Exhibit 10.31
CONFIDENTIAL TREATMENT
REQUESTED
CONFIDENTIAL TREATMENT REQUESTED: INFORMATION FOR
WHICH CONFIDENTIAL TREATMENT HAS
BEEN REQUESTED IS OMITTED AND IS NOTED AS FOLLOWS **REDACTED**.
AN
UNREDACTED VERSION OF THIS DOCUMENT HAS BEEN FILED SEPARATELY WITH
THE SECURITIES AND
EXCHANGE COMMISSION.
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LICENSE AND COLLABORATION
AGREEMENT
THIS LICENSE AND COLLABORATION
AGREEMENT (the “
Agreement ”) is entered into this 26th day of
July 2006 (the “ Effective Date ”) by and
between Santaris Pharma A/S , a Danish corporation having
its principal place of business at Hørsholm, Denmark
(“ Santaris ”), and Enzon Pharmaceuticals,
Inc. , a Delaware corporation having its principal place of
business at Bridgewater, New Jersey 08807 (“ Enzon
”). Santaris and Enzon may be referred to herein individually
as a “ Party ” or collectively, as the “
Parties ”.
BACKGROUND
Enzon is a pharmaceutical company
engaged in the discovery, development, marketing, manufacture and
distribution of pharmaceutical products. Santaris is a
pharmaceutical company engaged in the discovery, development and
manufacture of, among other molecules, RNA antagonists for the
treatment of oncology indications, and has developed RNA
antagonists referred to as SPC2968 and SPC3042. Santaris and Enzon
desire to enter into an arrangement pursuant to which (a) Enzon
will obtain rights to develop SPC2968 and SPC3042 for
commercialization in the Enzon Territory and provide data for use
by Santaris in the Santaris Territory, and (b) Santaris will design
and synthesize RNA antagonists directed against six (6) Targets (as
defined below) selected by Enzon, and each Party will have the
right to develop such antagonists and to commercialize such
antagonists pursuant to the terms of this Agreement.
The Parties agree as follows:
1. DEFINITIONS
1.1
“ Abandoned Target
” shall have the meaning set forth in Section 5.8.
1.2
“ Accepted LNA
Compound” shall have the meaning set forth in Section
5.4.
1.3
“ Acquisition
Transaction ” shall have the meaning set forth in Section
2.6.
1.4
“ Additional Targets
” shall have the meaning set forth in Section 5.2.
1.5
“ Affiliate ”
means a Person that controls, is controlled by or is under common
control with a Party. For the purposes of this Section, the word
“control” (including, with correlative meaning, the
terms “controlled by” or “under the common
control with”) means the actual power, either directly or
indirectly, through one or more intermediaries, to direct the
management and policies of such Person, whether by ownership of at
least 50% of the voting rights or other ownership interests of such
Person, by contract, or otherwise.
1.6
“ Business Day ”
means a day other than a Saturday, Sunday, bank or other public
holiday in the state of New Jersey or, to the extent applicable to
Santaris, Denmark.
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1.7
“ Chugai ” means
Chugai Pharmaceutical Co., Ltd.
1.8
“ Chugai License
” means that certain License Agreement, dated as of 30 June
2000, between Chugai and Exiqon.
1.9
“ Claim ” shall
have the meaning set forth in Section 12.1.
1.10 “ Collaboration Coordinator ”
shall have the meaning set forth in Section 4.1.
1.11 “ Combination Product ” means
a Product that contains a Selected LNA Compound and one or more
other therapeutically active ingredients. [**Redacted**]
.
1.12 “ Commercialize ” or
“ Commercialization ” means all activities that
are undertaken after approval of an MAA for a Product and that
relate to the commercial marketing and sale of such Product,
including advertising, marketing, promotion, distribution, and
Phase IV Trials.
1.13 “ Competing Product ” means
any pharmaceutical product, other than a Product, that contains as
an active ingredient any LNA compound, protein, small molecule
compound or other chemical or biological substance that
specifically and directly modulates the expression of an Enzon
Target.
1.14 “ Compound Acceptance Criteria
” shall have the meaning set forth in Section 5.4.
1.15 “ Compound Selection Process
” shall have the meaning set forth in Section 5.4.
1.16 “ Confidentiality Agreement ”
means the Confidentiality Agreement between the Parties dated
November 14, 2005.
1.17 “ Confidential Information ”
means all non-public, proprietary data or information and materials
received by either Party from the other Party pursuant to this
Agreement or the Confidentiality Agreement, subject to the
exceptions set forth in Section 9.2.
1.18 “ Conflict ” shall have the
meaning set forth in Section 5.1.
1.19 “ Control” or
“Controlled ” means, with respect to any
Know-How, Development Data or other intellectual property right
that a Party owns or has a license to such item or right, and has
the ability to grant a license or sublicense in or to such item or
right, without violating the terms of any agreement or other
arrangement with any Third Party.
1.20 “ Control Target ” means a
Target identified by the GenBank No. from the NCBI Database, or a
similar recognized database, selected by Enzon to serve as a
control for selecting specific LNA Compounds directed against the
Additional Targets.
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1.21 “ Cover ” or “
Covering ” means, on a country-by-country basis, that
the manufacture, use, import, offer for sale, or sale of a Product
(including any LNA Monomer or Selected LNA Compound contained
therein) would infringe a Valid Claim in such country.
1.22 “ Damages ” shall have the
meaning set forth in Section 12.1.
1.23 “ Develop ” or “
Development ” means the performance of all
non-clinical, clinical, process and formulation development and
regulatory activities of a Selected LNA Compound that are necessary
or useful to obtain Regulatory Approval of a Product.
1.24 “ Development Data ” means
all data generated by or for either Party in connection with the
Development of a Product or otherwise compiled or submitted in any
Regulatory Filing or otherwise relating to a Selected LNA Compound
or Product that is Controlled at any time during the Term by either
Party or any of its Affiliates, including all non-clinical,
chemistry, manufacturing and control, formulation, process and
clinical development and Phase IV Trial data.
1.25 “ Development Plan” shall
have the meaning set forth in Section 6.1(c) .
1.26 “ Discovery Program ” means
the research program conducted by the Parties under Sections 5.3
through 5.6 to identify and recommend Selected LNA
Compounds.
1.27 “ Diligent Efforts ” means
efforts that are not less than those efforts a Party makes with
respect to other products in its portfolio (but, in any event, not
less than the efforts that would be exerted by a reasonably prudent
and diligent biopharmaceutical company similarly situated to such
Party to accomplish similar objectives), taking into account, among
other things, medical and clinical considerations, the
product’s labeling (target or actual) and market potential,
financial return, competitive market conditions in the therapeutic
area, regulatory environment and other relevant factors at the time
such efforts are due. Diligent Efforts shall apply on a Selected
LNA Compound-by-Selected LNA Compound, and Product-by-Product
basis, and the failure to exercise Diligent Efforts with respect to
a particular Selected LNA Compound or a particular Product shall
not constitute a breach of either Party’s obligation to use
Diligent Efforts with respect to any other Selected LNA Compound or
Product.
1.28 “ EMEA ” shall have the
meaning set forth in Section 6.2(e) .
1.29 “ Enzon Know-How ” means all
Know-How and Inventions that (a) are Controlled by Enzon or its
Affiliates as of the Effective Date or acquired or developed by or
on behalf of Enzon or its Affiliates during the Term, and (b) (i)
are necessary or useful for the Development, manufacture or
Commercialization of LNA Monomers, oligonucleotides comprised of
one or more of such LNA Monomers, Selected LNA Compounds or
Products, or (ii) relate to any of the Enzon Targets and are
necessary or useful for the discovery of LNA Compounds (and, in
each such case, all Patents claiming any such Know How or
Inventions); excluding , in each such case, Enzon Pegylation
Technology, LNA Platform Technology and LNA Compound
Patents.
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1.30 “ Enzon Pegylation Know-How ”
means all Know-How and Inventions that (a) are (i) Controlled by
Enzon or its Affiliates as of the Effective Date or acquired or
developed or conceived or reduced to practice by or on behalf of
Enzon or its Affiliates during the Term or (ii) developed,
conceived or reduced to practice by Santaris or jointly by the
Parties or their Affiliates during the course of performing
activities under this Agreement, and (b) comprise or relate to
Pegylation but that are not specific to any Enzon Target, Selected
LNA Compound or Product.
