Research Agreement
This Research Agreement ("Agreement") effective as of May 8, 2000 ("Effective
Date") made by and between MICROCIDE PHARMACEUTICALS, INC., a corporation
organized and existing under the laws of California, and having its offices at
850 Maude Avenue, Mountain View, CA 94043, U.S.A. ("MPI") and Daiichi
Pharmaceutical Co., Ltd., a corporation organized and existing under the laws of
Japan, and having its offices at 16-13, Kita-Kasai 1-Chome, Edogawa-ku, Tokyo
134-8630, Japan ("Daiichi")
WITNESSETH THAT:
WHEREAS, Daiichi and MPI jointly carried out research in finding
pharmaceutical candidates in the field of bacterial efflux pump inhibitors
("EPIs") under JOINT RESEARCH AGREEMENT dated on November 6, 1995, which is
supplemented by SUPPLEMENT TO THE JOINT RESEARCH AGREEMENT dated on March 25,
1998 and amended by AMENDMENT TO JOINT RESEARCH AGREEMENT dated on February 4,
2000 (collectively called "JRA"), until the end of March in 1999; and
WHEREAS, thereafter Daiichi and MPI respectively are conducting
Independent Research and MPI Independent Research (as respectively defined in
the JRA) under JRA; and
WHEREAS, Daiichi has looked for the contractor of research in the field
of EPIs to carry out some studies on behalf of Daiichi; and
WHEREAS, Daiichi decided to consign those studies to MPI and proposed
MPI to carry out the studies regarding EPIs; and
WHEREAS, MPI is willing to accept such proposal.
NOW THEREFORE, in consideration of the promises and mutual covenants contained
in this Agreement, the parties agree as follows:
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ARTICLE 1. GENERAL SCOPE OF STUDIES
1.1 During one (1) year period starting from the Effective Date ("Study
Period"), MPI shall perform following studies ("Studies"), in accordance with
the terms and conditions set forth in this Agreement and the protocols in Annex
A attached hereto ("Protocols"):
1. Medicinal chemistry on [*].
2. Characterization of synthesized compounds.
3. Surveillance and profiling of expression of efflux pumps (Mex pumps) in
clinical isolates of Pseudomonas aeruginosa from western countries (at
least U.S.A., Canada, and Europe).
4. Investigation of current trends and efficacy (satisfaction by physicians)
in the treatment for Pseudomonas infections in western countries.
The parties may engage in good faith negotiation to adjust the contents of the
Protocols from time to time.
1.2 Daiichi agrees that MPI carries out the Studies in the Field (as
defined in the JRA) under this Agreement notwithstanding the provision of
Section 10.7 (b) of JRA. MPI understands that the Studies carried out by MPI
under this Agreement are a part of the Independent Research of Daiichi.
ARTICLE 2. COST AND PAYMENT
2.1 As consideration for carrying out the Studies, Daiichi shall pay to MPI
a total amount of [*] US dollars (US $[*]) in accordance with the following
payment schedule.
Within thirty (30) days after the Effective Date:
[*] US dollars (US $[*])
Within thirty (30) days after Daiichi's receipt of the final report
pursuant to Section 3.1 below:
[*] US dollars (US $[*])
The above payment includes all applicable indirect costs due MPI. The actual
costs incurred by MPI during the Study Period shall not exceed the research fee
above. If the actual costs incurred by MPI for the Studies during the Study
Period are lower than the research fee above, MPI shall refund to Daiichi an
amount equal to the research fee paid by Daiichi to MPI less the actual costs
incurred by MPI. Payment would be within ninety (90) days following the end of
the Study Period.
[*] Confidential Treatment Requested
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2.2 All payments from Daiichi to MPI shall be made by bank wire transfer
directed to:
[*]
2.3 MPI's chief financial officer (or designee) shall submit to Daiichi
financial reports of expenditures incurred during the Study Period. The report
shall be submitted, on quarterly basis, within thirty (30) days after the end of
each financial quarter.
2.4 MPI shall keep accurate records of MPI's actual costs incurred for the
Studies during the Study Period. Such records shall be kept at MPI for at least
five (5) years following the end of the Study Period. Such records will be
available for inspection during one (1) year after the end of the Study Period,
by an independent auditor of Daiichi for the purpose of verifying the financial
reports mentioned in paragraph 2.3 hereof. Such inspection may be made no more
than once a year at reasonable times mutually agreed by MPI and Daiichi.
Daiichi's independent auditor will be obliged to execute a Confidentiality
Agreement prior to commencing any such inspection. Inspections conducted under
this paragraph shall be at the expense of Daiichi.
