Document:

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                                              *Text Omitted and Filed Separately
                                               Confidential Treatment Requested
                                           Under 17 C.F.R. Sections 200.80(b)(4)
                                                              200.83 and 240b-2

                       COLLABORATION AND LICENSE AGREEMENT

                                 BY AND BETWEEN

                           ISIS PHARMACEUTICALS, INC.

                                       AND

                                 HYBRIDON, INC.

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                                TABLE OF CONTENTS
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                                                                            PAGE
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ARTICLE I  DEFINITIONS.........................................................1

   SECTION 1.1  "AFFILIATE"....................................................1

   SECTION 1.2  "AMINO PATENT RIGHTS"..........................................2

   SECTION 1.3  "ANTISENSE PRODUCTS"...........................................2

   SECTION 1.4   "ANTISENSE TECHNOLOGY"........................................2

   SECTION 1.5  "CONFIDENTIAL INFORMATION".....................................2

   SECTION 1.6  "DOCKET 104"...................................................2

   SECTION 1.7  "DOCKET 105"...................................................3

   SECTION 1.8  "DRUG POTENTIATION PATENT RIGHTS"..............................3

   SECTION 1.9  "EXHIBIT K PATENTS"............................................3

   SECTION 1.10  "FACILITATOR PATENT RIGHTS"...................................3

   SECTION 1.11  "FINDERON PATENT RIGHTS"......................................3

   SECTION 1.12  "HYBRIDON ANTISENSE DRUG".....................................4

   SECTION 1.13  "HYBRIDON ANTISENSE PATENT RIGHTS"............................4

   SECTION 1.14  "HYBRIDON EXCLUDED PATENT RIGHTS".............................5

   SECTION 1.15  "HYBRIDON INTELLECTUAL PROPERTY"..............................5

   SECTION 1.16  "IMMUNE STIMULATION PATENT RIGHTS"............................5

   SECTION 1.17  "ISIS INTELLECTUAL PROPERTY RIGHTS"...........................5

   SECTION 1.18  [*]

   SECTION 1.19  "MOTIFS"......................................................6

   SECTION 1.20  "NAKED SUBLICENSE"............................................6

   SECTION 1.21  "NON-PARENT AFFILIATE"........................................6

   SECTION 1.22  "OPTIMIZATION"................................................6

   SECTION 1.23  "PARTY".......................................................6

   SECTION 1.24  "RIBOZYMES"...................................................6

   SECTION 1.25  "RIBOZYME TECHNOLOGY".........................................6

   SECTION 1.26  "RNASEH DEPENDENT MECHANISMS OF ACTION".......................7

   SECTION 1.27  "SUBLICENSE INCOME"...........................................7

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   SECTION 1.28  "SUBLICENSEE".................................................7

   SECTION 1.29  "SUBSIDIARY"..................................................7

   SECTION 1.30  "THIRD PARTY LICENSE AGREEMENTS"..............................8

   SECTION 1.31  "TULLIS NET SALES"............................................8

   SECTION 1.32  "TULLIS PATENTS"..............................................8

   SECTION 1.33  "TULLIS PRODUCT"..............................................8

   SECTION 1.34  "UMASS PATENT RIGHTS".........................................8

   SECTION 1.35  "VALID CLAIM".................................................8

ARTICLE II  GRANT OF RIGHTS BY HYBRIDON........................................9

   SECTION 2.1  LICENSE GRANT..................................................9

   SECTION 2.2  SUBLICENSING RIGHT............................................11

   SECTION 2.3  NO IMPLIED LICENSES; RETAINED RIGHTS..........................13

   SECTION 2.4  COMMERCIALIZATION EFFORTS.....................................13

   SECTION 2.5  LICENSE AGREEMENTS TO WHICH HYBRIDON IS A PARTY...............13

   SECTION 2.6  METHYLGENE LICENSE AGREEMENT..................................14

   SECTION 2.7  ORIGENIX LICENSE AGREEMENT....................................14

   SECTION 2.8  AFFILIATES....................................................14

ARTICLE III  GRANT OF RIGHTS BY ISIS..........................................14

   SECTION 3.1  LICENSE GRANT.................................................14

   SECTION 3.2  SUBLICENSING RIGHT............................................14

   SECTION 3.3  TULLIS PATENTS................................................15

   SECTION 3.4  SCOPE OF LICENSE..............................................16

   SECTION 3.5  NO IMPLIED LICENSES...........................................17

   SECTION 3.6  LIMITATION ON LICENSE GRANT WITH RESPECT TO TARGET
                     VALIDATION AND GENE FUNCTIONALIZATION ACTIVITIES.........17

   SECTION 3.7  NOTICE OF HYBRIDON ANTISENSE DRUGS............................17

   SECTION 3.8  AFFILIATES....................................................18

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ARTICLE IV PAYMENT OBLIGATIONS................................................18

   SECTION 4.1  CONSIDERATION FOR LICENSES OF HYBRIDON INTELLECTUAL
                      PROPERTY AND ISIS INTELLECTUAL PROPERTY.................18

   SECTION 4.2  CONSIDERATION FOR SUBLICENSE OF TULLIS PATENTS................18

   SECTION 4.3  ISIS SUBLICENSE INCOME........................................19

   SECTION 4.4  RECORDS; AUDITS...............................................19

   SECTION 4.5  PAYMENT CURRENCY..............................................19

   SECTION 4.6  LATE PAYMENTS; COLLECTIONS....................................19

ARTICLE V  COLLABORATION......................................................20

ARTICLE VI INTELLECTUAL PROPERTY PROTECTION...................................20

   SECTION 6.1  PATENT PROSECUTION AND COOPERATION............................20

   SECTION 6.2  ENFORCEMENT OF HYBRIDON ANTISENSE PATENT RIGHTS...............24

ARTICLE VII  CONFIDENTIALITY..................................................27

   SECTION 7.1  CONFIDENTIAL INFORMATION......................................27

ARTICLE VIII  DISPUTE RESOLUTION..............................................28

ARTICLE IX TERM AND TERMINATION...............................................29

   SECTION 9.1  TERM..........................................................29

   SECTION 9.2  TERMINATION OF LICENSES AND SUBLICENSES FOR BREACH............30

   SECTION 9.3  TERMINATION OF SUBLICENSE OF TULLIS PATENTS...................31

   SECTION 9.4  SURVIVAL......................................................31

   SECTION 9.5  SUBLICENSE SURVIVAL...........................................31

   SECTION 9.6  FAILURE TO MAKE MASTER AGREEMENT DELIVERIES...................32

ARTICLE X MISCELLANEOUS PROVISIONS............................................32

   SECTION 10.1  INDEMNIFICATION..............................................32

   SECTION 10.2  GOVERNING LAW................................................33

   SECTION 10.3  ASSIGNMENT...................................................33

   SECTION 10.4  ENTIRE AGREEMENT; AMENDMENTS.................................33

   SECTION 10.5  NOTICES......................................................33

   SECTION 10.6  FORCE MAJEURE................................................35

   SECTION 10.7  DISCLOSURE OF PROVISIONS OF AGREEMENT........................35

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   SECTION 10.8  INDEPENDENT CONTRACTORS......................................36

   SECTION 10.9  NO STRICT CONSTRUCTION.......................................36

   SECTION 10.10  HEADINGS....................................................36

   SECTION 10.11  NO IMPLIED WAIVERS; RIGHTS CUMULATIVE.......................36

   SECTION 10.12  SEVERABILITY................................................37

   SECTION 10.13  EXECUTION IN COUNTERPARTS...................................37

   SECTION 10.14  NO CONSEQUENTIAL DAMAGES....................................37

   SECTION 10.15  PATENT VALIDITY.............................................37
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EXHIBITS:
---------

Exhibit A through Exhibit G    - Omitted
<S>                <C>
Exhibit H-1   -    Third Party License Agreements
Exhibit H-2   -    Other License Agreements
Exhibit I     -    Tullis Patents
Exhibit J     -    UMass Agreement
Exhibit K     -    Excluded Hybridon Intellectual Property
Exhibit L     -    UMass Patent Rights
Exhibit M     -    Drug Potentiation Patent Rights
Exhibit N     -    Tullis Agreement
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                       COLLABORATION AND LICENSE AGREEMENT

      This Collaboration and License Agreement (the "Agreement") is entered into
as of the 24th day of May, 2001 (the "Effective Date") by and between Isis
Pharmaceuticals, Inc., a corporation organized and existing under the laws of
the State of Delaware ("Isis"), and Hybridon, Inc., a corporation organized and
existing under the laws of the State of Delaware ("Hybridon").

                                  INTRODUCTION

      1. Hybridon is the owner or has the right to use under license certain
patents and patent applications relating to the practice of Antisense Technology
(as defined below).

      2. Isis is the owner or has the right to use under license certain patents
and patent applications relating to the practice of Antisense Technology.

      3. Hybridon and Isis are interested in licensing or sublicensing to the
other party these patents and patent applications and in collaborating from time
to time on the further research and development of Antisense Products.

      4. Hybridon and Isis have entered into a Master Agreement dated as of the
date hereof (the "Master Agreement").

5. Isis and Hybridon each recognizes that the other Party has expended
significant efforts and resources in the research and development of Antisense
Technology and the payments to be made under the Master Agreement to each Party
for the patent licenses and sublicenses granted hereunder will allow each Party
to recoup such expenditures.

      NOW, THEREFORE, Hybridon and Isis agree as follows:

                                   ARTICLE I
                                   DEFINITIONS

When used in this Agreement, each of the following terms shall have the meanings
set forth in this Article I:

      Section 1.1 "AFFILIATE". Affiliate shall mean, with respect to a person or
entity, any corporation, company, partnership, joint venture or other entity
which controls, is controlled by, or is under common control with such person or
entity. For purposes of this Section 1.1 and Section 1.21, "control" shall mean
(a) in the case of corporate entities, direct or indirect ownership of fifty
percent (50%) or more of the stock or shares having the right to vote for the
election of directors, and (b) in the case of non-corporate entities, direct or
indirect ownership of fifty percent (50%) or more of the equity interest with
the

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power to direct the management and policies of such non-corporate entities,
provided that in either such case such person or entity has the power to direct
the management and policies of such entities, whether by contract or through
representation on the board of directors or other governing body of such
entities.

      Section 1.2 "AMINO PATENT RIGHTS". Amino Patent Rights shall mean the
claims of all patents and patent applications set forth on EXHIBIT A hereto and
any continuations or divisions thereof, any patent issued with respect to any
such patent applications, any reissue, reexamination, renewal or extension
(including any supplemental patent certificate) of any such patent, any
confirmation patent or registration patent or patent of addition based on any
such patent, and all foreign counterparts of any of the foregoing.

      Section 1.3 "ANTISENSE PRODUCTS". Antisense Products shall mean
oligonucleotides or oligonucleotide analogs or mimics thereof targeted to a
specific sequence of RNA that hybridize to such sequence and through such
hybridization modulate the production of the targeted gene product. The term
Antisense Products shall not include Ribozymes.

      Section 1.4 "ANTISENSE TECHNOLOGY". Antisense Technology shall mean the
use of any oligonucleotide or oligonucleotide analog or mimic thereof targeted
to a specific sequence of RNA that hybridizes to such sequence and through such
hybridization modulates the production of the targeted gene product. The term
Antisense Technology shall not include Ribozyme Technology.

      Section 1.5 "CONFIDENTIAL INFORMATION". Confidential Information shall
mean all information, including, without limitation, proprietary information and
materials (whether or not patentable) regarding a Party's technology, products,
business information or objectives, which is designated as confidential in
writing by the disclosing Party, whether by letter or by the use of an
appropriate stamp or legend, prior to or at the time any such information is
disclosed by the disclosing Party to the other Party. Notwithstanding the
foregoing, all information which is orally, electronically or visually disclosed
by a Party, or is disclosed in writing without an appropriate letter, stamp or
legend, shall constitute Confidential Information of a Party if the disclosing
Party, within thirty (30) days after such disclosure, delivers to the other
Party a written document or documents describing the information and referencing
the place and date of such oral, visual, electronic or written disclosure and
the names of the persons to whom such disclosure was made.

      Section 1.6 "DOCKET 104". Docket 104 shall mean all patents and patent
applications set forth on EXHIBIT B-1 hereto and any continuations or divisions
thereof, any patent issued with respect to any such patent applications, any
reissue, reexamination, renewal or extension (including any

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supplemental patent certificate) of any such patent, any confirmation patent or
registration patent or patent of addition based on any such patent, and all
foreign counterparts of any of the foregoing.

      Section 1.7 "DOCKET 105". Docket 105 shall mean all patents and patent
applications set forth on EXHIBIT B-2 hereto and any continuations or divisions
thereof, any patent issued with respect to any such patent applications, any
reissue, reexamination, renewal or extension (including any supplemental patent
certificate) of any such patent, any confirmation patent or registration patent
or patent of addition based on any such patent, and all foreign counterparts of
any of the foregoing.

      Section 1.8 "DRUG POTENTIATION PATENT RIGHTS". Drug Potentiation Patent
Rights shall mean the claims of all patents and patent applications set forth on
EXHIBIT M hereto and any continuations or divisions thereof, any patent issued
with respect to any such patent applications, any reissue, reexamination,
renewal or extension (including any supplemental patent certificate) of any such
patent, any confirmation patent or registration patent or patent of addition
based on any such patent, and all foreign counterparts of any of the foregoing.

      Section 1.9 "EXHIBIT K PATENTS". Exhibit K Patents shall mean the claims
of all patents and patent applications set forth on EXHIBIT K hereto and any
continuations or divisions thereof, any patent issued with respect to any such
patent applications, any reissue, reexamination, renewal or extension (including
any supplemental patent certificate) of any such patent, any confirmation patent
or registration patent or patent of addition based on any such patent, and all
foreign counterparts of any of the foregoing.

      Section 1.10 "FACILITATOR PATENT RIGHTS". Facilitator Patent Rights shall
mean the claims of all patents and patent applications set forth on EXHIBIT C
hereto and any continuations or divisions thereof, any patent issued with
respect to any such patent applications, any reissue, reexamination, renewal or
extension (including any supplemental patent certificate) of any such patent,
any confirmation patent or registration patent or patent of addition based on
any such patent, and all foreign counterparts of any of the foregoing.

      Section 1.11 "FINDERON PATENT RIGHTS". Finderon Patent Rights shall mean
the claims of all patents and patent applications set forth on EXHIBIT D hereto
and any continuations or divisions thereof, any patent issued with respect to
any such patent applications, any reissue, reexamination, renewal or extension
(including any supplemental patent certificate) of any such patent, any
confirmation patent or registration patent or patent of addition based on any
such patent, and all foreign counterparts of any of the foregoing.

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      Section 1.12 "HYBRIDON ANTISENSE DRUG". Hybridon Antisense Drug shall mean
an Antisense Product which is a therapeutic or prophylactic product for the
treatment or prevention of disease in a human or an animal that is discovered,

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developed and/or Optimized either by Hybridon or a Subsidiary alone or as
part of a "bona fide drug discovery collaboration".

      For purposes of this Section 1.12 only, a "bona fide drug discovery
collaboration" is an arrangement between Hybridon or a Subsidiary and a third
party (i) in which the intent of the collaborators in engaging in discovery,
development and/or Optimization activities is to discover, develop, Optimize and
commercialize an Antisense Product. [*] Initiation of IND supporting
toxicology is the initiation of animal toxicity studies in support of the filing
of an Investigational New Drug application with the U.S. Food and Drug
Administration or a similar regulatory filing with a similar regulatory
authority in another jurisdiction. If a contractor (which is not the third party
collaborator) in the business of performing preclinical studies provides such
services through the performance of IN VIVO animal studies under the supervision
of Hybridon or a Subsidiary, the services so provided shall be treated as work
performed directly by Hybridon or a Subsidiary for purposes of this definition.
Work performed by a contractor of, and paid for by, Hybridon or a Subsidiary
under the supervision of Hybridon or a Subsidiary shall be treated as work
performed directly by Hybridon or a Subsidiary for purposes of this definition.
The Parties acknowledge that a part of the discovery, development and
Optimization of an Hybridon Antisense Drug may involve the validation and
prioritization of gene targets to form the basis for antisense drug discovery
activities.

      In the event of a sale or other transfer of the assets of Hybridon, no
Antisense Product developed by the acquiring company prior to the acquisition
will be deemed to be a Hybridon Antisense Drug unless (i) such acquiring company
acquires all or substantially all of the assets of the antisense business of
Hybridon, and (ii) such Antisense Product [*]by the acquiring company prior to
the acquisition; provided, however, that an Antisense Product that would qualify
as a Hybridon Antisense Drug irrespective of the acquisition will not lose its
status as such as a result of such acquisition.

      Section 1.13 "HYBRIDON ANTISENSE PATENT RIGHTS". Hybridon Antisense Patent
Rights shall mean the claims of all patents and patent applications and any
continuations or divisions thereof, whether now existing, now filed or later
filed on inventions invented, licensed or sublicensed by Hybridon prior to April
26, 2001, any patent issued with respect to any such patent applications, any
reissue, reexamination, renewal or extension (including any supplemental patent
certificate) of any such patent, any confirmation patent or registration patent
or patent of addition based on any such patent, and all foreign counterparts of
any of the foregoing, which Hybridon owned or had the right to sublicense as of
April 26, 2001 and which are necessary or useful to practice Antisense
Technology, including without limitation the patents and patent applications set
forth on EXHIBIT E, but not including the Hybridon Excluded Patent Rights and
the patents and patent

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applications licensed to Hybridon (the "Hybridon IDT Patent Rights") pursuant
to the Non-Exclusive License Agreement dated as of March 12, 1999 between
Integrated DNA Technologies, Inc. ("IDT") and Hybridon.

      Section 1.14 "HYBRIDON EXCLUDED PATENT RIGHTS". Hybridon Excluded Patent
Rights shall mean the Amino Patent Rights, Docket 104, Docket 105, Facilitator
Patent Rights, Finderon Patent Rights, Immune Stimulation Patent Rights, Drug
Potentiation Patent Rights and the Exhibit K Patents.

      Section 1.15 "HYBRIDON INTELLECTUAL PROPERTY". Hybridon Intellectual
Property shall mean collectively the Hybridon Antisense Patent Rights and the
Hybridon Excluded Patent Rights (all solely to the extent licensed to Isis under
Section 2.1), but shall exclude the Hybridon IDT Patent Rights.

      Section 1.16 "IMMUNE STIMULATION PATENT RIGHTS". Immune Stimulation Patent
Rights shall mean the claims of all patents and patent applications set forth on
EXHIBIT F hereto and any continuations or divisions thereof, any patent issued
with respect to any such patent applications, any reissue, reexamination,
renewal or extension (including any supplemental patent certificate) of any such
patent, any confirmation patent or registration patent or patent of addition
based on any such patent, and all foreign counterparts of any of the foregoing.

      Section 1.17 "ISIS INTELLECTUAL PROPERTY RIGHTS". Isis Intellectual
Property Rights shall mean the claims that cover Motifs or RNaseH Dependent
Mechanisms of Action of all patents and patent applications and any
continuations or divisions thereof, whether now existing, now filed or later
filed on inventions invented, licensed or sublicensed by Isis prior to April 26,
2001, any patent issued with respect to any such patent applications, any
reissue, reexamination, renewal or extension (including any supplemental patent
certificate) of any such patent, any confirmation patent or registration patent
or patent of addition based on any such patent, and all foreign counterparts of
any of the foregoing, which Isis owned or had the right to sublicense as of
April 26, 2001, including without limitation the patents and patent applications
set forth on EXHIBIT G hereto; provided, however, that Isis Intellectual
Property Rights shall not include manufacturing methods, including without
limitation reagents, synthons and processes used in manufacturing and analyzing
oligonucleotides; chemistries, including without limitation modifications made
to the backbone, sugar or base of an oligonucleotide and oligonucleotide
conjugates (including the chemistries of the conjugate and the conjugation
methods); formulations, including without limitation methods and reagents for
delivery and uptake of oligonucleotides; gene-related patents, including without
limitation patents to specific gene structures, gene targets and treatments
based upon a genetic target; and patents and patent applications licensed to

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Isis pursuant to the Non-Exclusive License Agreement dated March 19, 1999
between IDT and Isis.

      Section 1.18 [*]

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      Section 1.19 "MOTIFS". Motifs shall mean hybrid oligonucleotide structures
that have at least two regions within the oligonucleotide that have different
chemistries, one of which will support cleavage via RNaseH Dependent Mechanisms
of Action. Motifs do not include specific chemistries necessary or useful to
create or Optimize such structures, whether or not such chemistries are also
disclosed by or claimed in the same patent or patent application.

