Document:

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                                                                   Exhibit 10.72

                                MASTER AGREEMENT

         RELATING TO THE CROSS LICENSE OF CERTAIN INTELLECTUAL PROPERTY
                                AND COLLABORATION
                                 BY AND BETWEEN
                                 HYBRIDON, INC.
                             a Delaware corporation

                                       AND

                           ISIS PHARMACEUTICALS, INC.
                             a Delaware corporation

                            DATED AS OF MAY 24, 2001

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                                TABLE OF CONTENTS
<TABLE>
<CAPTION>
                                                                                                               PAGE
                                                                                                               ----
<S>     <C>                                                                                                      <C>
ARTICLE 1- DEFINED TERMS..........................................................................................1

         1.1      Definitions.....................................................................................1

ARTICLE 2 - COLLABORATION AND LICENSE AGREEMENT AND OTHER
         CONSIDERATION............................................................................................6

         2.1      Execution of Collaboration and License Agreement................................................6
         2.2      Additional Hybridon Consideration...............................................................7
         2.3      Additional Isis Consideration..................................................................11
         2.4      Restrictive Legend.............................................................................16

ARTICLE 3 - REPRESENTATIONS AND WARRANTIES OF HYBRIDON...........................................................16

         3.1      Organization and Good Standing; Power..........................................................16
         3.2      Authorization..................................................................................17
         3.3      No Violation...................................................................................17
         3.4      No Consent Required............................................................................17
         3.5      Issuance.......................................................................................18
         3.6      Litigation.....................................................................................18
         3.7      Investment Representations.....................................................................18
         3.8      SEC Filings....................................................................................19
         3.9      Brokers or Finders.............................................................................19

ARTICLE 4 - REPRESENTATIONS AND WARRANTIES OF ISIS...............................................................19

         4.1      Organization and Good Standing; Power..........................................................19
         4.2      Authorization..................................................................................19
         4.3      No Violation...................................................................................20
         4.4      No Consent Required............................................................................20
         4.5      Issuance.......................................................................................20
         4.6      Litigation.....................................................................................20
         4.7      Investment Representations.....................................................................21
         4.8      SEC Filings....................................................................................21
         4.9      Brokers or Finders.............................................................................21

ARTICLE 5 - CLOSING DELIVERIES OF ISIS...........................................................................22

ARTICLE 6 - CLOSING DELIVERIES OF HYBRIDON.......................................................................22

ARTICLE 7 - REGISTRATION RIGHTS..................................................................................22

         7.1      Hybridon Registration Obligations..............................................................22
         7.2      Isis Registration Obligations..................................................................24
         7.3      Filing Requirements............................................................................25
         7.4      Limitation on Registration Obligations.........................................................26

ARTICLE 8 - POST EFFECTIVE COVENANTS.............................................................................27

         8.1      Isis's Voting Restrictions.....................................................................27
</TABLE>

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<TABLE>
<S>     <C>                                                                                                      <C>
         8.2      Hybridon's Voting Restrictions.................................................................27
         8.3      Restrictions on Isis's Sale of its Hybridon Common Stock.......................................27
         8.4      Restrictions on Hybridon's Sale of its Isis Common Stock.......................................28
         8.5      Certain Transactions Prohibited................................................................28
         8.6      Waiver of Restrictions.........................................................................29
         8.7      Reservation of Shares..........................................................................29
         8.8      Change in Control of Hybridon..................................................................29
         8.9      Change in Control of Isis......................................................................29

ARTICLE 9 - INDEMNIFICATION AND CONTRIBUTION.....................................................................29

         9.1      Indemnification................................................................................29

ARTICLE 10 - TERM AND EVENTS OF DEFAULT..........................................................................31

         10.1     Term...........................................................................................31
         10.2     Events of Default..............................................................................31
         10.3     Remedies Upon an Event of Default..............................................................32
         10.4     Survival.......................................................................................32
         10.5     Failure to Make Master Agreement Deliveries....................................................32

ARTICLE 11 - MISCELLANEOUS PROVISIONS............................................................................33

         11.1     Adjustments for Dividends, Splits, Reorganizations, Reclassifications, Etc.....................33
         11.2     Successors and Assigns.........................................................................33
         11.3     Notices........................................................................................34
         11.4     Entire Agreement; Amendments; Attachments......................................................35
         11.5     Severability...................................................................................35
         11.6     Investigation of the Parties...................................................................35
         11.7     Expenses.......................................................................................35
         11.8     Governing Law..................................................................................36
         11.9     Section Headings...............................................................................36
         11.10    Counterparts...................................................................................36
         11.11    Waiver and Modification........................................................................36
         11.12    No Waiver......................................................................................36
         11.13    Further Assurances.............................................................................36
         11.14    Dispute Resolution.............................................................................36
         11.15    No Consequential Damages.......................................................................36
         11.16    Confidentiality................................................................................37
</TABLE>

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                                MASTER AGREEMENT

     This Master Agreement (this "MASTER AGREEMENT") dated as of May 24, 2001,
is entered into by and between Hybridon, Inc., a Delaware corporation with its
principal place of business at Cambridge, Massachusetts ("HYBRIDON"), and Isis
Pharmaceuticals, Inc., a Delaware corporation with its principal place of
business at Carlsbad, California ("ISIS").

                                   WITNESSETH:

     WHEREAS, each of Hybridon and Isis owns or licenses intellectual property
that it wishes to license to the other; and

     WHEREAS, as partial consideration for such license of intellectual
property, Hybridon and Isis each intends to issue shares of common stock to the
other and Isis intends to pay Hybridon a cash payment contemporaneously with the
execution of this Master Agreement; and

     WHEREAS, each of the parties has expended significant efforts and resources
in the research and development of antisense technology and the payments to be
made under this Master Agreement to each party hereto will allow each party
hereto to recoup such expenditures; and

     WHEREAS, the parties hereto wish to enter into a binding agreement with
respect to the specific transactions and agreements set forth in this Master
Agreement; and

     WHEREAS, each of the parties to this Master Agreement desires to make
certain representations, warranties and agreements in connection with the
transactions contemplated hereby and also to prescribe various conditions
thereto.

     NOW, THEREFORE, in consideration of the foregoing recitals, the provisions
and the respective agreements hereinafter set forth, and other good and valuable
consideration, the receipt and sufficiency of which are hereby acknowledged, the
parties agree as follows:

                                   ARTICLE 1

                                  DEFINED TERMS
                                  -------------

     1.1 DEFINITIONS. Capitalized terms used herein and not otherwise defined
shall have the meanings set forth below:

     "AFFILIATE" means, 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 definition, "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-

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corporate entities, direct or indirect ownership of fifty percent (50%) or more
of the equity interest with the power to direct the management and policies of
such non-corporate entities.

     "AVERAGE CLOSING PRICE" means the Closing Prices of either Isis Common
Stock or Hybridon Common Stock, as the context requires, averaged over any
number of trading days as specified in this Master Agreement.

     "CHANGE IN CONTROL TRANSACTION" means (a) any sale or transfer of all or
substantially all of the assets of a Party to another individual, corporation or
entity ("Type A"), (b) any merger, consolidation, reorganization, share exchange
or business combination of a Party into or with another corporation or entity,
with the result that, upon conclusion of the transaction, the voting securities
of such Party immediately prior thereto do not represent (either by remaining
outstanding or by being converted into voting securities of the surviving
entity) more than 40% of the combined voting power of the voting securities of
the continuing or surviving corporation or entity of such consolidation, merger,
reorganization, share exchange or business combination ("Type B"), (c) any
direct or indirect acquisition of securities in which a "person" or "group" (as
used in Rule 13d-1 of the Exchange Act) directly or indirectly acquires
beneficial or record ownership of voting securities of a Party representing at
least 60% of the outstanding voting securities of such Party ("Type C"), or (d)
any event that results in the securities of a Party issued or issuable under
SECTION 2.2 (including SECTION 2.2(c)) or SECTION 2.3 (including SECTION
2.3(c)), as the case may be, no longer being a class of securities registered
with the Commission pursuant to Section 12 of the Exchange Act ("Type D").

     "CLOSING PRICE" means the midpoint of the high and low sale price of a
share of the Hybridon Common Stock or the Isis Common Stock, as applicable, on
any given day as reported on the Stock Market on which such security is traded.

     "COMMISSION" means the Securities and Exchange Commission.

     "EFFECTIVE DATE" means the date on which this Master Agreement is executed
by the Parties.

     "EXCHANGE ACT" means the Securities Exchange Act of 1934, as amended.

     "HYBRIDON COMMON STOCK" means the common stock, $.001 par value per share,
of Hybridon.

     "HYBRIDON INTELLECTUAL PROPERTY" shall have the meaning set forth in the
License Agreement.

     "HYBRIDON MARKET PRICE" means the Market Price of Hybridon Common Stock.

     "HYBRIDON MAXIMUM PRICE" means $3 for the first Hybridon Tranche Period, $4
for the second Hybridon Tranche Period and $5 for the third Hybridon Tranche
Period, each as may be adjusted from time to time pursuant to SECTION 11.1.

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     "HYBRIDON MINIMUM PRICE" means $1, as may be adjusted from time to time
pursuant to SECTION 11.1.

     "HYBRIDON RESTRICTED STOCK" means all shares of Hybridon Common Stock
issued to Isis pursuant to this Master Agreement and all shares of capital stock
which may, from time to time, be issued in respect of any such shares of capital
stock, including, without limitation, all shares issued as a stock dividend, as
a result of a stock split or pursuant to any reorganization, recapitalization,
merger, consolidation or similar event.

     "HYBRIDON TRANCHE PAYMENT" means the stock issuance to be made by Hybridon
to Isis with respect to a Hybridon Tranche Period or, if permitted, the cash to
be paid by Hybridon to Isis in lieu of such stock issuance.

     "HYBRIDON TRANCHE PAYMENT DATE" means, as to a Hybridon Tranche Period, the
next business day following the last day of the Hybridon Tranche Period or, if
prior to such day, the date on which the Hybridon Tranche Payment for such
Hybridon Tranche Period becomes payable pursuant to SECTION 2.2(b).

     "HYBRIDON TRANCHE PERIOD" means any one of the three successive
twelve-month periods commencing on the Effective Date.

     "ISIS COMMON STOCK" means the common stock, $.001 par value per share, of
Isis.

     "ISIS INTELLECTUAL PROPERTY" shall have the meaning set forth in the
License Agreement.

     "ISIS MARKET PRICE" means the Market Price of the Isis Common Stock.

     "ISIS MAXIMUM PRICE" means $14 for the first Isis Tranche Period, $20 for
the second and third Isis Tranche Period, and $26 for the fourth Isis Tranche
Period, each as may be adjusted from time to time pursuant to SECTION 11.1.

     "ISIS MINIMUM PRICE" means $7, as may be adjusted from time to time
pursuant to SECTION 11.1.

     "ISIS RESTRICTED STOCK" means all shares of Isis Common Stock issued to
Hybridon pursuant to this Master Agreement and all shares of capital stock which
may, from time to time, be issued in respect of any such shares of capital
stock, including, without limitation, all shares issued as a stock dividend, as
a result of a stock split or pursuant to any reorganization, recapitalization,
merger, consolidation or similar event.

     "ISIS TRANCHE PAYMENT" means the stock issuance to be made by Isis to
Hybridon with respect to an Isis Tranche Period or, if permitted, the cash to be
paid by Isis to Hybridon in lieu of such stock issuance.

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     "ISIS TRANCHE PAYMENT DATE" means, as to a Isis Tranche Period, the next
business day following the last day of the Isis Tranche Period or if prior to
such day, the date on which the Isis Tranche Payment becomes payable pursuant to
SECTION 2.3(b).

     "ISIS TRANCHE PERIOD" means any one of the four successive six-month
periods commencing on the Effective Date.

     "LOST PROFITS" means the product of (i) the number of shares of stock that
should have been (but were not) issued to the non-breaching Party (the "UNISSUED
STOCK") on the date specified in this Master Agreement (the "REQUIRED ISSUANCE
DATE") and (ii) the excess, if any, of (a) the highest Closing Price on any date
during the period from and including the Required Issuance Date (or the trading
day immediately preceding the Required Issuance Date if the required Issuance
Date is not a trading day on the Stock Market on which the stock of the
breaching Party trades) up to the date the Unissued Stock is actually issued to
the non-breaching Party (the "ACTUAL ISSUANCE DATE"), over (b) the Closing Price
on the Actual Issuance Date (or the trading day immediately preceding the Actual
Issuance Date if the Actual Issuance Date is not a trading day on the Stock
Market on which the stock of the breaching Party trades). In the event that the
breaching Party shall have distributed any dividends in cash, stock or other
property on or after the Required Issuance Date and on or prior to the Actual
Issuance Date, or fixed a record date for the determination of stockholders
entitled to receive a distribution of any dividends in cash, stock or other
property which record date occurs on or after the Required Issuance Date and on
or prior to the Actual Issuance Date, then Lost Profits shall also include the
total dividends in cash, stock or other property which the non-breaching Party
would have been otherwise entitled to receive if the Unissued Stock had been
issued to the non-breaching Party on the Required Issuance Date.

     "MARKET PRICE" means the Average Closing Price of Isis Common Stock or
Hybridon Common Stock, as the case may be, for the 20 trading days immediately
preceding a specified date.

     "PARTY" means Hybridon or Isis and "PARTIES" means Hybridon and Isis. As
used in this Master Agreement, references to third parties do not include a
Party or its Affiliates.

     "PER SHARE TRANSACTION VALUE" means

          (a) in the case of Type A Change in Control Transaction, the value, as
determined in good faith by the board of directors of the Party whose assets are
being sold, of the distributions which the holder of one share of Hybridon or
Isis Common Stock, as the case may be, would be entitled to receive (including
the dilutive effect of the Hybridon or Isis Common Stock to be issued under
Section 2.2(b)(iv) or Section 2.3(b)(iv), as the case may be, and of all other
shares of Hybridon or Isis Common Stock which may be issued upon the conversion
or exercise of securities of Hybridon or Isis, as the case may be, the issuance
of which would be dilutive in light of the amount that will be available for
distribution upon liquidation) if the Party selling its assets were to be
liquidated upon consummation of the Change in Control Transaction, PROVIDED,
HOWEVER, that in determining Per Share Transaction Value under this subparagraph
(a)

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no consideration shall be given to any earn-outs or any other future payments to
be determined after the consummation of the Change in Control Transaction,
except any payments of amounts held in escrow; or

          (b) in the case of a Type B Change in Control Transaction,

               (i) if the agreement of merger or other instrument governing the
     consideration to be issued provides for a cash purchase price exclusively,
     the cash purchase price that shall be paid in exchange for one share of
     Hybridon or Isis Common Stock, as the case may be, pursuant to the terms of
     the agreement of merger or other instrument governing the consideration to
     be issued;

               (ii) if the agreement of merger or other instrument governing the
     consideration to be issued provides for a fixed exchange ratio exclusively
     pursuant to which each share of Hybridon or Isis Common Stock, as the case
     may be, will be exchanged in the Change in Control Transaction solely for
     capital stock of the acquiror or other surviving entity (the acquiror or
     other surviving entity, the "Surviving Entity"), the value of the shares of
     capital stock of the Surviving Entity exchanged for one share of Hybridon
     or Isis Common Stock, as the case may be, pursuant to the terms of the
     agreement of merger or other instrument governing the consideration to be
     issued, which value shall be determined by multiplying:

                   (A) the average of the midpoint of the high and low sale
          price of a share of such Surviving Entity's capital stock on the Stock
          Market on which such capital stock is traded for the 20 trading days
          immediately preceding the date the Change in Control Transaction is
          consummated (or, if the Surviving Entity is not traded on a Stock
          Market, the fair market value of a share of such Surviving Entity's
          capital stock on the date immediately preceding the date the Change in
          Control Transaction is consummated, as determined in good faith by the
          board of directors of the Party which is a party to the Change in
          Control Transaction), by

                   (B) the number of shares of such Surviving Entity's capital
          stock to be exchanged in the Change in Control Transaction for each
          share of Hybridon or Isis Common Stock, pursuant to the terms of the
          agreement of merger or other instrument governing the consideration to
          be issued;

               (iii) if the agreement of merger or other instrument governing
     the consideration to be issued provides that the number of shares of
     capital stock of the Surviving Entity to be issued in exchange for one
     share of Hybridon or Isis Common Stock, as the case may be, shall be
     determined based on a fixed dollar amount of the Surviving Entity's capital
     stock, the fixed dollar value attributed by the parties to the Change in
     Control Transaction to one share of Hybridon or Isis Common Stock, as the
     case may be, pursuant to the terms of the agreement of merger or other
     instrument governing the consideration to be issued; or

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               (iv) if the agreement of merger or other instrument governing the
     consideration to be issued provides that the consideration to be exchanged
     in the Change in Control Transaction for one share of Hybridon or Isis
     Common Stock, as the case may be, shall consist of any combination of cash,
     stock (including stock issued pursuant to a fixed exchange ratio or a fixed
     dollar value) or other property of the Surviving Entity, the value of the
     consideration to be exchanged in the Change in Control Transaction for one
     share of Hybridon or Isis Common Stock, as the case may be, as determined
     in good faith by the Board of Directors of the Party which is a party to
     the Change in Control Transaction, which determination shall reflect the
     valuation methodologies provided in clauses (i), (ii) and/or (iii) above to
     the extent that an element or elements of the consideration is covered by
     clauses (i), (ii) and/or (iii);

     PROVIDED, HOWEVER, that in determining Per Share Transaction Value under
     this subparagraph (b) no consideration shall be given to any earn-outs or
     any other future payments to be determined after the consummation of the
     Change in Control Transaction, except any payments of amounts held in
     escrow; or

          (c) in the case of a Type C Change in Control Transaction, the Market
Price as of the date that such Change in Control Transaction becomes effective.

