1
Exhibit 10.2
CONFIDENTIAL TREATMENT REQUESTED
CONFIDENTIAL TREATMENT REQUESTED: PAGES WHERE CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED ARE MARKED "CONFIDENTIAL TREATMENT REQUESTED" AND APPROPRIATE
SECTIONS, WHERE TEXT HAS BEEN OMITTED, ARE NOTED WITH "[CONFIDENTIAL TREATMENT
REQUESTED]." AN UNREDACTED VERSION OF THIS DOCUMENT HAS BEEN FILED SEPARATELY
WITH THE SECURITIES AND EXCHANGE COMMISSION.
6/10/97
RESEARCH AND DEVELOPMENT AGREEMENT
THIS RESEARCH AND DEVELOPMENT AGREEMENT dated as of June 18, 1997 (the
"Agreement"), is entered into between TREGA BIOSCIENCES, INC., a Delaware
corporation ("TREGA"), having a place of business at 0000 Xxxxxxx Xxxxxxx Xxxxx,
Xxx Xxxxx, Xxxxxxxxxx 00000, U.S.A., and ONO PHARMACEUTICAL CO., LTD., a
Japanese corporation ("ONO"), having a place of business at 0-0 Xxxxxxxxxx,
0-xxxxx, Xxxx-xx, Xxxxx 000, Xxxxx.
W I T N E S S E T H:
WHEREAS, TREGA possesses pharmaceutical drug discovery technologies
using certain combinatorial libraries, in vivo and in vitro assays, and
synthesis and high-throughput screening technologies which, when applied, may
reduce the time and expense of identifying and developing potentially useful
compounds for the diagnosis, prevention, treatment and monitoring of diseases,
states and conditions in humans, and has established certain technologies that
may enable it to discover and identify orally active small molecules to modulate
the production of [CONFIDENTIAL TREATMENT REQUESTED] and [CONFIDENTIAL TREATMENT
REQUESTED] by specifically and selectively binding to melanocortin receptor 1.
WHEREAS, ONO desires to have TREGA conduct a research program to attempt
to identify such compounds, and to gather data and information which may be
useful to develop such compounds for medical use in humans.
WHEREAS, TREGA and ONO desire to utilize such technologies, compounds,
assays, data and information resulting from such research program to develop and
commercialize products for medical use in humans.
NOW, THEREFORE, in consideration of the foregoing premises and the
mutual covenants set forth below, the parties hereby agree as follows:
ARTICLE 1
DEFINITIONS
1.1 "Affiliate" shall mean, with respect to any Person, any other Person
which directly or indirectly controls, is controlled by, or is under common
control with, such Person. A Person shall be regarded as in control of another
Person if it owns, or directly or indirectly controls, greater than fifty
-1-
2
CONFIDENTIAL TREATMENT REQUESTED
percent (50%) of the voting stock or other ownership interest of the other
Person (or greater than forty percent (40%) in those jurisdictions where
majority ownership by foreign Persons is prohibited), or if it directly or
indirectly possesses the power to direct or cause the direction of the
management and policies of the other Person by any means whatsoever.
1.2 "Benchmarks" shall mean the benchmarks as set forth in Exhibit A
attached to this Agreement. They are further defined as [CONFIDENTIAL TREATMENT
REQUESTED] Benchmarks which shall mean the benchmarks at the [CONFIDENTIAL
TREATMENT REQUESTED] following the Effective Date and as [CONFIDENTIAL TREATMENT
REQUESTED] Benchmarks which shall mean the benchmarks at the [CONFIDENTIAL
TREATMENT REQUESTED] following the Effective Date.
1.3 "Development Period" shall mean that period of time commencing with
ONO's choice of a Research Lead Compound for further pre-clinical and clinical
development by it pursuant to Section 6.1 herein and ending upon the earlier of
(i) termination of this Agreement pursuant to Section 11.2 herein or (ii)
marketing approval of Licensed Product in Japan.
1.4 "Effective Date" shall mean the date of the execution of this
Agreement by both parties as of the date written on the first page of this
Agreement.
1.5 "Europe" shall mean those member states of the European Union at the
time of the first NDA approval in any such member state, Norway and Switzerland.
1.6 "First Commercial Sale" shall mean, with respect to any Licensed
Product, the first sale for use or consumption by the general public of such
Licensed Product.
1.7 "IND" shall mean an Investigational New Drug notification filed with
the Koseisho, or its equivalent filed with the governing health authority in any
other country in the ONO Territory.
1.8 "Koseisho" shall mean the Japanese governmental agency responsible
for the review and approval of therapeutic or diagnostic products intended for
human use or its successor.
1.9 "Licensed Products" shall mean those ethical pharmaceutical products
comprised of, containing, or developed through the use of, or manufactured using
any of the Research Lead Compounds or TREGA Post Research Period Compounds,
whether modified, derivatized, or otherwise related thereto.
1.10 "Modified Compound" shall mean with respect to the Research Period
or thereafter any chemical substance prepared by ONO, which modulates the
production of [CONFIDENTIAL TREATMENT REQUESTED] and [CONFIDENTIAL TREATMENT
REQUESTED] by binding selectively to melanocortin receptor 1, using chemical
synthesis through use of the TREGA Technology or
-2-
3
CONFIDENTIAL TREATMENT REQUESTED
the TREGA Material including derivatives which are structurally similar to a
TREGA Material in that it is a Homolog, Isomer, Bioisostere, Analog or derived
from a TREGA Material requiring more than a [CONFIDENTIAL TREATMENT REQUESTED]
transformation (e.g. (i) [CONFIDENTIAL TREATMENT REQUESTED]; (ii) [CONFIDENTIAL
TREATMENT REQUESTED]; (iii) [CONFIDENTIAL TREATMENT REQUESTED]; (iv)
[CONFIDENTIAL TREATMENT REQUESTED]; and (v) [CONFIDENTIAL TREATMENT REQUESTED];
"Analog" herein shall mean a substance differing from a TREGA Material by
replacement of a [CONFIDENTIAL TREATMENT REQUESTED] by an analogous element
(i.e. [CONFIDENTIAL TREATMENT REQUESTED] vice versa, one [CONFIDENTIAL TREATMENT
REQUESTED] for another, a [CONFIDENTIAL TREATMENT REQUESTED], and [CONFIDENTIAL
TREATMENT REQUESTED], or [CONFIDENTIAL TREATMENT REQUESTED] in an aromatic
ring), "Bioisostere" herein shall mean the interchange of [CONFIDENTIAL
TREATMENT REQUESTED], [CONFIDENTIAL TREATMENT REQUESTED], [CONFIDENTIAL
TREATMENT REQUESTED] and [CONFIDENTIAL TREATMENT REQUESTED] group and other well
established bioisosteric interchanges and "Homolog" herein shall mean a compound
differing from a TREGA Material by a [CONFIDENTIAL TREATMENT REQUESTED] or
[CONFIDENTIAL TREATMENT REQUESTED].
1.11 "NDA" shall mean the application required to be filed with the
Koseisho for approval to market a product for the treatment of humans or such
other essentially equivalent product license application filed with the
governing health authority in any other country.
1.12 "Net Sales" shall mean, with respect to any Licensed Product, the
invoiced sales price of such Product billed to independent customers who are not
Affiliates, less to the extent included in the invoiced sales price, (a)
credits, allowances, discounts and rebates to, and chargebacks from the account
of, such independent customers (b) any deductions for spoiled, damaged,
out-dated, and returned but not replaced Licensed Product; (c) actual
contributions made by ONO to the Japanese Fund for Sufferers for Adverse Drug
Events, but not to exceed [CONFIDENTIAL TREATMENT REQUESTED] of what would be
Net Sales without giving effect to this section 1.12(b); (d) actual freight and
insurance costs incurred in transporting such Licensed Product in final form to
such customers; (e) cash, quantity and trade discounts and other price reduction
programs; (f) sales, use, value-added and other direct taxes incurred; and (g)
customs duties, surcharges and other governmental charges incurred in connection
with the exportation or importation of such Licensed Product in final form.
1.13 "ONO Know-How" shall mean all information and data, which is
possessed, owned by or licensed (other than by TREGA) to ONO during the Research
Period and Development Period, is not generally known (including, but not
limited to, formulae, procedures, protocols, techniques and results of
pre-clinical and clinical experimentation and testing), and is necessary or
useful to conduct screening or to develop, make, use, sell, offer for sale,
import or seek regulatory approval in the TREGA Territory to market a Licensed
Product; all to the extent and only to the
-3-
4
CONFIDENTIAL TREATMENT REQUESTED
extent that ONO now has or hereafter will have the right to grant licenses,
immunities or other rights thereunder. ONO Know-How shall exclude all
information and data (including, but not limited to, formulae, procedures,
protocols, techniques and results of experimentation and testing) related to the
creation, assembly, generation, synthesis or manipulation of the ONO Libraries
and compounds (other than those embodied in the Research Lead Compounds).
1.14 "ONO Library" shall mean a collection of compounds owned by or
licensed to ONO and submitted by ONO to TREGA for screening pursuant to Section
3.2 herein and accepted by TREGA for such purpose hereunder.
1.15 "ONO Materials" shall mean any item provided hereunder by ONO to
TREGA and its affiliates or to third parties at the behest of ONO.
1.16 "ONO Mimetic Compound" shall mean a compound (other than
Preclinical Lead Compound Candidates) which meets [CONFIDENTIAL TREATMENT
REQUESTED] Benchmarks, modulates the production of [CONFIDENTIAL TREATMENT
REQUESTED] and [CONFIDENTIAL TREATMENT REQUESTED] by binding selectively to
melanocortin receptor 1 and is directly or indirectly conceived, designed,
synthesized or developed by ONO, its Affiliates or (sub)licensees and
incorporates, uses, is the result of, is based upon, is derived from or by use
of, or is a by-product of the TREGA Technology or the ONO Technology or a
biological receptor characterized in whole or in part by use of the TREGA
Technology or the ONO Technology.
1.17 "ONO Patent Rights" shall mean (a) all patent applications
heretofore or hereafter filed or having legal force in any country owned by or
licensed to ONO (other than by TREGA) or to which ONO otherwise acquires rights,
which claim (i)any compounds identified, conceived or derived from or through
the use of the ONO Libraries; or (ii) ONO Mimetic Compounds or (iii) the use or
the manufacturing process of the compositions described in clauses (i) and (ii)
above ; or (iv) the ONO Improvements pursuant to Section 10.1 herein, together
with any and all patents that have issued or in the future issue therefrom,
including utility, model and design patents and certificates of invention, and
(b) all divisionals, continuations, continuations-in-part, reissues, renewals,
extensions or additions to any such patents and patent applications; all to the
extent and only to the extent that ONO now has or hereafter will have the right
to grant licenses, immunities or other rights thereunder. Notwithstanding the
foregoing, "ONO Patent Rights" shall exclude all technology, information, patent
rights, methods, processes and all intellectual property rights related to the
generation, assembly, synthesis, creation or manipulation of the ONO Libraries
and compounds (other than the Research Lead Compounds) and iterations therefrom.
1.18 "ONO Research and Development Results" shall mean the information
and data resulting from work done solely by ONO, its
-4-
5
CONFIDENTIAL TREATMENT REQUESTED
Affiliates, or Persons on behalf of ONO relating directly or indirectly to the
Research Lead Compounds, during the Research Period and the Development Period
including, but not limited to, work done to confirm or complement the Research
Work in respect of the Research Lead Compounds and all pre-clinical, clinical,
manufacturing, and formulation and evaluation work done in respect of the
Research Lead Compounds and Licensed Products.
1.19 "ONO Royalty Term" shall mean, with respect to each Licensed
Product in each country in the ONO Territory, the period of time equal to
[CONFIDENTIAL TREATMENT REQUESTED] until the expiration of the last TREGA Valid
Patent Claim if the manufacture, use or sale of such Licensed Product in such
country was covered by a TREGA Valid Patent Claim, the term for which such TREGA
Valid Patent Claim was in effect and would, if in an issued patent, be infringed
but for the license granted by this Agreement.
1.20 "ONO Technology" shall mean, collectively, the ONO Patent Rights,
the ONO Know-How, and the ONO Research and Development Results.
1.21 "ONO Territory" shall mean the countries of Japan, Taiwan, China
and South Korea.
1.22 "ONO Valid Patent Claim" shall mean either (a) a claim of an issued
and unexpired patent included within the ONO Patent Rights, which has not been
held permanently revoked, unenforceable or invalid by a decision of a court or
other governmental agency of competent jurisdiction, unappealable or unappealed
within the time allowed for appeal, and which has not been admitted to be
invalid or unenforceable through reissue or disclaimer or otherwise or (b) a
claim of a pending patent application included within the ONO Patent Rights,
which claim was filed in good faith and has not been abandoned or finally
disallowed without the possibility of appeal or refiling of such application.