      Section 1.20 "NAKED SUBLICENSE". Naked Sublicense shall mean any license
or sublicense of intellectual property granted by a Party or a Subsidiary to a
third party other than a license or sublicense which is granted as part of a
bona fide research, development, manufacturing or commercialization
collaboration between the Party or a Subsidiary and the third party (it being
agreed by the Parties that the definition of the term "collaboration" in this
Section 1.20 shall not be interpreted by reference to the definition of
collaboration used in Section 1.12). For purposes of this definition, a bona
fide research, development, manufacturing or commercialization collaboration may
include collaborative research and discovery, including without limitation gene
functionalization and target validation.

      Section 1.21 "NON-PARENT AFFILIATE". Non-Parent Affiliate shall mean, with
respect to a person or entity, any Affiliate of such person or entity other than
any corporation, company, partnership, joint venture or other entity which
controls (as defined in Section 1.1) such person or entity.

      Section 1.22 "OPTIMIZATION". Optimization shall mean the process by which
the properties of an Antisense Product are improved by making chemical
modifications to such Antisense Product or by selecting a different sequence of
RNA for such Antisense Product.

      Section 1.23 "PARTY". Party shall mean Isis or Hybridon; "Parties" shall
mean Isis and Hybridon. As used in this Agreement, references to "third parties"
do not include a Party or its Subsidiaries.

      Section 1.24 "RIBOZYMES". Ribozymes shall mean oligonucleotides or
oligonucleotide analogs or mimics containing a catalytic core having a bulge or
stem loop and regions flanking the catalytic core that hybridize to a targeted
RNA and modulate the targeted RNA by cleavage at a site next to a specific
ribonucleotide triplet by an oligonucleotide catalyzed transesterification
reaction.

      Section 1.25 "RIBOZYME TECHNOLOGY". Ribozyme Technology shall mean the use
of any oligonucleotides or oligonucleotide analogs or mimics thereof containing
a catalytic core having a bulge or stem loop and regions flanking the catalytic
core that hybridize to a targeted RNA and modulate the

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targeted RNA by cleavage at a site next to a specific ribonucleotide triplet
by an oligonucleotide catalyzed transesterification reaction.

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      Section 1.26 "RNASEH DEPENDENT MECHANISMS OF ACTION". RNaseH Dependent
Mechanisms of Action shall mean methods of using RNaseH enzymes to cleave a
targeted RNA in vitro or in vivo. RNaseH Dependent Mechanisms of Action do not
include chemistries necessary or useful to facilitate or Optimize such cleavage,
whether or not such chemistries are also disclosed by or claimed in the same
patent or patent application.

      Section 1.27 "SUBLICENSE INCOME". Sublicense Income shall mean all
consideration received from Sublicensees by Isis or a Subsidiary pursuant to a
Naked Sublicense by Isis or a Subsidiary which covers, in whole or in part,
Hybridon Intellectual Property and all consideration received from Sublicensees
by Isis or an Affiliate pursuant to a Naked Sublicense not involving Hybridon
Intellectual Property if such Naked Sublicense arose out of the same transaction
as, or was otherwise related to, a Naked Sublicense which covers, in whole or in
part, Hybridon Intellectual Property. Sublicense Income does not include (i)
payments made by a Sublicensee in consideration for the issuance of equity or
debt securities of Isis to the extent such payments do not exceed the fair
market value of the securities being issued. [*] If non-monetary consideration
is received from Sublicensees by Isis or its Subsidiaries, then a commercially
reasonable monetary value will be assigned for purposes of calculating
Sublicense Income.

      Section 1.28 "SUBLICENSEE". Sublicensee shall mean any third party granted
the right hereunder by a Party, its Subsidiaries or a Sublicensee having the
right to grant further sublicenses, to discover, develop, make, have made, use,
sell, have sold, offer to sell, import or have imported products covered by the
Hybridon Intellectual Property (in the case of a Sublicensee of Isis, its
Subsidiaries or a Sublicensee having the right to grant further sublicenses) or
Isis Intellectual Property or Tullis Patents (in the case of a Sublicensee of
Hybridon, its Subsidiaries or a Sublicensee having the right to grant further
sublicenses).

      Section 1.29 "SUBSIDIARY". Subsidiary shall mean with respect to a Party,
any corporation, company, partnership, joint venture or other entity, 100% of
the equity securities of which are directly or indirectly owned by such Party;
provided, however, that if such Party does not directly or indirectly own 100%
of the equity securities of the entity, such entity shall nevertheless be deemed
a Subsidiary for purposes of this definition if the equity securities not owned
directly or indirectly by such Party consist solely of: (a) director qualifying
shares, (b) equity securities of the entity owned by employees, directors or
officers of the Party or the entity so long as such ownership by employees,
directors and officers does not exceed 10% of the equity securities of the
entity and/or (c) in the case of entities, the operations of which are
substantially conducted outside the United States, equity securities of the
entity owned by financial investors so long as such ownership by financial
investors does not exceed 20% of the equity securities of the entity. For

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purposes of this Section 1.29, indirect ownership shall mean ownership through
an entity or a chain

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      Section 1.30 of entities as to each member of which the Party or another
entity in the chain owns 100% of the equity securities (other than director
qualifying shares).

      Section 1.31 "THIRD PARTY LICENSE AGREEMENTS". Third Party License
Agreements shall mean those agreements set forth on EXHIBIT H-1 attached hereto
pursuant to which Hybridon has licensed Hybridon Intellectual Property to third
parties.

      Section 1.32 "TULLIS NET SALES". Tullis Net Sales shall mean the gross
sales revenues received by Hybridon, its Subsidiaries or Sublicensees from the
sale of Tullis Products, minus (a) all sales, use, and excise taxes, and customs
duties or other charges; (b) transportation and handling charges (including
transport insurance) actually incurred and paid by the buyer as part of the
purchase price; and (c) amounts repaid or credited by reason of rejections or
returns. Sales of a Tullis Product by Hybridon to a Subsidiary of Hybridon for
sale by the Subsidiary shall not be considered a sale of Tullis Products
hereunder.

      Section 1.33 "TULLIS PATENTS". Tullis Patents shall mean the Technology
Rights (as defined in the Non-Exclusive Patent License Agreement dated September
14, 1992 (the "Tullis Agreement") between Isis and Molecular Biosystems, Inc.
("MBI")) licensed by Isis from MBI under the Tullis Agreement, including without
limitation the patents and patent applications set forth on EXHIBIT I hereto.

      Section 1.34 "TULLIS PRODUCT". Tullis Product shall mean any product whose
use, manufacture or sale by Hybridon, its Subsidiaries or Sublicensees, in any
jurisdiction in which a patent which is a Tullis Patent has been allowed, would
but for the provisions of Section 3.3 constitute an infringement of such patent.

      Section 1.35 "UMASS PATENT RIGHTS". UMass Patent Rights shall mean the
Patent Rights (as defined in the UMass Agreement (as defined below)) licensed by
Hybridon from UMass under the UMass Agreement, including without limitation the
patents and patent applications set forth on EXHIBIT L hereto.

      Section 1.36 "VALID CLAIM". Valid Claim shall mean a claim which (i) in
the case of any unexpired United States or foreign patent, shall not have been
donated to the public, disclaimed or held invalid or unenforceable by a court of
competent jurisdiction in an unappealed or unappealable decision, or (ii) in the
case of any United States or foreign patent application, shall not have been
permanently cancelled, withdrawn, abandoned or been pending for more than seven
(7) years.

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                                   ARTICLE II
                           GRANT OF RIGHTS BY HYBRIDON

Section 2.1 LICENSE GRANT.

            (a) License Grant to Hybridon Antisense Patent Rights. Subject to
the terms and conditions of this Agreement, including without limitation
Hybridon's retained rights under Section 2.3 and Section 2.5(a) of this
Agreement, Hybridon hereby grants to Isis and its Subsidiaries an exclusive
worldwide license or sublicense, as applicable, under the Hybridon Antisense
Patent Rights, to practice Antisense Technology and to discover, develop, make,
have made, use, sell, have sold, offer to sell, import and have imported
Antisense Products. These rights shall only be sublicensable as explicitly
provided in Section 2.2.

            (b) Limited License Grant to Hybridon Excluded Patent Rights.
Subject to the terms and conditions of this Agreement, including without
limitation Hybridon's retained rights under Section 2.3 and Section 2.5(a) of
this Agreement, Hybridon hereby grants to Isis and its Subsidiaries the limited
worldwide licenses or sublicenses, as applicable, under the Hybridon Excluded
Patent Rights to practice Antisense Technology and to discover, develop, make,
have made, use, sell, have sold, offer to sell, import and have imported
Antisense Products, in each case solely to the extent specifically described
below. These rights shall only be sublicensable as explicitly provided in
Section 2.2.

                     (i)   [*]

                     (ii)  [*]

            (iii)    under the Immune Stimulation Patent Rights (A) to discover,
                     develop, make, have made, use, sell, have sold, offer to
                     sell, import and have imported Antisense Products which
                     contain modifications which have neutralized the immune
                     stimulation caused by an immunostimulatory CpG dinucleotide
                     in such Antisense Products, (B) to practice Antisense
                     Technology using oligonucleotides which contain
                     modifications which have neutralized the immune stimulation
                     caused by an immunostimulatory CpG dinucleotide in such
                     oligonucleotides, and (C) to discover, develop, make, have
                     made, use, sell, have sold, offer to sell, import and have
                     imported Antisense Products which target genes involved in
                     immunity modulation;

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            (iv)     under the Facilitator Patent Rights to discover, develop,
                     make, have made, use, sell, have sold, offer to sell,
                     import and have imported Antisense Products and practice
                     Antisense Technology, provided that neither such Antisense
                     Products nor such Antisense Technology use, or are used
                     with, a Ribozyme or Ribozyme Technology;

            (v)      under the Finderon Patent Rights to discover, develop,
                     make, have made, use, sell, have sold, offer to sell,
                     import and have imported Antisense Products and practice
                     Antisense Technology, provided that neither such Antisense
                     Products nor such Antisense Technology use, or are used
                     with, a Ribozyme or Ribozyme Technology;

            (vi)     under the Amino Patent Rights to discover, develop, make,
                     have made, use, sell, have sold, offer to sell, import and
                     have imported Antisense Products and practice Antisense
                     Technology, provided that such Antisense Products and
                     Antisense Technology use, or are used with, the technology
                     covered by the claims of the Amino Patent Rights solely for
                     the conjugation of functional groups for therapeutic or
                     prophylactic purposes only;

            (vii)    under the Drug Potentiation Patent Rights to discover,
                     develop, make, have made, use, sell, have sold, offer to
                     sell, import and have imported Antisense Products and
                     practice Antisense Technology, which Antisense Products and
                     Antisense Technology primarily act against a gene target
                     implicated in cancer through an antisense mechanism, but
                     which may incidentally potentiate an anti-cancer prodrug;
                     and

            (viii)   under the Exhibit K Patents to discover, develop, make,
                     have made, use, sell, have sold, offer to sell, import and
                     have imported Antisense Products and practice Antisense
                     Technology; provided, however, that the license
                     contemplated by this clause (viii) shall not extend to
                     Antisense Products or Antisense Technology related to
                     specific claimed gene targets or pseudo-cyclic
                     oligonucleotide structures and applications.

      The Parties agree that if, during the term of the license and sublicense
granted by Hybridon to Isis and its Subsidiaries in this Section 2.1(b), a claim

                                     - 10 -
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issues from any patent application included in Hybridon Excluded Patent Rights
that is necessary or useful for the practice of Antisense Technology, Hybridon
shall not use such claim to preclude or otherwise interfere with the ability of
Isis or its Subsidiaries to discover, develop, make, have made, use, sell, have
sold, offer to sell, import and have imported Antisense Products and practice
Antisense Technology; provided, however, that to the extent that the license or
sublicense grant set forth above in this Section 2.1(b) is limited in scope as
to its application to Antisense Products or Antisense Technology, such
limitation shall also be applicable to the restrictions on Hybridon's rights to
preclude or otherwise interfere with Isis and its Subsidiaries set forth in this
paragraph (i.e., if the license or sublicense grant is not applicable, Hybridon
shall not be restricted from precluding or interfering).

                  (c) The licenses and sublicenses granted by Hybridon to Isis
      and its Subsidiaries in Sections 2.1(a) and (b) to the extent such
      licenses or sublicenses cover UMass Patent Rights are subject to, without
      limitation Sections 2.2(a), 2.2(b), 2.2(d), 2.6, 2.7, 4.3(a), 4.3(d), 7.1,
      10.4 and 12.4(a) of the License Agreement dated as of February 21, 1990
      and restated as of September 8, 1993 by and between Hybridon and
      University of Massachusetts Medical Center (formerly the Worcester
      Foundation for Biomedical Research, Inc. and referred to herein as
      "UMass") (the "UMass Agreement"). A copy of the UMass Agreement is
      attached to this Agreement as EXHIBIT J. Hybridon hereby represents and
      warrants as of the date hereof: (i) that Exhibit J is a true, correct and
      complete copy of the UMass Agreement and all amendments and/or other
      changes thereto, (ii) that the UMass Agreement is in full force and
      effect, (iii) that Hybridon is not in default thereunder and (iv) that
      there has been no waiver of rights by Hybridon thereunder. Hybridon
      further represents and warrants as of the date hereof that Isis shall have
      no payment obligation to UMass arising out of the execution and delivery
      of this Agreement or the sublicensing by Hybridon of the UMass Patent
      Rights hereby and that any payment obligations that do arise under the
      UMass Agreement shall be the sole responsibility of Hybridon; provided
      that Isis may have payment obligations to UMass directly in the case of a
      termination of the UMass Agreement pursuant to the last paragraph of
      Section 2.2(c) of the UMass Agreement.

      Section 2.2 SUBLICENSING RIGHT.

                  (a) Isis and its Subsidiaries shall have the right to grant
      sublicenses under the licenses and sublicenses from Hybridon set forth in
      Section 2.1 above to third parties. Each such sublicense shall be subject
      and subordinate to, and consistent with, the terms and conditions of this
      Agreement, and shall provide that any Sublicensee shall have no right to
      grant further sublicenses except on terms consistent with this Section
      2.2. In the event of a material default by any

                                     - 11 -
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      Sublicensee under a sublicense agreement, Isis will inform Hybridon and
      take commercially reasonable efforts to cause the Sublicensee to cure
      the default or will terminate the sublicense or, if Isis is not the
      sublicensor under such sublicense, Isis will cause the sublicensor under
      such sublicense to take commercially reasonable efforts to cause the
      Sublicensee to cure the default or to terminate such sublicense; provided,
      however that none of Isis, its Subsidiaries or the sublicensor under such
      sublicense shall be responsible to Hybridon for the default by the
      Sublicensee under the sublicense agreement.

                  (b) (i) Isis shall provide UMass with a copy of any sublicense
      granted pursuant to this Section 2.2 by Isis or its Subsidiaries or
      Sublicensees which includes a sublicense of UMass Patent Rights, within
      thirty (30) days after the grant of such sublicense. Hybridon shall use
      its reasonable best efforts to cause UMass to enter into a confidentiality
      agreement with Isis with respect to sublicenses provided to UMass under
      this clause (i) (it being understood that Hybridon shall not be obligated
      to make any payment or to provide any other consideration to UMass for
      such confidentiality agreement by UMass).

                      (ii) Isis shall provide Hybridon with written notice of
any sublicense (an "Isis Sublicense") granted pursuant to this Section 2.2 by
Isis or its Subsidiaries or Sublicensees within thirty (30) days after the grant
of such sublicense, such written notice specifying the name of the Sublicensee,
the date of the sublicense and whether such Isis Sublicense includes UMass
Patent Rights or is a Naked Sublicense. Hybridon shall have the right, not more
than twice during any calendar year, to have any Isis Sublicense reviewed by an
independent third party chosen by Hybridon to ascertain whether such Isis
Sublicense includes UMass Patent Rights or is a Naked Sublicense. Isis shall
cooperate in all reasonable respects with the review of such Isis Sublicense by
the independent third party under this Section 2.2(b)(ii), including without
limitation responding to questions directed at determining whether such Isis
Sublicense includes UMass Patent Rights or is a Naked Sublicense. Hybridon shall
pay all costs of such review; provided, however, that if, contrary to the
information provided by Isis in the written notice provided to Hybridon in
connection with the grant of such Isis Sublicense, such Isis Sublicense does in
fact include UMass Patent Rights or is a Naked Sublicense, Isis shall reimburse
Hybridon for the costs of such review. If the independent third party determines
that such Isis Sublicense includes UMass Patent Rights or is a Naked Sublicense,
such independent third party shall notify Isis and Hybridon. If Isis disagrees
with the determination of the independent third party, the third party shall be
permitted hereunder to provide Hybridon with a copy of the Isis Sublicense.

                                     - 12 -
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                  (c) Any Naked Sublicense of Hybridon Intellectual Property by
      Isis or its Subsidiaries to (i) third parties which are parties to license
      or sublicense agreements with Isis or its Affiliates or Subsidiaries not
      involving Hybridon Intellectual Property and (ii) Affiliates of Isis or
      its Subsidiaries shall be made by Isis or its Subsidiaries on commercially
      reasonable terms. Isis and its Subsidiaries shall not sublicense Hybridon
      Intellectual Property separately from any intellectual property of Isis or
      its Affiliates or Subsidiaries, including without limitation the Isis
      Intellectual Property, for the purpose of reducing the amount of
      Sublicense Income payable by Isis or its Subsidiaries to Hybridon under
      Section 4.3.

      Section 2.3 NO IMPLIED LICENSES; RETAINED RIGHTS. Other than those rights
and licenses explicitly granted herein, no right or license under the Hybridon
Intellectual Property is granted to Isis or its Subsidiaries or Sublicensees.
Notwithstanding the rights and licenses granted herein, Hybridon shall retain
its rights under the Hybridon Intellectual Property for all purposes, including
without limitation its rights to discover, develop, make, have made, use, sell,
have sold, offer to sell, import and have imported Antisense Products, to
practice Antisense Technology and to license or sublicense Hybridon Intellectual
Property; provided, that, except for licenses and sublicenses provided under the
Third Party License Agreements, Hybridon and its Subsidiaries shall not grant
any Naked Sublicenses of the Hybridon Antisense Patent Rights to any third
parties (other than Subsidiaries).

      Section 2.4 COMMERCIALIZATION EFFORTS. Isis hereby agrees to undertake
reasonable efforts to bring one or more products covered by a claim of the UMass
Patent Rights into commercial use as quickly as is reasonably possible.

      Section 2.5 LICENSE AGREEMENTS TO WHICH HYBRIDON IS A PARTY.

                  (a) Notwithstanding Section 2.1 of this Agreement, Hybridon
      shall not and is not licensing or sublicensing to Isis or its Subsidiaries
      any rights under the Hybridon Intellectual Property to the extent that
      such Hybridon Intellectual Property has been licensed or sublicensed by
      Hybridon under the Third Party License Agreements.

                  (b) Hybridon hereby represents and warrants as of the date
      hereof that, except for the agreements set forth on EXHIBIT H-2 attached
      hereto: (i) Hybridon has not entered into any agreement under which it has
      licensed from another party any of the Hybridon Intellectual Property and
      (ii) Hybridon has not entered into any agreement under which it has
      licensed to another party any of the Hybridon Intellectual Property other
      than the Third Party License Agreements.

                                     - 13 -
<Page>

                  (c) Hybridon agrees that it shall not amend or expand any
      Third Party License Agreement in a manner that is inconsistent with this
      Agreement, including without limitation amending any Third Party License
      Agreement to grant any new exclusive license under the Hybridon Antisense
      Patent Rights, without the prior written consent of Isis, which consent
      shall not be unreasonably withheld or delayed.

                  (d) Hybridon hereby represents and warrants as of the date
      hereof as to the Third Party License Agreements: (i) that it has provided
      true

                                     - 14 -
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      and correct copies of all such agreements to Isis, (ii) that all such
      agreements are in full force and effect, (iii) that Hybridon is not in
      default under any such agreement and (iv) that there has been no waiver of
      rights by Hybridon thereunder.

      Section 2.6 METHYLGENE LICENSE AGREEMENT. If Methylgene Inc.
("Methylgene") designates a target which Methylgene desires to select as a
Second Molecular Target or a Third Molecular Target (as such terms are defined
in the Amended and Restated License Agreement made effective as of January 4,
1996, as amended and restated on September 21, 2000 (the "Methylgene License
Agreement")) pursuant to the terms of the Methylgene License Agreement [*].