1.31 “ Enzon Pegylation Patents ”
means any Patents that claim any Inventions included in Enzon
Pegylation Know How.
1.32 “ Enzon Pegylation Technology
” means the Enzon Pegylation Know-How and the Enzon
Pegylation Patents.
1.33 “ Enzon Quarter ” means each
of the three (3) month periods commencing January 1, April 1, July
1 and October 1 of each calendar year.
1.34 “ Enzon Target ” means the
Survivin Target, the Hif-1± Target, and any Additional
Target for which Enzon has paid Santaris the milestone payment set
forth in Section 7.2; provided, however, that a Target will
cease to be an Enzon Target if Enzon’s rights under this
Agreement to all Selected LNA Compounds modulating protein
synthesis by such Target have been terminated for any
reason.
1.35 “ Enzon Technology ” means
the Enzon Know-How and the Enzon Pegylation Technology.
1.36 “ Enzon Territory ” means all
countries and other geographic territories of the world except the
Santaris Territory; provided, that Japan shall be included
in the Enzon Territory subject to the terms of Section
3.1.
1.37 “ Exiqon ” means Exiqon
A/S.
1.38 “ Exiqon License ” means that
certain License Agreement between Exiqon and Santaris (as
successor-in-interest to Cureon A/S) date April 10, 2003, as
amended by an agreement dated April 29, 2005, and extended by the
agreements dated November 15, 2005 and June 20, 2006.
1.39 “ FDA ” means the United
States Food and Drug Administration, or any successor federal
agency thereto.
1.40 “ Field ” means use in humans
or animals for the prevention, treatment, cure, control or
mitigation of disease or other medical condition, and specifically
excludes all uses excluded, as of the Effective Date, under the
grants to Santaris under the Third Party Licenses.
1.41 “ Good Clinical Practices ”
or “ GCP ” means current Good Clinical Practices
as stated in any Laws or regulatory guidance from time to time,
including EC Directive 2001/20/EC, as amended, and 21 CFR Parts 50,
56, and 312 et seq ., and all FDA and ICH guidelines,
including the ICH Consolidated Guidelines on Good Clinical
Practices.
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1.42 “ Good Laboratory Practices ”
or “ GLP ” means current Good Laboratory
Practices as stated in any Laws or regulatory guidance from time to
time, including EC Directives 87/18 EEC, 88/320/EEC, and 1999/11/EC
and 21 CFR § 58 and all applicable FDA and ICH
guidelines.
1.43 “ Good Manufacturing Practices
” or “ GMP ” means current Good
Manufacturing Practices and standards as provided for (and as
amended from time to time) in European Community Directive
91/356/EEC (Principles and Guidelines of Good Manufacturing
Practice for Medicinal Products) and in the Current Good
Manufacturing Practice Regulations of the United States Code of
Federal Regulations (21 CFR §§ 210-211) in relation to
the production of pharmaceutical intermediates and active
pharmaceutical ingredients, as interpreted by ICH Harmonized
Tripartite Guideline ICH Q7A, Good Manufacturing Practice Guide for
Active Pharmaceutical Ingredients.
1.44 “ Governmental Authority ”
means any court, agency, department or other instrumentality of any
foreign, federal, state, county, city or other political
subdivision (including any supra-national agency such as in the
European Union).
1.45 “
Hif-1α Target ” means the human Hif-1±
gene [**Redacted**] .
1.46 “ ICH ” shall mean the
International Conference on Harmonization.
1.47 “ IND ” means an
Investigational New Drug Application filed with the FDA or the
equivalent clinical trial application or filing filed with any
equivalent agency or Governmental Authority outside of the United
States necessary to commence human clinical trials in such
jurisdiction, and including all regulations at 21 CFR § 312
et. seq. and equivalent foreign regulations.
1.48 “ Indemnified Party ” shall
have the meaning set forth in Section 12.4.
1.49 “ Indemnifying Party ” shall
have the meaning set forth in Section 12.4.
1.50 “ Invention ” means all
inventions, discoveries and improvements (whether or not
patentable) that are (a) Controlled by either Party or its
Affiliates as of the Effective Date or (b) acquired (through
license or otherwise) or developed, conceived or reduced to
practice during the Term by any employees, consultants or
contractors of either Party or any of its Affiliates (or other
persons obligated to assign such inventions, discoveries and
improvements to a Party or one of its Affiliates).
1.51 “ Joint Discovery Project Team
” or “JDPT” shall have the meaning set
forth in Section 4.3.
1.52 “ Joint Steering Committee ”
or “JSC” shall have the meaning set forth in
Section 4.1.
1.53 “ Know-How ” means any
non-public, proprietary information and other data, instructions,
processes, methods, formulae, materials, expert opinions, results,
databases, inventions, practices, techniques, specifications, and
know-how, including pharmacological,
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biological, chemical,
biochemical, toxicological, pharmaceutical, physical, analytical,
clinical, safety, manufacturing, quality control data, and
stability data.
1.54 “ Launch ” means the first
shipment of a Product in commercial quantities for commercial sale
by Enzon, its Affiliates or its Marketing Sublicensees to an
unaffiliated Third Party in a country after receipt by Enzon of the
first Regulatory Approval for such Product in such
country.
1.55 “ Law ” or “
Laws ” means all applicable laws, statutes, rules,
regulations, orders, codes, judgments and/or ordinances of any
Governmental Authority, or listing authority (e.g., New York Stock
Exchange, Nasdaq National Stock Market or Copenhagen Stock
Exchange).
1.56 “ LNA Compound ” means any
oligonucleotide that is comprised of one or more LNA Monomers that
selectively modulates protein synthesis by an Enzon
Target.
1.57 “ LNA Compound Patent ” means
any Patent claiming the composition of matter of an LNA Compound or
use of an LNA Compound for a medical use, including the Patents
listed on Schedule 1.57 .
1.58 “ LNA Monomer ” means any of
the [**Redacted**] compositions claimed under any of the
[**Redacted**] .
1.59 “ LNA Platform ” means the
use of LNA Monomers and locked nucleic acid single-stranded chains
of nucleotides to target and modulate specific protein expressions
within a cell and the methods of design, selection, identification,
synthesis, manufacture and screening of such nucleotides and LNA
Monomers.
1.60 “ LNA Platform Know-How ”
means all Know-How and Inventions that (a) are (i) Controlled by
Santaris or its Affiliates as of the Effective Date or acquired or
developed or conceived or reduced to practice by or on behalf of
Santaris or its Affiliates during the Term or (ii) developed,
conceived or reduced to practice by Enzon or jointly by the Parties
or their Affiliates during the course of performing activities
under this Agreement, and (b) comprise or relate to LNA Platform
but that are not specific to any Enzon Target, Selected LNA
Compound or Product.
1.61 “ LNA Platform Patents ”
means any Patents that claim any Inventions included in LNA
Platform Know How, including the existing Patents listed on
Schedule 1.61, but excluding LNA Compound
Patents.
1.62 “ LNA Platform Technology ”
means the LNA Platform Know-How and the LNA Platform
Patents.
1.63 “ MAA ” means a new drug
application, marketing authorization application, notice of
submission, biologic license application or other application
seeking approval from a Regulatory Authority to sell a Product in a
country or other geographic territory.
1.64 “ Marketing Sublicensee
” means a Third Party to whom Enzon grants a sublicense under
any rights licensed hereunder to distribute, promote the sale of or
sell the
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Products, or otherwise grants
rights to distribute, promote or sell the Products (other than
wholesalers and physical distributors).
