Document:

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                                                                  EXHIBIT 10.166

                                                THE IMMUNE RESPONSE CORPORATION

[ ]                                             NOTICE OF GRANT OF STOCK OPTIONS

[ ]                                             ID: 33-0255679

                                                AND OPTION AGREEMENT

[ ]                                             5931 Darwin Court

[ ]                                             Carlsbad, CA  92008

JOHN N. BONFIGLIO                               OPTION NUMBER:     00003391
13195 SEAGROVE STREET                           PLAN:              2003
SAN DIEGO, CA 92130                             ID:                ###-##-####

Effective 12/20/2004, you have been granted a(n) Non-Qualified Stock Option to
buy 75,000 shares of The Immune Response Corporation (the Company) stock at
$1.1900 per share.

The total option price of the shares granted is $89,250.00.

Shares in each period will become fully vested on the date shown.

               Shares         Vest Type         Full Vest         Expiration

                     75,000     On Vest Date         1/1/2005       1/1/2015

By your signature and the Company's signature below, you and the Company agree
that these options are granted under and governed by the terms and conditions of
the Company's Stock Option Plan as amended and the Option Agreement, all of
which are attached and made a part of this document.

/s/ Michael K. Green
------------------------------------
 The Immune Response Corporation                     Date  December 22, 2004
                                                           -----------------

/s/ John N. Bonfiglio
------------------------------------
 John N. Bonfiglio                                   Date  December 22, 2004
                                                           -----------------
<PAGE>
                                                THE IMMUNE RESPONSE CORPORATION

[ ]                                             NOTICE OF GRANT OF STOCK OPTIONS

[ ]                                             ID: 33-0255679

                                                AND OPTION AGREEMENT

[ ]                                             5931 Darwin Court

[ ]                                             Carlsbad, CA  92008

JOHN N. BONFIGLIO                               OPTION NUMBER:     00003392
13195 SEAGROVE STREET                           PLAN:              2003
SAN DIEGO, CA 92130                             ID:                ###-##-####

Effective 12/20/2004, you have been granted a(n) Non-Qualified Stock Option to
buy 175,000 shares of The Immune Response Corporation (the Company) stock at
$1.1900 per share.

The total option price of the shares granted is $208,250.00.

Shares in each period will become fully vested on the date shown.

               Shares         Vest Type         Full Vest         Expiration

                     175,000    Daily                1/1/2007       1/1/2015

By your signature and the Company's signature below, you and the Company agree
that these options are granted under and governed by the terms and conditions of
the Company's Stock Option Plan as amended and the Option Agreement, all of
which are attached and made a part of this document.

/s/ Michael K. Green
------------------------------------
 The Immune Response Corporation                     Date  December 22, 2004
                                                           -----------------

/s/ John N. Bonfiglio
------------------------------------
 John N. Bonfiglio                                   Date  December 22, 2004
                                                           -----------------
<PAGE>
IT IS UNLAWFUL TO CONSUMMATE A SALE OR TRANSFER OF THIS SECURITY, OR ANY
INTEREST THEREIN, OR TO RECEIVE ANY CONSIDERATION THEREFOR, WITHOUT THE PRIOR
WRITTEN CONSENT OF THE CALIFORNIA CORPORATIONS COMMISSIONER OF THE STATE OF
CALIFORNIA, EXCEPT AS PERMITTED IN THE COMMISSIONER'S RULES.

                         THE IMMUNE RESPONSE CORPORATION
                                 2003 STOCK PLAN
                                OPTION AGREEMENT
                                (STANDARD GRANT)

THE IMMUNE RESPONSE CORPORATION (the "Company"), pursuant to its 2003 Stock Plan
as adopted by the Board of Directors of the Company effective February 25, 2003
(the "Plan"), grants to Optionholder the right to purchase the number of shares
of the Company's Common Stock set forth in the Notice of Grant of Stock Options
("Grant Notice") delivered with this document to Optionholder, on the terms and
conditions set forth below and in the Grant Notice and the Plan (such right is
hereinafter referred to as the "Option"). This document and the Grant Notice
together comprise the option agreement for the Option (this "Option Agreement").

                          GENERAL TERMS AND CONDITIONS

The Option is granted subject to the following terms and conditions. Defined
terms not explicitly defined in this Option Agreement but defined in the Plan
shall have the same definitions as in the Plan.