1.23 "Person" shall mean an individual, corporation, partnership,
limited liability company, trust, business trust, association, joint stock
company, joint venture, pool, syndicate, sole proprietorship, unincorporated
organization, governmental authority or any other form of entity not
specifically listed herein.
1.24 "Preclinical Lead Compound Candidate" shall mean any and all
compounds satisfying the [CONFIDENTIAL TREATMENT REQUESTED] Benchmarks which
modulate the production of [CONFIDENTIAL TREATMENT REQUESTED] and [CONFIDENTIAL
TREATMENT REQUESTED] by binding selectively to melanocortin receptor 1 and which
TREGA presents in accordance with Sections 3.1 and 3.3 herein without prejudice
to ONO's right provided in Section 3.3.2 herein.
1.25 "Research Lead Compound" shall mean, collectively,
-5-
6
Preclinical Lead Compound Candidates, Modified Compounds, ONO Mimetic Compounds
and TREGA Post-Research Period Compounds.
1.26 "Research Period" shall mean the period commencing on the Effective
Date and expiring on the second anniversary thereof, subject to ONO's earlier
right of termination set forth in Section 11.2.2, and further subject to
extension upon mutual agreement of the parties.
1.27 "Research Work" shall mean the screening, testing, evaluation, and
other activities conducted solely by TREGA, its Affiliates, or Persons acting on
behalf of TREGA during the Research Period, as set forth in the Research Plan
attached hereto as Exhibit A as hereafter modified.
1.28 "Third Party" shall mean any Person other than TREGA, ONO and their
respective Affiliates.
1.29 "TREGA Assays" shall mean those certain assays and the protocols,
data, methods, information, know-how and materials relating thereto which are
owned by or licensed to TREGA as of the Effective Date or during the Research
Period, as listed on Exhibit A hereto and hereafter modified.
1.30 "TREGA Know-How" shall mean the information and data which is
possessed, owned by or licensed (other than by ONO) to TREGA during the Research
Period and Development Period, is not generally known (including, but not
limited to, formulae, procedures, protocols, techniques, and results of
experimentation and testing), and is necessary or useful to conduct screening or
to develop, make, use, sell, offer for sale, import, or seek regulatory approval
to market a Licensed Product in the ONO Territory; all to the extent and only to
the extent that TREGA now has or hereafter acquires the right to grant licenses,
immunities, or other rights thereunder. TREGA Know-How shall exclude all
information and data (including, but not limited to, formulae, procedures,
protocols, techniques and results of experimentation and testing) related to the
creation, assembly, generation, synthesis or manipulation of the TREGA Libraries
and compounds (other than those embodied in the Research Lead Compounds).
1.31 "TREGA Libraries" shall mean those certain synthetic compound
libraries owned by or licensed to TREGA as of the Effective Date and during the
Research Period, each of which comprises a group of compounds having defined
permutations of one or more selected structural components of such compounds;
all to the extent and only to the extent that TREGA now has or hereafter will
have the right to grant licenses, immunities or other rights to ONO thereunder;
provided however, that TREGA Libraries shall not include (a) libraries initially
developed by Third Parties without a license from TREGA or its Affiliates or
licensees, using means other than those used by TREGA prior to the Effective
Date, and which are acquired by TREGA as part of the acquisition of such
-6-
7
CONFIDENTIAL TREATMENT REQUESTED
Third Party's on-going business; nor (b) any TREGA libraries that have been or
are hereafter developed by TREGA in the first instance as an internal or
external custom project under a written agreement with a Third Party which
provides that such Third Party shall have the exclusive rights to such custom
library.
1.32 "TREGA Materials" shall mean any item provided hereunder by TREGA
to ONO and its Affiliates or to Third Parties by TREGA at the behest of ONO.
1.33 "TREGA Post-Research Period Compound" shall mean a compound (other
than Preclinical Lead Compound Candidates) which meets [CONFIDENTIAL TREATMENT
REQUESTED] Benchmarks and modulates the production of [CONFIDENTIAL TREATMENT
REQUESTED] and [CONFIDENTIAL TREATMENT REQUESTED] by binding selectively to
melanocortin receptor 1, is directly or indirectly conceived, designed,
synthesized or developed by TREGA or its Affiliates within [CONFIDENTIAL
TREATMENT REQUESTED] years after the Research Period and incorporates, uses, is
the result of, is based upon, is derived from or by use of, or is a by-product
of the TREGA Technology or the ONO Technology or a biological receptor
characterized in whole or in part by use of the TREGA Technology or the ONO
Technology but only to the extent that TREGA has the right to sublicense the
same.
1.34 "TREGA Patent Rights" shall mean (a) all patent applications
heretofore or hereafter filed or having legal force in any country owned by or
licensed to TREGA (other than by ONO) or to which TREGA otherwise acquires
rights, which claim (i) the TREGA Assays, the TREGA Libraries, or any compounds
identified, conceived or derived from or through the use of such TREGA Assays or
TREGA Libraries; or (ii) TREGA Post-Research Period Compounds; or (iii) the use
or the manufacturing process of the compositions described in clauses (i) and
(ii) above or (iv) TREGA Improvements pursuant to Section 10.1 herein, together
with any and all patents that have issued or in the future issue therefrom,
including utility, model and design patents and certificates of invention, and
(b) all divisionals, continuations, continuations-in-part, reissues, renewals,
extensions or additions to any such patents and patent applications; all to the
extent and only to the extent that TREGA now has or hereafter will have the
right to grant licenses, immunities or other rights thereunder. Notwithstanding
the foregoing, "TREGA Patent Rights" shall exclude all technology, information,
patent rights, methods, processes and all intellectual property rights related
to the generation, assembly, synthesis, creation or manipulation of the TREGA
Libraries and compounds (other than the Research Lead Compounds) and iterations
therefrom.
1.35 "TREGA Research Results" shall mean the information and data
resulting from the Research Work done solely by TREGA, its Affiliates or Persons
on behalf of TREGA relating directly or indirectly to the Research Lead
Compounds during the Research Period; all to the extent and only to the extent
that TREGA now has or hereafter acquires the right to grant licenses,
immunities, or other rights thereunder. TREGA Research Results shall exclude
-7-
8
CONFIDENTIAL TREATMENT REQUESTED
all information and data (including, but not limited to, formulae, procedures,
protocols, techniques and results of experimentation and testing) related to the
creation, assembly, generation, synthesis or manipulation of TREGA Libraries and
compounds (other than those embodied in Research Lead Compounds).
1.36 "TREGA Royalty Term" shall mean, with respect each Licensed Product
in each country in the TREGA Territory, the period of time equal to
[CONFIDENTIAL TREATMENT REQUESTED] until the expiration of the last ONO Valid
Patent Claim if the manufacture, use or sale of such Licensed Product in such
country was covered by an ONO Valid Patent Claim, the term for which such ONO
Valid Patent Claim was in effect and would, if in an issued patent, be infringed
but for the license granted by this Agreement.
1.37 "TREGA Technology" shall mean, collectively, the TREGA Patent
Rights, the TREGA Know-How and the TREGA Research Results.
1.38 "TREGA Territory" shall mean all of the countries of the world not
included in the ONO Territory or Europe.
1.39 "TREGA Valid Patent Claim" shall mean either (a) a claim of an
issued and unexpired patent included within the TREGA Patent Rights, which has
not been held permanently revoked, unenforceable or invalid by a decision of a
court or other governmental agency of competent jurisdiction, unappealable or
unappealed within the time allowed for appeal, and which has not been admitted
to be invalid or unenforceable through reissue or disclaimer or otherwise or (b)
a claim of a pending patent application included within the TREGA Patent Rights,
which claim was filed in good faith and has not been abandoned or finally
disallowed without the possibility of appeal or refiling of such application.
ARTICLE 2
REPRESENTATIONS AND WARRANTIES
Each party hereby represents and warrants to the other party as follows:
2.1 Existence and Power. Such party (a) is duly organized, validly
existing and in good standing under the laws of the jurisdiction where it is
organized; (b) has the requisite power and authority and the legal right to own
and operate its property and assets, to lease the property and assets it
operates under lease, and to carry on its business as it is now being conducted,
and (c) is in compliance with all requirements of applicable law, except to the
extent that any noncompliance would not have a
-8-
9
material adverse effect on the properties, business, financial or other
condition of such party and would not materially adversely affect such party's
ability to perform its obligations under this Agreement.
2.2 Authorization and Enforcement of Obligations. Such party (a) has the
requisite power and authority and the legal right to enter into this Agreement
and to perform its obligations hereunder, and (b) has taken all necessary action
on its part to authorize the execution and delivery of this Agreement and the
performance of its obligations hereunder. This Agreement has been duly executed
and delivered on behalf of such party, and constitutes a legal, valid, binding
obligation, enforceable against such party in accordance with its terms.
2.3 Consents. All necessary consents, approvals and authorizations of
all governmental authorities and other Persons required to be obtained by such
party in connection with this Agreement have been obtained.
2.4 No Conflict. The execution and delivery of this Agreement and the
performance of such party's obligations hereunder (a) do not conflict with or
violate any requirement of applicable laws or regulations, and (b) do not
conflict with, or constitute a default under, any contractual obligation of such
party.
2.5 DISCLAIMER OF WARRANTIES.
2.5.1 NOTHING IN THIS AGREEMENT SHALL BE CONSTRUED AS A REPRESENTATION
MADE OR WARRANTY GIVEN BY EITHER PARTY THAT ANY PATENT WILL ISSUE BASED UPON ANY
PENDING PATENT APPLICATION WITHIN EITHER PARTY'S PATENT RIGHTS, THAT ANY PATENT
WITHIN EITHER PARTY'S PATENT RIGHTS WHICH ISSUES WILL BE VALID, OR THAT THE USE
OF ANY EITHER PARTY'S MATERIALS OR ANY EITHER PARTY'S TECHNOLOGY WILL NOT
INFRINGE THE PATENT OR PROPRIETARY RIGHTS OF ANY OTHER PERSON.
2.5.2 THE TREGA MATERIALS ARE PROVIDED BY TREGA "AS IS" AND WITHOUT
WARRANTY OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING WITHOUT LIMITATION THE
WARRANTIES OF DESIGN, MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE,
NONINFRINGEMENT OF THE INTELLECTUAL PROPERTY RIGHTS OF THIRD PARTIES OR
WARRANTIES ARISING FROM A COURSE OF DEALING, USAGE OR TRADE PRACTICES. IN NO
EVENT WILL TREGA OR ANY OF ITS THIRD PARTY LICENSORS WHOSE TECHNOLOGY IS
UTILIZED IN PROVIDING TREGA MATERIALS HEREUNDER BE LIABLE FOR ANY INCIDENTAL,
SPECIAL OR CONSEQUENTIAL DAMAGES RESULTING FROM EXERCISE OF THE LICENSE RIGHTS
BY ONO HEREUNDER OR USE OF THE TREGA MATERIALS OR ANY LICENSED PRODUCTS.
2.5.3 THE ONO MATERIALS ARE PROVIDED BY ONO "AS IS" AND WITHOUT
WARRANTY OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING WITHOUT LIMITATION
THE WARRANTIES OF DESIGN, MERCHANTABILITY,
-9-
10
CONFIDENTIAL TREATMENT REQUESTED
FITNESS FOR A PARTICULAR PURPOSE, NONINFRINGEMENT OF THE INTELLECTUAL PROPERTY
RIGHTS OF THIRD PARTIES OR WARRANTIES ARISING FROM A COURSE OF DEALING, USAGE OR
TRADE PRACTICES. IN NO EVENT WILL ONO OR ANY OF ITS THIRD PARTY LICENSORS WHOSE
TECHNOLOGY IS UTILIZED IN PROVIDING ONO LIBRARIES HEREUNDER BE LIABLE FOR ANY
INCIDENTAL, SPECIAL OR CONSEQUENTIAL DAMAGES RESULTING FROM EXERCISE OF THE
LICENSE RIGHTS BY TREGA HEREUNDER OR USE OF THE ONO MATERIALS OR ANY LICENSED
PRODUCTS.
2.6 TREGA hereby represents that it has acquired a non-exclusive
license to a U.S. patent entitled DNA Encoding Melanocyte Stimulating
Hormone Receptor (Cone et al. No.5,532,347) and a patent application
entitled Mammalian Melanocyte Stimulating Hormone Receptors and Uses
(Cone et al WO93/21316), subject to the limitation set forth in Sections
5.1 and 5.2.