1.65 “ Net Sales ”
means:
(a)
with respect to each Product, the
amount invoiced by Enzon, its Affiliates or its Marketing
Sublicensees, for sales of Products to Third Parties, and less the
following deductions: (i) sales returns and allowances actually
paid, granted or accrued, including trade, quantity and cash
discounts; (ii) credits and refunds in connection with price
adjustments, billing errors, rejected goods, damaged or defective
goods, recalls, and returns actually paid, granted or accrued;
(iii) rebates, chargeback rebates, reimbursements or similar
payments, including any fees granted or given to wholesalers or
other distributors, buying groups, health care insurance carriers,
governmental or regulatory authority, government-subsidized program
or managed care organization or other institutions, and adjustments
arising from consumer discount programs actually paid, granted or
accrued,; and (iv) to the extent reflected in such invoice, customs
or excise duties, sales tax, consumption tax, value-added tax, and
other taxes (except income taxes) or duties relating to sales, and
freight and insurance (to the extent that Enzon bears the cost of
freight and insurance for such a Product).
(b)
Net Sales of any Product that is
sold as a Combination Product in a particular country will be
determined by multiplying the total Net Sales of the Combination
Product by the fraction A/(A+B), where A is the average invoice
price per unit dose of the Product when sold separately in finished
form in such country and B is the sum of the average invoice prices
of the products containing the other active ingredients in the
Combination Product when sold separately in finished form in such
country. If such average invoice price cannot be determined for
both the Product and the product(s) containing such other
ingredient(s), the Parties will negotiate in good faith regarding
the calculation of Net Sales for the applicable Combination
Product, based on the relative value contributed by each
component.
(c)
Each of the foregoing deductions
shall be determined as incurred in the ordinary course of business
in type and amount consistent with good industry practice and in
accordance with generally accepted accounting principles in the
United States on a basis consistent with Enzon’s audited
consolidated financial statements. All deductions for payments in
respect of sales to any Governmental Authority, any
government-subsidized program, or any managed care or similar
organization, which deductions apply collectively to multiple
pharmaceutical products, shall be fairly allocated to the amounts
invoiced for Products.
1.66 “ Nominated Target ” shall
have the meaning set forth in Section 5.1.
1.67 “ Patent ” means: (a) an
issued, unexpired patent (including inventor’s certificate),
including any substitution, extension, supplementary protection
certificates, registration, confirmation, reissue, reexamination,
renewal or any like filing thereof; or (b) any pending patent
application, including any continuation, division or
continuation-in-part thereof and any provisional
application.
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1.68 “ Pegylation ” with a
correlative meaning for “ Pegylated ,” means the
conjugation (covalent chemical bonding) of PEG (including
conjugation through linking groups) with or to other materials,
including single chain antibodies. “Pegylation” will
include the synthesis, derivatization, characterization, and
modification of PEG for such purposes, together with the synthesis,
derivatization, characterization, and modification of the raw
materials and intermediates for the manufacture of PEG reagents or
products incorporating such PEG reagents by means of conjugation,
and all methods of making and using each and all of the foregoing.
As used in this definition, “ PEG ” means
polyethylene glycol and derivatives thereof, including
methoxy-polyethylene glycol.
1.69 “ Pegylated Product ” means a
pharmaceutical product that contains a Pegylated Selected LNA
Compound.
1.70 “ Pegylated Selected LNA Compound
” means a Pegylated form of a Selected LNA
Compound.
1.71 “ Person ” means an
individual, corporation, partnership, company, joint venture,
unincorporated organization, limited liability company or
partnership, sole proprietorship, association, bank, trust company
or trust, whether or not legal entities, or any governmental entity
or agency or political subdivision thereof.
1.72 “ Phase II Trial ” means a
clinical trial of a Product on patients, the principal purpose of
which is to establish clinical proof of principle and to obtain
sufficient information about such Product’s safety and
efficacy to permit the design of further clinical trials, and that
would satisfy the requirements of 21 CFR § 312.21(b)
.
1.73 “ Phase III Trial ” means a
clinical trial that provides for a pivotal human clinical trial of
a Product, which trial is designed to: (a) establish that a Product
is safe and efficacious for its intended use; (b) define warnings,
precautions and adverse reactions that are associated with the
Product in the dosage range to be prescribed; (c) support
Regulatory Approval of such Product; and (d) that would satisfy the
requirements of 21 CFR § 312.21(c) .
1.74 “ Phase IV Trial ” means
clinical trial of a Product commenced in a particular country after
Regulatory Approval for such Product in such country in order to
(a) support Commercialization of the Product, or (b) fulfill a
post-approval study commitment or undertaking imposed by the
applicable Regulatory Authority in such country.
1.75 “ Product ” means any
pharmaceutical product that contains a Selected LNA Compound.
Product shall include any Pegylated Product.
1.76 “ Product Trademarks ” means
one or more trademarks or logos that are used for the marketing and
sale of a Product. Product Trademark does not include the logo or
tradename of either Party or the trademark or tradename of another
product sold by either Party.
1.77 “ Regulatory Approval ” means
any and all approvals (including supplements, amendments, pre- and
post-approvals, and pricing and reimbursement approvals even if
such pricing and reimbursement approvals are not legally required
to sell the applicable Product),
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licenses, registrations or
authorizations of any national, supra-national (e.g., the European
Commission or the Council of the European Union), regional, state
or local regulatory agency, department, bureau, commission, council
or other governmental entity, that are necessary (except for
pricing and reimbursement approvals, which need not be necessary)
for the manufacture, distribution, use or sale of a Product in a
regulatory jurisdiction.
1.78 “ Regulatory Authority ”
means any Governmental Authority with responsibility for granting
any licenses or approvals necessary for the marketing and sale of
pharmaceutical products, including the FDA and any equivalent
regulatory authority of countries of the European Union and Japan,
and where applicable any ethics committee or any equivalent review
board.
1.79 “ Regulatory Filing ” means a
MAA, IND any other filings required by Regulatory Authorities
relating to the Development or Commercialization of any
Product.
1.80 “ Representatives ” shall
have the meaning set forth in Section 12.1.
1.81 “ Reservation Period ” shall
have the meaning set fort in Section 5.2.
1.82 “ Royalty Term ” means on a
country-by-country and Product-by-Product basis, the period ending
upon the last to expire Valid Claim of an LNA Platform Patent or an
LNA Compound Patent, in each case, Covering such Product in the
country of sale of such Product, in any event, with respect to each
Product, not to exceed twenty one (21) years from the first filing
of the first LNA Compound Patent covering the Selected LNA Compound
contained in such Product. With respect to the Survivin Target, US
Provisional Patent Application No. 60/446372, filed on February 10,
2003, is such LNA Compound Patent and in connection therewith the
Royalty Term shall expire no later than February 10, 2024, and with
respect to the Hif-1a Target, US Provisional Patent Application No.
60/370126, filed on April 5, 2002, is such first LNA Compound
Patent and in connection therewith the Royalty Term shall expire no
later than April 5, 2023.
1.83 “ Santaris Know-How ” means
all Know-How and Inventions that are (a) Controlled by Santaris or
its Affiliates as of the Effective Date or acquired or developed by
or on behalf of Santaris or its Affiliates during the Term, and (b)
necessary or useful for the Development, manufacture or
Commercialization of LNA Monomers contained in Selected LNA
Compounds, Selected LNA Compounds or Products (and, in each such
case, all Patents claiming any such Know How or Inventions);
excluding , in each such case, Enzon Pegylation Technology,
LNA Platform Technology and LNA Compound Patents.
1.84 “ Santaris Technology ” means
the Santaris Know-How and the LNA Platform Technology.
1.85 “ Santaris Territory ” means
the countries comprising Europe that are listed in Schedule
1.85 .
1.86 “ Selected LNA Compounds ”
means SPC2968, SPC3042 and such Accepted LNA Compounds that are
selected by Enzon for Development under Section 5.5, and any
[**Redacted**] of such LNA Compound.
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1.87 “ SPC 2968 ” means the
oligonucleotide now being developed by Santaris as an antagonist of
the Hif-1α Target and which is further described in
Schedule 1.87 .
1.88 “ SPC 3042 ” means the
oligonucleotide now being developed by Santaris as an antagonist of
the Survivin Target a`nd which is further described in Schedule
1.88 .
1.89 “ Sponsoring Party ” shall
have the meaning set forth in Section 6.1(d)(iii).
1.90 “ Survivin Target ” means the
human Survivin gene [**Redacted**] .
1.91 “ Target ” means the pre-mRNA
and any mature mRNAs arising from a human gene or any of its
naturally occurring allelic variants.
