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EXHIBIT 10.36
RESTATED p53 and K-ras AGREEMENT
BY AND AMONG
AVENTIS PHARMACEUTICALS PRODUCTS INC.,
AVENTIS PHARMA S.A.,
AND
INTROGEN THERAPEUTICS, INC.
JUNE 30, 2001
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RESTATED p53 AND K-ras AGREEMENT
This RESTATED p53 AND K-ras AGREEMENT (this "Agreement"), dated as of June
30, 2001 and effective as of the date of the Closing (as that term is defined in
the Stock Purchase Agreement, as hereinafter defined) (the "Effective Date"), is
made by and among Aventis Pharmaceuticals Products Inc. (formerly Xxxxx-Xxxxxxx
Xxxxx Pharmaceuticals Inc.), a Pennsylvania corporation ("APPI"), Aventis Pharma
S.A., a company organized under the laws of France ("APSA" and, together with
APPI, the "Aventis Parties"), and Introgen Therapeutics Inc., a Delaware
corporation ("Introgen Therapeutics"), and amends, supercedes and restates in
its entirety (i) that certain Collaboration Agreement (p53 Products) by and
between APPI and Introgen Therapeutics dated as of October 7, 1994, as amended
to date (the "Original p53 Agreement"); and (ii) that certain Collaboration
Agreement (K-ras Products) by and between APPI and Introgen Therapeutics dated
as of October 7, 1994, as amended to date (the "Original K-ras Agreement").
RECITALS
WHEREAS, APPI and Introgen Therapeutics entered into the Original p53
Agreement to establish a collaborative relationship for developing and
commercializing novel p53 gene-therapy products for the treatment of human
cancer. Since entering into the Original p53 Agreement, the Parties have made
substantial progress toward obtaining regulatory approval of INGN 201, up to and
including the commencement of Phase III clinical trials.
WHEREAS, APPI and Introgen Therapeutics also entered the Original K-ras
Agreement to establish a collaborative relationship for developing and
commercializing products relating to Introgen Therapeutics' Retroviral and
Adenoviral K-ras related Transduction Vectors. Since entering into the Original
K-ras Agreement, the Parties have made some progress towards developing a
product based on K-ras but have not conducted clinical trials under the Original
K-ras Agreement.
WHEREAS, the Parties have agreed to restructure the Original p53 Agreement
and the Original K-ras Agreement, so that Introgen Therapeutics takes over from
the Aventis Parties the further development and commercialization of the gene
therapy products for the delivery of the p53 and K-ras inhibition genes,
including the INGN 201 product, and that Aventis retain a potential economic
upside in those products by making an additional equity investment in Introgen
Therapeutics, Inc., all as set forth more fully herein.
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AGREEMENT
NOW, THEREFORE, for and in consideration of the mutual covenants,
conditions, and undertakings hereinafter set forth, and for other good and
valuable consideration, the receipt and sufficiency of which are hereby
acknowledged, the Parties, intending to be legally bound, hereby agree as
follows:
1. DEFINITIONS
1.1 "Additional Aventis Patent Rights" means any patent rights that:
(i) the Aventis Parties or their respective Affiliates own or Control; (ii)
cover subject matter invented before the Effective Date of this Agreement; (iii)
cover the manufacture, sale, offering for sale, importation or use of INGN 201,
as conducted at any time during the Term of this Agreement; and (iv) are not
described on Exhibit 1.8.
1.2 "Affiliate" means, with respect to a Party, any entity that
controls, is controlled by or is under common control with that Party. An entity
shall be regarded as in control of another entity if it owns or controls more
than [*] of the shares of the subject entity entitled to vote in the election of
directors (or, in the case of an entity that is not a corporation, for the
election of the corresponding managing authority).
1.3 "Applicable Laws" means, with respect to any Person, any
statute, law, regulation, ordinance, rule, judgment, rule of common law, order,
decree, award, governmental approval, concession, grant, franchise, license,
agreement, directive, guideline, policy, requirement, or other governmental
restriction or any similar form of decision of, or determination by, or any
interpretation or administration of any of the foregoing by, any governmental
authority, whether in effect as of the Effective Date or thereafter, and in each
case as amended, applicable to such Person or its subsidiaries or their
respective assets.
1.4 "Assigned Marks" means those Marks listed on Exhibit 1.4 hereof
as used for INGN 201.
1.5 "Aventis" means APPI, APSA and their respective Affiliates.
1.6 "Aventis Delivery Patents" means those patents and patent
applications described in Exhibit 1.6 and any parent applications thereof (the
"Existing Aventis Delivery Patents"), as well as all divisions, continuations,
continuations-in-part, patents of addition and substitutions, with respect to
any of the foregoing applications and patents, and all patents, registrations,
reissues, reexaminations, extensions and other rights of any kind anywhere in
the world issuing on or with respect to any of the foregoing, in each case that
are owned, controlled, or licensed from a Third Party by the Aventis Parties or
their respective Affiliates. Notwithstanding the foregoing,
continuations-in-part, applications, foreign counterparts thereof, and patents
issuing thereon shall only be included in the Existing Aventis Delivery Patents
to the extent they claim subject matter conceived or reduced to practice as of
or prior to the Effective Date.
1.7 "Aventis K-ras Technology" means:
1.7.1 Those patents and patent applications described in
Exhibit 1.7 and any parent applications thereof (the "Existing Aventis K-ras
Patents"), as well as all divisions, continuations, continuations-in-part,
patents of addition and substitutions, with respect to any of the foregoing
applications and patents, and all patents, registrations, reissues,
reexaminations, extensions and other rights of any kind anywhere in the world
issuing on or with respect to any of the foregoing, in each case that are owned,
controlled or licensed from a Third Party by the Aventis Parties or their
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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respective Affiliates as of the Effective Date (collectively the "Aventis K-ras
Patents"). Notwithstanding the foregoing, continuations-in-part, applications,
foreign counterparts thereof, and patents issuing thereon shall only be included
in the Existing Aventis K-ras Patents to the extent they claim subject matter
conceived or reduced to practice as of or prior to the Effective Date.
1.7.2 Information and materials that embody or relate to the
practice of inventions within the patents and applications described in Section
1.7.1, including techniques, methods, data, manufacturing information,
biological materials and the like with respect to such inventions or to products
embodying or utilizing such inventions, which in each case are owned or
controlled by the Aventis Parties or their respective Affiliates as of the
Effective Date.
1.8 "Aventis p53 Patents" means those patents and patent
applications described in Exhibit 1.8 and any parent applications thereof (the
"Existing Aventis p53 Patents"), as well as all divisions, continuations,
continuations-in-part, patents of addition, substitutions, with respect to any
of the foregoing applications and patents, and all patents, registrations,
reissues, reexaminations, extensions and other rights of any kind anywhere in
the world issuing on or with respect to any of the foregoing, in each case that
are owned, controlled or licensed from a Third Party by the Aventis Parties or
their respective Affiliates as of the Effective Date. Notwithstanding the
foregoing, continuations-in-part, applications, foreign counterparts thereof,
and patents issuing thereon shall only be included in the Existing Aventis p53
Patents to the extent they claim subject matter conceived or reduced to practice
as of or prior to the Effective Date.
1.9 "Aventis S.A." means Aventis S.A., a company organized under the
laws of France, and its Affiliates.
1.10 "Aventis Targeting Technologies" means
1.10.1 Those patents and patent applications described in
Exhibit 1.10 and any parent applications thereof (the "Existing Aventis
Targeting Patents"), as well as all divisions, continuations,
continuations-in-part, patents of addition, substitutions, with respect to any
of the foregoing applications and patents, and all patents, registrations,
reissues, reexaminations, extensions and other rights of any kind anywhere in
the world issuing on or with respect to any of the foregoing, in each case that
are owned, controlled or licensed from a Third Party by the Aventis Parties or
their respective Affiliates as of the Effective Date. Notwithstanding the
foregoing, continuations-in-part, applications, foreign counterparts thereof,
and patents issuing thereon shall only be included in the Existing Aventis
Targeting Patents to the extent they claim subject matter conceived or reduced
to practice as of or prior to the Effective Date.
1.10.2 Information and materials that embody or relate to the
research use of a cationic lipid p53, including techniques, methods, data, bench
scale formulations, purification, biological materials and the like.
1.11 "Clinical Trial Agreements" means those certain agreements
between Aventis and a Third Party listed on Exhibit 1.11.
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1.12 "Confidentiality Agreement" means that certain Confidential
Disclosure Agreement, dated as of January 26, 2001, by and between Introgen
Therapeutics and APPI.
1.13 "CRADA Side Letter" means that certain Side Letter dates
October 8, 1998, between Introgen Therapeutics and Xxxxx-Xxxxxxx Xxxxx
Pharmaceuticals, relating to the "Proposed Collaborative Research and
Development Agreement (CRADA) with the National Cancer Institute". attached as
Exhibit 1.13.
1.14 "Exchange Act" means the Securities Exchange Act of 1934, as
amended.
1.15 "FDA" means the U.S. Food and Drug Administration.
1.16 "Gencell" means a company to be formed by Aventis after the
Effective Date to own and operate gene therapy product applications and to
develop platform technologies for delivery of genes for gene therapy.
1.17 "Gendux" means Gendux AB, a subsidiary corporation of Introgen
Therapeutics, Inc., formed under the laws of the Kingdom of Sweden.
1.18 "Gene Therapy Product" means a product for the delivery of one
or more genes. It is understood that a single Gene Therapy Product comprises one
or more genes in one or more vector constructs (e.g., a construct for a gene
such as [*], and a separate construct for a cytokine); provided that all of
the compositions represented in a combination product are the subject of a
single BLA (or equivalent application for approval), and are in all cases (i)
approved together only as a single drug; and (ii) marketed only as a single
product.
1.19 "Governmental Entity" means any court, arbitrator,
administrative, regulatory or other governmental department, agency, commission,
authority or instrumentality, domestic or foreign, including, inter alia, the
French Ministry of Industry, the French Ministry of Research, CNRS, INSERM, IGR,
the U.S. National Institutes of Health and related entities, the University of
Texas System and M.D. Xxxxxxxx Cancer Center.
1.20 "Granting Party" means, as applicable, the Aventis Parties
where they are granting a license or transferring rights to Introgen
Therapeutics under the Licensed Aventis Patents or Licensed Aventis Technologies
under this Agreement, and Introgen Therapeutics where it is granting a license
or transferring rights to the Aventis Parties under the Licensed Introgen
Therapeutics Patents under this Agreement.
1.21 "[*] Gene" means a wild-type [*] gene, and/or analogues,
homologues and derivatives thereof.
1.22 "IND" means an Investigational New Drug Application for a
product, as defined in the U.S. Food, Drug and Cosmetic Act and the regulations
promulgated at 21 C.F.R. Section 312 et seq., and any comparable filing in any
country other than the United States.
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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1.23 "INGN 201" means that certain product described in BB-IND 6165
(head and neck cancer) and BB-IND 6026 (lung cancer) and any foreign
counterparts thereof, as such filings exist as of the Effective Date or as they
may be modified during the term of this Agreement.
1.24 "Introgen Therapeutics" means Introgen Therapeutics, Inc., a
Delaware corporation, and its Affiliates.
1.25 "Introgen Therapeutics Adenoviral Patents" means those patents
and patent applications described in Exhibit 1.25 and any parent applications
thereof (the "Existing Introgen Therapeutics Adenoviral Patents"), as well as
all divisions, continuations, continuations-in-part, patents of addition,
substitutions, with respect to any of the foregoing applications and patents,
and all patents, registrations, reissues, reexaminations, extensions and other
rights of any kind anywhere in the world issuing on or with respect to any of
the foregoing, in each case that are owned, controlled or licensed from a Third
Party by Introgen Therapeutics. Notwithstanding the foregoing, continuations-
in-part, applications, foreign counterparts thereof, and patents issuing thereon
shall only be included in the Existing Introgen Therapeutics Adenoviral Patents
to the extent they claim subject matter conceived or reduced to practice as of
or prior to the Effective Date.
1.26 "K-ras Collaboration Product" means the gene therapy products
within the K- ras Field that were developed by Introgen Therapeutics and Aventis
from time to time pursuant to the Early Stage Development Program, as specified
in the Program Plan and Budget to the extent one exists, and as further defined
in Section 6.1 of the Original K-ras Agreement.
1.27 "K-ras Documentation" means, to the extent such documentation
exists, any (i) data, documentation and information owned or controlled by
Aventis with respect to the any K-ras Collaboration Product, including but not
limited to, any study results, investigator reports and correspondence,
investigator brochures, or other documentation required by United States and
international good laboratory practice regulations and guidelines, expert
opinions and analyses, computer databases, computer database validation and
verification reports, analytical methodologies and vendor information; (ii)
regulatory filings (including sponsorship thereof), electronic information in
databases related to regulatory information and filings, correspondence with
regulatory authorities, and the like with respect to any K-ras Collaboration
Product; (iii) any plans for the research and development of any K-ras
Collaboration Product; and (iv) other data, documentation and information in a
tangible medium pertaining to the K-ras Collaboration Product.
1.28 "K-ras Gene" means a wild-type K-ras gene, and/or analogues,
homologues and derivatives thereof.
1.29 "K-ras Materials" means, to the extent such materials exist,
any materials acquired by Aventis in connection with the Original K-ras
Agreement or that are otherwise owned or controlled or controlled by Aventis,
that Aventis created, devised or acquired in connection with the research or
development of any K-ras Collaboration Product, including but not limited to,
any tangible research materials, master viral bank stocks, cell lines, cell
banks, reagents, supplies of K-ras Collaboration Products that Aventis has
purchased or ordered from Introgen Therapeutics, intermediate work-in-progress,
formulation materials and the like.
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1.30 "Later Stage Clinical Development" means all clinical
development, regulatory affairs and other activities necessary to continue the
development of INGN 201 and to obtain all governmental approvals required to
market INGN 201. Later Stage Clinical Development shall include the conduct and
support of the Ongoing Clinical Trials.
1.31 "Licensed Aventis Patents" means those patents and patent
applications listed in Exhibits 1.6, 1.7, 1.8 and 1.10 that are licensed or
transferred by the Aventis Parties to Introgen Therapeutics under this
Agreement.
1.32 "Licensed Introgen Therapeutics Patents" means those patents
and patent applications listed in Exhibit 1.25 licensed or transferred by
Introgen Therapeutics to the Aventis Parties under this Agreement.
1.33 "Licensed Technologies" means the Aventis K-ras Technology, any
p53 Collaboration Product and Aventis Targeting Technology licensed or
transferred by the Aventis Parties to Introgen Therapeutics under this
Agreement.
1.34 "Licensed Patents" means, as applicable, the Licensed Aventis
Patents (where the Aventis Parties are the Granting Parties and Introgen
Therapeutics the Licensee Party) and the Licensed Introgen Therapeutics Patents
(where Introgen Therapeutics is the Granting Party and the Aventis Parties are
the Licensee Parties).
1.35 "Licensee Party" means, as applicable, the Aventis Parties
where they are the licensee or transferee of Licensed Introgen Therapeutics
Patents under this Agreement, and Introgen Therapeutics where it is the licensee
or transferee of Licensed Aventis Patents or Licensed Aventis Technologies under
this Agreement.
1.36 "Xxxx" means any trademark, service, xxxx, trade name, domain
name, or the like, or any other word, name, symbol or device, or any combination
thereof, used or intended of use to either identify or to distinguish the
collaboration product, INGN 201, including all registrations and applications
therefor throughout the world and all common law and other rights therein
throughout the world.
1.37 "Ongoing Clinical Trials" means those certain clinical trials
of INGN 201 listed in Exhibit 1.37 hereto.
1.38 "p53 Collaboration Product" means the gene therapy products
that were developed by Introgen Therapeutics and Aventis from time to time
pursuant to the Early Stage Development Program, as specified in the Program
Plan and Budget in effect from time to time, and as further defined in Section
6.1 of the Original p53 Agreement.
1.39 "p53 Documentation" means all (i) data, documentation and
information owned or Controlled by Aventis with respect to any p53 Collaboration
Product, including but not limited to, all study results, clinical and
pre-clinical data, safety data, investigator reports, clinical-trial protocols
and protocol amendments, batch records, patient records, statistical analyses
and reports, copies of case report forms, clinical site monitoring, inspection
and audit reports, clinical trial standard operating procedures, adverse-event
reports, institutional review board and ethics committee
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approvals and correspondence, informed consents, investigator brochures,
documentation required by United States and international good clinical practice
regulations and guidelines, documentation required by United States and
international good laboratory practice regulations and guidelines, documentation
required for clinical trial quality assurance and quality control, clinical
trial master files, expert opinions and analyses, computer databases, computer
database validation and verification reports, analytical methodologies, bulk-
and final-product manufacturing processes, vendor information, and manufacturing
data; (ii) regulatory filings (including sponsorship thereof), electronic
information in databases related to regulatory information and filings,
correspondence with regulatory authorities, and the like with respect to any p53
Collaboration Product; (iii) marketing forecasts and information, and all plans
for the research, development and commercialization of any p53 Collaboration
Product; and (iv) other data, documentation and information in a tangible medium
pertaining to any p53 Collaboration Product.
1.40 "p53 Gene" means a wild-type p53 gene, and/or analogues,
homologues and derivatives thereof.
1.41 "p53 Materials" means materials acquired by Aventis in
connection with the Original p53 Agreement or that are otherwise owned or
controlled or controlled by Aventis, which Aventis created, devised or acquired
in connection with the research or development of any p53 Collaboration Product,
including but not limited to, tangible research materials, master viral bank
stocks, cell lines, cell banks, reagents, supplies of INGN 201 that Aventis has
purchased or ordered from Introgen Therapeutics, final product, bulk drug
substance, intermediate work-in-progress, formulation materials and the like.
1.42 "Parties" means APPI, APSA and Introgen Therapeutics.
1.43 "Person" means an individual, partnership, corporation, limited
liability company, trust, unincorporated organization, association, or joint
venture or a government, agency, political subdivision, or instrumentality
thereof.
1.44 "Registration Rights Agreement" means the Registration Rights
Agreement, of even date herewith, by and among Introgen Therapeutics, APPI and
RPRIH, substantially in the form as that attached hereto as Exhibit 1.44.
1.45 "RPRIH" means Xxxxx-Xxxxxxx International (Holdings), Inc., a
Delaware corporation and a subsidiary of Aventis S.A.
1.46 "Safety Database" means all information related to the safety
of administering the p53 Collaboration Product in humans and animals that was
gathered during the course of development of the p53 Collaboration Product.
1.47 "Stock Purchase Agreement" shall mean the Introgen
Therapeutics, Inc. Series A Non-Voting Convertible Preferred Stock Purchase
Agreement, of even date herewith, by and between Introgen Therapeutics and APPI,
in the form as that attached hereto as Exhibit 1.47.
1.48 "Term Sheet" means that certain Letter of Intent dated April 2,
2001 by and between Introgen Therapeutics and APPI, including Exhibit A thereto.
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1.49 "Third Party" means, with respect to any Party, any Person that
is not an Affiliate of such Party.
1.50 "Third Party Agreements" means collectively those agreements of
the Parties identified or described in Exhibit 1.50, as such agreements exist on
the Effective Date.
1.51 "TK Gene Therapy Product" means a Gene Therapy Product in which
at least the HSK-tk Gene together with the GM-CSF gene are contained in one or
more adenoviral vectors.
1.52 "Transaction Agreements" means this Agreement, the Stock
Purchase Agreement, the Registration Rights Agreement, and the Voting Agreement.
1.53 "Transition Assets" means any agreements, rights, reagents, p53
Materials, p53 Documentation or other subject matter related to any p53
Collaboration Product required to be transferred during the Transition Period
pursuant to Article 2.