      Section 2.7 ORIGENIX LICENSE AGREEMENT. Hybridon shall [*] License
Agreement dated as of January 22, 1999 (the "OriGenix License Agreement")
between Hybridon and OriGenix Technologies Inc. ("OriGenix")) and shall [*]

      Section 2.8 AFFILIATES. Hybridon hereby represents and warrants as of the
date hereof that no Affiliate of Hybridon owns or controls any patents, patent
applications or inventions invented, licensed or sublicensed by such Affiliate
prior to April 26, 2001 which are necessary or useful to practice Antisense
Technology.

                                  ARTICLE III
                             GRANT OF RIGHTS BY ISIS

      Section 3.1 LICENSE GRANT. Subject to the terms and conditions of this
Agreement, Isis hereby grants to Hybridon and its Subsidiaries a worldwide
non-exclusive license or sublicense, as applicable under the Isis Intellectual
Property Rights to discover, develop, make, have made, use, sell, have sold,
offer to sell, import and have imported Hybridon Antisense Drugs. These rights
shall only be sublicensable as explicitly provided in Section 3.2.

      Section 3.2 SUBLICENSING RIGHT. Hybridon and its Subsidiaries shall have
the right to grant sublicenses under the license from Isis set forth in Section
3.1 above to third parties only to discover, develop, make, have made, use,
sell, have sold, offer to sell, import and have imported Hybridon Antisense
Drugs. Each such sublicense shall be subject and subordinate to, and consistent
with, the terms and conditions of this Agreement, and shall provide that any
Sublicensee shall have no right to grant further sublicenses except on

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terms consistent with this Section 3.2. In the event of a material default by
any Sublicensee under a sublicense agreement, Hybridon will inform Isis and
take commercially reasonable efforts to cause the Sublicensee to cure the
default or will terminate the sublicense or, if Hybridon is not the sublicensor
under such sublicense, Hybridon will cause the sublicensor under such
sublicense to take commercially reasonable efforts to cause the Sublicensee
to cure the default or to terminate such sublicense; provided however that none
of Hybridon, its Subsidiaries or the sublicensor under such sublicense shall
be responsible to Isis for the default by the Sublicensee under the sublicense
agreement. Notwithstanding the rights granted under this Section 3.2, Hybridon
and its Subsidiaries shall [*]

      Section 3.3 TULLIS PATENTS.

                  (a) Subject to the terms and conditions of this Agreement,
      Isis hereby grants to Hybridon and its Subsidiaries a worldwide
      non-exclusive sublicense, with the right to grant sublicenses as provided
      in Section 3.3(b), under the Tullis Patents to discover, develop, make,
      have made, use, sell, have sold, offer to sell, import and have imported
      Hybridon Antisense Drugs, provided that such Hybridon Antisense Drugs
      employ technology covered by the Isis Intellectual Property as a material
      element thereof.

                  (b) (i) Hybridon and its Subsidiaries shall have the right to
      grant sublicenses under the license from Isis set forth in Section 3.3(a)
      to third parties (x) provided that such sublicense may only be granted to
      third parties in connection with the grant of a sublicense to such third
      parties of Isis Intellectual Property under Section 3.2, and (y) solely to
      discover, develop, make, have made, use, sell, have sold, offer to sell,
      import and have imported Hybridon Antisense Drugs that employ technology
      covered by the Isis Intellectual Property as a material element thereof.
      Each such sublicense shall be subject and subordinate to, and consistent
      with, the terms and conditions of this Agreement, and shall provide that
      any such Sublicensee shall have no right to grant further sublicenses
      except on terms consistent with this Section 3.3(b).

                      (ii) Hybridon shall provide MBI with a copy of any
sublicense granted by Hybridon or its Subsidiaries or Sublicensees pursuant to
this Section 3.3(b) within thirty (30) days after the grant of such sublicense.
Isis shall use its reasonable best efforts to cause MBI to enter into a
confidentiality agreement with Hybridon with respect to sublicenses provided to
MBI under this Section 3.3(b) (it being understood that Isis shall not be
obligated to make any payment or to provide any other consideration to MBI for
such confidentiality agreement by MBI). In the event that MBI does not sign such
a confidentiality agreement with Hybridon, Isis shall enforce against MBI, for
and on behalf of Hybridon, the confidentiality provisions of the Tullis

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Agreement with respect to the sublicenses provided by Hybridon, its Subsidiaries
or Sublicensees to MBI and with respect to any other confidential information
of Hybridon or a Subsidiary or Sublicensee of Hybridon that MBI receives.

                      (iii)  In the event of a material default by any
Sublicensee under a sublicense agreement pursuant to this Section 3.3(b),
Hybridon will inform Isis and take commercially reasonable efforts to cause the
Sublicensee to cure the default or will terminate the sublicense, or if Hybridon
is not the sublicensor under such sublicense, Hybridon will cause the
sublicensor under such sublicense to take commercially reasonable efforts to
cause the Sublicensee to cure the default or to terminate such sublicense;
provided however that none of Hybridon, its Subsidiaries or the sublicensor
under such sublicense shall be responsible to Isis for the default by the
Sublicensee under the sublicense agreement. Notwithstanding the rights granted
under this Section 3.3(b), Hybridon shall [*]

                  (c) A copy of the Tullis Agreement is attached to this
      Agreement as EXHIBIT N. Isis hereby represents and warrants as of the date
      hereof: (i) that Exhibit N is a true, correct and complete copy of the
      Tullis Agreement and all amendments and/or other changes thereto that
      affect the rights of Hybridon as a sublicensee thereunder, (ii) that the
      Tullis Agreement is in full force and effect, (iii) that Isis is not in
      default thereunder and (iv) that there has been no waiver of rights by
      Isis thereunder. Isis further represents and warrants as of the date
      hereof that Hybridon shall have no payment obligation to MBI arising out
      of the execution and delivery of this Agreement or the sublicensing by
      Isis of the Tullis Patents hereby and that any payment obligations that do
      arise shall be the sole responsibility of Isis.

      Section 3.4 SCOPE OF LICENSE. Hybridon acknowledges that Isis claims
intellectual property covering numerous chemical modifications to
oligonucleotides including without limitation modifications to backbone
linkages, sugars, heterocyclic bases and conjugates and to methods of making the
same, including methods of making various oligonucleotide intermediates (the
"Isis Chemistry Intellectual Property"). Hybridon acknowledges and agrees that
no Isis Chemistry Intellectual Property is included in the Isis Intellectual
Property being licensed or sublicensed to Hybridon and its Subsidiaries pursuant
to Section 3.1 of this Agreement, except as expressly set forth below in this
Section 3.4. [*] Isis hereby agrees that any patents owned or controlled by
Isis or an Affiliate as of the date hereof or any patents that may issue in the
future to Isis or an Affiliate from or in respect of any patent applications
which Isis or an Affiliate owned or had the right to sublicense as of April 26,
2001, which would otherwise be infringed by the practice of the Hybridon 2'-O
Methyl Chemistry, shall constitute Isis Intellectual Property for all purposes
of this Agreement, including without limitation the license grant provided in
Section

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3.1; provided, however, that the license grant with respect to such patents
shall only provide Hybridon and its Subsidiaries with the right to discover,
develop, make, have made, use, sell, have sold, offer to sell, import and have
imported Hybridon Antisense Drugs which incorporate the Hybridon 2'-O

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Methyl Chemistry. If any patent of Isis or an Affiliate includes claims to a
combination of modifications to both substitution with 2'-O-methyl and Isis
Chemistry Intellectual Property in addition to 2'-O-methyl substituents, nothing
in this Section 3.4 shall be deemed to be a grant of rights to Hybridon or its
Subsidiaries to practice the Isis Chemistry Intellectual Property other than
2'-O-methyl substituents.

      Section 3.5 NO IMPLIED LICENSES. Other than those rights and licenses
explicitly granted herein, no right or license under the Isis Intellectual
Property or the Tullis Patents is granted to Hybridon or its Subsidiaries or
Sublicensees.

      Section 3.6 LIMITATION ON LICENSE GRANT WITH RESPECT TO TARGET VALIDATION
AND GENE FUNCTIONALIZATION ACTIVITIES. Notwithstanding anything to the contrary
in Sections 3.1 and 3.3(a), the licenses set forth in Sections 3.1 and 3.3(a)
above do not grant Hybridon and its Subsidiaries the right:

                  (a) to use the Isis Intellectual Property and the Tullis
      Patents for target validation and gene functionalization activities,
      except when, and only to the extent that, (i) such activities are directed
      to the discovery, development, Optimization and commercialization of a
      Hybridon Antisense Drug and (ii) such activities are performed only by
      Hybridon or a Subsidiary and not by a contractor or a collaborator, or

                  (b) to use, or enable any third party to use, any information
      that is developed during such target validation and gene functionalization
      activities in the development of a drug other than a Hybridon Antisense
      Drug, including without limitation, small molecules, ribozymes, proteins
      and pseudocyclic oligonucleotide structures.

      Section 3.7 NOTICE OF HYBRIDON ANTISENSE DRUGS. Hybridon shall provide
Isis with written notice of any Hybridon Antisense Drugs developed under a
sublicense granted by Hybridon or its Subsidiaries under Section 3.2 (a
"Hybridon Antisense Drug Sublicense") promptly after such Hybridon Antisense
Drug is developed. Isis shall have the right, not more than twice during any
calendar year, to have any Hybridon Antisense Drug Sublicense reviewed by an
independent third party chosen by Isis to confirm whether such Hybridon
Antisense Drug qualifies as a Hybridon Antisense Drug as defined under this
Agreement. Hybridon shall cooperate in all reasonable respects with the review
of such Hybridon Antisense Drug Sublicense by the independent third party under
this Section 3.6, including without limitation responding to questions directed
at determining whether such Hybridon Antisense Drug qualifies as a Hybridon
Antisense Drug. Isis shall pay all costs of such review; provided, however, that
if such Hybridon Antisense Drug does not qualify as a Hybridon Antisense Drug as
defined under this Agreement, Hybridon shall reimburse Isis for the costs of
such review. If the independent third party determines that such Hybridon
Antisense Drug does not qualify as

                                     - 17 -
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a Hybridon Antisense Drug as defined under this Agreement, such independent
third

                                     - 18 -
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party shall notify Hybridon and Isis. If Hybridon disagrees with the
determination of the independent third party, the third party shall be permitted
to provide Isis with a copy of the Hybridon Antisense Drug Sublicense.

      Section 3.8 AFFILIATES. Isis hereby represents and warrants as of the date
hereof that no Affiliate of Isis owns or controls any patents, patent
applications or inventions invented, licensed or sublicensed by such Affiliate
prior to April 26, 2001 which cover or claim Motifs or RNaseH Dependent
Mechanisms of Action.

                                   ARTICLE IV
                               PAYMENT OBLIGATIONS

      Section 4.1 CONSIDERATION FOR LICENSES OF HYBRIDON INTELLECTUAL PROPERTY
AND ISIS INTELLECTUAL PROPERTY. In consideration of the licenses and sublicenses
granted under Sections 2.1 and 3.1 of this Agreement and the restrictions on use
agreed to by Hybridon under this Agreement, Hybridon and Isis each shall pay to
the other the consideration set forth in the Master Agreement and Section 4.2
and Section 4.3 of this Agreement. Isis and Hybridon each recognizes that the
other Party has expended significant efforts and resources in the research and
development of Antisense Technology and the payments to be made under the Master
Agreement to each Party for the patent licenses and sublicenses granted
hereunder will allow each Party to recoup such expenditures.

      Section 4.2 CONSIDERATION FOR SUBLICENSE OF TULLIS PATENTS. In
consideration of the sublicense granted by Isis to Hybridon under Section 3.3 of
this Agreement, Hybridon shall pay to Isis the annual maintenance fee and
royalties provided below:

                  (a) On the date hereof and each anniversary of such date
      thereafter (until the earlier of the termination of the sublicense grant
      under Section 3.3 or the date on which there ceases to be any Valid Claims
      included in the Tullis Patents), an annual maintenance fee of [*]

                  (b) Hybridon shall pay to Isis earned royalties at the rate of
      [*] of Tullis Net Sales of Tullis Products. Hybridon shall be obligated
      to pay such royalties on a country-by-country basis, so long as there
      continues to be a Valid Claim included in the Tullis Patents which covers
      the manufacture, use or sale of the applicable Tullis Product in such
      country. During the term of the sublicense under Section 3.3 and for so
      long thereafter as Hybridon is required to report royalties payable under
      this Section 4.2, Hybridon shall deliver to Isis within thirty (30) days
      after March 31, June 30, September 30 and December 31 of each year a
      report indicating (i) Tullis Net Sales for each Tullis Product, on a
      Tullis

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      Product-by-Tullis Product and country-by-country basis, including an
      accounting of the deductions from Tullis Net Sales permitted by the
      definition thereof and (ii) total royalties owed. Simultaneously with the
      delivery of each such report, Hybridon shall pay to Isis the royalty
      payments due under this Agreement for the period covered by such report.
      If no royalties are due, it shall be so reported.

      Section 4.3 ISIS SUBLICENSE INCOME. Isis shall pay to Hybridon [*] of all
Sublicense Income, [*] in respect of Sublicense Income received in connection
with a Naked Sublicense [*]. Such payment by Isis shall be paid to Hybridon
within 30 days after the calendar quarter in which the Sublicense Income was
received by Isis or a Subsidiary. Isis shall deliver to Hybridon with such
payment a report describing such Sublicense Income and how such Sublicense
Income was calculated, all on a country-by-country and product-by-product basis.

      Section 4.4 RECORDS; AUDITS. For a period not less than three (3) years
after the relevant period, each Party shall keep full, true and accurate books
of account sufficient to determine the amounts payable pursuant to Section
4.2(b) or 4.3, as the case may be. Each Party shall have the right, not more
than once during any calendar year, to have the books and records of the other
Party audited by a qualified independent accounting firm of its choosing, under
appropriate confidentiality provisions, to ascertain the accuracy of the reports
and payments hereunder and compliance by the other Party and its Subsidiaries
and Sublicensees with their obligations under Section 4.2(b) or 4.3, as the case
may be. Such audit shall be conducted upon at least ten (10) days' advance
notice during normal business hours and in a manner that does not interfere
unreasonably with the business of the audited entity. Any underpayment or
overpayment determined by such audit shall promptly be paid or refunded by
Hybridon or Isis, as the case may be. If a Party has underpaid an amount due
under Section 4.2(b) or 4.3, as the case may be, by more than five percent (5%),
such Party shall also reimburse the other Party for the cost of such audit (with
the cost of the audit to be paid by the other Party in all other cases).

      Section 4.5 PAYMENT CURRENCY. All amounts due under this Agreement shall
be paid to the designated Party in United States currency by wire transfer to an
account in a United States bank specified by such Party or in such other form
and/or manner as such Party may reasonably request. The payments due on sales in
currencies other than United States dollars shall be calculated using the
appropriate exchange rate of such currency quoted in the Wall Street Journal on
the close of business on the last business day prior to which such payment is
made.

      Section 4.6 LATE PAYMENTS; COLLECTIONS. Any amount not paid when due under
this Agreement or the Master Agreement shall bear interest at the lesser

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of (i) one and one-half percent (1.5%) per month, compounded monthly, or (ii)
the highest rate permitted by law. Each Party agrees to pay all costs of
collection, including reasonable attorneys' fees, incurred by the other Party in
enforcing the payment obligations of the first Party under this Agreement and
the Master Agreement.

                                    ARTICLE V
                                 COLLABORATION

      In addition to the collaboration between the Parties with respect to
intellectual property protection under Article VI, the Parties shall further
collaborate hereunder through a committee (the "Collaboration Committee")
consisting of two representatives of each Party. The Parties shall establish the
Collaboration Committee within thirty (30) days after the Effective Date. The
Collaboration Committee shall meet at least twice each calendar year in person
or by video conference during the term of this Agreement to review the progress
of Isis' development efforts with respect to Isis' Antisense Products that are
covered by Hybridon Intellectual Property. The Parties intend that the
Collaboration Committee shall act as a forum for the Parties to work
cooperatively [*] The Parties also anticipate that the Collaboration Committee
may recommend to the Parties from time to time that certain aspects of the drug
development process be performed by Hybridon for Isis or that the Parties
consider entering into further collaborations. Neither Party shall be bound by
any recommendation of the Collaboration Committee but shall consider its
recommendations in good faith. In addition, neither Party shall be obligated to
disclose any Confidential Information to the Collaboration Committee.

                                   ARTICLE VI
                        INTELLECTUAL PROPERTY PROTECTION

      Section 6.1 Patent Prosecution and Cooperation.

                  (a) PROSECUTION AND MAINTENANCE OF HYBRIDON ANTISENSE PATENT
      RIGHTS.

                      (i) Hybridon will be responsible for prosecuting and
maintaining the Hybridon Antisense Patent Rights. Hybridon shall promptly
forward to Isis' patent counsel any substantive actions prepared for or received
from the U.S. Patent and Trademark Office or any foreign patent office which may
materially affect patent rights, e.g., claim scope or patent term. Isis' patent
counsel shall provide any comments to Hybridon in sufficient time for Hybridon
to reflect such comments in any response. Any comments made by Isis shall be
made in good faith and shall be directed to maximizing the claims covered by the
Hybridon Antisense Patent Rights.

                      (ii)  If Hybridon agrees with the comments of Isis' patent
counsel, it shall reflect such comments in its response. If Hybridon

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disagrees with such comments, it shall notify Isis, and either Party may then
submit such dispute (a "Patent Comment Dispute") for resolution by an
intellectual property lawyer (the "Neutral Lawyer") with at least five years of
experience and a background in biotechnology or pharmaceutical patent matters.
The Neutral Lawyer shall be selected by mutual agreement of the Parties;
provided, however, that if the Parties

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cannot agree on a Neutral Lawyer within five days of a Party's request for a
Neutral Lawyer under this provision, the Neutral Lawyer shall be selected by the
American Arbitration Association in Washington, D.C. Each Party shall submit its
position as to the Patent Comment Dispute to the Neutral Lawyer, who shall
resolve the dispute by agreeing to one of the submitted positions of the Parties
without any changes to such position. The Parties agree that the position agreed
to by the Neutral Lawyer shall be reflected in the action or response being
prepared and that the costs of the Neutral Lawyer shall be paid by the Party
whose position is not agreed to by the Neutral Lawyer. The decision of the
Neutral Lawyer shall be final and binding on the Parties. In light of the
foregoing dispute resolution mechanism, neither Party shall submit a Patent
Comment Dispute to binding arbitration in accordance with the provisions of
Article VIII. The Parties shall cooperate in all respects to resolve any Patent
Comment Dispute in sufficient time to avoid any loss of rights, including
without limitation jointly instructing the Neutral Lawyer to make a decision in
sufficient time to avoid any loss of rights.

                      (iii)  Isis will be responsible for and pay fifty percent
(50%) of Hybridon's costs incurred in prosecuting and maintaining the Hybridon
Antisense Patent Rights, net of amounts paid to Hybridon for such costs by other
licensees and not including any costs of Hybridon incurred in connection with a
Patent Comment Dispute (except as otherwise specified in the foregoing Section
6.1(a)(ii)). Hybridon shall direct its counsel to invoice Isis directly for
Isis' share of such costs as such costs are incurred.

                  (b) JOINT PATENT COMMITTEE. Hybridon and Isis will, within
      sixty (60) days after the execution of this Agreement, establish a
      committee (the "Joint Patent Committee") consisting of three
      representatives of each Party. The Joint Patent Committee shall confer
      twice each calendar year or as necessary to support timely decision making
      during the term of this Agreement to discuss patent prosecution issues,
      budgets and strategies relating to the Hybridon Antisense Patent Rights.
      The Joint Patent Committee shall also, as set forth in Section 5.2(b),
      determine which Party faces the greatest competitive threat in the event
      of infringement by a third party of any of the Hybridon Antisense Patent
      Rights. In the event that the Joint Patent Committee is unable to resolve
      any matter presented for resolution,. either Party shall have the right to
      submit such matter to binding arbitration in accordance with the
      provisions of Article VIII.