     "RESTRICTION PERIOD" shall mean ten (10) years or such lesser period as is
provided for in SECTION 8.8, in the case of Hybridon, or in SECTION 8.9, in the
case of Isis.

     "SECURITIES ACT" means the Securities Act of 1933, as amended.

     "STOCK MARKET" means the New York Stock Exchange, the American Stock
Exchange, the Nasdaq National Market, or the OTC Bulletin Board.

     "TRANSACTION DOCUMENTS" means this Master Agreement, the License Agreement,
and any other document or agreement executed in connection herewith or therewith
on the Effective Date.

                                   ARTICLE 2

           COLLABORATION AND LICENSE AGREEMENT AND OTHER CONSIDERATION
           -----------------------------------------------------------

     2.1 EXECUTION OF COLLABORATION AND LICENSE AGREEMENT. Subject to and upon
the terms and conditions set forth in this Master Agreement, and in reliance
upon the respective representations and warranties made herein by each of the
Parties on the Effective Date, each of Hybridon and Isis shall execute and
deliver to the other the Collaboration and License Agreement attached hereto as
EXHIBIT A (the "LICENSE AGREEMENT").

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     2.2 ADDITIONAL HYBRIDON CONSIDERATION.

          (a) HYBRIDON TRANCHE PAYMENTS. In consideration for the agreements
contained in this Master Agreement, and the licenses contemplated by the License
Agreement, unless paid or issued earlier pursuant to SECTION 2.2(b), on the next
business day following the end of each Hybridon Tranche Period, Hybridon shall
issue to Isis a number of shares of Hybridon Common Stock equal to $2,000,000
divided by the Hybridon Market Price as of the last day of such Hybridon Tranche
Period; provided however, that if such Hybridon Market Price is greater than the
Hybridon Maximum Price applicable to such Hybridon Tranche Period then such
Hybridon Market Price shall be deemed to be the Hybridon Maximum Price
applicable to such Hybridon Tranche Period for purposes of calculating the
number of shares issuable hereunder for such Hybridon Tranche Period; and
provided further, that if such Hybridon Market Price is less than the Hybridon
Minimum Price, then such Hybridon Market Price shall be deemed to be the
Hybridon Minimum Price for purposes of calculating the number of shares issuable
hereunder for such Hybridon Tranche Period.

          (b) ACCELERATION OF HYBRIDON TRANCHE PAYMENTS.

               (i) ACCELERATION EVENTS DURING FIRST HYBRIDON TRANCHE PERIOD. If
     at any time after the Effective Date the Hybridon Market Price as of any
     date on or before the last day of the first Hybridon Tranche Period:

                    (A) is greater than $5.00, then within ten (10) business
          days of such date, Hybridon shall issue to Isis 1,566,667 shares of
          Hybridon Common Stock less any shares previously issued or then
          issuable to Isis pursuant to SECTIONS 2.2(b)(i)(B) or (C), in lieu of
          all Hybridon Tranche Payments, and upon such date Hybridon shall have
          no further obligations under this SECTION 2.2 other than to issue the
          shares of Hybridon Common Stock that are otherwise issuable as of such
          date and as provided for under this SECTION 2.2(b)(i)(A).

                    (B) is greater than $4.00, but not greater than $5.00, then
          within ten (10) business days of such date, Hybridon shall issue to
          Isis 1,166,667 shares of Hybridon Common Stock less any shares
          previously issued or then issuable to Isis pursuant to SECTION
          2.2(b)(i)(C), in lieu of the first and second Hybridon Tranche
          Payments, and upon such date Hybridon shall have no further
          obligations under SECTION 2.2 with respect to the first and second
          Hybridon Tranche Periods, under this SECTION 2.2(b)(i)(B) or under
          SECTION 2.2(B)(i)(c) other than to issue the shares of Hybridon Common
          Stock that are otherwise issuable as of such date and as provided for
          under this SECTION 2.2(b)(i)(B).

                    (C) is greater than $3.00, but not greater than $4.00, then
          within ten (10) business days of such date, Hybridon shall issue to
          Isis 666,667 shares of Hybridon Common Stock in lieu of the first
          Hybridon Tranche Payment and upon such date Hybridon shall have no
          further obligations under SECTION 2.2 with respect to the first
          Hybridon Tranche Period or under this SECTION 2.2(b)(i)(c)

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          other than to issue the shares of Hybridon Common Stock provided for
          under this SECTION 2.2(b)(i)(C).

               (ii) ACCELERATION EVENTS DURING SECOND HYBRIDON TRANCHE PERIOD.
     If the Hybridon Market Price as of any date which ends after the last day
     of the first Hybridon Tranche Period and on or before the last day of the
     second Hybridon Tranche Period:

                    (A) is greater than $5.00, then within ten (10) business
          days of such date, Hybridon shall issue to Isis 900,000 shares (or
          400,000 shares if shares have been previously issued or are then
          issuable to Isis pursuant to SECTION 2.2(b)(i)(B)) of Hybridon Common
          Stock less any shares previously issued or then issuable to Isis
          pursuant to SECTION 2.2(b)(ii)(B), in lieu of all remaining Hybridon
          Tranche Payments, and upon such date Hybridon shall have no further
          obligations under this SECTION 2.2 other than to issue the shares of
          Hybridon Common Stock that are otherwise issuable as of such date and
          as provided for under this SECTION 2.2(b)(ii)(A).

                    (B) is greater than $4.00, but not greater than $5.00, and
          no shares have been previously issued or are then issuable to Isis
          pursuant to SECTION 2.2(b)(i)(B), then within ten (10) business days
          of such date, Hybridon shall issue to Isis 500,000 shares of Hybridon
          Common Stock in lieu of the second Hybridon Tranche Payment, and upon
          such date Hybridon shall have no further obligations under SECTION 2.2
          with respect to the second Hybridon Tranche Period or under this
          SECTION 2.2(b)(ii)(B) other than to issue the shares of Hybridon
          Common Stock provided for under this SECTION 2.2(b)(ii)(B).

                    (C) is less than $1.00, then within ten (10) business days
          of such date, Hybridon shall, at its option, either: (x) issue to Isis
          4,000,000 shares (or 2,000,000 shares if shares have been previously
          issued or are then issuable to Isis pursuant to either SECTION
          2.2(b)(i)(b) or SECTION 2.2(b)(ii)(B)) of Hybridon Common Stock or (y)
          pay to Isis $4,000,000 (or $2,000,000 if shares have been previously
          issued or are then issuable to Isis pursuant to either SECTION
          2.2(b)(i)(B) or 2.2(b)(ii)(B)), in lieu of all remaining Hybridon
          Tranche Payments, and upon such date Hybridon shall have no further
          obligations under this SECTION 2.2 other than to issue the shares of
          Hybridon Common Stock that are otherwise issuable as of such date and
          to issue the shares of Hybridon Common Stock or pay the cash provided
          for under this SECTION 2.2(b)(ii)(C).

               (iii) ACCELERATION EVENTS DURING THIRD HYBRIDON TRANCHE PERIOD.
     If the Hybridon Market Price as of any date which ends after the last
     day of the second Hybridon Tranche Period and on or before the last day of
     the third Hybridon Tranche Period:

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                    (A) is greater than $5.00, then within ten (10) business
          days of such date, Hybridon shall issue to Isis 400,000 shares of
          Hybridon Common Stock in lieu of all remaining Hybridon Tranche
          Payments, and upon such date Hybridon shall have no further
          obligations under this SECTION 2.2 other than to issue the shares of
          Hybridon Common Stock that are otherwise issuable as of such date and
          as provided for under this SECTION 2.2(b)(iii)(A).

                    (B) is less than $1.00, then within ten (10) business days
          of such date, Hybridon shall, at its option, either (x) issue to Isis
          2,000,000 shares of Hybridon Common Stock or (y) pay to Isis
          $2,000,000, in lieu of all remaining Hybridon Tranche Payments, and
          upon such date Hybridon shall have no further obligations under this
          SECTION 2.2 other than to issue the shares of Hybridon Common Stock
          that are otherwise issuable as of such date and to issue the shares of
          Hybridon Common Stock or pay the cash provided for under this SECTION
          2.2(b)(iii)(B).

               (iv) ACCELERATION FOR CHANGE IN CONTROL TRANSACTIONS. In the
     event of a Type A, Type B or Type C Change in Control Transaction that will
     be consummated prior to the third Hybridon Tranche Payment Date (such
     consummation date, the "HYBRIDON CLOSING DATE"), then immediately prior to
     such Hybridon Closing Date (or in the event of a Type C Change in Control
     Transaction, within five business days of such Hybridon Closing Date), in
     lieu of ALL OTHER remaining payments or share issuance obligations under
     this SECTION 2.2 (other than those Hybridon Tranche Payments for which the
     applicable Hybridon Tranche Payment Date is prior to the Hybridon Closing
     Date), Hybridon shall issue to Isis such number of shares of Hybridon
     Common Stock as is equal to the following:

                    $2,000,000 DIVIDED BY the Per Share Transaction Value of
                    such Change in Control Transaction, PROVIDED, HOWEVER, that
                    if the Per Share Transaction Value is less than the Hybridon
                    Minimum Price, then the $2,000,000 shall instead be DIVIDED
                    BY the Hybridon Minimum Price, and, PROVIDED FURTHER, that
                    if the Per Share Transaction Value is greater than the
                    Hybridon Maximum Price applicable to the third Hybridon
                    Tranche Period, then the $2,000,000 shall instead be DIVIDED
                    BY such Hybridon Maximum Price.

               PLUS, IF AND ONLY IF the Hybridon Closing Date is prior to the
               second Hybridon Tranche Payment Date:

                    an additional $2,000,000 DIVIDED BY the Per Share
                    Transaction Value of such Change in Control Transaction,
                    PROVIDED, HOWEVER, that if the Per Share Transaction Value
                    is less than the Hybridon Minimum Price, then the $2,000,000
                    shall instead be DIVIDED BY the Hybridon Minimum Price and
                    PROVIDED FURTHER that if the Per

                                     - 9 -

<PAGE>   13

                    Share Transaction Value is greater than the Hybridon Maximum
                    Price applicable to the second Hybridon Tranche Period, then
                    the $2,000,000 shall instead be DIVIDED BY such Hybridon
                    Maximum Price.

               PLUS, IF AND ONLY IF the Hybridon Closing Date will be or is
               prior to the first Hybridon Tranche Payment Date:

                    an additional $2,000,000 DIVIDED BY the Per Share
                    Transaction Value of such Change in Control Transaction,
                    PROVIDED, HOWEVER, that if the Per Share Transaction Value
                    is less than the Hybridon Minimum Price, then the $2,000,000
                    shall instead be DIVIDED BY the Hybridon Minimum Price and
                    PROVIDED FURTHER that if the Per Share Transaction Value is
                    greater than the Hybridon Maximum Price applicable to the
                    first Hybridon Tranche Period, then the $2,000,000 shall
                    instead be DIVIDED BY that Hybridon Maximum Price.

               (v) TYPE D CHANGE IN CONTROL TRANSACTION. On each Hybridon
     Tranche Payment Date from and after the occurrence of a Type D Change in
     Control Transaction, Hybridon shall pay to Isis $2,000,000 in cash in lieu
     of the shares of Hybridon Common Stock that Hybridon would otherwise be
     required to issue to Isis on such Hybridon Tranche Payment Date.

               (vi) Notwithstanding the other provisions of this SECTION 2.2(b),
     if Hybridon would be obligated under this Master Agreement to issue a
     number of shares of Hybridon Common Stock as would subject such issuance to
     the approval of Hybridon's stockholders under the rules and regulations of
     any Stock Market on which the Hybridon Common Stock is then traded,
     Hybridon may elect to not seek or obtain such approval and instead may
     issue such lesser number of shares as would not require such approval and
     may satisfy the balance of its obligation by a cash payment.

          (c) SUCCESSOR ENTITIES. In the event that Hybridon consummates a
merger, consolidation, reorganization, share exchange or business combination
which does not qualify as a Change in Control Transaction and Hybridon is not
the surviving corporation or entity following the consummation of such merger,
consolidation, reorganization, share exchange or business combination, then
Hybridon shall cause such surviving corporation or entity to comply with and be
bound by and subject to (i) the provisions of SECTIONS 2.2(a) and (b), including
requiring the surviving corporation or entity to issue common stock of such
surviving corporation or entity to Isis, and (ii) the registration obligations
and other provisions of this Master Agreement related to the stock so issued by
such surviving corporation or entity, to the same extent as such provisions were
applicable to Hybridon prior to the consummation of such merger, consolidation,
reorganization, share exchange or business combination.

                                     - 10 -

<PAGE>   14

     2.3 ADDITIONAL ISIS CONSIDERATION.

          (a) INITIAL CASH PAYMENT AND ISIS TRANCHE PAYMENTS. In consideration
for the agreements contained in this Master Agreement and the licenses
contemplated by the License Agreement, Isis shall: (i) unconditionally, and
irrespective of any breach of this Master Agreement or the License Agreement by
Hybridon, on or prior to 5:00 p.m. (Boston time), on Friday, June 1, 2001, pay
to Hybridon by wire transfer in immediately available funds, the sum of Fifteen
Million Dollars ($15,000,000), and (ii) unless paid or issued earlier pursuant
to SECTION 2.3(b), on the next business day following the end of each Isis
Tranche Period, issue to Hybridon such number of shares of Isis Common Stock
equal to $5,000,000 ($4,500,000 in the case of the fourth Isis Tranche Period),
divided by the Isis Market Price as of the last day of such Isis Tranche Period;
provided, however, that if such Isis Market Price is greater than the Isis
Maximum Price applicable to such Isis Tranche Period, then such Isis Market
Price shall be deemed to be the Isis Maximum Price applicable to such Isis
Tranche Period for purposes of calculating the number of shares issuable
hereunder for such Isis Tranche Period; and provided, further, that if such Isis
Market Price is less than the Isis Minimum Price applicable to such Isis Tranche
Period, then such Isis Market Price shall be deemed to be the Isis Minimum Price
applicable to such Isis Tranche Period for purposes of calculating the number of
shares issuable hereunder for such Isis Tranche Period. The Parties acknowledge
and agree that all payments to be made to Hybridon by Isis pursuant to this
Master Agreement will allow Hybridon to recoup the expenditures incurred by
Hybridon in the research and development of antisense technology undertaken by
Hybridon.

          (b) ACCELERATION OF ISIS TRANCHE PAYMENTS

               (i) ACCELERATION EVENTS DURING FIRST ISIS TRANCHE PERIOD. If at
     any time after the Effective Date the Isis Market Price as of any date
     which ends on or before the last day of the first Isis Tranche Period:

                    (A) is greater than $26.00, then within ten (10) business
          days of such date, Isis shall issue to Hybridon 1,030,220 shares of
          Isis Common Stock less any shares previously issued or then issuable
          to Hybridon pursuant to SECTION 2.3(b)(i)(B) or SECTION 2.3(b)(i)(C),
          in lieu of all Isis Tranche Payments, and upon such date Isis shall
          have no further obligations under this SECTION 2.3 other than to issue
          the shares of Isis Common Stock that are otherwise issuable on such
          date and as provided for under this SECTION 2.3(b)(i)(A).

                    (B) is greater than $20.00, but not greater than $26.00,
          then within ten (10) business days of such date, Isis shall issue to
          Hybridon 857,143 shares of Isis Common Stock less any shares
          previously issued or then issuable to Hybridon pursuant to SECTION
          2.3(b)(i)(C), in lieu of the first, second and third Isis Tranche
          Payments, and upon such date Isis shall have no further obligations
          under SECTION 2.3 with respect to the first, second and third Isis
          Tranche Periods, under this SECTION 2.3(b)(i)(B) or under SECTION
          2.3(b)(i)(C) other than to issue the

                                     - 11 -

<PAGE>   15

          shares of Isis Common Stock that are otherwise issuable on such date
          and as provided for under this SECTION 2.3(b)(i)(B).

                    (C) is greater than $14.00, but not greater than $20.00,
          then within ten (10) business days of such date, Isis shall issue to
          Hybridon 357,143 shares of Isis Common Stock in lieu of the first Isis
          Tranche Payment, and upon such date Isis shall have no further
          obligations under SECTION 2.3 with respect to the first Isis Tranche
          Period or under this SECTION 2.3(b)(i)(C) other than to issue the
          shares of Isis Common Stock provided for under this SECTION
          2.3(b)(i)(C).

