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Exhibit 10.1

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

SETTLEMENT, RELEASE, AND LICENSE GRANT AGREEMENT

        This SETTLEMENT, RELEASE, AND LICENSE GRANT AGREEMENT (hereinafter the
"Agreement") is made and entered into effective on September 6, 2002, by and
between Isis Pharmaceuticals, Inc. on the one hand and Sequitur, Inc. on the
other hand.

        Whereas, Isis Pharmaceuticals, Inc. is the owner of all rights, title
and interest to United States Patent Number 6,001,653, 6,326,199, 5,959,097,
5,958,773, 6,043,090 and 6,096,543;

        Whereas, on July 9, 2001, Isis Pharmaceuticals, Inc. instituted suit
against Sequitur, Inc. in the United States District Court for the Southern
District of California, Case No. 01 CV 1223 B JFS (hereinafter the "First
Action"), seeking injunctive relief and damages against Sequitur, Inc. based on
the allegation that Sequitur, Inc. was infringing U.S. Patent No. 6,001,653;

        Whereas, Sequitur, Inc. denied all allegations of infringement in the
First Action and Sequitur, Inc. further filed a counterclaim alleging that it
was entitled to declaratory judgment of non-infringement, invalidity and/or
unenforceability, and alleging claims of breach of contract, unfair competition
under the Lanham Act, Antitrust Violations and unfair competition under
California Law (the "Counterclaim");

        Whereas, Isis Pharmaceuticals, Inc. denied all allegations of breach of
contract, unfair competition and antitrust violations in the Counterclaim;

        Whereas, on December 12, 2001, Isis Pharmaceuticals, Inc. instituted
suit against Sequitur, Inc. in the United States District Court for the Southern
District of California, Case No. 01 CV 2286 B JFS (hereinafter the "Second
Action"), seeking injunctive relief and damages against Sequitur, Inc. based on
the allegation that Sequitur, Inc. was infringing U.S. Patent No. 6,326,199;

        Whereas, Sequitur, Inc. denied all allegations of infringement in the
Second Action;

        Whereas, on May 2, 2001, Isis Pharmaceuticals, Inc. instituted suit
against Sequitur, Inc. in the United States District Court for the Southern
District of California, Case No. 02 CV 0842 B JFS (hereinafter the "Third
Action"), seeking injunctive relief and damages against Sequitur, Inc. based on
the allegation that Sequitur, Inc. was infringing U.S. Patent Nos. 5,959,097,
5,958,773, 6,043,090 and 6,096,543;

        Whereas, Sequitur, Inc. denied all allegations of infringement in the
Third Action; and

        Whereas, the parties to this Agreement deny any and all liability to one
another, but desire to fully compromise and resolve all of the claims between
them arising from or in any way related to the First Action, Second Action,
Third Action and the Counterclaim ("the Lawsuit");

        Now, Therefore, to reconcile their differences and in consideration of
the promises and covenants and agreements contained herein, the parties agree as
follows:

1.    Definitions.

        1.1  Antisense Oligonucleotides. As used herein, the term "Antisense
Oligonucleotides" means a sequence of nucleotides which is designed to be
complementary to and bind to a specific sequence of nucleotides in an mRNA
target to inhibit production of the protein encoded by the target mRNA.

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        1.2  Change of Control. As used herein, the term "Change in Control"
shall be deemed to occur upon (i) the acquisition of all or substantially all of
the assets of Sequitur, Inc. or (ii) an acquisition of Sequitur, Inc. by another
corporation or entity by consolidation, merger or other reorganization in a
transaction (or series of transactions) in which the holders of Sequitur, Inc.'s
outstanding voting stock immediately prior to such transaction (or series of
transactions) own, immediately after such transaction (or series of
transactions), securities representing less than fifty percent (50%) of the
voting power of the corporation or other entity surviving such transaction (or
series of transactions).

        1.3  Existing Customer. As used herein, the term "Existing Customer"
means a customer of Sequitur's Target Validation Program, whether inside or
outside the U.S., to whom Sequitur has supplied or used on their behalf
Antisense Oligonucleotides prior to June 30, 2002, as set forth in Exhibit A
attached hereto.

