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EXHIBIT 10.90
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS,
HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE 24B-2 OF THE SECURITIES AND EXCHANGE ACT OF 1934, AS
AMENDED.
Warner-Lambert Company September 21, 1998
2800 Plymouth Road
Ann Arbor, Michigan 48105
Attn: Vice President & Chairman
Parke-Davis Pharmaceutical Research
COLLABORATION AGREEMENT BETWEEN WARNER-LAMBERT COMPANY AND
SEQUANA THERAPEUTICS, INC. (DBA AXYS PHARMACEUTICALS, INC.) DATED
OCTOBER 31, 1997 ("AGREEMENT")
Dear Sir/Madam:
We refer to the Agreement and confirm that it is the mutual agreement of the
parties to amend the Agreement to delete Exhibit A in its entirety and replace
it with the new Exhibit A attached hereto.
In addition, the parties have further agreed that all references in the
Agreement to BioAgent DB and SequaSearch shall be deemed to be references to the
Target Validation System (TVS) as described in new Exhibit A.
We are enclosing duplicate copies of this letter. If the above is acceptable to
you, please have the copies signed on behalf of the Warner-Lambert Company by a
duly authorized signatory and return one fully signed copy to us for our
records.
Sincerely,
/s/ DANIEL H. PETREE
- -----------------------------------
Daniel H. Petree
President & Chief Operating Officer
Accepted this 30 day of September, 1998
Warner-Lambert Company
/s/ RONALD M. CRESSWELL
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Per: Prof. Ronald M. Cresswell, Ph.D., Hon.D.Sc., FRSE
Title: Vice President and Chairman
Parke-Davis Pharmaceutical Research
Warner Lambert Company
cc: Warner-Lambert Company
Attn: Vice President, General Counsel
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EXHIBIT A
SEQUANA TECHNOLOGY
This exhibit provides details regarding the Sequana Technology that is defined
in Section 1.43 of the Agreement. Elements of Sequana Technology are:
Target Validation Support System
PD LIMS
High-throughput DBA sequencing protocols
High-throughput genotyping protocols
Micro-Array technology protocols
Each of these elements is described in more detail below. In addition, for each
element, the following information is provided as appropriate:
A description of "establishment" of the technology at Warner under
Section 5.2 of the Agreement that is required to be complete before
payment of the Technology Access Fee.
Additional technology that will be established at Warner under this
Agreement but which is not required to be complete as a condition for
payment of the Technology Access Fee.
A discussion of the level of support that will be provided to Warner as
a part of this Agreement.
TARGET VALIDATION SUPPORT SYSTEM (TVS)
TVS is designed to provide a convenient system to integrate and curate the key
public and proprietary information that supports the association of a candidate
gene with a disease state or validates a gene product as a drug target. One goal
of TVS is to automate the integration of public data with proprietary data.
Another goal is to permit the integration of TVS with various systems and
research processes (including high-throughput processes) that identify and
populate the system with potential targets.
TVS consists of a gemstone database with a java user interface. The interface is
a java applet which is launched from Netscape or Internet Explorer. TVS will run
on Windows NT, Windows 95 and SUN Unix systems.
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TVS for the Field will be housed at Sequana and a mechanism will be put in place
to provide Warner's Ann Arbor, MI research facility access to the data. Sequana
will transfer the TVS system in September 1998 to the Warner Alameda, CA
research facility for utilization within Warner in other disease areas.
Researchers at other Warner facilities will have access to the version of TVS
installed at Alameda via the Warner intranet.
[*]
Analysis subsystem of TVS
[*]
Required Hardware [*]
The original SequaSearch modules that were part of BioAgentDB are detailed in
the attached Appendix, [*]
TVS will be "established" at Warner for the purposes of Section 5.2 of the
Agreement upon achievement of installation of TVS 1.0 as described above [*]. To
verify installation, Sequana will perform a series of basic functionality tests
directed at the core functionality in collaboration with Warner Lambert staff.
This release will satisfy the payment of the access fee. Sequana will transfer
to Warner TVS 2.0 when completed, [*] This release is not tied to the license
access fee.
TVS will be supported in the following manner at Warner:
(a) At least one Warner employee will be designated the "Super User"
and will be trained at Sequana on the full functionality of TVS.