                    (D) is less than $3.00, then within ten (10) business days
          of such date, Isis shall, at its option either: (x) issue to Hybridon
          2,785,714 shares less any shares previously issued or are then
          issuable to Hybridon pursuant to SECTION 2.3(b)(i)(B) or SECTION
          2.3(b)(i)(C), or (y) pay to Hybridon $19,500,000 (or $4,500,000 if
          shares have been previously issued or are then issuable to Hybridon
          pursuant to SECTION 2.3(b)(i)(B) or $14,500,000 if shares have been
          previously issued or are then issuable to Hybridon pursuant to SECTION
          2.3(b)(i)(C)), in lieu of all remaining Isis Tranche Payments, and
          upon such date Isis shall have no further obligations under this
          SECTION 2.3 other than to issue the shares of Isis Common Stock that
          are otherwise issuable on such date and to issue the shares of Isis
          Common Stock or pay the cash provided for under this SECTION
          2.3(b)(i)(D).

          (ii) ACCELERATION EVENTS DURING SECOND ISIS TRANCHE PERIOD. If the
Isis Market Price as of any date which ends after the last day of the first Isis
Tranche Period and on or before the last day of the second Isis Tranche Period:

               (A) is greater than $26.00, then within ten (10) business days of
     such date, Isis shall issue to Hybridon 673,077 shares (or 173,077 shares
     in the event shares have been previously issued or are then issuable to
     Hybridon pursuant to SECTION 2.3(b)(i)(B) or SECTION 2.3(b)(ii)(B)) of Isis
     Common Stock in lieu of all remaining Isis Tranche Payments, and upon such
     date Isis shall have no further obligations under this SECTION 2.3 other
     than to issue the shares of Isis Common Stock that are otherwise issuable
     on such date and as provided for under this SECTION 2.3(b)(ii)(A).

               (B) is greater than $20.00, but less than $26.00, and no shares
     have been previously issued or are then issuable to Hybridon pursuant to
     SECTION 2.3(b)(i)(B), then within ten (10) business days of such date, Isis
     shall issue to Hybridon 500,000 shares of Isis Common Stock in lieu of the
     second and third Isis Tranche Payments, and upon such date Isis shall have
     no further obligations under SECTION 2.3 with respect to the second and
     third Isis Tranche Periods or under this SECTION 2.3(b)(ii)(B) other than
     to issue shares of Isis Common Stock provided for under this SECTION
     2.3(b)(ii)(B).

                                     - 12 -

<PAGE>   16

               (C) is less than $3.00, then within ten (10) business days of
     such date, Isis shall, at its option, either: (x) issue to Hybridon
     2,071,429 shares (or 642,857 shares if shares have been previously issued
     or are then issuable to Hybridon pursuant to either SECTION 2.3(b)(i)(B) or
     SECTION 2.3(b)(ii)(B)) of Isis Common Stock or (y) pay to Hybridon
     $14,500,000 (or $4,500,000 if shares have been previously issued or are
     then issuable to Hybridon pursuant to either SECTION 2.3(b)(i)(B) or
     SECTION 2.3(b)(ii)(B)), in lieu of all remaining Isis Tranche Payments, and
     upon such date Isis shall have no further obligations under this SECTION
     2.3 other than to issue the shares of Isis Common Stock that are otherwise
     issuable on such date and to issue the shares of Isis Common Stock or pay
     the cash provided for under this SECTION 2.3(b)(ii)(C).

          (iii) ACCELERATION EVENTS DURING THIRD ISIS TRANCHE PERIOD. If the
Isis Market Price as of any date which ends after the last day of the second
Isis Tranche Period and on or before the last day of the third Isis Tranche
Period:

               (A) is greater than $26.00, then within ten (10) business days of
     such date, Isis shall issue to Hybridon 423,077 shares (or 173,077 shares
     if shares have been previously issued or are then issuable to Hybridon
     pursuant to SECTION 2.3(b)(i)(B), SECTION 2.3(b)(ii)(B) or SECTION
     2.3(b)(iii)(b)) of Isis Common Stock, in lieu of all remaining Isis Tranche
     Payments, and upon such date Isis shall have no further obligations under
     this SECTION 2.3 other than to issue the shares of Isis Common Stock that
     are otherwise issuable on such date and as provided for under this SECTION
     2.3(b)(iii)(A).

               (B) is greater than $20.00, but not greater than $26.00, and no
     shares have been previously issued or are then issuable to Hybridon
     pursuant to SECTION 2.3(b)(i)(B) or SECTION 2.3(b)(ii)(B), then within ten
     (10) business days of such date, Isis shall issue to Hybridon 250,000
     shares of Isis Common Stock in lieu of the third Isis Tranche Payments, and
     upon such date Isis shall have no further obligations under SECTION 2.3
     with respect to the third Isis Tranche Period or under this SECTION
     2.3(b)(iii)(B) other than to issue the shares of Isis Common Stock provided
     for under this SECTION 2.3(b)(III)(B).

               (C) is less than $7.00, then within ten (10) business days of
     such date, Isis shall, at its option, either: (x) issue to Hybridon
     1,357,143 shares (or 642,857 shares if shares have been previously issued
     or are then issuable to Hybridon pursuant to SECTION 2.3(b)(i)(B), SECTION
     2.3(b)(ii)(B) or SECTION 2.3(b)(iii)(B)) of Isis Common Stock or (y) pay to
     Hybridon $9,500,000 (or $4,500,000 if shares have been previously issued or
     are then issuable to Hybridon pursuant to SECTION 2.3(b)(i)(B), SECTION
     2.3(b)(ii)(B) or SECTION 2.3(b)(iii)(B)), in lieu of all remaining Isis
     Tranche Payments, and upon such date Isis shall have no further obligations
     under this SECTION 2.3 other than to issue the shares of

                                     - 13 -

<PAGE>   17

     Isis Common Stock that are otherwise issuable on such date and to issue the
     shares of Isis Common Stock or pay the cash provided for under this SECTION
     2.3(b)(III)(C).

          (iv) ACCELERATION EVENTS DURING FOURTH ISIS TRANCHE PERIOD. If the
Isis Market Price as of any date which ends after the last day of the third Isis
Tranche Period and on or before the last day of the fourth Isis Tranche Period:

               (A) is greater than $26.00, then within ten (10) business days of
     such date, Isis shall issue to Hybridon 173,077 shares of Isis Common Stock
     in lieu of all remaining Isis Tranche Payments, and upon such date Isis
     shall have no further obligations under this SECTION 2.3 other than to
     issue the share of Isis Common Stock that are otherwise issuable on such
     date and as provided for under this SECTION 2.3(b)(iv)(A).

               (B) is less than $7.00, then within ten (10) business days of
     such date, Isis shall, at its option either: (x) issue to Hybridon 642,857
     shares of Isis Common Stock or (y) pay Hybridon $4,500,000, in lieu of all
     remaining Isis Tranche Payments, and upon such date Isis shall have no
     further obligations under this SECTION 2.3 other than to issue the shares
     of Isis Common Stock that are otherwise issuable on such date and to issue
     the shares of Isis Common Stock or pay the cash provided for under this
     SECTION 2.3(b)(iv)(B).

          (v) ACCELERATION FOR CHANGE IN CONTROL TRANSACTIONS. In the event of a
Type A, Type B or Type C Change in Control Transaction that will be consummated
prior to the fourth Isis Tranche Payment Date (such consummation date, the "ISIS
CLOSING DATE"), then immediately prior to such Isis Closing Date (or in the
event of a Type C Change in Control Transaction, within five business days of
such Isis Closing Date), in lieu of ALL OTHER remaining payments or share
issuance obligations under this SECTION 2.3 (other than those Isis Tranche
Payments for which the applicable Isis Tranche Payment Date is prior to the Isis
Closing Date), Isis shall issue to Hybridon such number of shares of Isis Common
Stock as is equal to the following:

                    $4,500,000 DIVIDED BY the Per Share Transaction Value,
                    PROVIDED, HOWEVER, that if the Per Share Transaction Value
                    is less than the Isis Minimum Price applicable to the fourth
                    Isis Tranche Period, then the $4,500,000 shall instead be
                    DIVIDED BY the Isis Minimum Price applicable to the fourth
                    Isis Tranche Period, and, PROVIDED FURTHER, that if the Per
                    Share Transaction Value is greater than the Isis Maximum
                    Price applicable to the fourth such Isis Tranche Period,
                    then the $4,500,000 shall instead be DIVIDED BY such Isis
                    Maximum Price.

               PLUS, IF AND ONLY IF the Isis Closing Date will be or is prior to
               the third Isis Tranche Payment Date:

                                     - 14 -

<PAGE>   18

                    an additional $5,000,000 DIVIDED BY the Per Share
                    Transaction Value, PROVIDED, HOWEVER, that if Per Share
                    Transaction Price is less than the Isis Minimum Price
                    applicable to the third Isis Tranche Period, then the
                    $5,000,000 shall instead be DIVIDED BY the Isis Minimum
                    Price applicable to the third Isis Tranche Period, and,
                    PROVIDED FURTHER, that if the Per Share Transaction Value is
                    greater than the Isis Maximum Price applicable to the third
                    Isis Tranche Period, then the $5,000,000 shall instead be
                    DIVIDED BY such Isis Maximum Price.

               PLUS, IF AND ONLY IF the Isis Closing Date will be or is prior to
               the second Isis Tranche Payment Date:

                    an additional $5,000,000 DIVIDED BY the Per Share
                    Transaction Price, PROVIDED, HOWEVER, that if the Per Share
                    Transaction Price is less than the Isis Minimum Price
                    applicable to the second Isis Tranche Period, then the
                    $5,000,000 shall instead be DIVIDED BY the Isis Minimum
                    Price applicable to the second Isis Tranche Period, and,
                    PROVIDED FURTHER, that if the Per Share Transaction Value is
                    greater than the Isis Maximum Price applicable to the second
                    Isis Tranche Period, then the $5,000,000 shall instead be
                    DIVIDED BY such Isis Maximum Price.

               PLUS, IF AND ONLY IF the Isis Closing Date will be or is prior to
               the first Isis Tranche Payment Date:

                    an additional $5,000,000 DIVIDED BY the Per Share
                    Transaction Price, PROVIDED, HOWEVER, that if Per Share
                    Transaction Price is less than the Isis Minimum Price
                    applicable to the first Isis Tranche Period, then the
                    $5,000,000 shall instead be DIVIDED BY the Isis Minimum
                    Price applicable to the first Isis Tranche Period, and,
                    FURTHER PROVIDED, that if the Per Share Transaction Value is
                    greater than the Isis Maximum Price applicable to the first
                    Isis Tranche Period, then the $5,000,000 shall instead be
                    DIVIDED BY such Isis Maximum Price.

               (vi) TYPE D CHANGE IN CONTROL TRANSACTION. On each Isis Tranche
     Payment Date from and after the occurrence of a Type D Change in Control
     Transaction, Isis shall pay to Hybridon $5,000,000 ($4,500,000 in the case
     of the fourth Isis Tranche Payment Date) in lieu of the shares of Isis
     Common Stock that Isis would otherwise be required to issue to Hybridon on
     such Isis Tranche Payment Date.

               (vii) Notwithstanding the other provisions of this SECTION
     2.3(b), if Isis would be obligated under this Master Agreement to issue a
     number of shares of Isis Common Stock as would subject such issuance to the
     approval of Isis's stockholders

                                     - 15 -

<PAGE>   19

     under the rules and regulations of the Stock Market on which the Isis
     Common Stock is then traded, Isis may elect to not seek or obtain such
     approval and instead may issue such lesser number of shares as would not
     require such approval and may satisfy the balance of its obligation by a
     cash payment.

          (c) SUCCESSOR ENTITIES. In the event that Isis consummates a merger,
consolidation, reorganization, share exchange or business combination which does
not qualify as a Change in Control Transaction and Isis is not the surviving
corporation or entity following such merger, consolidation, reorganization,
share exchange or business combination, then Isis shall cause such surviving
corporation or entity to comply with and be bound by and subject to (i) the
provisions of SECTIONS 2.3(a) and (b), including requiring the surviving
corporation or entity to issue common stock of such surviving corporation or
entity to Hybridon, and (ii) the registration obligations and other provisions
of this Master Agreement related to the stock so issued by Isis or such
surviving corporation or entity, all to the same extent as such provisions were
applicable to Isis prior to the merger, consolidation, reorganization, share
exchange or business combination.

          2.4 RESTRICTIVE LEGEND. Each certificate for the shares of Hybridon
Common Stock or Isis Common Stock, whichever is applicable, issuable under this
ARTICLE 2 shall be stamped or otherwise imprinted with legends in substantially
the following form:

                  "THE SECURITIES REPRESENTED BY THIS CERTIFICATE HAVE BEEN
         ACQUIRED FOR INVESTMENT AND HAVE NOT BEEN REGISTERED UNDER THE
         SECURITIES ACT OF 1933. NEITHER THESE SECURITIES NOR ANY INTEREST
         THEREIN MAY BE SOLD, PLEDGED, HYPOTHECATED, TRANSFERRED OR OTHERWISE
         DISPOSED OF IN THE ABSENCE OF SUCH REGISTRATION AND IN COMPLIANCE WITH
         APPLICABLE STATE SECURITIES LAWS OR THE DELIVERY OF AN OPINION
         REASONABLY SATISFACTORY TO THE COMPANY STATING THAT THERE IS A VALID
         EXEMPTION THEREFROM UNDER SUCH ACT AND THE RULES AND REGULATIONS
         THEREUNDER AND SUCH STATE SECURITIES LAWS."

                                   ARTICLE 3

                   REPRESENTATIONS AND WARRANTIES OF HYBRIDON
                   ------------------------------------------

     As an inducement to Isis to enter into and perform its obligations under
this Master Agreement and License Agreement, Hybridon hereby represents
and warrants to Isis as of the date hereof as follows:

     3.1 ORGANIZATION AND GOOD STANDING; POWER. Hybridon is a corporation duly
organized, validly existing and in good standing under the laws of the State of
Delaware and has full power and authority to execute and deliver this Master
Agreement and the other Transaction Documents to which it is a party, to perform
its obligations hereunder and thereunder and to consummate the transactions
contemplated hereby and thereby.

                                     - 16 -

<PAGE>   20

     3.2 AUTHORIZATION. The execution and delivery by Hybridon of this Master
Agreement and the other Transaction Documents to which it is a party, the
performance by Hybridon of its obligations hereunder and thereunder, and the
consummation by Hybridon of the transactions contemplated hereby and thereby
have been duly authorized by all necessary corporate action on the part of
Hybridon. This Master Agreement and the other Transaction Documents have been
duly executed and delivered by Hybridon and constitute the legal, valid and
binding obligations of Hybridon, enforceable against Hybridon in accordance with
their respective terms, except (a) that enforcement may be limited by (i)
applicable bankruptcy, insolvency, reorganization, arrangement, moratorium or
other similar laws affecting creditors' rights, and (ii) general equity
principles and limitations on the availability of equitable relief, including
specific performance, and (b) that any rights to indemnity or contribution
hereunder or thereunder may be limited by state and federal securities laws and
by public policy considerations.

     3.3 NO VIOLATION. The execution, delivery and performance by Hybridon of
this Master Agreement and the other Transaction Documents to which it is a party
and the consummation by Hybridon of the transactions contemplated hereby and
thereby do not and will not:

          (a) conflict with, result in the breach, modification, termination or
violation of, or loss of any benefit under, constitute a default under,
accelerate the performance required by, result in or give rise to a right to
amend or modify the terms of, result in the creation of any lien upon any assets
or properties, or in any manner release any party thereto from any obligation
under, any mortgage, note, bond, indenture, contract, agreement, lease, license
or other instrument or obligation to which Hybridon is a party or by which
Hybridon's assets or property are bound;

          (b) conflict with, violate or result in any loss of benefit under, any
permit, concession, franchise, order, judgment, writ, injunction, regulation,
statute or decree; to which it is subject, or

          (c) conflict with or violate any provision of the Certificate of
Incorporation or Bylaws, each as heretofore amended, of Hybridon,

     except where, in the case of (a) and (b) above, such event would not,
individually or in the aggregate with other such events, adversely affect the
rights of Isis under this Master Agreement and the Transaction Documents or
subject Isis to any material liability (contingent or otherwise).

     3.4 NO CONSENT REQUIRED. No consent, approval, order or authorization of,
or declaration, filing or registration with, any person, entity or governmental
authority is required to be made or obtained by Hybridon in connection with the
authorization, execution, delivery or performance of this Master Agreement, the
other Transaction Documents to which it is a party or the transactions
contemplated hereby or thereby, except for the filing of registration statements
and other reports with the Commission, filings related to compliance with the
Securities Act, the

                                     - 17 -

<PAGE>   21

Exchange Act and state securities laws and any filings with the Stock Market on
which the Hybridon Common Stock is traded.

     3.5 ISSUANCE. The shares of Hybridon Restricted Stock to be delivered by
Hybridon hereunder have been duly authorized and, when issued and delivered in
accordance with the terms of this Master Agreement, will be validly issued,
fully paid and non-assessable and will not be issued in violation of any
preemptive rights, rights of first refusal or similar rights.

     3.6 LITIGATION. There is no litigation or governmental or administrative
proceeding or investigation pending or, to the knowledge of Hybridon, threatened
in writing against Hybridon or its Affiliates which, individually or in the
aggregate, reasonably would be expected to have a material adverse effect on the
Hybridon Intellectual Property or which would prevent or hinder Hybridon from
performing its obligations under this Master Agreement or the other Transaction
Documents to which it is a party.