        1.4  First Generation Oligonucleotides. As used herein, the term "First
Generation Oligonucleotides" means Antisense Oligonucleotides having:
phosphorothioate, phosphodiester, or mixed phosphorothiote/phosphodiester
backbones; unmodified Adenine, Cytosine, Thymine, Guanine, bases; and,
unmodified deoxy sugars. First Generation Oligos may contain fluorescent dyes or
other non-nucleotide end-blocks incorporated at either or both the 3' and 5'
ends.

        1.5  Isis. As used herein, the term "Isis" shall mean Isis
Pharmaceuticals, Inc., and its successors in interest.

        1.6  Isis First Generation Oligonucleotide Patents. As used herein, the
term "Isis First Generation Oligonucleotide Patents" means Patents owned by Isis
on the Effective Date, including U.S. Patent No. 6,001,653, which have claims
which read on First Generation Oligonucleotides. Isis First Generation
Oligonucleotide Patents does not include Isis Patents that claim specific
nucleotide sequences, or Patents claiming oligonucleotides designed to inhibit
specific genes identified in the patent, or methods of using such
oligonucleotides.

        1.7  Next Generation Oligonucleotides. As used herein, the term "Next
Generation Oligonucleotides" means Antisense Oligonucleotides with a combination
of 2' hydrogen and 2' modified sugars that elicit RNase H cleavage as a
mechanism of action.

        1.8  Patents. As used herein, the term "Patents" means all U.S. patents
and patent applications, divisions, continuations, reissues, re-examinations,
extensions, supplementary protection, and any provisional applications, of any
such patents or patent applications, and any foreign or international equivalent
of any of the foregoing. The term Patents includes the claim of any
continuation-in-part, and any foreign or international equivalents of such
continuation-in-part, only to the extent that such claim is to an embodiment
that does not include new matter.

        1.9  Provide. As used herein, the term "Provide" will mean that Sequitur
may supply Existing Customers with Next Generation Oligonucleotides, which are
presently in the possession of Sequitur.

        1.10 Resupply. As used herein, the term "Resupply" will mean that
Sequitur can have Trilink or another supplier make an additional quantity of
Next Generation Oligonucleotides to provide not more than 10mg of such Next
Generation Oligonucleotides to an Existing Customer.

        1.11 Sequitur. As used herein, the term "Sequitur" shall mean
Sequitur, Inc.

        1.12 Sequitur's Target Validation Program. As used herein, "Sequitur's
Target Validation Program" shall mean internal use by Sequitur, and/or provision
by Sequitur to its customers (for internal use only, and not for resale), of
Antisense Oligonucleotides, wherein such use or provision of Antisense
Oligonucleotides by Sequitur or use by its customers is for the purposes of

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performing research regarding the validation or functionalization of gene
targets or confirmation of such function.

2.    Releases

        2.1  Isis hereby releases, acquits and forever discharges Sequitur and
each of its predecessors, successors, receivers, assigns, affiliated entities,
parent and subsidiary entities, past or present owners, shareholders, partners,
investors, employees, agents, representatives, consultants, officers, directors,
managers, and any other person, firm or corporation acting by, through, under or
in concert with it, from any and all claims, demands, actions, causes of action,
suits, obligations, damages, restitution, promises, controversies, contracts,
agreements, expenses, costs, fees, and losses or liabilities of any type or
nature whatsoever, in equity or at law, by statute or common law, whether or not
now known, suspected, disclosed, or claimed, whether or not now known,
suspected, disclosed, or claimed, which Isis ever had, now has or claims to have
against Sequitur, up to and including the Effective Date of this Agreement,
including but not limited to all claims for attorney's fees and costs. Isis also
releases, acquits, and forever discharges Sequitur customers from claims of
patent infringement based on the use of oligonucleotides purchased from Sequitur
under Sequitur's Target Validation Program that Isis ever had, now has or claims
to have against such customers, up to and including the Effective Date of this
Agreement.