                  (c) INTERFERENCE BETWEEN ISIS INTELLECTUAL PROPERTY AND
      HYBRIDON ANTISENSE PATENT RIGHTS. If an interference is declared between
      any of the Isis Intellectual Property and any of the Hybridon Antisense
      Patent Rights (other than the UMass Patent Rights), each Party shall be
      represented by its own counsel in the interference proceedings; provided,
      however, that Hybridon's counsel shall be jointly selected by Isis and

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      Hybridon; and provided further that if Hybridon and Isis can not agree on
      counsel for Hybridon, a patent lawyer with at least five years of
      experience in interference practice and a background in biotechnology or
      pharmaceutical patent matters shall be selected to represent Hybridon by
      the American Arbitration Association in Washington, D.C. Each Party shall
      seek to resolve the interference in a manner that maximizes the value to
      both parties of the combined portfolio of the Hybridon Antisense Patent
      Rights and the Isis Intellectual Property. If an interference is declared
      between any UMass Patent Rights and any Isis Intellectual Property,
      Hybridon will cooperate with Isis in the resolution thereof to the extent
      permitted under the UMass Agreement or, if Hybridon cannot so cooperate
      due to obligations to UMass, Isis will not be obligated to reimburse
      Hybridon for any expenses related to the interference proceedings. If an
      interference is declared between any of the Hybridon Antisense Patent
      Rights and the intellectual property of a third party or between any of
      the Isis Intellectual Property and the intellectual property of a third
      party, then Hybridon or Isis, as the case may be, shall have sole control
      of prosecuting the interference.

                  (d) PATENT COOPERATION. Isis hereby represents and warrants as
      of the date hereof that since April 26, 2001, neither Isis nor any of its
      Affiliates has challenged, opposed or taken any action to provoke any
      interference with any Hybridon Intellectual Property, and Isis agrees that
      from and after the date of this Agreement Isis shall not, and shall cause
      its Non-Parent Affiliates to not, challenge, oppose or take any action to
      provoke any interference with, or maintain any current challenge or
      opposition to, any Hybridon Intellectual Property. Hybridon hereby
      represents and warrants as of the date hereof that since April 26, 2001,
      neither Hybridon nor any of its Affiliates has challenged, opposed or
      taken any action to provoke any interference with any Isis Intellectual
      Property, and Hybridon agrees that from and after the date of this
      Agreement Hybridon shall not, and shall cause its Non-Parent Affiliates to
      not, challenge, oppose or take any action to provoke any interference
      with, or maintain any current challenge or opposition to, any Isis
      Intellectual Property. Hybridon further agrees that it will not use any
      Hybridon Antisense Patent Rights to challenge or interfere with any
      patents owned by Isis arising out of inventions invented, licensed or
      sublicensed by Isis prior to April 26, 2001, including those included in
      the Isis Intellectual Property, and that Hybridon will not oppose any
      patents claiming inventions invented, licensed or sublicensed by Isis
      prior to April 26, 2001, including those included in the Isis Intellectual
      Property, that cover chemical modifications to antisense oligonucleotides.
      The foregoing obligations not to challenge, oppose or interfere include,
      without limitation obligations not to directly or indirectly provoke an
      interference, participate in an opposition or make any claims of
      invalidity; PROVIDED THAT either Party and its Affiliates may raise a
      claim

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      of invalidity as a defense in a lawsuit filed by the other Party or its
      Affiliates. In addition, in the context of any interference between any of
      the Isis Intellectual Property and any of the Hybridon Antisense Patent
      Rights provoked by the U.S. Patent and Trademark Office, the Parties shall
      use commercially reasonable efforts to reach a settlement that maximizes
      the value to both Parties of the combined portfolio of the Hybridon
      Antisense Patent Rights and the Isis Intellectual Property.

                  (e) Notwithstanding any provision of this Section 6.1 to the
      contrary, nothing in this Section 6.1 shall (x) prevent Hybridon from
      complying with its obligations with respect to the Hybridon Intellectual
      Property under the UMass Agreement or the Third Party License Agreements,
      as applicable, or (y) limit the rights of the third parties under such
      agreements with respect to the Hybridon Intellectual Property, including
      as to clauses (x) and (y):

      (i)   UMass' right to prepare, file, prosecute and maintain certain
            patents and patent applications in the name of UMass pursuant to
            Section 8.1 of the UMass Agreement;

            (ii)  Hybridon's obligation to use counsel acceptable to UMass
            and to consult with UMass regarding the preparation, filing,
            prosecution or maintenance of certain patents and patent
            applications pursuant to Section 8.1 of the UMass Agreement;

            (iii) Hybridon's obligation pursuant to Section 8.2 of the
            UMass Agreement (A) to provide notice to UMass prior to abandoning,
            or failing to make payment or take other necessary actions to
            maintain, certain patents and patent applications and (B) to
            continue the prosecution or maintenance of such patents after notice
            has been provided and before UMass has had sufficient time to assume
            the prosecution or maintenance of such patent;

            (iv) Methylgene's right under Section 5.5 of the Methylgene License
            Agreement to take measures to ensure the registration and
            maintenance of certain patents and patent applications if Hybridon
            fails to register and maintain such patents and patent applications;

            (v) Methylgene's right under Section 5.5 of the Methylgene License
            Agreement to (A) approve the patent agent selected to prosecute
            certain patents and patent applications, (B) be kept informed
            regarding progress or problems related to certain patents and patent
            applications and (C) have its comments on such progress or problems
            be considered;

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            (vi) OriGenix's right under Section 5.5 of the OriGenix License
            Agreement to take measures to ensure the registration and
            maintenance of certain patents and patent applications if Hybridon
            fails to register and maintain such patents and patent applications;

            (vii) OriGenix's right under Section 5.5 of the OriGenix License
            Agreement to (A) approve the patent agent selected to prosecute
            certain patents and patent applications, (B) be kept informed
            regarding progress or problems related to certain patents and patent
            applications and (C) have its comments on such progress or problems
            be considered;

            (viii) EpiGenesis' right pursuant to Section 6.2.2 of the
            Development and License Agreement between EpiGenesis
            Pharmaceuticals, Inc. and Hybridon, dated as August 9, 2000 (the
            "EpiGenesis License Agreement") to file, prosecute and maintain
            certain patents and patent applications if Hybridon elects not to
            continue to seek or maintain patent protection on such patents or
            patent applications;

            (ix) EpiGenesis' right pursuant to Section 6.2.2 of the EpiGenesis
            License Agreement to (A) have Hybridon consult with EpiGenesis
            regarding the prosecution of certain patents and patent
            applications, (B) have a reasonable amount of time to consider and
            comment on any document to be filed in connection with the
            prosecution of such patents and patent applications and (c) have its
            comments on such comments be seriously considered;

            (x) Hybridon's obligation pursuant to Section 6.2.3 of the
            EpiGenesis License Agreement (A) to provide notice to EpiGenesis
            prior to abandoning, or failing to make payment or take other
            necessary actions to maintain certain patents and patent
            applications and (B) to continue the prosecution or maintenance of
            such patents and patent applications after notice has been provided
            and before EpiGenesis has had sufficient time to assume the
            prosecution or maintenance of such patents and patent applications;
            and

            (xi) Boston Biosystems, Inc.'s (BBI) right and Avecia Holdings plc's
            right to prosecute or maintain certain patents and patent
            applications if Hybridon declines to prosecute or maintain such
            patents or patent applications pursuant to (A) Section 4.03 of the
            PNT Monomer Patent License and Option Agreement dated as of
            September 20, 2000 by and between Hybridon and BBI, (B) Section 4.03
            of the Oligonucleotide Purification Patent License Agreement

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<Page>

            dated as of September 20, 2000 by and between Hybridon and BBI, and
            (C) Section 5.03 of the Interference Patent Sublicense Option
            Agreement dated as of September 20, 2000 by and between Hybridon and
            BBI.

      Section 6.2 ENFORCEMENT OF HYBRIDON ANTISENSE PATENT RIGHTS

              (a) NOTICE. If Hybridon or Isis becomes aware that any of the
      Hybridon Antisense Patent Rights is infringed by a third party or is
      subject to a declaratory judgment action relating to infringement or
      invalidity, Hybridon or Isis, as the case may be, shall promptly notify
      the other Party.

              (b) FIRST RIGHT OF ENFORCEMENT. In the event of infringement of
      the Hybridon Antisense Patent Rights by a third party, the Party facing
      the greatest competitive threat from the infringement shall have the first
      right (but not the obligation), at its sole expense, to undertake such
      action as it shall determine, in its discretion, appropriate to enforce
      the Hybridon Antisense Patent Rights; provided, however, that such Party
      shall not admit the invalidity or unenforceability of any Hybridon
      Antisense Patent Rights, grant a license to the allegedly infringing third
      party or enter into any settlement agreement without the other Party's
      prior written consent. The determination of which Party faces the greatest
      competitive threat from the infringement shall be made by the Joint Patent
      Committee. If the Joint Patent Committee determines that neither Party
      faces a greater competitive threat than the other Party, then Hybridon
      shall have the first right to enforce the Hybridon Antisense Patent
      Rights. The Party enforcing the Hybridon Antisense Patent Rights shall
      keep the other Party reasonably informed on a quarterly basis, in person
      or by telephone, prior to and during any such enforcement. The other Party
      shall assist the Party enforcing the Hybridon Antisense Patent Rights,
      upon the enforcing Party's request and at the enforcing Party's sole
      expense, in taking any action to enforce the Hybridon Antisense Patent
      Rights and shall join in any such action if deemed by a court of competent
      jurisdiction to be a necessary party. Neither Party shall incur liability
      to the other Party as a consequence of such litigation or any unfavorable
      decision resulting therefrom, including any decision holding any of the
      Hybridon Antisense Patent Rights invalid, not infringed or unenforceable.
      Notwithstanding the foregoing, if Isis is the Party enforcing the Hybridon
      Antisense Patent Rights under this Section 6.2(b) and such Hybridon
      Antisense Patent Rights are included in the claims that are the subject
      matter of the UMass Agreement or are licensed by Hybridon under the Third
      Party License Agreements, Isis' rights to enforce such Hybridon Antisense
      Patent Rights shall be limited to the rights of Hybridon to enforce such
      Hybridon Antisense Patent Rights, and subject to and limited by the rights
      of the other parties to the

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      UMass Agreement and the Third Party License Agreements, as set forth in
      the UMass Agreement or the Third Party License Agreements, as applicable,
      including:

      (i)   UMass's right pursuant to Section 9.2 of the UMass Agreement to
            prosecute any infringements of certain patents and patent
            applications licensed to Hybridon pursuant to the UMass Agreement;

            (ii) Hybridon's obligation pursuant to Section 9.3 of the UMass
            Agreement to seek the consent of UMass to any settlement, consent
            judgement or other voluntary final disposition of a suit involving
            certain patents and patent applications licensed to Hybridon
            pursuant to the UMass License;

            (iii) UMass' right to intervene and take over the sole defense of a
            declaratory judgment action pursuant to Section 9.6 of the UMass
            Agreement;

            (iv) Methylgene's right pursuant to Section 5.1(b) of the Methylgene
            License Agreement to initiate infringement actions related to
            certain patents and patent applications as it may in its discretion
            deem necessary or desirable;

            (v) OriGenix's right pursuant to Section 5.1(v) of the OriGenix
            License Agreement to initiate infringement actions related to
            certain patents and patent applications as it may in its discretion
            deem necessary or desirable; and

            (vi) EpiGensesis' right pursuant to Section 6.6 of the EpiGenesis
            License Agreement to initiate infringement actions related to
            certain patents and patent applications and to consent to any
            settlement of infringement litigation that would materially diminish
            the rights of EpiGenesis in certain patents and patent applications.

Items (i) through (vi) of this Section 6.2(b) are collectively referred to as
the "Other Enforcement Rights".

                  (c) ENFORCEMENT BY OTHER PARTY. If the Party having the first
      right to enforce the Hybridon Antisense Patent Rights pursuant to Section
      5.2(b) above fails to file an action to abate an infringement of the
      Hybridon Antisense Patent Rights, within six (6) months after a written
      request from the other Party to do so, or if such Party fails to
      diligently prosecute or discontinues the prosecution of any such action,
      the other Party at its sole expense may, in its discretion, undertake such
      action as it determines appropriate (other than the grant of a license to
      the allegedly infringing third party) to enforce such Hybridon Antisense

                                     - 26 -
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      Patent Rights. Such other Party shall keep the Party that had the first
      right to enforce the Hybridon Antisense Patent Rights reasonably informed
      on a quarterly basis, in person or by telephone, prior to and during any
      such enforcement. In such case, the Party that had the first right to
      enforce the Hybridon Antisense Patent Rights shall assist such other
      Party, upon such other Party's request and at such other Party's sole
      expense, in taking any action to enforce the Hybridon Antisense Patent
      Rights and shall join in any such action if deemed by a
      court of competent jurisdiction to be a necessary party. Neither Party
      shall incur liability to the other Party as a consequence of such
      litigation or any unfavorable decision resulting therefrom, including any
      decision holding any of the Hybridon Antisense Patent Rights invalid, not
      infringed or unenforceable. Notwithstanding the foregoing, if Isis is the
      Party enforcing the Hybridon Antisense Patent Rights under this Section
      6.2(c) and such Hybridon Antisense Patent Rights are included in the
      claims that are the subject matter of the UMass Agreement or are licensed
      by Hybridon under the Third Party License Agreements, Isis' rights to
      enforce such Hybridon Antisense Patent Rights shall be limited to the
      rights of Hybridon to enforce such Hybridon Antisense Patent Rights, and
      subject to and limited by the rights of the other parties to the UMass
      Agreement and the Third Party License Agreements, as set forth in the
      UMass Agreement or the Third Party License Agreements, as applicable,
      including the Other Enforcement Rights.

                  (d) RECOVERIES. All monies recovered upon the final judgment
or settlement of any action involving the enforcement of Hybridon Antisense
Patent Rights as contemplated by this Section 6.2 shall be allocated in the
following order of priority: (i) first to reimburse the costs and expenses
(including reasonable attorney fees and costs) incurred by the Parties in
prosecuting such action, and (ii) any remaining portion of the recovery shall be
divided between the Parties in proportion to the respective total losses,
determined by aggregating both past and prospective losses, each Party would
have been reasonably likely to have suffered had such infringement continued
unabated. Notwithstanding the foregoing, if the Hybridon Antisense Patent Rights
that were the subject of the action are included in the claims that are the
subject matter of the UMass Agreement or are licensed by Hybridon under the
Third Party License Agreements, the provisions of this Section 6.2(d) shall only
apply to such monies recovered upon the final judgment or settlement of such
action as remain following payment of monies to third parties as required under
the UMass Agreement and the Third Party License Agreements.

                                   ARTICLE VII
                                 CONFIDENTIALITY

      Section 7.1 CONFIDENTIAL INFORMATION. Each Party agrees that all
Confidential Information of a Party that is disclosed by a Party to the other

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Party (a) shall be maintained in confidence by the receiving Party and shall not
be used by the receiving Party for any purpose other than as permitted under
this Agreement, and (b) shall not be disclosed by the receiving Party to any
third party who is not a Subsidiary of the receiving Party, or a consultant or
an advisor to the receiving Party or a Subsidiary of the receiving Party,
without the prior written consent of the disclosing Party; provided, however,
that Confidential Information may only be disclosed by the receiving Party to
Subsidiaries or consultants or advisors to the receiving Party or its
Subsidiaries if such Subsidiaries, consultants or advisors, as the case may be,
have agreed in writing to be bound by the obligations of the
receiving Party under this Section 7.1. Notwithstanding the foregoing, the
receiving Party shall be entitled to use and disclose Confidential Information
that:

                  (a) was known or used by the receiving Party or its
      Subsidiaries prior to its date of disclosure to the receiving Party as
      demonstrated by legally admissible evidence available to the receiving
      Party or its Subsidiaries; or

                  (b) either before or after the date of the disclosure to the
      receiving Party is lawfully disclosed to the receiving Party or its
      Subsidiaries by sources other than the disclosing Party rightfully in
      possession of the Confidential Information and not bound by
      confidentiality obligations to the disclosing Party or its Subsidiaries;
      or

                  (c) either before or after the date of the disclosure to the
      receiving Party is or becomes published or otherwise is or becomes part of
      the public domain through no breach hereof on the part of the receiving
      Party or its Subsidiaries; or

                  (d) is independently developed by or for the receiving Party
      or its Subsidiaries without reference to or reliance upon the Confidential
      Information as demonstrated by competent written records; or

                  (e) is reasonably necessary to conduct clinical trials or for
      regulatory approval of products or for the filing, prosecution and
      maintenance of patents and patent applications, PROVIDED THAT the
      receiving Party provides prior written notice of such disclosure to the
      disclosing Party and takes reasonable and lawful actions to avoid and/or
      minimize the degree of such disclosure; or

                  (f) is required to be disclosed by the receiving Party to
      comply with applicable laws, to defend or prosecute litigation or to
      comply with governmental regulations, PROVIDED THAT the receiving Party
      provides prior written notice of such disclosure to the disclosing Party

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      and takes reasonable and lawful actions to avoid and/or minimize the
      degree of such disclosure.

                                  ARTICLE VIII
                               DISPUTE RESOLUTION

Section 8.1 Except as set forth in Section 6.1(a)(ii), each Party must submit
any dispute under this Agreement or the Master Agreement to arbitration by
notifying the other Party, in writing, of such dispute. Within 30 days after
receipt of such notice, the Parties shall designate in writing one arbitrator to
resolve the dispute; PROVIDED, that if the Parties cannot agree on an arbitrator
within such 30 days period, the arbitrator shall be selected by the office of
the American
Arbitration Association in the city where arbitration will take place. The
arbitrator shall not be an employee, consultant, officer, director or
stockholder of any Party or its Affiliates. If neither the Parties nor the
applicable office of the American Arbitration Association is able to identify an
individual to serve as the arbitrator, the American Arbitration Association
shall select an arbitrator from the CPC Panel of Distinguished Neutrals of the
CPR Institute for Dispute Resolution.

      Section 8.2 Within 30 days after the designation of the arbitrator, the
arbitrator and the Parties shall meet, at which time the Parties shall be
required to set forth in writing all disputed issues and a proposed ruling on
the merits of each such issue.

      Section 8.3 The arbitrator shall set a date for a hearing, which shall be
no later than 45 days after the submission of written proposals to discuss each
of the issues identified by the Parties. Each Party shall have the right to be
represented by counsel. Except as provided herein, the arbitration shall be
governed by the Commercial Arbitration Rules of the American Arbitration
Association; PROVIDED, HOWEVER, that the Federal Rules of Evidence shall apply
with regard to the admissibility of evidence and the arbitration shall be
conducted by a single arbitrator.

      Section 8.4 The arbitrator shall use his or her best efforts to rule on
each disputed issue within 30 days after the completion of the hearings. The
determination of the arbitrator as to the resolution of any dispute shall be
final and binding and conclusive upon all parties hereto. All determinations of
the arbitrator shall be in writing and shall be delivered to the Parties. The
determinations of the arbitrator may be entered in any court of competent
jurisdiction.

      Section 8.5 The attorneys' fees of the Parties in any arbitration, the
fees of the arbitrator, and the costs and expenses of the arbitration
(collectively, the "Arbitration Costs") shall be borne by the Parties as
determined by the arbitrator.

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      Section 8.6 The arbitration shall take place in Boston, Massachusetts if
brought by Isis and in San Diego, California if brought by Hybridon.

      Section 8.7 Nothing in this Article VIII shall prevent either Party from
seeking a preliminary injunction, temporary restraining order or similar relief
in order to prevent or limit and irreparable harm that might occur in the
absence thereof from a court of competent jurisdiction.

                                   ARTICLE IX
                              TERM AND TERMINATION

      Section 9.1 TERM. This Agreement shall commence as of the date hereof and
shall continue until the last of the patents and patent applications included in
the Hybridon Intellectual Property, the Isis Intellectual Property and the
Tullis Patents has expired, subject to earlier termination of this Agreement in
accordance with this Article IX. Notwithstanding the foregoing, the licenses or
sublicenses granted hereunder shall terminate on a country-by-country basis
concurrently with the expiration or termination of the applicable Valid Claim
under the Hybridon Intellectual Property, the Isis Intellectual Property or the
Tullis Patents, as the case may be, in the applicable country.

      Section 9.2 TERMINATION OF LICENSES AND SUBLICENSES FOR BREACH.

