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Drug Discovery Collaboration Agreement |
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2000 |
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$46 |
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#1252108 |
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DISCOVERWORKS(TM)
DRUG DISCOVERY COLLABORATION AGREEMENT
THIS DISCOVERWORKS(TM) DRUG DISCOVERY COLLABORATION AGREEMENT is made as of July
7, 2000 by and between 3-Dimensional Pharmaceuticals, Inc., a Delaware
corporation having its principal place of business at Eagleview Corporate
Center, 665 Stockton Drive, Suite 104, Exton, PA 19341 ("3DP"), and Bristol-
Myers Squibb Company, a Delaware corporation having its principal place of
business at Route 206 & Province Line Road, P.O. Box 4000, Princeton, New Jersey
08543 ("BMS"). 3DP and BMS may be referred to herein as a "Party" or,
collectively, as the "Parties."
WHEREAS, 3DP is engaged in discovery research for a variety of biologically-
active compounds and the development of technologies to facilitate such
research, and 3DP has developed and is patenting systems for identifying and
generating chemical compounds having desired pharmaceutical properties;
WHEREAS, BMS is a major pharmaceutical company engaged in research, development
and commercialization of biologically-active compounds for the treatment of
human diseases;
WHEREAS, 3DP and BMS desire to enter into a research and development
collaboration to identify Initial Hits, Improved Hits, Program Lead Compounds
and Pre-Clinical Lead Compounds (as such terms are defined herein) active
against selected targets, and suitable, if required, for medicinal chemistry
optimization, that may be developed and commercialized by BMS;
NOW, THEREFORE, in consideration of the various promises and undertakings set
forth herein, the Parties agree as follows:
ARTICLE 1
DEFINITIONS
The terms in this Agreement with initial letters capitalized, whether used in
the singular or the plural, shall have the meaning set forth below or, if not
listed below, the meaning designated in places throughout this Agreement.
1.1 "Active Compound" means a Program Lead Compound or a Pre-Clinical Lead
Compound identified in the course of the Research Program, or a
compound further optimized from such a Program Lead Compound or a Pre-
Clinical Lead Compound.
1.2 "Affiliate" means, with respect to either Party, any corporation or
other business entity, which controls, is controlled by, or is under
common control with such Party. A corporation or other entity shall be
regarded as in control of another corporation or entity if it owns or
directly or indirectly controls at least fifty percent (50%) of the
voting stock or other ownership interest of the other corporation or
entity (or alternatively, if it owns the maximum such ownership
interest permitted by law), or if it possesses, directly or
indirectly, the power to direct or cause the direction of the
management and policies of the corporation or other entity or the
power to elect
** Certain portions of this Exhibit have been omitted based upon a request for
confidential treatment that has been filed with the Commission. The omitted
portions have been filed separately with the Commission.
<PAGE>
or appoint at least fifty percent (50%) of the members of the
governing body of the corporation or other entity.
1.3 "Agreement" means this DiscoverWorks(TM) Drug Discovery Collaboration
Agreement, including its Exhibits, as may be amended from time to
time.
1.4 "Back-up Compound" means a compound identified in the course of the
Research Program which has activity against a Target in a Target
Field, that is intended to be reserved as a back-up for an Active
Compound or Licensed Product having activity against the same Target
in the same Target Field, and is not intended to be developed or
commercialized unless development and/or commercialization of such
Active Compound or Licensed Product is terminated.
1.5 "BMS" means Bristol-Myers Squibb Company, as identified above, and is
understood to include its Affiliates, when appropriate.
1.6 "Chemical Optimization" means the design, synthesis and identification
of Improved Hits, Program Lead Compounds and Pre-Clinical Lead
Compounds using DiscoverWorks Technology and other technologies
selected by the JSMC.
1.7 "Combination Product" means a Licensed Product that includes one or
more active ingredients other than an Active Compound.
