EXHIBIT 10.27
*** TEXT OMITTED AND FILED SEPARATELY
PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST
UNDER 17 C.F.R. SECTION 200.80(b)(4)
AND RULE 406 UNDER THE SECURITIES
ACT OF 1933, AS AMENDED
CONFIDENTIAL
COLLABORATION AGREEMENT
THIS COLLABORATION AGREEMENT (the "AGREEMENT") is made and entered into as
of December 1, 2003 (the "EFFECTIVE DATE") by and between STRUCTURAL GENOMIX,
INC. a Delaware corporation located at 00000 Xxxxxxx Xxxxxx, Xxx Xxxxx, XX
00000, U.S.A., ("SGX"), and UROGENE, S.A., a corporation incorporated under the
laws of France with a principal place of business at 0 Xxx Xxxxxx Xxxxxxxx -
Xxxxxxxx, 00000 Evry, Cedex, France, ("UG"). SGX and UG may be referred to
herein individually as a "Party" and collectively as the "Parties".
BACKGROUND
WHEREAS, SGX has expertise in the field of structure directed drug
discovery;
WHEREAS, UG has research and development programs in the area of urology;
WHEREAS, the Parties wish to collaborate in the development of therapeutic
products directed at inhibiting the protein kinase XXX, primarily for
application in the field of bladder cancer;
NOW, THEREFORE, in consideration of the foregoing and the covenants and
promises contained in this Agreement, the Parties hereby agree as follows:
1. DEFINITIONS
1.1 "Active Party" has the meaning ascribed to such term in Section 6.1.
1.2 "Affiliate" means, with respect to a Party hereto, a corporation,
company or other entity that is owned or controlled by such Party by virtue of
such Party's direct or indirect ownership or control of fifty percent (50%) or
more of the outstanding shares or securities (representing the right to vote for
the election of directors or other managing authority) of such corporation,
company or other entity, but such corporation, company or other entity shall be
deemed to be an Affiliate only so long as such ownership or control exists.
1.3 "Clinical Development" means development activities conducted on a
Collaboration Product commencing upon the filing of an IND, up to and including
generation of an International Registration Dossier.
1.4 "Collaboration" means the activities conducted by the Parties under
the Research Plan and the Development Plan.
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1.5 "Collaboration Product" means any product that comprises or contains
or is developed or manufactured based on a Safety Assessment Candidate, and is
directed at inhibiting, modulating or altering the activity of the Target.
Collaboration Products do not include SGX Products or UG Products.
1.6 "Collaboration Technology" means Patent Rights and Know-How which are
conceived or reduced to practice or otherwise developed by or on behalf of UG or
SGX, or jointly by UG and SGX, in each case during and in the performance of the
Collaboration, including without limitation, Collaboration Products and
Information but excluding SGX Compounds, UG Compounds, SGX Background
Technology, and UG Background Technology.
1.7 "Collaboration Term" means the period commencing on the Effective Date
and ending on a Collaboration Product-by-Collaboration Product and
country-by-country basis, upon Registration of each such Collaboration Product.
1.8 "Competing Product" means a product developed outside of the
Collaboration for application in the Therapeutic Field, which has activity in an
[...***...] against the Target.
1.9 "Controls" or "Controlled" means possession of the ability to grant
the licenses or sublicenses as provided for herein, without violating the terms
of any agreement or other arrangement with a Third Party.
1.10 "Development Budget" has the meaning ascribed to such term in Section
3.7.
1.11 "Development Plan" means, with respect to a particular Collaboration
Product, the plan prepared by the JDC and approved by the Parties pursuant to
Section 3.7 setting forth the detailed plan, Development Budget and process for
the Parties' collaborative efforts to conduct development of, and seek
Registration for, such Collaboration Product in the UG Territory and SGX
Territory.
1.12 "Drug Candidate" means a Safety Assessment Candidate selected by the
JDC for Clinical Development under Section 3.2(b).
1.13 "Excess Expenses" means, with respect to a particular Collaboration
Product, the costs and expenses associated with such Collaboration Product that
the Parties have agreed pursuant to Section 3.9 shall be creditable against
certain royalty payments in accordance with Section 4.3.
1.14 "Expanded Therapeutic Field" means the Therapeutic Field, [...***...]
cancer, [...***...] carcinomas, and [...***...] cancer.
1.15 "FTE" means a full time equivalent person year (consisting of
[...***...] hours per year) of scientific or technical work carried out by or on
behalf of SGX or UG under the Collaboration.
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1.16 "First Commercial Sale" means the first sale of a Collaboration
Product to a Third Party in a Territory after all Registrations required to
permit such sale have been granted, or such sale is otherwise permitted by the
regulatory authority in such country.
1.17 "IND" means an Investigational New Drug application, as defined in
the U.S. Food, Drug and Cosmetic Act ("FDCA") and the regulations promulgated
thereunder or any corresponding foreign application, registration or
certification.
1.18 "Inactive Party" has the meaning ascribed to such term in Section
6.1.
1.19 "Information" means data specifically relating to research,
development, Registration, manufacture, sale or use of Collaboration Products,
including without limitation, pharmacological, toxicological and clinical test
data, analytical and quality control data, regulatory submissions,
correspondence and communications, and data relating to adverse events.
1.20 "International Registration Dossier" means the collection of
Information comprising the requirements for applications for Registration of
Collaboration Products under the FDCA and any regulations promulgated
thereunder, and as required by the Committee for Proprietary Medicinal Products
representing the medicine authorities of the European Community member states.
1.21 "Joint Research Committee" or "JRC" means the Joint Research
Committee established pursuant to Section 2.4.
1.22 "Joint Development Committee or "JDC" means the Joint Development
Committee established pursuant to Section 3.2.
1.23 "Know-How" means all ideas, data (including without limitation data
from clinical and preclinical studies and test data including pharmacological,
toxicological and clinical test data), inventions, information, (including
without limitation information related to compounds and their structure,
function and formulation, regulatory filings and submissions), instructions,
designs, processes, formulas, software, materials, methods, processes and
techniques.
1.24 "Lead Compound" means a compound with the properties designated by
the JRC as required properties for a Lead Compound, which is designated by the
JRC as a Lead Compound in accordance with Section 2.4(b)(v).
1.25 "Net Sales" means the total amount received by UG or SGX or their
respective Affiliates or sublicensees, as the case may be, for sales to third
parties (other than sublicensees) in arm's length transactions of Products less:
(i) ordinary and customary prompt payment and other trade or quantity discounts
actually allowed and taken; (ii) credits, rebates and returns (including, but
not limited to, wholesaler and retailer returns) actually extended and taken;
(iii) freight, postage and duties (including insurance premiums) actually
incurred; (iv) excise taxes, other consumption taxes, customs duties and
compulsory payments to governmental authorities actually paid and separately
identified on the invoice or other documentation maintained in the ordinary
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course of business. A "sale" shall include any transfer or other disposition for
consideration, and Net Sales shall include the fair market value of all other
consideration received by UG or SGX or their respective Affiliates or
sublicensees in respect of any grant of rights to make, use, sell or otherwise
distribute Products, whether such consideration is in cash, payment in kind,
exchange or other form.
1.26 "NDA" means a New Drug Application, as defined in the U.S. Food, Drug
and Cosmetic Act and the regulations promulgated thereunder, and any
corresponding foreign application, registration or certification.
1.27 "Patent Rights" means patent applications filed in any country
worldwide, including provisionals, utilities, continuations (in whole or in
part), divisionals, reissues, reexaminations and foreign counterparts thereof,
any patents issued on such applications and any extensions of term,
registrations or confirmations of such patents.
1.28 "Phase 1", "Phase 2", "Phase 3" and "Phase 4" means Xxxxx 0, Xxxxx 0,
Xxxxx 3 and Phase 4 clinical trials, respectively, in each case as prescribed by
the U.S. Food and Drug Administration or any successor entity (the "FDA"), and
agencies of other governments of other countries having similar jurisdiction
over the development, manufacturing and marketing of pharmaceuticals.
1.29 "Phase 2A" means the Phase 2A or Phase 1/2 clinical trials, as
prescribed by the FDA and agencies of other governments of other countries
having similar jurisdiction over the development, manufacturing and marketing of
pharmaceuticals, designed to evaluate efficacy and initial clinical proof of
concept.
1.30 "Preclinical Development" means drug development activities conducted
by the Parties from the nomination by the JRC of a Safety Assessment Candidate
for Preclinical Development, and up to but not including filing of an IND.
1.31 "Product" means a Collaboration Product, SGX Product or UG Product.
1.32 "Registration" means any approvals (including supplements, amendments
and post-approvals and price approvals), licenses, registrations or
authorizations of any national, supra-national (e.g., the European Commission or
the Council of the European Union), regional or local regulatory agency,
department, bureau, or other governmental entity, necessary for the manufacture,
distribution, use, sale, pricing or reimbursement, of Collaboration Products in
a regulatory jurisdiction.
1.33 "Research Plan" has the meaning ascribed to such term in Section 2.1
1.34 "Safety Assessment Candidate" or "SAC" means a Lead Compound with the
properties designated by the JRC as required properties for a SAC, which is
designated by the JRC as a SAC in accordance with Section 2.4(b)(vi).
1.35 "SGX Background Technology" means all Patent Rights and Know-How
which are: (a) owned or Controlled by SGX prior to the Effective Date or during
the Collaboration Term; (b) developed by or on behalf of SGX (i) outside the
Collaboration
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or (ii) within the Collaboration and comprise methodologies, protocols or
technologies which have application to targets or compounds in addition to the
Target and compounds the subject of the Collaboration; and (c) necessary for the
conduct of the Collaboration.
1.36 "SGX Compounds" means all Patent Rights and Know-How which are
conceived or reduced to practice or otherwise developed by or on behalf of SGX
during and in the performance of the Collaboration, covering compounds
identified and developed by SGX, which are not selected by the JRC as Lead
Compounds.
1.37 "SGX Product" means any product that comprises or contains or is
developed or manufactured based on or utilizing or is derived from, a Lead
Compound or any part thereof which was selected by the JRC for lead
optimization, and which has primary application in the SGX Retained Field.
1.38 "SGX Retained Field" means kinase inhibitors (other than MET)
developed for clinical indications other than the Expanded Therapeutic Field.
1.39 "SGX Territory" means the United States, Canada and Mexico.
1.40 "Sublicensee Information" has the meaning ascribed in Section 4.6.
1.41 "Sublicensing Revenue" means all amounts (including, without
limitation, payments received for the purchase of equity in excess of the fair
market value of such equity, license fees, milestone and other time or event
based payments and royalties on sales of products, but excluding any research
funding payments received and actually used for such purpose) received by a
Party under an agreement or license attributable to Collaboration Products or
from sales of Collaboration Products to end users less any withholding tax or
other tax related reductions.