1.92 “ Target Submission Materials
” means, in respect of a Target submitted to Santaris, the
following information: (a) the Genebank accession number for the
Target, and an electronic file with the DNA sequence; (b)
information on known allelic forms of the gene; (c) information on
known mRNA splice-variants; (d) instructions to Santaris as to how
information under (b) and (c) should be taken into account in the
process of designing LNA oligonucleotides against the Target; (e)
the Genebank accession number for the Control Target, and an
electronic file with the DNA sequence; (f) any information known or
in the possession of Enzon or its Affiliates in regard to cell
lines that express both the Target and the Control Target and PCR
protocols for amplifying said Target and Control Target; (g)
information on any patents and other intellectual property rights
held by Enzon or a Third Party that Enzon believes, in its
reasonable judgment, should be taken into account in the design of
the LNA oligonucleotide against the Target; and (h) available
information, if any, concerning the expected clinical indications
and any market analysis for Products for such Target.
1.93 “ Term ” shall have the
meaning set forth in Section 10.1.
1.94 “ Third Party ” means a
person or entity other than Enzon, Santaris or an Affiliate of
either of them.
1.95 “ Third Party Claim ” shall
have the meaning set forth in Section 12.4.
1.96 “ Third Party Licenses ”
means the license agreements entered into by Santaris that are
listed on Schedule 1.96 .
1.97 “ University of Copenhagen License
” means that certain agreement between Santaris and the
Laboratory of Experimental Oncology, University of Copenhagen,
dated August 23, 2004.
1.98 “ Valid Claim ” means a claim
of any issued, unexpired LNA Platform Patent Controlled by Santaris
or its Affiliates or an LNA Compound Patent that has not been
dedicated to the public, disclaimed, abandoned or held invalid or
unenforceable by a court or other body of competent jurisdiction in
an unappealed or unappealable decision, and that has not been
explicitly disclaimed, or admitted by Santaris in writing to be
invalid or unenforceable or of a scope not covering Products
through reissue, disclaimer or otherwise.
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2. LICENSES AND RELATED RIGHTS
2.1
Licenses to Enzon
. Subject to the terms of this
Agreement, Santaris grants to Enzon under the Santaris Technology,
Development Data, Regulatory Approvals and Santaris’ rights
in any LNA Compound Patents the following:
(a)
the exclusive (even as to Santaris)
license, including the right to sublicense, to Develop, import,
offer for sale, sell and otherwise Commercialize Selected LNA
Compounds and Products in the Field in the Enzon
Territory;
(b)
the exclusive (even as to Santaris)
license, including the right to sublicense, to manufacture or have
manufactured anywhere in the world Selected LNA Compounds and
Products for the sole purpose of selling, offering for sale and
otherwise Commercializing such Selected LNA Compounds and Products
in the Enzon Territory; Enzon may so manufacture such Selected LNA
Compounds and Products only from LNA Monomers supplied by Santaris
(or a Third Party designated by Santaris) or manufactured by Enzon
pursuant to the license granted under Section 2.1(c);
and
(c)
the exclusive (except as to
Santaris, its Affiliates and licensees and each of their
contractors) license, without the right to sublicense, to
manufacture anywhere in the world LNA Monomers for use in Selected
LNA Compounds.
2.2
Licenses to Santaris
. Subject to the terms of this
Agreement, Enzon grants to Santaris under the Enzon Technology,
Development Data, Regulatory Approvals and Enzon’s rights in
any LNA Compound Patents the following royalty-free
licenses:
(a)
the exclusive (even as to Enzon)
license, including the right to sublicense, to Develop, import,
offer for sale, sell and otherwise Commercialize Selected LNA
Compounds and Products in the Field in the Santaris Territory;
provided, that, in each such case, the license grant shall
not include the Enzon Pegylation Technology unless and until Enzon
elects, in its sole discretion, to Pegylate a Selected LNA Compound
and/or Product pursuant to Section 6.1(d)(i), and then the license
to the Enzon Pegylation Technology shall only be with respect to
such Pegylated Selected LNA Compound and/or Pegylated
Product;
(b)
the exclusive (even as to Enzon)
license, with the right to sublicense, to manufacture anywhere in
the world Selected LNA Compounds and Products (other than Pegylated
Selected LNA Compounds and Pegylated Products) for the sole purpose
of selling, offering for sale and otherwise Commercializing such
Selected LNA Compounds and Products in the Santaris
Territory;
(c)
the exclusive license, without the
right to sublicense, to manufacture anywhere in the world Pegylated
Selected LNA Compounds and Pegylated Products for the sole purpose
of selling, offering for sale and otherwise Commercializing such
Pegylated Selected LNA Compounds and Pegylated Products in the
Santaris Territory; provided, that, in each such case, the
license grant shall not include the Enzon Pegylation Technology
unless and until Enzon elects, in its sole discretion, to Pegylate
a Selected LNA Compound and/or Product pursuant to Section
6.1(d)(i), and then the license to the Enzon Pegylation
Technology
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shall only be with respect to
such Pegylated Selected LNA Compound and/or Pegylated Product;
and
(d)
the perpetual, exclusive (except as
granted to Enzon pursuant to Section 2.1(c)) license, including the
right to sublicense, to manufacture anywhere in the world LNA
Monomers and oligonucleotides comprised of one or more of such LNA
Monomers, and to develop, use, import, sell and otherwise
commercialize anywhere in the world such LNA Monomers and such
oligonucleotides; provided , that such license shall not
include any rights under any Enzon Peglyation
Technology.
The licenses granted to Santaris
under paragraphs (a), (b) and (c) above are not subject to
expiration or termination for any reason, except to the extent
Enzon terminates this Agreement under Section 10.3 or terminates
such licenses under Section 10.4(c)(ii); provided, that upon
expiration of the LNA Compound Patent claiming a Product in a
country in the Santaris Territory, the licenses granted under
Sections 2.2(a), (b) and (c) in respect of such country and Product
shall convert to perpetual, non-exclusive licenses.
2.3
Rights in Bankruptcy
. All rights and licenses granted
under or pursuant to this Agreement by the Parties 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 except as may otherwise be
required by any provision under Danish insolvency Laws. 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 to the extent
not otherwise mandatorily provided for under Danish insolvency
Laws. 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, or commencement of insolvency
proceeding by or against a Party under the Danish Bankruptcy Act as
the case may be, the Party hereto that is not a Party to such
proceeding 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-subject Party’s possession, will be promptly
delivered to it (a) upon any such commencement of a bankruptcy
proceeding upon the non-subject Party’s written request
therefore, unless the Party subject to such proceeding continues to
perform all of its obligations under this Agreement or (b) if not
delivered under clause (a) above, following the rejection of this
Agreement by or on behalf of the Party subject to such proceeding
upon written request therefore by the non-subject Party. Santaris
agrees not to interfere with Enzon’s exercise under any
bankruptcy code of rights and licenses to intellectual property
licensed hereunder and embodiments thereof in accordance with this
Agreement and agrees to use commercially reasonable efforts to
assist Enzon to obtain such intellectual property and embodiments
thereof in the possession or control of Third Parties as reasonably
necessary or useful for Enzon to exercise such rights and licenses
in accordance with this Agreement. The Parties hereto acknowledge
and agree that all payments by Enzon to Santaris hereunder other
than the payments pursuant to Article 7 do not constitute royalties
within the meaning of United States Bankruptcy Code
§365(n).
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2.4
Sublicenses
.
(a)
Enzon . Enzon may sublicense the rights granted under
Sections 2.1(a) and 2.1(b) without the prior written consent of
Santaris; provided, that (a) in the case of each such
sublicense, (i) Enzon shall be liable to Santaris as if Enzon is
exercising such sublicensed rights itself under this Agreement,
including all payment, diligence, access to Development Data and
other information, rights in Know-How and other intellectual
property rights and reporting obligations; and (ii) Enzon shall
provide all reasonable assurances that its sublicensees comply with
confidentiality, indemnity, reporting, audit rights, access to data
(including Development Data and regulatory filings), and
information obligations comparable to those set forth in this
Agreement; and (b) in the case of a sublicense to sell the Product
in the United States or Japan, such Marketing Sublicensees shall
possess such capabilities, personnel and other resources and
experience as may be required to allow Enzon to satisfy its
obligations hereunder to use Diligent Efforts to Commercialize such
Product in such country.