     3.7 INVESTMENT REPRESENTATIONS.

          (a) Hybridon is capable of evaluating the merits and risks of an
investment in Isis Restricted Stock. Hybridon has not been formed solely for the
purpose of entering into the transactions contemplated in this Master Agreement
and is acquiring the Isis Restricted Stock for investment for its own account,
not as a nominee or agent, and not with the view to, or for resale, distribution
or fractionalization thereof (except in connection with a registered offering),
in whole or in part, and no other person has a direct or indirect interest,
beneficial or otherwise in the Isis Restricted Stock, except in compliance with
securities laws.

          (b) Hybridon acknowledges its understanding that the private placement
and sale to Hybridon of the Isis Restricted Stock to it is exempt from
registration under the Securities Act by virtue of the provisions of Regulation
D. In furtherance thereof, Hybridon represents and warrants that it is an
"accredited investor" as that term is defined in Regulation D.

          (c) Hybridon agrees that it shall not sell or otherwise transfer any
of the Isis Restricted Stock without registration under the Securities Act
unless it shall deliver to Isis an opinion of counsel reasonably satisfactory to
Isis that an exemption from registration is available. Hybridon fully
understands and agrees that it must bear the total economic risk of its purchase
of Isis Restricted Stock for an indefinite period of time because, among other
reasons, the Isis Restricted Stock will not have been registered under the
Securities Act or under the securities laws of any applicable state or other
jurisdiction and, therefore, cannot be resold, pledged, assigned or otherwise
disposed of unless subsequently registered under the Securities Act and under
applicable state securities laws or unless an exemption from such registration
is available. Hybridon understands that Isis is under no obligation to register
the Isis Restricted Stock on its behalf with the exception of certain
registration rights as set forth herein. Hybridon understands the lack of
liquidity and the restrictions on transfer on the Isis Restricted Stock and that
the acquisition of Isis Restricted Stock is suitable only for a person or entity
of adequate financial means that has no need for liquidity of its investment and
that can afford a total loss of its investment.

                                     - 18 -

<PAGE>   22

     3.8 SEC FILINGS. Except for the filing of its Annual Report on Form 10-K
for the year ended December 31, 1999, which was not timely filed, since January
1, 1998, Hybridon has filed with the Commission all forms, reports, schedules,
statements, exhibits and other documents (collectively, the "SEC FILINGS")
required to be filed by Hybridon pursuant to Section 13, 14 or 15(d) of the
Exchange Act on or before the date required to be filed with the Commission. At
the time filed, Hybridon's SEC Filings, including without limitation, any
financial statements, exhibits and schedules included therein or documents
incorporated therein by reference, to Hybridon's knowledge, (i) did not contain
any untrue statement of a material fact or omit to state a material fact
required to be stated therein or necessary in order to make the statements
therein, in light of the circumstances under which they were made, not
misleading and (ii) complied in all material respects with the applicable
requirements of the Securities Act or the Exchange Act, as the case may be.

     3.9 BROKERS OR FINDERS. There have been no investment bankers, brokers or
finders used by Hybridon in connection with the transactions contemplated by the
Transactions Documents and no such persons or entities are entitled to a fee or
compensation in respect thereof.

                                   ARTICLE 4

                     REPRESENTATIONS AND WARRANTIES OF ISIS
                     --------------------------------------

     As an inducement to Hybridon to enter into and perform its obligations
under this Master Agreement and the License Agreement, Isis hereby represents
and warrants to Hybridon as of the date hereof as follows:

     4.1 ORGANIZATION AND GOOD STANDING; POWER. Isis is a corporation duly
organized, validly existing and in good standing under the laws of the State of
Delaware and has full power and authority to execute and deliver this Master
Agreement and the other Transaction Documents to which it is a party, to perform
its obligations hereunder and thereunder and to consummate the transactions
contemplated hereby and thereby.

     4.2 AUTHORIZATION. The execution and delivery by Isis of this Master
Agreement and the other Transaction Documents to which it is a party, the
performance by Isis of its obligations hereunder and thereunder, and the
consummation by Isis of the transactions contemplated hereby and thereby have
been duly authorized by all necessary corporate action on the part of Isis. This
Master Agreement and the other Transaction Documents have been duly executed and
delivered by Isis and constitute the legal, valid and binding obligations of
Isis, enforceable against Isis in accordance with their respective terms, except
(a) that enforcement may be limited by (i) applicable bankruptcy, insolvency,
reorganization, arrangement, moratorium or other similar laws affecting
creditors' rights, and (ii) general equity principles and limitations on the
availability of equitable relief, including specific performance, and (b) that
any rights to indemnity or contribution hereunder or thereunder may be limited
by state and federal securities laws and by public policy considerations.

                                     - 19 -

<PAGE>   23

     4.3 NO VIOLATION. The execution, delivery and performance by Isis of this
Master Agreement and the other Transaction Documents to which it is a party and
the consummation by Isis of the transactions contemplated hereby and thereby do
not and will not:

          (a) conflict with, result in the breach, modification, termination or
violation of, or loss of any benefit under, constitute a default under,
accelerate the performance required by, result in or give rise to a right to
amend or modify the terms of, result in the creation of any lien upon any assets
or properties, or in any manner release any party thereto from any obligation
under, any material mortgage, note, bond, indenture, contract, agreement, lease,
license or other instrument or obligation to which Isis is a party or Isis's
assets or property are bound;

          (b) conflict with, violate or result in any loss of benefit under, any
permit, concession, franchise, order, judgment, writ, injunction, regulation,
statute or decree to which it is subject; or

          (c) conflict with or violate any provision of the Certificate of
Incorporation or Bylaws, each as heretofore amended, of Isis,

     except where, in the case of (a) and (b) above, such event would not,
individually or in the aggregate with other such events, adversely affect the
rights of Hybridon under this Master Agreement and the other Transaction
Documents or subject Hybridon to any material liability (contingent or
otherwise).

     4.4 NO CONSENT REQUIRED. No consent, approval, order or authorization of,
or declaration, filing or registration with, any person, entity or governmental
authority is required to be made or obtained by Isis in connection with the
authorization, execution, delivery or performance of this Master Agreement, the
other Transaction Documents to which it is a party or the transactions
contemplated hereby or thereby, except for the filing of registration statements
and other reports with the Commission, filings related to compliance with the
Securities Act, the Exchange Act and state securities laws and any filings with
the Stock Market on which the Isis Common Stock is listed.

     4.5 ISSUANCE. The shares of Isis Restricted Stock to be delivered by Isis
hereunder have been duly authorized and, when issued and delivered in accordance
with the terms of this Master Agreement, will be validly issued, fully paid and
non-assessable and will not be issued in violation of any preemptive rights,
rights of first refusal or similar rights.

     4.6 LITIGATION. There is no litigation or governmental or administrative
proceeding or investigation pending or, to the knowledge of the Isis, threatened
in writing against Isis or its Affiliates which, individually or in the
aggregate, reasonably would be expected to have a material adverse effect on the
Isis Intellectual Property or which would prevent or hinder Isis from performing
its obligations under this Master Agreement or the other Transaction Documents
to which it is a party.

                                     - 20 -

<PAGE>   24

     4.7 INVESTMENT REPRESENTATIONS.

          (a) Isis is capable of evaluating the merits and risks of an
investment in Hybridon Restricted Stock. Isis has not been formed solely for the
purpose of entering into the transactions contemplated in this Master Agreement
and is acquiring the Hybridon Restricted Stock for investment for its own
account, not as a nominee or agent, and not with the view to, or for resale,
distribution or fractionalization thereof, (except in connection with a
registered offering), in whole or in part, and no other person has a direct or
indirect interest, beneficial or otherwise in the Hybridon Restricted Stock.

          (b) Isis acknowledges its understanding that the private placement and
sale to Isis of the Hybridon Restricted Stock to it is exempt from registration
under the Securities Act by virtue of the provisions of Regulation D. In
furtherance thereof, Isis represents and warrants that it is an "accredited
investor" as that term is defined in Regulation D.

          (c) Isis agrees that it shall not sell or otherwise transfer any of
the Hybridon Restricted Stock without registration under the Securities Act
unless it shall deliver to Hybridon an opinion of counsel reasonably
satisfactory to Isis that an exemption from registration is available. Isis
fully understands and agrees that it must bear the total economic risk of its
purchase of Hybridon Restricted Stock for an indefinite period of time because,
among other reasons, the Hybridon Restricted Stock will not have been registered
under the Securities Act or under the securities laws of any applicable state or
other jurisdiction and, therefore, cannot be resold, pledged, assigned or
otherwise disposed of unless subsequently registered under the Securities Act
and under applicable state securities laws or unless an exemption from such
registration is available. Isis understands that Hybridon is under no obligation
to register the Hybridon Restricted Stock on its behalf with the exception of
certain registration rights as set forth herein. Isis understands the lack of
liquidity and the restrictions on transfer on the Hybridon Restricted Stock and
that the acquisition of Hybridon Restricted Stock is suitable only for a person
or entity of adequate financial means that has no need for liquidity of its
investment and that can afford a total loss of its investment.

     4.8 SEC FILINGS. Since January 1, 1998, Isis has filed with the Commission
all SEC Filings required to be filed by Isis pursuant to Section 13, 14 or 15(d)
of the Exchange Act on or before the date required to be filed with the
Commission. At the time filed, Isis's SEC Filings, including without limitation,
any financial statements, exhibits and schedules included therein or documents
incorporated therein by reference, to Isis's knowledge, (i) did not contain any
untrue statement of a material fact or omit to state a material fact required to
be stated therein or necessary in order to make the statements therein, in light
of the circumstances under which they were made, not misleading and (ii)
complied in all material respects with the applicable requirements of the
Securities Act or the Exchange Act, as the case may be.

     4.9 BROKERS OR FINDERS. There have been no investment bankers, brokers or
finders used by Isis in connection with the transactions contemplated by the
Transactions Documents and no such persons or entities are entitled to a fee or
compensation in respect thereof.

                                     - 21 -

<PAGE>   25

                                   ARTICLE 5

                           CLOSING DELIVERIES OF ISIS
                           --------------------------

     Isis hereby unconditionally agrees, irrespective of any breach of this
Master Agreement or the License Agreement by Hybridon, to deliver to Hybridon at
or prior to 5:00 p.m. (Boston time) on Friday, June 1, 2001:

          (a) An executed counterpart of the License Agreement;

          (b) A certificate of the appropriate officer of Isis certifying as to
the resolutions adopted by the board of directors authorizing the execution,
delivery, and performance by Isis of this Master Agreement and the License
Agreement and the consummation of the transactions contemplated hereby and
thereby;

          (c) An opinion of counsel to Isis which shall address the Isis Common
Stock to be issued under this Master Agreement in regards to its due
authorization and, when issued, its being legally and validly issued, fully paid
and non-assessable.

          (d) The cash payment referred to in SECTION 2.3(a) above.

                                   ARTICLE 6

                         CLOSING DELIVERIES OF HYBRIDON
                         ------------------------------

     Isis shall have received at or prior to the Effective Date:

          (a) An executed counterpart of the License Agreement;

          (b) A certificate of the appropriate officer of Hybridon certifying as
to the resolutions adopted by the board of directors authorizing the execution,
delivery, and performance by Hybridon of this Master Agreement and the License
Agreement and the consummation of the transactions contemplated hereby and
thereby; and

          (c) An opinion of counsel to Hybridon which shall address the Hybridon
Common Stock to be issued under this Master Agreement in regards to its due
authorization, and, when issued, its being legally and validly issued, fully
paid and non-assessable.

                                   ARTICLE 7

                               REGISTRATION RIGHTS
                               -------------------

          7.1 HYBRIDON REGISTRATION OBLIGATIONS.

          (a) For each issuance of Hybridon Common Stock hereunder, Hybridon
shall, at its own expense:

                                     - 22 -

<PAGE>   26

               (i) prepare and file, within ten (10) business days of each such
     issuance of Hybridon Common Stock, with the Commission a registration
     statement to register for resale on the Stock Market on which Hybridon's
     Common Stock is then traded, the Hybridon Common Stock so issued and use
     its best efforts to cause such registration statement to be declared
     effective by the Commission as promptly as practicable; and

               (ii) prepare and file with the Commission such amendments and
     supplements to such registration statement and the prospectus used in
     connection therewith as may be necessary to keep such registration
     statement effective until the first anniversary of the date of such
     issuance of Hybridon Common Stock, or, if earlier, until such time as Isis
     shall have completed the distribution of all Hybridon Common Stock covered
     by the registration statement, and comply with the provisions of the
     Securities Act with respect to the disposition of all securities covered by
     such registration statement during such effective period in accordance with
     the intended methods of disposition by Isis, and cause the prospectus to be
     supplemented by any required prospectus supplement, and as so supplemented
     to be filed pursuant to Rule 424 under the Securities Act. Hybridon is
     entitled to withdraw such registration statement at such time as it no
     longer is required to keep such registration statement effective under this
     clause (ii) and following such withdrawal Isis shall have no further right
     to offer or sell any Hybridon Common Stock pursuant to such registration
     statement; and

               (iii) provide a transfer agent and registrar for all Hybridon
     Common Stock so issued to Isis not later than the effective date of such
     registration statement.

          (b) Isis will furnish to Hybridon in writing such information as
Hybridon may reasonably require from Isis, and otherwise reasonably cooperate
with Hybridon, in connection with any registration statement to be filed
pursuant to subparagraph (a) above.

          (c) Subject to SECTION 9.1, Hybridon will indemnify Isis against any
and all claims, losses, damages and liabilities (or actions in respect thereof)
arising out of or based on any untrue statement (or alleged untrue statement) of
any material fact contained in any prospectus, offering circular or other
document incident to any registration, qualification or compliance (or in any
related registration statement, notification or the like) or any omission (or
alleged omission) to state therein any material fact required to be stated
therein or necessary to make the statements therein, in light of the
circumstances in which they were made, not misleading, or any violation by
Hybridon of any rule or regulation promulgated under federal and state
securities laws applicable to Hybridon and relating to any action or inaction
required of Hybridon in connection with any such registration, qualification or
compliance, and Hybridon will reimburse Isis for any legal and any other
expenses reasonably incurred in connection with investigating or defending any
such claim, loss, damage, liability or action; provided, however, that Hybridon
will not be liable in any such case to the extent that any such claim, loss,
damage or liability arises out of or is based on any untrue statement or
omission based upon written information furnished to Hybridon in an instrument
duly executed by Isis for use in such

                                     - 23 -

<PAGE>   27

prospectus, offering circular or other document (or in any related registration
statement, notification or the like).

          (d) Subject to SECTION 9.1, Isis will indemnify Hybridon against any
and all claims, losses, damages and liabilities (or actions in respect thereof)
arising out of or based on any untrue statement (or alleged untrue statement) of
any material fact contained in any prospectus, offering circular or other
document incident to any registration, qualification or compliance (or in any
related registration statement, notification or the like) or any omission (or
alleged omission) to state therein any material fact required to be stated
therein or necessary to make the statement therein, in light of the circumstance
in which they were made, not misleading, and Isis will reimburse Hybridon for
any legal and any other expenses reasonably incurred in connection with
investigating or defending any such claim, loss, damage, liability or action;
provided, however, that this paragraph (e) shall apply only if (and only to the
extent that) such statement or omission was made in reliance upon written
information furnished to Hybridon in an instrument duly executed by Isis for use
in such prospectus, offering circular or other document (or related registration
statement, notification or the like) or any amendment or supplement thereto;
and, provided further, that Isis's liability hereunder with respect to any
particular registration shall be limited to an amount equal to the net proceeds
received by Isis from the Hybridon Common Stock sold by Isis under such
registration statement.

     7.2 ISIS REGISTRATION OBLIGATIONS.

          (a) For each issuance of Isis Common Stock hereunder, Isis shall, at
its own expense:

               (i) prepare and file, within ten (10) business days of each such
     issuance of Isis Common Stock, with the Commission a registration statement
     to register for resale on the Stock Market on which Isis's Common Stock is
     then traded, the Isis Common Stock so issued and use its best efforts to
     cause such registration statement to be declared effective by the
     Commission as promptly as practicable;

               (ii) prepare and file with the Commission such amendments and
     supplements to such registration statement and the prospectus used in
     connection therewith as may be necessary to keep such registration
     statement effective until the first anniversary of the date of such
     issuance of Isis Common Stock, or, if earlier, until such time as Hybridon
     shall have completed the distribution of all Isis Common Stock covered by
     the registration statement, and comply with the provisions of the
     Securities Act with respect to the disposition of all securities of all
     Isis Common Stock covered by such registration statement during such
     effective period in accordance with the intended methods of disposition by
     Hybridon, and cause the prospectus to be supplemented by any required
     prospectus supplement, and as so supplemented to be filed pursuant to Rule
     424 under the Securities Act. Isis is entitled to withdraw such
     registration statement at such time as it no longer is required to keep
     such registration statement effective under this clause (ii) and following
     such withdrawal Hybridon shall have no further right to offer or sell any
     Isis Common Stock pursuant to such registration statement; and

                                     - 24 -

<PAGE>   28

               (iii) provide a transfer agent and registrar for all Isis Common
     Stock so issued to Hybridon not later than the effective date of such
     registration statement.

          (b) Hybridon will furnish to Isis in writing such information as Isis
may reasonably require from Hybridon, and otherwise reasonably cooperate with
Isis in connection with any registration to be filed pursuant to subparagraph
(a) above.