        2.2  Sequitur hereby releases, acquits and forever discharges Isis, and
each of its predecessors, successors, receivers, assigns, affiliated entities,
parent and subsidiary entities, past or present owners, shareholders, partners,
investors, employees, agents, representatives, consultants, officers, directors,
managers, and any other person, firm or corporation acting by, through, under or
in concert with it, from any and all claims, demands, actions, causes of action,
suits, obligations, damages, restitution, promises, controversies, contracts,
agreements, expenses, costs, fees, and losses or liabilities of any type or
nature whatsoever, in equity or at law, by statute or common law, whether or not
now known, suspected, disclosed, or claimed, which Sequitur ever had, now has or
claims to have against Isis up to and including the Effective Date of this
Agreement, including but not limited to all claims for attorney's fees and
costs. Without limiting the generality of the foregoing, Sequitur expressly
agrees to withdraw, release, acquit and forever discharge Isis, and each of its
predecessors, successors, receivers, assigns, affiliated entities, parent and
subsidiary entities, past or present owners, shareholders, partners, investors,
employees, agents, representatives, consultants, officers, directors, managers,
and any other person, firm or corporation acting by, through, under or in
concert with it, from any and all claims for recovery of sanctions or contempt
arising from or related to the Lawsuit.

        2.3  Each Party understands and expressly waives any rights or benefits
available under Section 1542 of the Civil Code of California, which provides:

"A general release does not extend to claims which the creditor does not know or
suspect to exist in his favor at the time of executing the release, which if
known by him must have materially affected his settlement with the debtor."

3.    Restrictions on Use

        3.1  During the term of this Agreement,:

        (a)  Sequitur will not make, have made, use, sell or offer to sell Next
Generation Oligonucleotides in the United States; Sequitur may or will, as
indicated below, however, perform the following activities with regard to Next
Generation Oligonucleotides as part of Sequitur's Target Validation Program and
its obligations hereunder:

        (i)    Sequitur may Provide and Resupply to an Existing Customer any
Next Generation Oligonucleotide ordered by Sequitur prior to January 6, 2002;

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        (ii)  Sequitur may Provide and Resupply to an Existing Customer any Next
Generation Oligonucleotide that was purchased by Sequitur for such Existing
Customer or provided to such Existing Customer by Sequitur prior to June 30,
2002;

        (iii) Sequitur may Provide and Resupply to an Existing Customer any Next
Generation Oligonucleotide that is Provided to such Existing Customer from
Sequitur's stock of approximately 38 Next Generation Oligonucleotides which were
ordered by Sequitur between January 4th, 2002 and June 30, 2002. Resupply will
be completed by December 31, 2002. Sequitur must inventory its Next Generation
Oligonucleotides on a first in, first out basis, and may only have additional
quantities of Next Generation Oligonucleotides made for Resupply after it has
depleted its currently on-hand stock of such Next Generation Oligonucleotides;

        (iv)  Sequitur will provide to an independent Third Party, at Sequitur's
expense a list of the currently existing Next Generation Oligonucleotides
referenced above, and a supplier of Sequitur's choice will confirm with such
Third Party its ability to make such Next Generation Oligonucleotides for
Sequitur;

        (v)  Sequitur's agreement regarding restrictions on making, having made,
using, selling or offering to sell use of Next Generation Oligonucleotides under
this Section will terminate 7 years from the Effective Date of this Agreement.
After 7 years from the Effective Date of this Agreement, Isis will, from time to
time, give Sequitur a list of all patents and applications certified by Isis'
patent counsel to cover Next Generation Oligonucleotides, and Sequitur agrees
that it will not infringe valid claims in issued patents covering Next
Generation Oligonucleotides on such list;

        (vi)  With regard to Sequitur's use or provision of Next Generation
Oligonucleotides outside of the U.S., Sequitur agrees that it will not infringe
any valid issued claims of any Isis owned or controlled European patents
covering Next Generation Oligonucleotides. If, in the opinion of Isis, Sequitur
does infringe any such patents outside the U.S., Isis may pursue any available
legal remedy, and will not be bound by the Dispute Resolution provision of
Section 15; and

        (vii) Sequitur will use reasonable efforts to avoid infringing any Isis
Patents.