(b)
Santaris . Santaris may sublicense the rights granted
under Section 2.2(a), 2.2(b) and 2.2(d) without the prior written
consent of Enzon; provided, that, in the case of each such
sublicense, (i) Santaris shall be liable to Enzon as if Santaris is
exercising such sublicensed rights itself under this Agreement,
including access to Development Data and other information, rights
in Know-How and other intellectual property rights and reporting
obligations; and (ii) Santaris shall provide all reasonable
assurances that its sublicensees comply with confidentiality,
indemnity, reporting, access to data (including Development Data
and regulatory filings), and information obligations comparable to
those set forth in this Agreement.
(c)
Notice . Each Party shall provide written notice and
copy of each license or sublicense relating to this Agreement, a
Selected LNA Compound and/or a Product promptly after execution of
any such license or sublicense agreement; provided, that the
terms that do not relate to the licensed or sublicensed rights
relating to this Agreement, Selected LNA Compound and/or Product
(including such terms referred to in paragraph (a) and (b) above)
and the financial terms therein may be redacted. All sublicenses
granted in violation of this Section 2.4 are void.
2.5
Exclusivity
. During the conduct of the
Discovery Program and the Royalty Term in each country, neither
Enzon and its Affiliates nor Santaris and its Affiliates shall,
except pursuant to this Agreement, directly or indirectly, by
itself or with any Third Party, develop, manufacture commercial
quantities of, promote the sale of or sell in such country any
Competing Product; provided, that after the
[**Redacted**] anniversary of the First Commercial Sale of a
Product and subject to the licenses granted hereunder, each Party
and its Affiliates may conduct research and development activities
with respect to the Enzon Target of such Product. For the avoidance
of doubt, once all of Enzon’s rights under this Agreement to
all Selected LNA Compounds modulating protein synthesis by an Enzon
Target have been terminated for any reason, such Target shall
deemed no longer to be an Enzon Target.
2.6
Acquisition of Competing
Product . Notwithstanding
the provisions of Section 2.5, which provisions shall not be deemed
breached as a result of an acquisition or merger described in this
Section 2.6 (unless such acquisition or merger involves a Third
Party whose sole pharmaceutical product is a Competing Product), if
Enzon acquires a Competing Product through an acquisition of the
whole or substantially the whole of the business or
assets
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of another Person or through a
merger with another Person (each, an “ Acquisition
Transaction ”), then Enzon shall, within ninety (90) days
from the date of the closing of such Acquisition Transaction,
notify Santaris of such Acquisition Transaction and as to whether
Enzon (i) is required by a Governmental Authority to, or elects to,
divest its right to develop or commercialize such Competing Product
or (ii) elects to retain such Competing Product. If Enzon is
required or elects to divest its interest in such Competing
Product, then Enzon shall use reasonable efforts to identify a
Third Party purchaser to whom Enzon will divest its interest in
such Competing Product and to enter into a definitive agreement
with such Third Party for such divestiture as soon as reasonably
practicable under the circumstances; provided , however,
that it is understood that nothing shall limit Enzon’s right
to receive licensing fees, royalty payments, or any other form of
compensation from such Third Party. If Enzon fails to enter into a
definitive agreement with a Third Party to divest such Competing
Product within [**Redacted**] after the closing of the
acquisition or merger for which Enzon has provided Santaris with
notice, or if Enzon elects not to divest such Competing Product,
then Enzon will pay royalties to Santaris on [**Redacted**]
as though such product were a Product.
2.7
No Other Rights
. Except as specifically provided
herein, no license is granted under this Agreement by either Party
to the other Party, either expressly or by implication, under any
trademarks, patent rights, information, know-how, or other
intellectual property right owned or Controlled by such
Party.
2.8
Exchange of
Information . Promptly
after execution of this Agreement, the Parties shall establish a
procedure and timeline for the exchange of Santaris Technology and
Enzon Technology, including from time to time throughout the Term
newly-developed or acquired Santaris Technology and Enzon
Technology, to the extent reasonable in connection with each
Party’s performance of its obligations and exercise of its
rights hereunder.
3. THIRD PARTY LICENSES
3.1
Exiqon/Chugai
. Enzon acknowledges that Santaris,
as a sublicensee through Exiqon under the Chugai License, is
subject to an obligation in respect of rights to commercialize the
Products in Japan [**Redacted**]:
[**Redacted**]
[**Redacted**]
.
3.2
Compliance
. Each of the licenses granted to
Enzon under the Santaris Technology licensed to Santaris under
Third Party Licenses is subject to (a) the rights reserved under
one or more of such Third Party Licenses, including non-exclusive
licenses to use for internal, non-commercial research purposes and
the non-exclusive licenses expressly described therein and excluded
from the grants to Santaris; and (b) the other terms and conditions
of such Third Party Licenses that are expressly required to apply
to a sublicense thereunder, as contained in the copies of such
Third Party Licenses provided to Enzon prior to the date
hereof.
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4. COLLABORATION GOVERNANCE
4.1
Joint Steering
Committee . The Parties
shall establish a Joint Steering Committee or “JSC
”, which shall be comprised of six (6) members, with three
(3) representatives designated by each Party. Members of the JSC
may be represented at any meeting by a designee appointed by such
member for such meeting. Each Party shall be free to change its
representative members on notice to the other Party. One of each
Party’s representatives on the JSC shall be designated by
such Party a “ Collaboration Coordinator
”.
4.2
Project Teams
. Enzon shall establish project
teams for the Development of each of SPC2968 and SPC3042 and each
Additional Target. In order to facilitate the sharing of
information between Enzon and Santaris, each of Enzon’s
internal project teams shall endeavor to meet on at least a monthly
basis, and up to three (3) representatives of Santaris will be
invited to participate telephonically or in person in such Enzon
project team meetings.
4.3
Joint Discovery Project
Team . The Parties shall
establish a “ Joint Discovery Project Team ” or
“ JDPT ”, comprised of two (2) representatives
of each Party, which shall be a subcommittee of the JSC and report
to it. The JDPT shall be responsible for monitoring, facilitating
and coordinating the Discovery Program and shall organize such
meetings as are appropriate and necessary between the Parties to
coordinate and complete the Discovery Program successfully. Each
Party may designate one of its representatives on the JDPT also to
be a representative member of the JSC.
4.4
Function of Joint Steering
Committee . The JSC
shall be responsible for reviewing and discussing: (i) past and
current material Development activities, and (ii) as appropriate,
future Development activities in the Santaris Territory and the
Enzon Territory for Products. The JSC shall have no decision-making
authority. Among other things, the JSC may:
(a)
review each Party’s
pre-clinical and clinical Development Plans from time to time; and
review the progress made in the Development of SPC2968, SPC3042,
and other Selected LNA Compounds;
(b)
foster the collaborative
relationship between the Parties;
(c)
facilitate all required technology
transfer;
(d)
review scientific publications and
public scientific presentations relating to the
Products;
(e)
such other matters as the Parties
may assign to the JSC from time to time;
(f)
monitor progress of the Discovery
Program and timely transfer of LNA Compounds and pre-clinical
development; and
(g)
attempt to resolve all disputes
between the Parties as provided in Section 13.1 but subject to
Section 10.4(c)(ii) .
4.5
Meetings of the JSC
. The JSC shall meet on an
approximately quarterly schedule, either by telephone conference,
videoconference, or in person. In person meetings will take place
at alternating sites – Bridgewater or Piscataway, New Jersey
(USA) and Hørsholm,
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Denmark, unless otherwise agreed
upon by the Parties. Enzon shall serve as the “host” of
the first JSC meeting, and the role of host will alternate
thereafter between the Parties. The JSC meetings will be convened
and chaired by the Collaboration Coordinator of the Party that is
the host of the meeting, and such individual shall be responsible
for all minutes. Other representatives of either Party may also
attend any of such meetings. The JSC shall keep accurate minutes of
its meetings, including all proposals or actions recommended or
taken. Drafts of the minutes shall be delivered to the other
Party’s Collaboration Coordinator promptly after the meeting.
