Document:

AMENDMENT TO JOINT RESEARCH AGREEMENT

DAIICHI PHARMACEUTICAL CO., LTD., a corporation organized and existing under the
laws of Japan, and having its registered  office at 14-10,  Nihonbashi  3-chome,
Chuo-Ku,   Tokyo,   Japan   (hereinafter   called   "DAIICHI")   and   MICROCIDE
PHARMACEUTICALS,  INC. a corporation  organized  and existing  under the laws of
California, and having its registered office at 850 Maude Avenue, Mountain View,
CA 94043,  U.S.A.  (hereinafter  called  "MPI")  hereby amend that certain Joint
Research Agreement they entered into as of November 6, 1995, and, its supplement
they  entered  into as of  March  25,  1998  (hereinafter  called  "Supplement")
(hereinafter collectively called "JRA").

                                   WITNESSETH

         WHEREAS,  MPI has carried out research in the field of bacterial efflux
pump inhibitors ("EPIs") ; and

         WHEREAS,  DAIICHI has engaged in the pharmaceutical  business including
the specialties based on the fluoro-quinolone chemical compounds; and

         WHEREAS,  DAIICHI  and MPI  agreed to  jointly  carry out  research  in
finding  pharmaceutical  candidates  in the field of bacterial  EPIs and entered
into the JRA to establish their joint effort; and

         WHEREAS,  MPI and  DAIICHI  have  conducted  the  Research  Program (as
defined in the JRA) in the field of bacterial efflux pump inhibitors pursuant to
the JRA; and

         WHEREAS, as of the conclusion of the Research Period (as defined in the
JRA) on March 31,  1999,  DAIICHI  has [*] (as that term is  defined in the JRA)
with  respect to any  compounds  identified  during  the course of the  Research
Program,  although  DAIICHI and MPI have  identified  [*]  Compunds  (as defined
hereinafter) as Collaboration Compunds (as defined in the JRA); and

         WHEREAS, both DAIICHI and MPI wish to continue their respective efforts
in the area of bacterial EPIs pursuant to the terms outlined below;

         NOW, THEREFORE,  for and in consideration of the premises and covenants
contained herein and pursuant to Article 15 of the JRA, DAIICHI and MPI agree to
amend the JRA as follows:

         1.       Section  1.2 is hereby  deleted and  replaced in its  entirety
                  with the  following:  "The term "Field"  means the  discovery,
                  development,  manufacture,  sale and/or use of compounds which
                  inhibit  efflux-pumps in Pseudomonas  aeruginosa  which confer
                  resistance to [*] antibiotics effluxed [*] P. aeruginosa."

[*] Confidential Treatment Requested

<PAGE>

         2.       Section  1.11 is hereby  deleted and  replaced in its entirety
                  with the following:  "The term "Collaboration  Compound" means
                  any composition of matter which is discovered,  identified, or
                  first  synthesized  by MPI  and/or  DAIICHI  in the  course of
                  performing  research  specifically  directed at  discovery  or
                  development  of product  within the Field  during the Research
                  Period  [*],  and which in each case  meets the  Criteria  (as
                  hereinafter  defined) in testing  performed prior to March 31,
                  2000.  For the  purpose  of the  definition  of  Collaboration
                  Compound,  "Criteria"  means:  [*]  in P.  aeruginosa  strains
                  [*], or [*] in P. aeruginosa strains [*]."

         3.       Subsection (i) in the first sentence of Section 1.12 is hereby
                  deleted and replaced  with the  following:  "is derived from a
                  Collaboration  Compound  and  synthesized  in  the  course  of
                  performing  the  Research  Program  prior  to  the  end of the
                  Research  Period,  but which fails to satisfy the  Criteria in
                  Section 1.11 herein, or."

         4.       Section 1.12 is hereby  amended by deleting  the  remainder of
                  Subsection  (ii)  in the  first  sentence  after  "or  pending
                  application" and replacing it with the following: "as of March
                  31, 2000."

         5.       Section 1.13 is hereby  amended by replacing "the first day of
                  the second year of the Independent Research Period" with [*].

         6.       Section 1.15 is hereby  amended by deleting  the  remainder of
                  the second  sentence after "within the Field" and replacing it
                  with the following:  "during the period beginning with the end
                  of the Research Period and ending on March 31, 2000."