          (c) Subject to SECTION 9.1, Isis will indemnify Hybridon against any
and all claims, losses, damages and liabilities (or actions in respect thereof)
arising out of or based on any untrue statement (or alleged untrue statement) of
any material fact contained in any prospectus, offering circular or other
document incident to any registration, qualification or compliance (or in any
related registration statement, notification or the like) or any omission (or
alleged omission) to state therein any material fact required to be stated
therein or necessary to make the statements therein, in light of the
circumstances in which they were made, not misleading, or any violation by Isis
of any rule or regulation promulgated under federal and state securities laws
applicable to Isis and relating to any action or inaction required of Isis in
connection with any such registration, qualification or compliance, and Isis
will reimburse Hybridon for any legal and any other expenses reasonably incurred
in connection with investigating or defending any such claim, loss, damage,
liability or action; provided, however, that Isis will not be liable in any such
case to the extent that any such claim, loss, damage or liability arises out of
or is based on any untrue statement or omission based upon written information
furnished to Isis in an instrument duly executed by Hybridon for use in such
prospectus, offering circular or other document (or in any related registration
statement notification or the like).

          (d) Subject to SECTION 9.1, Hybridon will indemnify Isis against any
and all claims, losses, damages and liabilities (or actions in respect thereof)
arising out of or based on any untrue statement (or alleged untrue statement) of
any material fact contained in any prospectus, offering circular or other
document incident to any registration, qualification or compliance (or in any
related registration statement, notification or the like) or any omission (or
alleged omission) to state therein any material fact required to be stated
therein or necessary to make the statement therein, in light of the
circumstances in which they were made, not misleading, and Hybridon will
reimburse Isis for any legal and any other expenses reasonably incurred in
connection with investigating or defending any such claim, loss, damage,
liability or action; provided, however, that this paragraph (e) shall apply only
if (and only to the extent that) such statement or omission was made in reliance
upon written information furnished to Isis in an instrument duly executed by
Hybridon for use in such prospectus, offering circular or other document (or
related registration statement, notification or the like) or any amendment or
supplement thereto; and, provided further, that Hybridon's liability hereunder
with respect to any particular registration shall be limited to an amount equal
to the net proceeds received by Hybridon from the Isis Common Stock sold by
Hybridon in such registration.

     7.3 FILING REQUIREMENTS. With a view to making available to each of the
Parties the benefits of Rule 144 promulgated under the Securities Act ("RULE
144") and any other rule or

                                     - 25 -

<PAGE>   29

regulation of the SEC that may at any time permit such Parties to sell their
respective shares of Hybridon Common Stock or Isis Common Stock issued under
this Master Agreement to the public without registration or pursuant to a
registration on Form S-3, each of Hybridon and Isis covenants and agrees to take
commercially reasonable efforts to: (i) make and keep public information
available, as those terms are understood and defined in Rule 144; (ii) file with
the Commission in a timely manner all reports and other documents required of
such Party under the Securities Act and the Exchange Act, and (iii) furnish to
the other Party upon the other Party's request, (A) a copy of such Party's most
recent annual or quarterly report, and (B) such other information as may be
reasonably requested by the other Party in order to avail the other Party of any
rule or regulation of the Commission that permits the selling pursuant to a
registration statement. Notwithstanding the foregoing, a Party's covenants and
agreements under this SECTION 7.3 shall terminate and be of no further force or
effect from and after such time as the other Party may resell all of the Common
Stock of such Party issued to the other Party under this Master Agreement
pursuant to paragraph (k) of Rule 144 under the Securities Act or, if earlier,
such date as the other Party shall have sold or otherwise distributed all of
such Common Stock.

     7.4 LIMITATION ON REGISTRATION OBLIGATIONS. Notwithstanding anything in
this Master Agreement to the contrary, if either Party (the "Blocking Party")
shall furnish to the other Party (the "Selling Party") a certificate signed by
the President or Chief Executive Officer of the Blocking Party, stating that its
Board of Directors has made the good faith determination (i) that continued use
by the Selling Party, of a registration statement filed pursuant to ARTICLE 7
for purposes of effecting offers or sales of Common Stock of a Blocking Party,
pursuant thereto would require, under the Securities Act, premature disclosure
in the registration statement (or the prospectus relating thereto) of material,
nonpublic information concerning the Blocking Party, its business or prospects
or any of its proposed material transactions, (ii) that such premature
disclosure would be materially adverse to the Blocking Party, then (x) the
Blocking Party may postpone the filing or effectiveness of such registration
statement, or (y) suspend the right of the Selling Party to use the registration
statement (and the prospectus relating thereto) for purposes of effecting offers
or sales of Common Stock of the Blocking Party pursuant thereto. Notwithstanding
the foregoing, neither Party shall under any circumstances be entitled to
exercise its right to postpone the filing or effectiveness of, or suspend the
use of, a registration statement more than two (2) times in any twelve (12)
month period, and the aggregate number of days during which the filing or
effectiveness of, or the suspension of the use of, the registration statement
may be postponed or suspended shall not exceed ninety (90) days in any such (12)
month period. Each Party hereby covenants and agrees that it will not sell any
Isis Common Stock or Hybridon Common Stock, as the case may be, pursuant to a
registration statement filed under this ARTICLE 7 during a period in which the
ability to sell thereunder is suspended as set forth in this SECTION 7.4 and
will maintain in confidence the fact and content of any notice provided under
this SECTION 7.4.

     The effectiveness of a registration statement may not be postponed and the
rights of a Selling Party to sell shares under a registration statement may not
be suspended under this SECTION 7.4 unless the Blocking Party has similarly
suspended distribution rights under any other effective registration statement
of which it is the registrant (except for registration statements on

                                     - 26 -

<PAGE>   30

Form S-8) and has similarly suspended the rights of its officers and directors
to trade in its securities for at least the same 90 day period.

                                   ARTICLE 8

                            POST EFFECTIVE COVENANTS
                            ------------------------

     8.1 ISIS'S VOTING RESTRICTIONS. Isis agrees that, at all times during the
Restriction Period, at any meeting or vote by written consent in lieu thereof of
the stockholders of Hybridon, however called, Isis shall cause all outstanding
shares of Hybridon Restricted Stock that are beneficially owned by Isis or its
Affiliates as of the record date fixed for such meeting or on the date of a vote
by written consent to be voted in accordance with and in the same proportion as
the votes of the other stockholders of Hybridon, not including abstentions. By
way of example, if at Hybridon's annual meeting, stockholders holding at least
70% of the combined voting power of Hybridon's voting securities then
outstanding, excluding Isis, vote in favor of a proposal, 10% against and 20%
abstain, then Isis shall be required to vote 87.5% of its Hybridon Common Stock
in favor of such proposal and 12.5% against.

     8.2 HYBRIDON'S VOTING RESTRICTIONS. Hybridon agrees that, at all times
during the Restriction Period, at any meeting or vote by written consent in lieu
thereof of the stockholders of Isis, however called, Hybridon shall cause all
outstanding shares of Isis Restricted Stock that are beneficially owned by
Hybridon or its Affiliates as of the record date fixed for such meeting or on
the date of a vote by written consent to be voted in accordance with and in the
same proportion as the votes of the other stockholders of Isis, not including
abstentions. By way of example, if at Isis's annual meeting, stockholders
holding at least 70% of the combined voting power of Isis's voting securities
then outstanding, excluding Hybridon, vote in favor of a proposal, 10% against
and 20% abstain, then Hybridon shall be required to vote 87.5% of its Isis
Common Stock in favor of such proposal and 12.5% against.

     8.3 RESTRICTIONS ON ISIS'S SALE OF ITS HYBRIDON COMMON STOCK. During the
Restriction Period, Isis may only sell, assign, transfer or otherwise dispose of
, or engage in any short selling or hedging transaction in respect of (for
purposes of SECTIONS 8.3 and 8.4, "sell"), any of the Hybridon Restricted Stock,
whether in a private or public sale, pursuant to the conditions and restrictions
in this SECTION 8.3, PROVIDED, HOWEVER, that nothing in this SECTION 8.3 shall
prohibit Isis from transferring the Hybridon Restricted Stock to an Affiliate of
Isis that has agreed, in writing with Hybridon, to be bound by the terms of this
ARTICLE 8. During the Restriction Period, Isis shall not sell in any 180-day
period a number of shares of Hybridon Restricted Stock in excess of one percent
(1%) of the total outstanding shares of Hybridon Common Stock determined on an
as-converted basis (which shall be calculated by adding the total number of
shares of Hybridon Common Stock outstanding and the total number of shares of
Hybridon Common Stock issuable upon conversion of outstanding convertible
securities of Hybridon (excluding options and warrants)); PROVIDED, HOWEVER,
that in the event the Hybridon Market Price as of a specified date is less than
the Hybridon Minimum Price, then in the following 180 day period, Isis shall be
allowed to sell a number of shares of Hybridon Restricted Stock that

                                     - 27 -

<PAGE>   31

does not exceed three percent (3%) of the total outstanding shares of Hybridon
Common Stock determined on an as-converted basis. For the purposes of this
SECTION 8.3, (i) the number of outstanding shares of Hybridon Common Stock and
the number of outstanding shares of Hybridon Common Stock issuable upon
conversion of outstanding convertible securities of Hybridon (excluding options
and warrants) shall be the actual numbers at the time if known by Isis or, if
not known, the stated numbers of such shares reflected in Hybridon's most recent
filing of a Form 10-Q or Form 10-K.

     8.4 RESTRICTIONS ON HYBRIDON'S SALE OF ITS ISIS COMMON STOCK. During the
Restriction Period, Hybridon may only sell any of the Isis Restricted Stock,
whether in a private or public sale, pursuant to the conditions and restrictions
in this SECTION 8.4, PROVIDED, HOWEVER, that nothing in this SECTION 8.4 shall
prohibit Hybridon from transferring the Isis Restricted Stock to an Affiliate of
Hybridon that has agreed, in writing with Isis, to be bound by the terms of this
ARTICLE 8. During the Restriction Period, Hybridon shall not sell in any 180-day
period a number of shares of Isis Restricted Stock in excess of one percent (1%)
of the total outstanding shares of Isis Common Stock determined on an
as-converted basis (which shall be calculated by adding the total number of
shares of Isis Common Stock outstanding and the total number of shares of Isis
Common Stock issuable upon conversion of outstanding convertible securities of
Isis (excluding options and warrants)); provided, however, that in the event the
Isis Market Price as of a specified date is less than the Isis Minimum Price for
the Isis Tranche Period during which such date occurs, then in the following 180
day period, Hybridon shall be allowed to sell a number of shares of Isis
Restricted Stock that does not exceed three percent (3%) of the total
outstanding shares of Isis Common Stock determined on an as-converted basis. For
the purposes of this SECTION 8.4, the number of outstanding shares of Isis
Common Stock and the number of shares of Isis Common Stock issuable upon
conversion of outstanding convertible securities of Isis (excluding options and
warrants) shall be the actual numbers at the time if known by Hybridon or, if
not known, the stated numbers of such shares reflected in Isis's most recent
filing of a Form 10-Q or Form 10-K.

     8.5 CERTAIN TRANSACTIONS PROHIBITED. Notwithstanding any provision herein
to the contrary, for so long as a Party shall hold Isis Restricted Stock or
Hybridon Restricted Stock, as the case may be such Party agrees that it will not
and will cause its Affiliates to not: (i) except pursuant to SECTION 2.2 and
SECTION 2.3, whichever is applicable, acquire, directly or indirectly, by
purchase or otherwise, of record or beneficially, any capital stock of the other
Party, any securities of the other Party convertible into capital stock of the
other Party (which for purposes of this Master Agreement shall include without
limitation convertible notes), or any rights, options or warrants to acquire
capital stock of the other Party; (ii) "solicit" proxies with respect to voting
securities of the other Party under any circumstances or become a "participant"
in any "election contest" relating to the election of directors of the other
Party, as such terms are defined in Regulation 14A under the Exchange Act; (iii)
deposit any voting securities of the other Party in a voting trust or subject
them to a voting agreement or other agreement of similar effect; (iv) initiate,
propose or otherwise solicit stockholders of the other Party for the approval of
one or more stockholder proposals at any time, or induce or attempt to induce
any other person to initiate any stockholder proposal; (v) present, or propose
to present, publicly or

                                     - 28 -

<PAGE>   32

otherwise, to the other Party, its Board of Directors or its stockholders any
proposal or offer for a merger, tender or exchange offer or other form of
business combination involving the other Party, or effect, propose to effect or
cause to occur any of the foregoing; (vi) take any action individually or
jointly with any person, corporation, entity or group or assist any person,
corporation, entity or group in taking any action such Party could not take
individually under the terms of this Master Agreement, or (vii) take any action
which would be reasonably likely to require such Party to make a public
announcement regarding a possible transaction involving such Party.

     8.6 WAIVER OF RESTRICTIONS. Notwithstanding anything to the contrary set
forth herein, either Party may, at any time and from time to time, waive in
writing any of the conditions or restrictions contained in this ARTICLE 8. Each
Party agrees to keep any request for a waiver and the approval or denial thereof
confidential under the terms of Section 7.1 of the License Agreement.

     8.7 RESERVATION OF SHARES.

          (a) BY HYBRIDON. Hybridon will at all times reserve and keep
available, solely for issuance and delivery pursuant to this Master Agreement,
such number of shares of Hybridon Common Stock equal to the maximum number of
shares of Hybridon Restricted Stock as from time to time may be issuable under
this Master Agreement assuming the Hybridon Market Price is the Hybridon Minimum
Price.

          (b) BY ISIS. Isis will at all times reserve and keep available, solely
for issuance and delivery pursuant to this Master Agreement, such number of
shares of Isis Common Stock equal to the maximum number of shares of Isis
Restricted Stock as from time to time may be issuable under this Master
Agreement assuming the Isis Market Price is the Isis Minimum Price.

     8.8 CHANGE IN CONTROL OF HYBRIDON. In the event of a Change in Control
Transaction by Hybridon, then Isis's obligations in SECTIONS 8.1, 8.3 and 8.5
shall terminate and the Hybridon Common Stock restricted pursuant thereto shall
be released from such restrictions.

     8.9 CHANGE IN CONTROL OF ISIS. In the event of a Change in Control
Transaction by Isis, then Hybridon's obligations in SECTIONS 8.2, 8.4 and 8.5
shall terminate and the Isis Common Stock restricted pursuant thereto shall be
released from such restrictions.

                                   ARTICLE 9

                        INDEMNIFICATION AND CONTRIBUTION
                        --------------------------------

     9.1 INDEMNIFICATION. The following provisions shall govern the rights and
the duties of the Parties in the event a Party seeks indemnity from the other
Party under the provisions of either SECTIONS 7.1 or 7.2, or both, as the case
may be.

                                     - 29 -

<PAGE>   33

          (a) Each party entitled to indemnification (the "INDEMNIFIED PARTY")
shall give notice to the party required to provide indemnification (the
"INDEMNIFYING PARTY") promptly after such Indemnified Party has actual knowledge
of any claim as to which indemnity may be sought, and shall permit the
Indemnifying Party to assume the defense of any such claim or any litigation
resulting therefrom; PROVIDED, that counsel for the Indemnifying Party, who
shall conduct the defense of such claim or litigation, shall be approved by the
Indemnified Party (whose approval shall not be unreasonably withheld); and,
PROVIDED, FURTHER, that the failure of any Indemnified Party to give notice as
provided herein shall not relieve the Indemnifying Party of its obligations
except to the extent that the Indemnifying Party is adversely affected by such
failure. The Indemnified Party may participate in such defense at such party's
expense; PROVIDED, HOWEVER, that the Indemnifying Party shall pay such expense
if representation of such Indemnified Party by the counsel retained by the
Indemnifying Party would be inappropriate due to actual or potential conflicting
interests between the Indemnified Party and any other party represented by such
counsel in such proceeding; PROVIDED FURTHER that in no event shall the
Indemnifying Party be required to pay the expenses of more than one law firm per
jurisdiction as counsel for the Indemnified Party. The Indemnifying Party also
shall be responsible for the expenses of such defense if the Indemnifying Party
does not elect to assume such defense. No Indemnifying Party, in the defense of
any such claim or litigation shall, except with the consent of each Indemnified
Party, consent to entry of any judgment or enter into any settlement which does
not include as an unconditional term thereof the giving by the claimant or
plaintiff to such Indemnified Party of a release from all liability in respect
of such claim or litigation, and no Indemnified Party shall consent to entry of
any judgment or settle such claim or litigation without the prior written
consent of the Indemnifying Party which consent shall not be unreasonably
withheld.