1.54 "Transition Period" means the period of time commencing on
[*] and continuing through [*].
1.55 "Voting Agreement" means the Voting Agreement of even date
herewith, by and among Introgen Therapeutics, APPI and RPRIH, in the form as
that attached hereto as Exhibit 1.55.
1.56 Additional Definitions. The following additional terms have the
meaning ascribed thereto in the Section indicated next to such term.
Defined Term Section
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Agreement Preamble
APPI Preamble
APSA Preamble
Aventis Parties Preamble
Effective Date Preamble
Original p53 Agreement Preamble
Original K-ras Agreement Preamble
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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2. TRANSITION OF p53 COLLABORATION PRODUCTS
2.1 Termination of Original p53 Agreement, Confidentiality
Agreement, CRADA Side Letter and Term Sheet. As of the Effective Date, except as
provided in Section 7.4, each of the Original p53 Agreement, Confidentiality
Agreement, CRADA Side Letter and Term Sheet and any other arrangement or
agreement entered into in connection with any of the foregoing shall terminate
in their entirety and no provision thereof (including any provision referenced
therein that was agreed to survive termination) shall be of any further force or
effect.
2.2 INGN 201. The Aventis Parties and Introgen Therapeutics agree
that the further development, manufacture and commercialization of INGN 201 will
be transferred to Introgen Therapeutics during the Transition Period, all as set
forth below.
2.2.1 Ongoing Trials. It is understood that the Ongoing
Clinical Trials are currently underway, and that Aventis has entered into the
Clinical Trial Agreements with Third Parties with respect to the performance of
the Ongoing Clinical Trials. The performance of the Clinical Trial Agreements
shall be continued through the Transition Period, or discontinued, at the
direction of Introgen Therapeutics, as follows:
(a) Introgen Therapeutics will have the right to
control all aspects of the Ongoing Clinical Trials. To that end, the Aventis
Parties will exercise such rights as they have, and will cause any of their
Affiliates, as appropriate, to do so under the Clinical Trial Agreements, as
directed by Introgen Therapeutics, including by requesting the other Party or
Parties to the Clinical Trial Agreements to take such actions, or to not take
such actions, as are permitted or required under the Clinical Trial Agreements
and under applicable laws, regulations and regulatory requirements, all as
Introgen Therapeutics may so direct. However, neither Aventis Party shall have
any duty to take such actions or fail to take such action unless an indemnity
reasonably satisfactory to the Aventis Parties is provided by Introgen
Therapeutics.
(b) Introgen Therapeutics shall promptly reimburse the
Aventis Parties for any amounts actually paid or accrued to any other Party or
Parties to a Clinical Trial Agreement with respect to the conduct of the Ongoing
Clinical Trials, to the extent such payments are for the costs of performing
activities under the Clinical Trial Agreements during the Transition Period and
such Party is not an Affiliate or such Parties are not Affiliates of the Aventis
Parties; provided that Introgen Therapeutics has approved such costs, which it
may do or not do in its sole discretion, in writing (including costs that
Introgen Therapeutics approved in writing or that were approved by the Joint
Project Team before or after the Effective Date of this Agreement). Any
requested reimbursement not made by Introgen Therapeutics within 30 days of
notification by the Aventis Parties of such requested reimbursement shall be
deemed late for purposes of Section 8.3.
(c) Upon request by Introgen Therapeutics from time to
time during the Transition Period, the Aventis Parties will cause to be
transferred to Introgen Therapeutics any or all of the Clinical Trial
Agreements. To effect any such transfer, Introgen Therapeutics will execute and
deliver to the Aventis Parties, and the Aventis Parties will cause to be
executed and delivered to Introgen Therapeutics, an Assignment and Assumption
Agreement substantially in the form of Exhibit 2.2.1(c). If any Clinical Trial
Agreement is not transferable to Introgen Therapeutics or a Party promptly
designated by Introgen Therapeutics, the Aventis Parties will, if possible,
terminate such Clinical Trial Agreements by or before the end of the Transition
Period. Introgen Therapeutics
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shall remain free to enter into its own agreements in place of those terminated.
In addition, after the Effective Date, the Aventis Parties will terminate any or
all such Clinical Trial Agreements as Introgen Therapeutics may so request. Any
reasonable costs incurred by Aventis in compliance with this Section 2.2.1(c)
shall be reimbursed by Introgen Therapeutics with the exception of costs
associated with the termination of Study [*], which costs shall be
borne by Aventis.
(d) The Aventis Parties agree to cooperate, and to take
such actions as Introgen Therapeutics may reasonably request, to enable Introgen
Therapeutics to exercise full control of the Ongoing Clinical Trials and to
obtain the benefits that were due to Aventis with respect to the Clinical Trial
Agreements and the Ongoing Clinical Trials. However, the Aventis Parties shall
have no duty to take such actions unless an indemnity reasonably satisfactory to
the Aventis Parties is provided by Introgen Therapeutics.
2.2.2 Other Support of Later Stage Clinical Development.
(a) The Aventis Parties will use reasonable
commercial efforts to continue performing the Later Stage Clinical Development
through the end of the Transition Period, subject to Section 2.2.1(c). These
activities will include, but not be limited to, those activities described in
Exhibit 2.2.2, it being understood that the Aventis Parties shall continue to
devote to the Later Stage Clinical Development the personnel and resources
reasonably necessary to carry out its obligations under Article 2.
Notwithstanding the foregoing, the Aventis Parties shall not be responsible to
incur out-of-pocket costs under the Clinical Trial Agreements for the Ongoing
Clinical Trials, except those to be reimbursed by Introgen Therapeutics under
Section 2.2.1, but the Aventis Parties shall continue to bear their internal
costs to continue the Later Stage Clinical Development through the end of the
Transition Period.
(b) In addition, the Aventis Parties agree to use
reasonable commercial efforts to:
(i) transition to Introgen Therapeutics the
ongoing conduct of the Later Stage Clinical Development during the Transition
Period; and
(ii) assist Introgen Therapeutics, as reasonably
requested, to understand and utilize the Transition Assets provided that the
Aventis Parties shall have no obligation under this Section 2.2.2(b)(ii) with
respect to any Transition Asset that has been in Introgen Therapeutics's
possession for more than ninety (90) days after having been transferred and
delivered by Aventis to Introgen Therapeutics under this Agreement.
2.2.3 Communication and Reporting.
(a) Introgen Therapeutics or its designee shall have
primary control over all material activities with respect to the conduct of
Later Stage Clinical Development, including primary responsibility for
communications with investigators, regulatory authorities, and all other Parties
outside Aventis, provided that the Aventis Parties shall not be obligated to
take any action, or refrain from taking any action, that would cause Aventis to
incur liability to a Third Party for which Introgen Therapeutics has not
provided indemnity or otherwise accepted responsibility, in
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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each case, pursuant to a separate written agreement in a form reasonably
acceptable to the Aventis Parties.
(b) Within 10 business days after a request by Introgen
Therapeutics from time to time, to the extent the request is compatible with
applicable laws, regulations or regulatory requirements, the Aventis Parties
shall deliver to Introgen Therapeutics, the FDA, other regulatory authorities,
clinical research organizations, investigators, Aventis employees and other
appropriate Parties, a letter authorizing Introgen Therapeutics to assume
primary correspondence with respect to all regulatory filings for, clinical
trials and other matters with respect to the Later Stage Clinical Development of
INGN 201.
(c) During the Transition Period, the Aventis Parties
shall keep Introgen Therapeutics reasonably informed of all activities it has
taken or is taking in connection with its performance of Later Stage Clinical
Development. The obligation of the Aventis Parties to keep Introgen Therapeutics
reasonably informed primarily includes, but is not limited to, making monthly
written reports in reasonable detail to Introgen Therapeutics, stating in each
such report the specific activities performed, the personnel and resources
devoted to such activities, and any estimated amounts that are reimbursable by
Introgen Therapeutics under Section 2.2.1(b). The Aventis Parties shall make
additional reports as reasonably requested by Introgen Therapeutics.
2.3 Transfer of p53 Materials, p53 Documentation and INGN 201 INDs.
2.3.1 Transfer. Subject to the terms of this Agreement and to
legal, contractual or regulatory restrictions, during the Transition Period, the
Aventis Parties shall assign and transfer, and cause their respective Affiliates
to assign and transfer to Introgen Therapeutics exclusively as to uses for Gene
Therapy Products utilizing the p53 Gene and non-exclusively for other Gene
Therapy Products , the right, title and interest of the Aventis Parties in and
to (i) p53 Materials; (ii) p53 Documentation; and (iii) INDs with respect to
INGN 201 and any other subject matter set forth in Exhibit 2.3.1. For p53
Materials not containing the p53 Gene, such as master cell banks, the Aventis
Parties shall retain a portion of such materials for uses for Gene Therapy
Products not utilizing the p53 Gene. The Parties shall mutually determine in
good faith the schedule of the transfer of such materials during the Transition
Period so as to not materially hinder the progress of the trials or the
scientific validity of the results. The preliminary schedule for such transfer
is attached as Exhibit 2.3.1.a.
2.3.2 Instrument of Transfer. The Parties shall effect the
transfers and deliveries of the (i) p53 Materials; (ii) p53 Documentation; and
(iii) INDs with respect to INGN 201 under Section 2.3.1 by entering into an
instrument of assignment substantially in the form of Exhibit 2.3.2 hereto (the
"p53 Assignment Agreement"), or where appropriate or required, by execution of
separate instruments of assignment.
2.3.3 Delivery. During the Transition Period, the Aventis
Parties shall deliver to Introgen Therapeutics all of the (i) p53 Materials;
(ii) p53 Documentation; and (iii) INDs with respect to INGN 201 except (a) as
may be required for the Aventis Parties to be able to fulfill their respective
legal and regulatory obligations, (b) where the conveyance, assignment or
transfer of such by its terms or by operation of law cannot be freely conveyed,
assigned or transferred, (c)
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where the delivery of such p53 Materials or p53 Documentation requires the prior
approval or consent of a Third Party pursuant to a Third Party Agreement or of a
Governmental Entity and such approval or consent cannot be obtained by Aventis.
To the extent the Aventis Parties are required to retain any records or
documentation relating to the p53 transfer as described above by reason of
regulatory requirements, the Aventis Parties shall make such records or
documentation available to regulatory authorities for inspection and use under
the supervision of the Aventis Parties and, if Introgen Therapeutics so elects,
in the presence of one or more representatives of Introgen Therapeutics, for as
long as either Aventis Parties has an obligation under applicable regulations to
retain such records or documentation. All other documents shall be transferred
to Introgen Therapeutics by the end of the Transition Period, and the Aventis
Parties shall have no ongoing duty whatsoever to retain such records or to allow
access to such records by Introgen Therapeutics.
2.3.4 Safety Database. Pursuant to its obligations under
Section 2.3, the Aventis Parties shall provide to Introgen Therapeutics all data
contained within the Safety Database as it exists as of the Effective Date.
(a) The Aventis Parties shall retain the right to use
the data contained within the Safety Database for purposes unrelated to the
Collaboration Product or other products employing the p53 Gene. However, the
Aventis Parties shall keep confidential and shall not publish or otherwise
disclose the data contained in the Safety Database or any other information
related to the data contained in the Safety Database to any Third Party without
Introgen Therapeutics' prior written consent, except as may be required by
Applicable Law or as requested by a Governmental Entity. Notwithstanding the
foregoing, the Aventis Parties shall be entitled to transfer the data contained
in the Safety Database to Gencell for use by Gencell. At the time or such
transfer, the right of the Aventis Parties to use the safety database shall be
deemed transferred to Gencell and shall no longer be owned by the Aventis
Parties.
(b) Notwithstanding the foregoing, the Aventis Parties,
or Gencell if the right of the Aventis Parties to use the data is transferred to
Gencell, may submit data contained within the Safety Database to applicable
Governmental Entities in connection with regulatory filings for products
unrelated to the p53 Collaboration Product.
(c) Nothing in the foregoing shall be deemed to in any
way limit the rights of Aventis in the software currently used in connection
with the Safety Database or to confer upon Introgen Therapeutics a license or
other rights to use such software.
2.4 Further Assurances. Nothing in this Agreement requires the
conveyance, assignment or transfer of any p53 Materials or p53 Documentation
that by its terms or by operation of law cannot be freely conveyed, assigned,
transferred or assumed. To the extent the Aventis Parties and Introgen
Therapeutics have been unable to obtain any governmental or Third-Party consents
or approvals required for the transfer of any p53 Materials or p53
Documentation, the Aventis Parties shall, without additional consideration for
doing so, exercise or exploit their rights in respect of such p53 Materials only
as Introgen Therapeutics reasonably directs, and Introgen Therapeutics shall
reimburse the reasonable out-of-pocket costs that the Aventis Parties incur at
Introgen's direction. Without limiting Section 2.2, the Aventis Parties shall
use reasonably diligent efforts to obtain required consents or approvals that
have not been obtained at the earliest practicable date for any
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conveyance, assignment or transfer of p53 Materials or p53 Documentation (other
than a Clinical Trial Agreement, the transfer of which is covered specifically
by Section 2.2.1). When any of these consents or approvals are obtained, the
appropriate Aventis Party shall promptly assign its rights and obligations under
the p53 Materials or p53 Documentation to Introgen Therapeutics without payment
of additional consideration. The Parties shall execute, and if necessary file
with the applicable entity, good and sufficient instruments as may be reasonably
necessary to evidence or perfect such assignment. Without limiting the
foregoing, the Aventis Parties shall provide to Introgen Therapeutics promptly
after the Effective Date letters of authorization or other instruments
authorizing Introgen Therapeutics to receive the benefits of any regulatory
filings within the p53 Documentation.
2.5 Exclusivity of Efforts. APPI and APSA shall not, and shall cause
Gencell to not, for a period of [*] years after the close of the
Transition Period, directly or indirectly through their Affiliates, develop or
commercialize a gene therapy product using the p53 Gene (a "Competing p53
Business") other than the continuance of the Later Stage Clinical Development in
accordance with Article 2 provided, however, that the foregoing shall not be
deemed breached as a result of (1) the acquisition, whether by merger,
consolidation, stock purchase or otherwise, of APPI, APSA or any of their
Affiliates by a Third Party whose operations involve a Competing p53 Business or
(2) the acquisition, whether by merger, consolidation, stock purchase or
otherwise, by APPI, APSA or any of their Affiliates of an interest in any Third
Party which, at the time of such acquisition, derives no more than [*] of its
revenues for its most recently completed fiscal year from a Competing p53
Business. This Section 2.5 shall not be deemed to limit the licenses or
exclusivity under Section 3.1 as to APPI, APSA or any of their Affiliates other
than a Person that becomes an Affiliate only by reason of a transaction covered
by clause (1) or (2) of the proviso above (for purposes of this Section 2.5, a
"New P53 Affiliate"). The Aventis Parties will not grant or provide to any New
P53 Affiliate that conducts a Competing p53 Business that falls within the
exceptions set forth in clauses (1) or (2) of the proviso above any licenses or
other rights to use p53 Documentation, p53 Materials or Aventis p53 Patents with
a Gene Therapy Product containing the p53 Gene.
3. p53, AVENTIS DELIVERY, AND TARGETING PATENT OR TECHNOLOGY LICENSES AND
INTROGEN THERAPEUTICS ADENOVIRAL PATENT LICENSES
3.1 Licenses to Introgen Therapeutics. The provisions of this
Section 3.1 shall be subject to the provisions of Section 7.2 and Section 7.3.
3.1.1 Aventis p53 Patents The Aventis Parties hereby grant to
Introgen Therapeutics a royalty-free (except as provided in Sections 7.2 and
7.3), worldwide, paid-up, license, including the right to grant and authorize
sublicenses in accordance with Section 3.3, under the Aventis p53 Patents to
make, have made, use, import, sell, offer to sell, and practice any method,
process or procedure with respect to or comprising:
(a) one or more products incorporating a p53 Gene; and
(b) one Gene-Therapy Product, selected by Introgen
Therapeutics in accordance with Article 5 that does not incorporate the p53
Gene.
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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The license under Section 3.1.1(a) shall be exclusive for all purposes
pertaining to the manufacture, sale or use of products incorporating a p53 Gene,
and the license under Section 3.1.1(b) shall be non- exclusive. The license
under Section 3.1.1(a) shall be exclusive even as to Aventis.
3.1.2 Aventis Delivery Patents. The Aventis Parties hereby
grant to Introgen Therapeutics a royalty-free (except as provided in Sections
7.2 and 7.3), worldwide, paid- up license, including the right to grant and
authorize sublicenses in accordance with Section 3.3, under the Aventis Delivery
Patents to make, have made, use, import, sell, offer to sell, and to practice
any method, process or procedure, with respect to or comprising:
(a) one or more products incorporating a p53 Gene; and
(b) one or more products that utilize an adenoviral
vector and that: (i) are for uses other than the treatment of cardiovascular
disease; and (ii) are not for the delivery of the [*] Gene.
The license under Section 3.1.2(a) shall be exclusive for all purposes
pertaining to the manufacture, sale or use of products incorporating a p53 Gene,
and the license under Section 3.1.2(b) shall be non-exclusive.
3.1.3 Aventis Targeting Technologies. The Aventis Parties
hereby grant to Introgen Therapeutics an exclusive, royalty-free (except as
provided in Sections 7.2 and 7.3), worldwide, paid-up license, including the
right to grant and authorize sublicenses in accordance with Section 3.3, under
the Aventis Targeting Technologies to make, have made, use, import, sell and
offer to sell, and to practice any method, process or procedure comprising or
with respect to products incorporating a p53 Gene, excluding ex vivo Gene
Therapy Products.
3.2 Introgen Therapeutics Adenoviral Patents. Introgen Therapeutics
hereby grants to the Aventis Parties a non-exclusive, royalty-free (except as
provided in Sections 7.2 and 7.3) worldwide, paid-up license, including the
right to grant and authorize sublicenses in accordance with Section 3.3, under
the Introgen Therapeutics Adenoviral Patents to make, have made, use, import,
sell and offer to sell, and practice any method, process or procedure with
respect to or comprising one Gene-Therapy Product selected by the Aventis
Parties in accordance with Article 5; provided that the selected Gene-Therapy
Product shall not include use of a p53 Gene.
3.3 Limitations on Sublicense Rights and Requirements for
Notification; Transfers.
3.3.1 Sublicenses. The Licensee Parties may grant and
authorize sublicenses under the rights licensed to them under the Licensed
Patents, as applicable, except that:
(a) Introgen Therapeutics shall not grant or authorize
any sublicense under its licensed rights in the Aventis p53 Patents, Aventis
Delivery Patents or Aventis Targeting Technologies for a product described in
Section 3.1.1(b), Section 3.1.2(b) or Section 3.1.3 unless Introgen Therapeutics
has conducted Substantial Development, as defined below, with respect to such
product.
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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(b) Neither Aventis Party shall grant or authorize any
sublicense under its licensed rights in the Introgen Therapeutics Adenoviral
Patents for a product described in Section 3.2 unless Aventis has conducted
Substantial Development with respect to such product. The Parties acknowledge
that, as of the Effective Date, Aventis has conducted Substantial Development of
the [*] Gene Therapy Product as referenced in Section 5.1 such that a right to
sublicense exists.
(c) For purposes of this Section 3.3, the phrase
"Substantial Development" means that Introgen Therapeutics (with respect to a
sublicense described in clause (a) above), or the Aventis Parties (with respect
to a sublicense described in clause (b) above), has conducted bona fide research
and/or development activities at a documented cost of $5 million or more with
respect to the subject matter to be made, used or sold pursuant to such
sublicense (the "Sublicensed Subject Matter"), whether for its own account, or
under a collaboration or other arrangement with a Third Party, and that Introgen
Therapeutics or one of the Aventis Parties, respectively, is granting rights to
other significant intellectual property Controlled by Introgen Therapeutics or
the Aventis Parties, respectively, which is incorporated in the Sublicensed
Subject Matter, its manufacture or use (i.e., other than the Licensed Patents or
Licensed Technologies that Introgen or the Aventis Parties is (or are) so
sublicensing).