1.       NUMBER OF SHARES AND EXERCISE PRICE. The Option may only be exercised
for whole shares of Common Stock, up to the total number of shares of Common
Stock set forth in the Grant Notice. The number of shares of Common Stock
subject to the Option and Optionholder's exercise price per share referenced in
Optionholder's Grant Notice may be adjusted from time to time for capitalization
adjustments, as provided in the Plan.

2.       VESTING. Subject to the limitations contained herein and in the Plan,
the Option will vest as provided in the vesting schedule set forth in the Grant
Notice, provided that Optionholder continues his or her Service with the Company
during such vesting schedule, until fully vested or terminated under the terms
of this Option Agreement and the Plan. The vesting of the Option shall cease
upon termination of Optionholder's Service with the Company.

3.       EXERCISABILITY OF THE OPTION. Optionholder may exercise only the vested
portion of the Option during its term by delivering a Notice of Exercise (on
such terms and on such form as may be designated by the Company) together with
the consideration for the exercise of the Option to the address provided in the
form of Notice of Exercise, or to such other person as the Company may
designate, during regular business hours, together with such additional
documents as the Company may then require. The Notice of Exercise must specify
the number of shares of Common Stock to be purchased by Optionholder upon the
exercise of the Option and how such shares shall be registered. The Notice of
Exercise shall be effective upon receipt by the Company.

4.       METHOD OF PAYMENT.

         (A) Payment of the exercise price is due in full upon exercise of all
or any part of the Option. Optionholder may elect to make payment of the
exercise price:

(i)      by personal check, cashier's check or money order;

(ii)     by cashless exercise, whereby Optionholder provides irrevocable
         direction to a securities broker approved by the Company to sell Common
         Shares underlying the Option and to deliver all or part of the sales
         proceeds to the Company in payment of all or part of the Exercise Price
         and any withholding taxes;

(iii)    by delivery and surrender to the Company of already-owned shares of
         Common Stock either that Optionholder has held for the period required
         to avoid a charge to the Company's reported earnings (generally six
         months) or that Optionholder did not acquire, directly or indirectly
         from the Company, that are owned free and clear of any liens, claims,
         encumbrances or security interests, and that are valued at Fair Market
         Value on the date of exercise.
<PAGE>
"Delivery" for these purposes, in the sole discretion of the Company at the time
Optionholder exercises the Option, shall include delivery to the Company of
Optionholder's attestation of ownership of such shares of Common Stock in a form
approved by the Company.

         (B) Notwithstanding the foregoing, Optionholder may not exercise the
Option by a cashless exercise or tender to the Company of Common Stock to the
extent such cashless exercise or tender would violate the provisions of any law,
regulation or agreement restricting the redemption of the Company's stock.

5.       SECURITIES LAW COMPLIANCE. Notwithstanding anything to the contrary
contained herein, Optionholder may not exercise the Option unless the Company
determines that (i) such exercise would be in material compliance with
applicable laws and regulations, and (ii) shares of Common Stock issuable upon
such exercise are then registered under the Securities Act or such exercise and
issuance would be exempt from the registration requirements of the Securities
Act and of any applicable state securities laws.

6.       RESTRICTIONS ON RESALE. Notwithstanding anything to the contrary
contained herein, Optionholder may not sell any shares issued upon exercise of
the Option at such time that applicable law or Company policy may prohibit such
a sale. This restriction on resale shall be applicable until the termination of
the Optionholder's Service.

7.       TAX WITHHOLDING OBLIGATIONS. At the time Optionholder exercises the
Option and as a condition for the exercise of the Option, in whole or in part,
or at any time thereafter as requested by the Company, Optionholder hereby
authorizes withholding from payroll and any other amounts payable to
Optionholder, and otherwise agrees to make adequate provision for (including by
means of a "cashless exercise"), any sums required to satisfy the applicable
federal, state, local and foreign tax withholding obligations of the Company or
an Affiliate, if any, which arise in connection with the Option.

8.       TERM. Optionholder may not exercise the Option before the commencement
of its term or after its term expires. The term of the Option commences on the
Date of Grant and expires upon the EARLIEST of the following:

(i)      ninety (90) days after the termination of Optionholder's Service for
         any reason other than for Optionholder's disability or death, provided
         that if during any part of such ninety (90) day period the Option is
         not exercisable solely because of the condition set forth in Section 5
         relating to "Securities Law Compliance," the Option shall not expire
         until the earlier of the Expiration Date or until it shall have been
         exercisable for an aggregate period of ninety (90) days after the
         termination of Optionholder's Service;

(ii)     six (6) months after the termination of Optionholder's Service due to
         Optionholder's disability;

(iii)    six (6) months after Optionholder's death if Optionholder dies either
         during Optionholder's Service or within ninety (90) days after
         Optionholder's Service terminates;

(iv)     the Expiration Date indicated in the Grant Notice; or

(v)      the day before the tenth (10th) anniversary of the date of grant of the
         Option.