          (b) In order to provide for just and equitable contribution in
circumstances in which the indemnification provided for in SECTIONS 7.1 and 7.2
is due in accordance with its terms but for any reason is held to be unavailable
to an Indemnified Party in respect to any expenses, losses, claims, damages and
liabilities referred to herein, then the Indemnifying Party shall, in lieu of
indemnifying such Indemnified Party, contribute to the amount paid or payable by
such Indemnified Party as a result of such losses, claims, damages or
liabilities to which such Party may be subject in such proportion as is
appropriate to reflect the relative fault of the Indemnified Party on the one
hand and the Indemnifying Party on the other in connection with the statements
or omissions which resulted in such losses, claims, damages or liabilities, as
well as any other relevant equitable considerations. The relative fault of the
Indemnified Party and the Indemnifying Party shall be determined by reference
to, among other things, whether the untrue or alleged untrue statement of a
material fact or the omission to state a material fact related to information
supplied by the Indemnified Party or the Indemnifying Party and the parties'
relative intent, knowledge, access to information and opportunity to correct or
prevent such statement or omission. Each Party agrees that it would not be just
and equitable if contribution pursuant to this SECTIONS 9.1(b) were determined
by pro rata allocation or by any other method of allocation which does not take
account of the equitable considerations referred to above. Notwithstanding the
provisions of this paragraph, (a) in no case shall any Party be liable or
responsible for any amount in excess of the net proceeds received by such Party
from

                                     - 30 -

<PAGE>   34

the offering of the securities of the other Party registered on its behalf under
either SECTION 7.1 or 7.2, as the case may be, and (b) the Party filing the
registration statement shall be liable and responsible for any amount in excess
of such proceeds; PROVIDED, HOWEVER, that no person guilty of fraudulent
misrepresentation (within the meaning of Section 11(f) of the Securities Act)
shall be entitled to contribution from any person who was not guilty of such
fraudulent misrepresentation. Any Party entitled to contribution will, promptly
after receipt of notice of commencement of any action, suit or proceeding
against such Party in respect of which a claim for contribution may be made
against another Party under this paragraph, notify such Party from whom
contribution may be sought, but the omission to so notify such Party from whom
contribution may be sought shall not relieve such Party from any other
obligation may have thereunder or otherwise under this paragraph except to the
extent that such Party is adversely affected by such failure. No Party shall be
liable for contribution with respect to any action, suit, proceeding or claim
settled without its prior written consent, which consent shall not be
unreasonably withheld.

                                   ARTICLE 10

                           TERM AND EVENTS OF DEFAULT
                           --------------------------

     10.1 TERM. This Master Agreement shall commence upon execution and remain
in effect for ten years.

     10.2 BREACH OF NONPAYMENT AND FAILURE TO COMPLY WITH ARBITRATION ORDER.

          (a) BREACH OF NONPAYMENT. In the event a Party is in breach of any its
obligations under either SECTION 2.2 or SECTION 2.3, then the non-breaching
Party may give written notice to the breaching Party of such breach. Within ten
(10) business days of the receipt by the breaching Party of such written notice,
the breaching Party shall cure the breach, 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, and (ii) at the same time, pay to the non-breaching Party the amount of
the payment which is not in dispute. Failure to either cure such breach OR take
the actions required under subsection (i) or (ii) above, whichever action is
applicable, shall be an "EVENT OF DEFAULT".

               If part or all of a payment is in dispute hereunder, either Party
may submit the dispute to arbitration pursuant to SECTION 11.14, in which case
the non-payment of the disputed portion shall not be deemed a breach during the
pendency of the arbitration. 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) attorneys' fees of the non-breaching Party, the fees of the
arbitrator and the costs and expenses of the arbitration, (B) any Lost Profits,
and (C) in the case the arbitrator finds that a cash payment was due, an

                                     - 31 -

<PAGE>   35

amount equal to interest at a 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.

          (b) FAILURE TO COMPLY WITH ARBITRATION ORDER. If an arbitrator has
rendered a ruling pursuant to Article VIII of the License Agreement that a Party
has materially breached this Master Agreement or the License 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 SECTION 2.2
or 2.3 as contemplated by SECTION 10.2(a) (the "ADVERSE RULING"), and 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 such failure shall be deemed an
"EVENT OF DEFAULT".

     10.3 REMEDIES UPON AN EVENT OF DEFAULT. Upon the occurrence of an Event of
Default and written notice to the defaulting Party, (i) the defaulting Party
shall have no further rights under this Master Agreement (except, in the event
that the licenses and sublicenses granted by the defaulting Party under the
License Agreement remain in effective under SECTION 9.2(d) of the License
Agreement, the right to receive Common Stock and cash of the non-defaulting
Party pursuant to SECTION 2.2 or 2.3, whichever is applicable and the right to
have such stock registered, and the provisions relating thereto under SECTION
7), but shall continue to be liable for all of its obligations under this Master
Agreement, including but not limited to the obligation to issue Isis or Hybridon
Common Stock or pay cash to the non-defaulting Party pursuant to SECTION 2.2 or
2.3, whichever is applicable, and (ii) the non-defaulting Party shall have no
further obligations under this Master Agreement other than its obligation to
issue Isis or Hybridon Common Stock or pay cash to the defaulting Party pursuant
to SECTION 2.2 or 2.3, whichever is applicable, and the obligations to register
such stock and the other obligations under SECTION 7 relating thereto, but shall
continue to have all of its rights under this Master Agreement, including but
not limited to the right to receive Common Stock and cash of the defaulting
Party pursuant to SECTION 2.2 or 2.3, whichever is applicable and the benefits
of any voting restrictions and trading restrictions imposed under ARTICLE 8 on
the other party, the benefits of any registration provisions under ARTICLE 7 and
rights arising out of any breach of representations or warranties or other
covenants of the defaulting Party under the Agreement.

     10.4 SURVIVAL. The terms and conditions in SECTIONS 7.1(a)(ii), 7.1(c),
7.1(d), 7.2(a)(ii), 7.2(c), 7.2(d) AND 7.4, ARTICLE 9 and SECTIONS 10.2, 10.3
and 11.14 shall survive termination or expiration of this Master Agreement.

     10.5 FAILURE TO MAKE MASTER AGREEMENT DELIVERIES. Notwithstanding any
provision in this Master Agreement to the contrary, if Isis breaches Section
2.3(a)(i) or Article 5 of this Master Agreement, Hybridon shall have the right,
at its sole election, effective immediately upon written notice to Isis, to
terminate this Master Agreement AB INITIO. The Parties hereby agree that
termination of this Master Agreement as provided in this Section 10.5 shall not
be the exclusive

                                     - 32 -

<PAGE>   36

remedy of Hybridon in the event of a breach of Section 2.3(a)(i) or Article 5 of
this Master Agreement by Isis and that Hybridon shall be entitled to seek any
and all other remedies to which Hybridon may be entitled at law or in equity,
including without limitation seeking to enforce the provisions of Section
2.3(a)(i) and Article 5 of this Master Agreement. In the event of any action by
Hybridon for payment under Section 2.3(a)(i) and Article 5 of this Master
Agreement, Hybridon shall be entitled to reimbursement of attorney's fees and
other collection costs incurred by Hybridon and 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 due commencing on the due
date through the date of actual payment.

                                   ARTICLE 11

                            MISCELLANEOUS PROVISIONS

     11.1 ADJUSTMENTS FOR DIVIDENDS, SPLITS, REORGANIZATIONS, RECLASSIFICATIONS,
ETC.

          (a) If after the date hereof (i) the outstanding shares of the Isis
Common Stock or Hybridon Common Stock, as the case may be (for purposes of this
SECTION 11.1(a), the "Subject Stock") shall be subdivided or split into a
greater number of shares or a dividend in Subject Stock shall be paid in respect
of such Subject Stock, (ii) the outstanding shares of Subject Stock are
combined, (iii) a Party shall pay a dividend in securities of the Party (other
than Subject Stock) or of the property (including cash) on the Subject Stock, or
(iv) there shall occur any merger, consolidation, capital reorganization or
reclassification in which the Subject Stock is converted or exchanged for
securities, cash or other property (other than as part of a Change of Control
Transaction), all dollar amounts and share quantities in this Master Agreement,
as well as the class or series of stock constituting the Subject Stock, shall be
adjusted to reflect such stock splits, stock dividend, combination, other
dividend, merger, consolidation, capital reorganization or reclassification
consistent with the economic intent of the parties, PROVIDED, HOWEVER, there
shall be no adjustments to the amount of any cash payments which either Party
may be obligated to make or have the election to make in lieu of the issuance of
shares of Subject Stock. After any event referenced in clauses (i) through (iv)
is consummated, if applicable, all references herein to Isis Common Stock or
Hybridon Common Stock, as the case may be, shall be deemed to refer to the
capital stock or property (including cash) into or for which the Subject Stock
was converted or exchanged, with the necessary changes in detail. All
calculations under this SECTION 11.1 shall be made to the nearest cent or whole
number amount for shares.

          (b) Upon the happening of any event referenced in clauses (i) through
(iv) in SECTION 11.1(a), the Party whose Common Stocks is so affected shall
forthwith give written notice thereof to the other Party stating the adjusted
figures and setting forth in reasonable detail the method of calculation and the
facts upon which such calculation is based.

     11.2 SUCCESSORS AND ASSIGNS. This Master Agreement shall be binding upon
and inure to the benefit of the Parties and their respective successors and
assigns, except that neither Party

                                     - 33 -

<PAGE>   37

may assign its respective obligations hereunder, including an assignment by
merger or by operation of law, without the prior written consent of the other
Party, unless such assignment is in connection with the sale or transfer of all
or substantially all of the business or assets of the assigning Party. Any
attempted assignment in contravention of this provision shall be void.

     11.3 NOTICES. All notices, requests, consents and other communications
hereunder shall be in writing and shall be delivered by hand, by facsimile, or
by certified mail, postage prepaid, return receipt requested:

          (a) If to Hybridon, at the address set forth below:

                       Hybridon, Inc.
                       345 Vassar Street
                       Cambridge, MA  02139
                       Attention:  President
                       Telephone:  617-679-5500
                       Facsimile:   617-679-5592

              WITH A COPY TO:

                       James Pollock, Esq.
                       Holland & Knight, LLP
                       10 St. James Avenue
                       Boston, MA  02116
                       Telephone:  (617) 523-2700
                       Facsimile:   (617) 523-6850

          (b) If to Isis:

                       Isis Pharmaceuticals, Inc.
                       2292 Faraday Avenue
                       Carlsbad, CA 92008
                       Attention:  President
                       Telephone:  (760) 931-9200
                       Facsimile:  (760) 931-9639l

                                     - 34 -

<PAGE>   38

              WITH A COPY TO:

                       L. Kay Chandler, Esq.
                       Cooley Godward LLP
                       4365 Executive Drive, Suite 1100
                       San Diego, CA  92121
                       Telephone:  (858) 550-6000
                       Facsimile:  (858) 453-3555

     Any notice or other communication so addressed and so delivered shall be
deemed to have been received on the date of hand delivery or facsimile or, if
sent by certified mail, return receipt requested, on the date of mailing.

     11.4 ENTIRE AGREEMENT; ATTACHMENTS.

          (a) This Master Agreement and all exhibits hereto, together with the
Transaction Documents, represent the entire understanding and agreement between
the Parties with respect to the subject matter hereof and supersede all prior
oral and written and all contemporaneous oral negotiations, commitments and
understandings between the Parties.

          (b) If the provisions of the License Agreement are inconsistent with
the provisions of this Master Agreement, the provisions of the License Agreement
shall prevail. The Exhibits are hereby incorporated as integral parts of this
Master Agreement.

     11.5 SEVERABILITY. Any provision of this Master Agreement which is invalid,
illegal or unenforceable in any jurisdiction shall, as to that jurisdiction, be
ineffective to the extent of such invalidity, illegality or unenforceability,
without affecting in any way the remaining provisions hereof in such
jurisdiction or rendering that or any other provision of this Master Agreement
invalid, illegal or unenforceable in any other jurisdiction. The language in
this Master Agreement is acknowledged by the Parties to be language chosen by
the Parties to express their mutual consent, and no rule of strict construction
against any Party shall apply to any term or provision hereof.

     11.6 INVESTIGATION OF THE PARTIES. All representations and warranties
contained herein which are made to the best knowledge of a Party shall require
that such Party investigate and inquire with respect thereto to the extent that
a reasonable business person would make such investigation and inquiry in light
of the circumstances at the time, without regard to this transaction.

     11.7 EXPENSES. Except as otherwise expressly provided herein, Hybridon, on
the one hand, and Isis on the other hand, will pay all fees and expenses
(including, without limitation, legal and accounting fees and expenses) incurred
by them in connection with the transactions contemplated hereby.

                                      - 35 -

<PAGE>   39

     11.8 GOVERNING LAW. This Master Agreement shall be governed by and
construed in accordance with the laws of the State of Delaware, without regard
to the conflict of laws rules of any jurisdiction.

     11.9 SECTION HEADINGS. The section headings are for the convenience of the
Parties and in no way alter, modify, amend, limit, or restrict the contractual
obligations of the Parties.

     11.10 COUNTERPARTS. This Master Agreement may be executed in one or more
counterparts, each of which shall be deemed to be an original, but all of which
shall be one and the same document. A copy or facsimile of a signature shall be
binding upon the signatory as if it were an original signature.

     11.11 WAIVER AND MODIFICATION. A Party may only waive the failure of
another Party to comply with any of such Party's obligations, agreements or
conditions as set forth herein expressly in writing. To the extent permitted by
law, this Master Agreement may be amended or modified in whole or in part by an
agreement in writing executed on behalf of the Parties at any time.

     11.12 NO WAIVER. No failure on the part of any Party to exercise, and no
delay in exercising (except where a specific time period is specified) any right
shall operate as a waiver thereof, nor shall any single or partial exercise by
any Party of any right preclude any other future exercise thereof or the
exercise of any other right. No investigation, review or audit by either party
of the other prior to or after the date hereof shall stop or prevent either
Party from exercising any right hereunder or be deemed to be a waiver of any
such right.

     11.13 FURTHER ASSURANCES. At any time and from time to time after the
Effective Date, each party shall promptly execute and deliver such instruments
of transfer, conveyance, assignment and confirmation, and take all such other
action as the other Party may reasonably request to carry out the purpose and
intent of this Master Agreement.

     11.14 DISPUTE RESOLUTION.

          (a) Any Party must submit any dispute under this Master Agreement to
arbitration pursuant to the terms and conditions set forth in Article VII of the
License Agreement.

          (b) Nothing in this SECTION 11.14 shall prevent either Party from
seeking from a court of competent jurisdiction a preliminary injunction,
temporary restraining order or similar relief in order to prevent or limit an
irreparable harm that may occur in the absence thereof.

     11.15 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.

                                     - 36 -

<PAGE>   40

     11.16 CONFIDENTIALITY. The Parties hereto agree that the provisions of the
License Agreement relating to confidentiality are incorporated herein by
reference.

                    [Remainder of page intentionally omitted]

                                      - 37 -

<PAGE>   41

     IN WITNESS WHEREOF, the parties hereto have caused this Master Agreement to
be executed as of the date first written above.

                                 HYBRIDON, INC.

                                 By: /s/ Sudhir Agrawal
                                    ---------------------------------------
                                    Title:  President and CSO
                                          ---------------------------------

                                 ISIS PHARMACEUTICALS, INC.

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

                                     - 38 -

<PAGE>   42

                                    EXHIBIT A

                                LICENSE AGREEMENT

Incorporated by reference to Exhibit 10.71 to Hybridon's Quarterly Report on
Form 10-Q for the quarterly period ended June 30, 2001.

                                     - 39 -<PAGE>   1

                                                                   EXHIBIT 10.73

================================================================================

                     --------------------------------------

                            SHARE PURCHASE AGREEMENT

                     --------------------------------------

                               FOR THE PURCHASE OF

                        COMMON SHARES OF METHYLGENE INC.

                                      FROM

                                 HYBRIDON, INC.

                                   THE SELLER

                                       BY

                            ROYAL BANK VENTURES INC.,

          FONDS DE SOLIDARITE DES TRAVAILLEURS DU QUEBEC (F.T.Q.), AND

                      ONTARIO TEACHERS' PENSION PLAN BOARD

                                 THE PURCHASERS

                                  MAY 11, 2001

================================================================================

<PAGE>   2

                                TABLE OF CONTENTS
<TABLE>
<CAPTION>

                                                                                            PAGE
                                                                                            ----
<S>                                                                                        <C>
ARTICLE I Purchase and Sale of Shares........................................................1

         1.1   Certain Definitions...........................................................1

         1.2   Purchase and Sale of Shares...................................................2

         1.3   Purchase Price................................................................2

         1.4   Material Adverse Change.......................................................3

ARTICLE II Representations and Warranties of the Seller......................................3

         2.1   Organization..................................................................3

         2.2   Authorization.................................................................3

         2.3   Validity......................................................................3

         2.4   Ownership of the Shares.......................................................4

         2.5   No other agreement to Purchase................................................4

         2.6   Realizations..................................................................4

         2.7   Litigation....................................................................4

         2.8   Compliance with Securities Laws...............................................4

         2.9   Third Parties Consents........................................................5

ARTICLE III Representations and Warranties of the Purchasers.................................5

         3.1   Organization..................................................................5

         3.2   Authorization.................................................................5

         3.3   Validity......................................................................5

         3.4   Purchase for Investment.......................................................5

ARTICLE IV Covenants.........................................................................6

         4.1   Cooperation...................................................................6

         4.2   Filings By Seller.............................................................6

         4.3   Transfer Taxes, Fees and Expenses.............................................6
</TABLE>

                                      -i-

<PAGE>   3

<TABLE>

<S>      <C>                                                                                <C>
         4.4   Consents and Waivers..........................................................7

ARTICLE V Closing Matters....................................................................7

         5.1   The Closing...................................................................7

         5.2   Delivery of Shares and Assignments............................................7

ARTICLE VI Conditions of Closing.............................................................8

         6.1   Conditions to the benefit of the Purchasers...................................8

         6.2   Conditions to the benefit of the Seller......................................10

ARTICLE VII Miscellaneous...................................................................11

         7.1   Survival of Representation and Warranties....................................11

         7.2   Additional Documents and Acts................................................11

         7.3   Specific Performance.........................................................12

         7.4   Notices......................................................................12

         7.5   Assignment...................................................................13

         7.6   Fees.........................................................................14

         7.7   Waiver.......................................................................14

         7.8   Entire Agreement.............................................................14

         7.9   Amendments, Supplements, Etc.................................................14

         7.10  Interpretation...............................................................14

         7.11  Headings and Captions........................................................15

         7.12  Counterparts.................................................................15

         7.13  Successors and Assigns.......................................................15

         7.14  Severability.................................................................15

         7.15  Governing Law................................................................15

         7.16  Language.....................................................................15
</TABLE>

                                      -ii-

<PAGE>   4

                            SHARE PURCHASE AGREEMENT

This Share Purchase Agreement is made and entered into as of May 11, 2001 (the
"AGREEMENT") by Royal Bank Ventures Inc., Fonds de Solidarite des Travailleurs
du Quebec (F.T.Q.) and Ontario Teachers' Pension Plan Board (collectively, the
"PURCHASERS" and each as a "PURCHASER"), and Hybridon, Inc. (the "SELLER").