         7.       Section 1.15 is further amended by adding the following at the
                  end of the Section:  "The parties  represent and warrant that,
                  as of the date of this  Amendment,  the only Joint Patents and
                  applications  for Joint  Patents  are those shown in Exhibit A
                  hereto.  The parties further represent and warrant that, as of
                  the date of this  Amendment,  the only chemical genera claimed
                  and  disclosed in the Joint Patents are those shown in Exhibit
                  A hereto."

         8.       Article 2 is hereby  amended  by adding a new  Section  2.3 as
                  follows:  " 2.3 In order for MPI to conduct certain scientific
                  investigations as mutually agreed with DAIICHI as mentioned in
                  Section 10.7 (a),  DAIICHI hereby grants MPI the  nonexclusive
                  license  under  the  Daiichi  Patent,   Joint  Patent,   Joint
                  Information and Daiichi Information to conduct research within
                  the Field during the Independent Research Period."

         9.       Section 4.8 is hereby amended by inserting the following after
                  "within  the  Field,"  in the  third  line:  "and to  disclose
                  DAIICHI Information  regarding the broad-spectrum  efflux pump
                  inhibitors [*] during the Independent Research Period.

         10.      Section  4.8  is  hereby  further  amended  by  inserting  the
                  following  after "DAIICHI  Information" in the last line: "and
                  MPI providing DAIICHI with one  comprehensive  data package in
                  advance of any such disclosure(s), which describes any and all
                  data which may be disclosed to such third parties by MPI."

[*] Confidential Treatment Requested
<PAGE>

         11.      Section 4.8 is hereby further  amended by adding the following
                  at the end of Section:  "Notwithstanding  the  foregoing,  MPI
                  shall not, however,  disclose any information on the compounds
                  [*] to any third party."

         12.      Section  4.9 is hereby  amended by  deleting  the first  three
                  sentences  in  their  entirety  and  replacing  them  with the
                  following:  "The  parties  shall  finally  confirm  in writing
                  whether  any  compound   generated  by  the  Research  Program
                  qualifies as a Collaboration Compound until March 31, 2000."

         13.      Section 6.1 is hereby  amended by inserting  the  following as
                  the second sentence in the Section: [*].

         14.      Section 6.1 is hereby further  amended by adding the following
                  sentence at the end of the Section: "However, if MPI discloses
                  a [*] Collaboration  Compound to DAIICHI pursuant to this JRA,
                  and DAIICHI  does not  exercise  its option under this Section
                  within ninety (90) days of such disclosure, the DAIICHI option
                  for Stage III with respect to such Compound will terminate."

         15.      Section 8.2(a) is hereby deleted in its entirety.

         16.      Section 8.2(c) is hereby deleted in its entirety.

         17.      Section 8.5(c) is hereby amended by deleting the last sentence
                  in its entirety.

         18.      The second  sentence  of Section  10.2 is hereby  deleted  and
                  replaced in its entirety with: "MPI shall provide  semi-annual
                  progress  reports to  DAIICHI  regarding  the MPI  Independent
                  Research (as defined hereinafter),  if any. In the case of MPI
                  Independent Research involving [*] Compounds [*], MPI will use
                  its reasonable efforts to include in such reports  information
                  on such  compounds to DAIICHI  consistent  with the foregoing.
                  However,  DAIICHI  agrees  that MPI's  failure to secure  such
                  disclosure  shall not  constitute  an  immaterial  or material
                  breach of any covenant or obligation of this Agreement, either
                  express or implied."

         19.      Section  10.6(a) is hereby  amended by deleting  the last four
                  lines  of the  Section  following  "Compound  Criteria")"  and
                  replacing them with "as defined in Section 1.11 herein."

         20.      Article  10 is hereby  amended  by adding  the  following  new
                  Section 10.7:

                  10.7     MPI Independent Research.

                           (a) MPI may, by itself or jointly with third parties,
                           conduct  research  during  the  Independent  Research
                           Period  with  respect to [*],  compounds  outside the
                           Field  (the "MPI  Independent  Research").  MPI shall
                           also conduct, at its own expense,  certain scientific
                           investigations   as  mutually  agreed  with  DAIICHI,
                           primarily   in  the   areas   of   microbiology   and
                           pharmacology, [*].