ARTICLE 3
TREGA RESEARCH PROGRAM
3.1 Research Work. During the Research Period, TREGA shall perform the
Research Work set forth in the Research Plan, in an effort to identify
Preclinical Lead Compound Candidates by using reasonable efforts comparable to
those used for TREGA's original research programs. TREGA shall not screen
libraries for ONO or deliver compounds therefrom or any other items to ONO which
would subject ONO to any obligations other than those set forth in the Agreement
without express written consent of ONO.
3.2 Supply of ONO Libraries. ONO shall supply TREGA with up to two ONO
Libraries within 4 months after the Effective Date.
3.3 Research Lead Compounds.
3.3.1 TREGA shall provide ONO with such reasonable quantity of any
Preclinical Lead Compound Candidate during the Research Period as determined by
the Management Committee together with the TREGA Research Results pertaining
thereto, provided that ONO shall not request a quantity of such Compound
exceeding TREGA's capability. ONO shall provide TREGA with the ONO Research and
Development Results pertaining to any Preclinical Lead Compound Candidate,
Modified Compound and/or ONO Mimetic Compound during the term of this Agreement.
A reasonable quantity of such Modified Compound and/or ONO Mimetic Compound
shall be provided to TREGA as determined by the Management Committee, for the
purpose of testing it only to confirm the ONO Research and Development Results.
3.3.2 ONO shall be entitled to request that TREGA provides ONO with such
reasonable quantity of a compound, as determined by the Management Committee,
satisfying the [CONFIDENTIAL TREATMENT REQUESTED] Benchmarks for the purpose of
testing it only to confirm the TREGA Research
-10-
11
Results, provided that ONO shall not request a quantity of such Compound
exceeding TREGA's capability.
3.4 Research Reports. Not later than 10 days following each month during
the Research Period, TREGA shall prepare and provide ONO with a brief written
research report, in reasonable detail describing the work performed and the
results obtained during such month.
3.5 Shipment of TREGA or ONO Materials.
3.5.1 Each shipment of the TREGA Materials or the ONO Materials under
this Agreement, whether Research Lead Compounds, or other items shall be
governed by the terms of this Agreement. None of the terms or conditions of any
order, invoices or similar instruments shall be applicable, except those
specifying quantity, delivery dates, designated carrier, special supply
instructions and invoice information, if any.
3.5.2 Title and risk of loss and damage to the TREGA Materials shall
pass to ONO upon release to ONO's designated carrier or, in the absence of such
designation by ONO, to a carrier designated by TREGA, subject to the provisions
of indemnity set forth in Article 12 hereto. Title and risk of loss and damage
to the ONO Materials shall pass to TREGA upon release to TREGA's designated
carrier or, in the absence of such designation by TREGA, to a carrier designated
by ONO, subject to the provisions of indemnity set forth in Article 12 hereto.
3.6 Restrictions on Use.
3.6.1 ONO shall have the right to test and evaluate the TREGA Materials
to confirm TREGA Research Results. ONO shall not, directly or indirectly, use,
modify or expand the TREGA Materials (other than the Research Lead Compounds
pursuant to Article 5) for any purpose other than as set forth in this
Agreement, or otherwise use them to build libraries, or authorize, cause or
assist in any way any Person in any of the foregoing.
3.6.2 TREGA shall have the right to test and evaluate the ONO Materials
to confirm the ONO Research and Development Results. TREGA shall not, directly
or indirectly, use, modify or expand the ONO Materials (other than the Research
Lead Compounds pursuant to Article 5) for any purpose other than as set forth in
this Agreement, or otherwise use them to build libraries, or authorize, cause or
assist in any way any Person in any of the foregoing.
3.6.3 Notwithstanding anything to the contrary in this Agreement,
TREGA shall be the sole owner of all TREGA Libraries and TREGA
Technology. TREGA shall have the sole right to prepare, file, prosecute,
maintain and abandon patents and patent applications on the TREGA
Technology. Nothing herein shall be deemed to grant to ONO rights in the
TREGA Materials or the TREGA Technology, except as expressly licensed to
ONO hereunder. ONO
-11-
12
shall not, directly or indirectly, (i) claim ownership to the TREGA Materials or
to the TREGA Technology, or (ii) transfer the TREGA Materials or TREGA
Technology to any Person other than to employees and consultants of ONO who are
working on activities directly related to this Agreement. Within thirty (30)
days after the expiration or earlier termination of the Research Period, ONO
shall return all unused TREGA Materials to TREGA.
3.6.4 Notwithstanding anything to the contrary in this Agreement, ONO
shall be the sole owner of all ONO Materials and ONO Technology. ONO shall have
the sole right to prepare, file, prosecute, maintain and abandon patents and
patent applications on the ONO Technology. Nothing herein shall be deemed to
grant to TREGA rights in the ONO Materials or the ONO Technology, other than as
expressly set forth in this Agreement. TREGA shall not, directly or indirectly,
(i) claim ownership to the ONO Materials or to ONO Technology, or (ii) transfer
the ONO Materials or the ONO Technology to any Person other than to employees
and consultants of TREGA who are working on activities directly related to this
Agreement. Within thirty (30) days after the expiration or earlier termination
of the Research Period, TREGA shall return all unused ONO Materials to ONO.
3.6.5 ONO UNDERSTANDS THAT THE TREGA MATERIALS ARE EXPERIMENTAL IN
NATURE, ARE FOR RESEARCH USE ONLY AND HAVE NOT BEEN APPROVED FOR USE IN THE
DIAGNOSIS OR TREATMENT OF HUMANS OR ANIMALS. EXCEPT AS OTHERWISE EXPRESSLY
PROVIDED IN THIS AGREEMENT, ONO SHALL NOT ADMINISTER THE TREGA MATERIALS TO
HUMANS IN ANY MANNER OR FORM.
3.6.6 TREGA UNDERSTANDS THAT THE ONO MATERIALS ARE EXPERIMENTAL IN
NATURE, ARE FOR RESEARCH USE ONLY AND HAVE NOT BEEN APPROVED FOR USE IN THE
DIAGNOSIS OR TREATMENT OF HUMANS OR ANIMALS. EXCEPT AS OTHERWISE EXPRESSLY
PROVIDED IN THIS AGREEMENT, TREGA SHALL NOT ADMINISTER THE ONO MATERIALS TO
HUMANS IN ANY MANNER OR FORM.
3.7 Management Committee. There shall be established a Management
Committee comprised of four representatives, two of whom shall be chosen from
time to time by ONO and two of whom shall be chosen from time to time by TREGA
to discuss between the parties hereto with respect to progress, direction and/or
modification of the Research Plan. Management Committee meetings shall (i) be
convened in person once each quarter during the Research Period and once each
year during the Development Period, or as otherwise reasonably requested by
either party hereto, (ii) take place alternating at between San Diego or Osaka,
(iii) be chaired by a representative of a party of the meeting place and (iv) be
participated in by the members of the Committee, provided, however, that each
party may have such other of its employees and consultants participate in the
meeting as may be required to adequately address the specific topics of the
meeting. The agenda of the meeting shall be coordinated between the parties and
established at least two (2) weeks prior to the meeting. In the
-12-
13
CONFIDENTIAL TREATMENT REQUESTED
event that a party wishes to present to the other party the TREGA Research
Results or the ONO Research and Development Results, such party shall furnish
the other with such results, to the extent available, at least two (2) weeks
prior to the meeting. A draft of meeting minutes reflecting matters addressed at
such meeting shall be prepared by the party of the meeting place and provided to
the other for its review and comments. Such minutes shall be considered accurate
only upon signing by representatives of both parties. The parties acknowledge
that such Committee meeting is not authorized to make any decision of the
parties with regard to any material issues including but not limited to
modification of Benchmarks which shall only be authorized by such executed
minutes of the meeting or any other written form. A party may authorize
alternate members to act in the place of members of the Management Committee due
to their absence or other unavailability. The initial meeting of the Management
Committee shall be convened approximately one (1) month following the Effective
Date.
ARTICLE 4
FUNDING
4.1 Funding.
4.1.1 ONO shall pay to TREGA the following nonrefundable, non-
creditable amounts at the times indicated below. During the Research Period
within forty-five (45) days following the end of each six (6) month period,
TREGA shall provide ONO with a written report summarizing in reasonable detail
the expenses used for the Research Work incurred by TREGA during such six (6)
month period for ONO's tax purposes. The amount of expense so reported shall
have no effect on ONO's obligation to make the payments set forth below at the
times indicated.
(a) within ten (10) days of the US $ [CONFIDENTIAL
Effective Date TREATMENT
REQUESTED]
(b) within 30 days of the Effective Date US $ [CONFIDENTIAL
for Research Work to be done during the TREATMENT
initial 12 months by TREGA under this REQUESTED]
Agreement,
(c) within 30 days of the first US $ [CONFIDENTIAL
anniversary of the Effective Date for TREATMENT
Research Work to be done during the REQUESTED]
second 12 months by TREGA under this
Agreement
(d) a one time payment upon commencement US $ [CONFIDENTIAL
by or on behalf of ONO of GLP non- TREATMENT
clinical studies with a Research Lead REQUESTED]
Compound
-13-
14
CONFIDENTIAL TREATMENT REQUESTED
(e) a one time payment upon commencement US $ [CONFIDENTIAL
by or on behalf of ONO of enrollment in a TREATMENT
Phase IIb clinical study with a Research REQUESTED]
Lead Compound
(f) a payment in respect of each TREGA US $ [CONFIDENTIAL
Post Research Period Compound, on a TREATMENT
product by product basis, upon the REQUESTED]
commencement of enrollment in an initial
Phase IIb clinical study
(g) a payment in respect of each Licensed US $ [CONFIDENTIAL
Product, on a product by product basis, TREATMENT
upon the commencement of enrollment in REQUESTED]
the initial Phase III clinical study in
Japan
(h) a payment in respect of each Licensed US $ [CONFIDENTIAL
Product, on a product by product basis, TREATMENT
upon the submission of an NDA in Japan REQUESTED]
(i) a payment in respect of each Licensed US $ [CONFIDENTIAL
Product, on a product by product basis, TREATMENT
upon each NDA approval (and XXX xxxxx REQUESTED]
listing) in Japan
4.2 Royalties Payable by ONO. During the ONO Royalty Term, ONO shall pay
to TREGA royalties on Net Sales in the ONO Territory by ONO, its Affiliates and
(sub)licensees (i) equal to [CONFIDENTIAL TREATMENT REQUESTED] of Net Sales of
each Licensed Product containing a Preclinical Lead Compound Candidate unless it
is a Modified Compound derived from a TREGA Library, and (ii) equal to
[CONFIDENTIAL TREATMENT REQUESTED] of Net Sales of each Licensed Product
containing a Preclinical Lead Compound Candidate derived from an ONO Library, a
Modified Compound, or an ONO Mimetic Compound. ONO, its Affiliates and
(sub)licensees shall not accept any consideration for the sale of Licensed
Products which is not expressly stated in the invoice for such Licensed Products
billed to independent customers who are not Affiliates.
4.3 Royalties Payable by TREGA. During the TREGA Royalty Term, TREGA
shall pay to ONO royalties on Net Sales in the TREGA Territory by TREGA, its
Affiliates and (sub)licensees, equal to [CONFIDENTIAL TREATMENT REQUESTED] of
Net Sales of each Licensed Product containing a Preclinical Lead Compound
Candidate derived from an ONO Library, a Modified Compound, or an ONO Mimetic
Compound. TREGA, its Affiliates, and (sub)licensees shall not accept any
consideration for the sale of such Licensed Products which is not expressly
stated in the invoice for such Licensed Products billed to independent customers
who are not Affiliates.
4.4 Royalty Reduction. Notwithstanding the provisions of Sections
4.2 and 4.3, the royalty rate for a Licensed Product shall be reduced on
a country by country basis by [CONFIDENTIAL TREATMENT REQUESTED]
-14-
15
CONFIDENTIAL TREATMENT REQUESTED
at the time of expiration or invalidation of such other party's Valid Patent
Claims covering such Licensed Product as far as generic versions of such
Licensed Product do not attain aggregate unit sales volume equal to
[CONFIDENTIAL TREATMENT REQUESTED] of the Licensed Product. At such time during
the TREGA Royalty Term or the ONO Royalty Term, as the case may be, that generic
versions of a Licensed Product attain aggregate unit sales volume equal to
[CONFIDENTIAL TREATMENT REQUESTED] of the Licensed Product in a particular
country of such party's Territory following the expiration or invalidation of
all Valid Patent Claims in such country, the applicable royalty rate for the
Licensed Product shall be eliminated.