        (b)  Sequitur will not advertise Next Generation Oligonucleotides, or
promote Sequitur's services with data generated through the use of Next
Generation Oligonucleotides after June 30, 2002;

        (c)  Sequitur's Existing Customers may use Next Generation
Oligonucleotides Provided and Resupplied by Sequitur hereunder as part of
Sequitur's Target Validation Program as expressly provided herein. Sequitur's
Existing Customers may use Next Generation Oligonucleotides that were provided
by Sequitur prior to June 30, 2002 at any time. Sequitur's Existing Customers
may use Next Generation Oligonucleotides Provided or Resupplied by Sequitur
after June 30, 2002 until June 30, 2003.

        3.2  If Isis licenses any supplier to provide Next Generation
Oligonucleotides to functional genomics service providers without restriction on
resale (or to Sequitur specifically), Sequitur may buy Next Generation
Oligonucleotides from such supplier.

4.    Mutual Covenants

        4.1  Isis and Sequitur each agree that it will not, and that its
executive officers will not, disparage the other, the other's products or
patents, or act as an advisor or expert witness for third parties against the
other at any time.

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        4.2  Except as provided in Section 8.3, Isis and Sequitur each agree
that for the period of 5 years from the Effective Date it will not, and that its
executive officers will not, discuss or characterize the First Action,
Counterclaim, Second Action, Third Action or the subject matter thereof, in
whole or in part, other than by stating that "the litigation between the parties
was settled on mutually satisfactory terms."

5.    License Grants / Change of Control

        5.1  Subject to the limitations and restrictions of Section 3.1, Isis
hereby grants to Sequitur a non-exclusive, non-sublicensable, non-transferable,
license under Isis First Generation Oligonucleotide Patents, to make, have made,
use, sell, or offer to sell, First Generation Oligonucleotides solely for use in
Sequitur's Target Validation Program. (For purposes of clarification, Sequitur's
clients can use First Generation Oligonucleotides provided by Sequitur for the
purposes of performing research regarding the validation or functionalization of
gene targets or confirmation of such function.) The license granted pursuant to
this Section extends to the termination of the last to expire licensed Patent,
unless earlier terminated as provided herein. In the event of a Change of
Control, the license granted in this Section 5.1 may be transferred to the
successor entity who assumes all of Sequitur's rights and obligations hereunder.

        5.2  In the event of a Change of Control:

a)    the successor entity may maintain the Section 5.1 license by making the
payments required in Section 6.1;

b)    the successor entity may complete the Section 3.1 concessions in
accordance with their terms; and

c)    the Section 15 agreement to mediate will terminate.

6.    Consideration

        6.1  In consideration of (i) the releases and covenants set forth above,
(ii) Isis' concessions regarding Sequitur's use of certain Next Generation
Oligonucleotides as set forth in Section 3.1, (iii) the license granted in
Section 5.1, (iv) the right granted to Sequitur to transfer the Section 5.1
license to the successor entity upon a Change of Control event, and (v) the
agreement to mediate in Section 15.1 and the agreement to delay mediation in
Section 15.2 below, Sequitur will pay Isis the amount of [***].

        6.2  If Sequitur fails to make any [***] payment, the Section 5.1
license and the Section 15 agreement to mediate will terminate.

7.    Statement of Confirmation

        7.1  Isis confirms that Integrated DNA Technologies, Inc. does not as of
the Effective Date have a license or right from Isis to supply Sequitur with
Next Generation Oligonucleotides for use in Sequitur's Target Validation
Program, and that Isis has not committed to provide such a license or right in
the future.

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8.    Confidentiality and Publicity

        8.1  Isis and Sequitur will not disclose to any third parties the terms
and conditions of this Agreement without the prior written consent of all
parties hereto except as otherwise provided herein.

        8.2  The parties shall be permitted to disclose this Agreement as
required by law. Should discovery of this Agreement be sought in a separate
civil litigation, the parties shall be permitted to disclose this Agreement to
certain qualified persons consented to by the non-producing party (either
Sequitur or Isis) and identified in a protective order entered in the separate
action.

        8.3  The parties shall be free to disclose that Isis and Sequitur have
reached a mutually agreeable business solution which settles the formerly
disputed claims in the Lawsuit and Counterclaim, as set forth in the press
release attached hereto as Exhibit B.

        8.4  In the event that a third party requests due diligence on this
Agreement, Sequitur may show the third party a version of this Agreement with
Section 6 redacted, under a Confidential Disclosure Agreement.