[*] Confidential Treatment Requested
<PAGE>

                           (b)   Neither   MPI  nor   any  of  its   third-party
                           collaborators  will  perform  research   specifically
                           directed at the discovery of  efflux-pump  inhibitors
                           for use with [*]  Pseudomonas  aeruginosa  during the
                           Independent Research Period.

                           (c) For purposes of this Section 10.7,  "MPI Class II
                           Compounds" means [*] Compounds that meet the Criteria
                           in  Section  1.11 and  directly  result  from a joint
                           research  effort between MPI and a third party during
                           the Independent Research Period specifically directed
                           at the  discovery  of EPIs for use outside the Field.
                           MPI Class II  Compounds  shall be subject to the same
                           provisions  of this  Agreement as are MPI  Compounds,
                           except that MPI need not disclose information on such
                           Compounds  to  DAIICHI   until  the  stage  at  which
                           GLP-pre-clinical toxicology has begun.

                           (d)  Notwithstanding  the  provision of Section 13.1,
                           MPI  may   disclose   MPI   Information   and   Joint
                           Information  to   third-parties   [*]  with  whom  it
                           collaborates during the Independent  Research Period,
                           except for  information  pertaining  to [*], provided
                           that MPI shall provide DAIICHI with one comprehensive
                           data  package in  advance of any such  disclosure(s),
                           which  describes  any  and  all  data  which  may  be
                           disclosed  to such  third-parties  by MPI,  and  such
                           third parties enter into  confidentiality  agreements
                           which  provide   substantially   the  same  level  of
                           protection  of   information  as  the  provisions  of
                           Article 13.

         21.      The  first  sentence  of  Section  12.2 is hereby  amended  by
                  deleting "8.2(c)" from the first line.

         22.      Section  13.1 is hereby  amended by  inserting  the  following
                  after "data" in the second line: ", in each case".

         23.      Section  20.2 is hereby  amended by deleting  "8.2(c) or" from
                  the second,  sixth,  seventh,  sixteenth,  twenty-second,  and
                  twenty-fourth  lines, and by deleting "Other Compound or" from
                  the second, sixth, and sixteenth lines, of that Section.

         24.      Exhibit B is hereby deleted in its entirety.

         25.      Section 1.2 of Exhibit D is hereby deleted and replaced in its
                  entirety  with the  following:  "The  term  "Field"  means the
                  discovery,  development,   manufacture,  sale  and/or  use  of
                  compounds which inhibit efflux-pumps in Pseudomonas aeruginosa
                  [*] by P. aeruginosa."

         26.      Section 1.6 of Exhibit D is hereby deleted and replaced in its
                  entirety  with  the   following:   "The  term   "Collaboration
                  Compound" means any composition of matter which is discovered,
                  identified,  or first synthesized by MPI and/or DAIICHI in the
                  course  of  performing  research   specifically   directed  at
                  discovery or  development  of product  within the Field during
                  the  Research  Period  [*],  and which in each case  meets the
                  Criteria (as hereinafter  defined) in testing  performed prior
                  to March  31,  2000.  For the  purpose  of the  definition  of
                  Collaboration Compound, "Criteria" means [*], in P. aeruginosa
                  [*] in P. aeruginosa [*]."

[*] Confidential Treatment Requested
<PAGE>

         27.      Subsection (i) in the first sentence of Section 1.7 of Exhibit
                  D is hereby  deleted  and  replaced  with the  following:  "is
                  derived from a  Collaboration  Compound and synthesized in the
                  course of performing the Research  Program prior to the end of
                  the Research  Period,  but which fails to satisfy the Criteria
                  in Section 1.11 herein, or."

         28.      Section  1.7 of Exhibit D is hereby  amended by  deleting  the
                  remainder of Subsection  (ii) in the first  sentence after "or
                  pending application" and replacing it with the following:  "as
                  of March 31, 2000."