3.3.2 Notification. The Licensee Party shall notify the
Granting Party of any sublicense of non-exclusively Licensed Patents or Licensed
Technologies within 60 days of such sublicense. Each such notification shall
include a summary of the material terms of the sublicense and, if applicable, an
explanation and evidence in reasonable detail of Substantial Development.
3.4 Transfers. The licenses granted under this Article 3 are
non-transferable, except as provided under Section 15.7.
4. K-ras TECHNOLOGY TRANSFER AND LICENSE
4.1 Termination of Original K-ras Agreement, Confidentiality
Agreement and Term Sheet. As of the Effective Date, the Original K-ras Agreement
and any other arrangement or agreement entered into in connection with such
agreement shall terminate in their entirety and no provision thereof (including
any provision referenced therein that was agreed to survive termination) shall
be of any further force or effect.
4.2 Transfer of K-ras Materials and K-ras Documentation.
4.2.1 Transfer. Subject to the terms of this Agreement and to
legal, contractual or regulatory restrictions, during the Transition Period, the
Aventis Parties shall assign and transfer, and cause their respective Affiliates
to assign and transfer to Introgen Therapeutics exclusively as to uses for Gene
Therapy Products utilizing the K-ras Gene and non-exclusively for other Gene
Therapy Products, the right, title and interest of the Aventis Parties in and to
K-ras Materials and K-ras Documentation. For any K-ras Materials not containing
the K-ras Gene, such as master cell banks, the Aventis Parties shall retain a
portion of such materials for uses for Gene Therapy Products not utilizing the
K-ras Gene.
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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4.2.2 Instrument of Transfer. The Parties shall effect the
transfers and deliveries of the K-ras Materials and K-ras Documentation under
Section 4.2.1 by entering into an instrument of assignment substantially in the
form of Exhibit 4.2.2 hereto (the "K-ras Assignment Agreement"), or where
appropriate or required, by execution of separate instruments of assignment.
4.2.3 Delivery. During the Transition Period, the Aventis
Parties shall deliver to Introgen Therapeutics all of the K-ras Materials and
K-ras Documentation except (a) where the conveyance, assignment or transfer of
such by its terms or by operation of law cannot be freely conveyed, assigned,
transferred or assumed, or (b) where the delivery of such the K-ras Materials
and K-ras Documentation requires the prior approval or consent of a Third Party
pursuant to a Third Party Agreement or of a Governmental Entity and such
approval or consent cannot be obtained by the Aventis Parties. To the extent the
Aventis Parties are required to retain any records or documentation relating to
the K-ras transfer as described above by reason of regulatory requirements, the
Aventis Parties shall make such records or documentation available to regulatory
authorities for inspection and use under the supervision of the Aventis Parties
and, if Introgen Therapeutics so elects, in the presence of one or more
representatives of Introgen Therapeutics, for as long as either Aventis Parties
has an obligation under applicable regulations to retain such records or
documentation. All other documents shall be transferred to Introgen Therapeutics
by the end of the Transition Period, and the Aventis Parties shall have no
ongoing duty whatsoever to retain such records or to allow access to such
records by Introgen Therapeutics.
4.2.4 Further Assurances. Nothing in this Agreement requires
the conveyance, assignment or transfer of any the K-ras Materials and K-ras
Documentation that by its terms or by operation of law cannot be freely
conveyed, assigned, transferred or assumed. To the extent Aventis and Introgen
Therapeutics have been unable to obtain any governmental or Third- Party
consents or approvals required for the transfer of any K-ras Materials and K-ras
Documentation, the Aventis Parties shall, without additional consideration for
doing so, exercise or exploit its rights in respect of such K-ras Material only
as Introgen Therapeutics reasonably directs, and Introgen Therapeutics shall
reimburse the reasonable out-of-pocket costs that the Aventis Parties incur at
Introgen's direction. Without limiting Section 4.1, the Aventis Parties shall
use reasonably diligent efforts to obtain all unobtained consents or approvals
at the earliest practicable date for any conveyance, assignment or transfer of
K-ras Materials and K-ras Documentation. When any of these consents or approvals
are obtained, each Aventis Party shall promptly assign its rights and
obligations under the K-ras Materials and K-ras Documentation to Introgen
Therapeutics without payment of additional consideration.
4.2.5 Exclusivity of Efforts. APPI and APSA shall not, and
shall cause Gencell to not, for a period of [*] years after the close of the
Transition Period, directly or indirectly through their Affiliates, conduct any
activities directed to the development or commercialization of any product
comprising the K-ras Gene (a "Competing K-ras Business") provided, however, that
the foregoing shall not be deemed breached as a result of (1) the acquisition,
whether by merger, consolidation, stock purchase or otherwise, of APPI, APSA or
any of their Affiliates by a Third Party whose operations involve a Competing
K-ras Business or (2) the acquisition, whether by merger, consolidation, stock
purchase or otherwise, by APPI, APSA or any of their Affiliates of an interest
in any Third Party which, at the time of such acquisition, derives no more than
[*] of its revenues for its most recently completed fiscal year from a Competing
K-ras
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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Business. The Aventis Parties will not grant or provide to any Person that
becomes an Affiliate only by reason of a transaction covered by clauses (1) or
(2) of the proviso above any licenses or other rights to use K-ras
Documentation, K-ras Materials or the Aventis K-ras Patents with a Gene Therapy
Product containing the K-ras Gene.
4.3 Licenses to Introgen Therapeutics. The provisions of this
Section 4 shall be subject to the provisions of Section 7.2 and Section 7.3.
4.4 Aventis K-ras Technology. The Aventis Parties hereby grant to
Introgen Therapeutics an exclusive, royalty-free (except as provided in Sections
7.2 and 7.3), worldwide, paid- up, license, including the right to grant and
authorize sublicenses under the Aventis K-ras Technology to make, have made,
use, import, sell and offer to sell, and practice any method, process or
procedure with respect to or comprising the K-ras Gene.
5. SELECTION OF GENE THERAPY PRODUCTS
5.1 Initial Selection of [*] Gene Therapy Product. Pursuant to the
license granted in Section 3.2.1, the Parties acknowledge that the Aventis
Parties have selected as their first Gene Therapy Product the [*] Gene Therapy
Product. This Gene Therapy Product shall be deemed approved upon execution of
this Agreement and shall not be subject to the selection mechanism described
below in the remainder of Article 5. The Aventis Parties will have the right to
select another Gene Therapy Product pursuant to the license granted in Section
3.2.1, and any such later selection will be subject to the selection mechanism
described below.
5.2 Initial Notice. At any time during the Term of this Agreement, a
Licensee Party under Section 3.1.1(b) or Section 3.2 may notify the Granting
Party that the Licensee Party wishes to designate a Gene Therapy Product for
purposes of its license under, as applicable, Section 3.1.1(b) or Section 3.2.
5.3 Notice of Availability. Within 30 business days following a
Granting Party's receipt of a Licensee Party's notice with regard to [*] Gene
Therapy Product, the Granting Party shall notify Licensee Party whether that
[*] Gene-Therapy Product is available for licensing to Licensee Party. A
selected Gene Therapy Product shall not be available for Licensee Party's use
under Section 3.1.1(b) or Section 3.2, as applicable, (i) to the extent that the
Granting Party has previously granted to a non-Affiliate Third Party rights
under the particular Licensed Patents that would conflict with the license
sought by the Licensee Party under Section 3.1.1(b) or Section 3.2,
respectively; or (ii) if as of the date Granting Party received Licensee Party's
notice of a desire to select such Gene Therapy Product, Granting Party: (x) has
initiated and is continuing negotiations with a non-Affiliate Third Party
relating to that Gene Therapy Product, or (y) has initiated and is continuing an
active program of bona fide research or development with respect to that Gene
Therapy Product, as shown by contemporaneous written records that existed before
Licensee Party's request for a license.
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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5.4 Exercising Option to License; Termination of Option.
5.4.1 If Granting Party notifies Licensee Party that the
particular Gene Therapy Product is available for licensing to Licensee Party
under, as applicable, Section 3.1.1(b) or Section 3.2, such Gene Therapy Product
shall be considered licensed under such section as of the date of the notice by
Granting Party. Following the license of a Gene Therapy Product under, as
applicable, Section 3.1.1(b) or Section 3.2, Licensee Party may later terminate
its license rights for such Gene Therapy Product, in which case Licensee Party
may select an alternative Gene Therapy Product in accordance with the procedures
set forth in this Article 5; provided that Licensee Party shall have license
rights for only one Gene Therapy Product under, as applicable, Section 3.1.1(b)
or Section 3.2, at any given time. If Licensee Party has not, at any time, so
exercised its right to select a particular Gene Therapy Product, it is
understood that Granting Party may grant a license, exclusive or otherwise, to a
Third Party under the Aventis p53 Technology (where the Aventis Parties are the
Granting Parties and Introgen Therapeutics is Licensee Party) or the Introgen
Therapeutics Adenoviral Technology (where Introgen Therapeutics is the Granting
Party and the Aventis Parties are the Licensee Parties) with respect to that
Gene Therapy Product.
5.4.2 The rights of a Licensee Party to license a Gene
Therapy Product under, as applicable, Section 3.1.1(b) or Section 3.2 shall
terminate upon the final approval for the marketing of such Gene Therapy Product
by either the FDA or the respective Ministries of Health (or similar regulatory
body or bodies) of any of [*].
5.5 Unavailability. If Granting Party notifies Licensee Party that
rights are not available with regard to a particular, selected Gene Therapy
Product, and provides Licensee Party with the necessary written evidence
therefor, Licensee Party will have no further license or other rights with
regard to that selected Gene Therapy Product under the Aventis p53 Patents
(where the Aventis Parties are the Granting Parties and Introgen Therapeutics is
Licensee Party) or the Introgen Therapeutics Adenoviral Patents (where Introgen
Therapeutics is the Granting Party and the Aventis Parties are the Licensee
Parties), unless the Parties agree otherwise in writing. However, this Section
5.5 shall not be deemed to prevent the Licensee Party from selecting such Gene
Therapy Product in accordance with this Article 5 at a later date, if such Gene
Therapy Product is then available.
5.6 Termination. The selection mechanism and all other provisions
described above in Article 5 shall be available only during the term of this
Agreement and shall terminate with any termination of this Agreement.
6. TRADEMARK LICENSES
6.1 Transfer of Registrations. For all registrations of or
applications for registration of Assigned Marks, Introgen Therapeutics shall be
responsible for taking all necessary action to transfer or assign such marks.
The Aventis Parties shall make available to Introgen Therapeutics any files
maintained by the Aventis Parties in connection with any such registration or
application for registration and shall provide such assistance as is reasonably
necessary to effectuate such transfers.
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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6.1.1 Preparation and Recordation of Assignments. The Aventis
Parties shall provide to Introgen Therapeutics the registration or serial
number, country and international class for every registration or application
for registration for all Assigned Marks. Introgen Therapeutics shall then be
responsible for drafting and providing to the Aventis Parties all assignment
documents necessary to effect the transfer of such registrations or
applications. Introgen Therapeutics shall also be responsible for the filing of
all assignment documents, unless the document must, by law, be filed by the
Aventis Parties, in which instance Introgen Therapeutics shall reimburse the
Aventis Parties for all filing and recordation fees as well as any other
reasonable out-of-pocket expenses associated with the filing.
6.1.2 Abandonment of Registrations. For all registrations
of Assigned Marks that have not been assigned to Introgen Therapeutics as of
[*], the Aventis Parties shall execute and file with the applicable Governmental
Entities or treaty organizations a notice of express abandonment of the
registration.
6.2 Transfer of Goodwill and Causes of Action. As of the Effective
Date, all goodwill of Aventis' p53 gene-therapy business appurtenant to the
Assigned Marks is hereby transferred to Introgen Therapeutics to be held and
enjoyed by Introgen Therapeutics and all its successors, assigns and/or
designees. Additionally, as of the Effective Date, all causes of action and
rights of recovery for past infringement, or misappropriation, of the Assigned
Marks are hereby transferred to Introgen Therapeutics and all its successors,
assigns and/or designees.
6.3 Limitations. Nothing in the above portions of Article 6 or in
Exhibit 1.4 shall be deemed a representation, warranty or guaranty that any
registrations, goodwill, or causes of action or rights of recovery actually
exist for the Assigned Marks.
7. CERTAIN OTHER MATTERS
7.1 Transaction Agreements; Closing.
7.1.1 Deliveries by Introgen Therapeutics at Closing. At the
Closing (as defined in the Stock Purchase Agreement) Introgen Therapeutics shall
execute and deliver or deliver, as appropriate, the following items:
(a) this Agreement;
(b) the Stock Purchase Agreement;
(c) the Registration Rights Agreement;
(d) the Voting Agreement;
(e) a certified copy of the Certificate of Designations
(as defined in the Stock Purchase Agreement) filed with the Secretary of State
of the State of Delaware;
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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(f) the Compliance Certificate (as described in section
6 of the Stock Purchase Agreement);
(g) the Secretary's Certificate (as described in
section 6 of the Stock Purchase Agreement); and
(h) [*] pursuant to Section 8.1 and Section
7.1.2(g).
7.1.2 Deliveries by the Aventis Parties at Closing. At the
Closing (as defined in the Stock Purchase Agreement), the Aventis Parties shall
execute and deliver or deliver, as appropriate, the following items (which shall
be executed by the proper Aventis Party):
(a) this Agreement;
(b) the Stock Purchase Agreement;
(c) the Registration Rights Agreement;
(d) the Voting Rights Agreement;
(e) the p53 Assignment Agreement (in accordance with
Section 2.3.2);
(f) the K-ras Assignment Agreement (in accordance with
Section 4.2.2); and
(g) a wire transfer of $25 million pursuant to the
Stock Purchase Agreement (which, for convenience, will be reduced by the first
[*] payment referenced in Section 8.1).
7.2 Third Party Consents. If a Granting Party under Article 3 or
Article 4 requires the consent of a non-Affiliate Third Party under any Third
Party Agreement to include within a license granted (or an assignment made) by
it to Licensee Party (or assignee) under those sections, any subject matter to
which the Granting Party otherwise has a right to use for its own purposes, then
the Granting Party shall use reasonably diligent efforts to obtain such consent
on terms no less favorable than those applicable to Granting Party. Regular
reporting of such efforts shall occur as summarized in Exhibit 7.2.
7.2.1 Covenant Not to Xxx. For those patent properties that
require Third Party consents, the Aventis Parties hereby grant to Introgen
Therapeutics a covenant not to xxx on behalf of the Aventis Parties and their
respective Affiliates, but not Third Parties, with respect to the patents listed
in Exhibits 1.6, 1.7, 1.8 and 1.10. The scope of the covenant shall be
coextensive with the scope of the licenses granted under Articles 3 and 4 and
will be subject to any Third Party obligations imposed by existing agreements to
which Aventis is a Party. Such obligations are described in greater detail in
Exhibits 1.6, 1.7, 1.8 and 1.10. The covenant is granted as of the Effective
Date for those licenses to be granted (or any future assignments to be made) to
Introgen Therapeutics with respect to which a Third Party consent has not been
obtained.
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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(a) The covenant will expire and terminate as to any
patent when a license is granted (or an assignment made) or upon the expiration
of [*] days after an offer of such a license (or assignment) is made but not
accepted by Introgen Therapeutics as specified in Section 7.3.1 below.
(b) The Aventis Parties will not transfer any rights in
any patents that are subject to a continuing covenant not to xxx to any Third
Party that will not agree to a similar covenant.
7.3 Payment Obligations. Introgen Therapeutics will not owe any
royalty to Aventis under the Licensed Patents or Licensed Technology. However,
Introgen Therapeutics shall, within 30 days of notification by either Aventis
Party, reimburse Aventis for any amounts that are payable by Aventis to
non-Affiliate Third Parties or a Government Entity pursuant to a Third Party
Agreement, including any royalties, license fees, milestone payments, or other
payments due to such Third Parties, which in each case become due after the
Effective Date as a result of a license granted to Introgen Therapeutics or
Introgen Therapeutics's exercise of any of the rights granted under Sections
3.1.1, 3.1.2 and 3.1.3 with respect to such Third Party Agreements.
7.3.1 Refusal of Licenses. Introgen Therapeutics shall have
the right to decline any license or assignment offered pursuant to Section 7.2
if it does not wish to pay any associated royalties, milestone payments, or
other payments due as a result of such license or assignment. However, pursuant
to Section 7.2.1(a) above, any covenant not to xxx under Section 7.2.1 shall
then expire and terminate at the end to [*] days after the offer of such license
or assignment.
7.3.2 Payments by the Aventis Parties. The Aventis Parties
shall remain responsible for any royalties, milestone payments, or other
payments owed to Third Parties that are incurred as a result of Aventis'
activities and not as a result of activities by Introgen Therapeutics.
7.4 CRADA Side Letter. The terms of the CRADA Side Letter are hereby
incorporated into, and made a part of, this Agreement. For the purposes of these
terms, the Original p53 Agreement shall be considered terminated such that, as
of the Effective Date of this Agreement, the termination provisions set forth in
Section 6 of the CRADA Side Letter shall be considered applicable to and binding
upon each of Introgen Therapeutics and APPI.
7.5 Safe Harbor Privacy Principles. The Parties hereby acknowledge
that certain patient information to be transferred under this Agreement, and
under Article 2 in particular, has been gathered or is held in a European Union
Member Country. This patient data may be governed by the European Commission
Directive on Data Protection (October, 1998) and may not be transferred to a
U.S. entity until such entity certifies its Adherence to the Safe Harbor with
the U.S. Department of Commerce. The form for such adherence may be found at
xxxx://xxx.xxx.xxx.xxx/xxxxxxxxxx/XXXxx.xxx/XxxxXxxxxx?XxxxXxxx> (accessed June
27, 2001). The Aventis Parties shall have no duty to convey to Introgen
Therapeutics any patient information that may not be freely conveyed to a United
States corporation under the European Commission Directive or any related
European Union member country law until such time as the Aventis Parties have
received confirmation of Introgen Therapeutic's Certification of Adherence to
the Safe Harbor.
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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Furthermore, Introgen Therapeutics shall indemnify Aventis for all damages
arising out of any violations of the Safe Harbor by Introgen Therapeutics.
8. COSTS AND PAYMENTS
8.1 Aventis Transition Costs. Introgen Therapeutics shall pay to the
Aventis Parties, without right of setoff or counterclaim, the sum of [*]. Such
amount shall be payable in [*] installments of [*] each, which payments shall be
due on [*] and on [*], respectively. The Parties acknowledge and agree that this
amount is not intended to reimburse the Aventis Parties for all of the costs it
incurs in performing its obligations under Article 2, and that the amount
specified in this Section 8.1 shall not in any way limit the obligations of the
Aventis Parties under Article 2.
8.2 Payment Method. Except as otherwise specifically agreed by the
Parties, all payments due under this Agreement shall be made by bank wire
transfer in immediately available funds from a U.S. account to an account that
the recipient designates. All payments under this Agreement shall be made in
U.S. dollars.
8.3 Late Payment. Any payments due under this Agreement that are not
paid within ten (10) days of the date such payments are due shall bear interest
to the extent permitted by applicable law at an annual rate equal to the prime
rate as reported by The Chase Manhattan Bank,
New York,
New York, on the date
such payment is due, plus an additional [*], calculated on the number of days
such payment is delinquent. This Section 8.3 in no way limits any other remedies
available to any Party.