1.42 "Target" means the human protein kinase XXX.
1.43 "Territory" means UG Territory or SGX Territory.
1.44 "Therapeutic Field" means superficial and invasive bladder cancer.
1.45 "Third Party" or "Third Parties" means any entity other that UG or
SGX or their respective Affiliates.
1.46 "UG Background Technology" means all Patent Rights and Know-How which
are: (a) owned or Controlled by UG prior to the Effective Date or during the
Collaboration Term; (b) developed by or on behalf of UG (i) outside the
Collaboration or (ii) within the Collaboration and comprises methodologies,
protocols or technologies which have application to targets or compounds in
addition to the Target and compounds that are the subject of the Collaboration;
and (c) necessary for the conduct of the Collaboration.
1.47 "UG Compounds" means all Patent Rights and Know-How which are
conceived or reduced to practice or otherwise developed by or on behalf of UG
during
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and in the performance of the Collaboration, covering compounds
identified and developed by UG, which are not selected by the JRC as Lead
Compounds.
1.48 "UG Product" means any product that comprises or contains or is
developed or manufactured based on or utilizing or is derived from, a Lead
Compound or any part thereof which was selected by the JRC for lead
optimization, and which has primary application in the UG Retained Field.
1.49 "UG Retained Field" means non-kinase inhibitors developed for
urological clinical application other than the Therapeutic Field.
1.50 "UG Territory" means the countries listed in the attached Exhibit A
("Europe")
1.51 "Valid Claim" means a claim of a pending patent application within
the Patent Rights or an issued and unexpired patent within the Patent Rights
which has not been held unenforceable or invalid by a court or other
governmental agency of competent jurisdiction, and which has not been disclaimed
or admitted to be invalid or unenforceable through reexamination, reissue,
opposition, or otherwise.
2. RESEARCH COLLABORATION.
2.1 Research Collaboration. Subject to the terms and conditions of this
Agreement UG and SGX will use commercially reasonable efforts to perform under
the Research Plan attached to this Agreement as Exhibit B ("Research Plan"),
based on the budget attached as Exhibit B1 ("Research Budget"). Research Plan
activities will be overseen by the JRC. The JRC will review the Research Plan on
an ongoing basis and may make changes to the Research Plan then in effect,
provided that the JRC may not increase the applicable Research Budget without
the written approval of each Party. On an annual basis commencing on the first
anniversary of the Effective Date and continuing until the conclusion of the
Parties' activities under the Research Plan, the JRC shall review the Research
Budget to ensure that the number of full time equivalent personnel (FTEs) of
each Party engaged under the Research Plan and the other costs of the Research
Plan activities, are being shared between the Parties on a 50/50 basis, and
shall make adjustments to each Party's responsibilities under the Research Plan
in order to effect such sharing to the greatest extent possible, taking into
account each Party's experience and expertise in the various Research Plan
activities.
2.2 Performance Standards; Records. Each Party shall conduct its
activities under the Collaboration in good scientific manner, and in compliance
in all material respects with the requirements of applicable laws and
regulations, to attempt to achieve its objectives efficiently and expeditiously.
Each Party shall maintain laboratories, offices and other facilities reasonably
necessary to carry out the activities to be performed by such Party pursuant to
the Collaboration. In conformity with standard pharmaceutical and biotechnology
industry practices and the terms and conditions of this Agreement, each Party
shall prepare and maintain, or shall cause to be prepared and maintained,
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complete and accurate written records, accounts, notes, reports and data with
respect to activities conducted pursuant to the Research Plan and Development
Plan and all results (including without limitation any inventions, discoveries
and developments) made pursuant to its efforts under the Collaboration, and,
upon the other Party's written request, shall send legible copies of the
aforesaid to the other Party. Such records shall be complete and accurate and
shall fully and properly reflect all work done and results achieved in the
performance of the Collaboration in sufficient detail and in good scientific
manner. Upon reasonable advance notice, each Party agrees to make its employees
and non-employee consultants reasonably available at their respective places of
business to consult with the other Party on issues arising in connection with
any request from any regulatory agency with respect to activities under this
Agreement, including, without limitation, regulatory, scientific, technical and
clinical testing issues. At least quarterly during the performance of the
Research Plan, the Parties shall have the obligation to prepare and provide to
the JRC written reports summarizing the progress of the work performed by such
Party in connection with the Research Plan during the preceding quarter.
2.3 Provision of Materials and Know-How. In the course of the
Collaboration, the Parties will provide each other, promptly upon request, with
materials and data within Collaboration Technology, as required for each Party
to perform its respective obligations under the Research Plan and Development
Plan. Neither Party will have the right to transfer or disclose materials
received from the other Party to any Third Party other than permitted
sublicensees or approved Third Party contractors under the Research Plan,
without the other Party's prior written consent.
2.4 Joint Research Committee
(a) Membership; Decisions. SGX and UG will establish a JRC to
oversee, review and recommend direction of the Research Plan. The JRC shall be
comprised of six (6) members, with three (3) members being appointed by SGX and
three (3) members being appointed by UG. Additional representatives of each
Party (for example the members of the individual project teams or consultants)
may attend JRC meetings at the election of each Party. The Parties may
subsequently agree to change the size of the JRC as appropriate to meet the
needs of the Parties' collaborative efforts under this Agreement. Each Party may
replace its JRC representatives at any time, with written notice to the other
Party. Each representative of SGX and UG shall have one vote on the JRC, which
vote may be cast by proxy. Decisions of the JRC shall be made by unanimous vote.
Any matter upon which the JRC is unable to agree shall be submitted to a senior
executive officer designated by each Party for such purpose.
(b) Responsibilities. The JRC will review, direct and supervise the
performance of the Research Plan. The JRC will be responsible for (i)
coordinating, monitoring and reporting research progress and ensuring open
exchange between the Parties with respect to Collaboration activities; (ii)
determining the research strategy, budget and time lines for the Research Plan;
(iii) determining whether to obtain licenses from Third Parties with respect to
intellectual property useful for the conduct of the Research Plan; (iv)
determining the required properties for compounds to be deemed
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Lead Compounds, including without limitation, potency, selectivity, in vivo
efficacy and bioavailability; and (v) selecting Lead Compounds for entry into
lead optimization; provided that no more than four (4) Lead Compound series will
be pursued in lead optimization under the Collaboration at any one time; and
(vi) determining the required properties for Lead Compounds to be deemed Safety
Assessment Candidates and selecting Safety Assessment Candidates for entry into
Preclinical Development.
(c) Meetings. During the term during which the Parties are
performing under the Research Plan, the JRC shall meet quarterly, in person or
via video-conference, or as the JRC may otherwise agree, to discharge its
responsibilities, with the expectation that meetings will alternate between
appropriate offices of each Party. Each Party will be responsible for paying its
own expenses in connection with participating in the meetings of the JRC. The
JRC shall prepare written minutes of each meeting and a written record of all
JRC decisions, whether made at a JRC meeting or otherwise.
3. DEVELOPMENT
3.1 Overview. SGX and UG agree that they will collaborate on development
of Collaboration Products pursuant to the terms of this Agreement, in a
coordinated international program aimed at producing an International
Registration Dossier and obtaining Registration of Collaboration Products in the
UG Territory and SGX Territory. All such collaborative development efforts of
the Parties, or either Party, shall be in accordance with the Development Plan
for each Collaboration Product. Except as otherwise provided in this Agreement,
each Party agrees that neither Party may conduct Preclinical Development or
Clinical Development on a Collaboration Product for sale or distribution, or
license any Third Party to do so, except collaboratively with the other Party or
as permitted by this Agreement. However, as discussed further in Article 6, it
is agreed that, if one Party determines that it does not wish to proceed with
such joint development of a particular Collaboration Product, the other Party
shall be permitted to do so on its own pursuant to the terms of Article 6.
3.2 Joint Development Committee. On a Collaboration Product-by-
Collaboration Product basis, once a Safety Assessment Candidate is selected by
the JRC for progression to Preclinical Development, the Parties shall form a JDC
for the development of such SAC, comprised of six (6) members, with three (3)
members being appointed and replaced by SGX and three (3) members being
appointed and replaced by UG. Additional representatives of each Party (for
example members of the individual project teams or consultants) may attend JDC
meetings at the election of each Party. The Parties may subsequently agree to
change the size of each JDC, as appropriate to meet the needs of the Parties in
managing the joint efforts under this Agreement. The JDC shall (a) prepare the
Development Plan for the Preclinical Development of the SAC, and modify or amend
it as appropriate, based on the results of the development efforts on such SAC,
during the development process; (b) select one or more SACs for Clinical
Development and prepare the Development Plan for such Clinical Development, (c)
determine whether and when to commence Xxxxx 0, Xxxxx 2 and Phase 3 for each
Collaboration Product; (d) oversee the Parties' activities under the Development
Plan, including supervision of
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regulatory activities and (e) perform such other duties and obligations as the
Parties specifically delegate to it in writing by mutual written agreement of
the Parties.
3.3 JDC Meetings. JDC meetings shall take place at such mutually
convenient times and places as determined by the JDC, with the expectation that
meetings will alternate between appropriate offices of each Party. Each Party
will be responsible for paying its own expenses in connection with participating
in JDC meetings. The JDC shall determine the frequency of its meetings and how
such meetings will be conducted and recorded.
3.4 Decision-Making and Issue Resolution. All decisions of the JDC shall
be unanimous by the members of such committee. If the JDC fails to reach
unanimous agreement on an issue needing resolution, the matter shall be referred
for good faith discussion and resolution by a senior executive officer
designated by each Party for such purpose.
3.5 Joint Development. For each SAC selected by the JRC for joint
development as a Collaboration Product hereunder by mutual written agreement,
SGX and UG agree that they will collaborate to generate an International
Registration Dossier, and will conduct, or have conducted, all Preclinical
Development and Clinical Development on such Collaboration Product in accordance
with the Preclinical and Clinical Development Plans developed by the JDC for
such Collaboration Product. The Parties will work together to develop a common
brand name for each Collaboration Product to be marketed under worldwide. Each
Party agrees not to incur any expenses or costs in excess of the Development
Budget (as defined below) within such Development Plan except as mutually agreed
in writing by the Parties. The collaborative development program will follow the
most expeditious path to the production of an International Registration Dossier
and Registration of Collaboration Products in the UG Territory and SGX
Territory, provided however it is understood that unless otherwise agreed by the
Parties, all commercialization activities with respect to such Collaboration
Product once Registration has been obtained, will be conducted by the Parties
independently, in each Party's respective Territory for such Collaboration
Product and that each Party will bear its own costs of such commercialization
activities. On a Collaboration Product-by-Collaboration Product basis, each
Party will be primarily responsible for regulatory activities in its applicable
Territories after Registration in such Territory, comprising regulatory
compliance, safety surveillance, adverse event reporting and all other necessary
support services, however the Parties will keep each other informed of such
activities and will work together in the conduct of such activities where
necessary or useful. The Parties will mutually agree on (i) the
commercialization strategy for countries outside of the Territories, including
outlicensing as necessary; and (ii) the engagement of a Third Party(ies) to
manufacture and supply bulk drug substance for Collaboration Product
development, and Collaboration Products for commercialization purposes, in the
Territories.