                  (a) Except as set forth in Section 9.2(b), (i) if an
      arbitrator has rendered a ruling pursuant to Article VIII that a Party or
      a Subsidiary has materially breached this Agreement or the Master
      Agreement, which ruling specified the remedies imposed on such breaching
      party for such breach, including without limitation a ruling on a dispute
      as to breach of a Party's obligation to issue stock or pay cash in lieu of
      stock as required under the Master Agreement (the "ADVERSE RULING"), and
      (ii) the breaching Party has failed to comply with the terms of the
      Adverse Ruling within the time period specified therein for compliance, or
      if such compliance cannot be fully achieved by such date, the breaching
      Party has failed to commence compliance and to use diligent efforts to
      achieve full compliance as soon thereafter as is reasonably possible, then
      the non-breaching Party shall be entitled to terminate the licenses and
      sublicenses granted to the breaching Party and its Subsidiaries by such
      non-breaching Party under this Agreement (without prejudice to any of the
      other rights of the non-breaching Party under this Agreement or the Master
      Agreement) upon written notice to the breaching Party.

                  (b) (i) If a Party breaches an obligation to issue stock or
      pay cash in lieu of stock as required under the Master Agreement, then the
      non-breaching Party may terminate the licenses and sublicenses granted to
      the breaching Party and its Subsidiaries by such

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      non-breaching Party under this Agreement immediately upon written notice
      to the breaching Party if the breaching Party fails to cure such breach
      within ten (10) business days of written notice of such breach from the
      non-breaching Party; provided, however, that if the breaching Party
      believes that a bona fide dispute exists as to the amount of any payment,
      then the breaching Party may, not later than five business days following
      the notice of the breach, (i) provide the non-breaching Party with a
      written notice setting forth the nature of the dispute and the amount in
      dispute, (ii) at the same time, pay to the non-breaching Party the amount
      of the payment which is not in dispute and (iii) promptly submit the
      dispute to binding arbitration pursuant to Article VIII, in which case the
      non-payment of the disputed portion shall not be deemed a breach during
      the pendency of the arbitration.

                                     - 31 -
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                      (ii) If the final arbitration order or ruling issued
in the arbitration proceeding resolves the dispute against the breaching Party
and orders the breaching Party to pay all or part of the disputed portion to the
non-breaching Party, then the arbitrator shall include in its award, in addition
to such other remedies as it deems appropriate, the following against the
breaching Party: (A) the Arbitration Costs, (B) [*] and (C) if the arbitrator
finds that a cash payment was due, an amount equal to interest at the rate equal
to the lower of 1.5% per month, compounded monthly, or the highest rate
permitted by law on the amount of cash determined to have been due commencing on
the due date determined by the arbitrator through the date of actual payment.

                  (c) The right of either Party to terminate the licenses and
      sublicenses granted by such Party under this Agreement pursuant to this
      Section 9.2 shall not be affected in any way by its waiver of, or failure
      to take action with respect to any previous default.

                  (d) If the licenses and sublicenses granted by Hybridon to
      Isis and its Subsidiaries under this Agreement are terminated by Hybridon
      pursuant to this Section 9.2, (i) Hybridon shall be entitled to retain the
      licenses granted to it and its Subsidiaries pursuant to Article III,
      subject to the payment obligations of Hybridon specified in the Master
      Agreement and in Article IV, and to continue to receive the stock of Isis
      issuable to it pursuant to Section 2.3 of the Master Agreement, and (ii)
      the provisions of Articles V and VI shall terminate in their entirety. If
      the licenses and sublicenses granted by Isis to Hybridon and its
      Subsidiaries under this Agreement are terminated by Isis pursuant to this
      Section 9.2, Isis shall be entitled to retain the licenses granted to it
      and its Subsidiaries pursuant to Article II, subject to the payment
      obligations of Isis specified in the Master Agreement and in Article IV,
      and to continue to receive the stock of Hybridon issuable to it pursuant
      to Section 2.2 of the Master Agreement.

      Section 9.3 TERMINATION OF SUBLICENSE OF TULLIS PATENTS. Hybridon shall
have the right to terminate the sublicense granted to it and its Subsidiaries
pursuant to Section 3.3 (and the related payment obligations under Section 4.2)
for any reason or no reason at any time upon fifteen (15) days prior written
notice to Isis.

      Section 9.4 SURVIVAL. The expiration or termination of this Agreement for
any reason shall not relieve the Parties of any obligation due and accruing, or
for any liability as to any breach occurring, prior to such expiration or
termination. In addition, the provisions of Section 4.4, Article VII, Article
VIII, Section 9.4, Section 9.5, and Article X shall survive the expiration or
termination of this Agreement.

*Confidential Treatment Requested    - 31 -
<Page>

      Section 9.5 SUBLICENSE SURVIVAL.

                  (a) Notwithstanding the termination of this Agreement or any
      of the licenses or sublicenses granted hereunder pursuant to this Article
      IX, any sublicenses to Isis Intellectual Property and the Tullis Patents
      granted by Hybridon or its Subsidiaries pursuant to Section 3.2 or 3.3(b)
      hereof prior to such termination shall survive such termination. In such
      event, Isis shall have the right to receive directly from the Sublicensee
      any payments or other consideration otherwise payable to Hybridon or its
      Subsidiaries as the sublicensor under such sublicense, and to otherwise
      exercise all of the rights of Hybridon or its Subsidiaries as the
      sublicensor under such sublicense; provided however that Isis shall not
      assume, and shall not be responsible for, any representations, warranties
      or obligations of Hybridon or its Subsidiaries as the sublicensor to any
      Sublicensees other than the licenses under such sublicenses.

                  (b) Notwithstanding the termination of this Agreement or any
      of the licenses or sublicenses granted hereunder pursuant to this Article
      IX, any sublicenses of Hybridon Intellectual Property granted by Isis or
      its Subsidiaries pursuant to Section 2.2 hereof prior to such termination
      shall survive such termination. In such event, Hybridon shall have the
      right to receive directly from the Sublicensee any payments or other
      consideration otherwise payable to Isis or its Subsidiaries as the
      sublicensor, under such sublicense and to otherwise exercise all of the
      rights of Isis or its Subsidiaries as the sublicensor under such
      sublicense; provided however that Hybridon shall not assume, and shall not
      be responsible for, any representations, warranties or obligations of Isis
      or its Subsidiaries as the sublicensor to any Sublicensees other than the
      licenses under such sublicenses.

      Section 9.6 FAILURE TO MAKE MASTER AGREEMENT DELIVERIES. Notwithstanding
any provision in this Agreement to the contrary, including without limitation
Article VIII, [*] Hybridon shall have the right, at its sole election, effective
immediately upon written notice to Isis, [*]

                                   ARTICLE X
                            MISCELLANEOUS PROVISIONS

      Section 10.1 INDEMNIFICATION. Each Party (the "Indemnifying Party") agrees
to defend the other Party and such other Party's Subsidiaries and their
respective directors, officers, employees and agents (the "Indemnified Parties")
at the Indemnifying Party's cost and expense, and shall indemnify and hold the
Indemnified Parties harmless from and against any losses, costs, damages, fees
or expenses arising out of any third party claim relating to (i) any breach by
the Indemnifying Party of any of its representations, warranties or obligations

*Confidential Treatment Requested    - 32 -
<Page>

pursuant to this Agreement, (ii) provided that the third party is not an
Affiliate of the Indemnified Parties, infringement of such third party's patents
resulting from the exercise by the Indemnifying Party or a Subsidiary or a
Sublicensee of the

*Confidential Treatment Requested    - 33 -
<Page>

rights granted by the Indemnified Parties to the Indemnifying Party hereunder or
(iii) product liability resulting from use of a product made, sold or imported
by or for the Indemnifying Party or by or for a Subsidiary or a Sublicensee
under the rights granted by the Indemnified Parties hereunder. In the event of
any claim against the Indemnified Parties by any third party for which
indemnification may be sought pursuant to this Agreement, the Indemnified
Parties shall promptly notify the Indemnifying Party in writing of the claim;
provided that the failure to promptly notify the Indemnifying Party of such
claim shall not result in the loss of rights of indemnification hereunder except
to the extent that the Indemnifying Party was materially prejudiced by such
failure. The Indemnifying Party shall assume, at its sole expense, the defense
of the claim and its settlement. The Indemnified Parties shall cooperate with
the Indemnifying Party and may, at their option and expense, be represented in
any such action or proceeding. The Indemnifying Party shall not be liable for
any litigation costs or expenses incurred by the Indemnified Parties. In
addition, the Indemnifying Party shall not be responsible for the
indemnification of any Indemnified Party arising from any negligent or wrongful
acts by such Indemnified Party, or as the result of any settlement or compromise
by the Indemnified Parties without the Indemnifying Party's prior written
consent. The Indemnifying Party may not settle or compromise any matter without
the consent of the Indemnified Parties unless such settlement or compromise
imposes no obligations on the Indemnified Parties and does not restrict the
rights of the Indemnified Parties.

      Section 10.2 GOVERNING LAW. This Agreement shall be construed and the
respective rights of the Parties determined according to the laws of the State
of Delaware (without regard to the conflict of law rules of any jurisdiction),
except matters of the intellectual property law, which shall be determined in
accordance with the national intellectual property laws relevant of the
intellectual property in question.

      Section 10.3 ASSIGNMENT. Neither Hybridon nor Isis may assign this
Agreement in whole or in part without the consent of the other Party, except if
such assignment occurs in connection with the sale or transfer of all or
substantially all of the business or assets of the assigning Party to which the
subject matters of this Agreement pertains.

      Section 10.4 ENTIRE AGREEMENT; AMENDMENTS. This Agreement, together with
the Master Agreement, constitutes the entire agreement between the Parties with
respect to the subject matter hereof, and supersedes all previous arrangements
with respect to the subject matter hereof, whether written or oral. Any
amendment or modification to this Agreement shall be made in writing signed by
both Parties.

      Section 10.5 NOTICES.

                                     - 33 -
<Page>

      Notices to Hybridon shall be addressed to:
               Hybridon, Inc.
               345 Vassar Street
               Cambridge, Massachusetts 02139
               Attention: Chief Executive Officer

      with a copy to:

               Holland and Knight, LLP
               10 St. James Avenue
               Boston, Massachusetts 02116
               Attention: James Pollock, Esq.

               And

               Hale and Dorr LLP
               60 State Street
               Boston, MA  02109
               Attention: David E. Redlick, Esq.

                                     - 34 -
<Page>

      Notices to Isis shall be addressed to:

               Isis Pharmaceuticals, Inc.
               2292 Faraday Avenue
               Carlsbad, California 92008
               Attention:  Chief Executive Officer
               Copy to: Executive Vice President

      Any Party may change its address by giving notice to the other Party in
the manner herein provided. Any notice required or provided for by the terms of
this Agreement shall be in writing and shall be (a) delivered personally, (b)
sent by registered or certified mail, return receipt requested, postage prepaid,
(c) sent via a reputable overnight courier service, or (d) sent by facsimile
transmission with an original to be followed the same day via a reputable
overnight courier service, in each case properly addressed in accordance with
the paragraph above. The effective date of notice shall be the actual date of
receipt by the Party receiving the same.

      Section 10.6 FORCE MAJEURE. No failure or omission by a Party in the
performance of any of its obligations of this Agreement shall be deemed a breach
of this Agreement or create any liability if the same shall arise from any cause
or causes beyond the control of such Party, including, but not limited to, the
following: acts of God; acts or omissions of any government; any rules,
regulations or orders issued by any governmental authority or by any officer,
department, agency or instrumentality thereof; fire; storm; flood; earthquake;
accident; war; rebellion; insurrection; riot; and invasion and provided that
such failure or omission resulting from one of the above causes is cured as soon
as is practicable after the occurrence of one or more of the above-mentioned
causes.

      Section 10.7 DISCLOSURE OF PROVISIONS OF AGREEMENT.

                  (a) Each Party agrees to hold as confidential the terms of
      this Agreement, except that (i) Hybridon may furnish a copy of this
      Agreement to UMass, Isis may furnish a copy of this Agreement to MBI
      (other than Exhibits containing information relating to patent
      applications of Hybridon) and each Party shall have the right to disclose
      the terms of this Agreement (other than the information on the Exhibits
      hereto relating to patent applications of Isis or Hybridon) to potential
      investors and other third parties in connection with financing activities
      and to potential collaborators, provided that any such third party has
      entered into a written obligation with the disclosing Party to treat such
      information and materials as confidential and to not use the information
      and materials for any purposes other than the evaluation of the potential

                                     - 35 -
<Page>

      investment or collaboration and that the disclosing Party shall enforce
      against the third party recipient of such information and materials, for
      and on behalf of the other Party, such written obligation, and (ii) each
      Party may furnish a copy of this Agreement or disclose the terms of this
      Agreement if such is required to be disclosed by the receiving Party to
      comply with applicable laws, to defend or prosecute litigation or to
      comply with governmental regulations, PROVIDED THAT the receiving Party
      provides prior written notice of such disclosure to the disclosing Party
      and takes reasonable and lawful actions to avoid and/or minimize the
      degree of such disclosure. At the request of the other Party, the
      disclosing Party shall use commercially reasonable efforts to enforce such
      obligations against such third parties.

                  (b) Notwithstanding Section 10.7(a) to the contrary, either
      Party may include this Agreement, in any report, statement or other
      document filed by such Party with the United States Securities and
      Exchange Commission (the "SEC"). In such event, the disclosing Party shall
      use reasonable efforts to obtain, to the extent permitted by law,
      confidential treatment from the SEC of any trade secrets and commercial or
      financial information of a privileged or confidential nature, including
      without limitation all information on the Exhibits hereto relating to
      patent applications of Isis or Hybridon, and shall notify the other Party
      as to such efforts and all related communications with the SEC; provided
      that notwithstanding the foregoing no Party shall submit a confidentiality
      request or include this Agreement without the prior review and approval of
      the confidentiality request by the other Party, which review and approval
      shall not be unreasonably withheld or delayed.

      Section 10.8 INDEPENDENT CONTRACTORS. It is understood and agreed that the
relationship between the Parties hereunder is that of independent contractors
and that nothing in this Agreement shall be construed as authorization for
either Party to act as agent for the other.

      Section 10.9 NO STRICT CONSTRUCTION. This Agreement has been prepared
jointly and shall not be strictly construed against any Party.

      Section 10.10 HEADINGS. The captions or headings of the Sections or other
subdivisions hereof are inserted only as a matter of convenience or for
reference and shall have no effect on the meaning of the provisions hereof.

      Section 10.11 NO IMPLIED WAIVERS; RIGHTS CUMULATIVE. No failure on the
part of either Party to exercise, and no delay in exercising, any right, power,
remedy or privilege under this Agreement, or provided by statute or at law or in
equity or otherwise, shall impair, prejudice or constitute a waiver of any such
right, power, remedy or privilege or be construed as a waiver of any breach of
this Agreement or as an acquiescence therein, nor shall any single or partial

                                     - 36 -
<Page>

exercise of any such right, power, remedy or privilege preclude any other or
further exercise thereof or the exercise of any other right, power, remedy or
privilege. In particular, the Parties hereby agree that termination of the
licenses or sublicenses granted under this Agreement as provided in Article IX
shall not be the exclusive remedy of a Party in the event of a breach of this
Agreement or the Master Agreement by the other Party and that the non-breaching
Party shall be entitled to seek any and all other remedies to which the
non-breaching Party may be entitled at law or in equity.

      Section 10.12 SEVERABILITY. If any provision hereof should be held
invalid, illegal or unenforceable in any respect in any jurisdiction, then, to
the fullest extent permitted by law, (a) all other provisions hereof shall
remain in full force and effect in such jurisdiction and shall be liberally
construed in order to carry out the intentions of the Parties as nearly as may
be possible and (b) such invalidity, illegality or unenforceability shall not
affect the validity, legality or enforceability of such provision in any other
jurisdiction.

      Section 10.13 EXECUTION IN COUNTERPARTS. This Agreement may be executed in
counterparts, each of which counterparts, when so executed and delivered, shall
be deemed to be an original, and all of which counterparts, taken together,
shall constitute one and the same instrument.

      Section 10.14 NO CONSEQUENTIAL DAMAGES. NEITHER PARTY HERETO WILL BE
LIABLE FOR SPECIAL, INCIDENTAL OR CONSEQUENTIAL DAMAGES ARISING OUT OF THIS
AGREEMENT OR THE EXERCISE OF ITS RIGHTS HEREUNDER, REGARDLESS OF ANY NOTICE OF
SUCH DAMAGES.

      Section 10.15 PATENT VALIDITY. Notwithstanding anything in this Agreement
to the contrary, neither Party represents and warrants or shall be deemed to
have represented and warranted to the other Party that the Hybridon Intellectual
Property (in the case of Hybridon) and the Isis Intellectual Property and the
Tullis Patents (in the case of Isis) are valid or otherwise enforceable.

                    [Remainder of page intentionally omitted]

                                     - 37 -
<Page>

         IN WITNESS WHEREOF, the Parties have executed this License Agreement as
of the Effective Date.

                                            ISIS PHARMACEUTICALS, INC.

                                            By: /s/ B. Lynne Parshall
                                                --------------------------------
                                            Name: B. Lynne Parshall
                                                  ------------------------------
                                            Title: Executive Vice President
                                                   -----------------------------

                                            HYBRIDON, INC.

                                            By: /s/ Sudhir Agrawal
                                                --------------------------------
                                            Name: Sudhir Agrawal
                                                  ------------------------------
                                            Title: President and CSO
                                                   -----------------------------
                                                   /s/ Robert Andersen, CFO

                                     - 38 -

<Page>

                                    EXHIBIT A

                                      [ * ]

*Confidential Treatment Requested

<Page>

                                   EXHIBIT B1

                                      [ * ]

*Confidential Treatment Requested

<Page>

                                   EXHIBIT B2

                                      [ * ]

*Confidential Treatment Requested

<Page>

                                    EXHIBIT C

                                      [ * ]

*Confidential Treatment Requested

<Page>

                                    EXHIBIT D

                                      [ * ]

*Confidential Treatment Requested

<Page>

                                    EXHIBIT E

                                       [*]

*Confidential Treatment Requested

<Page>

                                    EXHIBIT F

                                      [ * ]

*Confidential Treatment Requested

<Page>

                                    EXHIBIT G

                                      [ * ]

*Confidential Treatment Requested

<Page>

                                   EXHIBIT H-1

                         THIRD PARTY LICENSE AGREEMENTS

Methylgene

AMENDED AND RESTATED LICENSE AGREEMENT MADE EFFECTIVE AS OF JANUARY 4, 1996, AS
AMENDED AND RESTATED ON SEPTEMBER 21, 2000.

Origenix

LICENSE AGREEMENT DATED AS OF JANUARY 22, 1999 BETWEEN HYBRIDON AND ORIGENIX.

Epigenesis

DEVELOPMENT AND LICENSE AGREEMENT BETWEEN EPIGENESIS PHARMACEUTICALS, INC. AND
HYBRIDON, INC., DATED AS OF AUGUST 9, 2000.

Boston Biosystems, Inc. (BBI)

PNT MONOMER PATENT LICENSE AND OPTION AGREEMENT DATED AS OF SEPTEMBER 20, 2000
BY AND BETWEEN HYBRIDON AND BBI.

OLIGONUCLEOTIDE PURIFICATION PATENT LICENSE AGREEMENT DATED AS OF SEPTEMBER 20,
2000 BY AND BETWEEN HYBRIDON AND BBI.

INTERFERENCE PATENT SUBLICENSE OPTION AGREEMENT DATED AS OF SEPTEMBER 20, 2000
BY AND BETWEEN HYBRIDON AND BBI.

<Page>

                                   EXHIBIT H-2

                            OTHER LICENSE AGREEMENTS

UMass Agreement

LICENSE AGREEMENT DATED AS OF FEBRUARY 21, 1990 AND RESTATED AS OF SEPTEMBER 8,
1993 BY AND BETWEEN HYBRIDON AND UNIVERSITY OF MASSACHUSETTS MEDICAL CENTER
(FORMERLY THE WORCESTER FOUNDATION FOR BIOMEDICAL RESEARCH, INC.)