1.8 "Confidential Information" means all technical and/or commercial
information that has or could have value or utility in a Party's
business, or the unauthorized disclosure of which could be detrimental
to the Party's interests, including information, inventions, Know-how,
data and materials relating to the Research Program or to the Licensed
Products, and shall include, without limitation, research, technical,
clinical development, manufacturing, marketing, financial, personnel
and other business information and plans, whether in oral, written,
graphic or electronic form, except to the extent that it can be
established by the Receiving Party (as defined in Section 7.1) that
such Confidential Information: (a) was already known to the Receiving
Party, other than under an obligation of confidentiality from the
Disclosing Party (as defined in Section 7.1); (b) was generally
available to the public or otherwise part of the public domain at the
time of its disclosure to the Receiving Party; (c) became generally
available to the public or otherwise part of the public domain after
its disclosure and other than through any act or omission of the
Receiving Party in breach of this Agreement; (d) was subsequently
lawfully disclosed to the Receiving Party by a Third Party; (e) can be
shown by written records to have been independently developed by or
for the Receiving Party without reference to the Confidential
Information received from the Disclosing Party and without breach of
any of the provisions of this Agreement; or (f) is information that
the Disclosing Party has specifically agreed in writing that the
Receiving Party may disclose.
** Certain portions of this Exhibit have been omitted based upon a request for
confidential treatment that has been filed with the Commission. The omitted
portions have been filed separately with the Commission.
2
<PAGE>
1.9 "Contract Year" means a twelve (12)-month period beginning upon the
Effective Date or an anniversary thereof.
1.10 "DirectedDiversity(R) Technology" means the descriptions, figures and
claims of: (a) the Patent Rights identified in EXHIBIT A, and (b)
associated proprietary 3DP Know-how used to identify potential
therapeutic compounds.
1.11 "DiscoverWorks Technology" means DirectedDiversity(R) Technology and
ThermoFluor(R) Technology."
1.12 "ECN" or "Early Candidate Nomination" means documentation within
which an Active Compound is nominated for clinical development by BMS
pursuant to technical criteria established by the JMSC upon selection
of the Target against which such a compound is active, or as soon
thereafter as practical, and pursuant to the then-applicable internal
policies and procedures of BMS.
1.13 "Effective Date" means the later of: (a) the date of this Agreement
as set forth above; or (b) the date on which all of the following
documents between the Parties have been executed: this Agreement, the
GPCR License and User Agreement, the DiscoverWorks(TM) Nonexclusive
License and Purchase Agreement, and the PERT Internal Use License and
Option Agreement.
1.14 "Extended Research Term" means a period of time, mutually agreed upon
by the Parties, following conclusion of the Research Term (as defined
below), or of an earlier Extended Research Term, during which the
Research Program is conducted.
1.15 "Field" means the research, development and commercialization of
chemical compounds for use in therapeutic and diagnostic products,
except for use in the treatment or cure of [**].
1.16 "First Commercial Sale" means, with respect to a given Licensed
Product, the first sale for use or consumption by the public of such
Licensed Product in a country after all required approvals, including
marketing and pricing approvals, have been granted by the applicable
governmental drug regulatory agency of such country. "First
Commercial Sale" shall not include the sale of any Licensed Product
for use in clinical trials or for compassionate use prior to the
grant of an NDA.
1.17 "Focused Library" means a library of compounds selected from the 3DP
Synthetically Accessible Library and synthesized by 3DP using
DirectedDiversity(R) Technology.
1.18 "FTE" means a full time equivalent scientific employee (i.e., one
full-time or multiple part-time employees aggregating to one full-
time employee) employed by 3DP and assigned to work on the Research
Program (or on development of ThermoFluor(R) II Instruments under the
License Agreement, where applicable) with such time and effort to
constitute one employee working on
** Certain portions of this Exhibit have been omitted based upon a request for
confidential treatment that has been filed with the Commission. The omitted
portions have been filed separately with the Commission.
3
<PAGE>
the Research Program (or under the License Agreement, where
applicable) on a full-time basis consistent with normal business and
scientific practice (at least forty (40) hours per week of dedicated
effort; on an annual basis, at least forty (40) hours per week of
dedicated effort for at least forty-eight (48) weeks per year). In no
event, does an FTE include a subcontractor.