                                   WITNESSETH

     WHEREAS, the Seller is the owner of the Shares (as hereinafter defined);
and

     WHEREAS, the Seller is a party to the Shareholders' Agreement (as
hereinafter defined) governing disposition of the Shares and granting certain
rights with respect to the Shares;

     WHEREAS, the Purchasers desire to purchase from the Seller, and the Seller
desires to sell to the Purchasers, the Shares upon the terms and subject to the
conditions set forth in this Agreement;

     NOW, THEREFORE, in consideration of the promises and the mutual agreements,
covenants, representations, warranties and indemnities contained in this
Agreement, the Purchasers and the Seller hereby agree as follows:

                                   ARTICLE I

                           PURCHASE AND SALE OF SHARES

1.1  CERTAIN DEFINITIONS.

     For purposes of this Agreement, the following terms shall have the meanings
set forth below:

     (a) "C$" shall mean Canadian dollars.

     (b) "CLOSING" shall have the meaning assigned to it in Section 5.1 hereof.

     (c) "CLOSING DATE" shall have the meaning assigned to it in Section 5.1
         hereof.

     (d) "COMPANY" shall mean MethylGene Inc., a corporation organized under the
         laws of Quebec.

     (e) "ENCUMBRANCE" shall mean any Lien pertaining to the sale, assignment,
         disposition, transfer or the voting rights of, on or pertaining to the
         Shares (including, without limitation, any consents or approvals of
         transfers, options, rights of first refusal and co-sale rights).

                                       1

<PAGE>   5

     (f) "LIEN", shall mean any lien, pledge, claim, security interest,
         encumbrance, charge, restriction or limitation of any kind, whether
         arising by agreement, operation of law or otherwise other than
         Permitted Encumbrances.

     (g) "MATERIAL ADVERSE CHANGE" shall have the meaning set forth in Section
         1.4 hereof.

     (h) "PERMITTED ENCUMBRANCES " shall mean those Encumbrances arising under
         the Shareholders' Agreement to the extent they do not relate or apply
         to the transactions contemplated by this Agreement.

     (i) "SHAREHOLDERS' AGREEMENT" shall mean, collectively (i) that certain
         Shareholders' Agreement, dated as of January 4, 1996, among Fonds de
         solidarite des travailleurs du Quebec (F.T.Q.) ("FONDS"), Fonds
         d'Investissement en Biotechnologie BioCapital II, societe en
         commandite ("BIOCAPITAL"), Societe Innovatech du Grand Montreal
         ("INNOVATECH"), Seller and the Company, as amended, and (ii) that
         certain Unanimous Shareholders' Agreement, dated as of January 4,
         1996, among Fonds, Biocapital, Innovatech, Seller and the Company, as
         amended.

     (j) "SHARES" shall mean 1,552,941 Common Shares of the Company, issued to
         Seller pursuant to the reorganization of the Company's Class A shares
         and Class B shares into a single class of shares described as "COMMON
         SHARES", to be acquired by the Purchasers at the Closing as
         contemplated by this Agreement.

     (k) "US DOLLAR EQUIVALENT" means, in respect of any amount expressed in
         Canadian dollars, an amount expressed in US dollars equal to the
         product obtained by multiplying (i) such Canadian dollar amount by
         (ii) 0.6504, being the exchange rate quoted by the National Bank of
         Canada on the Closing Date for exchanging Canadian dollars into US
         dollars.

1.2   PURCHASE AND SALE OF SHARES.

     Upon the terms and subject to the conditions set forth in this Agreement,
the Seller shall sell, assign, transfer and DELIVER to the Purchasers at the
Closing and the Purchasers shall purchase and acquire from the Seller at the
Closing, all right, title and interest in and to that number of the Shares as
set forth opposite each such Purchaser's name on SCHEDULE 1.2 hereto, free and
clear of all Liens (other than the Permitted Encumbrances to the extent they do
not apply to the transactions contemplated by this Agreement).

1.3   PURCHASE PRICE.

     The purchase price due and payable at Closing (the "PURCHASE PRICE") for
the Shares to be sold pursuant to this Agreement shall be the US Dollar
Equivalent of C$4,425,881.80 or C$2.85 per share (less the value of the CCRA
Withholding or the RQ Withholding as defined in section 6.1(g), if any, and less
the legal fees incurred by each Purchaser in connection with this transaction)
and shall be paid to the Seller by each of the Purchasers, in the proportions
set forth

                                       2

<PAGE>   6

opposite each Purchaser's name in SCHEDULE 1.2, by wire transfer of funds or
other immediately available funds, to the account designated by the Seller or as
Seller may otherwise direct in writing before Closing.

1.4   MATERIAL ADVERSE CHANGE.

     From the Date of this Agreement until the Closing Date, in the event of a
material adverse change in the Company or the value of the Shares ("MATERIAL
ADVERSE CHANGE"), any Purchaser, in its sole discretion, upon written notice to
the Seller, may terminate this Agreement with respect to its obligations
hereunder.

                                   ARTICLE II

                  REPRESENTATIONS AND WARRANTIES OF THE SELLER

     The Seller hereby represents and warrants to each Purchaser as follows:

2.1   ORGANIZATION.

     The Seller is duly formed, validly existing and in good standing under the
laws of the state of Delaware.

2.2   AUTHORIZATION.

     The Seller has all necessary power and authority to enter into, execute and
deliver this Agreement and to perform all of the obligations to be performed by
it hereunder. This Agreement has been duly authorized, executed and delivered by
the Seller and constitutes its valid and binding obligation, enforceable against
the Seller in accordance with its terms.

2.3   VALIDITY.

     Neither the execution and delivery of this Agreement nor the performance or
consummation of the transactions contemplated hereby or thereby will conflict
with, result in a breach or violation of, constitute a default under, or
accelerate the performance provided by the terms of: (i) any law, any rule or
regulation of any government or any agency of any government or any judgment,
order, writ, decree, permit or license of any court or other agency of any
government to which the Seller may be subject; (ii) the certificate of
incorporation or the by-laws of the Seller; or (iii) or any contract, agreement,
commitment or instrument to which the Seller is a party or by which it or any of
its assets is bound or committed. Neither the execution and delivery of this
Agreement nor the performance or consummation of the transactions contemplated
hereby or thereby will constitute an event which, with the lapse of time or
action by a third party, could result in the default under any of the foregoing
or result in the creation of any Lien upon the Shares. Other than the
registrations, filings, consents and approvals that have been made or obtained
and the filings required to be made by Seller pursuant to Section 4.2 below, the
execution and delivery of this Agreement and the performance and consummation of
the transactions )::s contemplated Hereby and thereby will not require any
registration, filing, consent or approval under any such law, rule, regulation,
judgment, order, writ, decree, permit, license,

                                       3

<PAGE>   7

consent or approval of, any third party, including, without limitation, any
governmental or regulatory authority or any party to any contract, agreement,
commitment or instrument.

2.4   OWNERSHIP OF THE SHARES.

     The Seller owns, all right, title and interest (legal and beneficial) in
and to the Shares being all of the shares in the capital of the Company owned by
Seller free and clear of all Liens. All of the Encumbrances potentially
applicable to the transaction contemplated by this Agreement will have been duly
waived or satisfied on or before the Closing Date, or, in the case of any rights
of first refusal, first offer, or co-sale will have been duly waived or all
applicable notice periods will have expired without such rights having been
exercised on or before the Closing Date, by all interested parties. Upon
delivery of the Shares identified as being owned by the Seller to the Purchasers
and payment therefor in accordance with this Agreement, the Purchasers will
acquire such Shares free and clear of all Liens. The Shares have been validly
subscribed and issued and are outstanding as fully paid and non-assessable.

2.5   NO OTHER AGREEMENTS TO PURCHASE.

     No, person other than the Purchasers has any written or oral agreement or
option or any right or privilege (whether by law, preemptive or contractual)
capable of becoming an agreement or option 1')r the purchase or acquisition from
the Seller of any of the Shares except for the shareholders under the
Shareholders Agreement.

2.6   REALIZATIONS.

     The Seller has no obligations pursuant to any letter of credit, guarantee,
pledge, hypothecation, borrowing or other similar arrangement in connection with
the acquisition of any of the Shares or any transaction with the Company.

2.7   LITIGATION.

     There is no (i) action, suit, claim, proceeding or investigation pending or
threatened against the Seller, at law or in equity, or before or by any federal,
provincial, state, municipal or other governmental department, commission,
board, bureau, agency court, or instrumentality, domestic or foreign, (ii)
arbitration proceeding relating to the Seller pending, or (iii) governmental
inquiry pending or threatened against the Seller, which, if adversely
determined. would question the validity of, or prevent the consummation of, the
transactions contemplated by this Agreement. There is no action or suit by the
Seller pending or threatened against others relating to the Shares.

2.8   COMPLIANCE WITH SECURITIES LAWS.

     Neither the Seller nor anyone acting on Seller's behalf has offered to sell
the Shares by means of any general solicitation or any advertising.

                                       4

<PAGE>   8

2.9   THIRD PARTIES CONSENTS.

     All required consents of third parties to the sale to the Purchasers of the
Shares pursuant hereto have been duly obtained.

                                  ARTICLE III

                REPRESENTATIONS AND WARRANTIES OF THE PURCHASERS

     Each Purchaser, severally as for itself only and not in respect of any
other Purchaser, hereby represents and warrants to the Seller as follows:

3.1   ORGANIZATION.

     The Purchaser is duly formed, validly existing and in good standing under
the laws of the jurisdiction in which it is organized.

3.2   AUTHORIZATION.

     The Purchaser has all necessary power and authority to enter into, execute
and deliver this Agreement and to perform all of the obligations to be performed
by it hereunder and thereunder. This Agreement has been duly authorized,
executed and delivered by the Purchaser and constitutes a valid and binding
obligation, enforceable against the Purchaser in accordance with its terms.

3.3   VALIDITY.

     Neither the execution and delivery of this Agreement nor the performance or
consummation of the transactions contemplated hereby or thereby will conflict
with, result in a breach or violation of, constitute a default under, or
accelerate the performance provided by the terms of (i) any law, any rule or
regulation of any government or any agency of any government, or any judgment,
order, writ, decree, permit or license of any court or other agency of any
government to which the Purchaser may be subject; (ii) any contract, agreement,
commitment or instrument to which the Purchaser is a party or by which the
Purchaser or any of its assets are bound or committed; or (iii) the Purchaser's
constituent charter documents or other governing instruments.

3.4   PURCHASE FOR INVESTMENT.

     (a) The Purchaser is purchasing the Shares as principal for its own
         account, and not for the benefit of any other person, and is either
         (A) purchasing a sufficient number of Shares that the aggregate
         acquisition cost of such Shares to the Purchaser is not less than
         C$150,000 or (B) a person or company referred to in clauses 72(1)(a)
         or (c) of the SECURITIES ACT (Ontario), if a resident of the Province
         of Ontario, section 44 of the SECURITIES ACT (Quebec), if a resident
         of the Province of Quebec, or analogous exemptions of securities
         legislation of the other Provinces of Canada, if a resident of another
         province;

                                       5

<PAGE>   9

     (b) The Purchaser was not created or established solely to acquire the
         Shares, or to permit purchase of the Shares without a prospectus;

     (c) The Purchaser was not provided with, has not requested, and does not
         need to receive an offering memorandum as defined in applicable
         securities laws. The offer and sale to the Purchaser of the Shares
         were not made through or as a result of, and the distribution of the
         Shares is not being accompanied by, any general solicitation or any
         advertisement; and

     (d) If the Purchaser is resident in Ontario and is a corporation or
         syndicate, partnership, trust, investment club or other unincorporated
         organization, it was not created or is not being used primarily to
         permit purchases without a prospectus, and the share or portion of
         each member or partner of the partnership, syndicate, investment club
         or unincorporated organization, each beneficiary of the trust or each
         shareholder of the corporation of the aggregate acquisition cost to
         the corporation, syndicate, partnership, trust, investment club or
         other unincorporated organization of the Shares is not less than
         C$150,000.

                                   ARTICLE IV

                                    COVENANTS

4.1   COOPERATION.

     The parties hereto shall cooperate fully with each other in furnishing any
information or performing any action reasonably requested by each to the other
party, which information or action is necessary to the prompt and successful
consummation of the transactions contemplated by this Agreement. Subject to its
further rights under this Agreement, each party hereto shall cause the Closing
to occur by the Closing Date or as soon thereafter as practicable.

4.2   FILINGS BY SELLER.

     The Seller shall, at its own expense, make in a timely manner, all
appropriate filings required to be made by the Seller with the Quebec Securities
Commission, the Ontario Securities Commission or any other Canadian regulatory
agency in connection with the sale of the Shares pursuant to this Agreement,
including the filing required to be made pursuant to Section 51 of the QUEBEC
SECURITIES Act and Section 72(2) of the SECURITIES ACT (Ontario).

4.3   TRANSFER TAXES, FEES AND EXPENSES.

     Subject to Section 7.6, each party shall bear responsibility for its own
expenses associated with the sale, purchase and transfer of the Shares. Any
expenses incurred in connection with the transfer o f the Shares and requested
to be paid by the Company shall be paid by the Seller.

                                       6

<PAGE>   10

4.4   CONSENTS AND WAIVERS.

     The Seller shall use its best efforts to obtain, prior to the Closing Date,
the necessary, appropriate or desirable, consents in writing to the transactions
contemplated by this Agreement and/or such amendments, assignments, waivers or
modifications of such documents or instruments as may be required so that the
transactions contemplated by this Agreement may be consummated and shall not
result in any default or breach of any of the articles or bylaws of the Company,
the Shareholders' Agreement or other contract, agreement, commitment or
instrument to which the Seller is a party or by which the Seller or any of the
Seller's assets are bound or committed, including waivers of all rights of first
refusal, first offer or co-sale rights potentially applicable to the sale,
assignment or transfer of the Shares.

                                   ARTICLE V

                                 CLOSING MATTERS

5.1   THE CLOSING.

     Subject to satisfaction or waiver of all conditions precedent set forth in
Article VI, the closing with respect to the transfer of the Shares (the
"CLOSING") shall be held at the offices of McCarthy Tetrault, at 11:00 a.m. on
May 11, 2001, or on such other date as the Purchaser and the Seller may agree
(the "CLOSING DATE"). If any condition in Article VI is not satisfied in any
respect (or is not duly waived) at the Closing, the party or parties whose
obligations are subject to such condition may extend the date of the Closing
(during which extension each of the other parties shall use all reasonable
efforts to cause all such conditions to be satisfied in all respects). If all
conditions are determined to be satisfied (or are duly waived) at the Closing
(whether or not delayed), the Closing shall be consummated.

5.2   DELIVERY OF SHARES AND ASSIGNMENTS.

     At the Closing, the Seller shall deliver, to the extent not previously
delivered, or cause to be delivered to the Purchasers (i) all of the instruments
and other documents that represent or constitute the Shares to be transferred at
the Closing, together with all transfer forms duly signed necessary to register
the transfer of the Shares to the Purchasers in the books of the Company, (ii)
such releases, approvals, consents, waivers and other supporting documents as
may in the reasonable opinion of the Purchasers be necessary to permit the
Purchasers to acquire the Shares free and clear of all Liens (other than the
Permitted Encumbrances), and (iii) the other documents and agreements referenced
in Section 6.1.

                                       7

<PAGE>   11

                                   ARTICLE VI

                              CONDITIONS OF CLOSING

6.1   CONDITIONS TO THE BENEFIT OF THE PURCHASERS.

     The obligations of the Purchasers under this Agreement to consummate the
transactions contemplated by this Agreement at the Closing are, at each of the
Purchaser's option, subject to the following conditions:

     (a) PERFORMANCE OF THIS AGREEMENT. All the terms, covenants and conditions
         of this Agreement to be complied with and performed by the Seller at
         or before the Closing shall have been fully complied with and
         performed in all material respects.