ARTICLE 5
GRANT OF LICENSES
5.1 ONO Research and Development License. Subject to the terms and
conditions of this Agreement, TREGA hereby grants to ONO a worldwide
royalty-free, nonexclusive license, under the TREGA Technology (but not with
respect to products intentionally designed to [CONFIDENTIAL TREATMENT REQUESTED]
to test, evaluate, and develop the Research Lead Compounds during the Research
Period and the Development Period, solely for the purpose of (a) performing
confirmatory and complementary work to the Research Work, (b) evaluating its
interest in Preclinical Lead Compound Candidates, and (c) performing its
development obligations hereunder. ONO may not grant sublicenses under such
license to any Third Party without the prior written consent of TREGA.
5.2 ONO Commercialization License. Subject to the terms and conditions
of this Agreement, TREGA hereby grants to ONO during the term of this Agreement
an exclusive, royalty-bearing license within the ONO Territory under the TREGA
Technology (but not with respect to products intentionally designed to
[CONFIDENTIAL TREATMENT REQUESTED], to the extent necessary to avoid
infringement, to test any and all Research Lead Compounds and Licensed Products
for the purpose of filing an NDA and to make, have made, use and sell the
Licensed Products within the ONO Territory. The foregoing license shall include
the right to grant sublicenses, subject to the terms and conditions of this
Agreement. ONO hereby agrees to remain liable for performance under this
Agreement by all such sublicensees. TREGA acknowledges that, subject to the
terms and conditions of this Agreement, a senyo jisshiken (an exclusive license
under the patent law of Japan) is granted hereby to ONO under the TREGA Patent
Rights to the extent such TREGA Patent Rights include patents issued in Japan
covering Research Lead Compounds or Licensed Products. Such senyo jisshiken will
be registered in the Japanese Patent Office under Article 77 of Patent Law of
Japan. ONO at its expense shall undertake such registration upon issuance of
such TREGA Patent Rights in Japan. TREGA shall at ONO's request sign legal
documents reasonably
-15-
16
requested by Ono for such purpose after having provided to TREGA English
language translations thereof. The foregoing senyo jisshiken shall not be
construed to cause the parties to be joint owners under Article 73 of the Patent
Law of Japan.
5.3 TREGA Research and Development License. Subject to the terms and
conditions of this Agreement, ONO hereby grants to TREGA a worldwide,
royalty-free, nonexclusive license under the ONO Technology to test, evaluate,
and use the ONO Libraries during the Research Period and to test, evaluate, use,
and develop compounds therefrom during the Development Period, solely for the
purpose of (a) performing the Research Work and (b) performing its obligations
hereunder. TREGA may not grant sublicenses under such license to any Third Party
without the prior written consent of ONO.
5.4 TREGA Commercialization License. Subject to the terms and conditions
of this Agreement, ONO hereby grants to TREGA during the term of this Agreement
an exclusive, royalty-bearing license within the TREGA Territory under the ONO
Technology to the extend necessary to avoid infringement, to test any and all
Research Lead Compounds and Licensed Products for the purpose of filing an NDA
and to make, have made, use and sell the Licensed Products within the TREGA
Territory. The foregoing licenses shall include the right to grant sublicenses,
subject to the terms and conditions of this Agreement. TREGA hereby agrees to
remain liable for performance under this Agreement by all such sublicensees.
5.5 Joint License. The parties hereto agree that they shall jointly
develop Licensed Products of their mutual choosing for manufacture, sale, and
use in Europe and shall reasonably cooperate to reach mutual decisions with
regard to such development. In this regard, the parties agree to cooperate to
seek a single (sub)licensee for development and/or marketing of such Licensed
Product. The parties hereto shall share equally in any consideration derived
therefrom, including, but not limited to, license fees and/or milestone
payments, or any other form of payment of a similar nature, and royalty
payments. The parties hereto further agree to discuss in good faith and to
negotiate cooperatively to reach agreement on such other terms and conditions of
such joint development and commercialization in Europe as may be necessary or
desirable.
5.5.1 Joint Development License to ONO. Subject to the terms and
conditions of this Agreement, TREGA hereby grants to ONO during the term of this
Agreement a co-exclusive (with TREGA) paid-up license in Europe under the TREGA
Technology, to the extent necessary to avoid infringement, to test any and all
Research Lead Compounds and Licensed Products for the purpose of jointly
developing such Research Lead Compounds and Licensed Products with TREGA, filing
an NDA with respect thereto, and to make, have made, use, and sell Licensed
Products in Europe.
5.5.2 Joint Development License to ONO. Subject to the
-16-
17
CONFIDENTIAL TREATMENT REQUESTED
terms and conditions of this Agreement, ONO hereby grants to TREGA during the
term of this Agreement a co-exclusive (with ONO) paid-up license in Europe under
the ONO Technology, to the extent necessary to avoid infringement, to test any
and all Research Lead Compounds and Licensed Products for the purpose of jointly
developing such Research Lead Compounds and Licensed Products with ONO, filing
an NDA with respect thereto, and to make, have made, use, and sell Licensed
Products in Europe.
5.6 Non-exclusive License on Improvements. Each party shall grant a
non-exclusive license to the other party within such other party's Territory
under such party's patents and patent applications relating to such party's
Improvements. Considerations for such non-exclusive license under this Section
5.6 shall be discussed in good faith based on the value of such Improvements.
5.7 Option to Acquire TREGA Post Research Period Compounds. During the
[CONFIDENTIAL TREATMENT REQUESTED] year period commencing with the end of the
Research Period, any TREGA Post Research Period Compounds, as to which TREGA has
rights to grant an exclusive license in the ONO Territory, shall be presented to
ONO, and promptly thereafter TREGA shall provide to ONO a reasonable quantity of
such TREGA Post Research Period Compounds as determined by the Management
Committee together with any data and information relating to such TREGA Post
Research Period Compounds for consideration under this Section 5.7. Following
presentation, ONO shall have [CONFIDENTIAL TREATMENT REQUESTED] months during
which to give notice to TREGA that such TREGA Post Research Period Compounds
shall be deemed to be a Preclinical Lead Compound Candidate hereunder, provided,
however, that ONO may extend such period, with the prior written consent of
TREGA. If such Compound is deemed by ONO to be a Preclinical Lead Compound
Candidate, Ono shall receive such Preclinical Lead Compound Candidate subject to
all the terms and conditions of this Agreement, except as expressly set forth
below, namely: (i) ONO shall pay [CONFIDENTIAL TREATMENT REQUESTED] to TREGA
upon designation of such compound as a Preclinical Lead Compound Candidate in
lieu of any payment under Section 4.1.1(d) herein; (ii) if such compound is the
second deemed Preclinical Lead Compound Candidate under this Section 5.7, the
payment set forth in clause (i) above shall be [CONFIDENTIAL TREATMENT
REQUESTED], and if such compound is the third or any subsequent deemed
Preclinical Lead Compound Candidate, the payment set forth in clause (i) above
shall be [CONFIDENTIAL TREATMENT REQUESTED] each; and (iii) the territory of
ONO's license rights to such deemed Preclinical Lead Compound Candidates shall
be limited to the ONO Territory and rights in Europe granted to ONO in Section
5.5 shall not apply to any TREGA Post Research Period Compound.
5.8 Termination for Failure to Commercialize.
5.8.1 At the time of [CONFIDENTIAL TREATMENT REQUESTED] in respect of a
Licensed Product in the ONO Territory, any licenses granted to ONO by TREGA
pursuant to Section 5.2 under the TREGA Technology related to any other Research
Lead Compounds which have not been actively developed for purposes of
[CONFIDENTIAL TREATMENT REQUESTED] in the ONO Territory for
-17-
18
CONFIDENTIAL TREATMENT REQUESTED
more than [CONFIDENTIAL TREATMENT REQUESTED] months shall revert to TREGA
automatically without further action by TREGA. At the time of [CONFIDENTIAL
TREATMENT REQUESTED], ONO shall inform TREGA as to which Research Lead Compounds
there has been no such activity for a period of [CONFIDENTIAL TREATMENT
REQUESTED] months. Further, if at any time ONO suspends development of all
Research Lead Compounds for a period of at least [CONFIDENTIAL TREATMENT
REQUESTED] months without any reasonable justification which is acceptable to
TREGA, all licenses granted to ONO pursuant to Section 5.2 shall revert to TREGA
automatically without further action by TREGA.
5.8.2 At the time of [CONFIDENTIAL TREATMENT REQUESTED] in respect of a
Licensed Product in the TREGA Territory, any licenses granted to TREGA by ONO
pursuant to Section 5.4 under the ONO Technology related to any other Research
Lead Compounds which have not been actively developed for purposes of
[CONFIDENTIAL TREATMENT REQUESTED] in the TREGA Territory for more than
[CONFIDENTIAL TREATMENT REQUESTED] months shall revert automatically to ONO
without further action by ONO. At the time of any NDA filing, TREGA shall inform
ONO as to which Research Lead Compounds there has been no such activity for a
period of [CONFIDENTIAL TREATMENT REQUESTED] months. Further, if at any time
TREGA suspends development of all Research Lead Compounds derived from ONO
Libraries for a period of at least [CONFIDENTIAL TREATMENT REQUESTED] months
without any reasonable justification which is acceptable to ONO, all licenses
granted to TREGA pursuant to Section 5.4 to ONO Libraries shall revert to ONO
automatically without further action by ONO.
5.9 No Third Party License. Each party hereby represents to the other
that it will not present to the other any Research Lead Compound or derivative
pursuant to Section 3.3, as to which it has previously granted rights to an
Affiliate or Third Party or then is undertaking a bona fide effort to develop.
5.10 TREGA Reservation of Rights. Notwithstanding anything to the
contrary in this Agreement, TREGA expressly reserves the right for itself, and
the right to grant to Affiliates and Third Parties the right, to use the TREGA
Technology and the TREGA Materials for research, screening, testing and
evaluation purposes.
5.11 ONO Reservation of Rights. Notwithstanding anything to the contrary
in this Agreement, ONO expressly reserves the right for itself, and the right to
grant to Affiliates and Third Parties the right, to use the ONO Materials and
the ONO Technology for research, screening, testing and evaluation purposes.
ARTICLE 6
DEVELOPMENT OF PRODUCTS
6.1 ONO Development and Commercialization Efforts. In the event ONO
decides to commence Good Laboratory Practice ("GLP") pre-clinical studies
pursuant to Section 6.1.2 herein, it thereafter shall use its reasonable good
faith efforts (a) to
-18-
19
conduct such further research and development activities as may be necessary or
desirable to develop such Research Lead Compounds, (b) to conduct such
preclinical and human clinical testing as necessary or desirable to obtain all
regulatory approvals to manufacture, use and sell such Research Lead Compounds
as ONO determines are commercially feasible, and (c) to diligently file and
prosecute such NDA with the applicable regulatory authorities to seek all
necessary approvals to manufacture, use and sell such Research Lead Compounds in
such countries of the ONO Territory as ONO determines are commercially feasible,
and (d) to commence marketing as soon as commercially practicable, and to
diligently market thereafter, each Research Lead Compound in each country in
which it has obtained all necessary regulatory approvals therefor. ONO shall be
responsible for funding the costs of all such research, development,
pre-clinical and clinical trials, regulatory approval and commercialization of
Licensed Products.
6.1.1 ONO shall initiate testing a Preclinical Lead Compound
Candidate promptly after its receipt of a quantity of such Compound in
accordance with Section 3.3 and shall diligently conduct such tests using
reasonable efforts comparable to those used for ONO's original research program
in order to determine its interest to commence GLP pre-clinical studies in
preparation for human clinical testing. ONO shall further furnish TREGA with the
ONO Research and Development Results related to such Preclinical Lead Compound
Candidate as soon as they become available. ONO shall notify TREGA within a
reasonable period of time whether or not ONO will commence GLP pre-clinical
studies with such Preclinical Lead Compound Candidate. ONO may also decide that
a Preclinical Lead Compound Candidate is subject to further modification,
derivatization or optimization, by ONO or through the use of ONO's own
technology by ONO's reasonable determination that Preclinical Lead Compound
Candidate is not commercially sufficient to develop and market in the ONO
Territory. ONO shall conduct such modification, derivatization or optimization
at its own discretion and expense and shall continue to provide TREGA with the
results related thereto.
6.1.2 In the event that ONO decides to commence GLP pre-clinical studies
with a Research Lead Compound and/or Licensed Product for the purpose of filing
an NDA with it in the ONO Territory, ONO shall provide TREGA from time to time
with its development plan as it changes. ONO shall further, at its own expenses,
use its reasonable best efforts comparable to other development programs of its
own to perform GLP pre- clinical and clinical studies for such purpose, to file
an NDA and/or to commence its marketing promptly after obtaining its approval of
the NDA in the ONO Territory.