1.19 "Improved Hit" means a compound resulting from the Chemical
Optimization of an Initial Hit that demonstrates improved
pharmacological and/or physical properties compared to those of the
corresponding Initial Hit, as determined and agreed upon by the JSMC.
1.20 "IND" means an application to be filed with the applicable regulatory
authority in a Major Country before the commencement of clinical
trials. In the U.S., IND means an Investigational New Drug
Application, or its equivalent, in the Food and Drug Administration
or successor agency.
1.21 "Initial Hit" means a compound in the 3DP Probe Library that [**],
as measured using ThermoFluor(R) Technology.
1.22 "Joint Steering and Management Committee" or "JSMC" shall have the
meaning and roles ascribed to it in Article 4.
1.23 "JRT" shall have the meaning ascribed to such term in Section 3.3.
1.24 "Know-how" means unpatented technical and other information which is
not in the public domain, including information comprising or
relating to concepts, discoveries, inventions, data, designs,
formulae, ideas, methods, models, assays, research plans, procedures,
designs for experiments and tests and results of experimentation and
testing (including results of research or development) processes
(including manufacturing processes, specifications and techniques),
laboratory records, chemical, pharmacological, toxicological,
clinical, analytical and quality control data, trial data, case
report forms, data analyses, reports or summaries and information
contained in submissions to, and information from, ethical committees
and regulatory authorities.
1.25 "License Agreement" means the DiscoverWorks Nonexclusive License and
Purchase Agreement entered into by the Parties and dated of even date
herewith.
1.26 "Licensed Product" means any commercial product containing an Active
Compound as an active ingredient.
1.27 "Major Country" means the United States, Japan, the United Kingdom,
France, Germany, Italy or Spain.
1.28 "NDA" means an application for the final approval required for
authorization for marketing of a Licensed Product in a Major Country
(including applicable regulatory, marketing and pricing
** Certain portions of this Exhibit have been omitted based upon a request for
confidential treatment that has been filed with the Commission. The omitted
portions have been filed separately with the Commission.
4
<PAGE>
approval), in accordance with the applicable laws and regulations of a
given country. In the U.S., NDA means a New Drug Application, or its
equivalent, in the Food and Drug Administration or successor agency.
1.29 "Net Sales" means the aggregate gross invoiced price of Licensed
Product sold in the Territory by BMS, its Affiliates and any licensees
or sublicensees, to an independent Third Party, including but not
limited to distributors, in bona fide, arms-length transactions, after
deduction of the following items (to the extent actually incurred): (i)
customary trade, quantity and cash discounts, wholesaler-charge backs,
or rebates (including rebates to governmental agencies and government-
mandated and managed healthcare negotiated rebates); (ii) customary
credits or allowances for rejection or return of previously sold
Licensed Products; (iii) any direct tax, duties, tariffs, surcharges or
government charge (other than an income tax) levied on the sale,
importation, exportation, transportation or delivery of a Licensed
Product and borne by the seller thereof; (iv) retroactive price
reductions; and (v) any charge for freight, insurance or other
transportation charges, if separately stated. Such amounts shall be
determined from the books and records of BMS, its Affiliates and any
licensees or sublicensees, as the case may be, which books are
maintained in accordance with the generally accepted accounting
principles, consistently applied. Any sales for resale of Licensed
Products by BMS, its Affiliates or any licensees or sublicensees to
another Affiliate, licensee or sublicensee of BMS shall not result in
any Net Sales. In such case, Net Sales shall occur upon such other
Affiliate's, licensee's or sublicensee's sale of such Licensed Product
to an independent Third Party. Further, the disposition of Licensed
Products for, or the use of Licensed Products in, pre-clinical or
clinical trials, seeding or other market-focused trials or free samples
shall not result in any Net Sales.