8.3.1 Commercial Purpose; Usury Savings. It is the intent of
the Parties to conform to and contract in strict compliance with applicable
usury law. In no way, nor in any event or contingency, shall interest exceed the
maximum nonusurious amount (the "Maximum Amount") permitted by Applicable Law.
If, from any possible construction of any document or from receipt of anything
of value by a Party, interest would otherwise be payable in excess of the
Maximum Amount, any such construction or receipt shall be subject to the
provisions of this Section 8.3.1 and such document shall be automatically
reformed and the interest payable shall be automatically reduced to the Maximum
Amount, without the necessity of execution of any amendment or new document, and
any interest in excess of the Maximum Amount shall be applied to the reduction
of the amount owing by such Party, or refunded to such Party or other payor
thereof if and to the extent such excessive amount exceeds such unpaid amount.
9. INTELLECTUAL PROPERTY
9.1 Patent Prosecution.
9.1.1 Prosecution by Granting Party. The Granting Party may,
at its expense, control the preparation, filing, prosecution and maintenance of
the patent applications and
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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patents within the Licensed Patents or Licensed Technologies worldwide, in such
countries as it deems appropriate, and conducting any interferences,
re-examinations, reissues, oppositions or requests for patent term extensions
and restorations relating to the Licensed Patents or Licensed Technology, using
counsel of its choice.
9.1.2 Prosecution by Licensee Party. Should the Granting
Party elect not to pursue the filing, support the U.S. and/or international
continued of, or continue the financial support or maintenance of patent
applications and patents within the Licensed Patents or Licensed Technologies,
the Granting Party shall notify the Licensee Party promptly and in writing. Such
notification shall be at least [*] days before any deadline by which action must
be taken to preserve a patent right. If the Granting Party fails to provide such
[*] day notification, then the Granting Party shall pay any necessary fees and
take any necessary action to prevent loss of the patent right. Upon receipt of
notification, the Licensee Party shall, within [*] days and in writing, notify
the Granting Party if the Licensee Party wishes to preserve the patent right.
Upon receipt of such notification the Granting Party shall promptly assign such
patent rights to the Licensee Party, subject to Section 9.3 and shall reasonably
provide the Licensee Party with copies of the documents relating to and
reasonably necessary to protect the interests in the patent or patent
application on a continuing basis. Until the assignment is completed, the
Granting Party shall, at the direction of the Licensee Party, take actions and
make payments to preserve the patent rights until such assignment may be
effected, subject to reimbursement from the Licensee Party.
9.1.3 Continuation of Oppositions. Notwithstanding anything to the
contrary in this Article 9, the Aventis Parties shall continue, until final
determinations are reached or the Parties otherwise agree, the current
opposition of the three p53-related oppositions now pending in the European
Patent Office, specifically, the opposition against the [*] patent. Introgen
Therapeutics shall reimburse each of the Aventis Parties for the reasonable
out-of-pocket expenses incurred in connection with its obligations to continue
these oppositions.
9.2 Enforcement of Exclusively Licensed Technology. If any patents
exclusively licensed under this agreement relating to INGN 201 or K-ras are
infringed by a Third-Party, or are subject to a declaratory judgment action
arising from such infringement, the Aventis Parties shall promptly notify
Introgen Therapeutics. The Aventis Parties have the initial right (but not the
obligation) to enforce INGN 201 or K-ras patents licensed under Licensed Patents
herein, or to defend any declaratory judgment action with respect thereto, at
their expense. If the Aventis Parties fail to initiate a suit to enforce any
such exclusively licensed patents against a commercially significant
infringement within [*] days of a request by Introgen Therapeutics, Introgen
Therapeutics may initiate such suit at its expense. The Party involved in any
such claim, suit or proceeding, shall keep the other Party hereto reasonably
informed of the progress of any such claim, suit or proceeding. Any recovery by
such Party received as a result of any such claim, suit or proceeding shall be
used first to reimburse such Party for all expenses (including attorneys and
professional fees) incurred in connection with such claim, suit or proceeding.
In either case, the remainder shall be shared equally by the Aventis Parties and
Introgen Therapeutics. The Aventis Parties and Introgen Therapeutics agree to
cooperate fully with one another in any such action, including, without
limitation, by joining as a Party, provided that the Party initiating the suit
reimburses the other for any out-of-pocket expenses that are reasonably incurred
in providing such cooperation. It is understood that nothing in
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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this Section 9.2 shall be deemed to grant the Aventis Parties or Introgen
Therapeutics the right to license any Third Party for activities within a field
licensed exclusively to Introgen Therapeutics or the Aventis Parties under this
Agreement, and the recoveries to be shared under this Section 9.2 shall not be
deemed to include any amounts received by Introgen Therapeutics or the Aventis
Parties with respect to a sublicense of INGN 201 or any K-ras Licensed Patents.
9.3 Third Party Rights. The foregoing provisions of this Article 9
are subject to and limited by any Third Party Agreements pursuant to which the
Granting Party acquired any particular Licensed Patents or Licensed
Technologies. It is understood that such agreements may require, for example,
that the licensor Party from whom the Granting Party acquired a license to such
Licensed Technology control the prosecution of particular patents and patent
applications and does not permit access or an opportunity to comment on any
documents filed in patent offices.
10. REPRESENTATIONS AND WARRANTIES
10.1 General Warranties. Each Party warrants and represents to the
other Parties that (i) it has the full right and authority to enter into this
Agreement, grant the rights and licenses granted herein and perform its
obligations hereunder, subject to the approval of certain Third Parties and
Governmental Entities, including, but not limited to those described in Exhibit
1.50 (ii) it has not previously granted and will not grant any rights in
conflict with the rights and licenses granted herein.
10.2 Additional Warranties of the Aventis Parties. In addition to
Section 10.1, the Aventis Parties represent and warrant to Introgen Therapeutics
that:
10.2.1 Neither of the Aventis Parties has, and neither of
them will, seek, or authorize any Third Party to seek, patent protection on any
invention made in the course of performing its responsibilities under Article 2.
10.2.2 The Assigned Marks described in Exhibit 1.4 include
all Marks, as of the Effective Date, Aventis (a) owns of controls, or in which
Aventis otherwise has rights, for INGN 201, (b) has used or has intended to use
in connection with INGN 201; to Aventis' knowledge, there are no pending
proceedings or litigation before any Governmental Entity (including the United
States Patent and Trademarks Office) or any other adverse claims, and no such
proceedings, litigation or any other adverse claims are threatened, by any
Person against the use by Aventis or any of its Affiliates with respect to any
Assigned Marks; and all material and necessary registration, maintenance and
renewal fees in connection with the Assigned Marks have been paid and all
material and necessary documents and certificates in connection with the
Assigned Marks have been filed with the relevant patent, copyright, trademark or
other authority in the United States or international or foreign jurisdictions,
as the case may be, for the purposes of maintaining the Assigned Marks except
(i) where the Aventis Parties have determined in the ordinary course of business
not to maintain such Assigned Marks; or (ii) where the failure to make such
payments or filings would not, in the aggregate, be reasonably expected to have
a material adverse effect upon the rights of the holder of such Assigned Xxxx.
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10.2.3 The Aventis Parties have provided to Introgen
Therapeutics true, complete and correct copies of all Clinical Trial Agreements;
Aventis is not in breach in any material respect of any Clinical Trial Agreement
or Third Party Agreement.
10.2.4 The patents and patent applications described in
Exhibit 1.8 include all patent rights that, as of the Effective Date: (i)
Aventis or its Affiliates own or Control; (ii) cover subject matter invented
before the Effective Date of this Agreement; and (iii) cover the manufacture,
sale, offering for sale, importation or use of INGN 201. To the knowledge of
Aventis, there are no Additional Aventis Patent Rights. In the event that any
Additional Patent Rights are discovered at a later time, the Aventis Parties
shall promptly grant a license to same to Introgen Therapeutics upon the same
terms and conditions provided in Section 3.1.1.
10.2.5 There are no existing or threatened actions, suits or
claims pending against Aventis with respect to the Licensed Aventis Patents,
Licensed Technologies, Transition Assets, INGN 201 or the right of the Aventis
Parties to enter into and perform their obligations under this Agreement.
Aventis has not previously granted, and will not grant during the term of this
Agreement, any right, license or interest that is in conflict with the rights or
licenses granted under this Agreement.
10.3 Additional Warranties of Introgen Therapeutics. In addition to
Section 10.1, Introgen Therapeutics represents and warrants to the Aventis
Parties that there are no existing or threatened actions, suits or claims
pending against it with respect to the Licensed Introgen Therapeutics Patents;
and it has not previously granted any right, license or interest that is in
conflict with the rights or licenses granted under this Agreement.
10.4 Disclaimer of Warranties. INTROGEN THERAPEUTICS AND THE AVENTIS
PARTIES EXPRESSLY DISCLAIM ANY WARRANTIES OR CONDITIONS, EXPRESS, IMPLIED,
STATUTORY OR OTHERWISE, OTHER THAN THOSE EXPRESSLY STATED IN THIS ARTICLE 10,
AND WITHOUT LIMITATION, EXPRESSLY DISCLAIM ANY WARRANTY OF MERCHANTABILITY,
NONINFRINGEMENT, OR FITNESS FOR A PARTICULAR PURPOSE, VALIDITY OF ANY PATENTS,
AND NON-INFRINGEMENT OF THE INTELLECTUAL PROPERTY RIGHTS OF THIRD PARTIES.
10.5 Effect of Representations and Warranties. It is understood that
if the representations and warranties under this Article 10 are not true and
accurate and either Introgen Therapeutics or either of the Aventis Parties
incurs liabilities, costs or other expenses as a result of such falsity,
Introgen Therapeutics or the Aventis Parties, as the case may be, shall
indemnify, defend and hold the other Party harmless from and against any such
liabilities, costs or expenses incurred, provided that the indemnifying Party
receives prompt notice of any claim against Introgen Therapeutics or the Aventis
Parties, as the case maybe, resulting from (i) such falsity; (ii) the
cooperation of the indemnified Party, as requested in connection with any such
claim; and (iii) the sole right to control the defense or settlement thereof.
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11. CONFIDENTIALITY
11.1 Confidential Information. Except as expressly provided herein,
the receiving Party shall keep confidential and shall not publish or otherwise
disclose and shall not use for any purpose any information furnished to it by
another Party pursuant to this Agreement ("Confidential Information") except to
the extent that it can be established by the receiving Party by competent proof
that such Confidential Information:
11.1.1 was already known to the receiving Party, other than
under an obligation of confidentiality, at the time of disclosure;
11.1.2 was generally available to the public or otherwise
part of the public domain at the time of its disclosure to the receiving Party;
11.1.3 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
11.1.4 was subsequently lawfully disclosed to the receiving
Party by a person other than a Party or developed by the receiving Party without
reference to any information or materials disclosed by the disclosing Party.
11.2 Previously Disclosed Confidential Information. Any confidential
information received by a Party or its Affiliate pursuant to the Original
Agreement or the Confidentiality Agreement shall be deemed to have been received
by such Party under this Agreement and to be Confidential Information under this
Agreement. Without limiting the generality of the preceding sentence, each of
the Parties will promptly return to the other Party all confidential information
and materials provided under the Confidentiality Agreement relating to subject
matter that was not incorporated into this Agreement, including but not limited
to [*] and [*] ("Unused Confidential Information"). Upon request of a
Party that disclosed Unused Confidential Information to another Party, the
receiving Party shall promptly return to the disclosing Party or destroy all
such information and certify in writing to the disclosing Party of such return
or destruction.
11.3 Permitted Disclosures. Each Party hereto may use and disclose
another's Confidential Information to the extent such disclosure is in
connection with the exercise of its rights hereunder (including in connection
with the grant of a sublicense), provided that if a Party is required to make
any such disclosure of another Party's Confidential Information, other than
pursuant to a confidentiality agreement, it will use reasonable efforts to
secure confidential treatment of such information prior to its disclosure.
11.4 Compelled Disclosure of Confidential Information.
Notwithstanding the foregoing, a Party may disclose another Party's Confidential
Information to the extent such disclosure is required by law or by a court;
provided, however, the receiving Party shall provide prompt written notice to
the disclosing Party of such requirement so that the disclosing Party may seek a
protective order or other appropriate remedy. In the event that no such
protective order or other remedy is obtained, the receiving Party shall disclose
only that portion of the Confidential Information that it is legally required to
disclose and shall exercise all reasonable efforts to obtain confidential
treatment for such Confidential Information.
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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12. INDEMNIFICATION
12.1 Indemnification of Introgen Therapeutics. The Aventis Parties
shall indemnify each of Introgen Therapeutics and the directors, officers,
employees, and counsel of Introgen Therapeutics and such Affiliates and the
successors and assigns of any of the foregoing (the "Introgen Therapeutics
Indemnitees"), pay on demand and protect, defend, save and hold each Introgen
Therapeutics Indemnitee harmless from and against, any and all liabilities,
damages, losses, settlements, claims, actions, suits, penalties, fines, costs or
expenses (including, without limitation, reasonable attorneys' fees and other
expenses of litigation) (any of the foregoing, a "Claim") incurred by any
Introgen Therapeutics Indemnitee, arising from or occurring as a result of: (i)
activities performed by or under the control of Aventis in connection with the
Ongoing Clinical Trials or Later Stage Development; and (ii) Third-Party claims,
including without limitation, product-liability claims relating to any products
used, sold or otherwise distributed by Aventis or sublicensees (other than
Introgen Therapeutics) of Aventis. For purposes of this Section 12.1, it is
understood that product- liability claims that arise out of the marketing or use
of a product by or under authority of Introgen Therapeutics in a country after
obtaining governmental approval to market such product shall not be deemed to
"arise from or occur as a result of" the activities of Aventis described above.
12.2 Indemnification of the Aventis Parties. Introgen Therapeutics
shall indemnify each of the Aventis Parties and the directors, officers,
employees, and counsel of the Aventis Parties and the Affiliates of the Aventis
Parties and the successors and assigns of any of the foregoing (the "Aventis
Indemnitees"), pay on demand and protect, defend, save and hold each Aventis
Indemnitee harmless from and against any and all liabilities, damages, losses,
settlements, claims, actions, suits, penalties, fines, costs or expenses
(including, without limitation, reasonable attorneys' fees and other expenses of
litigation) (any of the foregoing, a "Claim") incurred by any Aventis
Indemnitee, arising from or occurring as a result of: (i) activities performed
by or under the direction or control of Introgen Therapeutics in connection with
the Ongoing Clinical Trials or Later Stage Clinical Development; and (ii)
Third-Party claims, including without limitation, product-liability claims,
relating to any products used, sold or otherwise distributed by Introgen
Therapeutics, its Affiliates or sublicensees (other than Aventis).
12.3 Procedure. A Party (the "Indemnitee") that intends to claim
indemnification under this Article shall promptly notify the other Party (the
"Indemnitor") in writing of any loss, claim, damage, liability or action in
respect of which the Indemnitee or any of its Affiliates, sublicensees or their
directors, officers, employees or agents intend to claim such indemnification,
and the Indemnitor shall have the right to participate in, and, to the extent
the Indemnitor so desires, to assume the defense thereof with counsel mutually
satisfactory to the Parties; provided, however, that Indemnitee shall have the
right to retain its own counsel, with the fees and expenses to be paid by the
Indemnitor, if representation of such Indemnitee by the counsel retained by the
Indemnitor would be inappropriate due to actual or potential differing interests
between such Indemnitee and any other Party represented by such counsel in such
proceeding. The indemnity agreement in this Article 12 shall not apply to
amounts paid by Indemnitee in settlement of any loss, claim, damage, liability
or action if such settlement is effected without the consent of the Indemnitor,
which consent shall not be withheld unreasonably. The failure to deliver written
notice to the Indemnitor within a reasonable time
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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 but the omission so to deliver written notice to
the Indemnitor shall not relieve it of any liability that it may have to any
Indemnitee otherwise than under this Article. The Indemnitee under this Article,
its employees and agents, shall cooperate fully with the Indemnitor and its
legal representatives in the investigation of any action, claim or liability
covered by this indemnification and the defense thereof.
13. MUTUAL RELEASE
13.1 Introgen Therapeutics Release. As of the Effective Date,
Introgen Therapeutics releases, acquits and forever discharges the Aventis
Parties, together with each of their respective present and former Affiliates,
officers, directors, employees, agents, attorneys, parent companies,
subsidiaries, successors and assigns, of and from any and all claims, causes of
action, demands, expenses and damages which Introgen Therapeutics or any of its
Affiliates may have had, or may now have, or may hereafter have, from the
beginning of time to the Effective Date, real or suspected, known or unknown,
actual or contingent, direct or derivative, including but not limited to any
such claims, causes of action, demands, expenses and damages relating to or
arising out of the Original p53 Agreement, Original K-ras Agreement,
Confidentiality Agreement, Term Sheet, CRADA Side Letter or any activities
undertaken pursuant to or in connection with such agreements.
13.2 Aventis Release. As of the Effective Date, the Aventis Parties
release, acquit and forever discharge Introgen Therapeutics, together with each
of its present and former Affiliates, officers, directors, employees, agents,
attorneys, parent companies, subsidiaries, successors and assigns, of and from
any and all claims, causes of action, demands, expenses and damages which
Aventis or any of its Affiliates may have had, or may now have, or may hereafter
have, from the beginning of time to the Effective Date, real or suspected, known
or unknown, actual or contingent, direct or derivative, including but not
limited to any such claims, causes of action, demands, expenses and damages
relating to or arising out of the Original p53 Agreement, Original K-ras
Agreement, Confidentiality Agreement, Term Sheet, CRADA Side Letter or any
activities undertaken pursuant to or in connection with such agreements.
14. TERM AND TERMINATION
14.1 Term. This Agreement shall become effective as of the Effective
Date and, unless earlier terminated pursuant to the other provisions of this
Article 14, shall continue in full force and effect until the expiration of the
last patent within the Licensed Patents or Licensed Technologies or the
abandonment of the last patent application within the Licensed Patents or
Licensed Technologies, whichever is later, unless earlier terminated under this
Article 14. Licenses to each particular patent terminate upon expiration of such
patent.
14.2 Termination for Cause. Either the Aventis Parties or Introgen
Therapeutics may terminate this Agreement if the other Party materially breaches
or defaults in the performance of
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any of its material obligations under this Agreement, and that material breach
or default continues for [*] days after the non-breaching Party provides written
notice to the breaching Party of the material breach or default. Any termination
shall become effective at the end of such [*]-day period unless the breaching
Party (or any other Party on its behalf) has cured any such breach or default
prior to the expiration of the [*]-day period.
14.3 Termination of Particular Patent or Technology License. The
Licensee Party may terminate its license under this Agreement with respect to
any or all of the Licensed Patents or Licensed Technologies, from time to time,
upon notice to the Granting Party. In such event, the technology specified in
such notice shall, from and after the date of such notice, cease to be within
the Licensed Patents or Licensed Technologies. Similarly, the Licensee Party may
terminate one or more of the licenses to it under this Agreement with respect to
a particular product or activity, from time to time, upon notice to the Granting
Party; and in such event such product or activity, as the case may be, shall not
be so licensed; provided, however, that if the Licensee Party elects to
terminate a license under this Section 14.3, such Licensee Party shall remain
liable to the Granting Party for any Third- Party payments during the period of
such license that would otherwise be required by Section 7.3. In the event of a
material breach by a Licensee Party of a license relating to a Licensed Patent
or Licensed Technology and that material breach continues for [*] days after the
Granting Party provides written notice to the breaching Licensee Party of the
material breach, the Granting Party may terminate such license with respect to
any or all of the Licensed Patent or Licensed Technology. Any such termination
shall become effective at the end of such [*]-day period unless the breaching
Licensee Party (or any other Party on its behalf) has cured any such breach
prior to the expiration of the [*]-day period. In the event such a termination
occurs, (i) the technology specified in such notice shall, from and after the
date of such notice, cease to be within the Licensed Patents or Licensed
Technologies, and (ii) such Licensee Party shall remain liable to the Granting
Party for any Third- Party payments during the period of such license that would
otherwise be required by Section 7.3.