6.1.3 At any time during the course of ONO's development pursuant to the
provision of Section 6.1.2 above, ONO may decide to i) terminate this Agreement
pursuant to Section 11.2.3, or ii) substitute such development for other
Research Lead Compounds and/or Licensed Products.
In the event that ONO decides to proceed
-19-
20
with the development of such other Research Lead Compounds and/or Licensed
Products, ONO shall conduct its development in compliance with the provision of
this Section 6.1.
6.2 TREGA Development and Commercialization Efforts. TREGA shall at its
own expenses use its reasonable efforts comparable to other development programs
of its own to perform, or shall seek a partner or a (sub)licensee to have it
perform, GLP pre-clinical and clinical studies with a Research Lead Compound
and/or Licensed Product, to file an NDA with it and commence its marketing
promptly after obtaining its approval of the NDA in the TREGA Territory.
6.3 Cooperation between the Parties for Commercialization of the
Research Lead Compounds and/or Licensed Products.
6.3.1 To the extent feasible and consistent with the parties' intended
indications, each party shall endeavor to consult with each other to perform GLP
pre-clinical and clinical studies with an identical Research Lead Compound
and/or Licensed Product for commercialization in its own Territory.
6.3.2 The parties hereto agree that each party and its Affiliates shall
consult with the other party, and shall endeavor to accept the other party's
suggestions, in the preparation of protocols for GLP pre- clinical and clinical
studies so as to allow such studies to be utilized by the other party's NDA in
its Territory and to avoid performing such studies in duplicate, taking into
account discussions taking place at International Conference on Harmonization of
Technical Requirements for Registration of Pharmaceuticals for Human Use,
provided, however, that the party performing such studies shall be entitled to
make the final decision on the protocols of such studies. In the event that
TREGA's (sub)licensees in the territories of U.S.A. and/or Canada conducts such
GLP pre-clinical and clinical studies, TREGA shall endeavor to arrange
discussions between ONO and such TREGA's (sub)licensees for the purpose of the
provision of this Section.
6.3.3 In the event that each party utilizes, for its NDA in its
Territory, the results and data of GLP pre-clinical studies, pharmacokinetic
studies, toxicology studies, clinical studies, and other studies related to
development and commercialization that have been developed by the other party or
such other party's Affiliates or (sub)licensees then such party shall reimburse
the party performing such study for a part of the expenses that such other party
expended in proportion to the size of its Territory and the degree to which such
study was used. In making such calculation Japan, Korea, Taiwan and China shall
be considered one-third of the world, Europe shall be considered one-third of
the world and the remaining countries of the world shall be considered one-third
of the world. Only those results and data that allow a party, in connection with
the pursuit of its NDA, to avoid repeating work already done by the other party
hereto shall be deemed to be used under this Section 6.3.3. Results and data
-20-
21
submitted, which do not comprise a fundamental portion of a party's NDA, but
which are relied upon or provided for informational purposes or in support of
safety shall not be deemed to have been used hereunder. Subject to the provision
of this Section, the parties shall freely share all studies, results, and data
arising by virtue of their activities in connection with this Agreement.
6.4 Records. ONO and TREGA shall maintain records, in sufficient detail
and in good scientific manner appropriate for product approval and patent
purposes, which shall reflect all work done and results achieved in the
performance of their respective research and development activities regarding
the Research Lead Compounds and/or Licensed Products(including all data in the
form required under all applicable laws and regulations).
6.5 Reports. In addition to any other research reports due under this
Agreement, during the term of this Agreement, each party shall prepare and
deliver to the other party every six (6) months written reports which shall
describe, in reasonably sufficient detail, information to update the prior
report filed hereunder with respect to the Research Lead Compounds and/or
Licensed Products under active development for filing an NDA in their respective
Territories, including without limitation, (a) a summary of respective research
and development performed to date, the work-in-progress and the current schedule
of anticipated events or milestones employing respective Research Results, (b)
the progress of the testing in human clinical trials, (c) the status of
obtaining the necessary approvals to manufacture and market the Research Lead
Compounds and/or Licensed Products, (d) the status of pre- launch marketing
plans, and (e) a summary of all activities relating to (sub)licensees employing
respective Research Results. In addition, each party shall provide the other
party with written notice of all regulatory filings and submissions regarding
the Research Lead Compounds and/or Licensed Products prior to the date of such
filings and submissions, and with written notice of all approvals obtained
promptly after obtaining such approvals.
6.6 Manufacturing. ONO shall at its own responsibility and expense have
the right to manufacture or have manufactured all its required quantities of
drug substance contained in the Licensed Product for use in the ONO Territory.
The parties hereto shall cooperate in, and exchange information regarding, the
reduction of the manufacturing costs of such drug substance. each party shall
transfer to the other copies of manufacturing data relating to such drug
substance as soon as they become available. Upon request of either party, both
parties agree to negotiate in good faith and reach an agreement as to which
party will manufacture and supply such drug substance, as well as to establish
commercially reasonable terms for such manufacture and supply.
ARTICLE 7
ROYALTY REPORTS AND ACCOUNTING
-21-
22
7.1 Reports, Exchange Rates. During the term of this Agreement following
the First Commercial Sale of each Licensed Product, each party, its Affiliates
or (sub)licensees shall furnish to the other a quarterly written report by
forty-five (45) days following the end of each fiscal quarter of each calendar
year showing in reasonably specific detail with regard to each Licensed Product,
on a country by country basis, (a) the invoiced prices to its customers, the
gross sales and the Net Sales in quantity and value, sold by each party, its
Affiliates and its (sub)licensees in its own Territory during the reporting
period ; (b) in ONO's case, the royalties payable in United States dollars which
shall have accrued hereunder based upon Net Sales of each Licensed Products sold
by ONO in the ONO Territory or in TREGA's case, the royalties payable in
Japanese Yen which shall have accrued hereunder based upon Net Sales of each
Licensed Products sold by TREGA in the TREGA Territory; (c) the withholding
taxes, if any, required by law to be deducted in respect of such sales; (d) the
date of the First Commercial Sales of each Licensed Product in each country
during the reporting period; and (e) the exchange rates used in determining the
amount of United States dollars in ONO's case and the amount of Japanese Yen in
TREGA's case. The exchange rates shall be the rate used for the remittance of
the royalty payment hereunder. Notwithstanding the foregoing, TREGA acknowledges
that ONO's fiscal term is semi-annual basis and any royalty payments for the Net
Sales of the first and third quarters are tentative and are calculated based the
conditions used for the previous quarter. If any over- or underpayments are
identified in the calculation of the royalty using the conditions of such
current term at the end of ONO's official semi-annual term (the second and forth
ONO's fiscal quarter), then such over- or underpayments shall de deducted or
added respectively from the royalty payments of the second or forth ONO's fiscal
quarter.
7.2 Audits.
7.2.1 ONO and TREGA shall keep and maintain complete, accurate and
proper books and records as necessary to determine accurately the gross sales,
Net Sales and the royalty payable to the other party hereunder, for a period of
five (5) years following the date on which such royalties are reported and paid
hereunder. Upon the written request of a royalty recipient hereunder and not
more than once in each calendar year, a royalty payer hereunder shall permit an
independent certified public accounting firm of internationally recognized
standing, selected by the royalty recipient and reasonably acceptable to the
royalty payer, to have access during normal business hours to such of the
records of the royalty payer as may be reasonably necessary to verify the
accuracy of the royalty reports hereunder. The accounting firm shall disclose to
the royalty recipient only whether the royalty reports are correct or not and
the specific details concerning any discrepancies. No other information shall be
shared.
-22-
23
7.2.2 If such accounting firm concludes that additional royalties were
owed during such period, the royalty payer shall pay the additional royalties
within thirty (30) days of the date the royalty recipient delivers to the
royalty payer such accounting firm's written report so concluding, provided,
however, that the royalty recipient shall no event be entitled to claim
underpayment of the royalty payer of more than retrospective five (5) years from
the original due date of such payment. The fees charged by such accounting firm
shall be paid by the royalty recipient; provided, however, if the audit
discloses that the royalties payable for the audited period are more than one
hundred and ten percent (110%) of the royalties actually paid for such period,
then the royalty payer shall pay the reasonable fees and expenses charged by
such accounting firm. If the overpayments are identified by such accounting
firm, an amount equivalent to such overpayments shall be deducted from the
following royalty payment owed by the royalty payer.
7.3 Confidential Financial Information. The parties shall treat all
financial information subject to review under this Article 7 as confidential,
and shall cause its accounting firm to retain all such financial information in
confidence.
ARTICLE 8
PAYMENTS
8.1 Payment Terms. Royalties shown to have accrued by each royalty
report provided for under Article 7 of this Agreement shall be due and payable
on the date such royalty report is due. Payment of royalties in whole or in part
may be made in advance of such due date.
8.2 Payment Method. Except as provided in this Section 8.2, all payments
under this Agreement shall be paid in United States dollars to TREGA and in
Japanese Yen to ONO by bank wire transfer in immediately available funds to such
account as designated by the recipient before such payment is due. Upon such
election by a recipient made in writing not less than thirty (30) days prior to
any payment date, the payer shall pay all royalties owing to the recipient
hereunder in the currency in which such royalties accrued, without conversion
into United States dollars or into Japanese Yen.
8.3 Exchange Control. If at any time legal restrictions prevent the
prompt remittance of part or all royalties with respect to any country where a
Licensed Product is sold, payment shall be made through such lawful means or
methods as the recipient reasonably shall determine.
8.4 Taxes. Other than (a) taxes imposed by the recipient's
jurisdiction on the recipient's income and (b) taxes imposed solely by
reason of a recipient having a permanent establishment in any
-23-
24
other country or a recipient otherwise being subject to taxation by such country
(except solely by reason of the licenses granted under this Agreement), any tax
paid or required to be withheld by a payer on an account of royalties payable to
the other party shall be deducted from the amount of royalties otherwise due.
Such payer shall provide the other party with proof of any taxes withheld and
paid by such payer for the purpose of avoiding double taxation.
8.5 Late Payments. Unless otherwise provided in this Agreement, a payer
shall pay interest to the recipient hereunder on the aggregate amount of any
payments that are not paid on or before the date such payments are due under
this Agreement, at a rate per annum equal to the lesser of the prime rate of
interest as reported by Bank of America NT&SA in San Francisco, California, from
time to time in case that ONO is a payer, and by the Tokai Bank, Ltd. in Osaka,
Japan for TREGA royalty payments from time to time in case TREGA is a payer,
plus two percent (2%), or the highest rate permitted by applicable law,
calculated on the number of days such payment is delinquent.
ARTICLE 9
CONFIDENTIALITY
9.1 Confidential Information. During the term of this Agreement, and for
a period of ten (10) years following the expiration or earlier termination
hereof, each party shall maintain in confidence all information of the other
party disclosed by the other party and identified as, or acknowledged to be,
confidential (the "Confidential Information"), and shall not use, disclose or
grant the use of the Confidential Information except for the sole purpose of
using the Confidential Information to perform its rights and obligations hereof
and further except on a need-to-know basis to those directors, officers,
Affiliates, employees, consultants, clinical investigators or contractors, to
the extent such disclosure is reasonably necessary in connection with such
party's activities as expressly authorized by this Agreement. The foregoing
shall not obligate the parties to seek confidentiality agreements with its
directors, officers, Affiliates, employees, consultants, clinical investigators,
or contractors for a term extending beyond five (5) years. To the extent that
disclosure is authorized by this Agreement, prior to disclosure, each party
hereto shall obtain agreement of any such Person to hold in confidence and not
make use of the Confidential Information for any purpose other than those
permitted by this Agreement.
9.2 Permitted Disclosures. The confidentiality obligations contained in
Section 9.1 above shall not apply to the extent that (a) any receiving party
(the "Recipient") is required (i) to disclose information by law, order or
regulation of a governmental agency or a court of competent jurisdiction, or
(ii)
-24-
25
to disclose information to any governmental agency for purposes of obtaining
approval to test or market any Licensed Product, provided in either case that
the Recipient shall provide written notice thereof to the other party and
sufficient opportunity to object to any such disclosure or to request
confidential treatment thereof; or (b) the Recipient can demonstrate that (i)
the disclosed information was public knowledge at the time of such disclosure to
the Recipient, or thereafter became public knowledge, other than as a result of
actions of the Recipient in violation hereof; (ii) the disclosed information was
rightfully known by the Recipient (as shown by its written records) prior to the
date of disclosure to the Recipient by the other party hereunder; (iii) the
disclosed information was disclosed to the Recipient on an unrestricted basis
from a source unrelated to any party to this Agreement and not under a duty of
confidentiality to the other party; or (iv) the disclosed information was
independently developed by the Recipient without access to or use of such
information.