        8.5  The parties shall be permitted to disclose the terms of this
agreement to such of their employees who have a need to know the terms hereof
and who are bound by written obligation of confidentiality to the disclosing
party. The parties may also disclose the terms of this agreement to their
customers under the terms of written confidentiality agreements. Section 6 will
be redacted in any event of disclosure under this Section 8.5 and, in the case
of Isis, Section 15.2 will also be redacted.

9.    Disposition of Pending Lawsuits and Allocation of Costs

        9.1  Isis and Sequitur agree, promptly upon execution of this Agreement,
to execute and cause to be filed a Stipulation of Dismissal of the Lawsuit, in
the form attached hereto as Exhibit C. All parties' claims and counterclaims are
dismissed with prejudice.

        9.2  Each party will bear its own costs, expenses, expert witness fees,
and attorneys' fees in connection with the Lawsuit and with this Agreement.

        9.3  This Agreement shall be governed by, and construed in accordance
with, the laws of the State of California.

        9.4  The parties consent to the jurisdiction and venue of the United
States District Court for the Southern District of California should any dispute
arise between or among the parties concerning the interpretation and enforcement
of this Agreement or the license grants hereunder not otherwise to be resolved
by binding mediation pursuant to Section 15. The parties agree to file a joint
stipulated Order consenting to jurisdiction with the Court in the form of
Exhibit D hereto within ten (10) days of the Effective Date.

        9.5  If the wording of Exhibits C and D cannot be agreed to by the
Parties, Judge Stiven will resolve the differences.

10.    Term and Termination

        10.1 Term:

a)    the releases and covenants in this Agreement will not terminate;

b)    the Section 3.1 concessions will terminate in accordance with their terms;

c)    the section 5.1 license will terminate with the last to expire Patent or
in accordance with the terms of Section 6; and

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d)    the Section 15 agreement to mediate will terminate in accordance with the
terms of Sections 5.2 and 6.2.

        10.2 Except as expressly provided herein, mediation (rather than
termination) shall be the sole remedy for a breach of this Agreement.

11.    Agreement Binding On Successors

        11.1 The provisions of this Agreement shall be binding upon and inure to
the benefit of the parties hereto, their permitted heirs, administrators,
successors and assigns, as noted below.

12.    Nonassignability

        12.1 The parties agree this Agreement imposes personal obligations on
Isis and Sequitur. Sequitur shall not assign any rights under this Agreement,
except in the event of a Change of Control, without the written consent of Isis.
Isis may not assign its rights hereunder without the written consent of
Sequitur. However, the releases and covenants are assigned to any successor in
interest of either party.

13.    Notices

        13.1 Any notice or other communication required or permitted hereunder
shall be in writing and shall be deemed given if: (i) delivered personally to an
officer of the party to be notified; (ii) sent by facsimile transmission to the
facsimile number set forth below; or (iii) sent by overnight courier or United
States registered or certified mail, postage prepaid, return receipt requested,
to the address set forth below:

If to Isis:

Isis Pharmaceuticals, Inc.
2292 Faraday Avenue
Carlsbad, California 92008
Attention: Executive Vice President
Facsimile: (760) 603-4650

with a copy to:

Attention: General Counsel
Facsimile: (760) 268-4922

If to Sequitur:

Sequitur, Inc.
14 Tech Circle
Natick, Massachusetts 01760
Attention: President
Facsimile: (508) 655-1625

or such other address or facsimile number as may be designated by any party
hereto by written notice to the other as herein above provided.

14.    Right to Review Records

        14.1 From the date of execution of this Agreement until the end of the
Term, Sequitur shall maintain records sufficient to reflect its purchase,
manufacture, use and sales of Antisense Oligonucleotides. The records shall be
kept by Sequitur for a period of at least 2 years following the calendar year to
which they pertain. Isis will have the right to review these records as
described below, solely for purposes of determining Sequitur's compliance with
Section 3.1 of this Agreement regarding Next Generation Oligonucleotides.