14.4 Effect of Breach or Termination.
14.4.1 Accrued Obligations. Termination of this Agreement for
any reason shall not release any Party hereto from any liability which, at the
time of 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.
14.4.2 Survival. Articles 2, 5, 7, 8, 10, 11, 12 and 14 of
this Agreement shall survive expiration or termination of this Agreement for any
reason. Notwithstanding the foregoing, (i) upon termination of this Agreement by
reason of a material breach by the Aventis Parties, Section 3.2 shall terminate
and not survive; and (ii) upon termination of this Agreement by reason of a
material breach by Introgen Therapeutics, Section 3.1 and Section 7.2 and the
licenses and covenants described in therein shall terminate and not survive.
14.5 Termination for Failure of Closing to Occur. This Agreement and
each other agreement and instrument executed by the Parties pursuant to the
provisions of this Agreement, including the Stock Purchase Agreement, the
Registration Rights Agreement, the Voting Agreement, the p53 Assignment
Agreement and the K-ras Assignment Agreement, shall be terminated and shall
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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be of no force or effect in the event that the Closing (as defined in the Stock
Purchase Agreement) shall not have occurred on or before 4 p.m., Central time,
on Monday, July 2, 2001.
15. MISCELLANEOUS
15.1 Governing Law. This Agreement and any dispute arising from the
performance or breach hereof shall be governed by and construed and enforced in
accordance with, the laws of the State of
New York without reference to
conflicts of laws principles.
15.2 Force Majeure. Nonperformance of any Party (except for payment
obligations) shall be excused to the extent that performance is rendered
impossible by strike, fire, earthquake, flood, governmental acts or orders or
restrictions, failure of suppliers, or any other reason where failure to perform
is beyond the reasonable control and not caused by the negligence or intentional
conduct or misconduct of the nonperforming Party.
15.3 No Implied Waivers; Rights Cumulative. No failure on the part
of Introgen Therapeutics or the Aventis Parties to exercise any right and no
delay in exercising any right under this Agreement, or provided by statute or at
law or in equity or otherwise, shall impair, prejudice or constitute a waiver of
any such right, nor shall any partial exercise of any such right preclude any
other or further exercise thereof or the exercise of any other right.
15.4 No Implied Obligations. Nothing in this Agreement shall be
deemed to require Introgen Therapeutics or the Aventis Parties to exploit the
Licensed Patents or Licensed Technologies nor prevent Introgen Therapeutics or
the Aventis Parties from commercializing products or other items similar to or
competitive with the Licensed Patents or Licensed Technologies, in addition to
or in lieu of the Licensed Patents or Licensed Technologies.
15.5 Independent Contractors. Nothing contained in this Agreement is
intended implicitly, or is to be construed, to constitute Introgen Therapeutics
or the Aventis Parties as partners in the legal sense. No Party hereto shall
have any express or implied right or authority to assume or create any
obligations on behalf of or in the name of any other Party or to bind any other
Party to any contract, agreement or undertaking with any Third Party.
15.6 Notices. All notices, requests and other communications
required or permitted to be given to a Party under this Agreement shall be in
writing and shall be deemed to have been duly given if (i) personally delivered
(by courier service or otherwise) or sent by registered or certified mail
(return receipt requested and postage prepaid), in each case to the respective
address specified below, or such other address as may be specified in writing by
such Party to the other Parties hereto; or (ii) sent by confirmed telecopier, as
follows:
APSA: 20 Avenue Xxxxxxx
XXXX F-92165
Antony
Cedex
France
Fax: 00 0 00 00 00 00
Attn: General Counsel
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with a copy (which shall not constitute notice) to:
(1) Xxxxxxx X. Xxxxxx
Vice President, Legal - Corporate Development
Xxxxx 000-000
Xxxxxxxxxxx, Xxx Xxxxxx 00000 - 0800
Fax: 000-000-0000
and to:
(2) Xxxxx Xxxxx L.L.P.
One Shell Plaza
000 Xxxxxxxxx Xxxxxx
Xxxxxxx, Xxxxx 00000
Attention: Xxx X. Xxxx
Fax: 000-000-0000
APPI: Xxxxx 000-000
Xxxxxxxxxxx, Xxx Xxxxxx 00000 - 0800
Fax: 000-000-0000
Attn: Senior Vice President -Corporate Development
with a copy (which shall not constitute notice) to:
(1) Xxxxxxx X. Xxxxxx
Vice President, Legal - Corporate Development
Xxxxx 000-000
Xxxxxxxxxxx, Xxx Xxxxxx 00000 - 0800
Fax: 000-000-0000
and to:
(2) Xxxxx Xxxxx L.L.P.
One Shell Plaza
000 Xxxxxxxxx Xxxxxx
Xxxxxxx, Xxxxx 00000
Attention: Xxx X. Xxxx
Fax: 000-000-0000
-31-
33
Introgen Therapeutics:
Introgen Therapeutics, Inc.
000 Xxxxxxxx Xxx.
Xxxxx 0000
Xxxxxx, Xxxxx 00000
Fax: (000) 000-0000
Attn: President
with a copy (which shall not constitute notice) to:
Xxxxxx Xxxxxx, Esq.
Xxxxxx & Xxxxxx, L.L.P.
000 Xxxxxxxx Xxxxxx
Xxxxxx, Xxxxx 00000
and
Xxxxxx Xxxxxxx Xxxxxxxx & Xxxxxx
Professional Corporation
000 Xxxx Xxxx Xxxx
Xxxx Xxxx, Xxxxxxxxxx 00000-0000
Attention: Xxxxxxx X. Xxxxx, Esq.
15.7 Assignment. Except as permitted by Section 15.7.1, neither this
Agreement nor any obligation hereunder shall be assignable or delegable by any
Party to any Third Party without the prior written consent of the other Parties
hereto; except that a Party may assign this Agreement without the other Parties'
consent to an entity that acquires substantially all of the business or assets
of such Party, whether by merger, acquisition or sale.
15.7.1 Assignment to Gencell. This entire Agreement and all
obligations hereunder may be assigned by the Aventis Parties to Gencell in the
event that Gencell is formed after the Effective Date. The Aventis Parties shall
notify Introgen Therapeutics within 60 days of any such assignment. Following
any such assignment to Gencell, Gencell shall stand in the place of the Aventis
Parties for the purposes of all rights and obligations under this Agreement
other than for the purposes of Section 2.3.3, Section 2.4, Section 2.5 and
Section 13. In connection with the formation of Gencell, the Aventis Parties
shall cause Gencell to agree to be bound by the provisions of Sections 2.5 and
4.2.5.
15.8 Successors and Assigns. The provisions of this Agreement shall
be binding on and inure to the benefit of, and be binding upon the Parties and
their respective successors and permitted assigns.
15.9 Affiliates. The Aventis Parties shall be responsible for all
actions or omissions of their respective Affiliates, and any action or omission
of any such Affiliate shall be deemed an action or omission of the Aventis
Parties, including for purposes of Section 12.2.
-32-
34
15.10 Amendment. No amendment or modification of any provision of
this Agreement shall be effective unless in writing signed by all of the
Parties. No provision of this Agreement shall be varied, contradicted or
explained by any oral agreement, course of dealing or performance or any other
matter not set forth in an agreement in writing and signed by all of the
Parties.
15.11 Severability. If any provision hereof should be held invalid,
illegal or unenforceable in any jurisdiction, all other provisions hereof shall
remain in full force and effect in such jurisdiction and shall be liberally
construed in order to carry out the intentions of the Parties as nearly as may
be possible. Such invalidity, illegality or unenforceability shall not affect
the validity, legality or enforceability of such provision in any other
jurisdiction.
15.12 Non-Disclosure. Each of the Parties agrees: (i) not to
disclose to any Third Party the financial terms of this Agreement without the
prior written consent of each other Parties, except to advisors, investors and
others on a need to know basis under circumstances that reasonably ensure the
confidentiality thereof, or to the extent required by law. Without limitation
upon any provision of this Agreement, each of the Parties shall be responsible
for the observance by its employees of the foregoing confidentiality
obligations.
15.13 Interpretation. The definitions set forth or referenced in
Article 1 shall apply equally to both the singular and plural forms of the terms
defined. Whenever the context may require, any pronoun shall include the
corresponding masculine, feminine and neuter forms. The words "herein," "hereof"
and "hereunder" and words of similar import refer to this Agreement (including
the Exhibits) in its entirety and not to any part hereof unless the context
shall otherwise require. As used herein, the phrase "to [a Party's] knowledge"
or any similar term relating to the knowledge of a Party means the actual
knowledge of any of the officers (determined in accordance with Rule 16a-1(f)
under the Exchange Act as in effect on the Effective Date) or directors of the
Company or any personnel who participated in the preparation or negotiation of
this Agreement. All references herein to Articles, Sections, Recitals and
Exhibits shall be deemed references to Articles, Sections and Recitals of, and
Exhibits to, this Agreement unless the context shall otherwise require. Unless
the context shall otherwise require, any references to any statute or regulation
are to it as amended and supplemented from time to time (and, in the case of a
statute or regulation, to any successor provisions). Any reference in this
Agreement to a "day" or number of "days" (without the explicit qualification of
"business") shall be interpreted as a reference to a calendar day or number of
calendar days. If any action or notice is to be taken or given on or by a
particular calendar day, and such calendar day is not a business day, then such
action or notice shall be deferred until, or may be taken or given on, the next
business day. References to the term "business day" shall mean any day which is
not a Saturday, Sunday or day on which banks in
New York,
New York are
authorized or required by law to close. As applied to the Aventis Parties, the
phrases "as soon as reasonably practicable," "as promptly as practicable" and
similar phrases shall mean "reasonably promptly under the circumstances, in
light of the other burdens on the time and attention of the directors, officers,
employees and agents of the Aventis Parties, as the case may be, and the
relative benefits to the Aventis Parties of this Agreement and such other
burdens."
15.14 Entire Agreement. Except as set forth in Section 2.1, Section
3 and Section 4, the Transaction Agreements constitute the entire agreement
among the Parties with respect to the
-33-
35
subject matter thereon, and supercede all prior or contemporaneous
understandings or agreements, whether written or oral, among the Parties with
respect to such subject matter.
15.15 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 and the same instrument.
15.16 Headings. Headings used herein are for convenience only and
shall not in any way affect the construction of or be taken into consideration
in interpreting this Agreement.
15.17 Patent Marking. Introgen Therapeutics and the Aventis Parties
agree to xxxx and have their Affiliates and sublicensees xxxx all products
developed under the Licensed Patents or Licensed Technologies they sell or
distribute pursuant to this Agreement in accordance with the applicable statute
or regulations in the country or countries of manufacture and sale thereof.
15.18 Export Laws. Notwithstanding anything to the contrary
contained herein, all obligations of Introgen Therapeutics and the Aventis
Parties are subject to prior compliance with United States export regulations
and such other United States laws and regulations as may be applicable, and to
obtaining all necessary approvals required by the applicable agencies of the
government of the United States. Introgen Therapeutics and the Aventis Parties
shall cooperate with each other and shall provide assistance to the other as
reasonably necessary to obtain any required approvals.
15.19 Telecopy Execution and Delivery. A facsimile, telecopy or
other reproduction of this Agreement may be executed by one or more Parties, and
an executed copy of this Agreement may be delivered by one or more Parties by
facsimile or similar electronic transmission device pursuant to which the
signature of or on behalf of such Party can be seen, and such execution and
delivery shall be considered valid, binding and effective for all purposes. At
the request of any Party hereto, all Parties shall execute an original of this
Agreement as well as any facsimile, telecopy or other reproduction hereof.
-34-
36
IN WITNESS WHEREOF, the Parties have caused this Agreement to be duly
executed and delivered in duplicate originals as of the date first above
written.
INTROGEN THERAPEUTICS, INC. AVENTIS PHARMACEUTICALS PRODUCTS, INC.
By: /s/ XXXXX XXXXX By: /s/ XX. XXXXXX XXXXXXXXXXX
----------------------------------- -----------------------------------
Name: Xxxxx Xxxxx Name: Xx. Xxxxxx Xxxxxxxxxxx
--------------------------------- ---------------------------------
Title: CEO Title: Senior Vice President
-------------------------------- --------------------------------
AVENTIS PHARMA S.A.
By: /s/ XXXXXXXX XXXXX
-----------------------------------
Name: Xxxxxxxx Xxxxx
---------------------------------
Title: Senior Vice President --
DIA France
--------------------------------
[SIGNATURE PAGE TO RESTATED
p53 and K-ras AGREEMENT]
-35-
37
EXHIBIT 1.4
ASSIGNED MARKS - AS RELATED TO INGN 201
[*]
(*) Some marks may not be transferred to a U.S. Company
(**) Aventis has learned through its trademark survey services that a
trademark application for the name [*] has been made by Bayer in Colombia,
Costa Rica, Indonesia, Nicaragua, New Zealand and Paraguay. Aventis has filed
oppositions in these countries in order to protect its prior rights on the
trademark [*]. Bayer has informed Aventis that its trademark is intended to
be used for 'pharmaceutical preparations, namely anti-infection preparations,
diagnostic preparations for medical purposes. Upon transfer of its rights to the
trademark [*] to Introgen, Introgen will have to decide whether it wishes to
continue the oppositions.
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
38
EXHIBIT 1.6
EXISTING AVENTIS DELIVERY PATENTS
FILE PCT NUMBER THIRD PARTY INVOLVEMENT TITLE
----------- ---------- ------------------------------------------- ------------------------------------------------
[*] [*] [*] [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
39
EXHIBIT 1.7
EXISTING AVENTIS K-RAS PATENTS
FILE PCT NUMBER THIRD PARTY INVOLVEMENT TITLE
------- ---------- ----------------------- -----------------------------------------------------
[*] [*] [*] [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
40
EXHIBIT 1.8
EXISTING AVENTIS p53 PATENTS
FILE PCT NUMBER THIRD PARTY INVOLVEMENT TITLE
---- ---------- ---------------------------- ----------------------------------------------------
[*] [*] [*] [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
41
EXHIBIT 1.10
EXISTING AVENTIS TARGETING PATENTS
FILE PCT NUMBER THIRD PARTY INVOLVEMENT TITLE
------- ---------- ----------------------- -----------------------------------------------
[*] [*] [*] [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
42
EXHIBIT 1.12
CLINICAL TRIAL AGREEMENTS
o Agreement for Central [*] Services (T301) dated December 1, 2000,
between Aventis Pharmaceuticals Inc. and [*] Central Laboratory
Srvcs., Inc.
o Agreement for Central [*] Services (T302) dated December 1, 2000,
between Aventis Pharmaceuticals Inc. and [*] Central Laboratory
Srvcs., Inc.
o Agreement for Clinical monitoring and data management Services (T301)
dated March 19, 2001 between Aventis Pharmaceuticals Products, Inc.
and [*]
o Agreement for Clinical monitoring and data management Services (T302)
dated March 19, 2001, between Aventis Pharmaceuticals Products, Inc.
and [*]
o Clinical Randomization services (T301) dated June 1, 2000, between
Aventis Pharmaceuticals Inc and [*]
o Clinical Randomization services (T302) dated June 1, 2000, between
Aventis Pharmaceuticals Inc and [*]
o Regulatory Affairs consulting Agreement dated August 14, 2000, between
Aventis Pharmaceuticals Inc. and [*]
o Service Contract (Contrat de Prestation) dated September 2000 (Clichy,
Septembre 2000), between Aventis Pharma (Aventis Pharma Recherche et
Developpement) and [*]( new contract to be established between
Introgen and [*] as the Aventis contract covers more that
p53)
o Convention on the Center of Reference IGR/ RPR (Convention Relative Au
Centre de Reference IGR / RPR) dated February 11, 2000 between
Xxxxx-Xxxxxxx Xxxxx Recherche-Developpment and [*] (No contract
transfer but facilitation of contract between [*] and Introgen)
ALL ASSIGNMENTS OF AGREEMENTS IN THIS EXHIBIT 1.12 SHALL BE MADE AS
PROVIDED IN SECTION 2.2.1(c) AND SUBSTANTIALLY IN THE FORM OF EXHIBIT 2.2.1(c).
AS NOTED ABOVE, CERTAIN CLINICAL TRIAL AGREEMENTS MAY NOT BE ASSIGNED TO
INTROGEN THERAPEUTICS AND OTHERS HAVE BEEN SUPERSEDED BY LATER AGREEMENTS
BETWEEN INTROGEN THERAPEUTICS AND THE NON-AVENTIS CLINICAL TRIAL PARTY. THE
AVENTIS PARTIES SHALL HAVE NO DUTY TO ASSIGN ANY NON-ASSIGNABLE OR SUPERSEDED
CLINICAL TRIAL AGREEMENT, AND ANY FAILURE TO DO SO SHALL NOT BE DEEMED A BREACH
OF THIS AGREEMENT. THE AVENTIS PARTIES SHALL ENDEAVOR TO TERMINATE ALL
NON-ASSIGNABLE OR SUPERSEDED CLINICAL TRIAL AGREEMENTS WHEN DIRECTED TO DO SO BY
INTROGEN THERAPEUTICS PURSUANT TO ARTICLE 2, OR AT THE END OF THE TRANSITION
PERIOD.
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
43
EXHIBIT 1.14
CRADA SIDE LETTER
EXECUTED COPY
INTROGEN THERAPEUTICS, INC.
000 Xxxxxxxx Xxxxxx, Xxxxx 0000
Xxxxxx, XX 00000
512) 320-5010
October 8, 1998
Xxxxx-Xxxxxxx Xxxxx Pharmaceuticals, Inc.
000 Xxxxxx Xxxx, X.X. Xxx 0000
Xxxxxxxxxxxx, XX 00000-0000 Attn:
re: PROPOSED COLLABORATIVE RESEARCH AND DEVELOPMENT AGREEMENT (CRADA) WITH
THE NATIONAL CANCER INSTITUTE
Gentlemen:
Introgen Therapeutics ("Introgen") and Xxxxx-Xxxxxxx Xxxxx Pharmaceuticals, Inc.
("RPRP") have been parties to a negotiation with the National Cancer Institute
(the "NCI") for the conduct of a collaborative research and development project,
pursuant to which the NCI will conduct certain [*] trials of Adv5CMV-p53 (INGN
201) to treat various cancers under an as yet to be executed agreement (the
"CRADA"). INGN 201 is a "Collaboration Product" under the Collaboration
Agreement (p53 Products) dated 7 October, 1994 between Introgen and RPRP (the
"Collaboration Agreement").
The purpose of this letter (the "Side Letter") is to establish and coordinate
the rights and obligations of Introgen and RPRP with respect to the CRADA, but
only in the event that the CRADA is executed by Introgen, RPRP, and the NCI.
In the event that the CRADA is so executed, Introgen and RPRP agree as follows:
1. Any capitalized term herein shall have the meaning as defined in the
Collaboration Agreement or the CRADA (as the case may be), unless
otherwise expressly defined in this Side Letter. In the event of any
conflict or inconsistency between the CRADA on the one hand, and this
Side Letter or the Collaboration Agreement on the other hand, then as
between Introgen and RPRP, this Side Letter and the Collaboration
Agreement shall control.