3.6 Access to Information. During the term of this Agreement each Party
(the "Providing Party") will provide the other Party (the "Recipient") in
English, for use in the Recipient's development and commercialization efforts
relating to a Collaboration
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Product, all Information that the Providing Party owns or Controls regarding
such Collaboration Product (including, without limitation, Sublicensee
Information), necessary or useful for making regulatory filings and seeking and
maintaining Registration, for Collaboration Products in the Recipient's
Territory for such Collaboration Product, as such Information becomes available.
The Recipient will have a right of access, and the right to use and incorporate
all Information provided by the Providing Party in regulatory filings for such
Collaboration Products in the Recipient's Territory. The Parties will report and
take other actions in relation to, adverse events with Collaboration Products,
to each other in accordance with a reporting protocol in a form to be agreed by
the JDC. Each Party will be entitled to receive copies of all correspondence
with regulatory authorities and will be entitled to be present at all meetings
with regulatory authorities in any Territory related to Collaboration Products.
3.7 Development Plans and Budgets. Promptly after the selection by the JRC
of a SAC for development as a Collaboration Product by the Parties, the JDC
shall prepare and provide to each Party for final approval a development plan
for such SAC (the "Development Plan"). The Development Plan shall include all
needed details regarding the Preclinical and Clinical Development, and other
work to be undertaken to develop and produce the International Registration
Dossier for such Collaboration Product, including an allocation of all such work
as appropriate to each Party (or to selected Third Party contractors, as
agreed), and shall establish a budget (the "Development Budget") for all costs
and expenses to be incurred by each Party in conducting the work allocated to it
under such Development Plan. The budget will be based on (i) an allocation of
Full Time Equivalent (FTE) personnel of each Party working under the Development
Plan, with each FTE costed at an annualized rate of U.S.$[...***...] (which rate
will be increased on each anniversary of the Effective Date by [...***...]%);
(ii) the actual extraordinary direct costs approved by the JDC, and (iii) the
actual costs of work performed by Third Parties as approved by the JDC. Each
Party shall diligently review the proposed Development Plan and shall either
approve the plan or provide the JDC any requested changes and comments. If a
Party provides such requested changes or comment to a proposed Development Plan,
the JDC shall review the proposed changes within thirty (30) days, and as
appropriate, thereafter prepare a revised draft of the Development Plan,
accommodating such changes and comments, and resubmit such revised Development
Plan for approval by the Parties as provided above. Once the Parties have agreed
on the Development Plan proposed by the JDC, such Development Plan shall be
effective and shall control and govern the Parties' development effort with
respect to the applicable Product, subject to any subsequent amendments or
modifications to such Development Plan as provided below. From time to time
during the development of such Collaboration Product, the JDC shall review the
Development Plan in light of the results of the development work and any other
relevant Information and shall amend or modify the Development Plan as
appropriate, provided that the JDC may not increase the applicable Development
Budget without the written approval of each Party. At least sixty (60) days
prior to January 1 of any year in which the Parties are developing a particular
Collaboration Product hereunder, the JDC shall review the applicable Development
Budget for such Collaboration Product and shall submit a revised and updated
Development Budget for the coming calendar year to each of the Parties for
approval as provided above. Upon such approval, the Development Budget shall be
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effective for the development of such Collaboration Product during such calendar
year, subject further to amendment of the applicable Development Plan.
3.8 Costs of the Collaboration. All costs and expenses incurred or
expended by a Party hereunder under the Research Budget and Development Budget
("Collaboration Costs") shall initially be borne by the Party incurring such
costs and expenses, subject to creditability of Excess Expenses as provided in
Section 4.3, provided however, on a Collaboration Product-by-Collaboration
Product basis, the costs of any country specific regulatory requirement (outside
of the International Registration Dossier and any Phase 4 studies required by a
regulatory body in a Territory), will be borne by the Party whose Territory for
such Collaboration Product includes such country. Each Party shall calculate and
maintain records of all the Collaboration Costs incurred or expended by the
Party during its performance of development on a Collaboration Product, in
accordance with generally accepted accounting procedures consistently applied
throughout such Party's organization and such other procedures to be agreed upon
between the Parties. Commencing on the formation of the JDC, each Party shall
report quarterly to the other on the Collaboration Costs it has incurred in each
calendar quarter, on a Collaboration Product-by- Collaboration Product basis,
and the purpose (referencing the activities within the applicable Development
Plan) for which such costs were incurred or expended, with such reports to be
submitted within sixty (60) days after the end of each of the first three (3)
calendar quarters and ninety (90) days after the end of the calendar year. The
Parties shall seek to resolve promptly and in good faith any questions or issues
related to such accounting statements, and in any event within ninety (90) days
following receipt.
3.9 Excess Expenses.
(a) For each particular calendar year during which Collaboration
Costs are incurred hereunder, and promptly following the First Commercial Sale
of each Collaboration Product hereunder, each Party shall review the
Collaboration Costs report submitted by the other Party and compare such
submission to the applicable Research Budget and Development Budget. The Parties
will then meet, if necessary, via designated senior officers from each Party
with financial accounting responsibility, to discuss the reports and reach
agreement on the total amount of Collaboration Costs that each Party may
properly apply to the Collaboration activities hereunder. It is understood and
agreed that a Party will not be entitled to obtain credit for any Collaboration
Costs incurred by the Party in excess of the amount set forth in the applicable
Research Budget or Development Budget for accomplishing the relevant task or
objective unless approved by the JRC or JDC. If such officers cannot reach
agreement promptly, the matter will be submitted to senior executive officers of
each Party for prompt resolution, with the understanding that each Party will
provide access to any information relating to the Collaboration activities
undertaken by such Party, and the actual calculation of costs and expenses
incurred therefor, with respect to Collaboration Products during such calendar
year for which such Party seeks credit hereunder for the related Collaboration
Costs .
(b) UG and SGX will share the total amount of Collaboration Costs
incurred by the Parties within the applicable Research Budget and Development
Budget
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for each Collaboration Product, up to and including the costs of Clinical
Development, on a 50/50 basis. Any Collaboration Costs incurred by a Party in
excess of [...***...]% of the total amount of Collaboration Costs incurred by
both Parties, will be deemed Excess Expenses of such Party (the "First Party")
and in the event that the Party which has not incurred Excess Expenses (the
"Second Party") does not elect to pay the First Party the amount of the Excess
Expenses in cash within [...***...] ([...***...]) months of the First Commercial
Sale of a Collaboration Product, the First Party may credit such Excess Expenses
in accordance with Section 4.3.
3.10 Audit Rights. Each Party shall have the right to have an independent
accounting firm audit the other Party's relevant records to determine the
accuracy of the Collaboration Costs reported by such other Party under Section
3.8 above. Such audit right shall be exercised under the terms of the audit
provisions set forth in Section 4.11 below.
3.11 Diligence. Each Party shall use commercially reasonable diligent
efforts to (i) develop and bring Safety Assessment Candidates nominated by the
JRC for Preclinical Development, to the market as Collaboration Products in such
Party's applicable Territory as soon as reasonably practicable, (ii) obtain such
Registrations as may be necessary to market such Collaboration Products in such
Territory, and (iii) after obtaining Registration for any such Collaboration
Products, launch such Collaboration Products and promote and meet the market
demand therefore. In connection with the above, each Party shall use efforts not
less than those efforts made by similarly situated companies in the
biotechnology industry with respect to comparable products of comparable
commercial potential, stage of development and patent protection.
3.12 Lack of Diligence. In the event that either Party fails to use or
continue to use diligent efforts to actively develop and commercialize a
Collaboration Product in accordance with Section 3.11 above (the "First Party"),
and the First Party fails to initiate diligent efforts within sixty (60) days of
receipt of notice from the other Party (the "Second Party") of such failure,
then the Second Party may terminate the First Party's rights under this
Agreement with respect to such Collaboration Product and, in such event, the
Second Party shall have the exclusive right to commercialize any such
Collaboration Product in the First Party's Territory and the Second Party shall
make payments to the First Party in accordance with Section 6.3.
3.13 Competing Products. During the period from the Effective Date to the
tenth anniversary of the Effective Date, each Party agrees not to, and to cause
its Affiliates not to, directly or indirectly, develop and commercialize a
Competing Product in any country in the other Party's Territory for the
applicable Collaboration Product. In the event that a Party (an "Acquiring
Party") purchases or otherwise takes control of a Third Party ("Acquisition")
which has developed or commercialized (and is continuing to produce or sell), or
is developing or commercializing a Competing Product (directly or indirectly) in
any such case, within the other Party's Territory for the applicable
Collaboration Product, the Parties will negotiate in good faith to agree on the
appropriate sharing between the Parties of the Acquiring Party's rights and
obligations in connection with the development and commercialization of the
Competing Product, and in the event
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that such agreement is not reached within twelve months after such Acquisition,
the Acquiring Party shall divest, or cause its applicable Affiliate to divest,
the Competing Product.
4. ROYALTY PAYMENTS
4.1 Royalties on Net Sales of Collaboration Products. No later than six
(6) months prior to the filing of the International Registration Dossier for the
first Collaboration Product, the Parties will negotiate in good faith a
commercialization plan for Collaboration Products including an agreement on the
appropriate royalty payments and shares of Sublicensing Revenue due to each
Party, recognizing the guiding principle of a 50/50 collaboration with equal
sharing of expenses and returns. In the event that no agreement is reached by
the Parties by the date that is six (6) months prior to the First Commercial
Sale of the first Collaboration Product, (i) UG will pay to SGX a royalty of
[...***...]% of Net Sales of Collaboration Products by or on behalf of UG in the
UG Territory or [...***...]% of Sublicensing Revenue received by UG in
connection with Collaboration Products; and (ii) SGX will pay to UG a royalty of
[...***...]% of Net Sales of Collaboration Products by or on behalf of SGX in
the SGX Territory or [...***...]% of Sublicensing Revenue received by SGX in
connection with Collaboration Products.