9.       NONSTATUTORY STOCK OPTION. The Option is a nonstatutory stock option
         and not an incentive stock option within the meaning of that term in
         Section 422 of the Internal Revenue Code of 1986, as amended

10.      OPTION NOT A SERVICE CONTRACT. Neither the Option nor this Option
         Agreement is an employment or service contract, and nothing in the
         Option Agreement or the Plan shall obligate the Company or an
         Affiliate, their respective shareholders, Boards of Directors, Officers
         or Employees to continue any relationship that Optionholder might have
         as an employee, Director or Consultant for the Company or an Affiliate.

11.      CONTROLLING DOCUMENTS.  In the event of any conflict among this
document, the Grant Notice and the Plan, the provisions of the Plan shall
supersede the provisions of this document and the Grant Notice, and the
provisions of this document shall supersede the provisions of the Grant Notice.

12.      APPLICABLE LAW.  This Option Agreement shall be governed by, and
construed in accordance with the laws of the State of California, as such laws
are applied to contracts entered into and performed in such state.
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THE IMMUNE RESPONSE CORPORATION               OPTIONHOLDER

By:  /s/ Michael K. Green                     /s/ John N. Bonfiglio
     ------------------------------------     ----------------------------------
                         Signature                            Signature

Title: Vice President, Finance and CFO        Date: December 22, 2004
       -------------------------------              ----------------------------

Date: December 22, 2004
      -----------------------------------<PAGE>

                                     [LOGO]

                                                                  EXHIBIT 10.167

February 3, 2005

Mr. Robert E. Knowling, Jr.

Dear Bob:

It is my pleasure to extend to you the offer to become the Chairman of The
Immune Response Corporation's Board of Directors. In this position, you will
work closely with me to lead this Company toward its ultimate goal of
commercializing its products for HIV and MS. Bob, as we have already discussed,
I believe that there is immense potential here to help alleviate human suffering
and we are on the brink of realizing that goal. Working together, we can more
than double the chances of our success.

Therefore, pursuant to this letter agreement (the "Agreement"), we are pleased
to make to you the following offer with The Immune Response Corporation (the
"Company"):

1.    Responsibilities

You will be elected to a Board of Directors seat with a three-year term ending
in 2006, and you will be elected Chairman of the Company's Board of Directors,
effective February 9, 2005 (the "Effective Date"). It is acknowledged that
continuation of your service as a Director shall be subject to your re-election
by the Company's stockholders, and continuation of your service as a Director
shall be at the Board's ongoing discretion. You will agree to devote to the
Company such time as is necessary to work on key initiatives for the Company,
including but not limited to, (a) strategic planning, licensing and business
development, (b) representing the Company in public forums, (c) assisting in
financing opportunities for the Company and (d) serving on such Board Committees
as the Board may from time to time decide.

2.    Compensation and Benefits

      As Chairman, you shall be entitled to the following:

      2.1 Subject to receipt of all requisite approvals of the Board of
      Directors, you shall receive a grant of stock options to purchase 750,000
      common shares. The exercise price for these stock options will be set
      equal to the closing price of the Company's common stock on the Effective
      Date. 200,000 of the options shall be vested immediately upon the
      Effective Date, and the remaining 550,000 options shall vest in equal
      daily installments from the day

<PAGE>

      after the Effective Date through the third anniversary of the Effective
      Date, subject to continuation of your service as Chairman of the Company.

      In view of this substantial initial stock option grant, you waive any
      ongoing cash or other equity compensation available to the Company's
      outside directors generally.

