Document:

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                                    AMENDMENT
                                     TO THE
                                LICENSE AGREEMENT
                                 BY AND BETWEEN
                                 HYBRIDON, INC.
                                       AND
                         YOON S. CHO-CHUNG, M.D., PH.D.

This Amendment, effective the 4th day of February, 2005, ("Effective Date") is
an Amendment to the License Agreement dated the 30th day of October, 1995, (the
"Agreement"), between Hybridon, Inc., a Delaware corporation, having its
principle place of business at 345 Vassar Street, Cambridge, MA 02139
(hereinafter "HYBRIDON") and Yoon S. Cho-Chung, M.D., Ph.D. (hereinafter
"CHO-CHUNG").

      WHEREAS Hybridon and Cho-Chung desire to reaffirm the terms and
obligations of the Agreement and to amend the Agreement as defined under this
Amendment hereto;

      NOW, THEREFORE, in consideration of the mutual agreement hereinafter set
forth, Hybridon and Cho-Chung hereby agree to amend the Agreement as follows:

      In SECTION 8.1 (a) insert the following text immediately before `; and' at
      the end of this Section:

"and thereafter by an additional two periods of one (1) year each by paying
CHO-CHUNG US$150,000 for each such extension Period, and thereafter by an
additional four periods of one (1) year each by paying CHO-CHUNG US$175,000 for
each such extension Period, and thereafter by an additional four periods of one
(1) year each by paying CHO-CHUNG US$200,000 for each such extension Period, all
such payments to be paid in two equal installments due on June 30th and December
31st of each year"

      In ARTICLE XII. NOTICES - change the respective notice addresses to:

      For CHO-CHUNG:                    FOR HYBRIDON:

      Yoon S. Cho-Chung, M.D., Ph.D.    Hybridon, Inc.
                                        345 Vassar Street
                                        Cambridge, Massachusetts 02139
                                        ATTN.: Robert G. Andersen, CFO
                                        and VP Operations

         IN ALL OTHER RESPECTS, THE AGREEMENT REMAINS IN FULL FORCE AND EFFECT.

      IN WITNESS WHEREOF, the parties hereto have executed this Agreement as of
the day and year set forth above.

HYBRIDON, INC.                             YOON S. CHO-CHUNG, M.D., PH.D.

By: /s/ Robert G. Andersen                 By: /s/ Yoon S. Cho-Chung
   ----------------------------------         ----------------------------------
Name: Robert G. Andersen                   Name: Yoon S. Cho-Chung, M.D., Ph.D.

Title: Chief Financial Officer and
       VP Operations

Date:     4 Feb. 2005                      Date:     4 Feb. 2005
     ----            ----------------           ----            ----------------

                                  Page 1 of 1                       Confidential<PAGE>
                                                                   EXHIBIT 10.46

               SUMMARY OF DIRECTOR COMPENSATION OF HYBRIDON, INC.

      The director compensation program for the members of the Board of
Directors of Hybridon,. Inc. (the "Company") involves the payment of meeting
fees, annual retainers and equity compensation.

Meeting Fees

      Members of the Board of Directors who are not employees of the Company are
paid $1,250 for personal attendance and $500 for telephonic attendance at Board
of Directors and committee meetings. These directors are reimbursed for their
expenses incurred in connection with their attendance at Board of Directors and
committee meetings.

      The Board has a policy under which non-employee directors may elect to
receive meeting fees in cash or in a number of shares of Common Stock determined
by dividing the fees for meetings attended by 85% of the fair market value of
the Company's Common Stock on the first business day of the quarter following
the quarter in which fees are earned.

Annual Retainers

      In addition to meeting fees, the Company pays the Chairman of the Board an
annual retainer of $60,000, which is paid in monthly installments, and pays the
Chairman of the Audit Committee an annual retainer of $15,000, which is paid in
quarterly installments. All other non-employee directors are paid an annual
retainer of $10,000, which is paid in quarterly installments.

Equity Compensation

      The Company's amended 1995 Director Stock Option Plan provides for the
grant of options to purchase 25,000 shares of Common Stock to each non-employee
director upon his or her initial election to the Board of Directors. In
addition, each non-employee director receives an automatic quarterly grant of
options to purchase 10,000 shares of Common Stock on the first day of each
calendar quarter, with options to purchase 3,750 of such shares being granted
under the Company's 1995 Director Stock Option Plan and options to purchase
6,250 of such shares being granted under the Company's Amended and Restated 1997
Stock Incentive Plan. All options are granted with exercise prices equal to the
fair market value of the Common Stock on the date of grant. All options vest on
the first anniversary of the date of grant. The vesting of all options granted
will be automatically accelerated upon the occurrence of a change in control of
the Company.<PAGE>
                                                                   Exhibit 10.47

                                 HYBRIDON, INC.