IDT Agreement

Non-Exclusive License Agreement dated as of March 12, 1999 between Integrated
DNA Technologies, Inc. and Hybridon

<Page>

                                    EXHIBIT I

                                      [ * ]

*Confidential Treatment Requested

<Page>

                                    EXHIBIT J

                                 UMASS AGREEMENT

Incorporated by reference to Exhibit 10.1 to Hybridon's Registration Statement
on Form S-1 (File No. 33-99024)

*Confidential Treatment Requested

<Page>

                                    EXHIBIT K

                                      [ * ]

*Confidential Treatment Requested

<Page>

                                    EXHIBIT L

                                      [ * ]

*Confidential Treatment Requested

<Page>

                                    EXHIBIT M

                                      [ * ]

*Confidential Treatment Requested

<Page>

                                    EXHIBIT N

                                TULLIS AGREEMENT

Incorporated by reference to Exhibit 10.1 to Isis's Quarterly Report Pursuant to
Section 13 or 15(d) of the Securities Exchange Act of 1934 for the quarterly
period ended September 30, 1992, on Form 10-Q (File No. 0-19125).<Page>
                                              *Text Omitted and Filed Separately
                                                Confidential Treatment Requested
                                           Under 17 C.F.R. Sections 200.80(b)(4)
                                                            200.83 and 240.24b-2

                  COLLABORATIVE RESEARCH AND LICENSE AGREEMENT

          This COLLABORATIVE RESEARCH AND LICENSE AGREEMENT (the "Agreement") is
made as of July 9, 2001 (the "Effective Date"), by and between ISIS
PHARMACEUTICALS, INC., a Delaware corporation ("Isis"), having a principal place
of business at Carlsbad Research Center, 2292 Faraday Avenue, Carlsbad,
California 92008 and PE CORPORATION (NY), a New York corporation, through the
CELERA GENOMICS GROUP, ("Celera"), having a principal place of business at 45
West Gude Drive, Rockville, Maryland 20850. Celera and Isis may be referred to
herein individually as a "Party" and collectively as the "Parties".

                                    RECITALS

          WHEREAS, Isis possesses proprietary technology and know-how related to
anti-sense technologies; and

          WHEREAS, Celera possesses proprietary technology and know-how related
to genomics; and

          WHEREAS, Celera and Isis desire collaborate to generate information on
gene function for up to [*] novel targets.

          NOW, THEREFORE, in consideration of the various promises and
undertakings set forth herein and other good and valuable consideration, the
receipt and sufficiency of which are hereby acknowledged, the Parties agree as
follows:

                                    ARTICLE 1

                                   DEFINITIONS

          1.1   "Affiliate" with respect to either Party, will mean any Person
controlling, controlled by, or under common control with such Party. For the
purposes of this Section 1.1 only, "control" will refer to (a) the possession,
directly or indirectly, of the power to direct the management or policies of a
Person, whether through the ownership of voting securities, by contract or
otherwise, together with (b) the ownership, directly or indirectly, of at least
fifty percent (50%) of the voting securities or other ownership interest of a
Person. Notwithstanding the foregoing, [*]

          1.2   "Agreement NPV" means the net present value of any agreement
calculated pursuant to Section Article 6.3(d) or as determined by the JEC by
unanimous recorded vote.

          1.3   "Antisense Inhibitor" means an Oligonucleotide that is designed
to inhibit protein synthesis at the nucleic acid level by specifically binding
to the sequence of a selected messenger or viral ribonucleic acid by
base-paring.

* Confidential Treatment Requested

<Page>

          1.4   "Celera Exclusive Collaboration Patents" means all Patent Rights
comprising method of use, method of prevention, treatment or diagnosis of a
disease or condition or other identification of gene function associated with a
Celera Exclusive Target arising out of the collaboration and for which
Collaboration Data is used in the prosecution, maintenance or defense of such
Patent Rights. Celera Exclusive Collaboration Patents specifically includes
Collaboration Patents to the extent they otherwise come under the definition of
Celera Exclusive Collaboration Patents.

          1.5   "Celera Exclusive Targets" means the Celera Gene Targets
selected by Celera pursuant to Section 3.2 (c), or any fragment or allelic
variant of such Celera Gene Target or degenerative sequence of the foregoing
encoding the identical amino acid sequence.

          1.6   "Celera Gene Availability Pool" means the Celera Gene Targets
available for Celera to designate for exclusive use pursuant to Section
3.2(c). Once the Option Period has expired for a specific Celera Gene Target
it will cease to be part of the Celera Gene Availability Pool.

          1.7   "Celera Gene Target" means a Gene selected for High Throughput
Gene Functionalization.

          1.8   "Celera Licensed Patents" means (i) all Patent Rights that
are Controlled by Celera prior to the selection of Celera Gene Target
pursuant to Section 3.1 that claim inventions consisting of any Celera Gene
Target or any fragment of such Celera Gene Target, and/or any nucleic acid
sequence, protein, peptide or other composition of matter encoded thereby,
including, without limitation, inventions claiming method of use or treatment
of a disease or condition by inhibiting such gene or other identification of
gene function, and (ii) all Patent Rights whether or not Controlled by Celera
not arising out of the collaboration where Collaboration Data is used in the
prosecution, maintenance or defense of such Patent Rights. Celera Licensed
Patents will specifically exclude Collaboration Patents, Celera Exclusive
Collaboration Patents, Joint Patents and any Patent Rights that are
Controlled by Celera claiming solely diagnosis of a disease or condition.

          1.9   "Celera Product" means any Gene Therapy Product, Protein
Therapeutic Product, Small Molecule Therapeutic Product or Vaccine Product
discovered by Celera alone or as part of a bona fide drug discovery
collaboration that, but for the licenses granted herein, would infringe a
Celera Exclusive Collaboration Patent.

          1.10  "Collaboration Data" means any and all data created using an
Antisense Inhibitor pursuant to the Research Plan, including without
limitation, in Isis's HGTF system.

          1.11  "Collaboration Patents" means all Patent Rights comprising
method of use, method of prevention, treatment or diagnosis of a disease or
condition or other identification of gene function associated with a Celera
Gene Target arising out of the collaboration and for which Collaboration Data
is included in or used in the prosecution,

                                       2
<Page>

maintenance or defense of such Patent Rights. Collaboration Patents specifically
excludes Oligonucleotide Patents. Collaboration Patents specifically includes
jointly invented Patent Rights to the extent that they otherwise come under the
definition of Collaboration Patents, and any such jointly invented Patent Rights
will not be Joint Patents.

          1.12  "Common Product" means (i) any and all Licensed Products that
are neither Isis Products nor Celera Products for a Celera Exclusive Target,
and (ii) any and all License Products that are not Isis Products for a Celera
Gene Target that is not a Celera Exclusive Target.

          1.13  "Confidential Information" means a Party's confidential
information, inventions, know-how, data and materials relating to the
Research, or the Celera Gene Targets, Celera Exclusive Targets, Lead Oligos or
Licensed Products, including without limitation research, technical, clinical
development, manufacturing, marketing, financial personnel and other business
information and plans, which, if disclosed in written, graphic or electronic
form, is marked or otherwise designated as "confidential" or "proprietary"
and, if disclosed orally, is summarized and designated as "confidential" or
"proprietary" in a writing provided to the receiving Party not later than
sixty (60) days after such disclosure. All information presented at the JRC,
Intellectual Property Committee or JEC meetings will be rebuttably presumed to
be Confidential Information, regardless of whether it would otherwise qualify
as such pursuant to the preceding sentence.

          1.14  "Control" means, with respect to an item of Information or an
intellectual property right, possession of the ability, whether by ownership
or license, to grant a license or sublicense as provided for herein under such
item or right without violating the terms of any agreement or other
arrangements with any Third Party.

          1.15  "Effective Date" means the effective date of this Agreement as
set forth in the first paragraph above.

          1.16  "Extended Term" has the meaning set forth in Section 5.1(e).

          1.17  "Gene" means a DNA or RNA sequences of human or other origin
that encodes a protein or other molecule.

          1.18  "Gene Therapy Product" means any nucleic acid molecule, other
than an Antisense Inhibitor or Oligonucleotide, that is introduced into human
cells for the treatment or prevention of any disease, condition or risk based
on modifying the expression of the target gene or modifying the genetic code
of the target gene.

          1.19  "High Throughput Gene Functionalization" or "HTGF" means Isis's
High Throughput Screening system and standard phenotypic assays as it may
exist from time-to-time and as more fully described in the Research Plan.

          1.20  "Information" means any data, results, information, know-how,
techniques, methods, development, material, or compositions of matter of any
type or kind.

                                       3
<Page>

          1.21  "Intellectual Property Committee" has the meaning set forth in
Section 6.2.

          1.22  "Isis Product" means any Oligonucleotide used in the treatment
or prevention of a disease or condition that, but for the licenses granted
herein, would infringe a Collaboration Patent.

          1.23  "Joint Executive Committee" or "JEC" means that committee to be
formed pursuant to Section 6.3.

          1.24  "Joint Patents" means all Patent Rights that claim inventions
that are made by employees or agents of Celera and Isis jointly and name as
inventors one or more employees of Celera and Isis together with one or more
employees or agents of the other Party. Joint Patents will not include any
Collaboration Patents or Oligonucleotide Patents.

          1.25  "Joint Research Committee" or "JRC" means that committee to be
formed pursuant to Section 6.1.

          1.26  "Lead Oligo" means an Antisense Inhibitor to a Celera Gene
Target which decreases expression of such Celera Gene Target by at least [ *].

          1.27  "Lead Oligo Reagent" means a Lead Oligo derived using the
2'-methoxyethyl gapmer with fully phosphorothioate backbone chemistry of the
HTGF system or an alternative for certain limited applications.

          1.28  "Licensed Product" means any composition, material, device,
kit, process or other product or process, the manufacture, use or sale of
which would infringe a Collaboration Patent.

          1.29  "Licensing Revenue" means revenue derived from the licensing of
Collaboration Patents to Third Parties including without limitation, license
fees, maintenance fees, milestones, and royalties but excluding payments for
research and development. If either Party licenses Collaboration Patents to
Third Parties together with other material intellectual property, the
consideration received for such license, will be allocated by such Party in
good faith among the components of the license. If payments are made in
non-cash consideration, such Party will, at its option, either provide the
other Party consideration in kind or in cash (based on a reasonable
determination of value).

          1.30  "Minimum Permitted Value" means a net present value of an
agreement equal to [*].

          1.31  "Oligonucleotide" means any compound containing between [* ]
nucleotides and/or nucleosides, including oligonucleotide analogs which may
include natural or modified heterocycles, sugars and or backbone linkages.

          1.32  "Oligonucleotide Patent" means all Patent Rights arising out of
the collaboration that claims Antisense Inhibitors or Oligonucleotides and/or
their method of use including without limitation the prevention or treatment
of a disease or condition.

*Confidential Treatment Requested     4
<Page>

Oligonucleotide  Patents will include any jointly  invented  Patent  Rights that
otherwise meets this definition.

          1.33  "Option" has the meaning set forth in Section 3.2(c).

          1.34  "Option Period" has the meaning set forth in Section 3.2(c).

          1.35  "Patent Right" means (i) an issued and existing patent,
including any extensions, supplemental protection certificates, registrations,
confirmations, reissues, reexaminations or renewals thereof, (ii) pending
applications, including any continuation, divisional, or continuation-in-part
application thereof, for any of the foregoing, and (iii) all counterparts to
any of the foregoing issued by or filed in any country or other jurisdiction.

          1.36  "Person" means any natural person, corporation, firm, business
trust, business unit, joint venture, association, organization, company,
limited liability company, partnership or other business entity, or any
government or agency or political subdivision thereof.

          1.37  "Protein Therapeutic Product" means a protein, peptide or
peptidomimetic analogous to a peptide or any derivative of the foregoing that
is used for the treatment or prevention of any disease, condition or risk
thereof.

          1.38  "Research" means the collaborative research program undertaken
by the Parties pursuant to the Research Plan during the Research Term.

          1.39  "Research Plan" means the specific plan for HTGF screening of
Celera Gene Targets, as described in Section 2.1, which will be attached
hereto as Exhibit A.

          1.40  "Research Term" means the period commencing on the Effective
Date and terminating eighteen (18) months thereafter (or such earlier date as
of which this Agreement is terminated hereunder).

          1.41  "Small Molecule Therapeutic Product" means a small organic or
inorganic molecule (less than 800 daltons) used for the treatment or
prevention of any disease, condition or risk thereof, excluding any such
molecule whose primary mode of activity is binding to RNA.

          1.42  "Sublicensee" means a Person other than an Affiliate of Isis or
Celera to which Isis or Celera has granted sublicense rights under the
licenses granted hereunder, which rights include at least the rights to make
and sell Licensed Products.

          1.43  "Third Party" means any Person other than Celera, Isis or
Affiliates of either of them, or any Sublicensee.

          1.44  "Vaccine Product" means a protein, peptide or a nucleic acid
molecule other than an Oligonucleotide, that stimulates an active specific
immune response for the treatment or prevention of a disease or condition.

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          1.45 "Valid Claim" means a claim of an issued and unexpired patent
which has not been revoked or held unenforceable or invalid by a decision of a
court or governmental agency of competent jurisdiction from which no appeal
can be taken or, after mutual consultation and agreement, an appeal is not
taken within the time allowed for appeal, and which has not been disclaimed,
denied or admitted to be invalid or unenforceable through reissue or
disclaimer or otherwise.

                                   ARTICLE 2

                                    RESEARCH

          2.1  Subject to the terms and conditions herein, the Parties will
each use commercially reasonable diligent efforts to conduct the Research on
a collaborative basis. Subject to Section 2.2(d) and other applicable
provisions, the Parties will conduct the Research as specified in the
Research Plan. The Research Plan attached hereto as Exhibit A describes the
HTGF screening process that will be used to create Antisense Inhibitors to
Celera Gene Targets and screen such Antisense Inhibitors in Isis' phenotypic
assays to provide information useful in gene functionalization and target
validation.

          2.2  Conduct of the Research.

               (a)   The Research will be managed and directed by the JRC, as
provided in 6.1.

               (b)   During the course of the  Research,  each Party will
disclose to the other such  Information as the other Party  reasonably  needs to
conduct its obligations and assigned tasks under the Research Plan.

               (c)   In  order  to  protect  the  Parties'  patent  rights  in
any  inventions  conceived  or reduced to practice  during or as a result of the
Research,  each Party agrees to implement a policy which  requires its employees
to record and maintain all data and information developed during the Research in
such a manner as to enable the  Parties to use such  records  to  establish  the
earliest date of invention and/or diligence to reduction to practice.

               (d)   The  Parties  agree to commit the  quality  and  quantity
of resources required to perform their obligations under the Research Plan.

          2.3  Liability. In connection with the conduct of the Research, each
Party will be responsible for, and hereby assumes, any and all risks of
personal injury or property damage attributable to the negligent acts or
omissions of that Party and its directors, officers, employees and agents.

                                   ARTICLE 3

             SELECTION OF CELERA GENE TARGETS AND CELERA EXCLUSIVE
                                    TARGETS

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          3.1   Selection of Celera Gene Targets.

                (a)  Celera will select Genes for functionalization studies
under the Research Plan ("Celera Gene Targets") and notify Isis of the identity
of such Celera Gene Target in writing.

                (b)  Genes selected by Celera under Section 3.1(a) will be
included in the HTGF queue unless prior to such selection: (i) such Genes were
prioritized by Isis for the HTGF queue; (ii) Isis had generated Antisense
Inhibitors to such Gene; or (iii) Isis has bona fide pre-existing agreement to
work on such Gene with a Third Party (Subsections (i), (ii) and (iii),
"Rejected Genes"); and provided that Isis notifies Celera of the identity of
any Rejected Gene in writing within ten (10) business days of Celera's
selection of such Gene. Celera may select a replacement Gene for any Rejected
Gene and such Rejected Gene will be treated as if it had never been selected by
Celera. The identity of any Celera Gene Target or Rejected Gene will be the
Confidential Information of Celera.

                (c)  Isis agrees to conduct the Research under the Research Plan
and will provide reports to the JRC on a quarterly basis. These reports will
contain all information necessary to keep the JRC fully informed regarding the
performance of the Research Plan. Notwithstanding the preceding sentence, the
Parties acknowledge that there is no guarantee that a Lead Oligo will be
discovered using the HTS process.

                (d)  Celera knows and understands that it will be the primary
source of Celera Gene Targets under the Research Plan and that Isis will not
conduct any patent due diligence regarding its freedom to synthesize or screen
Antisense Inhibitors to such targets or to provide Antisense Inhibitors to
Celera hereunder. Subject to Sections 10.1 and 10.3, Celera will indemnify and
hold Isis harmless from any liability to Third Parties by reason of the use by
Isis of Celera Gene Targets solely for Isis' work under the Research Plan
during the Research Term. For clarification, Celera will not indemnify Isis,
and Celera will not be liable to Isis for any use of Celera Gene Targets after
Isis is notified to cease use of any Celera Gene Target, any use of Celera Gene
Targets in any Isis database, any use of Celera Gene Targets outside the
Research Plan, or any use of Celera Gene Targets in the development and/or
commercialization of Common Products or Isis Products.

          3.2   Selection of Celera Exclusive Targets.

                (a)  Isis will perform the work described in the Research Plan
and deliver any resulting data to the JRC and the Intellectual Property
Committee in a timely fashion ("Collaboration Data"). Such Collaboration Data
will include the assay and phenotype data as set forth in the Research Plan.

                (b)  Promptly after receiving the Collaboration Data with regard
to a Celera Gene Target, the JRC and the Intellectual Property Committee will
review the Collaboration Data. Upon delivery of the Collaboration Data, such
Celera Gene Target will become part of a pool of Celera Gene Targets available
to Celera for its use in accordance with the terms of this Agreement (the
"Celera Gene Availability Pool"). If Isis informs the JRC that it is unable to
create an optimized Antisense Inhibitor to such

                                       7
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Celera Gene Target and, as a result, will not be delivering Collaboration Data
to the JRC for such Celera Gene Target, such Celera Gene Target will not be
included in the Celera Gene Availability Pool.

                (c)  Celera will have the option, on a rolling basis, to
designate up to [* ] Celera Gene Targets from the Celera Gene Availability
Pool, together with the Collaboration Data for such Celera Gene Targets, for
Celera's exclusive use ("Celera Exclusive Targets") for Celera Products
pursuant to Section 4.3(a) (the "Option"). For any given Celera Gene Target,
Celera will exercise such Option, if at all, by giving written notice to Isis
during a period commencing on the date that the JRC determines that no further
work will be done on such Celera Gene Target and Isis delivers the
Collaboration Data as outlined in the Research Plan for such target to the JRC
and ending [* ] (the "Option Period"). Celera may replace any Celera Exclusive
Target with any Celera Gene Target in the Celera Gene Availability Pool
provided (i) the number of Celera Exclusive Targets does not [*] and (ii) the
Option Period for any such Celera Gene Target has not expired. For
clarification, only Celera Gene Targets in the Celera Gene Availability Pool
will be subject to the Option. If Celera does not exercise its Option for any
given Celera Gene Target during the applicable Option Period, or if Celera
notifies Isis in writing that it will not exercise its Option for such Celera
Gene Target, such Celera Gene Target will be deemed excluded from the Celera
Gene Availability Pool. After any such exclusion, such Celera Gene Target will
cease to be a Celera Gene Target, and Celera may not exercise its Option with
regard thereto.

                                   ARTICLE 4

                            LICENSES AND OTHER RIGHTS

          4.1   Licenses to Conduct the Research. Subject to the other
provisions of this Agreement, Celera hereby grants to Isis during the Research
Term a nonexclusive worldwide, paid up right and license, without the right to
sublicense, under the Celera Licensed Patents solely to conduct the Research.

          4.2   Isis Database. Isis will have the right to commercialize the
Collaboration Data in a database format unless such Collaboration Data (i) is
subject to Celera's Option during the Option Period pursuant to Section 3.2, or
(ii) contains or comprises in whole or in part any Collaboration Data for a
Celera Exclusive Target. Notwithstanding the foregoing, Celera may provide
Isis, upon Isis's written request, with written approval to use any
Collaboration Data in a database format, which would be otherwise restricted
from use under the first sentence of this Section. Isis will inform its
subscribers regarding the Collaboration Data added to the Isis Database
pursuant to this Section 4.2 that Collaboration Patents, if any, associated
with such data are subject to the licensing requirements set forth in Section
4.3.

          4.3   Use of the Joint Patents, Collaboration Patents and Other
Data. Both Parties will have the right to practice the Joint Patents and the
Collaboration Patents and use the Collaboration Data and the data provided by
a Party to the other Party pursuant to Section 5.1(c), for internal research
purposes; provided however,

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                (a)  Isis hereby grants Celera an exclusive right and license
(including with regard to Isis), with the right to sublicense and without
obligation to Isis, under Isis's rights in the Joint Patents and the Celera
Exclusive Collaboration Patents, to conduct development on, and to make, have
made, import, use, sell and have sold Celera Products;

                (b)  Celera hereby grants Isis an exclusive right and license
(including with regard to Celera), with the right to sublicense and without
obligation to Celera, under Celera's rights in the Joint Patents and the
Collaboration Patents, to conduct development on, and to make, have made,
import, use, sell and have sold Isis Products; and

                (c)  Both Parties will have the right and license, without
obligation of notice or payment to the other Party, to conduct development on,
and to make, import, use, sell and offer for sale Common Products with the
limited right to sublicense solely for development and commercialization.