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
44
Xxxxx-Xxxxxxx Xxxxx Pharmaceuticals, Inc.
October 8, 1998
Page 2
2. It is understood that [*] and [*] (or such substitutes as RPRP or
Introgen, respectively, may designate in accordance with the CRADA)
will each be a Principal Investigator under the CRADA, and that (as
between the two) [*] will be the primary Principal Investigator,
primary contact and NCI correspondent with respect to [*] and later
clinical trials conducted under the CRADA; and (ii) that [*] will be
the primary Principal Investigator, primary contact and NCI
correspondent with respect to [*] clinical trials conducted under the
CRADA. For purposes of this Side Letter, a [*] trial will be
considered a [*] trial. RPRP and Introgen (respectively, the
"Receiving Party") each agree to send to the other ("Non-Receiving
Party"), copies of all correspondence and any other materials or
information that the Receiving Party receives from the NCI relating to
the CRADA or INGN 201 (including detailed written reports of any
information received orally or in other nontangible form) in each case
within three business day of the time that such items are received
(except in the case where the NCI has already provided such materials
to each Party). In addition, RPRP and Introgen (respectively, the
"Submitting Party") each agree to provide to the other (the
"Non-Submitting Party") copies of all correspondence, materials and
information that the Submitting Party proposes to provide or disclose
to the NCI relating to the CRADA or INGN 201 (including detailed
descriptions of any information to be communicated orally or in other
nontangible form), in each case at least three full business days
prior to first providing or disclosing the same to NCI, and such items
shall be provided to NCI only after RPRP and Introgen have discussed
such submission during said three day period. RPRP and Introgen agree
that their respective personnel will meet with NCI in respect of the
CRADA only after mutual consultation and at times and places that are
mutually acceptable for RPRP, Introgen and NCI. [*] As used in this
Paragraph 2, "NCI" shall include the NCI and any other person or
entity that is acting under authority from or in association with NCI
in performing work relating to the Research Plan.
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
45
Xxxxx-Xxxxxxx Xxxxx Pharmaceuticals, Inc.
October 8, 1998
Page 3
3. RPRP shall reimburse Introgen for the costs incurred by Introgen to
supply Agent (and any other biological materials that Introgen is
required to supply under the CRADA) to NCI pursuant to the CRADA that
are used for [*] trials or [*] required to be performed prior to the
initiation of a [*] trial; for all other Agent supplied to NCI
pursuant to the CRADA, RPRP shall pay to Introgen the [*].
4. Except as contemplated in Paragraph 6 below, neither Introgen nor RPRP
shall terminate the CRADA without the prior written agreement of the
other, except that RPRP or Introgen may request that the NCI delete
the requesting party as a CRADA party thereby transforming the CRADA
into a two party CRADA, with the deleted party retaining no rights
resulting from the CRADA. In such event, it is understood that the
non-requesting party will not be obligated to assume any financial
obligations of the requesting party under the CRADA.
5. It is understood that RPRP and Introgen have certain reciprocal rights
to Introgen and RPRP Technology, respectively, pursuant to the
Collaboration Agreement, and that such Technologies would generally
include applicable intellectual property licensed from NCI pursuant to
Article 7 of the CRADA. Accordingly, RPRP agrees not to exercise its
right under such Article 7 to obtain a license with respect to any
intellectual property pursuant to the CRADA with respect to any
Subject Invention, other than a Subject Invention, made in connection
with a [*] trial conducted under the CRADA, and Introgen agrees not to
exercise its right under such Article 7 to obtain a license with
respect to any Subject Invention made in connection with a [*] trial
conducted under the CRADA. Similarly, RPRP agrees that any information
received from NCI in connection with the conduct of a [*] clinical
trial conducted under the CRADA shall be deemed to be confidential
information of RPRP pursuant to the Collaboration Agreement, and any
information received from NCI other than in connection with a Phase II
clinical trials conducted under the CRADA shall be deemed to be
confidential information of Introgen pursuant to the Collaboration
Agreement.
6. In the event the Collaboration Agreement terminates, then
notwithstanding any of the foregoing Paragraphs of this Side Letter,
the following shall apply:
(a) (i) Except in the case where termination is by RPRP under
Section 18.2 of the Collaboration Agreement for breach by
Introgen, RPRP shall use its best efforts to have the CRADA
amended to remove itself as a party to the CRADA, such that
Introgen and PHS (NCI) are the only parties
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
46
Xxxxx-Xxxxxxx Xxxxx Pharmaceuticals, Inc.
October 8, 1998
Page 4
to the CRADA, and such that RPRP has no further surviving
rights pursuant to the CRADA. Pending such amendment, RPRP
shall use its best efforts to ensure that all rights and
benefits of the CRADA inure to Introgen and/or Introgen's
designee(s). In this connection RPRP shall take such
actions, or refrain from taking such actions, as Introgen
may request in writing, including promptly exercising such
rights, or refraining from exercising such rights, as may
then be provided for RPRP under the CRADA, and executing
such documents or instruments as Introgen may request to
effect the foregoing. This would include, for example,
approving or not approving any action requiring RPRP's
approval under the CRADA, terminating the CRADA, or the
like, immediately upon the request of Introgen. However,
Introgen shall indemnify RPRP (in accordance with the
indemnification procedures set forth in Section 17.3 of the
Collaboration Agreement) from and against any liabilities or
expenses incurred by RPRP as a result of claims made by NCI
against RPRP as a result of RPRP's taking or refraining to
take such actions at Introgen's request pursuant to this
Paragraph 6(a).
(ii) The obligations pursuant to Paragraphs 2 and 4 shall
terminate.
(iii) RPRP's obligations under Paragraph 3 above shall terminate;
provided, however, that if (i) within [*] business days
following the termination of the Collaboration Agreement,
Introgen notifies the NCI in writing that the CRADA is to be
terminated and that Introgen wishes to be released from its
post-CRADA termination supply obligations as set forth in
the CRADA as of the date of the termination of the
Collaboration Agreement and (ii) NCI refuses to release
Introgen from such obligations, then RPRP's obligations
under Paragraph 3 above shall continue [*] and until such
time as [*] or such obligations terminate.
(b) (i) Where termination is by RPRP under Section 18.2 of the
Collaboration Agreement for breach by Introgen, Introgen
shall use its best efforts to have the CRADA amended to
remove itself as a party to the CRADA, such that the RPRP
and PHS(NCI) are the only parties to the CRADA, and such
that Introgen has no further surviving rights pursuant to
the CRADA. Pending such amendment Introgen shall use its
best efforts to ensure that all rights and benefits of the
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
47
Xxxxx-Xxxxxxx Xxxxx Pharmaceuticals, Inc.
October 8, 1998
Page 5
CRADA inure to RPRP and/or RPRP's designee(s). In this
connection Introgen shall take such actions, or refrain from
taking such actions, as RPRP may request in writing,
including promptly exercising such rights, or refraining
from exercising such rights, as may then be provided for
Introgen under the CRADA, and executing such documents or
instruments as RPRP may request to effect the foregoing,
This would include, for example, approving or not approving
any action requiring Introgen's approval under the CRADA,
terminating the CRADA, or the like, immediately upon the
request of RPRP. However, RPRP shall indemnify Introgen (in
accordance with the indemnification procedures set forth in
Section 17.3 of the Collaboration Agreement) from and
against any liabilities or expenses incurred by Introgen as
a result of claims made by NCI against Introgen as a result
of Introgen's taking or refraining to take such action at
RPRP's request pursuant to this Paragraph 6(b).
7. This Side Letter shall be deemed a part of the Collaboration
Agreement, and any breach of this Side Letter shall be deemed a breach
of the Collaboration Agreement. This Side Letter, together with the
Collaboration Agreement and all duly executed amendments and addenda
thereto, constitute the entire agreement with respect to the subject
matter hereof, and supersede all prior or contemporaneous
understanding or agreements, whether written or oral, between Introgen
and RPRP with respect to the subject matter hereof. That certain
Agreement between RPRP and Introgen entered into as of November 21,
1995 is therefore superseded and terminated by this Side Letter.
AGREED AND ACCEPTED:
INTROGEN THERAPEUTICS, INC. XXXXX-XXXXXXX XXXXX
PHARMACEUTICALS, INC.
By: /s/XXXXX XXXXX By: (illegible)
---------------------------------- ----------------------------------
Name: Xxxxx Xxxxx Name: (illegible)
-------------------------------- --------------------------------
Title: President Title: (illegible)
------------------------------- -------------------------------
Date: October 30, 1998 Date: 10/13/98
-------------------------------- --------------------------------
48
EXHIBIT A
APPROVED PROTOCOLS
1. The following protocols were approved in connection with the original
Letter of Intent between the NCI, RPR and Introgen:
- [*]
- [*]
- [*]
- [*]
- [*]
2. Two additional protocols, titled as follows:
- "A Pilot Trial of Adenovirus p53 in [*], and
- [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
49
EXHIBIT 1.26
EXISTING INTROGEN THERAPEUTICS ADENOVIRAL PATENTS
TECHNOLOGY
CASE NUMBER THIRD PARTY INVOLVEMENT (DESCRIPTION)
------------- ---------------------------- ----------------------------------------
INRP: 058, o AS OF THE EFFECTIVE DATE, o PROCESS
WO98/22588 INTROGEN DOES NOT HAVE (Producing purified adenovirus)
U.S. Patent KNOWLEDGE OF ANY SPECIFIC
No. 6,194,191 THIRD-PARTY INVOLVEMENT.
INRP:081, o o PROCESS
US99/26966 (Preparing recombinant adenovirus)
INRP: 067, o o FORMULATION
US99/27177 (Storage stable adenovirus formulations)
INRP: 014, o o GENERAL p53
US Reg. (Determining % of inactive viral vectors
5,637,456 in a sample)
50
EXHIBIT 1.38
ONGOING CLINICAL TRIALS
[*]
[*]
[*]
[*]
[*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
51
EXHIBIT 1.44
REGISTRATION RIGHTS AGREEMENT
This REGISTRATION RIGHTS AGREEMENT (this "Agreement") is entered into
as of June 30, 2001, by and between Introgen Therapeutics, Inc., a Delaware
corporation (the "Company"), and Aventis Pharmaceuticals Products Inc., a
Pennsylvania corporation ( "APPI"). In addition, Xxxxx-Xxxxxxx Xxxxx
International (Holdings), Inc., a Delaware corporation ("RPRIH"), is entering
into this Agreement for the purpose of Section 8.1 only.
RECITALS
WHEREAS, RPRIH is presently the owner of 3,968,893 shares of the
Company's Common Stock (the "Existing Shares"); and
WHEREAS, the Company and APPI are parties to that certain Restated
p53
and K-ras Agreement of even date herewith, whereby the Company and APPI, among
other things, have agreed to enter into this Agreement; and
WHEREAS, pursuant to that certain Series A Non-Voting Convertible Stock
Purchase Agreement, of even date herewith, by and among the Company, APPI and
RPRIH (the "Stock Purchase Agreement"), the Company has agreed to sell, and APPI
has agreed to purchase, at the Closing, 100,000 shares of the Company's Series A
Non-Voting Convertible Preferred Stock (the "Series A Shares"); and
WHEREAS, as an inducement to enter into the Stock Purchase Agreement
and as additional consideration to APPI, the Stock Purchase Agreement
contemplates, among other things, that the Company, APPI and RPRIH enter into
this Agreement and that this Agreement become effective upon the Closing of the
purchase and sale of the Series A Shares under the Stock Purchase Agreement;
AGREEMENT
NOW, THEREFORE, in consideration of the premises and the mutual
covenants contained herein, and for other good and valuable consideration, the
receipt and sufficiency of which are hereby acknowledged, the parties hereto,
intending to be legally bound, hereby agree as follows:
1. CERTAIN DEFINITIONS. As used in this Agreement, the following terms
shall have the following respective meanings:
1.1 "Closing" shall have the meaning assigned to such term in the
Stock Purchase Agreement.
1.2 "Common Stock" shall mean the common stock of the Company, par
value $0.001 per share.
52
EXHIBIT 1.44
FORM OF REGISTRATION RIGHTS AGREEMENT
1.3 "Effective Date" shall mean the date of the Closing of the
purchase and sale of the Series A Shares under the Stock Purchase Agreement.
1.4 "Exchange Act" shall mean the United States Securities Exchange
Act of 1934, as amended, and the rules and regulations of the SEC promulgated
thereunder.
1.5 "Holder" shall mean APPI and any other person or entity to whom
Registrable Securities and the rights to cause the Company to register the
Registrable Securities hereunder are transferred or assigned in accordance with
Section 9.
1.6 "Initiating Holders" means the person or persons who hold at
least a majority of the then outstanding Registrable Securities.
1.7 The terms "register," "registered" and "registration" refer to a
registration effected by preparing and filing a registration statement in
compliance with the Securities Act, and the declaration or ordering of the
effectiveness of such registration statement.
1.8 "Registrable Securities" shall mean (i) the shares of Common
Stock issuable or issued upon conversion of the Series A Shares and (ii) any
other shares of Common Stock issued as (or issuable upon conversion or exercise
of any warrant, right or other security that is issued as) a dividend or other
distribution with respect to or exchange for or replacement of the Series A
Shares, excluding in all cases, however, any Registrable Securities sold by a
person in a transaction in which a Holder's registration rights under this
Agreement are not assigned; provided, however, that Registrable Securities shall
not include any shares of Common Stock which have been sold to the public either
pursuant to a registration statement or Rule 144 under the Securities Act.
1.9 "Securities Act" shall mean the United States Securities Act of
1933, as amended, and the rules and regulations of the SEC promulgated
thereunder, all as the same shall be in effect at the time.
1.10 "SEC" shall mean the United States Securities and Exchange
Commission or any other federal agency at the time administering the Securities
Act.
2. PIGGYBACK REGISTRATION RIGHTS.
2.1 Registration. If the Company shall determine to register any of
its securities under the Securities Act (including for this purpose a
registration effected by the Company for stockholders other than the Holders,
but excluding any registration requested under Section 7.2 of the Company's
Series C Preferred Stock Purchase Agreement dated as of November 30, 1995 (the
"Series C Agreement") in which any Existing Shares are requested to be
registered), other than (a) a registration relating solely to employee benefit
plans, (b) a registration, including a registration on Form S-4, relating solely
to a transaction subject to Rule 145 promulgated under the Securities Act, or
(c) a registration on any registration form which does not permit secondary
sales or does not
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include substantially the same information as would be required to be included
in a registration statement covering the sale of Registrable Securities, the
Company will:
(i) promptly give to each Holder written notice thereof; and
(ii) include in such registration, and in any underwriting
involved therein, all of the Registrable Securities specified in a written
request or requests made by any Holder within twenty (20) days after receipt of
the written notice from the Company described in clause (i) above, except as set
forth in Section 2.2 below. Such written request may specify all or a part of a
Holder's Registrable Securities. 2.2 Underwriting. If the registration of which
the Company gives notice is for an underwritten offering, the Company shall so
advise the Holders as a part of the written notice given pursuant to Section
2.1. In such event, the right of any Holder to registration pursuant to this
Section 2 shall be conditioned upon such Holder's participation in such
underwriting and the inclusion of such Holder's Registrable Securities in the
underwriting to the extent provided herein. All Holders proposing to distribute
their securities through such underwriting shall (together with the Company and
any other stockholders proposing to distribute their securities through such
underwriting) enter into an underwriting agreement in customary form with a
nationally-recognized underwriter selected by the Company, subject to the
approval of such Holders, which approval shall not be unreasonably withheld.
Notwithstanding any other provision of this Section 2, if the managing
underwriter in any underwritten offering subject to this Section 2 determines
that marketing factors require a limitation on the number of shares to be
offered in the underwritten offering, the managing underwriter may (subject to
the allocation priority set forth below) exclude from such registration and
underwriting up to all of the Registrable Securities that would otherwise be
underwritten pursuant to this Section 2. The Company shall so advise all holders
of securities requesting registration, and the number of shares of securities
that are entitled to be included in the registration and underwriting under this
Section 2 by persons other than the Company shall be allocated in the following
priority: first, among any stockholders requesting registration pursuant to the
Series C Agreement or the Company's Registration Rights Agreement, dated as of
October 31, 1997 (the "1997 Rights Agreement"); second, among all Holders; and
third, among all other stockholders in proportion, as nearly as practicable, to
the respective amounts of securities that they had requested to be included in
such registration at the time of filing the registration statement. If any
Holder or other stockholder disapproves of the terms of any such underwriting,
such Holder may elect to withdraw therefrom by written notice to the Company and
the managing underwriter. Any Registrable Securities or other securities
excluded or withdrawn from such underwriting shall be withdrawn from such
registration.
2.3 Right to Terminate Registration. The Company shall have the
right to terminate or withdraw any registration initiated by the Company under
this Section 2 without liability prior to the effectiveness of such
registration, whether or not any Holder has elected to include securities in
such registration.
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2.4 Termination of Piggyback Rights. The rights granted pursuant to
this Section 2 shall terminate upon the earliest to occur of (X) after a Holder
has sold any Shares pursuant to a registration under this Section 2 on three (3)
occasions; provided, however, that if the number of Shares requested to be
included in an underwritten offering are reduced as a result of the allocation
priority in Section 2.2, then such offering pursuant to this Section 2 shall not
be counted for purposes of counting the number of registrations under this
clause (X), (Y) as to any Holder, such time at which all Registrable Securities
held by such Holder, together will all Existing Shares held by RPRIH or any
other affiliate of APPI, can be sold in any three-month period without
registration in compliance with Rule 144 of the Securities Act (or any successor
rule thereof), or (Z) four (4) years from the Effective Date of this Agreement;
provided, however, that such four (4) year period shall be extended for the
total number of days of any and all Suspension Periods (as defined in Section
4.1(a)).
3. DEMAND REGISTRATION.
3.1 Request for Registration. If the Company shall receive from the
Initiating Holders, at any time after the one-year anniversary of the Effective
Date, a written request that the Company effect any registration with respect to
any of the then outstanding Registrable Securities which would result in an
aggregate offering of at least $5,000,000 (or any lesser aggregate offering if
such request for registration is with respect to all the Registrable Securities
of such Initiating Holder under this Agreement), the Company will:
(a) within 10 days of such request, give written notice of the
proposed registration to all other Holders; and
(b) as soon as practicable, and in any event with 60 days of
such request, file with the SEC and thereafter use its best efforts to effect
such registration (including, without limitation, the execution of an
undertaking to file post effective amendments, appropriate qualification under
applicable blue sky or other state securities laws and appropriate compliance
with applicable regulations issued under the Securities Act) as may be so
requested and as would permit or facilitate the sale and distribution of all or
such portion of such Registrable Securities as are specified in such request,
together with all or such portion of the Registrable Securities of any Holders
joining in such request as are specified in a written request delivered to the
Company within twenty (20) days after receipt of such written notice from the
Company; provided that the Company shall not be obligated to effect, or to take
any action to effect, any such registration pursuant to this Section 3:
(i) in any particular jurisdiction in which the Company
would be required to execute a general consent to service of process in
effecting such registration, qualification or compliance, unless the Company is
already subject to service in such jurisdiction and except as may be required by
the Securities Act;
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(ii) after the Company has effected three (3) such
registrations pursuant to this Section 3.1 and such registrations have been
declared or ordered effective and the sales of such Registrable Securities have
closed; provided, however, that if the effectiveness of any such registration is
not maintained for a period of at least ninety (90) days (or any lesser period
of time in the event the distribution contemplated by the registration is fully
completed), then such registration shall not be counted as a registration for
the purposes of this clause (ii);
(iii) during the period starting with the date fifty-five
(55) calendar days prior to the Company's good faith estimate of the date of
filing of, and ending on a date one-hundred-fifty (150) calendar days after the
effective date of, any registration statement pertaining to a public offering of
securities for the Company's account; provided that the Company is actively
employing in good faith its reasonable best efforts to cause such registration
statement to be effective; or
(iv) during the period starting with the date six (6) months
prior to the Company's good faith estimate of the effective date of, and ending
on a date six (6) months after the effective date of, any registration statement
pertaining to a public offering of securities for the account of any stockholder
requesting registration pursuant Section 7.2(a) of the Series C Agreement or
pursuant to Section 2 of the 1997 Rights Agreement; provided that the Company is
actively employing in good faith its reasonable best efforts to cause such
registration statement to be effective and provided further that if the Company
has begun to effect a registration pursuant to this Section 3 and receives a
request for registration from a stockholder pursuant Section 7.2(a) of the
Series C Agreement or pursuant to Section 2 of the 1997 Rights Agreement, then
the Company shall immediately inform the Holders and cease and have no further
obligation to take any action to effect the registration begun pursuant to
Section 3.1.