           Non-Employee Director Nonstatutory Stock Option Agreement
                     Granted Under 1997 Stock Incentive Plan

1.    Grant of Option.

      This agreement evidences the grant by Hybridon, Inc., a Delaware
corporation (the "Company"), on [__________] (the "Grant Date") to [_________],
a non-employee director of the Company (the "Participant"), of an option to
purchase, in whole or in part, on the terms provided herein and in the Company's
1997 Stock Incentive Plan (the "Plan"), a total of [__________] shares (the
"Shares") of common stock, $0.001 par value per share, of the Company ("Common
Stock") at a price of $[_______] per Share.

      It is intended that the option evidenced by this agreement shall not be an
incentive stock option as defined in Section 422 of the Internal Revenue Code of
1986, as amended, and any regulations promulgated thereunder (the "Code").
Except as otherwise indicated by the context, the term "Participant", as used in
this option, shall be deemed to include any person who acquires the right to
exercise this option validly under its terms.

2.    Vesting Schedule.

      Except as otherwise provided in this Agreement, this option may be
exercised, in whole or in part, with respect to all of the Shares covered hereby
at any time on or after the first anniversary of the Grant Date and prior to the
tenth anniversary of the Grant Date (hereinafter the "Expiration Date").
Notwithstanding the foregoing, this option shall immediately become exercisable
in full in the event a Change of Control Event (as defined in the Plan) occurs.

3.    Exercise of Option.

      (a) Form of Exercise. Each election to exercise this option shall be in
writing, signed by the Participant, and received by the Company at its principal
office, accompanied by this agreement and payment in cash or a check to the
order of the Company in an amount equal to the purchase price of the Shares
purchased. The Participant may purchase less than the number of shares covered
hereby, provided that no partial exercise of this option may be for any
fractional share.

      (b) Continuous Relationship with the Company Required. Except as otherwise
provided in this Section 3, this option may not be exercised unless the
Participant, at the time he or she exercises this option, is, and has been at
all times since the Grant Date, a director or consultant of the Company (an
"Eligible Participant").

      (c) Termination of Relationship with the Company. If the Participant
ceases to be an Eligible Participant for any reason, then, except as provided in
paragraph (d) below, the right to exercise this option shall terminate sixty
(60) days after such cessation (but in no event after the Expiration Date),
provided that this option shall be exercisable only to the extent that the

<PAGE>

Participant was entitled to exercise this option on the date of such cessation.
Notwithstanding the foregoing, if the Participant, prior to the Expiration Date,
violates the non-competition or confidentiality provisions of any
confidentiality and nondisclosure agreement or other agreement between the
Participant and the Company, the right to exercise this option shall terminate
immediately upon such violation.

      (d) Exercise Period Upon Death or Disability. If the Participant dies or
becomes disabled (within the meaning of Section 22(e)(3) of the Code) prior to
the Expiration Date while he or she is an Eligible Participant, this option
shall be exercisable, within the period of one hundred eighty (180) days
following the date of death or disability of the Participant, by the Participant
(or in the case of death by an authorized transferee), provided that this option
shall be exercisable only to the extent that this option was exercisable by the
Participant on the date of his or her death or disability, and further provided
that this option shall not be exercisable after the Expiration Date.

4.    Withholding.

      No Shares will be issued pursuant to the exercise of this option unless
and until the Participant pays to the Company, or makes provision satisfactory
to the Company for payment of, any federal, state or local withholding taxes
required by law to be withheld in respect of this option.

5.    Nontransferability of Option.

      This option is personal and may not be transferred other than by will or
the laws of descent and distribution or pursuant to a qualified domestic
relations order as defined by the Code or Title I of the Employee Retirement
Income Security Act, and this option shall be exercised during the lifetime of
the Participant only by the Participant or his or her guardian or legal
representative. No rights granted hereunder may be transferred, assigned,
pledged or hypothecated in any way (whether by operation of law or otherwise)
nor shall any such rights be subject to execution, attachment or similar
process. Upon any attempt to transfer, assign, pledge, hypothecate or otherwise
dispose of this option or of such rights contrary to the provisions hereof, or
upon the levy of any attachment or similar process upon this option or such
rights, this option and such rights shall, at the election of the Company,
become null and void.

6.    Provisions of the Plan.

      This option is subject to the provisions of the Plan, a copy of which is
furnished to the Participant with this option.

                                      -2-
<PAGE>

      IN WITNESS WHEREOF, the Company has caused this option to be executed
under its corporate seal by its duly authorized officer. This option shall take
effect as a sealed instrument.

                                    HYBRIDON, INC.

Dated:                              By:
       ---------                        ------------------------------------
                                            Name:
                                                  -----------------------------
                                            Title:
                                                   ----------------------------

                                      -3-
<PAGE>

                            PARTICIPANT'S ACCEPTANCE

      The undersigned hereby accepts the foregoing option and agrees to the
terms and conditions thereof. The undersigned hereby acknowledges receipt of a
copy of the Company's 1997 Stock Incentive Plan.

                                    PARTICIPANT:

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

                                    Address:
                                              -------------------

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

                                      -4-

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