration, supplementary protection certificate, etc.) thereof
and know-how necessary or useful to carry out the Research Plan.
- - "Joint [***] Patent(s)" shall mean all joint issued patents and joint
patent applications, together with any reissues, reexamination
certificates, divisions, continuations or continuations-in-part and
extensions (patent term restoration, supplementary protection
certificate, etc.) thereof relating to antagonism of [***] activity
covered by the Collaborative Agreement.
- - "Net Sales" shall mean the gross invoiced price charged by BI or Isis
(as appropriate) or its respective Affiliates or licensees (including
sub-licensees), as the case may be, for a given product to an
independent Third Party less the following customary deductions:
*CONFIDENTIAL TREATMENT REQUESTED
18
<PAGE> 19
(i) trade and quantity discounts actually granted;
(ii) credits for returns or allowances;
(iii) the amount of any sales tax or other taxes assessed directly on
the sale of such product which is not refunded;
(iv) charge back payments or rebates granted to managed health care
organizations or federal, state and local governments, their
agencies, purchasers and reimbursers.
In the case of sales of a given product by a Party's licensee or
sub-licensee under an agreement in the ordinary course of a Party's
business containing terms customary for the pharmaceuticals industry, if
net sales are calculated under such agreement differently than Net Sales
are calculated hereunder, "Net Sales" hereunder shall be deemed to be
calculated in the manner calculated under the applicable agreement,
provided that such calculation of net sales shall be reasonably
consistent with this definition of "Net Sales." Each Party shall be
obligated to notify the other Party on a timely basis of the method of
calculation of net sales under all such agreements with licensees or
sub-licensees.
- - "Party" shall mean BI or Isis and "Parties" shall mean BI and Isis
collectively.
- - "Program Intellectual Property" shall mean all patents and patent
applications together with any reissues, reexamination certificates,
divisions, continuations or continuations-in-part and extensions (patent
term restoration, supplementary protection certificate, etc.) thereof
and know-how conceived, created or developed by either Party, solely or
jointly, during and as part of the Research Plan.
- - "Research Management Committee" (RMC) shall mean the joint committee
composed of an equal number of representatives of BI and Isis
responsible for overseeing the Research Plan as described in Section 3.4
of this Agreement.
- - "Research Period" shall mean the time period commencing on the Effective
Date and ending on December 31, 1999.
- - "Research Plan" shall mean a description of the activities as defined by
the RMC to be performed by BI and Isis during the Research Period of the
Research Plan, consisting of the design and performance of experiments
for the purpose of evaluating the Ibis technology and functional
genomics using antisense technology.
- - "Stock Purchase Agreement" shall mean that certain Stock Purchase
Agreement, dated July 18, 1995, between Isis and BI.
- - "Third Party" shall mean any entity other than Isis and BI and their
respective Affiliates and licensees (which shall include sub-licensees).
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<PAGE> 1
EXHIBIT 10.2
AMENDMENT TO THE STOCK PURCHASE AGREEMENT
This AMENDMENT TO THE STOCK PURCHASE AGREEMENT (this
"Amendment"), made this 31st day of August, 1999, by and between Isis
Pharmaceuticals, Inc., a Delaware corporation ("Isis"), and Boehringer Ingelheim
International GmbH, a German corporation ("Boehringer"),
W I T N E S S E T H :
WHEREAS, Isis and BI entered into that certain stock purchase agreement,
dated as of July 18, 1995 (the "Stock Purchase Agreement");
WHEREAS, Paragraph 11.5 of the Stock Purchase Agreement provides that
any term thereof may be amended in a writing agreed to by Isis and Boehringer;
and
WHEREAS, Isis and Boehringer have agreed to amend the Stock Purchase
Agreement as provided herein,
NOW, THEREFORE, in consideration of the mutual agreements and covenants
set forth herein, and for other good and valuable consideration, the parties
hereby agree that the Stock Purchase Agreement shall be amended as of the date
hereof as follows:
Section 1. Sub-paragraphs (b), (c) and (d) of Paragraph 3.1 and the
final paragraph of Paragraph 3.1 of the Stock Purchase Agreement (Agreement to
Sell and Purchase the Additional Shares) shall be deleted in their entirety.
Section 2. Paragraph 3.2 of the Stock Purchase Agreement (Delivery of
Additional Shares at a Subsequent Closing; Purchase price) shall be deleted in
its entirety.
Section 3. The first sentence of Paragraph 10 of the Stock Purchase
Agreement (Termination) shall be amended to read in its entirety as follows:
This Agreement shall terminate upon (i) any Change in Control of
Isis, (ii) the Bankruptcy of Isis or (iii) the termination of
the New Agreement pursuant to Article 10 thereof.
Section 4. Sub-paragraph (e) of Paragraph 8.1 (Board Representation) is
amended in its entirety to read as follows:
(e) Paragraph 8.1 shall terminate upon the earliest to occur
of:
(i) May 1, 2000;
(ii) The effectiveness of any Change in Control; or
(iii) Boehringer ceases to hold at least 2,000,000
shares of
Common Stock (appropriately adjusted for stock splits, stock
dividends, recapitalization and the like). If Paragraph 8.1
terminates, the BI Designate shall resign from the Board.
Section 5. In Exhibit A, the definition of "Additional Shares shall be
amended to read in its entirety as follows:
<PAGE> 2
"ADDITIONAL SHARES" shall mean the shares issued to Boehringer
Ingelheim under Paragraph 3.1 of the Agreement prior to the
effective date of the Amendment.
Section 6. Exhibit A shall be amended by the addition of the following
definitions:
"AMENDMENT" shall mean that certain Amendment to the Stock
Purchase Agreement, dated August 31, 1999, by and between Isis
and Boehringer.
"NEW AGREEMENT" shall mean that certain Agreement, dated as of
August 31, 1999, by and between Boehringer and Isis.
Section 7. This Amendment shall be governed by and construed in
accordance with the laws of the State of Delaware and the federal law of the
United States of America.
2
<PAGE> 3
IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be
executed by their duly authorized representatives as of the day and year first
above written.
ISIS PHARMACEUTICALS, INC.
By: __________________________________
Name:
Title:
BOEHRINGER INGELHEIM INTERNATIONAL GMBH
By: __________________________________
Name:
Title:
By: __________________________________
Name:
Title:
3