The non-hosting Party’s Collaboration Coordinator shall
approve such minutes or state his/her objections in writing within
five (5) days following delivery. The Collaboration Coordinators
shall meet or engage in telephone or video conferences as necessary
and appropriate and at the reasonable request of either Party.
L
5. TARGET SELECTION AND DISCOVERY
PROGRAM
5.1
Enzon Right to Submit Targets;
Target Submissions .
(a)
Within three (3) Business Days after
the Effective Date, Enzon shall nominate in writing to Santaris
[**Redacted**] Targets (“ Nominated Targets
”) for the Discovery Program and provide the Target
Submission Materials specified in clause (a) of the definition
thereof for each such Target and confirm that Enzon is not a party
to any contract that would prevent either Party from exercising any
of the rights granted hereunder with respect to such Target. Within
three (3) Business Days after such submission, Santaris shall
notify Enzon in writing if Santaris opposes the nomination of any
of the Nominated Targets on grounds that such Nominated Target is
subject to a previously existing active Santaris internal research
program or a previously existing written agreement with a Third
Party that would prevent Santaris from granting rights thereto (in
each case, a “ Conflict ”). If Santaris does not
so notify Enzon that there is a Conflict with any of the Nominated
Targets within such three (3) Business Day period, then each
Nominated Target shall be deemed to be confirmed and accepted by
Santaris. If Santaris does so notify Enzon that there is a Conflict
with any such Nominated Target within such three (3) Business Day
period, then such opposed Nominated Target shall be replaced by a
new Nominated Target designated by Enzon in writing to Santaris
within five (5) Business Days after notice of such Conflict (or
within five (5) Business Days after the confirmation by an
independent law firm of such Conflict as described below). Within
three (3) Business Days after the designation of any replacement
Nominated Target, Santaris shall notify Enzon in writing if
Santaris opposes the nomination of such replacement Nominated
Target on the grounds that a Conflict exists, and the procedures of
the two immediately preceding sentences shall apply with respect to
such replacement Nominated Target. Such procedures shall continue
to apply until there are [**Redacted**] accepted and
confirmed Nominated Targets. Promptly after acceptance and
confirmation of each Nominated Target, Enzon shall provide to
Santaris the applicable Target Submission Materials that were not
previously provided.
(b)
Enzon shall have the right to
request that an independent U.S. law firm selected by Enzon and
reasonably acceptable to Santaris confirm the existence of the
Conflict. Such law firm shall not have any current or prior
representation of either Party. The Parties shall use their
commercially reasonable efforts to engage such law firm within
three (3) Business Days after such request. Such request must be
made by Enzon in writing to Santaris
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within three (3) Business Days
after notice by Santaris to Enzon of such Conflict. Santaris shall
provide as promptly as practicable (but in no event later than the
five (5) Business Days) to such law firm such records and
documentation as may reasonably be required for such law firm to
confirm that an appropriate basis for the Conflict exists. Such law
firm shall make its determination as to whether a Conflict exists
as promptly as practicable after the receipt of such records and
documentation. If such law firm determines that no Conflict exists,
then such Nominated Target shall be deemed confirmed and accepted
by Santaris. The determination of such law firm shall be conclusive
and binding on the Parties. The fees of such law firm shall be
borne equally by the Parties.
5.2
Target Reservation
.
(a)
From the date a Nominated Target is
confirmed and accepted up to and including the day that is
[**Redacted**] days after the Effective Date (the “
Reservation Period ”), Santaris will not grant to any
Third Party any rights to such Nominated Target, or otherwise enter
into any agreement or arrangement that would prevent Santaris from
granting exclusive rights to any such Nominated Target to Enzon. On
or prior to the last day of the Reservation Period, Enzon shall
designate six (6) Targets for generation and delivery of LNA
Compounds (the “ Additional Targets ”) and shall
make the payment referred to in Section 7.2. Such Additional
Targets may be selected from the confirmed and accepted Nominated
Targets or from any other Targets; provided that such other
Targets are not opposed by Santaris in writing within three (3)
Business Days after such designation as a result of a Conflict; and
provided , further, however, Santaris will be free to grant
to Third Parties rights to any Target other than the
[**Redacted**] confirmed and accepted Nominated Targets
during the Reservation Period.
(b)
Enzon shall only designate
Additional Targets for which it has conducted a worldwide analysis
of the intellectual property relating to the freedom to operate
with respect to such Additional Target and for which, in
Enzon’s sole discretion, such analysis reflects that there
exists an acceptable freedom to operate that is not
disproportionately adverse in the Santaris Territory as compared to
the Enzon Territory. Enzon shall also disclose to Santaris a
summary of the results of such analysis. Santaris hereby
acknowledges and agrees that (i) such analysis will be provided
only for Santaris’s convenience and none of Santaris or its
Affiliates, licensees or contractors shall be entitled to rely upon
such analysis for any other purpose, (ii) neither Enzon nor any of
its Affiliates makes any representations or warranties as to the
accuracy, completeness or sufficiency of the analysis, and (iii)
neither Enzon nor any of its Affiliates shall have any liability
(whether in contract, in equity, in tort or otherwise) to Santaris
or its Affiliates, licensees or contractors related to such
analysis. Similarly, Enzon hereby acknowledges and agrees that (A)
it assumes sole responsibility for designating any Additional
Target, (B) neither Santaris nor any of its Affiliates makes any
representations or warranties as to whether the use of any
Additional Target is free of any patent or other intellectual
property rights of Third Parties, and (C) neither Santaris nor any
of its Affiliates shall have any liability (whether in contract, in
equity, in tort or otherwise) to Enzon or its Affiliates, licensees
or contractors related to the use of any Additional Target. If at
the end of the Reservation Period, Enzon designates an Additional
Target that was not one of the Nominated Targets and as a result of
a Conflict Santaris is unable to accept such Additional Target,
Enzon shall have an additional fifty (50) days to designate an
Additional Target that is
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not subject to a Conflict. After
the expiration of 150 days after the Effective Date, Enzon shall
have no further rights to designate Additional Targets without the
consent of Santaris.
5.3
Generation and Delivery of LNA
Compounds . Following the
designation of the Additional Targets, Santaris shall then, at its
sole cost and expense, use its Diligent Efforts to design,
identify, synthesize, screen and select in cell culture LNA
Compounds that meet the applicable Compound Acceptance Criteria and
to generate and deliver to Enzon LNA Compounds for all Additional
Targets in roughly equal intervals within a [**Redacted**]
period.
5.4
Compound Selection
. Each LNA Compound delivered by
Santaris to Enzon will be identified by Santaris pursuant to the
selection process set forth in Schedule 5.4A (the “
Compound Selection Process ”), and shall satisfy the
acceptance criteria set forth for such Additional Target in
Schedule 5.4B (the “ Compound Acceptance
Criteria ”). Following the Compound Selection Process,
Santaris shall provide Enzon with a written report detailing the
results of such process, including its design, synthesis and
screening efforts, as well as the sequences of any and all LNA
Compounds resulting from such process that meet the Compound
Acceptance Criteria. Upon delivery by Santaris of at least
[**Redacted**] of substance for at least two (2) LNA
Compounds meeting the applicable Compound Acceptance Criteria for
an Additional Target (each of which is an “ Accepted LNA
Compound ”), Enzon shall pay the amount required under
Section 7.3. Enzon shall have the right to synthesize or have
synthesized by a Third Party, at Enzon’s sole cost,
additional quantities of any and all LNA Compounds delivered by
Santaris, as well as quantities of any additional LNA Compounds
disclosed in the written report provided by Santaris pursuant to
this Section 5.4 that also meets the applicable Compound Acceptance
Criteria (each such additional LNA compound synthesized by or for
Enzon, if any shall also be an Accepted LNA Compound).
5.5
In-Vitro and In-Vivo Profiling
by Enzon . Enzon shall
conduct such additional in vitro and in vivo testing
as it deems appropriate in its sole discretion to select Accepted
LNA Compounds for further Development. Enzon shall use its Diligent
Efforts to determine, within [**Redacted**] after delivery
of the Accepted LNA Compound against each Additional Target from
Santaris, whether it wishes to select any Accepted LNA Compound to
commence pre-clinical toxicology studies. Each such Accepted LNA
Compound selected by Enzon in writing to Santaris shall be
designated a “ Selected LNA Compound
.”