Subject to the foregoing clauses (i) through (iv), the Company shall
file a registration statement covering the Registrable Securities so requested
to be registered as soon as practicable, after receipt of the request or
requests of the Initiating Holders; provided, however, that if the Company shall
furnish to such Holders a certificate signed by the President of the Company (a
"President's Certificate") stating that in the good faith judgment of the Board
of Directors of the Company, it would be seriously detrimental to the Company
and its stockholders for such registration statement to be filed on or before
the time filing would be required and it is therefore essential to defer the
filing of such registration statement, the Company shall have the right to defer
such filing (but not more than once during any twelve-month period) for a period
that the Board of Directors of the Company in its good faith judgment deems
reasonably necessary but in no event shall such period be more than
one-hundred-eighty (180) days after receipt of the request of the Initiating
Holders.
The registration statement filed pursuant to the request of the
Initiating Holders may, subject to the provisions of Section 3.2 below, include
other securities of the Company that are held by officers or directors of the
Company or that are held by persons who, by virtue of agreements with the
Company, are entitled to include their securities in any such registration.
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3.2 Underwriting.
(a) If the Initiating Holders intend to distribute the Registrable
Securities covered by their request by means of an underwriting, they shall so
advise the Company as a part of their request made pursuant to this Section 3,
and the Company shall include such information in the written notice referred to
in Section 3.1(a). The right of any Holder to registration pursuant to Section 3
shall be conditioned upon such Holder's participation in such underwriting and
the inclusion of such Holder's Registrable Securities in the underwriting to the
extent provided herein. A Holder may elect to include in such underwriting all
or a part of such Holder's Registrable Securities.
(b) All Holders proposing to distribute their securities through an
underwritten offering pursuant to this Section 3 shall enter into an
underwriting agreement in customary form with the underwriter or underwriters.
The managing underwriters or underwriters for any such underwritten offering
shall be selected by the Initiating Holder, subject to approval by the Company,
which approval will not be unreasonably withheld.
(c) Notwithstanding any other provision of this Section 3, if the
underwriter advises the Initiating Holders that marketing factors require a
limitation on the number of shares to be underwritten, then the Initiating
Holders shall so advise all Holders of Registrable Securities that would
otherwise be underwritten pursuant hereto, and the number of shares of
Registrable Securities that may be included in the underwriting shall be
allocated among all Holders thereof, in proportion (as nearly as practicable) to
the amount of Registrable Securities owned by each Holder; provided, however,
that the number of shares of Registrable Securities to be included in such
underwriting shall not be reduced unless all other shares of Common Stock are
first entirely excluded from such underwriting. If any Holder disapproves of the
terms of any such underwriting, such Holder may elect to withdraw therefrom by
written notice to the Company and the underwriter. Any Registrable Securities
excluded or withdrawn from such underwriting shall be withdrawn from such
registration. If the underwriter has not limited the number of Registrable
Securities or other securities to be underwritten, the Company may include its
securities for its own account in such registration if the underwriter so agrees
and if the number of Registrable Securities and other securities that would
otherwise have been included in such registration and underwriting will not
thereby be limited.
3.3 Termination of Demand Rights. The rights granted pursuant to
this Section 3 shall terminate upon the earlier to occur of (X) as to any
Holder, such time at which all Registrable Securities held by such Holder,
together with all Existing Shares held by RPRIH or any other affiliate of APPI,
can be sold in any three-month period without registration in compliance with
Rule 144 of the Securities Act (or any successor rule thereof), or (Y) four (4)
years from the Effective Date of this Agreement; provided, however, that such
four (4) year period shall be extended for the total of (i) any and all
Suspension Periods; (ii) any and all periods that any Holder is prevented from
exercising the rights granted pursuant to this Section 3 by operation of Section
3.1(b)(iii) or Section 3.1(b)(iv); and (iii) any and all periods that any Holder
is prevented from exercising the rights
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granted pursuant to this Section 3 by the Company's delivery of a President's
Certificate under Section 3.1, unless any Suspension Period or any limitation on
the exercisability of the rights granted pursuant to this Section 3 by operation
of Section 3.1(b)(iv) is caused by any Holder requesting registration of
Existing Shares pursuant to the Series C Agreement.
4. REGISTRATION PROCEDURES.
4.1 Company Procedures. Whenever required under this Agreement to
effect the registration of any Registrable Securities, the Company shall, as
expeditiously as reasonably possible:
(a) Prepare and file with the SEC a registration statement with
respect to such Registrable Securities and use its best efforts to cause such
registration statement to become effective, and, upon the request of the Holders
of a majority of the Registrable Securities registered thereunder, keep such
registration statement effective for a period of up to ninety (90) days or any
lesser period of time in the event the distribution described in such
registration statement has been fully completed; provided, however, that the
Company shall not be obligated to keep such registration statement effective if
the Company receives a request for registration pursuant Section 7.2(a) of the
Series C Agreement (other than from a Holder) or pursuant to Section 2 of the
1997 Rights Agreement on or prior to the date that six (6) months after the
effective date of, such registration statement. Any such period during which the
Company is excused by operation of this Section 4.1(a) from maintaining the
effectiveness of the registration statement is referred to as a "Suspension
Period."
(b) Prepare and file with the SEC such amendments and
supplements to such registration statement and the prospectus used in connection
with such registration statement as may be necessary to comply with the
provisions of the Securities Act with respect to the disposition of all
securities covered by such registration statement.
(c) Furnish to the Holders such numbers of copies of a
prospectus, including a preliminary prospectus, in conformity with the
requirements of the Act, and such other documents as they may reasonably request
in order to facilitate the disposition of Registrable Securities owned by such
Holders.
(d) Use its best efforts to register and qualify the securities
covered by such registration statement under such other securities or Blue Sky
laws of such jurisdictions as shall be reasonably requested by the Holders,
provided that the Company shall not be required in connection therewith or as a
condition thereto to qualify to do business or to file a general consent to
service of process in any such states or jurisdictions.
(e) In the event of any underwritten public offering, enter into
and perform its obligations under an underwriting agreement, in usual and
customary form, with the managing underwriter of such offering.
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(f) Notify in writing each Holder of Registrable Securities
covered by such registration statement at any time when a prospectus relating
thereto is required to be delivered under the Securities Act of the happening of
any event as a result of which the prospectus included in such registration
statement, as then in effect, includes an untrue statement of a material fact or
omits to state a material fact required to be stated therein or necessary to
make the statements therein not misleading in the light of the circumstances
then existing.
(g) Notify in writing each Holder of Registrable Securities
covered by such registration statement, (a) when such registration statement or
the prospectus included therein or any amendment or supplement or post-effective
amendment has been filed, and, with respect to such registration statement or
any post-effective amendment, when the same has become effective, (b) of any
comments made to the Company or its counsel by the SEC with respect thereto or
any request made to the Company or its counsel by the SEC for amendments or
supplements to such registration statement or prospectus or for additional
information (and furnish counsel for the selling Holder(s) copies of such
comment letters and requests), (c) of the issuance by the SEC of any stop order
suspending the effectiveness of such registration statement or the initiation or
threatening of any proceedings for that purpose, (d) of the receipt by the
Company of any notification with respect to the suspension of the qualification
of the Registrable Securities for sale in any jurisdiction or the initiation or
threatening of any proceeding for such purpose.
(h) Use its reasonable best efforts to obtain the withdrawal of
any order suspending the effectiveness of such registration statement or any
post-effective amendment thereto at the earliest practicable date and notify
each Holder of Registrable Securities covered by such registration statement of
the withdrawal of any such order.
(i) Furnish, at the request of any Holder requesting
registration of Registrable Securities pursuant to this Agreement, on the date
that such Registrable Securities are delivered to the underwriters for sale in
connection with a registration pursuant to this Agreement, if such securities
are being sold through underwriters, or, if such securities are not being sold
through underwriters, on the date that the registration statement with respect
to such securities becomes effective, (i) an opinion, dated such date, of the
counsel representing the Company for the purposes of such registration, in form
and substance as is customarily given to underwriters in an underwritten public
offering, addressed to the underwriters, if any, and to the Holders requesting
registration of Registrable Securities and (ii) a letter dated such date, from
the independent certified public accountants of the Company, in form and
substance as is customarily given by independent certified public accountants to
underwriters in an underwritten public offering, addressed to the underwriters,
if any, and to the Holders requesting registration of Registrable Securities.
(j) Make generally available to its securityholders as soon as
practicable but in any event not later than eighteen months after the effective
date of such registration statement, an earning statement (which need not be
audited) complying with Section 11(a) of the Securities Act (including, at the
Company's option, Rule 158 thereunder).
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4.2 Selling Stockholder Procedures. In connection with a request for
registration of any Registrable Securities pursuant to this Agreement, any
selling Holder shall, as expeditiously as reasonably possible:
(a) Furnish to the Company all such information concerning such
Holder necessary for the Company to complete the registration statement and such
Holder will notify the Company promptly if any such information so furnished is
no longer true and correct in all material respects or if such information so
furnished omits any material fact necessary to make such information not
misleading.
(b) In the event of any underwritten public offering, enter into
and perform its obligations under an underwriting agreement, in usual and
customary form, with the managing underwriter of such offering. (c) In the event
of any underwritten public offering, furnish, at the request of the Company, on
the date that such Registrable Securities are delivered to the underwriters, an
opinion, dated as of such date, of the counsel representing the selling Holders
in connection with such registration, in form and substance as is customarily
given on behalf of selling stockholders in an underwritten public offering,
addressed to the underwriters and the Company.
5. EXPENSES OF REGISTRATION. All expenses (other than underwriting
discounts and commissions and fees and disbursements of a special counsel of a
selling stockholder) incurred in connection with registrations, filings or
qualifications pursuant to Sections 2 and 3, including (without limitation) all
registration, federal and state filing and qualification fees and expenses,
printer's fees, accounting fees and fees and disbursements of counsel for the
Company shall be borne by the Company; provided, however, that the Company shall
not be required to pay for any expenses of any registration begun pursuant to
Section 3 if such registration request is subsequently withdrawn at the request
of the Holders of at least a majority of the Registrable Securities to be
registered (in which case all participating Holders shall bear such expenses),
unless the Holders of at least a majority of the Registrable Securities agree to
forfeit their right to one demand registration pursuant to Section 3; provided
further, however, that if at the time of such withdrawal, the Holders have
learned of a material adverse change in the condition, business, or prospects of
the Company from that known to the Holders at the time of their request and have
withdrawn the request following disclosure by the Company of such material
adverse change, then the Holders shall not be required to pay any of such
expenses and shall not forfeit their right to one demand registration pursuant
to Section 3.
6. INDEMNIFICATION.
6.1 To the extent permitted by law, the Company will indemnify and
hold harmless each Holder, each Holder's officers, directors, employees and
agents, any underwriter (as defined in the Securities Act) for such Holder, and
each person, if any, who controls any such Holder or underwriter within the
meaning of the Securities Act, against any and all claims, losses, damages
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and liabilities (joint or several) to which they may become subject under the
Securities Act or other federal or state law, insofar as such claims, losses,
damages or liabilities (or actions in respect thereof) arise out of or are based
on: (i) any untrue statement (or alleged untrue statement) of a material fact
contained in any registration statement, prospectus, offering circular or other
document incident to any such registration, qualification or compliance, (ii)
any omission (or alleged omission) to state therein a material fact required to
be stated therein or necessary to make the statements therein, in light of the
circumstances in which they were made, not misleading or (iii) any violation (or
alleged violation) by the Company of the Securities Act, the Exchange Act, any
state securities law, or any rule or regulation promulgated under the Securities
Act, Exchange Act or any state securities law; and the Company will pay each
such Holder, officer, director, employee, agent, underwriter or controlling
person, as incurred, any legal or other expenses reasonably incurred by them in
connection with investigating and defending any such claim, loss, damage,
liability or action; provided, however, that the indemnity agreement contained
in this Section 6.1 shall not apply to the extent that any such claim, loss,
damage, liability or expense arises out of or is based on any untrue statement
(or alleged untrue statement), omission (or alleged omission) or violation (or
alleged violation) based upon written information furnished to the Company by
such Holder or underwriter and stated to be specifically for use in any such
registration statement, prospectus, offering circular or other document;
provided further, however, that the indemnity agreement contained in this
Section 6.1 shall not apply to amounts paid in settlement of any such loss,
claim, damage, liability or action if such settlement is effected without the
consent of the Company (which consent shall not be unreasonably withheld).
6.2 To the extent permitted by applicable law, each Holder will,
indemnify and hold harmless the Company, each of the Company's officers,
directors employees and agents, each person, if any, who controls the Company
within the meaning of the Securities Act, any underwriter, any other Holder
selling securities pursuant to the registration and any controlling person of
any such underwriter or other Holder, against any and all claims, losses,
damages and liabilities (joint or several) to which they may become subject
under the Securities Act or other federal or state law, insofar as such claims,
losses, damages or liabilities (or actions in respect thereof) arise out of or
are based on: (i) any untrue statement (or alleged untrue statement) of a
material fact contained in any registration statement, prospectus, offering
circular or other document incident to any such registration, qualification or
compliance, (ii) any omission (or alleged omission) to state therein a material
fact required to be stated therein or necessary to make the statements therein,
in light of the circumstances in which they were made, not misleading or (iii)
any violation (or alleged violation) by the Holder of the Securities Act, the
Exchange Act, any state securities law, or any rule or regulation promulgated
under the Securities Act, Exchange Act or any state securities law; and such
Holder will pay the Company, each of the Company's officers, directors employees
and agents, each person controlling the Company, each underwriter, each other
Holder selling securities pursuant to the registration and each person
controlling any such underwriter or other Holder, as incurred, any legal or
other expenses reasonably incurred by them in connection with investigating of
defending any such claim, loss, damage, liability or action, in each case to the
extent (and only to the extent) that such untrue statement (or alleged untrue
statement), omission (or alleged omission) or violation (or alleged violation)
is made in such registration statement, prospectus, offering circular or other
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document in reliance upon and in conformity with written information furnished
to the Company by such Holder and stated to be specifically for use therein;
provided, however that the indemnity agreement contained in this Section 6.2
shall not apply to amounts paid in settlement of any such loss, claim, damage,
liability or action if such settlement is effected without the consent of the
Holder (which consent shall not be unreasonably withheld); provided further,
however, that in no event shall the aggregate liability of a Holder for
indemnification under this Section 6.2 exceed the proceeds received by such
Holder from the sale of Registrable Securities in such offering.
6.3 Each person entitled to indemnification under this Section 6
(the "Indemnified Party") shall give notice to the party required to provide
indemnification (the "Indemnifying Party") promptly after such Indemnified Party
has actual knowledge of any claim as to which indemnity may be sought and shall
permit the Indemnifying Party to assume the defense of any such claim or any
litigation resulting therefrom, provided that counsel for the Indemnifying
Party, who shall conduct the defense of such claim or any litigation resulting
therefrom, shall be approved by the Indemnified Party (whose approval shall not
unreasonably be withheld), and the Indemnified Party may participate in such
defense at such Indemnified Party's expense, and provided further that the
failure of any Indemnified Party to give notice as provided herein shall not
relieve the Indemnifying Party of its obligations under this Agreement, except
to the extent that the Indemnified Party is prejudiced thereby. Each Indemnified
Party shall furnish such information regarding itself or the claim in question
as an Indemnifying Party may reasonably request and as shall be reasonably
required in connection with defense of such claim and litigation resulting
therefrom. An Indemnified Party shall have the right to retain its own counsel,
with the fees and expenses to be paid by the Indemnifying Party, if
representation of such Indemnified Party by the counsel retained by the
Indemnifying Party would be inappropriate due to actual or potential differing
interests between such Indemnified Party and any other party represented by such
counsel in such proceeding, provided that in no event shall the Indemnifying
Party be required to pay the fees and expenses of more than one such separate
counsel for each Indemnified Party.
6.4 If the indemnification provided for in this Section 6 is held by
a court of competent jurisdiction to be unavailable to an Indemnified Party with
respect to any losses, claims, damages or liabilities referred to herein, the
Indemnifying Party, in lieu of indemnifying such Indemnified Party thereunder,
shall to the extent permitted by applicable law contribute to the amount paid or
payable by such Indemnified Party as the result of such loss, claim, damage or
liability in such proportion as is appropriate to reflect the relative fault of
the Indemnifying Party on the one hand and of the Indemnified Party on the other
in connection with the allegation(s) that resulted in such loss, claim, damage
or liability, as well as any other relevant equitable considerations. The
relative fault of the Indemnifying Party and of the Indemnified Party shall be
determined by a court of law by reference to, among other things, whether the
untrue or alleged untrue statement of a material fact or the omission to state a
material fact relates to information supplied by the Indemnifying Party or by
the Indemnified Party and the parties' relevant intent, knowledge, access to
information and opportunity to correct or prevent such statement or omission;
provided that in no event shall any contribution by a Holder hereunder exceed
the proceeds from the sale of Registrable Securities received by such Holder.
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6.5 The obligations of the Company and Holders under this Section 6
shall survive the completion of any offering of Registrable Securities in a
registration statement and the termination of this Agreement. No Indemnifying
Party, in the defense of any such claim or litigation, shall, except with the
prior written consent of each Indemnified Party (which consent shall not be
unreasonably withheld), consent to the entry of any judgment or enter into any
settlement. Unless waived by the Indemnified Party, all judgments and
settlements must include as an unconditional term thereof the giving by the
claimant or plaintiff to such Indemnified Party of a release from all liability
in respect to such claim or litigation.
7. RULE 144 REPORTING. With a view to making available the benefits of
certain rules and regulations of the SEC that may permit the sale of the
Registrable Securities to the public without registration, the Company agrees
to:
7.1 Make and keep public information available as those terms are
understood and defined in Rule 144 under the Securities Act, at all times;
7.2 File with the SEC in a timely manner all reports and other
documents required of the Company under the Securities Act and the Exchange Act;
7.3 furnish to any Holder, so long as the Holder owns any
Registrable Securities, forthwith upon request (i) a written statement by the
Company that it has complied with the reporting requirements of Rule 144 and of
the Securities Act and the Exchange Act, or that it qualifies as a registrant
whose securities may be resold pursuant to Form S-3; and (ii) such information
as may be reasonably requested in availing any Holder of any rule or regulation
of the SEC (exclusive of Rule 144) that permits the selling of any such
securities without registration or pursuant to such form.
8. STANDOFF AGREEMENT.
8.1 Prior to October 3, 2001, RPRIH shall not, without the consent
of the Company, sell or otherwise transfer or dispose of (other than to donees
who agree to be similarly bound) any Existing Shares.