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        14.2 Upon the written request of Isis, which shall be limited to no more
than once per calendar year, Sequitur agrees to provide to an independent
reviewer designated by Isis and reasonably agreed to by Sequitur records
sufficient to determine Sequitur's compliance with the Restrictions on Use set
forth in Section 3.1 of this Agreement. Sequitur shall not charge to produce the
records, but Isis shall bear the costs for such review of records provided by
Sequitur as provided above, unless the results of such review establish a
violation by Sequitur of Section 3.1 of this Agreement, in which case Sequitur
shall bear the cost of such review.

        14.3 All such records produced pursuant to a request in accord with
Section 14.1 or 14.2 shall be considered and maintained as confidential and
shall not be disclosed to anyone except as provided herein. Records produced by
Sequitur in response to a request by Isis pursuant to this Section 14 shall not
be disclosed to anyone other than Isis's independent reviewer. If Isis' reviewer
determines that a violation by Sequitur of Section 3.1 has occurred, records
sufficient to establish such violation may be disclosed to a mediator pursuant
to the Dispute Resolution provision of Section 15. Mediation regarding any
violation discovered according to the review of this Section will proceed
immediately, and will not be subject to the provision of Section 15 requiring
45 days of negotiation by the business principals of Isis and Sequitur.

15.    Dispute Resolution

        15.1 Isis and Sequitur agree that any real or perceived violations of
this Settlement Agreement or other alleged future infringement of patents or
future disputes regarding actions contemplated by this Agreement will be
addressed in a face-to-face meeting of business principals of each company who
will attempt to resolve any such issue. Isis and Sequitur agree to negotiate in
good faith for a period of up to 45 days the nature of the violation and/or
infringement and the magnitude of damages (if any). If Isis and Sequitur fail to
reach agreement, the parties will submit to binding mediation to resolve the
dispute. The mediator will be able to reasonably request documents from each
Party to enable decision-making and will decide the claim scope and validity of
any patents (only in regard to Sequitur). If the mediator determines that
Sequitur or Isis is infringing it will immediately stop infringing.
Notwithstanding the foregoing, if Sequitur has complied with Section 3.1
(vii) and, nevertheless, has infringed an Isis Patent, as long as Sequitur
agrees to cease such infringement immediately, there will be no damages for
infringement that occurs within 120 days of issuance of the patent, or use of
oligonucleotides synthesized prior to 120 days after the patent issuance. The
mediator cannot impose a license. The mediator will be selected mutually by the
parties at a mutually agreed location. Such mutual agreement must be reached
within two weeks. The mediator will be instructed that the parties desire to
have the mediation process as inexpensive and rapid as possible consistent with
achieving an accurate result and informed decision. Any mediator must have no
affiliation in the past or present with any party or their employees. The
mediator will decide what discovery if any is needed (and the time to comply
with such discovery) and will have authority to obtain that discovery and impose
penalties for non-compliance. All requests to the mediator will be made in
letter format with no formal requirements except that a copy must be sent to the
other party. The parties submit to the authority of the mediator in the place of
any court and will be bound by all decisions of the mediator without recourse to
any court or appeal therefrom. The mediator's decisions are final and if not
followed may be enforced by a court of competent jurisdiction with all cost and
attorney fees for such enforcement being paid by the losing party.

        15.2 [***]

16.    Integration

        16.1 The provisions contained herein constitute the entire understanding
between the parties with respect to the subject matter hereof, and revoke or
supersede all prior Agreements between the parties with respect to the subject
matter hereof, and is intended as a final expression of their

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Agreement. This Agreement shall take precedence over any other documents that
may be in conflict with said Agreement.

17.    Effect of Headings

        17.1 The headings and subheadings of the sections of this Agreement are
inserted for convenience of reference only and shall not control or affect the
meaning or construction of any of the Agreements, terms, covenants and
conditions of this Agreement in any manner.

18.    Severability

        18.1 If any term or provisions of this Agreement shall be found to be
void or contrary to law, such term or provision shall, but only to the extent
necessary to bring this Agreement within the requirements of law, be deemed to
be severable from the other terms and provisions hereof, and the remainder of
this Agreement shall be given effect as if the parties had not included the
severed term herein.

19.    Amendments

        19.1 No provision of this Agreement may be modified, waived or amended
except by written instrument duly executed by each of the parties hereto and
specifically referring to this Agreement. Any such modifications, waivers or
amendments shall not require additional consideration to be effective.