      2.2 In the event of the occurrence of a Change of Control (as described
      below), the stock options described in paragraph 2.1 (or any substituted
      stock options) shall, as of the date of such Change of Control, vest in
      full and become fully exercisable to the extent not previously vested or
      exercisable, and all options so vested or previously vested shall continue
      to be exercisable for a period of six (6) months or until the applicable
      expiration date of such options (in accordance with their terms),
      whichever period is shorter. For purposes of this Agreement, "Change of
      Control" shall mean any of the following events:

            (1)   a sale, lease or other disposition of all or substantially all
                  of the assets of the Company so long as the Company's
                  stockholders immediately prior to such transaction will,
                  immediately after such transaction, fail to possess (as such)
                  direct or indirect beneficial ownership of more than fifty
                  percent (50%) of the voting power of the acquiring entity (for
                  purposes of this section, any person who acquired securities
                  of the Company prior to the occurrence of such asset
                  transaction in contemplation of such transaction and who after
                  such transaction possesses direct or indirect ownership of at
                  least ten percent (10%) of the securities of the acquiring
                  entity immediately following such transaction shall not be
                  included in the group of stockholders of the Company
                  immediately prior to such transaction);

            (2)   either a merger or consolidation in which the Company is not
                  the surviving corporation and the stockholders of the Company
                  immediately prior to the merger or consolidation fail to
                  possess (as such) direct or indirect beneficial ownership of
                  more than fifty percent (50%) of the voting power of the
                  securities of the surviving corporation (or if the surviving
                  corporation is a controlled subsidiary of another entity, then
                  the required beneficial ownership shall be determined with
                  respect to the securities of that entity which controls the
                  surviving corporation and is not itself a controlled
                  subsidiary of any other entity) immediately following such
                  transaction, or a reverse merger in which the Company is the
                  surviving corporation and the stockholders of the Company
                  immediately prior to the reverse merger fail to possess direct
                  or indirect beneficial ownership of more than fifty percent
                  (50%) of the securities of the Company (or if the Company is a
                  controlled subsidiary of another entity, then the required
                  beneficial ownership shall be determined with respect to the
                  securities of that entity which controls the Company and is
                  not itself a controlled subsidiary of any other entity)
                  immediately following the reverse merger (for purposes of this
                  section, any person who acquired securities of the Company
                  prior to the occurrence of a merger, reverse merger, or
                  consolidation in contemplation of such transaction and who
                  after such transaction possesses (as such) direct or indirect
                  beneficial ownership of at least ten percent (10%) of the
                  securities of the Company or the surviving corporation (or if
                  the Company or the surviving corporation is a controlled
                  subsidiary, then of the appropriate entity as determined
                  above)

<PAGE>

                  immediately following such transaction shall not be included
                  in the group of stockholders of the Company immediately prior
                  to such transaction);

            (3)   an acquisition by any person, entity or group within the
                  meaning of Section 13(d) or 14(d) of the Securities Exchange
                  Act of 1934, as amended (the "Exchange Act"), or any
                  comparable successor provisions (excluding Kevin Kimberlin and
                  also excluding any employee benefit plan, or related trust,
                  sponsored or maintained by the Company or a subsidiary or
                  other controlled Subsidiary of the Company) of the beneficial
                  ownership (within the meaning of Rule 13d-3 promulgated under
                  the Exchange Act, or comparable successor rule) of securities
                  of the Company representing at least fifty percent (50%) of
                  the combined voting power entitled to vote in the election of
                  directors; or

            (4)   the individuals who, as of the date of this Agreement, are
                  members of the Board (the "Incumbent Board") cease for any
                  reason to constitute at least fifty percent (50%) of the
                  Board. If the election, or nomination for election by the
                  Company's stockholders, of any new director was approved by a
                  vote of at least fifty percent (50%) of the Incumbent Board,
                  such new director shall be considered as a member of the
                  Incumbent Board.

                        Notwithstanding the foregoing, a public offering of the
                        common stock of the Company shall not be considered a
                        "Change of Control."

      2.3 You shall be entitled to reimbursement from the Company for all
      reasonable and customary expenses incurred by you in performing services
      under this Agreement, including travel expenses and other out-of-pocket
      expenses, in accordance with the Company's reimbursement policies and
      provided that you shall submit to the Company reasonable documentation
      evidencing such expenses.

3.    Confidentiality and Non-Competition

      Subject to any provisions of any confidentiality agreement into which you
      and the Company may enter, you agree that you will not, during the term of
      the service on the Board and at any time thereafter, without the prior
      written consent of the Company, divulge, disclose or use, directly or
      indirectly, except in the course of your directorship, any Confidential
      Information (as defined below) without the prior written approval of the
      Company.

      In addition, you hereby agree that you will not, directly or indirectly,
      as an individual proprietor, partner, stockholder, officer, employee,
      director, joint venture, investor, lender, or in any other capacity
      whatsoever (other than as the holder of not more than two percent (2%) of
      the total outstanding stock of a publicly-held company), and in any city,
      county, state or other geographic area where the Company is then marketing
      or selling its products or providing services, engage in the business of
      developing, producing, marketing or selling products or providing services
      of the kind or type reasonably related to the products or services being
      developed, produced, marketed, sold or provided directly or indirectly by
      the Company.