         29.      Section 1.8 of Exhibit D is hereby  amended by replacing  "the
                  first  day of the  second  year  of the  Independent  Research
                  Period" [*]

         30.      Section  1.10 of Exhibit D is hereby  amended by deleting  the
                  remainder of the second  sentence after "within the Field" and
                  replacing  it  with  the  following:  "after  the  end  of the
                  Research Period and until March 31, 2000."

         31.      Section  1.10 of  Exhibit D is  further  amended by adding the
                  following  at the end of the Section:  "The parties  represent
                  and warrant that, as of the date of this  Amendment,  the only
                  Joint  Patents and  applications  for Joint  Patents are those
                  shown in Exhibit A hereto.  The parties further  represent and
                  warrant  that,  as of the  date of this  Amendment,  the  only
                  chemical genera claimed and disclosed in the Joint Patents are
                  those shown in Exhibit A hereto."

         32.      Section 2.7 of Exhibit D is hereby deleted in its entirety.

         33.      Section  5.1(a) of Exhibit D is hereby deleted in its entirety
                  and  replaced  with the  following:  "During  the term of this
                  Agreement prior to the third  anniversary after the end of the
                  Research Period,  MPI shall not (i) grant to any third party a
                  license,  under the Licensed Patent, Joint Patent or any other
                  MPI  composition  of matter patent and patent  application  to
                  commercialize  any MPI Compound or MPI Class II Compound (both
                  as hereinafter  defined) and Other Compound for use within the
                  Field.  Except as set forth in paragraph 5.1 (b) below, during
                  the term of this  Agreement  MPI  shall not grant to any third
                  party a right  or  license  to  sell an MPI  Compound  for use
                  within the Field. "MPI Compound" means compounds, other than a
                  Collaboration Compound or Other Compound, that are discovered,
                  identified, or first synthesized by or on behalf of MPI in the
                  course of performing the research  specifically  directed,  at
                  the time the right or  license  is  granted,  at the Field and
                  which meet the  Criteria  defined in Section 1.6 herein.  "MPI
                  Class II  Compounds"  means  [*]  Compounds  [*] that meet the
                  Criteria  in  Section  1.6 and  directly  result  from a joint
                  research  effort  between  MPI and a third  party  during  the
                  Independent  Research  Period  specifically  directed  at  the
                  discovery  of EPIs for use  outside  the  Field.  MPI Class II
                  Compounds  shall be  subject  to the same  provisions  of this
                  Agreement  as are MPI  Compounds,  except  that  MPI  need not
                  disclose  information  on such  Compounds to DAIICHI until the
                  stage at which GLP-pre-clinical toxicology has begun."

[*] Confidential Treatment Requested
<PAGE>

         34.      Section 8.1 is hereby amended by inserting the following after
                  "data" in the first line: ",in each case".

         35.      Exhibit B to Exhibit D is hereby deleted in its entirety.

         36.      Supplement 2 of SUPPLEMENT is hereby deleted in its entirety.

SIGNATURES AND AGREEMENT

         THIS  AMENDMENT AND THE JRA AS AMENDED BY THIS AMENDMENT SETS FORTH THE
ENTIRE  AGREEMENT AND  UNDERSTANDING  OF THE PARTIES WITH RESPECT TO THE SUBJECT
MATTER HEREOF, AND SUPERSEDES ALL PRIOR DISCUSSIONS,  AGREEMENTS AND WRITINGS IN
RELATION  THERETO.  ALL MATERIAL  REPRESENTATIONS  AND  WARRANTIES  ON WHICH THE
PARTIES HAVE RELIED IN CONNECTION  WITH THE  NEGOTIATION OF THIS  AMENDMENT,  IF
ANY, ARE STATED EXPRESSLY IN THIS AMENDMENT.

         Except as stated in this Amendment,  all other elements of the original
JRA and Exhibits remain unchanged.

         This Amendment may be executed in counterparts,  each of which shall be
deemed an original, but both of which together shall constitute one and the same
instrument.

         IN  WITNESS  WHEREOF,   the  parties  hereto  have  caused  their  duly
authorized representatives to execute this Agreement.

DAIICHI PHARMACEUTICAL CO., LTD.          MICROCIDE PHARMACEUTICALS, INC.