ARTICLE 3. RECORDKEEPING AND REPORTING
3.1 MPI shall prepare and maintain complete and accurate records in writing
generated from the Studies. MPI shall give Daiichi a progress report of the
Studies every one (1) week hereof, and shall provide Daiichi in writing with a
final report including all the results generated from the Studies ("Results")
within thirty (30) days following the end of the Study Period.
3.2 MPI shall preserve the originals of the raw data resulting from the
Studies in MPI's facilities for five (5) years form termination of this
Agreement.
ARTICLE 4. INFORMATION
4.1 Promptly after the execution of this Agreement, Daiichi shall disclose
in writing information possessed by Daiichi and which Daiichi considers
necessary for the Studies ("Information").
4.3 MPI agrees that the Information shall be used only for the purpose of
carrying out the Studies hereunder, and that the Informaiton shall be used only
within MPI's laboratories and shall not be made available, transferred or
provided to any third party without Daiichi's prior written approval.
[*] Confidential Treatment Requested
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ARTICLE 5. DISCUSSION
5.1 Daiichi and MPI shall, from time to time, discuss the matter concerning
the Studies and decide the plan of Studies. The meeting between Daiichi and MPI
shall be held in August or September in 2000, and in February or March in 2001
to discuss the Results.
ARTICLE 6. RESULTS AND NEW INVENTIONS AND DISCOVERIES
6.1 Daiichi shall solely own the Results and MPI shall not use, have used
and disclose any Results for any purpose other than performance of this
Agreement.
6.2 MPI shall disclose to Daiichi in writing any New Inventions or
Discoveries promptly after the discovery of such New Inventions or Discoveries.
"New Inventions or Discoveries" shall mean any patentable Results generated
hereunder. Further in the event sufficient compound made by MPI remains after
Studies, MPI shall provide Daiichi with such compound, together with the final
report set forth in Section 3.1 hereof.
6.3 Title to al New Inventions or Discoveries conceived or reduced to
practice in the course of performance of this Agreement shall be solely owned by
Daiichi.
ARTICLE 7. SECRECY
7.1 MPI shall hold in confidence any information disclosed to it by Daiichi
or generated hereunder, including, but not limited to, the Information and
Results, and shall not disclose said information to any third party except to
such of its employees and officers as have been made aware that said information
is confidential and are bound to treat it as such and to whom disclosure is
necessary in order to carry out the Studies, except:
(a) information and data which at the time of disclosure by Daiichi are
in the public domain;
(b) information and data which after disclosure by Daiichi enter the
public domain through no improper conduct of MPI;
(c) information and data which prior to disclosure by Daiichi were
already in the possession of MPI as evidenced by written records; or
(d) information and data which subsequent to disclosure hereunder are
obtained by MPI from third parties who are lawfully in possession of such
information and data and who do not require MPI to refrain from disclosing such
information and data to others.
7.2 The obligation in this Article 7 shall survive for a period of ten (10)
years after the termination of this Agreement.
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ARTICLE 8. TERM
8.1 This Agreement shall become effective on the Effective Date and
continue in full force and effect until completion of last payment by Daiichi as
set forth in Section 2.1 hereof. Further, this Agreement may be extended by
mutual written consent of the parties not less than thirty (30) days prior to
the termination for the agreed period of time.
ARTICLE 9. RIGHTS AND DUTIES UPON TERMINATION
9.1 Termination of this Agreement shall terminate all outstanding
obligation and liabilities, between the parties from this Agreement except those
described in Section 3.2, Article 6., Article 10. and Section 11.3. hereof.
9.2 Upon the termination of this Agreement, MPI shall not use for any
reason whatsoever or transfer to any third party the Compound provided to MPI
hereunder without Daiichi's prior written consent. Daiichi may require that MPI
either destroy or return to Daiichi the unused Compound provided to MPI.
ARTICLE 10. INDEMNIFICATION
10.1 MPI shall indemnify and hold harmless Daiichi, its employees, officers
and agents from and against all loss or expense by reason of any liability
imposed by law upon Daiichi relating to the handling of the Compound or carrying
out the Studies or any other work directly or indirectly relating to the Studies
by MPI; provided that such loss or expense is not due to negligence or willful
acts or omissions by Daiichi.
ARTICLE 11. MISCELLANEOUS
11.1 Any modification and addition to this Agreement, including
modifications in the Protocols, shall be valid only if they are confirmed in
writing by the duly authorized officers of both parties hereto.
11.2 This Agreement constitutes the full and complete agreement and
understanding between the parties hereto regarding the subject matter hereof and
shall supersede any and all prior written and oral agreements thereof.