5.6
Additional Santaris
Activities . Santaris
shall, at Enzon’s request, conduct such additional work or
provide such additional quantities of Selected LNA Compounds as may
be agreed by the Parties, to assist Enzon in its testing activities
referred to in Section 5.5. The costs of such additional work or
supply shall by paid by Enzon in accordance with commercially
reasonable terms.
5.7
Discovery Program
Procedures .
(a)
Reports . Periodically during the Discovery Program, and
upon the reasonable request of the other Party, each Party shall
provide such other Party’s representatives on the JSC with a
written summary report that shall summarize the work
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performed on the Discovery
Program. Notwithstanding the foregoing, under no circumstances
shall either Party be required to provide such summary reports more
than twice per calendar year.
(b)
Records . Each Party shall maintain lab notebooks and
other records, in sufficient detail for patent and regulatory
purposes, that shall be complete and accurate and shall properly
reflect all work done and results achieved in the performance of
the Discovery Program. Each Party shall have the right, which shall
be exercised in a reasonable manner and upon reasonable notice, to
request copies of such records for the sole purpose of carrying out
its obligations and exercising its rights under this Agreement, or
to secure or enforce Patents licensed under this
Agreement.
5.8
Abandoned Targets
.
(a)
If, in respect of any Additional
Target and despite the use of Diligent Efforts, including carrying
out at least [**Redacted**] rounds of LNA Compound design,
synthesis and in vitro screening of not less than
[**Redacted**] in each round, Santaris is unable to identify
any LNA Compounds against an Additional Target that meet the
applicable Compound Acceptance Criteria and reasonably believes
that technical issues relating to such Additional Target prevent
such identification, Santaris shall have the right to cease its
Discovery Program activities in respect of such Additional Target
upon notice to Enzon. Enzon shall then have the right to designate
a replacement Additional Target. Such right may be exercised only
once with respect to each Additional Target and shall be subject to
all of the terms set forth in this Article 5, except that Enzon
shall not be required to pay any additional fees to designate such
replacement Additional Target. All Additional Targets for which
Santaris exercises its right to cease its Discovery Program
activities pursuant to this Section 5.8, shall no longer be
Additional Targets and shall be designated as “ Abandoned
Targets ”. If Enzon designates a replacement Additional
Target pursuant to this Section 5.8 and such replacement Additional
Target itself becomes an Abandoned Target, then Santaris shall
within [**Redacted**] Business Days refund to Enzon $
[**Redacted**] of the amount paid by Enzon pursuant to
Section 7.2. Enzon acknowledges that it shall have no replacement
right with respect to any Additional Targets for which the
applicable Compound Acceptance Criteria are met and thereafter such
LNA Compounds may fail to result in successful preclinical or other
studies.
(b)
Santaris shall be prohibited from
granting any rights to, or performing work on behalf of, any Third
Party with respect to any Abandoned Targets without first complying
with the terms of this Section 5.8(b). If Santaris proposes, within
[**Redacted**] after an Abandoned Target is so abandoned
pursuant to Section 5.8(a), to grant any rights to any Third Party
with respect to such Abandoned Target, Enzon shall have a first
right of refusal to acquire such rights upon the same terms and
conditions (including economic terms and conditions) as are
provided herein as if such Abandoned Target were an Additional
Target. If Santaris proposes, later than [**Redacted**]
months after an Abandoned Target is so abandoned pursuant to
Section 5.8(a), to grant any rights to any Third Party with respect
to such Abandoned Target, Enzon shall have a first right of refusal
to acquire such rights upon terms and conditions no less favorable
than those by which Santaris proposes to grant such
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rights to the Third Party. Enzon
shall have ninety (90) days to exercise such right of first refusal
in either event.
6. DEVELOPMENT AND COMMERCIALIZATION
6.1
Development
.
(a)
Development Efforts
. Enzon shall use Diligent Efforts
to Develop Selected LNA Compounds in accordance with the
Development Plan applicable to such Selected LNA Compound and in
accordance with GLP, GCP and GMP, and shall use Diligent Efforts to
meet the timelines described below; provided, that
Enzon’s failure to achieve any of the milestones set forth
below in the prescribed timelines despite its use of Diligent
Efforts shall not constitute a breach of its obligations under this
Agreement. Notwithstanding the forgoing or any obligation under
Section 6.2, but subject to Section 6.1(b), if Enzon fails to
achieve the Development timelines set forth below in respect of any
Enzon Target, Santaris may terminate this Agreement in respect of
such Enzon Target pursuant to Section 10.3(d):
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Development Milestone
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Time to Achieve
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[**Redacted**]
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[**Redacted**] after delivery
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by Santaris of
the Accepted LNA
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Compound
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[**Redacted**]
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(a)
[**Redacted**] in respect
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of
[**Redacted**] as long as
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[**Redacted**] ;
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(b)
[**Redacted**] after the
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[**Redacted**] in respect of
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[**Redacted**] ; and
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(c) in respect
of other Selected
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LNA
Compounds,
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[**Redacted**] after
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[**Redacted**]
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(b)
Extension of Time to Achieve
Development Milestones .
With respect to each Enzon Target [**Redacted**] , Enzon
shall have the right, at any time prior to the date of each
milestone set forth in Section 6.1(a), to extend the date for each
milestone for an additional [**Redacted**] month period. For
each such milestone for which Enzon desires such extension, Enzon
shall pay to Santaris an amount equal to [**Redacted**] of
the amount that otherwise would have been due upon the achievement
of such milestone for such Enzon Target pursuant to Section
7.4(a)(i) or 7.4(a)(ii). If Enzon makes any such ex tension payment
and subsequently achieves the milestone for which such extension
payment was made, Enzon shall pay only the remaining
[**Redacted**] of such milestone payment pursuant to Section
7.4(a).
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(c)
Development Plans
.
(i)
Enzon shall use Diligent Efforts to
prepare a plan for the Development of SPC2968, SPC3042 and each
Selected LNA Compound, which plans will be designed to enable, as
appropriate, the filing and receipt of Regulatory Approval in the
Enzon Territory for a Product containing SPC2968, SPC3042 and each
Selected LNA Compound (each such plan, an “ Enzon
Development Plan ”).
(ii)
If Santaris plans on conducting any
Development activities for SPC2968, SPC3042 or any other Selected
LNA Compound, Santaris shall use Diligent Efforts to prepare a plan
for such Development activities, which plans will be designed to
enable, as appropriate, the filing and receipt of Regulatory
Approval in the Santaris Territory for a Product containing
SPC2968, SPC3042 and each Selected LNA Compound (each such plan, a
“ Santaris Development Plan ”, and each Enzon
Development Plan and Santaris Development Plan, a “
Development Plan ”).
(iii)
The initial draft of each
Development Plan shall be provided to the JSC promptly after the
Party completes such initial draft. Each Development Plan will set
forth the objectives and planned tasks for the conduct of the
Development activities, and shall contain such details as contained
in the Party’s regularly prepared development plans for its
other products. Each Party shall provide a copy of such initial
drafts and any material changes to each Development Plan to the
other Party and consider in good faith any comments such other
Party may have with respect thereto.
(d)
Development Activities; Clinical
Trials .
(i)
Enzon shall discuss with Santaris,
but shall have the sole discretion to determine, whether to advance
a non-Pegylated or a Pegylated Selected LNA Compound modulating a
particular Enzon Target through Development. If Enzon chooses to
advance only the Pegylated Selected LNA Compound modulating a
particular Enzon Target through Development, neither Santaris nor
its Affiliates (either alone or with or through a Third Party)
shall have the right to Develop, make, use or Commercialize the
non-Pegylated Selected LNA Compound either in the Santaris
Territory or the Enzon Territory for so long as such Target remains
an Enzon Target, except with the consent of Enzon in its judgment
after taking into account in good faith the relevant rationale for
such request.
