Document:

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                                                                   EXHIBIT 10.41

                             CONFIDENTIAL TREATMENT

           AMENDMENT NUMBER 3 TO RESEARCH AND LICENSE AGREEMENT BY AND
          BETWEEN MICROCIDE PHARMACEUTICALS, INC., ORTHO PHARMACEUTICAL
         CORPORATION AND R.W. JOHNSON PHARMACEUTICAL RESEARCH INSTITUTE

This Amendment Number 3 ("AMENDMENT NO. 3"), dated this 17th day of December,
2001, is made to the RESEARCH AND LICENSE AGREEMENT (hereinafter called the
"AGREEMENT"), made as of October 24, 1995, as amended by Amendment Number 1
thereto, dated as of October 23, 1998, and Amendment Number 2 thereto, dated as
of December 19, 2000, by and between:

MICROCIDE PHARMACEUTICALS, INC., a corporation organized under Delaware law
having its principal office at 850 Maude Avenue, Mountain View, California 94043
(hereinafter called "MICROCIDE")

ON THE ONE HAND, AND:

ORTHO MCNEIL PHARMACEUTICAL, INC. (hereinafter called "ORTHO"), a company
organized under Delaware law, having its principal office at U.S. Route 202,
Raritan, New Jersey 08869 (successor to Ortho Pharmaceutical Corporation); and

The R.W. JOHNSON PHARMACEUTICAL RESEARCH INSTITUTE (hereinafter called
"RWJPRI"), a division of Ortho McNeil Pharmaceutical, Inc., having its principal
office at U.S. Route 202, Raritan, New Jersey 08869 (ORTHO and RWJPRI
hereinafter collectively called "LICENSEE")

ON THE OTHER HAND,

WITNESSETH:

A.    WHEREAS, MICROCIDE and LICENSEE have entered into the AGREEMENT providing
for a collaborative research drug discovery program in the FIELD as generally
described in the RESEARCH PLAN attached thereto as Appendix A;

B.    WHEREAS, the RESEARCH PLAN provided for several projects to be completed
by the parties over a three year RESEARCH TERM which was extended for an
additional period to conduct collaborative research into the discovery of an
orally active cephalosporin, but which will expire on December 31, 2001, in
accordance with the terms of the AGREEMENT;

C.    WHEREAS, the parties wish to enter into an agreement to extend the
RESEARCH TERM and provide for an extension of the RESEARCH PROGRAM;

D.    WHEREAS, MICROCIDE has changed its name to ESSENTIAL THERAPEUTICS, INC.:

* CONFIDENTIAL TREATMENT REQUESTED: MATERIAL HAS BEEN OMITTED AND FILED
  SEPARATELY WITH THE COMMISSION.

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NOW, THEREFORE, in consideration of the premises and the performance of the
covenants herein contained, the parties agree to amend the AGREEMENT as follows:

1.    Unless otherwise defined herein, all capitalized terms used herein shall
have the same meaning as set forth in the AGREEMENT.

2.    In accordance with the terms of this Amendment Agreement, the RESEARCH
TERM under Section 2.3.3 of the AGREEMENT shall be extended for an additional
period commencing upon signature of this Amendment Agreement and terminating on
the first anniversary thereof, unless further extended by written agreement of
the parties.

3.    Section 2.4 of the AGREEMENT shall be amended by adding the following
section 2.4 (e):

"(e) Toward the performance of the ORAL CEPHALOSPORIN RESEARCH PROGRAM by
Microcide hereunder, RWJPRI is obligated upon signing of this agreement to pay
MICROCIDE [*] dollars ($ [*]) within thirty days of the execution of this
Amendment Agreement."

4.    Except as amended herein, all of the terms and conditions of the AGREEMENT
shall remain in full force and effect.

5.    This AGREEMENT may be executed by telefax transmission and in one or more
counterparts, each of which shall for all purposes be deemed to be an original
but all of which together shall constitute but one and the same agreement.

                     [SIGNATURES ARE ON THE FOLLOWING PAGE]

* CONFIDENTIAL TREATMENT REQUESTED: MATERIAL HAS BEEN OMITTED AND FILED
  SEPARATELY WITH THE COMMISSION.

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IN WITNESS WHEREOF, the parties hereto have hereunto set their hands and duly
executed this Amendment Agreement on the date(s) indicated below, to be
effective the day and year first above written.

For and on Behalf of ESSENTIAL THERAPEUTICS, INC.

By:      /s/      Mark Skaletsky
         -----------------------
Name:    Mark Skaletsky
Title:   Chief Executive
Date:    12/14/01

For and on Behalf of LICENSEE

By:      /s/      Per A. Peterson
         ------------------------
Name:    Per A. Peterson, MD, Ph D
Title:   Chairman Research & Development, Pharmaceuticals
Date:    12/21/01

* CONFIDENTIAL TREATMENT REQUESTED: MATERIAL HAS BEEN OMITTED AND FILED
  SEPARATELY WITH THE COMMISSION.<PAGE>
                                                                   Exhibit 10.42

                                                               December 11, 2001

                              CONSULTING AGREEMENT
                              --------------------

John P. Walker
126 Isabella Avenue
Atherton, CA 94027

Dear John:

     Essential Therapeutics, Inc., a Delaware corporation (formerly known as
Microcide Pharmaceuticals, Inc.) (the "Company"), wishes to obtain your services
as a consultant. This letter shall constitute an agreement between you and the
Company (the "Agreement"), effective as of November 1, 2001 (the "Effective
Date"), and contains all the terms and conditions relating to the performance of
such services.