(b) At least one Warner employee will be designated "Systems Support"
and will be trained at Sequana on the systems support issues related to
TVS (i.e. UNIX, Mac, Windows, web server system administration).
(c) The Super User will handle all user and data support issues and
questions that arise at Warner.
(d) The System Support personnel will handle all system support issues
and questions that arise at Warner.
(e) Any questions or problems that the Super User or System Support
cannot resolve will be forwarded to the Sequana Help Desk which will be
open Monday - Friday, 7 AM to 5 PM PST and staffed by qualified
personnel.
(f) Sequana guarantees a response to (but not necessarily complete
resolution of any Warner inquiry within 24 hours, and Sequana and
Warner will cooperate to promptly resolve any such question or problem.
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(g) Customization of TVS will be done by Warner, or by Sequana under a
separate contract arrangement. However, any changes to the source code
that are made by Warner that result in incompatibilities with future
upgrades provided by Sequana will be the responsibility of Warner to
resolve.
PD LIMS
The PD LIMS system is the non-microsatellite genotyping components of the
Sequana LIMS system that are necessary to perform basic phenotype/genotype
correlations. [*]
PD LIMS will be "established" at Warner for the purposes of Section 5.2 of the
Agreement upon achievement of the following:
Installation of the database schema and lookup tables on the Warner
Sybase server at Warner facility Installation of the 4D server at
Warner facility Installation of the Web Server at Warner facility
Installation of 4D client software on DNA intake clients and up to four
(4) additional clients at Warner facility.
Additional installation efforts at Warner related to PD LIMS that are required
under this agreement but which will not be necessary before the payment of the
License Access Fee described in Section 5.2 include: Super User and System
Support on-site training and support during initial installation.
[*]
PD LIMS will be supported in the following manner at Warner:
(a) At least one Warner employee will be designated the "Super User"
and will be trained at Sequana on the full functionality of PD LIMS.
(b) At least one Warner employee will be designated "Systems Support"
and will be trained at Sequana on the systems support issues related to
PD LIMS (i.e. UNIX, Sybase, Mac administration).
(c) The Super User will handle all user and data support issues and
questions that arise at Warner.
(d) The System Support personnel will handle all system support issues
and questions that arise at Warner.
(e) Any questions or problems that the Super User or System Support
cannot resolve will be forwarded to the Sequana Help Desk which will be
open Monday - Friday, 7 AM to 5 PM PST and staffed by qualified
personnel.
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(f) Sequana guarantees a response to but not necessarily complete
resolution of any Warner inquiry within 24 hours and Sequana and Warner
will cooperate to promptly resolve any such question or problem.
(g) Customization of PD LIMS will be done by Warner, or by Sequana
under a separate contract arrangement. However, any changes to the
source code that are made by Warner that result in incompatibilities
with future upgrades provided by Sequana will be the responsibility of
Warner to resolve.
Year 2000 compliance of both TVS and PD-LIMS
Sequana further represents and warrants that the Software Products are Year 2000
compliant and in no case do the Software Products use or depend on two digit
strings for storage or computation of dates or times; provided, however, that if
dates from legacy applications are imported non-compliance may result unless the
legacy application provides year 2000 compliant dates as inputs to the Software
Products.
High-throughput DNA Sequencing
Sequana has established a high-throughput, high accuracy DNA sequencing
laboratory through the development and utilization of several novel sequencing
strategies and systems. Strict quality control procedures are developed and
built in each and every important step of high throughput sequence production to
ensure maximum efficiency and accuracy.
Sequana will transfer to Warner Sequana's DNA sequencing Standard Operating
Procedures (SOPs) and provide on-site training of up to three person-weeks
total. The SOPs to be transferred to Warner include:
[*]
Installation of high-throughput sequencing at Warner under Section 5.2 of the
agreement will be considered to be achieved upon transfer of the SOPs and
completion of the training at Sequana.
Sequana is not obligated to provide Warner with additional consulting services
or support with respect to DNA sequencing.
High throughput genotyping
Sequana has established a high-throughput, high accuracy polymorphism detection
and non-microsatellite genotyping laboratory through the development and
utilization of several molecular systems. Sequana will transfer to Warner
Sequana's non-microsatellite polymorphism detection and genotype determination
Standard Operating Procedures (SOPs) outlined below and provide on-site training
of Warner scientists for up to three person weeks total. The SOPs to be
transferred to Warner include:
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[*]
Installation of high throughput genotyping at Warner under Section 5.2 of the
agreement will be considered to be achieved upon transfer of the SOPs and
completion of the training at Sequana.