In the event that all the active ingredients of a Combination Product
are also sold separately and in identical strengths to those contained
in the Combination Product, then Net Sales shall be calculated as set
forth above on the basis of the gross invoice price of a Licensed
Product containing the same weight of Active Compound sold
independently [ A ] divided by the sum of the gross invoice price of
each of the active ingredients contained in the Combination Product
sold independently [ B + A ], multiplied by the gross invoice price of
the Combination Product, as shown by the following formula:
Net Sales = [ A ]__ x [gross invoice price of the Combination Product]
---------
[ B + A ]
In the event that the Active Compound and/or any of the other active
ingredients of a Combination Product are not sold separately in
identical strengths to those contained in the Combination Product, then
the Parties agree to negotiate in good faith the calculation of Net
Sales with regard to such Combination Product based upon the relative
value of the active ingredients as determined by the Parties hereto in
good faith.
** Certain portions of this Exhibit have been omitted based upon a request for
confidential treatment that has been filed with the Commission. The omitted
portions have been filed separately with the Commission.
5
<PAGE>
1.30 "Patent Rights" means all U. S. patent applications or issued
patents, including, but not limited to, provisionals, divisionals,
continuations, continuations-in-part, reissues, reexaminations, and
extensions derived therefrom, such as patent term restorations,
supplementary protection certificates, etc., as well as all foreign
patents (including PCTs) and foreign patent counterparts to the
foregoing.
1.31 "Pre-Clinical Lead Compound" means a further-optimized Program Lead
Compound that is the subject of any ECN and that the JSMC determines
possesses the pharmacological, toxicological, pharmacokinetic and
pharmaceutical properties from preliminary studies that are
indicative of a high probability for successful development, and that
the JSMC recommends for evaluation as a potential clinical candidate.
Pre-Clinical Lead Compounds will meet specific program objectives as
determined and defined by the JSMC.
1.32 "Program Lead Compound" means a compound that meets Target-specific
criteria, as determined by the JSMC, indicating that the compound is
suitable for optimization and has a high potential to lead to the
identification of a Pre-Clinical Lead Compound.
1.33 "Research Plan" means the detailed description of the research and
development activities of the Parties for particular Targets in the
performance of the Research Program, including an allocation of FTEs
to be used for various tasks and a timeline for such tasks. A draft
of the Research Plan is attached hereto as EXHIBIT C. The JSMC shall
finalize the Research Plan for the first Contract Year within 30 days
after the Effective Date. Thereafter, the Research Plan shall be
updated by the JSMC in writing as changes are made to the Research
Program on at least an annual basis.
1.34 "Research Program" means the collaborative discovery and optimization
activities of the Parties, as described in Article 2, that are
intended to lead to the discovery of Initial Hits, Improved Hits,
Program Lead Compounds and Pre-Clinical Lead Compounds.
1.35 "Research Program Know-how" means Know-how conceived or developed
during the conduct of the Research Program and relates to Improved
Hits, Program Lead Compounds, Pre-Clinical Lead Compounds and/or
Licensed Products.
1.36 "Research Program Patent Rights" means those Patent Rights that claim
discoveries or inventions that are conceived in the course of the
Research Program and reduced to practice during either the term of
the Research Program or a period of one-year following the
termination of the Research Program, regardless of their ownership.
1.37 "Research Term" means the period, from the Effective Date through the
third anniversary thereof, during which the Research Program is
conducted.
** Certain portions of this Exhibit have been omitted based upon a request for
confidential treatment that has been filed with the Commission. The omitted
portions have been filed separately with the Commission.
6
<PAGE>
1.38 "Stage I" means the research activities undertaken by the Parties
pursuant to Article 2 as part of the Research Program.
1.39 "Stage II" means the research activities undertaken by the Parties
pursuant to Article 2 as part of the Research Program.
1.40 "Stage III" means the research activities undertaken by the Parties
pursuant to Article 2 as part of the Research Program.
1.41 "Synthetically Accessible Library" means 3DP's virtual compound
library from which 3DP Probe Libraries have been selected, and from
which Focused Libraries will be selected.
1.42 "Target" means a protein against which Initial Hits, Improved Hits,
Program Lead Compounds and Pre-Clinical Lead Compounds are to be
developed. Until March 7, 2003, Target shall not include the use of
any proteins to discover or develop a drug that exerts a therapeutic
effect in Hepatitis C infection, and no more than three Targets in
total may involve antiviral Targets.