4.2 Royalties on Net Sales of UG Products and SGX Products. In
consideration of the rights granted hereunder:
(a) SGX shall pay to UG [...***...]% of Net Sales of SGX Products by
or on behalf of SGX in the SGX Territory or [...***...]%] of Sublicensing
Revenue received by SGX in connection with SGX Products; and
(b) UG shall pay to SGX [...***...]% of Net Sales of UG Products by
or on behalf of UG worldwide or [...***...]% of Sublicensing Revenue received by
UG in connection with UG Products.
4.3 Creditable Payments. Each Party may credit any Excess Expenses
(including interest calculated at the rate equal to the prime rate as reported
by the Chase Manhattan Bank, New York, New York, plus [...***...] percent
([...***...]%), compounded annually) it has incurred, as determined in
accordance with Section 3.9, against any royalty payments it is required to make
under Section 4.1, up to a maximum of [...***...]% of the royalties due from
such Party in any calendar quarter. In the event that a Collaboration Product
has been registered in one Party's Territory but the First Commercial Sale of a
Collaboration Product in the other Party's Territory is delayed or likely to be
delayed by more than twelve (12) months, and such delayed Party has Excess
Expenses the Parties will negotiate in good faith an agreement to ensure that
during such period until there is Registration and Net Sales of such
Collaboration Product in each Party's Territory, the Parties will share expenses
and returns under the Collaboration recognizing the guiding principle of a 50/50
collaboration with equal sharing of expenses and returns.
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4.4 Royalty Term. The obligation of each Party to pay royalties under
Sections 4.1 and 4.2 shall continue for each Product on a Product-by-Product
basis, until the later of (i) such time as there are no Valid Claims in such
country covering such Product and (ii) [...***...] ([...***...]) years from the
First Commercial Sale of such Product.
4.5 Third Party Royalties. UG shall be responsible for the payment of any
amounts due from UG to third parties for intellectual property necessary for the
manufacture, use, import or sale of Products in UG Territory and SGX shall be
responsible for the payment of any amounts due from SGX to third parties for
intellectual property necessary for the manufacture, use, import or sale of
Products in SGX Territory; provided that, in the event that Third Party licenses
are required for a particular Collaboration Product in the applicable UG
Territory and SGX Territory, the Parties will share the costs of obtaining such
licenses in accordance with Section 3.9(b).
4.6 Sublicensees. Each Party shall include in each permitted sublicense
granted according to Article 5, a provision requiring the sublicensee to make
reports to the sublicensor, to exchange and permit each Party to use,
Information owned or Controlled by the sublicensee ("Sublicensee Information")
in accordance with Section 3.8, to keep and maintain records of sales made
pursuant to such sublicense and to grant access to such records by the other
Party's accounting firm to the same extent required of the sublicensor under
Section 4.8.
4.7 Withholding Taxes. Any income or other tax that either Party is
required to withhold and pay on behalf of the other Party with respect to the
milestone and royalties payable under this Agreement, shall be deducted from and
offset against said milestone and royalty payments prior to remittance to the
receiving Party; provided however, that in regard to any tax so deducted, the
paying Party shall give or cause to be given to the receiving Party such
assistance as may reasonably be necessary to enable the receiving Party to claim
exemption or credit, and in each case, the paying Party shall furnish to the
receiving Party proper evidence of the taxes paid on its behalf.
4.8 Reports; Payments. The royalties due under Sections 4.1 and 4.2 shall
be paid quarterly within sixty (60) days after the close of each calendar
quarter, or earlier if practicable, immediately following each quarterly period
in which such royalties are earned. With each such quarterly payment, the paying
Party shall furnish the receiving Party a royalty statement setting forth in
reasonable detail on a country-by-country and Product-by-Product basis: (i) the
total number of units of each Product sold hereunder for the quarterly period
for which the royalties are due; (ii) the calculation of Net Sales pursuant to
Section 1.23; (iii) the calculation of Excess Expenses pursuant to Section 3.9
and the amount of Excess Expenses to be credited against royalties pursuant to
Section 4.3; (iv) the royalties due the receiving Party in such quarter; and (v)
details of payments (if any) to third parties pursuant to third party licenses
as described in Section 4.5 above. If no royalties are due, the paying Party
shall so report.
4.9 Currency Conversion. All amounts required to be paid under this
Agreement by UG to SGX shall be paid in United States dollars and all amounts
required to be paid by SGX to UG shall be paid in Euros. Royalties earned shall
first be
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determined in the currency of the country in which they are earned and then
converted to its equivalent in United States dollars or Euros, as applicable,
using the average daily exchange rate for the last month of the quarterly period
in which royalties were earned, as customarily used by each Party in its
respective accounting practice.
4.10 Late Payments. Any payments or portions thereof due hereunder which
are not paid on the date such payments are due, shall bear interest at the rate
equal to the lesser of the prime rate as reported by the Chase Manhattan Bank,
New York, New York, plus [...***...] percent ([...***...]%) or the maximum
amount permitted by law, compounded monthly. This Section 4.10 shall in no way
limit any other remedies available to each Party.
4.11 Audits. Each Party shall maintain accurate books and records which
enable the calculation of Excess Expenses and royalties payable under this
Agreement to be verified. Each Party shall maintain the books and records for
each quarterly period for three (3) years after the submission of the
corresponding reports under Sections 3.8 and 4.8. Upon thirty (30) days prior
notice, independent accountants selected by a Party (the "Inspecting Party"),
reasonably acceptable to the other Party, may have access to such Party's books
and records after executing a reasonable confidentiality agreement, during such
Party's normal business hours at mutually agreed times to conduct a review or
audit no more than once per calendar year, for the sole purpose of verifying the
accuracy of such Party's payments and compliance with this Agreement. The
accounting firm shall report to the Inspecting Party whether there has been a
royalty underpayment and, if so, the extent thereof. In the event such
accounting firm concludes that amounts were overpaid by the other Party during
such period, the Inspecting Party shall repay the other Party the amount of such
overpayment within ninety (90) days of the date the Inspecting Party delivers to
the other Party such accounting firm's written report so concluding. Any such
inspection shall be at the Inspecting Party's expense, however, in the event
that an inspection reveals underpayment of five percent (5%) or more in any
audit period or a similar discrepancy or deviance in any Excess Expenses, the
other Party shall pay the costs of the inspection. Any underpayments identified
in such an inspection shall be promptly paid to the Inspecting Party, with
interest calculated in accordance with Section 4.10.
5. LICENSES
5.1 License to UG. Subject to the terms and conditions of this Agreement,
SGX hereby grants to UG, the following licenses:
(a) an exclusive license (with the right to grant sublicenses in
accordance with Section 5.4 below) under SGX'S interest in Collaboration
Technology to make, have made, use, import, offer for sale and sell
Collaboration Products in the UG Territory;
(b) an exclusive, worldwide license (with the right to grant
sublicenses in accordance with Section 5.4 below) Under SGX's interest in
Collaboration Technology, to make, have made, use, import, offer for sale and
sell UG Products;
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(c) a non-exclusive, worldwide, royalty-free license under SGX's
interest in SGX Background Technology, solely as necessary to conduct the
Collaboration; and
(d) solely in the event that UG becomes an Active Party under
Section 6.1, an exclusive, worldwide license (with the right to grant
sublicenses in accordance with Section 5.4 below) under SGX's interest in
Collaboration Technology, to make, have made, use, import, offer for sale and
sell Collaboration Products.
(e) an exclusive, worldwide, royalty-free license (with the right to
grant sublicenses under Section 5.4 below), under SGX's interest in UG
Compounds, to make, have made, use, import, offer for sale and sell products.
5.2 License to SGX. Subject to the terms and conditions of this Agreement,
UG hereby grants to SGX, the following licenses:
(a) an exclusive license (with the right to grant sublicenses in
accordance with Section 5.4 below) under UG's interest in Collaboration
Technology to make, have made, use, import, offer for sale and sell
Collaboration Products in the SGX Territory;
(b) an exclusive, worldwide license (with the right to grant
sublicenses in accordance with Section 5.4 below) under UG's interest in
Collaboration Technology to make, have made, use, import, offer for sale and
sell SGX Products;
(c) a non-exclusive, worldwide, royalty-free license under UG's
interest in UG Background Technology, solely as necessary to conduct the
Collaboration; and
(d) solely in the event that SGX becomes an Active Party under
Section 6.1, an exclusive, worldwide license (with the right to grant
sublicenses in accordance with Section 5.4 below) under UG's interest in
Collaboration Technology, to make, have made, use, import, offer for sale and
sell Collaboration Products.
(e) an exclusive, worldwide, royalty-free license (with the right to
grant sublicenses in accordance with section 5.4 below), under UG's interest in
SGX Compounds, to make, have made, use, import, offer for sale and sell
products.
5.3 Cross Licenses. Each Party hereby grants to the other:
(a) a non-exclusive, non-transferable, license to use and practice
such Party's interest in Collaboration Technology solely to conduct the
Collaboration; and
(b) subject to Section 5.6(d), a non-exclusive, worldwide license
(with the right to grant sublicenses in accordance with Section 5.4 below) under
each Party's interest in Collaboration Technology to make, have made, use,
import, offer for sale and
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sell products directed at inhibiting, modulating or altering the activity of MET
for application outside the Therapeutic Field.
5.4 Sublicenses. Each Party may sublicense the rights granted in Sections
5.1(a), (b) and (d), 5.2(a), (b) and (d) and 5.3(b) to its Affiliates and to
Third Parties, provided that (i) prior to entering into any such sublicense with
a Third Party (other than under Sections 5.1(d) or (e) or 5.2(d) or (e)), the
other Party is first offered such rights on terms no less favorable than those
offered or proposed to be offered to the Third Party, and the Parties then
negotiate in good faith the terms of such agreement during the following
forty-five day period; and (ii) such sublicense granted is consistent with all
of the terms and conditions of this Agreement. The sublicensing Party shall
remain responsible for all of each such sublicensee's obligations under this
Agreement.
5.5 No Unauthorized Use. UG hereby covenants to SGX that it will not use
or practice the SGX Background Technology or SGX Compounds for any purpose other
than as expressly permitted under this Agreement. SGX hereby covenants to UG
that it will not use or practice the UG Background Technology or UG Compounds
for any purpose other than as expressly permitted under this Agreement.