(ii)
In designing protocols and
Development Plans for the Enzon Territory, Enzon will use
commercially reasonable efforts to design a Development strategy to
support filings for Regulatory Approvals in both the Enzon
Territory and, subject to Section 6.1(d)(iii), the Santaris
Territory; provided that, in all cases, Enzon’s
Development activities comply with applicable Laws and other
requirements of Regulatory Authorities of the Enzon Territory. In
designing protocols and Development Plans for the Santaris
Territory, Santaris will use commercially reasonable efforts to
design a Development strategy to support filings for Regulatory
Approvals in both the Santaris Territory and, to the extent
Santaris or any of its Affiliates, licensees or sublicensees choose
to conduct Development activities relating to the development of
indications not being developed by Enzon or otherwise relating to
Development with a scope greater than to address requirements
specific to the Santaris
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Territory, the Enzon Territory;
provided, that, in all cases, Santaris’s Development
activities comply with applicable Laws and other requirements of
Regulatory Authorities of the Santaris Territory.
(iii)
Each Party (the “
Sponsoring Party ”) shall provide a copy of the
proposed Development Plan and any proposed material amendment and
any proposed protocol for each clinical trial to the other Party in
advance of filing an IND or commencing a clinical trial for such
protocol in order for the other Party to notify the Sponsoring
Party if it believes any modifications to such Development Plan or
protocol would be required to perform different or additional
Development in order to support a Regulatory Filing in the Santaris
Territory or, in the case of Santaris, to the extent required in
paragraph (d)(ii) above, the Enzon Territory. Such other Party
shall have up to five (5) Business Days to review each such
Development Plan and protocol for such purpose, and provide
comments thereto. If such other Party reasonably believes that any
changes are necessary in order to support a Regulatory Filing in
the Santaris Territory or, to the extent applicable, the Enzon
Territory, the Parties shall discuss the extent and nature of such
additional Development activities. If the Parties agree that the
additional Development work in order to support such Regulatory
Filings would add no cost or delay to the Sponsoring Party’s
proposed Development activities, the Sponsoring Party shall
incorporate the other Party’s reasonable scientific and
medical comments into such protocol prior to filing any IND or
commencing a clinical study for such protocol and the Sponsoring
Party shall conduct all such Development activities at its cost and
expenses. If the Parties agree that the additional Development work
in order to support such Regulatory Filings would be minimal
relative to the scope of the protocol, the Sponsoring Party shall
incorporate the other Party’s reasonable scientific and
medical comments into such protocol prior to filing any IND or
commencing a clinical study for such protocol and the Sponsoring
Party shall conduct all such additional Development activities at
the other Party’s cost and expenses. If the Parties agree
that the Development work necessary to support such Regulatory
Filings would be more than minimal, the Sponsoring Party shall have
the right, but not the obligation, at its sole discretion, to amend
the Development Plan or protocol to accommodate such additional
Development activities at the other Party’s cost and expense.
If the Sponsoring Party does not agree to undertake such additional
Development activities, such other Party shall be solely
responsible for undertaking such additional Development activities
at its sole cost and expense.
(iv)
Neither Party (nor any of its
Affiliates, licensees or sublicensees) shall be entitled to conduct
any clinical trials with respect to any Product in the other
Party’s Territory without the other Party’s prior
written approval. If a Party desires to conduct a clinical study in
the other Party’s Territory, such Party shall provide notice
to the other Party of such desire and the Parties shall discuss in
good faith the conduct of such clinical study, including whether
the other Party will act as a contract research organization to
conduct such study and the grant of such license rights as may be
required to conduct such study. If the Parties agree that the other
Party will act as a contract research organization, the Parties
will negotiate in good faith a separate agreement to govern such
contract research organization arrangement.
(e)
Development Costs
. Subject to Section 6.1(d)(iii),
Enzon shall be responsible for all costs associated with the
Development of Products for the Enzon Territory
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and Santaris shall be responsible
for all costs associated with the Development of Products for the
Santaris Territory.
(f)
Santaris Assistance
. In regard to the Development of
SPC2968, Santaris shall provide, at no additional cost to Enzon,
such assistance as may be reasonably requested by Enzon (and to the
extent Santaris possesses the necessary expertise) in the
preparation and filing of an IND in the United States. If,
following acceptance of such IND, Enzon requests Santaris to assist
it further in the implementation of any aspect of the Development
of a Product aimed at MAA submissions in the Enzon Territory,
Santaris shall conduct such additional work as may be agreed by the
Parties. The costs of such additional work shall by paid by Enzon
in accordance with commercially reasonable terms.
(g)
Ongoing Disclosure
. Each Party will keep the other
Party fully-informed about its efforts to Develop Selected LNA
Compounds for such Party’s territory, including summaries of
all results and data from such Development efforts, and all
significant findings and developments. Such disclosures will be
made in written reports to the other Party’s representatives
on the JSC at least once annually. Without limiting the generality
of the foregoing, such reports will contain disclosure of the
following:
(i)
summary of clinical and non-clinical
Development Data, progress of initiation of sites and enrollment of
patients in clinical trials, and any significant events occurring
in the clinical development program;
(ii)
filing of an IND or MAA or other
Regulatory Filings with respect to any Selected LNA Compound in any
jurisdiction;
(iii)
initiation of any clinical study
with respect to any Selected LNA Compound in any jurisdiction;
and
(iv)
identification of significant
development results and clinical trial progress and Regulatory
Approvals with respect to Selected LNA Compounds in any
jurisdiction.
(h)
Development Records
. The Parties shall maintain any
Development Data, related records, documents, and raw data in
sufficient detail as will properly reflect all work done and
results achieved in the Development of the Products. Each Party
shall have the right, which shall be exercised in a reasonable
manner, to copy the other Party’s Development Data for the
sole purpose of carrying out its obligations and exercising its
rights under this Agreement. To the extent not otherwise provided
for herein, upon reasonable request of one Party, the other Party
will provide copies of final reports and all material data relating
to clinical studies performed by such other Party on Selected LNA
Compounds or Products that are required to be submitted in
connection with seeking Regulatory Approvals for Products, and any
other information or data reasonably requested by the requesting
Party that is necessary for its continued Development and
Commercialization of Products in its territory.
(i)
Adverse Events
. Promptly following the Effective
Date, Enzon and Santaris will enter into a safety data exchange
agreement setting forth procedures governing the coordination of
collection, investigation, reporting, and exchange of
information
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concerning adverse events
sufficient to permit each Party, its Affiliates, sublicensees or
licensees to comply with its legal obligations. The safety data
exchange procedures will be promptly updated if required by changes
in legal requirements or by agreement between the Parties. In any
event, each Party shall inform the other Party of any Adverse Event
of which it becomes aware in a timely manner commensurate with the
seriousness of the Adverse Event. Each Party shall establish and
maintain a database for all Adverse Events in its Territory in
accordance with mutually agreed specifications and shall provide
information from such database to the other Party, as set forth in
the safety data exchange agreement to be entered into by the
Parties, for Regulatory Filings and other purposes solely in
connection with the Development and Commercialization of the
Products in such other Party’s territory. Enzon will be
responsible for reporting all Adverse Events to the FDA and other
Regulatory Authorities in the Enzon Territory in accordance with
the Laws of the relevant countries and authorities and Santaris
will be responsible for reporting all Adverse Events to the
appropriate Regulatory Authorities in the Santaris Territory in
accordance with the Laws of the relevant countries and authorities.
Enzon will ensure that its Affiliates, licensees and sublicensees
comply with all such reporting obligations, and Santaris will
ensure that its Affiliates, licensees and sublicensees comply with
all such reporting obligations. Each Party will designate a safety
liaison to be responsible for communicating with the other Party
regarding the reporting of Adverse Events. For the purpose of this
Section 6.1(i), “ Adverse Event ” means any
adverse drug reaction or experience as defined in the then current
edition of ICH Guidelines, 21 CFR §310.305, 21 CFR
§314.80 and any other relevant regulations or regulatory
guidelines.
6.2
Regulatory Affairs
.
(a)
After the Effective Date, Enzon
shall assume sole ownership, controland responsibility for all
Regulatory Filings in the Enzon Territory, and shall use Diligent
Efforts to obtain Regulatory Approvals for at least one Product
containing each Selected LNA Compound in the Enzon
Territory.
(b)
Each Party shall grant the other
Party and such other Party’s Affilia