1.43 "Target Field" with respect to each Target means the disease state(s)
that are a focus of a collaborative research effort by the Parties
pursuant to the Research Program with the objective of identifying
compounds with potential diagnostic and/or therapeutic utility for
the treatment/management of said disease state(s), as determined by
the JSMC pursuant to Section 2.1. For example, a program focused on
the discovery of a novel thrombin inhibitor would be within the
Target Field of anticoagulants. Therefore, other protease inhibitors
that are not anticoagulants would be outside the Target Field. For
purposes of this definition, anti-infectives shall be considered a
single Target Field.
1.44 "Territory" means the entire world.
1.45 "ThermoFluor(R) Technology" means (a) the Patent Rights identified in
EXHIBIT B, and (b) associated proprietary 3DP Know-how used to
evaluate ligand-binding parameters.
1.46 "Third Party" means an individual, corporation or other entity other
than a Party or any of its Affiliates.
1.47 "3DP Probe Library" means 3DP's collection of approximately [**]
small molecule chemical compounds that have been synthesized by 3DP
for the purpose of screening new Targets and against which Targets
are screened to identify Initial Hits.
1.48 "Valid Claim" means a claim of a Patent Right that has not lapsed or
become abandoned or been declared invalid or unenforceable by a court
or agency of competent jurisdiction from which no appeal can be or
has been taken.
** Certain portions of this Exhibit have been omitted based upon a request for
confidential treatment that has been filed with the Commission. The omitted
portions have been filed separately with the Commission.
7
<PAGE>
ARTICLE 2
RESEARCH PROGRAM
STAGE I -- INITIAL SCREENING AND CHEMICAL OPTIMIZATION
2.1 Supply of Targets. BMS shall supply 3DP with [**] Targets during each
Contract Year. The actual number of Targets to be provided to 3DP
under this Section shall be determined by the JSMC in connection with
preparation of the Research Plan for such Contract Year. Such Targets
shall be supplied in the form of [**]. During the [**] Contract Year
of the Research Program all Targets must be derived from [**]. After
the [**] Contract Year, Targets may be derived from any organism;
however, any Targets may be disapproved by 3DP solely in order to
avoid potential conflicts with respect to prior contractual
obligations and current internal 3DP programs. In connection with the
selection and approval of Targets to be included as part of the
Research Program, the JSMC shall determine the Target Field relating
to such Target.
2.2 Initial Screening and Initial Hits. Depending on the nature and source
of each Target, 3DP shall screen the Target against a screening
library, created from the 3DP Probe Library, totaling no more than
[**] compounds per Target that are selected by [**] to identify
Initial Hits. The JSMC may ask 3DP to screen [**] from the 3DP Probe
Library [**]. This additional screening, if any, shall be subject to
the overall disposition of Research Program FTE resources as
determined by the JSMC, and 3DP's screening capacity available to the
Research Program.
2.3 Initial Chemical Optimization. At the request of the JSMC, 3DP will
initially undertake [**] Chemical Optimization of Initial Hits for any
Target, synthesizing Focused Libraries containing up to [**] to be
screened against the Target, in order to identify Improved Hits. 3DP
will undertake additional rounds of Chemical Optimization of Initial
Hits, as requested by the JSMC, following the first [**] Chemical
Optimization, subject to the number of FTE's available under the
Research Program and 3DP's capacity available to the Research Program.
The precise number of such compounds in any such Focused Libraries,
the number of rounds of Chemical Optimization and the extent of any
additional screening of the 3DP Probe Libraries as described above in
each Contract Year will be determined by the JSMC, taking into
consideration the total number of Targets selected and approved by the
JSMC for evaluation in Stage I of the Research Program.
2.4 Site of Stage I Activities. All Research Program activities to be
conducted in Stage I of the Research Program shall be performed at
3DP.
2.5 Additional Targets and Extended Term for Research Program. An increase
in the number of Targets being screened by 3DP beyond [**] at any
given time during the Research Program, or an extension of the
Research Program beyond the initial three-year term may be requested
by BMS. In the case of such additional Targets, where possible, the
JSMC shall agree upon a reallocation of FTEs to be used under the
Research Program. Otherwise, or in the case of an
** Certain portions of this Exhibit have been omitted based upon a request for
confidential treatment that has been filed with the Commission. The omitted
portions have been filed separately with the Commission.