5.6 Retained Rights. Notwithstanding anything in this Agreement to the
contrary:
(a) SGX will have the right to develop and commercialize SGX
Compounds, without accounting to UG, for any therapeutic indication and UG will
have the right to develop and commercialize UG Compounds, without accounting to
SGX, for any therapeutic indication;
(b) SGX will have the right to develop and commercialize any Lead
Compounds selected by the JRC for lead optimization, in the SGX Retained Field,
provided that: (i) such Lead Compound is at least [...***...] in an [...***...]
against another kinase (other than MET), as it is against XXX; (ii) such lead
compound is not selected by the JRC as a SAC and (iii) SGX does not develop such
Lead Compound solely for application in the Expanded Therapeutic Field;
(c) UG will have the right to develop and commercialize any Lead
Compounds selected by the JRC for lead optimization, in the UG Retained Field,
provided that: (i) such Lead Compound is at least [...***...] in an [...***...]
against a non-kinase target, as it is against XXX; (ii) such lead compound is
not selected by the JRC as a SAC and (iii) UG does not develop such Lead
Compound solely for application in the Expanded Therapeutic Field;
(d) Each Party (the "Developing Party") will have the right to
develop and commercialize any Lead Compound selected by the JRC for lead
optimization, as a MET inhibitor, provided that (i) such Lead Compound is at
least [...***...] in an [...***...] against MET as it is against XXX; and (ii)
prior to commencing any preclinical development activities with such Lead
Compound, the Developing Party first offers the other Party (the "Other Party")
the right to collaborate with the Developing
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Party on the development of such Lead Compound, on substantially the same terms
and conditions as under this Agreement, which right the Other Party has sixty
(60) days to evaluate and accept or decline.
(e) SGX and UG will jointly and equally own any Safety Assessment
Candidates and Drug Candidates identified under the Collaboration provided that
neither Party will have the right to develop or commercialize such SACs or Drug
Candidates outside of the Collaboration without the other Party's prior written
consent.
5.7 Third Party Licenses. In the event that the JRC determines that it is
necessary or useful to acquire a license from any Third Party specifically for
the conduct of the Collaboration, the Parties shall discuss which Party shall
acquire such license provided however, that the costs of any such license shall
be shared equally by the parties.
5.8 Reports. Each Party shall keep the other Party fully informed of its
activities subject to this Agreement, including its activities in connection
with the development and commercialization of SGX Products and UG Products and
the commercialization of Collaboration Products. On or before January 31 and
July 31 of each year during the term of this Agreement, each Party shall provide
the other with a written report summarizing such events and activities.
6. SINGLE PARTY DEVELOPMENT
6.1 Single Party Development. Subject to the terms of this Article 6, if
the JDC cannot agree on whether to clinically develop a particular Safety
Assessment Candidate pursuant to Section 2.4, or if a Party decides to terminate
its Preclinical or Clinical development activities with regard to a particular
Collaboration Product pursuant to Section 6.2, the Party which wants to proceed
with or continue such clinical development (the "Active Party") may do so, at
its discretion, without the financial support or involvement of the other Party
(the "Inactive Party"). If a Party becomes an Inactive Party, the Active Party
shall have the rights under Section 5.1(d) or 5.2(d), as applicable.
6.2 Termination of Preclinical or Clinical Development. Each Party may
terminate in its sole discretion, its research, Preclinical Development or
Clinical Development obligations with regard to a particular Collaboration
Product upon written notice, within the ninety (90) day period immediately
following the completion of any of the events described in paragraphs (a)
through (g) below. Upon any such termination, the terms of Sections 6.1, 6.3 and
6.4 will apply and the Active Party shall have no further obligations to the
Inactive Party with regard to such Collaboration Product, except as set forth in
such Sections.
(a) Failure to obtain, as determined by the JRC, a crystal structure
of the Target at better than [...***...] resolution within [...***...]
([...***...]) months following the Effective Date.
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(b) Selection by the JRC of a [...***...] for entry into
[...***...].
(c) Selection by the JRC of a [...***...] for [...***...].
(d) Decision by the JDC to [...***...].
(e) Completion of [...***...] for [...***...].
(f) Decision of the JDC to [...***...].
(g) [...***...] of a [...***...].
6.3 Royalties. The Active Party shall pay the Inactive Party a royalty on
the sales of Collaboration Products as follows. No royalties will be payable to
the Inactive Party in the event that a Party becomes an Active Party under
Section 6.2(a):
(a) Where a Party became an Active Party under Section 6.2(b):
[...***...]% of Net Sales by the Active Party or [...***...]% of Sublicensing
Revenue received by the Active Party in connection with such Collaboration
Product.
(b) Where a Party became an Active Party under Section 6.2(c):
[...***...]% of Net Sales by the Active Party or [...***...]% of Sublicensing
Revenue received by the Active Party in connection with such Collaboration
Product.
(c) Where a Party became an Active Party under Section 6.2(d):
[...***...]% of Net Sales by the Active Party or [...***...]% of Sublicensing
Revenue received by the Active Party in connection with such Collaboration
Product.
(d) Where a Party became an Active Party under Section 6.2(e):
[...***...]% of Net Sales by the Active Party or [...***...]% of Sublicensing
Revenue received by the Active Party in connection with such Collaboration
Product.
(e) Where a Party became an Active Party under Section 6.2(f):
[...***...]% of Net Sales by the Active Party or [...***...]% of Sublicensing
Revenue received by the Active Party in connection with such Collaboration
Product
(f) Where a Party became an Active Party under Section 6.2(g):
[...***...]% of Net Sales by the Active Party or [...***...]% of Sublicensing
Revenue received by the Active Party in connection with such Collaboration
Product.
6.4 Recovery of Investments. If a Party becomes the Inactive Party
pursuant to Section 6.2, the Active Party shall pay the Inactive Party, in
addition to the royalties set forth in Section 6.3, a royalty equal to
[...***...]% of the Net Sales based upon sales of the applicable Collaboration
Product sold by the Active Party, its Affiliates, or any of its
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Sublicensees in the Party's applicable Territory, or [...***...]% of
Sublicensing Revenue, until such time as the sum of the royalties paid to the
Inactive Party pursuant to this Section 6.4 is equal to the sum of any Excess
Expenses incurred by the Inactive Party in accordance with the applicable
Development Budget for the applicable Collaboration Product prior to such
Party's inactivity.
7. INTELLECTUAL PROPERTY
7.1 Ownership of Technology.
(a) By SGX. SGX Background Technology, and Collaboration Technology
made solely by SGX will be owned solely by SGX.
(b) By UG. UG Background Technology, and Collaboration Technology
made solely by UG will be owned solely by UG
(a) Joint. Collaboration Technology made jointly by SGX and UG will
be owned jointly by SGX and UG. Notwithstanding any joint ownership of any
Collaboration Technology under this Agreement, neither Party will have the right
to exploit such Collaboration Technology other than as expressly permitted under
the terms and conditions of this Agreement.
(d) Law. Inventorship of inventions and, subject to the terms of
this Agreement, ownership rights with respect thereto, shall be determined in
accordance with the patent laws of the United States.
7.2 Patent Prosecution.
(a) Background Technology. UG shall be responsible, at its expense,
for the preparation, filing, prosecution and maintenance of the patent
applications and patents claiming inventions within UG Background Technology, in
countries selected by UG, and for conducting any interferences, reexaminations,
reissues, oppositions, or request for patent term extension relating thereto.
SGX shall be responsible, at its expense, for the preparation, filing,
prosecution and maintenance of the patent applications and patents claiming
inventions within SGX Background Technology in countries selected by SGX, and
for conducting any interferences, reexaminations, reissues, oppositions, or
request for patent term extension relating thereto.
(b) Collaboration Technology. The JRC or the JDC, as applicable
shall have initial responsibility for reviewing all potentially patentable
inventions and determining the strategy for the filing, prosecuting and
maintaining of inventions within Collaboration Technology, (collectively
"Collaboration Inventions"), and the JRC or JDC shall then recommend to the
Parties whether to file Collaboration Inventions applications, and in which
countries such Collaboration Inventions shall be first filed and will develop a
global filing strategy for each Collaboration Invention. Unless the JRC or JDC,
as applicable, otherwise agrees, SGX shall be responsible for filing,
prosecuting and maintaining such Collaboration Inventions and the cost and
expense of filing, prosecuting
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or maintaining patent application with respect to any Collaboration Inventions
shall be borne equally by the Parties. SGX shall provide UG with copies of all
documents, correspondence, materials and proof of costs relating to the
prosecution by SGX of such Collaboration Invention. Such copies shall be
provided promptly after receipt, with respect to communications to or from
applicable patent authorities, and sufficiently in advance of SGX's filing or
otherwise communicating any such documents to allow UG reasonable time to review
such materials and comment thereon prior to filing.
(c) Cooperation. Each Party agrees to cooperate with the other and
take all reasonable additional actions as may be reasonably required to achieve
the intent of this Article 7, including, without limitation, the execution and
provision of necessary and appropriate instruments and documents.
(d) Patent Enforcement. In the event either Party becomes aware of
any interference, opposition, or request for reexamination, or similar
proceedings, involving a patent application or patent filed in accordance with
Section 7.2(b) within Collaboration Technology (a "Collaboration Patent"), it
shall promptly notify the other Party hereto, and the Parties shall agree on the
steps which shall be taken to protect the pertinent Collaboration Patent. In the
event either Party becomes aware of any possible infringement of a Collaboration
Patent or misappropriation of an invention within the Collaboration Technology,
it shall promptly notify the other Party hereto, providing a written description
of the potentially infringing or misappropriation activities. SGX shall have the
right, but not the obligation to institute, prosecute and control any action or
proceeding with respect to infringement of Collaboration Patents in the SGX
Territory. UG shall have the right, but not the obligation, to institute,
prosecute and control any action or proceeding with respect to infringement of
Collaboration Patents in the UG Territory. If a Party given the right to enforce
a Collaboration Patent pursuant to this Section fails to bring an action or
proceeding against a suspected infringer within a period of ninety (90) days
after having notice of such infringement in the Party's Territory, the other
Party shall have the right to bring and control an action against such infringer
by counsel of its own choice, and the non-enforcing Party shall have the right
to be represented in any such action by counsel of its own choice at its own
expense. The Party controlling an action involving any infringement of a
Collaboration Patent shall consider in good faith the interests of the other
Party in so doing, and shall not settle or consent to an adverse judgment in any
such action which would have a material adverse effect on the rights or
interests of the other Party without the prior express written consent of such
other Party. If one Party brings any such action or proceeding, the other Party
agrees to be joined as a Party plaintiff if necessary to prosecute the action
and to give the first Party reasonable assistance and authority to file and
prosecute the suit. In each case relating to infringement of a Collaboration
Patent, each Party shall bear the costs of its enforcement of the Patent rights
discussed in this section and retain for its own account any amounts received
from Third Parties; provided, however, that any such recovery over the costs of
the enforcement of the Patent Rights shall be deemed Net Sales of the infringed
Collaboration Product, subject to a royalty of [...***...]%.