20.    Interpretation.

        20.1 This Agreement, including the Exhibits hereto, is the result of
bilateral negotiations between the parties and shall be construed without regard
to the party or parties responsible for its preparation. In resolving any
ambiguity or uncertainty existing herein, the parties agree that no
consideration or weight shall be given to the identity of the party drafting
this Agreement.

21.    Counterparts

        21.1 This Agreement may be executed in two or more counterparts, each of
which shall be deemed an original but all of which together shall constitute one
and the same instrument.

The parties have duly authorized and caused this Agreement to be executed as
follows:

Dated: September 6, 2002   By:   /s/ Grantland E. Bryce,
VP, Legal and General Counsel

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Isis Pharmaceuticals, Inc.          
Dated: September 6, 2002
 
By:
 
/s/ Tod Woolf, President

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Sequitur, Inc.

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Exhibit A

Sequitur's Existing Customers

        [***]

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Exhibit B

Press Release (attached as Exhibit 99.1 to 8-K)

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Exhibit C
Stipulated Dismissal and Proposed Order Thereon (attached)

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STEPHEN P. SWINTON (106398)
KENT M. WALKER (173700)
COOLEY GODWARD LLP
4401 Eastgate Mall
San Diego, CA 92121-1909
Telephone: (858) 550-6000
Facsimile: (858) 550-6420

JOSEPH LUCCI (admitted pro hac vice)
WOODCOCK WASHBURN LLP
1 Liberty Place, 46th Floor
Philadelphia, PA 19103
Telephone: (215) 568-3100
Facsimile: (215) 568-3439

Attorneys for Plaintiff and Counterclaim Defendant
ISIS PHARMACEUTICALS, INC.

RICHARD WARBURG (155223)
ARTHUR A. WELLMAN, JR. (178309)
FOLEY & LARDNER
402 W. Broadway, 23rd Floor
San Diego, CA 92101-3542
Telephone: (619) 234-6655
Facsimile: (619) 234-3510

Attorneys for Defendant and Counterclaimant
SEQUITUR, INC.

UNITED STATES DISTRICT COURT

SOUTHERN DISTRICT OF CALIFORNIA

ISIS PHARMACEUTICALS, INC., a Delaware corporation,   No. 01 CV 1223, 01 CV
2286, and 02 CV 0842 B (JFS)
Plaintiff,
 
Stipulated Dismissal and [Proposed]
Order thereon
            v.
 
 
SEQUITUR, INC., a Delaware corporation,
 
 
Defendant.
 
 
And Related Counterclaims.
 
 

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        Plaintiff and Counterclaim Defendant Isis Pharmaceuticals, Inc. and
Defendant and Counterclaimant Sequitur, Inc., through their respective
undersigned counsel, hereby stipulate that all

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claims and counterclaims in the above-captioned actions are to be dismissed with
prejudice, the parties bearing their own costs and fees of the actions.

Dated: September            , 2002   Respectfully submitted,
 
 
COOLEY GODWARD LLP
STEPHEN P. SWINTON (106398)
KENT M. WALKER (173700)
 
 
By:
 
         

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Kent M. Walker
 
 
Attorneys for Plaintiff and Counterclaim
Defendant, ISIS PHARMACEUTICALS, INC. Dated: September            , 2002        
    FOLEY & LARDNER
RICHARD WARBURG (155223)
ARTHUR A. WELLMAN, JR. (178309)
 
 
By:
 
         

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Richard Warburg
Arthur A. Wellman, Jr.
 
 
Attorneys for Defendant and Counterclaimant SEQUITUR, INC.

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ORDER

        Based on the stipulation of the parties, and good cause being shown, IT
IS HEREBY ORDERED that all claims and counterclaims in the above-captioned
actions are dismissed with prejudice, the parties bearing their own costs and
fees of the actions.

        IT IS SO ORDERED.