Sequana is not obligated to provide Warner with additional consulting services
or support with respect to high-throughput genotyping.
Micro-Array Protocols
Sequana is a participant in the Molecular Dynamics/Amersham Microarray
Technology Access Program. As a member of the Early Access Program, Sequana is
gaining considerable lead time in the utilization and development of the
MD/Amersham Microarray System ("System"). [*] During this period, the Microarray
Group within Sequana will be focusing on extending the capabilities of the
System in collaboration with MD/Amersham as follows:
[*]
- Optimizing the immobilization chemistry and labeling protocols
to detect rare mRNAs from small quantities of tissue;
- Adapting the Microarray System to work in the "Northern" mode
(useful in monitoring the expression of a set of genes in a
large number of tissue samples) in as well as the more common
"reverse Northern" mode;
- Developing proprietary bioinformatics tools to analyze the
data generated by the System and present results in a
queriable, user-friendly front-end.
As part of the technology transfer to Warner, Sequana will transfer operating
know-how related to the System to the extent that it is permitted under the
agreement with Molecular Dynamics/Amersham. The objective of this sharing of
proprietary know-how is to allow Warner to better evaluate the unique features
of this System with respect to the other commercially available chip-based
technologies for gene expression studies. Based on the terms of its agreement
with Molecular Dynamics/Amersham, Sequana will be able to share data generated
by the System with Warner anytime after January 1, 1998.
It will not be necessary to transfer the micro-array protocols to Warner as a
condition for payment of the License Access Fee described in Section 5.2 of the
Agreement.
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APPENDIX TO EXHIBIT A
The following are descriptions of the original SequaSearch modules that were a
part of BioAgent DB along with their status in TVS.
VIRTUAL-LIBRARIAN
"Monitors the PubMed literature which pertains to a disorder of interest.
The information is then retrieved, reformatted, parsed and deposited into
the BioAgentDB. The agent distinguishes new literature from previously
reported literature. E-mail alerts (with URLs) are sent to the scientists
informing them when new information becomes available. PubMed is a National
Library of Medicine ("NLM") web-based product which provides free access to
MEDLINE which is the NLM's database of bibliographic citations (e.g.,
authors, title, and journal reference) and author abstracts from about
3,800 biomedical journals."
[*]
CANDIDATEVL
"Monitors the literature (PubMed) pertaining to candidate genes which are
in common with the disorder. The information is then retrieved,
reformatted, parsed and deposited into the BioAgentDB with hyperlinks to
the candidate gene. The agent distinguishes new literature from previously
reported literature. E-mail alerts (with URLs) are sent to the scientists
informing them when new information becomes available."
[*]
ESTAGENT
"Monitors the National Center of Biotechnology Information ("NCBI")
Integrated Gene Map for sequences which are newly mapped to genomic regions
of interest (such as a linkage region). It retrieves the mapped sequences
together with higher resolution mapping information, flanking markers, and
possible identification of the mapped sequences. This information is
automatically retrieved, reformatted, and deposited in the BioAgentDB such
that genomic maps are automatically generated. The NCBI's Integrated Gene
Map is a map of more than 16,000 human genes which have been mapped
relative to a gramework map that contains about 1000 polymorphic genetic
markers. This gene map unifies the existing genetic and physical maps with
the nucleotide and protein sequence database."
[*]
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GENEINTEGRATOR
"Monitors Swiss-Prot and GenPept for new biological attributes (site of
expression, map location, function, developmental stage, polymorphisms) of
candidate genes. It automatically retrieves, reformats, parses, and
deposits the information into the candidate gene record in BioAgentDB."
[*]
GENEWIZARD
"Monitors sequence databases for new matches to sequences of interest and
reports those which meet threshold requirements. GeneWizard is currently
under development."
[*]
TRANSCRIPTSCANNER
"Monitors the UniGene database at the National Center for Biotechnology
Information for clones and mapped EST contigs for those connected with a
disorder of interest. TranscriptScanner is currently under development."
[*]
SYNTENYAGENT
"Monitors the mouse genome databases for genes that are syntenic with
regions of interest in the human genome. SyntenyAgent is currently under
discussion."
[*]
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