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8. CONFIDENTIALITY AND PUBLICITY
8.1 Confidential Information. Except as expressly provided herein, the
parties agree that, for the Term of the Agreement, the receiving Party shall not
publish or otherwise disclose and shall not use for any purpose, except as
expressly permitted herein, any information or material furnished to it by the
other Party hereto pursuant to this Agreement which if disclosed in tangible
form is marked "Confidential" or with other similar designation to indicate its
confidential or proprietary nature, or if disclosed orally is confirmed as
confidential or proprietary by the Party disclosing such information at the time
of such disclosure or within thirty (30) days thereafter ("Confidential
Information"). Notwithstanding the foregoing, it is understood and agreed that
Confidential Information shall not include information or material that, in each
case as demonstrated by written documentation:
(a) was already known to the receiving Party, other than under an
obligation of confidentiality, at the time of disclosure;
(b) was generally available to the public or otherwise part of the
public domain at the time of its disclosure to the receiving Party;
(c) became generally available to the public or otherwise part of
the public domain after its disclosure and other than through any act or
omission of the receiving Party in breach of this Agreement; or
(d) was subsequently lawfully disclosed to the receiving Party by a
person other than a Party hereto or developed by the receiving Party without
reference to any Confidential Information disclosed by the disclosing Party.
8.2 Permitted Disclosures. The restrictions contained in Section 8.1 shall
not apply to Confidential Information that is (i) provided by the receiving
Party to a Third Party or sublicensee under confidentiality provisions at least
as stringent as those in this Agreement, for consulting, research, development,
manufacturing, external testing or marketing trials; or (ii) reasonably required
to be disclosed in filing or prosecuting patent applications within the Patent
Rights, prosecuting or defending litigation, complying with applicable
governmental regulations or conducting preclinical or clinical trials, or
submitting information to tax or other governmental authorities, provided that
if a Party is required to make any such disclosure of another Party hereto's
Confidential Information, to the extent it may legally do so, it will give
reasonable advance written notice to the other Party of such disclosure and
except to the extent inappropriate in the case of patent applications, will use
its reasonable efforts to secure confidential treatment of such Confidential
Information prior to its disclosure (whether through protective orders or
otherwise).
8.3 Publication. Any public disclosure (oral, written or graphic) by
either Party describing the scientific results of the Research Collaboration
will require prior review and approval of the other Party at least thirty (30)
days prior to its submission for publication or other public disclosure. If the
reviewing Party so requests, the proposed
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public disclosure will be delayed for forty-five (45) days from the date of each
request for the filing of patent application(s) related to the proposed public
disclosure.
8.4. Publicity. The parties agree to make a mutually agreed press release
regarding this Agreement promptly following the Effective Date. Except as
expressly provided in this Agreement, each Party agrees not to disclose any
terms of this Agreement to any third party without the prior written consent of
the other Party; provided however, that disclosures may be made as required by
securities or other applicable laws, or to actual or prospective investors or
strategic partners under obligations of confidence, or to a party's professional
advisors.
9. INDEMNIFICATION
9.1 Indemnification of SGX. UG shall indemnify, defend, and hold harmless
SGX, the directors, officers, and employees of SGX and the successors and
assigns of any of the foregoing (the "SGX Indemnitee(s)") from and against all
claims, losses, costs, and liabilities (including, without limitation, payment
of reasonable attorneys' fees and other expenses of litigation), and shall pay
any damages (including settlement amounts) finally awarded, with respect to any
claim, suit or proceeding (any of the foregoing, a "Claim") brought by Third
Party against a SGX Indemnitee, arising out of or relating to: (a) the
performance by UG of the Collaboration; (b) the exercise by UG of the rights
granted UG under this Agreement; (c) a material breach by UG of its obligations
under this Agreement; (d) a breach of UG's representations and warranties under
Section 10; (e) any Products developed, manufactured, use, sold or otherwise
distributed by or on behalf of UG, its Affiliates or permitted sublicensees
pursuant to Article 5, (including without limitation, product liability claims),
(f) the handling, storage or transfer by UG or UG's permitted transferee of
materials provided by SGX to UG hereunder, (g) the negligence or willful
misconduct of UG or (h) a claim that the use by SGX or UG of the UG Background
Technology, infringes the intellectual property rights of a Third Party, except,
in each case, to the extent caused by the gross negligence or willful misconduct
of a SGX Indemnitee.
9.2 Indemnification of UG. SGX shall indemnify, defend and hold harmless
UG, the directors, officers, and employees of UG, and the licensors, successors
and assigns of any of the foregoing (the "UG Indemnitee(s)") from and against
all Claims (as defined in Section 9.1) brought by third Party against a UG
Indemnitee, arising out of or relating to: (a) the performance by SGX of the
Collaboration; (b) the exercise by SGX of the rights granted SGX under this
Agreement; (c) a material breach by SGX of its obligations under this Agreement;
(d) a breach of SGX's representations and warranties under Section 10; (e) any
Products developed, manufactured, use, sold or otherwise distributed by or on
behalf of SGX, its Affiliates or permitted sublicensees pursuant to Article 5,
(including without limitation, product liability claims) (f) the handling,
storage or transfer by SGX of materials provided by UG to SGX hereunder; (g) the
negligence or willful misconduct of SGX, or (h) a claim that the use by SGX or
UG of the SGX Background Technology, infringes the intellectual property rights
of a Third Party, except, in each case, to the extent due to the gross
negligence or willful misconduct of a UG Indemnitee.
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9.3 Indemnification Procedures. An Indemnitee that intends to claim
indemnification under this Article 9 shall promptly notify the other Party (the
"Indemnitor") in writing of any claim in respect of which the Indemnitee intends
to claim such indemnification, and the Indemnitor shall have sole control of the
defense and/or settlement thereof, provided that the indemnified Party may
participate in any such proceeding with counsel of its choice at its own
expense. The indemnity agreement in this Article 9 shall not apply to amounts
paid in settlement of any Claim if such settlement is effected without the
consent of the Indemnitor, which consent shall not be withheld unreasonably. The
failure to deliver written 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 such Indemnitor of any liability to the
Indemnitee under this Article 9 but the omission so to deliver written notice to
the Indemnitor shall not relieve the Indemnitor of any liability that it may
have to any Indemnitee other than under this Article 9. The Indemnitee under
this Article 9, its employees and agents, shall cooperate fully with the
Indemnitor and its legal representatives and provide full information in the
investigation of any Claim covered by this indemnification. Neither Party shall
be liable for any costs or expenses incurred by the other Party without its
prior written authorization.
10. REPRESENTATIONS AND WARRANTIES
10.1 Each Party. Each Party represents and warrants to the other (i) that
it has the legal power, authority and right to enter into this Agreement and to
perform its respective obligations under this Agreement; (ii) that it is not a
Party to any agreement or arrangement with any Third Party or under any
obligation or restriction which in any way limits or conflicts with its ability
to fulfill any of its obligations under this Agreement, (including without
limitation, the licenses granted in Article 5), and shall not enter into any
such agreement or arrangement during the term of this Agreement; (iii) each
employee or person engaged in the Collaboration on behalf of UG or SGX has
entered into a written agreement which provides for the assignment to UG or SGX,
respectively, of all inventions and discoveries made by such employee or person
during the course of his or her employment or engagement with UG or SGX.
10.2 Representations and Warranties of UG. UG represents and warrants that
to the knowledge of UG, (i) it is not aware of any asserted or unasserted
claims, interference, oppositions or demands of any Third Party against the
Target in existence as of the Effective Date and (ii) the Parties' use of the
Target as contemplated under this Agreement will not infringe any patent or any
other proprietary rights of any Third Party.
10.3 Disclaimer. SGX and UG specifically disclaim any guarantee that the
Collaboration will be successful, in whole or in part. The failure of the
parties to develop Products or to meet any of the estimated time lines in the
Research Plan or Development Plan will not constitute a breach of any
representation or warranty or other obligation under this Agreement. EXCEPT AS
OTHERWISE EXPRESSLY PROVIDED IN THIS AGREEMENT, UG AND SGX MAKE NO
REPRESENTATIONS AND EXTEND NO WARRANTIES OF ANY KIND, EITHER EXPRESS OR IMPLIED,
WITH RESPECT TO THE SGX BACKGROUND TECHNOLOGY, UG BACKGROUND
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TECHNOLOGY, OR COLLABORATION TECHNOLOGY OR PRODUCTS OF EACH PARTY, INCLUDING
WITHOUT LIMITATION, ANY WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR
PURPOSE OR NON-INFRINGEMENT OF THE INTELLECTUAL PROPERTY OR OTHER RIGHTS OF ANY
THIRD PARTY.
11. TERM AND TERMINATION
11.1 Term of the Agreement. The term of this Agreement shall commence on
the Effective Date and unless terminated earlier, will terminate on a
Product-by-Product basis upon the later of (i) expiration of the last to expire
patent within the Patent Rights covering such Product and (ii) fifteen years
after the First Commercial Sale of such Product.
11.2 Termination for Cause. Either UG or SGX may terminate this Agreement
by written notice, stating such Party's intent to terminate in the event the
other Party shall have materially breached or defaulted in the performance of
any of its obligations hereunder, and such default shall have continued for
sixty (60) days after written notice thereof was provided to the breaching Party
by the nonbreaching Party.
11.3 Termination for Insolvency. Either Party may terminate this
Agreement, if at any time the other Party files in any court or agency pursuant
to any statute or regulation of any state or country, a petition in bankruptcy
or insolvency or for reorganization or for any arrangement of for the
appointment of a receiver or trustee of the Party or of substantially all of its
assets, or if the other Party is served with an involuntary petition against it
in any insolvency proceeding and such petition is not dismissed within six (6)
months after the filing thereof, or if the other Party makes an assignment of
substantially all of its assets for the benefit of creditors.
11.4 Bankruptcy Code Section 365(n). All rights and licenses granted under
or pursuant to this Agreement are, and will otherwise be deemed to be, for
purposes of Section 365(n) of the United States Bankruptcy Code, licenses of
rights to "intellectual property" as defined under Section 101 of the United
States Bankruptcy Code. The Parties agree that the Parties, as licensees of such
rights under this Agreement, will retain and may fully exercise all of their
rights and elections under the United States Bankruptcy Code. The Parties
further agree that, in the event of the commencement of a bankruptcy proceeding
by or against a Party under the United States Bankruptcy Code, the non-bankrupt
Party will be entitled to a complete duplicate of (or complete access to, as
appropriate) any such intellectual property and all embodiments of such
intellectual property, which, if not already in the non-bankrupt Party's
possession, will be promptly delivered to it unless the Party subject to such
proceeding continues to perform all of its obligations under this Agreement.