                (d)  Celera will have the exclusive right and license (including
with regard to Isis), to grant sublicenses to make, import, use, sell and offer
for sale Common Products under the Celera Exclusive Collaboration Patents
(subject to the provisions of Section 7.2 regarding Revenue Sharing). Isis will
have the exclusive right and license (including with regard to Celera), to
grant sublicenses to make, import, use, sell, and offer for sale Common
Products under the Joint Patents and the Collaboration Patents except the
Celera Exclusive Collaboration Patents (subject to the provisions of Section
1.63 regarding Revenue Sharing).

          4.4   License to Celera Licensed Patents. Celera hereby grants Isis a
nonexclusive right and license, without the right to sublicense except in
connection with the sublicense of an Isis Product discovered by Isis alone or
as part of a bona fide drug discovery collaboration, under Celera's rights in
the Celera Licensed Patents, to conduct development on, and to make, have made,
import, use, sell and have sold Isis Products. Notwithstanding the foregoing,
if Isis is unable to generate a Lead Oligo to a Celera Gene Target pursuant to
the Research Plan, any and all Patent Rights that claim such Celera Gene Target
will be excluded from the license set forth in the preceding sentence.

          4.5   Negative Covenants.

                (a)  Isis covenants to Celera that Isis will not research,
develop or commercialize or license any Third Party or an Affiliate to
research, develop or commercialize any Celera Product claimed by Celera
Exclusive Collaboration Patents.

                (b)  Celera covenants to Isis that:

                  (i)   Celera will not research, develop or commercialize, or
license any Third Party or an Affiliate to research, develop or commercialize
any Isis Product claimed by Collaboration Patents; and

                  (ii)  Celera will not enter into any agreement with any Third
Party whose core business includes the provision of Antisense Inhibitors for
gene functionalization during the Research Term.

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          4.6   Limited Rights. Nothing in this Agreement is intended or will be
interpreted as granting to Isis or any Third Party any right or interest in any
Patent Rights, Information, trade secrets, copyrights, trademarks, trade names
or other intellectual property rights (a) invented, discovered, developed, or
otherwise created by PE Corporation (NY), or its Affiliates, other than by the
Celera Genomics Group, or (b) acquired or licensed by PE Corporation (NY), or
its Affiliates, other than solely for the benefit of the Celera Genomics Group.

                                    ARTICLE 5

                                 OTHER SERVICES

          5.1   Supply of Antisense Inhibitors.

                (a)  Isis will provide Lead Oligo Reagent to each Celera
Exclusive Target and to [* ] Celera Gene Targets that are not Celera Exclusive
Targets claimed by Celera Licensed Patents as provided in Section 4.4, at a
rate of [* ] per order for up to [* ] of a Lead Oligo, for Celera's internal
research and development of Celera Products and/or Common Products as
applicable ("Other Services"). Celera may request and Isis may agree to
negotiate commercially reasonable terms for the provision to Celera of
additional Lead Oligo Reagent to other Celera Gene Targets.

                (b)  Except as otherwise provided under this Agreement, all such
Antisense Inhibitors delivered to Celera will be used only in furtherance of
the Research, will not be used or delivered to or for the benefit of any Third
Party without the prior written consent of Isis, and will not be used in
research or testing involving human subjects. The Antisense Inhibitors supplied
under this Section 5.1 must be used with prudence and appropriate caution in
any experimental work, since not all of their characteristics may be known.

                (c)  THE ANTISENSE INHIBITORS BEING PROVIDED TO CELERA HEREUNDER
ARE PROVIDED "AS IS" AND WITHOUT ANY REPRESENTATION OR WARRANTY, EXPRESS OR
IMPLIED, INCLUDING WITHOUT LIMITATION ANY IMPLIED WARRANTY OF MERCHANTABILITY
OR OF FITNESS FOR ANY PARTICULAR PURPOSE OR ANY WARRANTY THAT THE USE OF THE
MATERIALS WILL NOT INFRINGE OR VIOLATE ANY PATENT OR OTHER PROPRIETARY RIGHTS
OF ANY THIRD PARTY.

                (d)  Celera agrees that it will not, nor will it request any
Third Party, to synthesize Antisense Inhibitors to any Celera Gene Target
during the Research Term or for the longer of [ *] thereafter or (ii) such time
as the discovery, manufacture, use or sale of such Antisense Inhibitors would
no longer infringe a Valid Claim of a Patent Right Controlled by Isis.

                (e)  Antisense Inhibitors discovered under the Research Plan are
identified using patented technology.

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                     (i)  During the Research Term and for [*] thereafter (the
"Extended Term"), if Celera derives any Information from research not under the
Research Plan using Lead Oligo Reagent provided by Isis to Celera pursuant to
Section 5.1(a), Celera will promptly provide such Information to Isis.
Notwithstanding the obligation to provide such Information, Celera hereby
grants Isis an exclusive right and license (including with regard to Celera),
without the right to sublicense, except in connection with the sublicense of an
Isis Product discovered by Isis alone or as part of a bona fide drug discovery
collaboration, and without obligation to Celera, under Celera's rights in any
Patents Rights in which information derived using such Lead Oligo Reagent
during and after the Extended Term is used in the filing prosecution,
maintenance or defense of such Patent Rights, to conduct development on, and to
make, have made, import, use, sell and have sold Isis Products.

                     (ii)  During the Extended Term, if Isis derives any
Information from research not under the Research Plan on Celera Exclusive
Targets using Antisense Inhibitors identified under the Research Plan, and/or
on Celera Gene Targets that are claimed by Celera Licensed Patent Rights as
provided in Section 4.4, Isis will promptly provide all data derived from such
research to Celera, excluding data derived from any use in humans.
Notwithstanding the obligation to provide such Information, Isis hereby grants
Celera a non-exclusive right and license, without the right to sublicense,
except in connection with the sublicense of a Celera Product discovered by
Celera alone or as part of a bona fide drug discovery collaboration, and
without obligation to Isis, under any Patent Rights claiming all Information
derived from such research during and after the Extended Term, to conduct
development on, and to make, have made, import, use, sell and have sold Celera
Products.

          5.2   Custom Target Validation. Celera will have an option to identify
up to [*] Celera Gene Targets for custom target validation. Custom target
validation may include pharmacology studies of effects of antisense inhibitor
in additional cell-based or animal models. Terms and conditions for custom
target validation will be negotiated in good faith but no less than Isis'
fully-burdened cost plus appropriate milestones and royalties.

                                   ARTICLE 6

                         MANAGEMENT OF THE COLLABORATION

          6.1   Creation and Structure of the Joint Research Committee.

                (a)  Within ten (10) business days of the Effective Date, the
Parties will create a Joint Research Committee of two (2) persons to facilitate
the research collaboration called for herein. The JRC will consist one (1)
representative nominated by each Party. Members of the JRC may be represented
at any meeting by a designee appointed by such member for such meeting. Each
Party will be free to change its representatives on notice to the other or to
send a substitute representative of equal qualification and authority to any
JRC meeting.

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                (b)  The JRC will meet as necessary but no less frequently than
every three (3) months during the Research Term. Meetings will be via
teleconference or videoconference. At its first meeting the JRC will determine
such procedures as it will reasonably require to conduct its business.

                (c)  During the Research Term, the JRC will be the primary
vehicle for interaction between the Parties with respect to the Research.
Without limiting the foregoing, the JRC will be responsible for (i) determining
for each Celera Gene Target whether to proceed to conduct Secondary Assays as
described in the Research Plan. (ii) reviewing and commenting upon the patent
filing strategies of the Collaboration Patents, the Celera Exclusive
Collaboration Patents and the Joint Patent Rights as provided in Article 8;
(iii) reviewing and commenting upon publications as contemplated by Section
9.2; and (iv) managing the activities of the Intellectual Property Committee.
The items in Subsections (ii) and (iii) will be delegated to the Intellectual
Property Committee.

                (d)  All decisions of the JRC will be made by the unanimous vote
of the members. If the members of the JRC cannot agree with respect to a
particular issue such issue will be referred to the JEC which will make a
reasonable good faith effort to reach agreement thereon within a ten (10)
business day period after such issue is presented to the JEC in writing.

          6.2   Creation and Structure of the Intellectual Property Committee.

                (a)  At the first meeting of the JRC, the JRC will create an
Intellectual Property Committee. The Intellectual Property Committee will be
managed and directed by the JRC. The Intellectual Property Committee will be
composed of the two (2) JRC members plus two (2) additional members, one from
each of Isis and Celera.

                (b)  The roles of the Intellectual Property Committee will be
(i) to conduct the IP mining described in the Research Plan, (ii) to review and
approve any publications containing Collaboration Data except inclusion of
Collaboration Data in the Isis database as anticipated by this Agreement, and
(iii) to manage the prosecution, defense and maintenance of the Collaboration
Patents and the Joint Patents.

                (c)  The Intellectual Property Committee will meet as needed
either in person, by teleconference or via videoconference. At the first
meeting of the Intellectual Property Committee, the Committee will adopt such
roles and procedures as it may deem necessary or appropriate to conduct their
business.

                (d)  All decisions of the Intellectual Property Committee will
be made by the unanimous vote of the members, if the members of the
Intellectual Property Committee cannot agree with respect to a particular issue
such issue will be referred to the JEC which will make a reasonable good faith
effort to reach agreement thereon within ten (10) business days after such
issue is presented to the JEC in writing.

                (e)  The Intellectual Property Committee will continue in effect
after the termination of this Agreement for so long as Collaboration Patents or
Joint Patents are

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being prosecuted and maintained, or such shorter time as mutually agreed to by
the Parties in writing.

          6.3   Creation and Structure of the Joint Executive Committee.

                (a)  Within ten (10) business days of the Effective Date, the
Parties will create a Joint Executive Committee of two (2) people, one from
each Party to oversee the research collaboration and commercialization
activities called for herein. The JEC will be composed of one (1)
representative appointed by each of Celera and Isis. Either Party may replace
one (1) its representative at any time upon written notice to the other Party
with a person of equal authority and expertise.

                (b)  The JEC will exist for so long as the JRC or
Intellectual Property Committee is in existence or either Party has the right
to conduct commercialization activities pursuant to Section 4.3(d). The JEC
will meet as requested by the JRC or Intellectual Property Committee. On
matters requiring the approval of the JEC, such approval will be by the
unanimous vote of all JEC members participating in the meeting. In the event
the JEC is unable to reach agreement on all issues, it will be resolved in
accordance with Section 12.11. The JEC will meet within thirty (30) days of
the Effective Date and thereafter as needed or at the request of either Party
to carry out the function set forth in this Section 6.3.

                (c)  The JEC will be the primary vehicle for oversight of the
research collaboration activities. Without limiting the foregoing, the JEC will
be responsible for (i) review and resolution of any material deviation from the
Research Plan; and (ii) review and resolution of any dispute elevated to it by
the JRC or the Intellectual Property Committee.

                (d)  Through the JEC the Parties will keep each other reasonably
informed on an ongoing basis of the substantive terms of any proposed agreement
to grant sublicenses pursuant to Section Article 4.3(d).

                     (i)      [*]

                     (ii)     [*]

                                   ARTICLE 7

                          PAYMENTS AND REVENUE SHARING

           7.1  Research Funding.

                (a)  Celera will pay Isis [*] to conduct the Research under the
Research Plan. Celera will pay Isis [*] of the Effective Date. Notwithstanding
the foregoing, if Isis fails in a material way to conduct the Research
according to the Research Plan Celera may withhold payment of the following [*]
until such material failure is remedied, whereupon such [*] will be paid in
full or in such fraction as the Parties shall reasonably agree. Any

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dispute with regard to such  payment  withholding  will be promptly  elevated to
dispute resolution pursuant to Section 12.11(a).

                (b)  Delivery schedule and funding for Other Services described
in Article 5 will be agreed upon and paid in advance in the amounts agreed to
by the Parties.

          7.2   [*].

          7.3   Mode of Payment and Reports. All payments to hereunder will be
made to the receiving Party within sixty (60) days of the end of the quarter in
which the receiving Party receives the payment by deposit of United States
Dollars in the requisite amount to such bank account as the receiving Party may
from time-to-time designate by notice to the paying Party. The paying Party
will provide to the receiving Party with each such payment a report in
sufficient detail to show the basis for such payment.

          7.4   Audits.

                (a)  Upon the written request of the receiving Party and not
more than once in each calendar year, the paying Party will permit an
independent certified public accounting firm of nationally recognized standing
selected by the paying Party, and reasonably acceptable to the receiving Party
at the receiving Party's expense, to have access during normal business hours,
and upon reasonable prior written notice, to such of the records of the paying
Party as may be reasonably necessary to verify the accuracy of the reports
under Section 7.3 for the prior calendar year only. The accounting firm will
disclose to the Parties only whether the reports are correct or incorrect and
the specific details concerning any discrepancies. No other information will be
provided to Celera.

                (b)  If such accounting firm concludes that additional payments
were owed during such period, the paying Party will pay the additional
payments, with interest from the date originally due at the prime rate, as
published in The Wall Street Journal (Eastern U.S. Edition) on the last
business day preceding such date, within thirty (30) days after the date the
receiving Party delivers to the paying Party such accounting firm's written
report. [*]

                (c)  For any sublicense granted by either Party hereunder which
triggers payments to the other Party pursuant to this Article 7, the grantor of
such sublicense will include in each sublicense granted by it pursuant to this
Agreement a provision requiring the Sublicensee to keep and maintain records of
sales made, pursuant to such sublicense and to grant access to such records by
the licensing Party's independent accountant to the same extent required by
such grantor under this Agreement.

                (d)  Celera and Isis will treat all information subject to
review under this Section 7.4 or under any sublicense agreement in accordance
with the confidentiality provisions of Article 9 of this Agreement.

         7.5    Taxes. If any taxes are required to be withheld by the
licensing Party, it will (a) deduct such taxes from the remitting payment,
(b) timely pay the taxes to the proper

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taxing authority, and (c) send proof of payment to the receiving Party and
certify its receipt by the taxing authority within sixty (60) days following
such payment.

                                   ARTICLE 8

                             INVENTIONS AND PATENTS

          8.1   Title to Inventions.

                (a)  Any Patent Rights covering inventions by the Parties during
the Collaboration that do not constitute Collaboration Patents will be owned
exclusively by the inventing party, subject to Subsection 8.1(c).

                (b)  Joint Patents will be jointly owned, subject to Subsection
8.1(c).

                (c)  Any inventions constituting Oligonucleotide Patents will be
solely owned and assigned to Isis. Inventions with an antisense component and a
broader compound will be broken into separate patent applications with the
antisense-related inventions filed separately as Oligonucleotide Patents.

                (d)  Any inventions constituting Celera Exclusive Collaboration
Patents will be solely owned and assigned to Celera (subject to the licenses
granted to Isis hereunder).

                (e)  Inventorship will be determined by the applicable laws of
the country or jurisdiction in which the particular Patent Right is sought.

                (f)  In the event that there is a dispute between the Parties as
to ownership under this Section, the Intellectual Property Committee will
establish a procedure to resolve such dispute, which may include engaging a
Third Party patent attorney completely unaffiliated and independent of the
Parties and jointly selected by the Parties, as an expert to resolve such
dispute.

          8.2   Patent Prosecution.

                (a)  The Parties expect that patent applications will be filed
and maintained as required to secure the Collaboration Patent Rights. Celera,
with reasonable and timely input from Isis, will be responsible for filing,
prosecuting and/or maintaining the Celera Exclusive Collaboration Patents
throughout the world. Isis with reasonable and timely input from Celera, will
be responsible for filing, prosecuting and/or maintaining the Collaboration
Patents other than Celera Exclusive Collaboration Patents throughout the world.
Celera and Isis will share equally the costs of filing, prosecuting and/or
maintaining such Patent Rights. Notwithstanding the above, either Party may
decline to pay its share of the costs for filing, prosecuting and/or
maintaining any Collaboration

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Patent(s) (a "Declining Party"), in which case such Declining Party will
notify the other Party promptly in writing and in good time to enable the
other Party to meet any applicable deadlines, and the other Party will have
the right, but not the obligation, to undertake the responsibility for
filing, prosecuting and/or maintaining such Collaboration Patents at its own
expense, and the Declining Party will reasonably cooperate with and assist
the other Party therein. A Declining Party will maintain its license under
such Collaboration Patent pursuant to Article 4, except that any right to
grant sublicenses therein (other than the sublicensing rights set forth in
Sections 4.3(a) 4.3(b)), and any right to receive Licensing Revenue pursuant to
Section 7.2 under such Collaboration Patents, will terminate as of the date a
Declining Party provides such written notice. Such terminated sublicense
rights shall be granted to the other Party, provided such other Party has
exercised its right of filing, prosecuting and/or maintaining such
Collaboration Patents.

                (b)  The Parties anticipate that there may be Joint Patents that
arise out of the Collaboration (that do not constitute Collaboration Patents or
Oligonucleotide Patents). To the extent that such a Joint Patent represents an
improvement of one Party's technology and not the other, the Party whose
technology is improved will have the sole right and responsibility, at its own
expense, to prosecute and maintain such Joint Patent. To the extent that such a
Joint Patent either represents an improvement to both Party's technology or
does not improve either Party's technology, the Intellectual Property Committee
will determine which of the Parties will be responsible for prosecution,
maintenance, enforcement and defense of such Patent and what procedures will be
put in place for coordination among the Parties including, without limitation,
cost-sharing and input.

                (c)  Isis will be solely responsible, at its own expense, for
prosecution, maintenance, defense and enforcement of any Oligonucleotide
Patents.

          8.3   Enforcement of Patents.

                (a)  If either Party considers that any Collaboration Patent is
being infringed by a Third Party, it will notify the other Party and provide it
with any evidence of such infringement which is reasonably available. Subject
to any limitations in the license agreements between Celera or Isis and Third
Party licensors covering licensed Patent Rights, the JEC will determine the
steps to take to attempt to remove such infringement by commercially
appropriate steps, including filing an infringement suit or taking other
similar action.

                (b)  The Party not enforcing the applicable Patent Rights will
provide reasonable assistance to the other Party, including providing access to
relevant documents and other evidence and making its employees available,
subject to the enforcing Party's reimbursement of any out-of-pocket expenses
incurred by the non-enforcing Party.

                (c)  Any amounts recovered by a Party pursuant to Section
8.3(a) whether by settlement or judgment, will be allocated in the following
order: (i) to reimburse Isis and Celera for their reasonable out-of-pocket
expenses in making such

                                       16
<Page>

recovery  (which amounts will be allocated pro rats if insufficient to cover the
totality of such  expenses);  and (ii) the  remainder  will be  allocated as the
Parties will reasonably agree based upon damages suffered.

                (d)  Except for Third Party infringement activities covered by
the provisions of Section (j) each Party will retain the sole and exclusive
right to enforce its Patent Rights against all infringers at its sole cost and
expense.

                                    ARTICLE 9

                                 CONFIDENTIALITY

          9.1   Confidentiality Obligations. Each Party agrees that, for the
term of this Agreement and for five (5) years thereafter, such Party will keep,
and will ensure that its officers, directors, employees and agents keep,
completely confidential and will not publish or otherwise disclose and will not
use for any purpose except as permitted hereunder any Confidential Information
furnished to it by the other Party pursuant to this Agreement (including,
without limitation, Know-How of the disclosing Party). The foregoing
obligations will not apply to any information to the extent that it can be
established by such receiving Party that such information:

                (a)  was already known to the receiving Party as evidenced by
its written records, other than under an obligation of confidentiality, at the
time of disclosure;

                (b)  was generally available to the public or was otherwise part
of the public domain at the time of its disclosure to the receiving Party;

                (c)  became generally available to the public or otherwise
becomes 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)  was subsequently lawfully disclosed to the receiving Party
by a Third Party other than in contravention of a confidentiality obligation of
such Third Party to the disclosing Party; or

                (e)  was developed or discovered by employees of the receiving
Party or its Affiliates who had no access to the Confidential Information of
the disclosing Party. Each Party may disclose the other's Confidential
Information to the extent such disclosure is reasonably necessary in filing or
prosecuting patent applications, prosecuting or defending litigation, advising
investors and the investment community of the results of the Research aid/or
development activities hereunder (subject to reasonable prior written notice
of, and good faith consultation about, such disclosure to the other Party),
complying with applicable governmental regulations, making a permitted
sublicense of its rights hereunder or otherwise in performing its obligations
or exercising its rights hereunder, provided that if a Party is required to
make any such disclosure of the other Party's Confidential Information, it will
give reasonable advance notice to that other Party of such disclosure
requirement, will cooperate with the other Party in its efforts to secure
confidential treatment of such Information prior to its disclosure, and, save
to the extent

                                       17
<Page>

inappropriate in the case of patent applications, will use all reasonable
efforts to secure confidential treatment of such information prior to its
disclosure (whether through protective orders or confidentiality agreement or
otherwise).