Dated: September            , 2002        

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Judge Rudi M. Brewster

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Exhibit D
Stipulated Consent to Jurisdiction and Proposed Order Thereon (attached)

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STEPHEN P. SWINTON (106398)
KENT M. WALKER (173700)
COOLEY GODWARD LLP
4401 Eastgate Mall
San Diego, CA 92121-1909
Telephone: (858) 550-6000
Facsimile: (858) 550-6420

JOSEPH LUCCI (admitted pro hac vice)
WOODCOCK WASHBURN LLP
1 Liberty Place, 46th Floor
Philadelphia, PA 19103
Telephone: (215) 568-3100
Facsimile: (215) 568-3439

Attorneys for Plaintiff and Counterclaim Defendant
ISIS PHARMACEUTICALS, INC.

RICHARD WARBURG (155223)
ARTHUR A. WELLMAN, JR. (178309)
FOLEY & LARDNER
402 W. Broadway, 23rd Floor
San Diego, CA 92101-3542
Telephone: (619) 234-6655
Facsimile: (619) 234-3510

Attorneys for Defendant and Counterclaimant
SEQUITUR, INC.

UNITED STATES DISTRICT COURT

SOUTHERN DISTRICT OF CALIFORNIA

ISIS PHARMACEUTICALS, INC., a Delaware corporation,   No. 01 CV 1223, 01 CV
2286, and 02 CV 0842 B (JFS)
Plaintiff,
 
Stipulated Consent to Jurisdiction
and [Proposed] Order thereon
            v.
 
 
SEQUITUR, INC., a Delaware corporation,
 
 
Defendant.
 
 
And Related Counterclaims.
 
 

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        Whereas Plaintiff and Counterclaim Defendant Isis Pharmaceuticals, Inc.
and Defendant and Counterclaimant Sequitur, Inc. executed a Settlement, Release,
and License Grant Agreement ("the Agreement") whereby the parties stipulated
that all claims and counterclaims in the above-captioned actions are to be
dismissed with prejudice, the parties bearing their own costs and fees of the
actions.

        Whereas in the Agreement the parties consented to the jurisdiction and
venue of the United States District Court for the Southern District of
California should any dispute arise between or among the parties concerning the
interpretation and enforcement of the Agreement or the license grants in the
Agreement not otherwise to be resolved by binding mediation pursuant to
Section 15 of the Agreement.

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        Therefore, the parties, by and through their respective attorneys of
record, hereby stipulate to the following:

        1.    The United States District Court for the Southern District of
California shall retain continuing jurisdiction over, and venue will be proper
in, any dispute that may arise between or among the parties concerning the
specific interpretation and enforcement of the Agreement and the license grants
in the Agreement not otherwise to be resolved by binding mediation pursuant to
Section 15 of the Agreement.

Dated: September            , 2002   Respectfully submitted,
 
 
COOLEY GODWARD LLP
STEPHEN P. SWINTON (106398)
KENT M. WALKER (173700)     By:            

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Kent M. Walker
 
 
Attorneys for Plaintiff and Counterclaim
Defendant, ISIS PHARMACEUTICALS, INC. Dated: September            , 2002        
    FOLEY & LARDNER
RICHARD WARBURG (155223)
ARTHUR A. WELLMAN, JR. (178309)
 
 
By:
 
         

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Richard Warburg
Arthur A. Wellman, Jr.
 
 
Attorneys for Defendant and Counterclaimant SEQUITUR, INC.

ORDER

        Based on the stipulation of the parties, and good cause being shown, IT
IS HEREBY ORDERED that the United States District Court for the Southern
District of California shall retain continuing jurisdiction over, and venue will
be proper in, any dispute that may arise between or among the parties concerning
the specific interpretation and enforcement of the Agreement and the license
grants in the Agreement not otherwise to be resolved by binding mediation
pursuant to Section 15 of the Agreement.

        IT IS SO ORDERED.

Dated: September            , 2002        

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Judge Rudi M. Brewster

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QuickLinks

SETTLEMENT, RELEASE, AND LICENSE GRANT AGREEMENT
Exhibit A Sequitur's Existing Customers
Exhibit B Press Release (attached as Exhibit 99.1 to 8-K)
Exhibit C Stipulated Dismissal and Proposed Order Thereon (attached)
ORDER
Exhibit D Stipulated Consent to Jurisdiction and Proposed Order Thereon
(attached)
ORDER