11.5 Effect of Termination.
(a) Accrued Rights and Obligations. Termination of this Agreement
for any reason shall not release any Party hereto from any liability which, at
the time of
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such termination, has already accrued to the other Party or which is
attributable to a period prior to such termination nor preclude either Party
from pursuing all rights and remedies it may have hereunder or at law or in
equity with respect to any breach of this Agreement.
(b) Licenses. In the event of termination of this Agreement by the
non-breaching or non-bankrupt Party pursuant to Sections 11.2 or 11.3, the
licenses granted the breaching Party or bankrupt Party under Article 5 shall
terminate concurrently and the non-breaching Party or non-bankrupt Party shall
have an exclusive, royalty free right under Collaboration Technology, to make,
have made, use, sell and import, Collaboration Products in the non-breaching or
non-bankrupt Party's applicable Territory. The breaching or bankrupt Party will
assist the non-breaching or non-bankrupt Party in every proper way to effect the
license granted above. The breaching Party shall further deliver to the
non-breaching Party such relevant tangible materials embodying Collaboration
Technology as may be necessary or useful to the exercise by the non-breaching
Party of the license hereunder.
(c) Survival. The provisions of Sections 3.9, 3.10, 3.13, 5.5, 5.6,
5.8, 6.3, 6.4, and Articles 4, 7, 8, 9, 10 and 12 shall survive the expiration
or termination of this Agreement for any reason.
12. MISCELLANEOUS
12.1 Arbitration. If the Parties are unable to resolve any dispute,
controversy or claim between them arising out of or relating to the validity,
construction, enforceability or performance of this Agreement, including
disputes relating to alleged breach or to termination of this Agreement (each, a
"Dispute"), the Dispute shall be finally settled under the Rules of Arbitration
of the International Chamber of Commerce by one or more arbitrators appointed in
accordance with the said Rules. Such arbitration shall be held in Geneva, and
shall be conducted in the English language. Pending the establishment of the
arbitral tribunal or pending the arbitral tribunal's determination of the merits
of the controversy, either Party may seek from a court of competent jurisdiction
any interim or provisional relief that may be necessary to protect the rights or
property of that Party.
12.2 Governing Law. This Agreement and all acts and transactions pursuant
hereto and the rights and obligations of the parties hereto shall be governed,
construed and interpreted in accordance with the laws of the State of Delaware,
without reference to rules of conflicts or choice of laws.
12.3 Notices. Any notice required or permitted by this Agreement shall be
in writing and shall be sent by prepaid registered or certified mail, return
receipt requested, internationally recognized courier or personal delivery, or
by fax with confirming letter mailed under the conditions described above in
each case addressed to the other Party at the address shown below or at such
other address for which such Party gives notice hereunder. Such notice shall be
deemed to have been given when delivered:
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If to SGX:
Structural GenomiX, Inc.
00000 Xxxxxxx Xxxxxx,
Xxx Xxxxx, XX 00000
Fax: + 0 000 000 0000
Attn: Chief Executive Officer
Copy to: Corporate Counsel
If to UG:
UroGene S.A.
0, Xxx Xxxxxx Xxxxxxxx - Xxxxxxxx
00000 Xxxx Xxxxx
Xxxxxx
Fax: + 00 0 00 00 00 00
Attn: Chief Executive Officer
12.4 Force Majeure. Neither Party shall lose any rights hereunder or be
liable to the other Party for damages or losses (except for payment obligations)
on account of failure of performance by the defaulting Party if the failure is
occasioned by war, strike, act of terrorism, fire, Act of God, earthquake,
flood, lockout, embargo, governmental acts or orders or restrictions, failure of
suppliers (including, without limitation, energy suppliers), or any other reason
where failure to perform is beyond the reasonable control and not caused by the
negligence, intentional conduct or misconduct of the nonperforming Party and the
nonperforming Party has exerted all reasonable efforts to avoid or remedy such
force majeure; provided, however, that in no event shall a Party be required to
settle any labor dispute or disturbance.
12.5 No Implied Rights. Only the rights granted pursuant to the express
terms of this Agreement shall be of any legal force or effect. No other rights
shall be created by implication or otherwise.
12.6 Assignment. This Agreement shall not be assignable by either Party to
any third Party hereto without the written consent of the other Party hereto,
except either Party may assign this Agreement, without such consent, to (i) an
Affiliate or (ii) an entity that acquires all or substantially all of the
business or assets of such Party to which this Agreement pertains, whether by
merger, reorganization, acquisition, sale, or otherwise.
12.7 Partial Invalidity. If any provision of this Agreement is held to be
invalid by a court of competent jurisdiction, then the remaining provisions
shall remain, nevertheless, in full force and effect. The Parties agree to
renegotiate in good faith any provision held invalid and to be bound by the
mutually agreed substitute provision in order to give the most approximate
effect originally intended by the Parties. This Agreement has been prepared in
the English language and the English language shall control its interpretation
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12.8 Independent Contractors. The relationship of UG and SGX established
by this Agreement is that of independent contractors, and nothing contained in
this Agreement shall be construed to (i) give either Party the power to direct
or control the day-to-day activities of the other, (ii) constitute the Parties
as partners, joint venturers, co-owners or otherwise as participates in a joint
or common undertaking, or (iii) allow a Party to create or assume any obligation
on behalf of the other Party for any purpose whatsoever.
12.9 No Waiver. No waiver of any term or condition of this Agreement shall
be valid or binding on either Party unless agreed in writing by the Party to be
charged. The failure of either Party to enforce at any time any of the
provisions of the Agreement, or the failure to require at any time performance
by the other Party of any of the provisions of this Agreement, shall in no way
be construed to be a present or future waiver of such provisions, nor in any way
affect the validity of either Party to enforce each and every such provision
thereafter.
12.10 Counterparts. This Agreement may be executed in two or more
counterparts, each of which shall be deemed an original and all of which
together shall constitute one instrument.
12.11. English Language. This Agreement has been prepared in the English
language and the English language shall control its interpretation.
12.12 Entire Agreement; Amendment. This Agreement, including the Exhibits
attached hereto, constitutes the entire agreement of the Parties with respect to
the subject matter hereof, and supersedes all prior or contemporaneous
understandings or agreements, whether written or oral, between UG and SGX with
respect to such subject matter. No amendment or modification hereof shall be
valid or binding upon the parties unless made in writing and signed by the duly
authorized representatives of both Parties.
IN WITNESS WHEREOF, the undersigned are duly authorized to execute this
Agreement on behalf of UG and SGX as applicable.
UROGENE S.A. STRUCTURAL GENOMIX, INC.
By: /s/ [Illegible] By: /s/ Xxxx Xxxx
---------------------------------- ---------------------------
Name: [Illegible] Name: MG Grey
Title: CEO Chairman of the Board Title: President
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EXHIBIT A
[COUNTRIES IN EUROPE]
FRANCE
GERMANY
ITALY
BELGIUM
LUXEMBOURG
NETHERLANDS
UNITED KINGDOM
IRELAND
DENMARK
GREECE
SPAIN
PORTUGAL
AUSTRIA
SWEDEN
FINLAND
SWITZERLAND
TURKEY
ICELAND
NORWAY
ANDORRA
MONACO
LIECHTENSTEIN
MALTA
SAN MARINO
VATICAN
POLAND
CZECH REPUBLIC
SLOVAKIA
HUNGARY
MACEDONIA
ROMANIA
BULGARIA
SLOVENIA
ALBANIA
MONTENEGRO
LATVIA
ESTONIA
LITHUANIA
BELARUS
UKRAINE
MOLDAVIA
GEORGIA
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EXHIBIT B
RESEARCH PLAN
[...***...]ST, [...***...] - [...***...]ST [...***...] RESEARCH PLAN
GOALS FOR [...***...] (END [...***...])
The overall Project goal for [...***...] is to obtain [...***...] of the
[...***...] kinase for the treatment of bladder cancer. This will be
accomplished by:
1. Solving the [...***...] of [...***...], either in the "[...***...]" form or
with a [...***...] [...***...] or [...***...],
2. Screening for [...***...] using [...***...] and [...***...]
3. Employing an [...***...] and [...***...] guided by [...***...],[...***...]
and [...***...] assays
4. Optimizing [...***...] and [...***...]
[...***...] DETERMINATION
A [...***...] encompassing the [...***...] kinase [...***...] ([...***...]) has
been identified that produces modest yields of [...***...]. Since different
[...***...] of a kinase domain can show substantial differences in (i)
[...***...], (ii) [...***...], (iii) [...***...], (iv) [...***...], and (v)
[...***...], several new constructs will be examined in parallel. Various
versions of the isolated kinase domain of [...***...], produced in [...***...],
will be purified and submitted for [...***...] and [...***...] to determine the
structure (see appendix, Figure 1). The following scheme will be followed:
- [...***...] additional constructs of the [...***...] of [...***...]
will be [...***...] and expressed using a [...***...] (see FIGURE
1). Different [...***...] will be used to produce proteins with
either [...***...]. This experiment will include one construct,
[...***...], which represents the [...***...] of [...***...]
([...***...],[...***...][...***...], see Figure 1).
- All proteins will be tested for solubility after [...***...] and
[...***...] on a small scale. All soluble proteins will be passed to
[...***...].
- A [...***...] kinase domain will be identified using an SGX
[...***...] and [...***...] ([...***...]) method, preferably using
[...***...] if it proves soluble.
- Based on the combined data at this stage new constructs may be made
to modify the exact [...***...] based on the [...***...] data and,
if necessary, [...***...] will be tried to alter the [...***...]
and/or solubility of the protein (see Figure 1).
- If necessary a variety of protocols to purify the most promising
soluble proteins will be explored. At this stage the effect of
parameters such as (i) [...***...], (ii) [...***...], and (iii)
[...***...] on the [...***...] behavior will be
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investigated. The optimal conditions will be used to generate
sufficient [...***...] for [...***...] trials.
- Suitable protein samples will be subjected to a broad series of
[...***...] to identify [...***...]. Information from these initial
[...***...] is used in [...***...] to home in on a suitable set of
conditions to produce [...***...].
- [...***...] that [...***...] to <[...***...] will be sent to SGX-CAT
at the APS to collect [...***...] that will be used to determine the
structure by [...***...] ([...***...]). Alternative strategies are
available in the unlikely event that no suitable [...***...] search
model is found.