<PAGE>

      Further, you hereby agree:

      3.1 Upon request, to return to the Company any information, documents and
      other property you may have received as a result of your directorship; and

      3.2 That the remedy at law for any breach of any of the foregoing will be
      inadequate and that the Company, in addition to any remedy at law, will be
      entitled to injunctive and other relief in cases of any such breach. The
      provisions of this Section 3 shall survive the termination of the term of
      this Agreement.

      3.3 As used herein, "Confidential Information" shall mean any and all
      information (oral and written) relating to the Company, whether prepared
      by or on behalf of the Company or by you or any third party including,
      without limitation, all information relating to trade secrets,
      intellectual property, software, technical or non-technical data, research
      and reports, customer information and lists, employee information,
      methods, techniques, financial data, financial plans or financial
      information, lists of actual or potential strategies, notes, marketing
      approaches, sales techniques, analyses, finances, business affairs or any
      other information, which, under all circumstances, ought reasonably to be
      treated as confidential and/or proprietary.

4.    Miscellaneous

      4.1 Governing Law. This Agreement shall be governed by and construed in
      accordance with the laws of the State of California without regard to
      principles of conflict of laws.

      4.2 Arbitration. Any controversy or claim based on, arising out of or
      relating to the interpretation and performance of this Agreement or any
      termination hereof or of your service as Chairman or as a Director shall
      be solely and finally settled by binding arbitration under the rules of
      the American Arbitration Association, and judgment on the award rendered
      in the arbitration may be entered in any court having jurisdiction
      thereof. Any such arbitration shall be in the state of California and
      shall be submitted to a single arbitrator appointed by the mutual consent
      of the parties or, in the absence of such consent, by application of any
      party to the American Arbitration Association. A decision of the
      arbitrator shall be final and binding upon the parties, and the arbitrator
      shall be authorized to apportion fees and expenses (including counsel fees
      and expenses), as the arbitrator shall deem appropriate.

      4.3 Entire Agreement; Amendment. This Agreement contains the complete
      understanding and agreement between the parties hereto with respect to the
      subject matter hereof, and supersedes all prior and contemporaneous
      understandings and agreements, written or oral, between the parties
      relating to the subject matter hereof. This Agreement may not be amended
      or waived except in a written document signed by you and the Company.

      4.4 Severability. In the event that any provision or portion of this
      Agreement shall be determined to be invalid or unenforceable for any
      reason, in whole or in part, the remaining

<PAGE>

      provisions of this Agreement shall be unaffected thereby and shall remain
      in full force and effect to the fullest extent permitted by law and any
      such invalidity or unenforceability shall be deemed replaced by a term or
      provision determined by the parties as coming closest to expressing the
      intention of the invalid or unenforceable term or provision.

      4.5 Notice. Any notice to be given hereunder shall be in writing and
      delivered either in person, by nationally recognized overnight courier, or
      by registered or certified first class mail, postage prepaid, addressed to
      such address of the parties as set forth on the first page hereof.

      4.6 Headings. The Section headings in this Agreement are for convenience
      of reference only and shall not affect its interpretation.

      4.7 Counterparts. This Agreement may be executed in counterparts, each of
      which shall be deemed an original, but all of which when together shall
      constitute one and the same agreement.

      4.8 Director & Officer Insurance. Director & Officer liability insurance
      shall be provided to you by the Company to the same extent, if any, that
      it is provided to the other Directors of the Company.

      4.9 Indemnification. To the extent and under the circumstances permitted
      by the Delaware General Corporation Law, the Company hereby indemnifies
      and holds you harmless against any and all losses, claims, suits,
      judgments, damages, liabilities, costs or expenses, including reasonable
      legal fees and expenses, to which you may become subject in connection
      with the good faith performance of your responsibilities under this
      Agreement. This provision will survive termination of this Agreement.

Bob, if the foregoing accurately represents our understanding, please sign below
and return it to us.

Warmest regards,

/s/ John N. Bonfiglio, PhD.
--------------------------
President & CEO
The Immune Response Corporation

ACCEPTED AND AGREED IN ALL RESPECTS THIS
8th DAY OF FEBRUARY 2005:

/s/ Robert E. Knowling, Jr.
--------------------------
Robert E. Knowling, Jr.

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