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
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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
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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
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(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
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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
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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
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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 Requested