- At this stage a validation set of [...***...] well-characterized
[...***...] will be used in the development of [...***...] and
soaking protocols. The [...***...] may include [...***...]
identified at UG or SGX and may include [...***...] kinase
[...***...] such as [...***...] and [...***...]. Such protocols will
form the basis of our ability to rapidly determine the structures of
[...***...] bound to (i) [...***...] (see below), (ii) [...***...]
(or [...***...]) [...***...] and (iii) the [...***...].
[...***...] DETERMINATION
A plan similar to that detailed for [...***...] will be pursued. Figure 2 in the
appendix illustrates the construct plans.
[...***...] SCREENING
UG and SGX will share experience in establishing [...***...] and [...***...]
activity assays and in establishing a screening regimen to identify [...***...]
hits (see Figure 3). For the SGX-FAST(TM) library screening a suitable substrate
will be identified from the SGX kinase substrate library. [...***...] and,
potentially, "[...***...]"[...***...] and/or [...***...], will be developed.
Alternative proteins of both [...***...] and [...***...] will be evaluated as
well as various [...***...] of each in the assays. The JRC will determine which
assay format(s), including which protein forms, to employ at the two sites and
establish a work flow for testing collaboration compounds.
- SGX-FAST(TM)
The FAST(TM) method will be employed to identify potent lead compounds. Two
screening systems will be used to survey the SGX FAST(TM) scaffold deck
([...***...] compounds) for [...***...] (which may be [...***...] binders), a
[...***...] at [...***...] and a [...***...] with [...***...]. From these
[...***...] the JRC will select [...***...] to pursue with FAST(TM) chemistry.
[...***...] will be elaborated by an [...***...] of [...***...], [...***...],
[...***...] and [...***...]. [...***...] will be continued until the [...***...]
meet the specifications determined by the JRC as required for a Lead Compound
(see Table 1). The Lead Discovery process is schematically represented in the
appendix, Figure 3.
- [...***...] Screening
A [...***...] will be screened against [...***...] using the UG technology.
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CELL ASSAYS: [...***...], [...***...] AND [...***...] ASSAYS
[...***...] is an [...***...] form of [...***...] which is [...***...] of
[...***...] for activation. [...***...] has been shown to enhance the
[...***...] and [...***...] capacities of [...***...] cells, a human
[...***...]. When [...***...] meet criteria determined by the JRC, these
compounds will be tested on stable bladder cell lines expressing [...***...] or
[...***...] cell lines expressing [...***...]. Control cell lines will be
[...***...] that do not express [...***...]. Three assays will be employed:
- The [...***...] measures the capacity of [...***...] to [...***...]
a [...***...] with [...***...] (a mixture of [...***...],
[...***...] and [...***...]).
- The [...***...] determines the ability of cells to [...***...] a
[...***...]
- [...***...] will be used to determine [...***...] levels by
[...***...] of [...***...].
The [...***...] activity of [...***...] in these assays will be
measured and calculated as an [...***...].
To investigate broader opportunities for selected lead candidates we may employ
a panel of cell lines (e.g. the [...***...]) to identify [...***...] or
[...***...] systems [...***...] by the [...***...].
In addition to [...***...] assays, other assays may be employed to characterize
compounds. Examples include [...***...] assays, [...***...] assays, [...***...]
assays and [...***...] assays.
SELECTIVITY SCREENING
UG and SGX will determine the details of how, and at what stage, to investigate
the selectivity profiles of the collaboration [...***...]. Generally, the SGX
kinase biochemical selectivity screen, which comprises a collection of kinases
for which both [...***...] and [...***...] are established, will be employed.
The exact composition of the assay panel will be determined by the JRC. Third
party selectivity paneling may also be utilized (e.g. from [...***...]) to
obtain information of the activity of lead compounds against a broader selection
of protein kinases.
The "[...***...]" and [...***...] may also be employed to determine the
[...***...] of the [...***...]. These cell lines have been established to
determine the [...***...] of kinase [...***...] on [...***...]: [...***...],
[...***...] [...***...] and [...***...].
[...***...] AND [...***...]
The [...***...] and [...***...] activities will follow the scheme illustrated in
Figure 3.
IN VITRO [...***...]
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When [...***...] meet criteria determined by the JRC, these compounds will be
evaluated for their effects on [...***...] and [...***...],[...***...], and
[...***...].[...***...] will also be determined using [...***...],[...***...]
and [...***...] as appropriate. Stability will be determined at [...***...] and
[...***...]. [...***...] will be checked using the [...***...] assay and by
measuring the effects on the [...***...] and [...***...] of selected cell lines.
[...***...] and [...***...] will be examined in [...***...] ([...***...]) and
other [...***...].
[...***...] ASSAYS
1. [...***...] in [...***...] or [...***...]
The [...***...] expressing [...***...] (see "Cell Assays" above) and control
cell lines will be used to establish [...***...] in [...***...]. These
[...***...] will receive compounds after a period of [...***...] to allow tumors
to reach a certain size. [...***...] will be administered at [...***...],
[...***...] or by [...***...]. Tumor weight and size will be monitored. The
[...***...] will be [...***...] and [...***...] checked by Western blot of
[...***...] with [...***...] or by [...***...] on [...***...].
2. [...***...] in [...***...]
To estimate efficacy via the [...***...] expressing [...***...] (see "Cell
Assays" above) and control cell lines will be [...***...] inside the [...***...]
and, after tumors reach a suitable size, compounds will be administered by
[...***...]. Depending on the chosen [...***...], the [...***...] may be used in
place of the [...***...].
3. [...***...] models
[...***...] ([...***...]) and [...***...] ([...***...]) [...***...] will be
[...***...] inside the [...***...] of the [...***...] model. After tumors reach
A suitable size [...***...] will be tested in [...***...] with [...***...] or
[...***...] to check for [...***...] or [...***...] effects on tumor regression.
[...***...] models 2 and 3 will be developed according to the [...***...]
selected.
[...***...]
Standard [...***...] and [...***...] will be monitored during the process of
lead optimization as outlined in Figure 3. [...***...] will be evaluated by
standard [...***...] and [...***...] will be monitored using [...***...].
[...***...] determined will include [...***...], [...***...], [...***...],
[...***...] and [...***...], [...***...], [...***...], and [...***...].
[...***...] will be examined to check [...***...]. An [...***...] will be
determined in [...***...] and/or [...***...].
APPENDIX
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[...***...]
Figure 1. ([...***...])
[...***...]
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[...***...]
Figure 1. [...***...] diagram of the [...***...] primary sequence (the
[...***...] of the [...***...] are not shown). The predicted [...***...] is in
white-on-black. Residues conserved in the kinase family are highlighted
red-on-grey and listed in the row labeled "conserved". The kinase domain
[...***...], as [...***...] by [...***...] ([...***...],[...***...]), are shown
on the row labeled "[...***...]". [...***...], based on the [...***...]
structure, is shown above the primary sequence (sheets are numbered, helices
alphabetized). Positions of forward (F) aND reverse (R) primers for [...***...]
constructs are shown green-on-grey (F) or red-on-grey (R) below the sequence.
Construct Plan:
The following combination of [...***...] and [...***...] will be used to
generate the initial set of [...***...]: [...***...], [...***...], [...***...],
[...***...] and [...***...]. These will be tested for [...***...] and used to
determine the [...***...] of the [...***...] kinase [...***...] by [...***...]
as described in the research plan and for [...***...]. (Note: one of these, the
[...***...] construct has been tested and shows [...***...] and [...***...]).
Figure 2. ([...***...])
[...***...]
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[...***...]
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[...***...]
Figure 2. [...***...] diagram of the [...***...] primary sequence (the first
[...***...] of the [...***...] are not shown). The predicted [...***...] is in
white-on-black. [...***...] in the kinase family are highlighted red-on-grey and
listed in the row labeled "conserved". The kinase domain [...***...], as defined
by [...***...] and [...***...] ([...***...] and [...***...],[...***...]), are
shown on the row labeled "[...***...]".[...***...], based on the [...***...]
structure, is shown above the primary sequence (sheets are numbered, helices
alphabetized). Positions of forward (F) and reverse (R) primers for [...***...]
constructs are shown green-on-grey (F) or red-on-grey (R) below the sequence.
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[...***...]
Figure 3. [...***...].
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[...***...]
Figure 3. [...***...].
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Table 1. Definition of a [...***...] (see also Figure 3).
[...***...] [...***...] to [...***...]
[...***...] [...***...]
[...***...] [...***...]
[...***...] [...***...]
[...***...] [...***...]
[...***...]
[...***...]
[...***...]
[...***...]
[...***...]
[...***...]
[...***...]
[...***...]
Table 2. Definition of an [...***...] (see also Figure 3).
[...***...] [...***...]available
[...***...] [...***...]
[...***...] [...***...]
[...***...] [...***...] and [...***...]
[...***...] [...***...]
[...***...] [...***...]
[...***...] [...***...] on [...***...])
[...***...] [...***...]; no [...***...];
[...***...] [...***...]
[...***...] [...***...] on [...***...] and [...***...]
[...***...] [...***...]; [...***...]
40 ***CONFIDENTIAL TREATMENT REQUESTED
CONFIDENTIAL
Table 3. [...***...] Resources
Goal FTE ESTIMATE (UG) FTE ESTIMATE (SGX)
---- ----------------- ------------------
[...***...] [...***...]
[...***...] [...***...] [...***...]
[...***...] [...***...]
[...***...] [...***...]
[...***...] [...***...]
[...***...] [...***...] [...***...]
[...***...] [...***...] [...***...]
[...***...] [...***...]
[...***...] [...***...] [...***...]
[...***...] [...***...]
[...***...] [...***...] [...***...]
[...***...] [...***...] [...***...]
Table 4 [...***...] Resources
Goal FTE ESTIMATE (UG) FTE ESTIMATE (SGX)
---- ----------------- ------------------
[...***...] [...***...]
[...***...] [...***...] [...***...]
[...***...] [...***...]
[...***...] [...***...]
[...***...] [...***...]
[...***...] [...***...] [...***...]
[...***...] [...***...] [...***...]
[...***...] [...***...]
[...***...] [...***...] [...***...]
[...***...] [...***...]
[...***...] [...***...] [...***...]
Table 5. Goals and Timelines.
Goal EXPECTED COMPLETION DATE (UG) EXPECTED COMPLETION DATE (SGX)
---- ----------------------------- ------------------------------
[...***...] [...***...]
[...***...] [...***...]
[...***...] [...***...]
[...***...] [...***...] [...***...]
[...***...] [...***...] [...***...]
[...***...] [...***...]
[...***...] of [...***...] [...***...]
[...***...] [...***...]
[...***...] [...***...]
41 ***CONFIDENTIAL TREATMENT REQUESTED