     1.  Term and Termination. This Agreement shall be effective as of the
         --------------------
Effective Date and terminate on the earlier of the date on which you (1) cease
to serve on the Company's Board of Directors, and (2) cease to provide services
to the Company under this Agreement. This Agreement may be terminated by either
party upon written notice to the other party at any time.

     2.  Consulting. During the term of this agreement, you will provide
         ----------
consulting services as may be reasonably requested by the Chief Executive
Officer of the Company.

     3.  Consideration. As a consideration for your services and other
         -------------
obligations, the Company agrees to pay you at the rate of $2,500.00 per fiscal
quarter, in arrears, with the first such quarterly payment to be due on March
31, 2002. For your services during the period from the Effective Date through
December 31, 2001, the Company agrees to pay you the sum of $1,666.66 on or
before December 31, 2001.

     4.  Support. As additional consideration for your services hereunder, the
         -------
Company will provide you with such support facilities and space as may be
required in the Company's judgment to enable you to properly perform your
services hereunder.

     5.  Expenses. You will be reimbursed for reasonable travel and other
         --------
out-of-pocket expenses incurred by you in connection with your services under
this agreement, provided that you provide receipts and an invoice on a monthly
basis and obtain prior approval of the Chief Executive Officer of the Company
for any significant expenses. Such reimbursements will be paid within fifteen
(15) days of receipt of the invoice.

     6.  Independent Contractor. Your relationship with the Company will be that
         ----------------------
of an independent contractor and not that of an employee. You will not be
eligible for any employee benefits, nor will the Company make deductions from
payments made to you for taxes, which will be your responsibility. You agree to
indemnity and hold the Company harmless from any liability for, or assessment
of, any such taxes imposed on the Company by relevant taxing authorities. You
will have no authority to enter into contracts that bind the Company or create

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                     Consulting Agreement -- John P. Walker
                                    Page -2-

obligations on the part of the Company without the prior written authorization
of the Company.

     7.  Reporting. All services to be performed by you will be as agreed
         ---------
between you and the Chief Executive Officer of the Company, with periodic
reports to the Board of Directors concerning your services performed under this
agreement. The nature and frequency of these reports will be left to the
discretion of the Board of Directors.

     8.  Confidentiality. You shall keep in confidence and shall not disclose or
         ---------------
make available to third parties or make any use of any information or documents
relating to your services under this agreement, the research and development
activities, or to the products, methods of manufacture, trade secrets,
processes, business or affairs or confidential or proprietary information of the
Company (other than information in the public domain through no fault of your
own), except with the prior written consent of the Company or to the extent
necessary in performing tasks assigned to you by the Company. Within five
business days of termination of this agreement, you will return to the Company
all documents and other materials related to the services provided hereunder or
furnished to you by the Company at any time. Your obligations under this
Paragraph 8 will survive termination of this agreement.

     9.  Amendment. Any amendment to this agreement must be in writing signed
         ---------
you and the Company.

     10. Notices. All notices, requests and other communications called for by
         -------
this agreement shall be deemed to have been given if made in writing and
personally delivered or mailed, postage prepaid, if to you at the address set
forth above and if to the Company at 1365 Main Street, Waltham, Massachusetts
02451, Attention: Chief Executive Officer, or to such other addresses as either
party shall specify to the other.

     11. Governing Law. The laws of the State of California shall govern the
         -------------
validity, performance and construction of this agreement.

     12. Arbitration. By signing this agreement, you acknowledge and understand
         -----------
that any disagreement regarding this agreement will be determined by submission
to arbitration as provided by Section 1230 et seq. of the California code of
Civil Procedure, and not by a lawsuit or resort to court process proceedings.
All parties to this Agreement, by entering into it, are giving up any right to
have any such dispute decided in a court before a jury, and instead are
accepting the use of arbitration.

     13. Prior Agreements. This agreement supersedes all other agreements
         ----------------
between you and the Company, including, but not limited to, that Consulting
Agreement, dated January 1, 2001.

<PAGE>

                     Consulting Agreement -- John P. Walker
                                    Page -3-

     If this agreement is satisfactory, you should execute and return the
original and one copy to us, retaining the third copy for your file.

                                     Very truly yours,

                                     By: /s/ Mark Skaletsky
                                        ------------------------------
                                         Mark Skaletsky, President and
                                         Chief Executive Officer

AGREED AND ACCEPTED

/s/ John P. Walker
----------------------
 John P. Walker

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