9.3 Terms of this Agreement. TREGA and ONO shall not disclose any terms
or conditions of this Agreement to any Third Party without the prior consent of
the other party, except as required by applicable law or to Persons with whom
ONO or TREGA has entered into or proposes to enter into a business relationship,
provided that such Persons shall enter into a confidentiality agreement with, or
otherwise owe a duty of confidentiality to TREGA or ONO, as applicable.
Notwithstanding the foregoing, prior to execution of this Agreement, ONO and
TREGA shall agree upon the substance of information that can be used to describe
the terms of this transaction, and ONO and TREGA may disclose such information,
as modified by mutual agreement from time to time, without the other party's
consent.
9.4 Public Announcement. Except for announcements as required by law,
order or regulation of a governmental agency or a court of competent
jurisdiction, no other announcement, public release or notice of any kind may be
issued without the express written consent of both parties, which consent shall
not be unreasonably held, provided, however, the parties shall prepare a joint
press release announcing the transaction set forth in this Agreement to be
issued promptly upon execution and delivery hereof.
ARTICLE 10
INVENTIONS AND PATENTS
10.1 Ownership of Inventions. The entire right and title in and to any
and all compounds contained within or derived from the ONO Libraries, whether
modified, derivatized or optimized, and uses of such compounds related to the
Research Work under this Agreement ("ONO Inventions"), and any patent
applications, patents or other intellectual property rights based thereon, shall
be owned solely by ONO. The entire right and title in and to any and all
-25-
26
compounds contained within or derived from the TREGA Libraries, whether
modified, derivatized or optimized, and uses of such compounds related to the
Research Work under this Agreement ("TREGA Inventions"), and any patent
applications, patents or other intellectual property rights based thereon, shall
be owned solely by TREGA. The entire right and title in all inventions,
discoveries and other technology including but not limited to uses,
pharmaceutical preparations or process thereof except for ONO and/or TREGA
Inventions as set forth in this Section 10.1 above, whether or not patentable,
and any patent applications, patents or other intellectual property rights based
thereon, conceived or reduced to practice during the Research Period and the
Development Period and arising as a result of the Research Work and the ONO
research and development work (collectively the "Improvements") (a) solely by
employees or others acting solely on behalf of TREGA or its Affiliates shall be
owned solely by TREGA (the "TREGA Improvements"), (b) solely by employees or
others acting solely on behalf of ONO or its Affiliates shall be owned solely by
ONO (the "ONO Improvements"), and (c) jointly by employees or others acting on
behalf of TREGA and by employees or others acting on behalf of ONO, or their
respective Affiliates, shall be owned jointly by TREGA and ONO (the "Joint
Improvements"). Each party promptly shall disclose to the other party the
conception or reduction to practice of Improvements by employees or others
acting on behalf of such party without prejudice to each party's right to
prepare patent applications related to each party's Inventions and/or
Improvements prior to such disclosure provided in Section 10.2 below. TREGA and
ONO each hereby represents that all employees and Persons acting on its behalf
in performing its obligations under this Agreement shall be obligated under a
binding written agreement to assign to it, or as it shall direct, all Inventions
or Improvements made or developed by such employees or Persons.
10.2 Patent Prosecution and Maintenance.
10.2.1 TREGA shall have the right, in its sole discretion and at its
sole expense, to control the preparation, filing, prosecution and maintenance of
all TREGA Patent Rights. TREGA shall be primarily responsible for filing,
prosecuting and maintaining the TREGA Valid Patent Claim which covers the
Research Lead Compounds and/or the Licensed Products under active development
and/or marketing in the ONO Territory, which is necessary to make, have made,
use and/or sell such Licensed Product in the ONO Territory and which would
infringe but the license granted in this Agreement. If TREGA elects not to file
a patent application or decides to abandon any pending application or issued
patent in any country in the ONO Territory which claims or pertains to a
Research Lead Compound, it shall provide reasonable notice to ONO and give ONO
the opportunity to file, prosecute or maintain such application or patent at its
own expense.
10.2.2 ONO shall have the right, in its sole discretion and at its
sole expense, to control the preparation, filing, prosecution and
maintenance of all ONO Patent Rights. ONO shall
-26-
27
be primarily responsible for filing, prosecuting and maintaining the ONO Valid
Patent Claim which covers the Research Lead Compounds and/or the Licensed
Products under active development and/or marketing in the TREGA Territory, which
is necessary to make, have made, use and/or sell such Licensed Product in the
TREGA Territory and which would infringe but the license granted in this
Agreement. If ONO elects not to file a patent application or decides to abandon
any pending application or issued patent in any country in the TREGA Territory
which claims or pertains to a Research Lead Compound, it shall provide
reasonable notice to TREGA and give TREGA the opportunity to file, prosecute or
maintain such application or patent at its own expense.
10.2.3 TREGA shall control the preparation, filing, prosecution and
maintenance of all patents and patent applications which claim the Joint
Improvements, and the parties shall share equally in the costs thereof. If
either party elects not to share such costs then such party shall transfer all
rights, title and interest of such patents and patent applications to the other
party, in which case such other party shall be entitled to take the
responsibility of the preparation, filing, prosecution and maintenance of such
patents and patent applications at its own name and expenses.
10.2.4 In the case of each patent application which claims a Research
Lead Compound, each party's Invention or Improvements or a Joint Improvement,
the controlling party shall use its good faith efforts to provide the other
party with an opportunity to review and comment on the text of each patent
application and selection of countries to file such application in such other
party's Territory before filing, and shall supply the other party with a copy of
such patent application as filed, together with notice of its filing date and
serial number.
10.2.5 Each party shall cooperate with the other party, execute all
lawful papers and instruments and make all rightful oaths and declarations as
may be necessary in the preparation, prosecution and maintenance of all
applications and patents described in this Section 10.2.
10.3 Enforcement of Patent Rights.
10.3.1 The party (the "Patent Party") with the right to control the
maintenance of the patents described in Section 10.2 above shall have the
primary responsibility for the appropriate course of action to take (or refrain
from taking) appropriate action i) to enforce such patents, ii) to xxxxx the
infringement thereof or iii) to control any litigation or other enforcement
action and to enter into, or permit, the settlement of any such litigation or
other enforcement action with respect to such patents if a claim or proceedings
are brought against the other party alleging that the use, development,
manufacturing or sale of the Licensed Product in such other party's Territory
infringes any Third Party's patents or patent applications or if such patents
-27-
28
are infringed by any Third Party, and shall consider, in good faith, the
interests of the other party in so doing, provided, however, that in the event
the Patent Party does not so desire, then it shall provide reasonable notice to
the other party and such other party shall have the right to succeed such
responsibility at its own expense, provided further that the provision of this
Section 10.3.1 shall be subject to the other party's appropriate notification to
the Patent Party of such infringement or such claim or proceeding brought by a
Third Party, and to entrusting the Patent Party's actions in compliance with the
provisions of Section 10.3.3 below.
10.3.2 In the case of each patent described in Section 10.2.1, 10.2.2 or
10.2.3 above which claims the Research Lead Compounds or each party's Inventions
or Improvements or Joint Improvements, if the Patent Party does not, within six
(6) months of receipt of notice from the other party of any infringement or any
claim or proceedings brought by a Third Party within its Territory, xxxxx the
infringement, file suit to enforce such patent against at least one infringing
party or take appropriate actions against such claim or proceedings, the other
party shall have the right to take whatever action it deems appropriate to
enforce such patent.
10.3.3 The party controlling any such enforcement action shall not
settle the action or otherwise consent to an adverse judgment in such action
that diminishes the rights or interests of the non-controlling party within its
Territory without the prior written consent of the other party. All moneys or
awards recovered upon the final judgment or settlement of any such suit in each
Territory shall be retained by the controlling party, except with regard to
Joint Improvements, in which case any moneys or awards shall be split between
the parties in accordance with their expenses incurred in undertaking
enforcement action.
10.3.4 Notwithstanding the foregoing, TREGA and ONO shall fully
cooperate with each other in the planning and execution of any action to enforce
the patents described in Sections 10.2.1, 10.2.2 and 10.2.3 above which claim
the Research Lead Compounds or each party's Inventions or Improvements or Joint
Improvements.
10.4 No Other Technology Rights. Except as otherwise provided in this
Agreement, under no circumstances shall a party, as a result of this Agreement,
obtain any ownership interest or other right in any technology, know-how,
patents, pending patent applications, patent or invention disclosures, products,
libraries, vaccines, antibodies, cell lines or cultures, or animals of the other
party, including items owned, controlled or developed by the other, or
transferred by the other to such party at any time pursuant to this Agreement.
It is understood and agreed by the parties that this Agreement does not grant to
either party any license or other right in basic technology of the other party
except to the extent set forth herein or necessary to enable the parties to
carry out their respective obligations hereunder.
-28-
29
CONFIDENTIAL TREATMENT REQUESTED
10.5 Third Party License. In the event that the use, development,
manufacturing or sale of a Licensed Product by the other party in such other
party's Territory infringes any Third Party's patents or patent applications and
such other party is required to acquire a license from such Third Party to
continue such use, development, manufacturing or sale of the Licensed Product
without further infringing such Third Party's patents or patent applications,
then the royalty rate to the Patent Party herein shall be reduced by the royalty
rate to be required to acquire such license from such Third Party as long as
necessary, provided, however, that in any case the effective royalty rate to the
Patent Party shall not be less than [CONFIDENTIAL TREATMENT REQUESTED] of the
rate stated herein.
ARTICLE 11
TERM AND TERMINATION
11.1 Expiration. Unless terminated earlier pursuant to Section 11.2
below, the term of this Agreement shall expire on the expiration of the parties'
obligations to pay royalties under this Agreement. The parties' obligations to
pay royalties under this agreement shall expire on a country by country basis.
11.2 Termination for Cause.
11.2.1 A party may terminate this Agreement upon or after the breach of
any material provision of this Agreement, if the breaching party has not cured
such breach within ninety (90) days after written notice thereof from the other
party. The licenses granted hereunder to the non-breaching party shall survive a
termination of this Agreement under this Section 11.2.1 and shall remain in full
force and effect, so long as such non-breaching party so desires and shall
continue to comply with its obligations under this Agreement to the breaching
party in respect of such licenses (including without limitation, any reporting,
payment, funding, development, commercialization, or royalty obligations) as if
this Agreement had not been terminated.
11.2.2 In the event that ONO reasonably determines that TREGA fails to
perform the Research Work set forth on Exhibit A or to achieve "[CONFIDENTIAL
TREATMENT REQUESTED] Benchmarks" required to be done during the initial
[CONFIDENTIAL TREATMENT REQUESTED] of the Research Period hereunder, ONO shall
be entitled to terminate this Agreement by delivering written notice of such
termination to TREGA in lieu of prompt payment of the amount required pursuant
to Section 4.1.1(c) herein. In order to be effective such notice shall be
delivered no later than the time required for such payment. Such notice shall
terminate all licenses granted hereunder, and neither party hereto shall have
any obligation to the other as a result of such termination.
11.2.3 This Agreement shall be terminated without further action
by the parties if ONO decides not to commence GLP
-29-
30
pre-clinical studies with any of the Research Lead Compounds pursuant to Section
6.1.1 of this Agreement. Such decision shall not affect any obligation of ONO to
make a payment hereunder which may have accrued prior to such decision.
11.2.4 ONO may terminate this Agreement after the Research Period, if
further development of a Research Lead compound and/or Licensed Product is not
justified due to ONO's reasonable determination that efficacy, safety, medical,
or scientific profile of, or the effectiveness of either party's Patent Rights
specifically related to, such Research Lead Compound and/or Licensed Product, or
substantial changes of economic factors prevents ONO from continuation of such
development, filing an NDA or obtaining an approval thereof in the ONO
Territory.
11.3 Effect of Expiration and Termination. Without prejudice to the
provision of Section 11.2.2 above, expiration or termination of this Agreement
shall not relieve the parties of any obligation accruing prior to such
expiration or termination. Upon expiration of this Agreement under Section 11.1
above, the licenses granted to ONO and/or TREGA under Article 5 shall survive
and thereafter shall be irrevocable without being required to pay any additional
consideration to the other party hereto. The provisions of Articles 9, 10 and 12
shall survive the expiration or termination of this Agreement.