          9.2   Publications.

                (a)  The Collaboration Data will be the Confidential Information
of Isis and Celera. Either Party may publish or present Collaboration Data
subject to the prior review by the Intellectual Property Committee for
patentability and protection of such other Party's Confidential Information.
The Intellectual Property Committee will review any proposed abstracts,
manuscripts or summaries of presentations which contain Collaboration Data. No
publication or presentation containing Collaboration Data may be submitted or
made without approval by the Intellectual Property Committee. The Intellectual
Property Committee may delay any such approval to ensure protection of Patent
Rights. Notwithstanding the foregoing, nothing contained herein will preclude
Isis from including the Collaboration Data in its marketed database in
accordance with the terms of this Agreement or presenting the Collaboration
Data to Isis' potential customers for such database or in connection with
either Parties active drug discovery programs, without approval of the
Intellectual Property Committee.

                (b)  To the extent appropriate and within the Party's control,
in any publication permitted under this Section 9.2, each Party will
acknowledge its collaboration with the other Party under this Agreement

          9.3   Press Releases. Except to the extent required by law or as
otherwise permitted in accordance with this Section 9.3, neither Party will
make any public announcements concerning this Agreement or the terms hereof
without the prior written consent of the other, which will not be unreasonably
withheld or delayed. Notwithstanding the foregoing, the Parties will issue a
joint press release promptly following execution of this Agreement announcing
(i) the execution of this Agreement; (ii) Celera and Isis will jointly identify
novel gene function utilizing Celera's expertise in genomics and Isis'
expertise in antisense technology; (iii) Celera will retain exclusive rights to
a limited number of genes for the research and development of certain
therapeutic products; and (iv) that functional information on [*] of these
genes will be incorporated into Isis' Gene Function Database, and agree that
each Party may desire or be required to issue subsequent press releases
relating to the Agreement or activities thereunder, and the Parties agree to
consult with each other reasonably and in good faith with respect to the text
and timing of such press releases prior to the issuance thereof, provided that
a Party may not unreasonably withhold consent to such releases, and that either
Party may issue such press releases as it determines, based on advice of
counsel, are reasonably necessary to comply with laws or regulations or for
appropriate market disclosure.

                                   ARTICLE 10

                                 INDEMNIFICATION

*Confidential Treatment Requested      18
<Page>

          10.1  Indemnification by Celera. Celera will indemnify, defend and
hold Isis and its agents, employees, officers and directors (the "Isis
Indemnitees") harmless from and against any and all liability, damage, loss,
cost or expense (including reasonable attorneys' fees) arising out of Third
Party claims or suits related to (a) Celera's performance of its obligations
under this Agreement; or (b) breach by Celera of its representations and
warranties set forth in Section 12.3 or (c) Isis' use of Celera Gene Targets
under the Research Plan pursuant to Section 3.1(d); PROVIDED, HOWEVER, that
Celera's obligations pursuant to this Section 10.1 will not apply to the extent
such claims or suits result from the gross negligence or willful misconduct of
any of the Isis Indemnitees. Notwithstanding the foregoing, Celera will have no
obligation to indemnify the Isis Indemnitees with respect to claims arising out
of breach by Isis of its representations and warranties set forth in Sections
12.3.

          10.2  Indemnification by Isis. Isis will indemnify, defend and hold
Celera and its Affiliates and each of their respective agents, employees,
officers and directors (the "Isis Indemnitees") harmless from and against any
and all liability, damage, loss, cost or expense (including reasonable
attorney's fees) arising out of Third Party claims or suits related to (a)
Isis's performance of its obligations under this Agreement; or (b) breach by
Isis of its representations and warranties set forth in Sections 12.3; provided
however, that Isis's obligations pursuant to this Section 10.2 will not apply
to the extent that such claims or suits result from the gross negligence or
willful misconduct of any of the Celera Indemnitees. Notwithstanding the
foregoing, Celera will have no obligation to indemnify the Celera Indemnitees
with respect to claims arising out of a breach by Celera of its representations
and warranties set forth in Section 12.3.

          10.3  Notification of Claims. Conditions to Indemnification
Obligations. As a condition to a Party's right to receive indemnification under
this Article 10 it will (i) promptly notify the other Party as soon as it
becomes aware of a claim or action for which indemnification may be sought
pursuant hereto, (ii) cooperate with the indemnifying Party in the defense of
such claim or suit, and (iii) permit the indemnifying Party to control the
defense of such claim or suit, including without limitation the right to select
defense counsel. In no event, however, may the indemnifying Party compromise or
settle any claim or suit in a manner which admits fault or negligence on the
part of the indemnified Party without the prior written consent of the
indemnified Party. The indemnifying Party will have no liability under this
Article 10 with respect to claims or suits settled or compromised without its
prior written consent.

                                   ARTICLE 11

                           TERMINATION AND EXPIRATION

          11.1  Term and Termination. This Agreement will commence upon the
Effective Date and, unless earlier terminated as provided herein, will expire
on the expiration of all royalty and other payment obligations herein.

          11.2  Termination upon Material Breach. Failure by a Party to comply
with any of its material obligations contained herein will entitle the Party not
in default to give to

                                       19
<Page>

the Party in default notice specifying the nature of the default, requiring
it to make good or otherwise cure such default, and stating its intention to
terminate if such default is not cured. If such default is not cured within
ninety (90) days after the receipt of such notice (or, if such default cannot
be cured within such ninety (90) day period, if the Party in default does not
commence and diligently continue actions to cure such default), the Party not
in default will be entitled, without prejudice to any of its other rights
conferred on it by this Agreement, and in addition to any other remedies
available to it by law or in equity, to terminate this Agreement; PROVIDED
HOWEVER, that such right to terminate will be stayed in the event that,
during such ninety (90) day period, the Party alleged to have been in default
will have initiated dispute resolution in accordance with Section 12.11 with
respect to the alleged default, which stay will last so long as the
initiating Party diligently and in good faith cooperates in the prompt
resolution of such dispute resolution proceedings.

          11.3  Consequences of Termination.

                (a)  Upon termination of this Agreement (but not upon expiration
of its term under Section 11.1);

                     (i)  each Party will promptly return all relevant records
and materials in its possession or control containing or comprising the other
Party's Confidential Information and to which the former Party does not retain
rights hereunder (except one copy of which may be retained in a Party's
confidential files in its legal department for archival purposes); and

                     (ii) all licenses granted under Sections 4.1, 4.1(a) and
4.3(d) will terminate; provided however, that all sublicenses previously
granted will survive termination. All licenses granted under Section 4.2 and
4.3 will survive termination.

                (b)  The right of a Party to terminate this Agreement, as herein
above provided, will not be affected in any way by its waiver or failure to
take action with respect to any prior default.

          11.4  Accrued Rights; Surviving Obligations.

                (a)  Termination, relinquishment or expiration of this Agreement
for any reason will be without prejudice to any rights which will have accrued
to the benefit of a Party prior to such termination, or expiration. Such
termination, relinquishment or expiration will not relieve a Party from
obligations which are expressly indicated to survive termination or expiration
of this Agreement.

                (b)  Without limiting the foregoing, Sections 2.3, 3.1(d),
4.3(a), 4.3(b), 4.3(c), 4.5, 4.6, 7.3, 7.4, 7.5, 8.1, 8.2, 9.1, 11.3, 11.4
and 11.5 and Articles 10 and 12 of this Agreement will survive the expiration
or termination of this Agreement for any reason.

          11.5  Rights in Bankruptcy. All rights and licenses granted under or
pursuant to this Agreement by Isis or Celera are, and will otherwise be deemed
to be, for purposes of

                                       20
<Page>

Section 365(n) of the U.S. Bankruptcy Code, licenses of right to "intellectual
property" as defined under Section 101 of the U.S. Bankruptcy Code. The Parties
agree that the Parties, as licensees of such rights under this Agreement, will
retain and may fully exercise all of their rights and elections under the U.S.
Bankruptcy Code. The Parties further agree that, in the event of the
commencement of a bankruptcy proceeding-by or against either Party under the
U.S. Bankruptcy Code, the Party hereto which is not a party to such proceeding
will be entitled to a complete duplicate of (or complete access to, as
appropriate) any such intellectual property and all embodiments of such
intellectual property, and same, if not already in their possession, will be
promptly delivered to them (i) upon any such commencement of a bankruptcy
proceeding upon their written request therefor, unless the Party subject to
such proceeding elects to continue to perform all of its obligations under this
Agreement, or (ii) if not delivered under (i) above, following the rejection of
this Agreement by or on behalf of the Party subject to such proceeding upon
written request therefor by the non-subject Party.

                                   ARTICLE 12

                            MISCELLANEOUS PROVISIONS

          12.1  Relationship of the Parties. Nothing in this Agreement is
intended or will be deemed to constitute a partnership, agency or
employer-employee relationship between the Parties. Neither Party will incur
any debts or make any commitments for the other.

          12.2  Assignments. Neither this Agreement nor any interest hereunder
will be assignable, nor any other obligation delegable, by a Party without the
prior written consent of the other Party; provided however, that either Party
may assign this Agreement without consent to any successor in interest by way
of merger or sale of all or substantially all of its assets in a manner such
that the assignor will remain liable and responsible for the performance and
observance of all of the assigning Party's duties and obligations hereunder,
except that no intellectual property of any Third Party acquirer of Celera or
Isis will be included in the licenses granted hereunder. This Agreement will be
binding upon the successors and permitted assigns of the Parties. Any
assignment not in accordance with this Section 12.2 will be void.

          12.3  Representations and Warranties. Each Party represents and
warrants to the other Party that, as of the date of this Agreement:

                (a)  Such Party is duly organized and validly existing under the
laws of the state of its incorporation and has full corporate power and
authority to enter into this Agreement and to carry out the provisions hereof;

                (b)  Such Party has taken all corporate action necessary to
authorize the execution and delivery of this Agreement and the performance its
obligations under this Agreement;

                (c)  This Agreement is a legal and valid obligation of such
Party, binding upon such Party and enforceable against such Party in accordance
with the terms of this Agreement The execution, delivery and performance of
this Agreement by such

                                       21
<Page>

Party does not conflict with any agreement, instrument or understanding, oral
or written, to which such Party is a party or by which such Party may be bound,
and does not violate any law or regulation of any court, governmental body or
administrative or other agency having authority over such Party. All consents,
approvals and authorizations from all governmental authorities or other Third
Parties required to be obtained by such Party in connection with this Agreement
have been obtained

                (d)  It has the full and exclusive right, power and authority to
enter into this Agreement, to perform the Research and to grant the licenses
granted under Article 4;

                (e)  There are no agreements between such Party and any Third
Parties which would preclude or otherwise limit such Party's ability to conduct
its tasks and obligations under the Research Plan or otherwise fulfill its
obligations under this Agreement;

                (f)  All individuals who will perform any activities on its
behalf in connection with the Research have assigned to it or its Affiliates
the whole of their rights in any intellectual property conceived or reduced to
practice by them as a result of the Research, and no Third Party will have any
rights to any such intellectual property.

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

          12.5  Further Actions. Each Party agrees to execute, acknowledge and
deliver such further instruments and to do all such other acts as may be
necessary or appropriate in order to carry out the purposes and intent of this
Agreement.

          12.6  Force Majeure. Neither Party will be liable to the other for
failure or delay in the performance of any of its obligations under this
Agreement for the time and to the extent such failure or delay is caused by
earthquake, riot, civil commotion, war, strike, flood, governmental acts or
restrictions or any other reason which is beyond the control of the respective
Party. The Party affected by force majeure will provide the other Party with
full particulars thereof as soon as it becomes aware of the same (including its
best estimate of the likely extent and duration of the interference with its
activities), and will use commercially reasonable efforts to overcome the
difficulties created thereby and to resume performance of its obligations as
soon as practicable. If the performance of any obligation under this Agreement
is delayed owing to a force majeure for any continuous period of more than six
(6) months, the Parties hereto will consult with respect to an equitable
solution, including the possibility of the mutual termination of this
Agreement.

          12.7  No Trademark Rights. Except as expressly set forth herein, no
right, express or implied, is granted by this Agreement to a Party to use in
any manner the name or any other trade name or trademark of a Party in
connection with the performance of this Agreement.

                                       22
<Page>

          12.8  Entire Agreement of the Parties; Amendments. This Agreement and
the exhibits hereto constitute and contain the entire understanding and
agreement of the Parties respecting the subject matter hereof and cancel and
supersede any and all prior negotiations, correspondence, understandings and
agreements between the Parties, whether oral or written, regarding such subject
matter. No waiver, modification or amendment of any provision of this Agreement
will be valid or effective unless made in writing and signed by a duly
authorized officer of each Party.

          12.9  Captions. The captions to this Agreement are for convenience
only, and are to be of no force or effect in construing or interpreting any of
the provisions of this Agreement

          12.10 Applicable Law. This Agreement will be governed by and
interpreted in accordance with the laws of the State of Delaware, USA,
applicable to contracts entered into and to be performed wholly within the
State of Delaware, excluding conflict of law principles.

          12.11 Disputes. In the event of any controversy or claim arising out
of, relating to or in connection with any provision of this Agreement or the
rights or obligations of the Parties hereunder, the Parties will try to settle
their differences amicably between themselves as contemplated herein. To the
extent not provided for herein, either Party may initiate such informal dispute
resolution by sending written notice of the dispute to the other Party, and
within ten (10) days after such notice.

                (a)  The Chief Business Officer of Celera and the President of
GeneTrove of Isis will meet for discussion and resolution. If such personnel
are unable to resolve such dispute within thirty (30) days of initiating such
negotiations, the Parties agree to settle any unresolved controversy or claim
arising out of, relating to or in connection with this Agreement (except as to
any issue relating to the ownership of intellectual property of either Party)
in Dallas, Texas by binding arbitration under the American Arbitration
Association in accordance with its Commercial Arbitration Rules as modified by
this Section, and judgment upon the award rendered by the arbitrators may be
entered in any court having jurisdiction thereof. Within fifteen (15) days
after the commencement of arbitration, each Party will select one (1) person to
act as arbitrator, and the two (2) selected by the Parties will select a third
arbitrator within ten (10) days of their appointment. The Parties agree that in
cases in which this Agreement explicitly provides that their disagreement will
be settled by this Section, the arbitration method to be employed will be
"baseball-style arbitration." This means that each Party will submit in writing
to the Panel and the other Party at an appropriate time its final, detailed
proposed resolution of the dispute. The panel will have the right to ask for
and receive (at the same time as the other Party) clarification of a Party's
proposed resolution. In its arbitration award, the panel will be limited to
choosing, without material modification, one of the two proposed resolutions,
together with an award of reasonable attorneys' fees to the prevailing Party.
The arbitrators will have no authority to award punitive damages or any other
damages not measured by the prevailing Party's actual damages, and may not, in
any event, make any ruling, finding or award that does not conform to the terms
and conditions of this Agreement. Neither Party nor the arbitrators may
disclose the existence,

                                       23
<Page>

content,  or results of any  arbitration  hereunder  without  the prior  written
consent of both Parties.

          12.12 Notices and Deliveries. Any notice, request, delivery, approval
or consent required or permitted to be given under this Agreement will be in
writing and will be deemed to have been sufficiently given if delivered in
person, transmitted by facsimile (receipt verified) or by express courier
service (signature required) or five (5) days after it was sent by registered
letter, return receipt requested (or its equivalent), to the Party to which it
is directed at its address or facsimile number shown below or such other
address or facsimile number as such Party will have last given by notice to the
other Party.

         If to Isis, addressed to:

                           Isis Pharmaceuticals, Inc.
                           2292 Faraday Drive
                           Carlsbad, California 92008
                           Attn: Richard Brown, B. Lynne Parshall
                           Cc:   GeneTrove President

         If to Celera, addressed to:

                           Celera Genomics
                           45 West Gude Drive
                           Rockville, Maryland
                           Attn: Peter Barrett, Ph.D.
                           Cc:   Group Counsel, Legal Affairs

          12.13 No Consequential Damages. IN NO EVENT WILL EITHER PARTY OR ANY
OF ITS RESPECTIVE AFFILIATES BE LIABLE TO THE OTHER PARTY OR ANY OF ITS
AFFILIATES FOR SPECIAL, INDIRECT, INCIDENTAL OR CONSEQUENTIAL DAMAGES, WHETHER
IN CONTRACT, WARRANTY, TORT, NEGLIGENCE, STRICT LIABILITY OR OTHERWISE,
INCLUDING, BUT NOT LIMITED TO, LOSS OF PROFITS OR REVENUE, OR CLAIMS OF
CUSTOMERS OF ANY OF THEM OR OTHER THIRD PARTIES FOR SUCH OR OTHER DAMAGES.

          12.14 Non-Solicitation. During the Research Term, and for a period of
one (1) year thereafter, neither Party will solicit, induce, encourage or
attempt to induce or encourage any employee of the other Party to terminate his
or her employment with such other Party or to breach any other obligation to
such other Party.

          12.15 Waiver. A waiver by either Party of any of the terms and
conditions of this Agreement in any instance will not be deemed or construed to
be a waiver of such term or condition for the future, or of any subsequent
breach hereof. All rights, remedies, undertakings, obligations and agreements
contained in this Agreement will be cumulative and none of them will be in
limitation of any other remedy, right, undertaking, obligation or agreement of
either Party.

                                       24
<Page>

          12.16 Compliance with Law. Nothing in this Agreement will be deemed
to permit a Party to export, re-export or otherwise transfer any Licensed
Product sold under this Agreement without compliance with applicable laws.

          12.17 Severability. When possible, each provision of this Agreement
will be interpreted in such manner as to be effective and valid under
applicable law, but if any provision of this Agreement is held to be prohibited
by or invalid under applicable law, such provision will be ineffective only to
the extent of such prohibition or invalidity, without invalidating the
remainder of this Agreement. The Parties will make a good faith effort to
replace the invalid or unenforceable provision with a valid one which in its
economic effect is most consistent with the invalid or unenforceable provision.

          12.18 Counterparts. This Agreement may be executed simultaneously in
any number of counterparts, any one of which need not contain the signature of
more than one Party but all such counterparts taken together will constitute
one and the same agreement

          IN WITNESS WHEREOF, the Parties have caused this Agreement to be
executed by their respective duly authorized officers as of the day and year
first above written, each copy of which will for all purposes be deemed to be
an original.

ISIS PHARMACEUTICALS, INC.            PE CORPORATION

By:                                   By:
    ----------------------------         ----------------------------
           (signature)                           (signature)

Name:  B. Lynne Parshall              Name:  Peter Barrett, Ph.D.

Title: Executive Vice President       Title: E.V.P. and Chief Business Officer

Date:                                 Date:
     ---------------------------           --------------------------

                                       25
<Page>

                                    EXHIBIT A
                                  RESEARCH PLAN

This Exhibit A to the Collaborative Research and License Agreement (the
"Agreement") dated as of July 9, 2001 addresses the conduct of the Research.
Capitalized terms will have the meanings set forth in the Agreement.

The generation of functional information on [* ] Celera Target Genes will follow
a multi-step process: prioritization of genes, generation and validation of lead
antisense oligos, and bioassay readout in four therapeutic areas (cancer,
angiogenesis, inflammation, and metabolic disease). After the Collaboration Data
is reviewed by the Joint Research Committee and Intellectual Property Committee
and appropriate patent applications filed, the information will be used to
populate the Gene Trove Gene Function Database, excluding information on [* ]
Celera Exclusive Targets.

Isis will provide reports to the JRC on a quarterly basis or more frequently.
These reports will contain all information necessary to keep the JRC fully
informed regarding the performance of the research plan.

[*]

*Confidential Treatment Requested      26
<Page>

                                    EXHIBIT B

[* ]

* Confidential Treatment Requested     27

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