11.3 The terms and conditions of this Agreement shall be construed,
interpreted, and enforced in accordance with the applicable statutes, without
regard to choice of law rules, of the State of California. All disputes,
controversies, or differences that may arise between the parties hereto, out of
or in relation to or in connection with this Agreement, or for the breach
thereof, shall be settled by arbitration. If the arbitration is initiated by
Daiichi, it shall be held in Los Angeles, California USA in accordance with the
International Arbitration Rules of the American Arbitration Association. If the
arbitration is initiated by MPI, it shall be held in Tokyo, Japan in accordance
with the rules of Japan Commercial Arbitration Association. The award shall be
final and binding upon the parties hereto.
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11.4 Any notice required or permitted under this Agreement shall be sent by
registered air mail, provided, however, that as for urgent matters facsimile may
be used, in which case the issuing party shall confirm its notice by registered
air mail. Said notice shall be sent to the following address of the receiving
party:
Daiichi Pharmaceutical Co., Ltd. Microcide Pharmaceuticals, Inc.
New Product Research Laboratories I
16-13, Kita-Kasai 1-Chome 850 Maude Ave. Mountain View,
Edogawa-ku, Tokyo 134-8630 Japan California
Attention: Isao Hayakawa Attention: James E. Rurka
Director President and CEO
Telephone No.: (3)-5696-8232 Telephone No.: (650)-428-3525
Facsimile No.: (3)-5696-8344 Facsimile No.: (650)-428-3545
IN WITNESS WHEREOF the parties hereto have caused this Agreement to be executed
by their duly authorized officers upon the date first above written in duplicate
original, one (1) original to be retained by each party hereto.
DAIICHI PHARMACEUTICAL CO., LTD. MICROCIDE PHARMACEUTICALS, INC.
By: /S/ Kiyoshi Morita By: /S/ James Rurka
---------------------- ----------------------
Name: Kiyoshi Morita Name: James Rurka
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Title: President Title: President and CEO
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Date: May 8, 2000 Date: April 20, 2000
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ANNEX A
The main goal of this project is to obtain potent and diverse compounds that are
specific inhibitors [*]. Compounds synthesized and Patents filed in the term of
this contractual study will belong to Daiichi.
[*]
The areas in which research will be carried out are:
1. Medicinal chemistry on [*]
The target compounds to be initially synthesized will be determined by Daiichi
with additional, more detailed information about structure-activity-relationship
being assessed at Daiichi before the Studies. Daiichi shall organize chemistry
plans for compounds which will be synthesized in the Studies. Compounds
synthesized at MPI will be sent to Daiichi after appropriate characterization at
MPI.
2. Characterization of synthesized compounds
Preliminary characterization will be performed on all compounds synthesized. The
method for characterization should be determined by both parties prior to start
of the contractual study. Compounds with sufficient activity will be submitted
for pharmacological studies (serum protein binding, pk and in vivo efficacy) as
jointly deemed appropriate.
3. Surveillance and profiling of expression of efflux pumps (Mex pumps)
in clinical isolates of Pseudomonas aeruginosa from western countries
(at least USA, Canada, and Europe).
MPI will collect appropriate numbers of clinical isolates of P. aeruginosa from
western countries. Those strains should consist of quinolone-sensitive and
-resistant isolates, and reflect the distribution of isolates in the clinical
setting. Characterization of the isolates will be performed at both MPI and
Daiichi. These studies are aimed at assessment for overall potential [*].
(MPI will perform this item within the range of costs of less than US $[*].
However, larger studies, if jointly deemed appropriate, will have to be funded
separately by Daiichi.)
[*] Confidential Treatment Requested
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4. Investigation of current trends and efficacy (satisfaction by
physicians) in the treatment for Pseudomonas infections in western
countries.
Approaches for this item could be sequential and initiated at appropriate times
depending upon the success of the research.
a.) MPI will discuss with infectious diseases experts on its
scientific advisory board the current state of therapy for P.
aeruginosa and opportunities [*].
b.) MPI scientists will discuss these issues with a larger group of
clinicians and pharmacy practitioners in telephone interviews and
at meetings, and send a report to Daiichi.
c.) MPI could ask its infectious disease consultant to survey a
number of colleagues and write a report.
d.) MPI could identify an existing marketing report that covers these
issues and which could be purchased by Daiichi.
e.) MPI could commission a marketing consultant to carry out a study
and write a report.
MPI will carry out a) and b) under the terms of the contract; the remaining
approaches could be setup and monitored by MPI but would require separate
funding by Daiichi.
[*] Confidential Treatment Requested