ARTICLE 12
INDEMNITY
12.1 Direct Indemnity. Each party shall indemnify and hold the other
party, its Affiliates, directors, officers, employees, agents, licensors, and
stockholders harmless and hereby forever releases and discharges the other
party, its Affiliates, directors, officers, employees, agents, licensors, and
stockholders from and against all losses, liabilities, damages and expenses
(including reasonable attorneys' fees and costs) that the other party, its
Affiliates, directors, officers, employees, agents and stockholders may suffer
or incur as a result of any claims, demands, actions or other proceedings made
or instituted by a Third Party against any of them arising out of or relating to
(a) any breach by the indemnifying party of its obligations under this
Agreement, or (b) the negligence, recklessness or intentional acts or omissions
in connection with the work performed by or on behalf of the indemnifying party
hereunder.
12.2 Other Indemnity. Subject to the provision of Section 12.1 above,
each party shall indemnify and hold the other party, its Affiliates, directors,
officers, employees, agents and stockholders harmless and hereby forever
releases and discharges the other party, its Affiliates, directors, officers,
employees, agents and stockholders from and against all losses, liabilities,
damages and expenses (including reasonable attorneys' fees and
-30-
31
costs) that the other party, its Affiliates, directors, officers, employees,
agents and stockholders may suffer or incur as a result of any claims, demands,
actions or other proceedings made or instituted by a Third Party against any of
them arising out of or relating to (a) the use by or on behalf of the
indemnifying party, its Affiliates or (sub)licensees of the indemnifying party's
Research Results, or (b) the research, development, manufacture, storage, use,
consumption, sale or advertisement of the indemnifying party's Licensed Product
developed or commercialized by or on behalf of the indemnifying party, its
Affiliates or (sub)licensees in its Territory.
12.3 Procedure. A party (the "Indemnitee") that intends to claim
indemnification under this Article 12 shall promptly notify the other party (the
"Indemnitor") of any claim, demand, action or other proceedings for which the
Indemnitee intends to claim such indemnification, and the Indemnitor shall have
the right to participate in, and, to the extent the Indemnitor so desires,
jointly with any other indemnitor similarly noticed, to assume the defense
thereof with counsel selected by the Indemnitor; provided, however, that the
Indemnitee shall have the right to retain its own counsel, with the fees and
expenses to be paid by the Indemnitor, if representation of the Indemnitee by
the counsel retained by the Indemnitor would be inappropriate due to actual or
potential differing interests between the Indemnitee and any other party
represented by such counsel in such proceedings. The indemnity obligations under
this Article 12 shall not apply to amounts paid in settlement of any loss,
claim, damage, liability or action if such settlement is effected without the
consent of the Indemnitor, which consent shall not be unreasonably withheld or
delayed. The failure to deliver notice to the Indemnitor within a reasonable
time after the commencement of any such action, if prejudicial to its ability to
defend such action, shall relieve the Indemnitor of any liability to the
Indemnitee under this Article 12, but the omission so to deliver notice to the
Indemnitor will not relieve it of any liability that it may have to the
Indemnitee otherwise than under this Article 12. The Indemnitor may not settle
the action or otherwise consent to an adverse judgment in such action that
diminishes the rights or interests of the Indemnitee without the express written
consent of the Indemnitee. The Indemnitee, its employees and agents, shall
cooperate fully with the Indemnitor and its legal representatives in the
investigation of any action, claim or liability covered by this indemnification.
12.4 Insurance.
ONO and TREGA each shall maintain, through self insurance or otherwise,
insurance with respect to the research, development, manufacture and sales of
the Licensed Products by ONO or TREGA, as the case may be, in such amount as ONO
or TREGA, respectively, customarily maintains covering its similar activities.
TREGA and ONO, as applicable, shall maintain such insurance for so long as each
continues to conduct such research, development, manufacture
-31-
32
or sales, and thereafter for so long as TREGA and ONO, as applicable, each
customarily maintains insurance for itself covering its similar activities.
ARTICLE 13
FORCE MAJEURE
Neither party shall be held liable or responsible to the other party nor
be deemed to have defaulted under or breached this Agreement for failure or
delay in fulfilling or performing any terms of this Agreement to the extent, and
for so long as, such failure or delay is caused by or results from causes beyond
the reasonable control of the affected party including but not limited to fire,
floods, embargoes, war, acts of war (whether war be declared or not),
insurrections, riots, civil commotions, strikes, lockouts or other labor
disturbances, acts of God or acts, omissions or delays in acting by any
governmental authority or the other party.
ARTICLE 14
ASSIGNMENT
This Agreement may not be assigned or otherwise transferred, nor, except
as expressly provided hereunder, may any right or obligations hereunder be
assigned or transferred to any Third Party by either party without the consent
of the other party; provided, however, that either TREGA or ONO may, without
such consent, assign this Agreement and its rights and obligations hereunder in
connection with the transfer or sale of all or substantially all of its
business, or in the event of its merger or consolidation or change in control or
similar transaction. Any permitted assignee shall assume all rights and
obligations of its assignor under this Agreement.
ARTICLE 15
SEVERABILITY
Each party hereby acknowledges that it does not intend to violate any
public policy, statutory or common laws, rules, regulations, treaty or decision
of any government agency or executive body thereof of any country or community
or association of countries. Should one or more provisions of this Agreement be
or become invalid, the parties shall substitute, by mutual consent, valid
provisions for such invalid provisions which valid provisions in their economic
effect are sufficiently similar to the invalid provisions that it can be
reasonably assumed that the parties would have entered into this Agreement with
such provisions. In case such provisions cannot be agreed upon, the invalidity
of one or
-32-
33
several provisions of this Agreement shall not affect the validity of this
Agreement as a whole, unless the invalid provisions are of such essential
importance to this Agreement that it is to be reasonably assumed that the
parties would not have entered into this Agreement without the invalid
provisions.
ARTICLE 16
DISPUTE RESOLUTION
In case of any disputes arising between the parties hereto or
arising out of the performance of the obligations of either party hereunder,
both parties shall endeavor to settle such disputes amicably between themselves.
If the parties fail to resolve such disputes, then such disputes shall be
finally resolved by arbitration. Any arbitration hereunder shall be conducted by
a panel of three (3) arbitrators under the UNCITRAL Arbitration Rules. In the
event that the arbitrators are not appointed (or replaced) under such Rules,
then the appointing authority shall be the Court of Arbitration of the
International Chamber of Commerce. The language of the arbitration shall be
English. Any arbitrator may be of any nationality and need not be a lawyer or
hold any other professional status or membership, provided, however, that the
third presiding arbitrator selected pursuant to the UNCITRAL Arbitration Rules
shall be of neither American nor Japanese citizenship or residency and shall be
a lawyer. The award of such arbitration panel shall be in writing, shall state
the reasons for the award, and shall be final and binding upon the parties. Any
such arbitration shall be held in San Diego, California, the United States or
any other mutually agreed location if the arbitration is demanded by ONO, and in
Osaka, Japan if the arbitration is demanded by TREGA, or any other mutually
agreed location.
ARTICLE 17
MISCELLANEOUS
17.1 Notices. Any consent, notice or report required or permitted to be
given or made under this Agreement by one of the parties to the other shall be
in writing, delivered personally or by facsimile (and promptly confirmed by
personal delivery, first class mail or courier), first class mail or courier,
postage prepaid (where applicable), addressed to such other party at its address
indicated below, or to such other address as the addressee shall have last
furnished in writing to the addresser and (except as otherwise provided in this
Agreement) shall be effective upon receipt by the addressee.
If to TREGA: TREGA Biosciences, Inc.
0000 Xxxxxxx Xxxxxxx Xxxxx
Xxx Xxxxx, Xxxxxxxxxx 00000
X.X.X.
-33-
34
Attention: President
Facsimile No. (000) 000-0000
with a copy to: Pillsbury Madison and Sutro LLP
000 Xxxxxxxxxx Xxxxxx, 00xx Xxxxx
Xxx Xxxxxxxxx, Xxxxxxxxxx 00000
U.S.A.
Attention: Xxxxxx X. Xxxxxx, Xx.
If to ONO: ONO Pharmaceutical Co., Ltd.
0-0 Xxxxxxxxxx, 0-xxxxx
Xxxx-xx, Xxxxx 000
Xxxxx
Attention: Director of Research
Headquarters
Facsimile No. x00 0 000 0000
17.2 Applicable Law and Language. This Agreement shall be governed by
and construed in accordance with the laws of the State of California, without
regard to the conflicts of law principles thereof. The English language shall be
the official language of this Agreement and all notices and reports which may be
delivered hereunder.
17.3 Compliance with Applicable Laws. Each party, its Affiliates and
(sub)licensees shall use reasonable efforts to comply with all applicable laws,
regulations and governmental orders in connection with their respective
activities related to this Agreement, including without limitation the research,
development, manufacture, use and sale of the Research Lead Compounds and/or the
Licensed Products. Without limiting the foregoing, each party, its Affiliates
and (sub)licensees shall use reasonable efforts to observe and comply with all
applicable United States, Japanese and foreign laws with respect to the transfer
of items and related technical data to foreign countries, including without
limitation, the International Traffic in Arms Regulations and the Export
Administration Regulations.
17.4 Entire Agreement. This Agreement contains the entire understanding
of the parties with respect to the subject matter hereof. All express or implied
agreements and understandings, either oral or written, heretofore made are
expressly superseded by this Agreement. This Agreement may be amended, or any
terms hereof modified, only by a written instrument duly executed by both
parties.
17.5 Headings. The captions to the several Articles and Sections hereof
are not a part of this Agreement, but are merely guides or labels to assist in
locating and reading the several Articles and Sections hereof.
17.6 Independent Contractors. It is expressly agreed that TREGA
and ONO shall be independent contractors and that the relationship
between the two parties shall not constitute a partnership, joint venture
or agency. Neither TREGA nor ONO shall
-34-
35
have the authority to make any statements, representations or commitments of any
kind, or to take any action, which shall be binding on the other, without the
prior consent of the party to do so.
17.7 Waiver. The waiver by either party of any right hereunder or the
failure to perform or of a breach by the other party shall not be deemed a
waiver of any other right hereunder or of any other breach or failure by said
other party whether of a similar nature or otherwise.
17.8 Counterparts. This Agreement may be executed in two or more
counterparts, each of which shall be deemed an original, but all of which
together shall constitute one and the same instrument.
IN WITNESS WHEREOF, the parties have executed this Agreement as of the
date first set forth above.
ONO PHARMACEUTICAL CO., LTD. TREGA BIOSCIENCES, INC.
By:/s/ Xxxxxx Xxxx By:/s/ Xxxxxx X. Xxxxxxxxx
------------------------------ ------------------------------
Xxxxxx Xxxx Xxxxxx X. Xxxxxxxxx
Title: President Title: President & CEO
-------------------------- --------------------------
-35-
36
CONFIDENTIAL TREATMENT REQUESTED
Exhibit A
Research Plan
Overview:
The objective of the [CONFIDENTIAL TREATMENT REQUESTED]-year Trega/Ono
research plan (the "Plan") is to identify promising compounds, which will be
predicted to be useful for the treatment for human disease by modulating the
production of [CONFIDENTIAL TREATMENT REQUESTED] by specific or highly selective
binding to the melanocortin receptor-l ("MC-1R"). Trega Biosciences, Inc.
("Trega") shall endeavor to identify such compounds by using its available
technologies which are in its possession at applicable times under the Plan,
such as combinatorial chemistry, high throughput screening systems, in vitro and
in vivo screening systems and technologies relating to melanocortin receptors
("MCRs"). Such promising compounds, when orally given to animals, should be
non-peptidic low molecular weight molecules which show biological advantages of
sufficient potency and safety so that clinical benefits can be predicted. All
words herein beginning with capital letters which are not specifically defined
herein shall have the same meanings as set forth in the Research and Development
Agreement to which this Plan is attached as Exhibit A (the "Research
Agreement"). In the event that there exists any conflict between the terms of
the Research Agreement and this Plan, the Research Agreement shall govern.
As necessary technologies for the success of the Plan within
[CONFIDENTIAL TREATMENT REQUESTED] years after initiation, Trega is in the
possession of combinatorial libraries consisting of over [CONFIDENTIAL TREATMENT
REQUESTED] representing [CONFIDENTIAL TREATMENT REQUESTED] structural templates,
and libraries of over [CONFIDENTIAL TREATMENT REQUESTED] single compounds.
Additional low molecular weight compounds which are released prior to the first
anniversary of the Effective Date of the Agreement shall be added to the
libraries. In addition,while under no affirmative obligation to screen libraries
of compounds which are released more than one year after the Effective Date of
the Agreement, in the event any such screening during the Research period
results in the identification of a compound with characteristics preferable over
compounds meeting [CONFIDENTIAL TREATMENT REQUESTED] Benchmarks, Trega shall
present such compounds to the Management Committee for discussion about the
possible development of such compounds.