By:  /s/ Kiyoshi Morita                   By:  /s/ James E. Rurka
     ---------------------------               --------------------------

Name:  Kiyoshi Morita                     Name:  James E. Rurka

Title:  President                         Title:  President and CEO

Date:  February 4, 2000                   Date:  January 7, 2000

<PAGE>

                                    Exhibit A

                                 "Joint Patent"

The  following  is a listing  of patent  applications  filed by both of  Daiichi
Pharmaceutical, Co., Ltd. and Microcide Pharmaceuticals, Inc. relating bacterial
efflux pump inhibitors.

The  inventors  are under duty to assign  their  rights to the  invention to the
companies above.

1.       Efflux Pump Inhibitors
         U.S. Serial No.: [*]
         Filed - [*]
         Inventors:  [*]

2.       Efflux Pump Inhibtors
         U.S. Serial No.: [*]
         Filed - [*]
         Inventors:  [*]

[*] Confidential Treatment RequestedAmendment to the Collaborative Research Agreement

         This  Agreement  (the "2000  Amendment") is entered into as of March 1,
2000 by and between Pfizer Inc. ("Pfizer"),  a Delaware  corporation,  having an
office at 235 East 42nd Street,  New York, New York 10017 and its Affiliates and
Microcide Pharmaceuticals,  Inc. ("Microcide"), a California corporation, having
an office at 850 Maude Avenue, Mountain View, California 94043.

         Whereas,  the parties  have  previously  entered  into a  Collaborative
Research Agreement (the "1996 Research Agreement") dated as of March 1, 1996 and
amended as of May 6, 1998,  (the "1998  Amendment")  and a License  and  Royalty
Agreement (the "1996 License Agreement") dated as of March 1, 1996.

Now Therefore,  in consideration of the mutual convenants and promises set forth
in the 1996  Research  Agreement  and the 1998  Amendment,  the parties agree as
follows:

1)       The following sentence s]hall be added to the end of Section 2.2 of the
         1996 Research Agreement:

"The Annual Research Plan for Commitment Year 5, shall be appended to and made a
part of the Agreement as Exhibit C and shall be effective as of March 1, 2000."

2)       Section  3.2 of the  1996  Research  Agreement  shall  be  deleted  and
         replaced by the following:

         Commitment Year                             Annual Commitment

               1                                          $4.2MM
               2                                          $4.2MM
               3                                          $4.2MM
               4                                          $4.2MM
               5                                          $2.1MM

3)       Section  3.3 of the  1996  Research  Agreement  shall  be  deleted  and
         replaced by the following:

"Payments  by Pfizer to cover  Microcide's  total,  full-time  employees  (FTEs)
devoted to the Research Program [*]. Such payments shall be used by Microcide to
perform the Research  Program.  Microcide shall dedicate at least [*] ([*]) FTEs
to perform the  Research  Program and conduct the Annual  Research  Program Plan
during [*]."

Certain  information on this page has been omitted and filed separately with the
Commission.  Confidential  treatment  has been  requested  with  respect  to the
omitted portions.

[*] Confidential Treatment Requested

<PAGE>

All other terms and  conditions  of 1996  Research  Agreement,  the 1996 License
Agreement and 1998 Amendment shall remain the same and in full force and effect.

Please indicate  agreement by signing below.  Return an executed original to Dr.
Edward D. Pagani at Pfizer Central Research.

Agreed:  Microcide Pharmaceuticals, Inc.  Agreed:  Pfizer Inc.

By:  /s/ James E. Rurka                   By:  /s/  George M. Milne, Jr.
     ----------------------------------        --------------------------------
         Mr. James E. Rurka                         Dr. George M. Milne, Jr.
         President and CEO                          President, Pfizer Central
                                                    Research

Date:    March 6, 2000                    Date:     March 1, 2000

<PAGE>

                                                 MICROCIDE PHARMACEUTICALS, INC.
                                                                    CONFIDENTIAL

                                    Exhibit C

                                       [*]

[*] Confidential Treatment Requested

<PAGE>

                                   Addendum A

                                      [*]

[*] Confidential Treatment Requested

<PAGE>

Pfizer-Microcide                                                      01/07/2000
Confidential

                                      [*]

                                   Addendum B

[*] Confidential Treatment Requested

Source: [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00011-of-00352.parquet"}, [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00011-of-00352.parquet"}]]