8
<PAGE>
extension of the Research Term (as hereinafter defined), the Parties
shall negotiate in good faith for sixty (60) days to reach agreement
on a fair and equitable increase in the compensation to 3DP for such
additional Targets or extended Research Term.
STAGE II - PROGRAM LEAD COMPOUND IDENTIFICATION
2.6 Commencement of Stage II. Stage II shall commence upon the achievement
of a level of success in Stage I of the Research Program to be
determined by the JSMC.
2.7 Selection of Hits for Continued Optimization. The JSMC shall select
some or all of the Improved Hits on a Target-by-Target basis for
further rounds of Chemical Optimization in this Stage II of the
Research Program. Such Chemical Optimization may utilize, by mutual
agreement, DirectedDiversity(R) Technology and ThermoFluor(R)
Technology, or a suitable biochemical or biological high throughput
screen. Any portion of such optimization may be undertaken by either
3DP or BMS, as determined by the JSMC.
2.8 No Grant of License to DiscoverWorks Technology. Notwithstanding any
provision to the contrary in this Agreement, no license to any portion
of the DiscoverWorks Technology, including any related Know-how, is
hereby granted by 3DP to BMS under this Agreement or otherwise, except
as specifically provided for under the License Agreement.
2.9 Site of Stage II Activities. The JSMC shall determine the site of
Stage II activities.
2.10 Continued Optimization at 3DP. If Stage II is conducted on any Initial
Hit or Improved Hit at 3DP, 3DP will perform iterative rounds of
Chemical Optimization, subject to the number of FTE's available under
the Research Program and 3DP's capacity available to the Research
Program and as otherwise directed by the JSMC, until:
2.10.1 a Program Lead Compound is identified; or
2.10.2 a maximum of [**] total rounds of Chemical Optimization are
performed (including the rounds of initial Chemical
Optimization in Stage I of the Research Program); or
2.10.3 a maximum of [**] novel compounds contained in Focused
Libraries are synthesized and screened using ThermoFluor(R)
Technology or another high throughput screen in Stage II of
the Research Program from the Synthetically Accessible
Library.
STAGE III - PRE-CLINICAL LEAD COMPOUND IDENTIFICATION
2.11 Development by 3DP of Pre-Clinical Lead Compounds. For at least two
Targets screened during the Research Term, BMS agrees that a Program
Lead Compound may be further
** Certain portions of this Exhibit have been omitted based upon a request for
confidential treatment that has been filed with the Commission. The omitted
portions have been filed separately with the Commission.
9
<PAGE>
optimized by 3DP to produce a Pre-Clinical Lead Compound(s), to
specifications and on a project timetable to be reasonably agreed upon
by both 3DP and BMS. [**] of such Targets may be selected by 3DP for
review and approval by the JSMC. Additional Targets shall be selected
by BMS for review and approval by the JSMC. For such Program Lead
Compounds to be further developed by 3DP, 3DP will be responsible for
selection and synthesis of compounds or libraries, and BMS will be
responsible for associated biological testing.
2.12 BMS Support for Pre-Clinical Lead Compounds. BMS shall provide
additional FTE support on a per Target basis, as determined by BMS, or
the FTE's currently being supported by BMS at that time shall be
reallocated, as determined by the JSMC, in order to allow for
execution of appropriate work by 3DP for Stage III activities. The
technical composition of this FTE team shall be determined by the
JSMC, consistent with 3DP's FTE allocation to the Research Program.
ARTICLE 3
RESEARCH AND DEVELOPMENT EFFORTS
3.1 Research Efforts. Each Party shall use good faith commercially
reasonable efforts to perform its responsibilities under this
Agreement. As used herein, the term "commercially reasonable efforts"
will mean efforts consistent with such Party's prudent scientific and
business judgment in accordance with its internal practices as applied
to other programs of similar scientific and commercial potential.
3.2 Allocation and Support of FTEs. Throughout the term of the Research
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