In order to screen these compounds, Trega is in the possession of cell
lines in which each line expresses one of the [CONFIDENTIAL TREATMENT
REQUESTED]. Trega is also in possession of various in vitro and in vivo
screening systems which have been utilized for testing [CONFIDENTIAL TREATMENT
REQUESTED].
Rationale:
[CONFIDENTIAL TREATMENT REQUESTED]
-36-
37
CONFIDENTIAL TREATMENT REQUESTED
Research Phase:
The Research Phase will consist of two major phases. The first phase is
the [CONFIDENTIAL TREATMENT REQUESTED]. The second phase will consist of
[CONFIDENTIAL TREATMENT REQUESTED]. For any specific candidate, the second phase
should be initiated as soon as possible following selection of a promising
chemical lead compound. The steps and research schedule are outlined in the
attached flowchart and table. TREGA shall not screen libraries for ONO or
deliver compounds therefrom or any other items to ONO which would subject ONO to
any obligations other than those set forth in the Agreement without express
written consent of ONO.
The identification of chemical lead compounds shall be [CONFIDENTIAL
TREATMENT REQUESTED] and Preclinical Lead Compounds shall be [CONFIDENTIAL
TREATMENT REQUESTED].
[CONFIDENTIAL TREATMENT REQUESTED] FOR THE IDENTIFICATION OF CHEMICAL
LEAD COMPOUNDS.
1. Screening of combinatorial libraries: identification of hits
Ono Libraries and Trega Libraries which are now in the possession of
Trega and which will be prepared by Trega initially will be screened for binding
to MC-1R. [CONFIDENTIAL TREATMENT REQUESTED] All nonpeptidic small molecule
Trega Libraries which are in the possession of and released by Trega before the
first anniversary of the Effective Date of the Agreement, as to which Trega has
the right to grant licenses, will be screened in this assay. Ono may also submit
Ono Libraries which, upon acceptance by Trega, will also be screened for binding
to MC-1R pursuant to the terms of the Research Agreement.
2. Confirmation and Deconvolution:
Single compounds and Trega Library pools which exhibit
significant binding to MC-lR and designated as hit compounds ("Hit
Compounds") or hit pools ("Hit Pools"), respectively, will be
subjected to confirmatory assays. Such Hit Compounds and Hit Pools
-37-
38
CONFIDENTIAL TREATMENT REQUESTED
will be selected by Trega and the results of such selection shall be reported to
Ono promptly. [CONFIDENTIAL TREATMENT REQUESTED]. Trega Libraries consist of
mixtures of variable numbers of related compounds. [CONFIDENTIAL TREATMENT
REQUESTED]. The pools which show significant activity of displacing
[CONFIDENTIAL TREATMENT REQUESTED] will be subjected to a confirmatory assay
followed by deconvolution in order to identify active single compounds.
Individual compounds will be screened [CONFIDENTIAL TREATMENT REQUESTED]. A
compound with significant displacement activity [CONFIDENTIAL TREATMENT
REQUESTED] assay.
Iterative deconvolution is a process by which the compounds in the pool
are prepared as a number of subpools containing correspondingly fewer compounds
than were present in the original mixture. The active subpools are identified
and further deconvolution is carried out until individual compounds are
prepared.
During the primary screening process, Hit Pools and Hit Compounds will
also be tested for MCR selectivity. This will [CONFIDENTIAL TREATMENT REQUESTED]
to license and which are or will be in the possession of Trega before the first
anniversary of the Effective Date of the Agreement.
3. Functional Assays:
The promising individual compounds [CONFIDENTIAL TREATMENT REQUESTED]
will be selected by Trega for further functional assays and the results of such
selection shall be reported to Ono promptly.
Activation of melanocortin receptors in cells leads to the [CONFIDENTIAL
TREATMENT REQUESTED]. The primary functional screen will consist of determining
the [CONFIDENTIAL TREATMENT REQUESTED]. It is also possible to assess the
activation of MC-1R in these cells by detecting [CONFIDENTIAL TREATMENT
REQUESTED].
Functional activation of human MC-1R may also be assessed by determining
the ability of compounds to [CONFIDENTIAL TREATMENT REQUESTED]. Functional
activity at [CONFIDENTIAL TREATMENT REQUESTED] may be similarly assessed.
Compounds which exhibit functional activity [CONFIDENTIAL TREATMENT
REQUESTED] in the above assays will be tested [CONFIDENTIAL TREATMENT
REQUESTED]. The primary in vivo assay will be an assessment of the ability of
such compounds [CONFIDENTIAL TREATMENT REQUESTED] and to enhance [CONFIDENTIAL
TREATMENT REQUESTED].
-38-
39
CONFIDENTIAL TREATMENT REQUESTED
Experimental protocols for such assays will be discussed at the Management
Committee and will be utilized by mutual agreement between the parties.
[CONFIDENTIAL TREATMENT REQUESTED].
4. Analogs and Directed Libraries for Structure-Activity Relationships
(SAR):
Compounds with promising functional properties will be selected by Trega
for [CONFIDENTIAL TREATMENT REQUESTED] and the results of such selection shall
be reported to Ono promptly. The goal of these efforts will be [CONFIDENTIAL
TREATMENT REQUESTED] to assess progress toward this goal. Trega chemistry
efforts may include [CONFIDENTIAL TREATMENT REQUESTED]. More traditional
[CONFIDENTIAL TREATMENT REQUESTED].
Molecules with the following properties are desirable as chemical lead
compounds:
1. [CONFIDENTIAL TREATMENT REQUESTED].
2. [CONFIDENTIAL TREATMENT REQUESTED].
3. [CONFIDENTIAL TREATMENT REQUESTED].
4. [CONFIDENTIAL TREATMENT REQUESTED].
5. Chemical Lead Compounds.
Compounds which are found promising in [CONFIDENTIAL TREATMENT
REQUESTED] including [CONFIDENTIAL TREATMENT REQUESTED], shall be designated as
chemical lead compounds upon the confirmation of [CONFIDENTIAL TREATMENT
REQUESTED]. Following the designation of such compounds by mutual agreement
between the parties, medicinal chemistry optimization and preclinical
characterization efforts will be undertaken by conducting the following work
product steps. The identification of the chemical lead compounds shall be
completed within [CONFIDENTIAL TREATMENT REQUESTED].
[CONFIDENTIAL TREATMENT REQUESTED] FOR THE IDENTIFICATION OF PRECLINICAL LEAD
COMPOUND CANDIDATES.
6. Medicinal Chemistry Optimization:
-39-
40
CONFIDENTIAL TREATMENT REQUESTED
Medicinal chemistry efforts for SAR determination will continue on
chemical lead compounds as described in step 4. In order to guide the
optimization process, Trega will use [CONFIDENTIAL TREATMENT REQUESTED]. The
goal of these medicinal chemistry efforts will be to continue to improve
[CONFIDENTIAL TREATMENT REQUESTED]. Trega will conduct all necessary and
appropriate efforts for this purpose.
7. Profiling Assays
Medicinal chemistry efforts in step 6 will also be guided by
[CONFIDENTIAL TREATMENT REQUESTED] biological activities and pharmacological
properties of chemical lead compounds [CONFIDENTIAL TREATMENT REQUESTED]. In
addition to the functional assays described in step 3, profiling assays will
include an [CONFIDENTIAL TREATMENT REQUESTED] subject to Trega's capabilities.
Examples of [CONFIDENTIAL TREATMENT REQUESTED] assays which may be used in this
process [CONFIDENTIAL TREATMENT REQUESTED].
8. Animal Models:
In the final stage of medicinal chemistry efforts, compounds with the
most promising properties will be tested in at least one animal model of acute
inflammatory disease in order to select Preclinical Lead Compounds. The specific
animal model(s) chosen for this process and the number of compounds to be tested
will be determined by the Management Committee.
Acute Anti-inflammatory Models:
- [CONFIDENTIAL TREATMENT REQUESTED]
- [CONFIDENTIAL TREATMENT REQUESTED]
- [CONFIDENTIAL TREATMENT REQUESTED]
- [CONFIDENTIAL TREATMENT REQUESTED]
- [CONFIDENTIAL TREATMENT REQUESTED]
No later than [CONFIDENTIAL TREATMENT REQUESTED] after the initiation of
the Plan, the Management Committee will choose the number and type of acute
and/or chronic disease models for testing efficacy of compounds with the most
promising properties and will discuss the experimental protocols for the chosen
models. [CONFIDENTIAL TREATMENT REQUESTED].
9. Preliminary Non-GLP Safety:
Preliminary non-GLP safety studies will be completed on those potential
Preclinical Lead Compound Candidates selected by the Management Committee.
-40-
41
CONFIDENTIAL TREATMENT REQUESTED
Potential Preclinical Lead Compound Candidates will be subjected to
studies in order to assess their safety. Safety studies and protocols will be
determined by the Management Committee.
10. Preclinical Lead Compound Candidates:
The following properties are desirable for the Preclinical Lead Compound
Candidates:
1. [CONFIDENTIAL TREATMENT REQUESTED]
2. [CONFIDENTIAL TREATMENT REQUESTED]
3. [CONFIDENTIAL TREATMENT REQUESTED]
4. [CONFIDENTIAL TREATMENT REQUESTED]
5. [CONFIDENTIAL TREATMENT REQUESTED]
6. [CONFIDENTIAL TREATMENT REQUESTED]
7. [CONFIDENTIAL TREATMENT REQUESTED]
8. [CONFIDENTIAL TREATMENT REQUESTED]
Ono will chose among Preclinical Lead Compound Candidates possessing the
above profile for further evaluation by Ono using necessary studies in order to
select Preclinical Lead Compounds which will be the subject of preclinical
development.
Benchmarks
In summary the overall objective of the Research Phase is the
identification of potential Preclinical Lead Compound Candidates.
[CONFIDENTIAL TREATMENT REQUESTED] Benchmarks for identification of
chemical lead compounds:
1. [CONFIDENTIAL TREATMENT REQUESTED]
-41-
42
CONFIDENTIAL TREATMENT REQUESTED
2. [CONFIDENTIAL TREATMENT REQUESTED]
3. [CONFIDENTIAL TREATMENT REQUESTED]
[CONFIDENTIAL TREATMENT REQUESTED] Benchmarks for identification of
Preclinical Lead Compound Candidates:
1. [CONFIDENTIAL TREATMENT REQUESTED]
2. [CONFIDENTIAL TREATMENT REQUESTED]
3. [CONFIDENTIAL TREATMENT REQUESTED]
-42-
43
CONFIDENTIAL TREATMENT REQUESTED
Research Plan
Flow Chart
----------------------
Lead Discovery Primary Screen
[CONFIDENTIAL
TREATMENT REQUESTED]
----------------------
--------------------
Confirmation
[CONFIDENTIAL
TREATMENT REQUESTED]
--------------------
--------------------
Deconvolution
--------------------
----------------------
--------------------- [CONFIDENTIAL
Functional Assay TREATMENT REQUESTED]
--------------------- ----------------------
------------------------------
Chemical Lead Compounds
Identified
------------------------------
Lead Optimization ---------------------- ----------------------
Medicinal Chemistry [CONFIDENTIAL
--------------- Optimization TREATMENT REQUESTED]
[CONFIDENTIAL ---------------------- ----------------------
TREATMENT
REQUESTED] ----------------------
[CONFIDENTIAL
--------------- TREATMENT REQUESTED]
----------------------
-------------------------------
Preliminary Safety
-------------------------------
----------------------------------------
Preclinical Lead Compound Candidates
----------------------------------------
---------------------------------
Preclinical Lead Compounds
---------------------------------
-43-
44
CONFIDENTIAL TREATMENT REQUESTED
Research Schedule
-----------------------------------------------------------------------
[CONFIDENTIAL TREATMENT REQUESTED]|[CONFIDENTIAL TREATMENT REQUESTED]
-----------------------------------------------------------------------
Medicinal Chemistry Efforts
Screening and Selection Efforts
--------------------------------------------
Identification of Chemical Lead Compounds
--------------------------------------------
- Screening of [CONFIDENTIAL TREATMENT REQUESTED]
- Confirmation
- Deconvolution
- Functional Assays
- [CONFIDENTIAL TREATMENT REQUESTED]
--------------------------------------------------------
Optimization of Chemical Lead Compounds
Identification Preclinical Lead Compounds Candidates
--------------------------------------------------------
- Lead Optimization
- [CONFIDENTIAL TREATMENT REQUESTED]
- Characterization Assays
- [CONFIDENTIAL TREATMENT REQUESTED]
- Preliminary Safety
-44-