     (b) ACCURACY OF REPRESENTATIONS AND WARRANTIES. The representations and
         warranties of the Seller set forth in this Agreement shall be true and
         correct both on the date of this Agreement and as of the Closing Date
         (with the same force and effect as if such representations and
         warranties were made anew at and as of the Closing Date, except (i) to
         the extent that such representations and warranties are by their
         express provisions made as of the date of this Agreement or another
         specified date and (ii) for the effect of any activities or
         transactions which may have taken place after the date of this
         Agreement which are contemplated by this Agreement).

     (c) LITIGATION. No action, suit, litigation, proceeding or investigation
         shall (i) have been formally instituted and be pending with regard to
         the transactions contemplated by this Agreement or (ii) be threatened
         with regard to the transactions contemplated by this Agreement. On the
         Closing Date, there shall not be in force any injunction, order or
         decree restricting or enjoining consummation of the transactions
         contemplated by this Agreement.

     (d) REQUIRED CONSENTS, WAIVERS AND NOTICES. The Seller shall have obtained
         all required consents in writing to the transactions contemplated by
         this Agreement and such amendments, assignments, waivers or
         modifications of such documents or instruments as may be required so
         that the transactions contemplated by this Agreement may be
         consummated and shall not result in any default or breach of the
         Shareholders' Agreement or any other agreement, contract, commitment
         or instrument to which the Seller is a party or by which the Seller or
         any of its assets are bound or committed, including waivers of all
         rights of first refusal, first offer or co-sale rights potentially
         applicable to the sale, assignment or transfer of the Shares. The
         Seller shall have given timely notice to all parties that may be
         required in order to effect the transfer of the Shares and all rights
         relating thereto. All such consents, waivers and approvals referred to
         in this Section 6.1(d) shall be in a form and substance which is
         satisfactory to the Purchasers, in their sole discretion.

                                       8

<PAGE>   12

     (e) MATERIAL ADVERSE CHANGE, INACCURACY OR BREACH. No fact or circumstance
         shall have come to the attention of the Purchasers which in the
         judgment of the Purchasers constitutes or would constitute a Material
         Adverse Change, or constitute a material breach of any covenant of the
         Seller hereunder or constitute or reflect any material inaccuracy in
         or breach of any representation and warranty made or to be made by the
         Seller in connection with this Agreement.

     (f)  LEGAL OPINION. The Purchasers shall have received from Holland &
          Knight a legal opinion, addressed to the Purchasers and dated as at
          the Closing Date, substantially in the form of EXHIBIT 6.1 (f)
          hereto.

     (g) TAX CLEARANCE CERTIFICATES. The Seller shall have received and
         provided to the Purchasers in a form satisfactory to each Purchaser,
         tax clearance certificates from each of the Canada Customs and Revenue
         Agency (the "CCRA CERTIFICATE") and the Minister of Revenue for Quebec
         (the "RQ CERTIFICATE") with respect to the sale of the Shares, in each
         case fixing a certificate limit or an estimated or actual amount of
         proceeds of disposition which, in the aggregate, shall not be less
         than the Purchase Price (the "CERTIFICATE LIMIT"), and the Purchasers
         shall have received copies of both the CCRA Certificate and RQ
         Certificate.

          (1) CCRA CERTIFICATE. The Purchasers may waive the preceding
              condition if the Seller has not received and delivered the CCRA
              Certificate at the Closing, in which case the Purchasers will
              withhold thirty-three and one-third percent (33 1/3%) of the
              Purchase Price (the "CCRA WITHHOLDING").

              If the Seller delivers to the Purchasers a clearance certificate
              for an amount less than the Certificate Limit, the Purchasers
              shall withhold from the Purchase Price thirty-three and one-third
              percent (33 1/3%) of the amount by which the Certificate Limit
              exceeds the amount of the clearance certificate so delivered (the
              "ADJUSTED CCRA WITHHOLDING").

              If the Seller delivers to the Purchasers the CCRA Certificate
              before the last business clay that is not more than twenty-seven
              (27) days after the last day of the month in which the Closing
              occurred (the "REMITTANCE DATE"), the Purchasers shall remit to
              the Seller forthwith upon the delivery of such CCRA Certificate
              the amount of the CCRA Withholding or the Adjusted CCRA
              Withholding, as the case may be. If the CCRA Certificate is not
              delivered to the Purchasers on or before the Remittance Date, the
              Purchasers shall remit the amount of the CCRA Withholding or the
              Adjusted CCRA Withholding, as the case may be, to the Receiver
              General of Canada in accordance with the INCOME TAX ACT (Canada).
              The Seller shall have no recourse against the Purchasers for
              having withheld and remitted any amount in compliance with this
              paragraph and the INCOME TAX ACT (Canada).

          (2) RQ CERTIFICATE. The Purchasers may waive the condition stated in
              this paragraph 6.1(g) if the Seller has not received and
              delivered the RQ

                                       9

<PAGE>   13

              Certificate at the Closing, in which case the Purchasers will
              withhold eighteen percent (18%) of the Purchase Price (the "RQ
              WITHHOLDING").

              If the Seller delivers to the Purchasers at the Closing a
              clearance certificate for an amount less than the Certificate
              Limit, the Purchasers shall withhold from the Purchase Price
              eighteen percent (18%) of the amount by which the Certificate
              Limit exceeds the amount of the clearance certificate so
              delivered (the "ADJUSTED RQ WITHHOLDING").

              If the Seller delivers to the Purchasers the RQ Certificate
              before the Remittance Date, the Purchasers shall remit to the
              Seller forthwith upon the delivery of such RQ Certificate the
              amount of the RQ Withholding or the Adjusted RQ Withholding, as
              the case may be. If the RQ Certificate is not delivered to the
              Purchasers on or before the Remittance Date, the Purchasers shall
              remit the amount of the RQ Withholding or the Adjusted RQ
              Withholding, as the case may be, to the Minister of Revenue for
              Quebec in accordance with the TAXATION ACT (Quebec). The Seller
              shall have no recourse against the Purchasers for having withheld
              and remitted any amount in compliance with this paragraph and the
              TAXATION ACT (Quebec).

     (h) NOTE HOLDER RELEASE. The Purchasers shall have received evidence, in a
         form and substance satisfactory to the Purchasers in their sole
         discretion, that the holders of the Seller's 8% notes due 2002 and the
         holders of the Seller's $6,000,000 notes due 2003, have released their
         security interest in the Shares.

     (i) RESIGNATION AS DIRECTOR. Hybridon shall have caused its nominee on the
         board of directors of the Company to resign, such resignation to be
         effective upon Closing.

6.2   CONDITIONS TO THE BENEFIT OF THE SELLER.

     The obligations of the Seller under this Agreement to consummate the
transactions contemplated by this Agreement at the Closing are, at its option,
subject to the following conditions:

     (a) PERFORMANCE OF THIS AGREEMENT. All terms, covenants and conditions of
         this Agreement to be complied with and performed by the Purchasers at
         or before the Closing shall have been fully complied with and
         performed in all material respects.

     (b) ACCURACY OF REPRESENTATIONS AND WARRANTIES. The representations and
         warranties of the Purchasers set forth in this Agreement shall have
         been true and correct both on the date of this Agreement and as of the
         Closing Date (with the same force and effect as if such
         representations and warranties were made anew at and as of the Closing
         Date, except (i) to the extent that such representations and
         warranties are by their express provisions made as of the date of this
         Agreement or another specified date and (ii) for the effect of any
         activities or transactions

                                       10

<PAGE>   14

         which may have taken place after the date of this Agreement which are
         contemplated by this Agreement).

     (c) LITIGATION. No action, suit, litigation, arbitration, proceeding or
         investigation shall (i) have been formally instituted and be pending
         with regard to the transactions contemplated by this Agreement or (ii)
         be threatened by any governmental authority of the United States, or
         any State thereof with regard to the transactions contemplated by this
         Agreement. On the Closing Date, there shall not be in force any
         injunction, order or decree restraining or enjoining consummation of
         the transactions contemplated by this Agreement.

     (d) REQUIRED CONSENTS AND WAIVERS. The Seller shall have obtained all
         required consents in writing to the transactions contemplated by this
         Agreement and such amendments, assignments, waivers or modifications
         of such documents or instruments as may be required so that the
         transactions contemplated by the Agreement may be consummated and
         shall not result in any default or breach of the Shareholders'
         Agreement, or any other agreement, contract, commitment or instrument
         to which the Seller is a party or by which the Seller or any of its
         assets are bound or committed, including waivers of all rights of
         first refusal and rights of co-sale potentially applicable to the
         sale, assignment or transfer of the Shares.

     (e) PROCEEDINGS. All proceedings to be taken by the Purchasers in
         connection with the transactions contemplated by this Agreement and
         all documents incident thereto shall be reasonably satisfactory in
         form and substance to the Seller, and the Seller shall leave received
         copies of all such documents and other evidence as the Seller may
         reasonably request to establish the consummation of such transactions
         and the taking of all proceedings in connection therewith.

                                  ARTICLE VII

                                  MISCELLANEOUS

7.1   SURVIVAL OF REPRESENTATION AND WARRANTIES.

     All representations and warranties of the parties to this Agreement shall
survive for twenty-four (24) months following the execution and delivery of this
Agreement except that Seller's representations and warranties pursuant to
Sections 2.1, 2.2, 2.3, 2.4 and 2.5 shall survive in perpetuity. Any
investigation or other examination that may have been made or may be made at any
time by or on behalf of the party to whom representations and warranties are
made shall not limit, diminish or in any way affect the representations and
warranties in this Agreement, and the parties may rely on the representations
and warranties in this Agreement irrespective of any information obtained by
them by any investigation, examination or otherwise.

7.2   ADDITIONAL DOCUMENTS AND ACTS.

     After the Closing, each of the parties hereto shall execute and deliver
such additional documents, certificates and instruments, and perform such
additional acts, as may be reasonably

                                       11

<PAGE>   15

requested and necessary or appropriate to carry out all of the provisions of
this Agreement and to consummate all of the transactions contemplated by this
Agreement.

7.3   SPECIFIC PERFORMANCE.

     Each of the parties hereto acknowledges that the other party will have no
adequate remedy at law if it fails to perform any of its obligations under this
Agreement. In such event, each of the parties agrees that the other party shall
have the right, in addition to any other rights it may have (whether at law or
in equity), to specific performance of this Agreement.

7.4   NOTICES.

     All notices, consents, waivers and other communications hereunder shall be
in writing and shall be deemed to have been duly given when delivered in person,
sent by facsimile transmission or posted by registered or certified mail, return
receipt requested, with postage prepaid, addressed as follows:

         if to the Purchasers:

               Royal Bank Ventures Inc.
               1, Place Ville Marie
               9th Floor
               Montreal, Quebec
               H2C 3A9

               Fax No.: (514) 874-2294
               ATTENTION:  Robert Bechard

               Folds de Solidarite des Travailleurs du Quebec (F.T.Q.)
               8717 Berri Street
               Montreal, Quebec
               H2M 2T9

               Fax No.:  (514) 383-2500
               ATTENTION:  Vice-President, Legal Affairs

         with a copy (not constituting notice) to:

               McCarthy Tetrault
               1170 Peel Street
               5th Floor
               Montreal, Quebec
               H3B 4S8

               Fax No.: (514) 397-4190
               ATTENTION:  Alida Gualtieri

                                       12

<PAGE>   16

               Ontario Teachers' Pension Plan Board
               5650 Yonge St.
               Toronto, Ontario
               M2M 4115

               Fax No. (416) 730-5082
               ATTENTION:  Director, Venture Capital

         with a copy to:

               Ontario Teachers' Pension Plan Board
               5650 Yonge St.
               Toronto, Ontario
               M2M 4H5

               Fax No. (416) 730-3771
               ATTENTION:  Legal Counsel, Investments

         if to the Seller:

               Hybridon, Inc.
               345 Vassar Street
               Cambridge, MA 02139

               Fax No.:  (617) 679-5592
               ATTENTION:  Robert Andersen

         with a copy (not constituting notice) to:

               Holland & Knight LLP
               10 St. James Avenue
               Boston, MA  02116

               Fax No.:  (617) 523-6850
               ATTENTION:  James Pollock, Esq.

or to such other address or addresses as the Purchasers or the Seller may from
time to time designate by notice as provided herein, except that notices of
changes of address shall be effective only upon receipt.

7.5   ASSIGNMENT.

     Neither party hereto may- assign or delegate this Agreement or any rights
or obligations hereunder to any person without the prior written consent of the
other.

                                       13

<PAGE>   17

7.6   FEES.

     Seller shall pay at Closing to each Purchaser all legal fees incurred by it
in connection with this transaction.

7.7   WAIVER.

     Each party hereto may, by express written notice to the other, (i) extend
the time for the performance of any of the obligations or other actions of the
other party under this Agreement; (ii) waive any inaccuracies in the
representations or warranties of the other party contained in this Agreement or
in any document delivered pursuant to this Agreement; (iii) waive compliance
with any of the conditions or covenants of the other party contained in this
Agreement; or (iv) waive or modify performance of any of the obligations of the
other party under this Agreement. Except as provided in the preceding sentence,
no action taken pursuant to this Agreement, including, without limitation, any
investigation by or on behalf of any party, shall be deemed to constitute a
waiver by the party taking such action of compliance by the other party with any
of the representations, warranties, covenants, conditions, agreements or
indemnities contained in this Agreement. The waiver by any party of a breach of
any provision of this Agreement shall not operate or be construed as a waiver of
any subsequent breach.

7.8   ENTIRE AGREEMENT.

     This Agreement, together with the Schedules and Exhibits hereto (which are
incorporated herein by reference) and certificates to be delivered at Closing
pursuant to this Agreement, supersedes any other agreement. negotiation,
understandings and discussions whether written or oral, that may have been made
-, or entered into by the parties hereto relating to the matters contemplated
hereby, and constitutes the entire agreement of the parties hereto with respect
to the subject matter hereof.

7.9   AMENDMENTS, SUPPLEMENTS, ETC.

     This Agreement may be amended or supplemented only by additional written
agreements, articles or certificates signed by the Purchasers and the Seller, as
may be determined by the parties hereto to be necessary, appropriate or
desirable to further the purposes of this Agreement, to clarify the intention of
the parties, or to add to or to modify the covenants, terms or conditions
hereof.

7.10  INTERPRETATION.

     When a reference is rondo in this Agreement to Articles, Sections,
Schedules, Exhibits or certificates such reference shall be to an Article,
Section, Schedule, Exhibit or certificate to this Agreement unless otherwise
indicated. The words "include," "includes" and "including" when used herein
shall be deemed in each case to be followed by the words "without limitation."
Neither party hereto shall be or ')e deemed to be the drafter of this Agreement
for the purposes of construing this Agreement again: A one party or the other.

                                       14

<PAGE>   18

7.11   HEADINGS AND CAPTIONS.

     The headings and captions in this Agreement are for convenience and
reference purposes only and shall not be considered a part of or affect the
construction or interpretation of any provision of this Agreement.

7.12   COUNTERPARTS.

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

7.13   SUCCESSORS AND ASSIGNS.

     This Agreement shall be binding upon, inure to the benefit of and may be
enforced by, each of the parties hereto and their respective permitted
successors and assigns.

7.14   SEVERABILITY.

     If any provision of this :agreement is held to be invalid or unenforceable,
the remaining provision shall nevertheless be given full force and effect.

7.15   GOVERNING LAW.

     This Agreement shall be governed by and construed, interpreted and enforced
in accordance with the laws of the Province of Quebec and the laws of Canada
applicable therein, without giving effect to the principles of conflicts of law
thereof. The Parties irrevocably and unconditionally agree to submit to the
non-exclusive jurisdiction of the courts of the province of Quebec, district of
Montreal, and all courts competent to hear-appeals therefrom.

7.16   LANGUAGE.

     The parties hereto agree that this Agreement be drafted in English. Les
parties aux presentes conviennent a ce que la presente convention soit redigee
en anglais.

                  [REMAINDER OF PAGE INTENTIONALLY LEFT BLANK]

                                       15

<PAGE>   19

     IN WITNESS WHEREOF, the Purchasers and the Seller have caused this Share
Purchase Agreement to lie duly executed and delivered as of the date first above
written.
<TABLE>
<S>                                                           <C>
SELLER:                                                       PURCHASERS:

HYBRIDON, INC.                                                ROYAL BANK VENTURES INC.

By: /s/ Robert Andersen                                       Per: /s/ Robert Bechard
   --------------------------------------------------             -------------------------------------------------
Name:  Robert Andersen                                                 Robert Bechard
Its:   Vice President and
       Chief Financial Officer

                                                              Per: /s/ Ghassan Dami
                                                                  -------------------------------------------------
                                                                       Ghassan Dami

                                                              FONDS DE SOLIDARITE DES TRAVAILLEURS DU QUEBEC
                                                              (F.T.Q.)

                                                              Per: /s/ Daniel Laporte
                                                                  -------------------------------------------------
                                                                       Daniel Laporte,
                                                                       ONTARIO TEACHERS'
                                                                       PENSION PLAN BOARD

                                                              Per: /s/ Rosemary Zigrossi
                                                                  -------------------------------------------------
                                                                       Rosemary Zigrossi,
                                                                       Director, Venture Capital
</TABLE>

                                       16

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