8.2 Notwithstanding anything to the contrary in this Agreement,
prior to July 2, 2002, APPI shall not, without the consent of the Company, sell
or otherwise transfer or dispose of (other than to donees who agree to be
similarly bound) any Registrable Securities.
9. TRANSFER OR ASSIGNMENT OF REGISTRATION RIGHTS. The rights to cause
the Company to register the Holder's securities granted by the Company under
Sections 2 and 3 hereof may be transferred or assigned by the Holder to a
transferee or assignee of any of the Registrable Securities; provided that (a)
such transfer is only to an "affiliate" of such Holder (as such term is defined
in Rule 12b-2 of the Exchange Act), (b) the Company is given written notice by
such Holder at the time of said transfer or assignment, stating the name and
address of said transferee or assignee and
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63
EXHIBIT 1.44
FORM OF REGISTRATION RIGHTS AGREEMENT
identifying the securities with respect to which such registration rights are
being transferred or assigned, and (c) the transferee or assignee of such rights
assumes the obligations of a Holder under this Agreement with respect to the
Registrable Securities that are transferred or assigned. To the extent APPI
creates a new subsidiary and transfers any of the Series A Shares to it, or
transfers any of the Series A Shares to any of its subsidiaries or affiliates
(as such term is defined in Rule 12b-2 of the Exchange Act), APPI shall cause
such transferee to become a signatory to this Agreement by a duly executed
addendum agreement (an "Addendum Agreement") substantially in the form as that
attached hereto as Exhibit A. The execution of an Addendum Agreement by such
transferee shall constitute a permitted amendment of this Agreement.
10. MISCELLANEOUS.
10.1 Governing Law. This Agreement shall be governed in all
respects by and in accordance with the laws of the State of Delaware, without
regard to the principles of conflicts of law thereof.
10.2 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 and the same instrument.
10.3 Titles and Subtitles. The titles and subtitles used in this
Agreement are used for convenience only and are not to be considered in
construing or interpreting this Agreement.
10.4 Notices. All notices, requests and other communications
required or permitted to be given to a party under this Agreement shall be in
writing and shall be deemed to have been duly given if (i) personally delivered
(by courier service or otherwise) or sent by registered or certified mail
(return receipt requested and postage prepaid), in each case to the respective
address specified below, or such other address as may be specified in writing by
such party to the other parties; or (ii) sent by confirmed telecopier, as
follows:
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64
EXHIBIT 1.44
FORM OF REGISTRATION RIGHTS AGREEMENT
RPRIH and APPI:
Aventis Pharmaceuticals Products Inc.
Xxxxx 000-000
Xxxxxxxxxxx, Xxx Xxxxxx 00000-0000
Facsimile: (000) 000-0000
Attn: Senior Vice President -- Corporate Development
and
Xxxxx-Xxxxxxx Xxxxx International (Holdings), Inc.
0000 Xxxxxxx Xxxx, Xxxxx 000
Xxxxxxxxxx, Xxxxxxxx 00000
Facsimile: (000) 000-0000
Attn: Xxxxxxx Xxxxxxx, President
with copies to (which shall not constitute notice):
Xxxxxxx X. Xxxxxx
Vice President, Legal - Corporate Development
Xxxxx 000-000
Xxxxxxxxxxx, Xxx Xxxxxx 00000-0000
Facsimile: (000) 000-0000
and
Xxx X. Xxxx
Xxxxx Xxxxx L.L.P.
Xxx Xxxxx Xxxxx
Xxxxxxx, Xxxxx 00000
Facsimile: (000) 000-0000
Company:
Introgen Therapeutics, Inc.
000 Xxxxxxxx Xxx., Xxxxx 0000
Xxxxxx, Xxxxx 00000
Facsimile: (000) 000-0000
Attn: Xxxxx X. Xxxxx
A-14
65
EXHIBIT 1.44
FORM OF REGISTRATION RIGHTS AGREEMENT
with copies to (which shall not constitute notice):
Xxxxxx Xxxxxx, Esq.
Xxxxxx & Xxxxxx, L.L.P.
000 Xxxxxxxx Xxxxxx
Xxxxxx, Xxxxx 00000
Facsimile: (512) 498- 9141
and
Xxxxxx Xxxxxxx Xxxxxxxx & Xxxxxx
Professional Corporation
0000 Xxxxxxx xx Xxxxx Xxxxxxx, Xxxxx 0000
Xxxxxx, Xxxxx 00000
Facsimile: (000) 000-0000
Attn: Xxxxxxxxxxx X. Xxxxxx, Esq.
10.5 Amendments. Except as permitted by Section 9, this Agreement
may only be amended with the written consent of the Company and the holders of
at least a majority of the outstanding shares of Registrable Securities at the
time of such amendment. Any amendment effected in accordance with Section 9 or
this Section
10.5 shall be binding upon the Company, the Holders, each
transferee of the Registrable Securities, each future holder of all such
Registrable Securities.
10.6 Severability. If any provision of this Agreement should be
held invalid, illegal or unenforceable in any jurisdiction, all other provisions
hereof shall remain in full force and effect in such jurisdiction and shall be
liberally construed in order to carry out the intentions of the parties as
nearly as may be possible. Such invalidity, illegality or unenforceability shall
not affect the validity, legality or enforceability of such provision in any
other jurisdiction.
10.7 Successors and Assigns. The provisions of this Agreement shall
be binding on and inure to the benefit of the parties and their respective
successors and permitted assigns.
10.8 Delays or Omissions; Waiver. No delay or omission to exercise
any right, power or remedy accruing to any party, upon any breach or default of
this Agreement by another party, shall impair any such right, power or remedy of
the non-breaching party, nor shall it be construed to be a waiver of any such
breach or default, or an acquiescence therein, or of or in any similar breach or
default thereafter occurring; nor shall any waiver of any single breach or
default be deemed a waiver of any other breach or default theretofore or
thereafter occurring. Any waiver, permit, consent or approval of any kind or
character on the part of any party of any breach or default under this Agreement
or any waiver on the part of any party of any provisions or conditions of this
Agreement, must be in writing and shall be effective only to the extent
specifically set forth in such
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EXHIBIT 1.44
FORM OF REGISTRATION RIGHTS AGREEMENT
writing. All remedies, either under this Agreement or by law or otherwise
afforded to any holder, shall be cumulative and not alternative.
10.9 Entire Agreement. This Agreement constitutes the entire
agreement among the parties with respect to the subject matter hereof, and
supersedes all prior or contemporaneous agreements and understandings, both
written or oral, among the parties with respect to such subject matter.
10.10 Telecopy Execution and Delivery. A facsimile, telecopy or
other reproduction of this Agreement may be executed by one or more parties, and
an executed copy of this Agreement may be delivered by one or more parties by
facsimile or similar electronic transmission device pursuant to which the
signature of or on behalf of such party can be seen, and such execution and
delivery shall be considered valid, binding and effective for all purposes. At
the request of any party hereto, all parties shall execute an original of this
Agreement as well as any facsimile, telecopy or other reproduction hereof.
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EXHIBIT 1.44
FORM OF REGISTRATION RIGHTS AGREEMENT
IN WITNESS WHEREOF, the parties hereto have executed this Registration
Rights Agreement of the day and year first above written.
Introgen Therapeutics, Inc.
By:
------------------------------------------
Xxxxx X. Xxxxx
President & Chief Executive Officer
Aventis Pharmaceuticals Products Inc.
By:
------------------------------------------
Name: Xx. Xxxxxx Xxxxxxxxxxx
----------------------------------------
Title: Senior Vice President
---------------------------------------
Xxxxx-Xxxxxxx Xxxxx International Holdings
Inc.
By:
------------------------------------------
Name: Xxxxxxx X. Xxxxxxx
----------------------------------------
Title: President
---------------------------------------
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INTROGEN THERAPEUTICS, INC.
REGISTRATION RIGHTS AGREEMENT
SIGNATURE PAGE
68
EXHIBIT 1.44
FORM OF REGISTRATION RIGHTS AGREEMENT
EXHIBIT A
FORM OF ADDENDUM AGREEMENT
This ADDENDUM AGREEMENT (this "Addendum Agreement") made this ___ day
of __________, 200__ by and between _______________ (the "New Holder") and
Introgen Therapeutics, Inc., a Delaware corporation (the "Company"), and
constitutes an amendment of that certain Registration Rights Agreement dated
June 30, 2001 (the "Agreement"), among the Company, Aventis Pharmaceuticals
Products Inc., a Pennsylvania corporation ("APPI") and, solely for the purposes
of Section 8.1 of the Agreement, Xxxxx-Xxxxxxx Xxxxx International (Holdings),
Inc., a Delaware corporation ("RPRIH").
RECITALS
WHEREAS, the Company and APPI entered into the Agreement in order to
impose certain obligations upon the parties thereto with respect to registration
and transfer of certain Registrable Securities; and
WHEREAS, New Holder is now or will be the holder of certain Registrable
Securities and is or wishes to be entitled to the rights and subject to the
obligations of a Holder under the Agreement; and
WHEREAS, the Agreement requires that all persons or entitled being
offered Registrable Securities by actions taken subsequent to the date of the
Agreement, must enter into an Addendum Agreement binding the New Holder to the
Agreement to the same extent as if the New Holder were an original party
thereto;
AGREEMENT
NOW, THEREFORE, in consideration of the premises and mutual covenants
contained herein, and for other good and valuable consideration, the receipt and
sufficiency of which are hereby acknowledged, the parties hereto, intending to
be legally bound, hereby agree as follows:
1. Capitalized terms used herein and not otherwise defined shall have
the meanings assigned to such terms in the Agreement.
2. New Holder shall be bound by, and shall have the benefit of, all the
terms and conditions set out in the Agreement to the same extent as if the New
Holder were a Holder under the Agreement.
3. This Addendum Agreement constitutes an amendment to the Agreement
shall be attached to and become a part of the Agreement.
69
EXHIBIT 1.44
FORM OF REGISTRATION RIGHTS AGREEMENT
Except as modified hereby, New Holder and the Company ratify and confirm the
terms of the Agreement.
EXHIBIT A TO REGISTRATION RIGHTS AGREEMENT
A-2
70
EXHIBIT 1.44
FORM OF REGISTRATION RIGHTS AGREEMENT
IN WITNESS WHEREOF, the parties hereto have executed this Addendum
Agreement as of the date first above written.
NEW HOLDER
-------------------------------------------
Print Name of New Holder
By:
----------------------------------------
Signature
----------------------------------------
Print Name of Signatory
----------------------------------------
Title (if applicable)
Address for notices under Section 10.4 of
the Agreement:
-------------------------------------------
-------------------------------------------
-------------------------------------------
INTROGEN THERAPEUTICS, INC.
By:
----------------------------------------
Name:
--------------------------------------
Title:
-------------------------------------
EXHIBIT A TO REGISTRATION RIGHTS AGREEMENT
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71
EXHIBIT 1.47
FORM OF
STOCK PURCHASE AGREEMENT
------------------------
INTROGEN THERAPEUTICS, INC.
SERIES A NON-VOTING CONVERTIBLE
PREFERRED STOCK PURCHASE AGREEMENT
June 30, 2001
------------------------
72
TABLE OF CONTENTS
Page
-----
Section 1 Authorization and Sale of Convertible Preferred Stock.......................................................1
1.1 Authorization of Convertible Preferred..............................................................1
1.2 Sale of Convertible Preferred.......................................................................1
Section 2 Closing Date; Delivery......................................................................................2
2.1 Closing Date........................................................................................2
2.2 Delivery............................................................................................2
Section 3 Representations and Warranties of the Company...............................................................2
3.1 Organization and Standing...........................................................................2
3.2 Capitalization; Ownership of Existing Subsidiaries..................................................3
3.3 Corporate Power; Authorization......................................................................3
3.4 No Conflict.........................................................................................3
3.5 Issuance and Delivery of the Shares and Conversion Shares...........................................4
3.6 SEC Documents; Financial Statements.................................................................4
3.7 Absence of Changes; Undisclosed Liabilities.........................................................4
3.8 Litigation..........................................................................................5
3.9 Governmental Authorization; Third Party Consents....................................................5
3.10 Compliance with Laws................................................................................5
3.11 Investment Company..................................................................................6
Section 4 Representations and Warranties of the Purchaser.............................................................6
4.1 Authorization.......................................................................................6
4.2 Investment Representations and Covenants of the Purchaser...........................................6
4.3 Receipt of Information..............................................................................7
4.4 Further Limitations on Disposition..................................................................7
4.5 Legends.............................................................................................7
Section 5 Covenants of the Company....................................................................................8
5.1 Use of Proceeds.....................................................................................8
5.2 Listing on The Nasdaq National Market...............................................................8
Section 6 Documents to be Delivered and Actions to be Taken Prior to the Closing Date.................................8
6.1 Execution and Delivery of Registration Rights Agreement.............................................8
6.2 Execution and Delivery of Voting Agreement..........................................................8
6.3 Filing and Delivery of Certificate of Designations..................................................8
6.4 Execution and Delivery of Compliance Certificate....................................................8
6.5 Execution and Delivery of Secretary's Certificate...................................................8
6.6 Delivery of Additional Documents....................................................................9
73
TABLE OF CONTENTS
(CONTINUED)
PAGE
----
Section 7 Termination of Aventis Board Representation.................................................................9
Section 8 Miscellaneous...............................................................................................9
8.1 Governing Law.......................................................................................9
8.2 Survival............................................................................................9
8.3 Successors and Assigns..............................................................................9
8.4 Entire Agreement; Amendment.........................................................................9
8.5 Notices.............................................................................................9
8.6 Delays or Omissions................................................................................10
8.7 Expenses...........................................................................................11
8.8 Counterparts.......................................................................................11
8.9 Telecopy Execution and Delivery....................................................................11
8.10 Severability.......................................................................................11
8.11 Further Assurances.................................................................................11
EXHIBITS:
A. Registration Rights Agreement
B. Voting Agreement
C. Certificate of Designations
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74
INTROGEN THERAPEUTICS, INC.
SERIES A NON-VOTING CONVERTIBLE
PREFERRED STOCK PURCHASE AGREEMENT
This Series A Non-Voting Convertible Preferred Stock Purchase Agreement
(this "Agreement") is made as of June 30, 2001 by and between Introgen
Therapeutics, Inc., a Delaware corporation (the "Company"), and Aventis
Pharmaceuticals Products Inc., a Pennsylvania corporation (the "Purchaser"). In
addition, Xxxxx-Xxxxxxx Xxxxx International (Holdings), Inc., a Delaware
corporation ("RPRIH"), is entering into this Agreement for the purpose of
Section 7 only.
RECITALS
WHEREAS, the Company and the Purchaser are each parties to that certain
Restated
p53 and K-ras Agreement of even date herewith (the "P53 Agreement"),
whereby each has agreed, among other things, to enter into (i) this Agreement,
(ii) a Registration Rights Agreement of even date herewith and substantially in
the form as that attached hereto as Exhibit A (the "Registration Rights
Agreement"), and (iii) a Voting Agreement of even date herewith and
substantially in the form as that attached hereto as Exhibit B (the "Voting
Agreement" and collectively with the P53 Agreement, this Agreement and the
Registration Rights Agreement, the "Transaction Agreements");
AGREEMENT
In consideration of the mutual promises and covenants hereinafter set
forth, the parties hereto mutually agree as follows:
SECTION 1
Authorization and Sale of Convertible Preferred Stock
1.1 Authorization of Convertible Preferred. The Company has authorized
the sale and issuance of up to 100,000 shares of its Series A Non-Voting
Convertible Preferred Stock, par value $0.001 (the "Convertible Preferred"),
having the rights, privileges, preferences, restrictions and limitations as set
forth in the Certificate of Designations (the "Certificate of Designations") in
the form attached to this Agreement as Exhibit C. The Company's Restated
Certificate of Incorporation filed with the Delaware Secretary of State on
October 17, 2000 (the "Restated Certificate") authorizes the issuance of up to
5,000,000 shares of preferred stock, par value $0.001 (the "Preferred Stock").
1.2 Sale of Convertible Preferred.Upon the terms of this Agreement, the
Company will issue and sell to the Purchaser, and the Purchaser will purchase
from the Company, at the Closing (as defined in Section 2.1), 100,000 shares of
Convertible Preferred (the "Shares") at a purchase price of $250.00 per share,
for the aggregate purchase price of $25,000,000 (the "Purchase Price").
75
SECTION 2
Closing Date; Delivery
2.1 Closing Date. The closing of the sale and purchase of the Shares
hereunder shall be held at the offices of Xxxxxx Xxxxxxx Xxxxxxxx & Xxxxxx,
Professional Corporation, 0000 Xxxxxxx xx Xxxxx Xxxxxxx, Xxxxx 0000, Xxxxxx,
Xxxxx 00000, at 12:00 p.m., local time, on July 2, 2001 (the "Closing") or at
such other time and place upon which the Company and the Purchaser shall
mutually agree (the date of the Closing is hereinafter referred to as the
"Closing Date").
2.2 Delivery. Subject to the conditions set forth in Section 6, at the
Closing, the Company will deliver to the Purchaser a certificate, registered in
the Purchaser's name, representing the number of Shares to be issued on the
Closing Date, against delivery of payment of the Purchase Price for the Shares
by wire transfer in accordance with the Company's instructions provided at least
one business day prior to the Closing. In addition, the parties will deliver the
certificates, agreements and other documents as provided in Section 6.
SECTION 3
Representations and Warranties of the Company
The Company hereby represents and warrants to the Purchaser as of the
Closing Date as follows:
3.1 Organization and Standing. Each of the Company and its subsidiaries
has been duly organized and is validly existing and in good standing as a
corporation under the laws of its respective jurisdiction of organization, with
the corporate power and authority to own, lease and operate its respective
properties and to conduct its business as is now being conducted. In addition,
each of the Company and its subsidiaries is duly qualified to do business and in
good standing as a foreign corporation in all other jurisdictions where its
ownership or leasing of properties or the conduct of its business requires such
qualification, except where the failure so to qualify or to be in good standing
would not cause a material adverse change in or affect on the condition
(financial or otherwise), properties, earnings, business, management, prospects,
net worth or results of operations of the Company and its subsidiaries
considered as a whole (a "Material Adverse Change"). No jurisdiction, other than
the State of Delaware and the Kingdom of Sweden, has claimed, in writing or
otherwise, that the Company or any of its subsidiaries is required to qualify as
a foreign corporation or other entity therein, and neither the Company nor any
of its subsidiaries files any franchise, income or other tax returns in any
other jurisdiction based upon the ownership or use of property therein or the
derivation of income therefrom or the conduct of business therein, unless so
qualified. Each of the Company and its subsidiaries possesses all necessary
consents, approvals, authorizations, orders, registrations, qualifications,
licenses and permits of and from all public regulatory or governmental agencies
and bodies, all of which are valid and in full force and effect, to conduct its
business as now being conducted, except where the failure to so possess would
not cause a Material Adverse Change, and no such consent, approval,
authorization, order, registration, qualification, license or permit contains a
materially burdensome restriction. The Company owns or controls, directly or
indirectly, only the following corporations, associations or other entities:
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76
Gendux, Inc., a Delaware corporation, Gendux AB, a corporation incorporated
under the laws of the Kingdom of Sweden and TMX Realty Corporation, a Delaware
corporation.
3.2 Capitalization; Ownership of Existing Subsidiaries.(a) The
authorized capital stock of the Company consists of 50,000,000 shares of common
stock, par value $0.001 per share ("Common Stock") and 5,000,000 shares of
Preferred Stock. As of June 22, 2001, 21,391,125 shares of Common Stock were
issued and outstanding and no shares of Preferred Stock were outstanding. The
outstanding shares of Common Stock have been duly authorized and validly issued
and are fully paid and nonassessable and have been issued in compliance with all
federal and state securities laws and were not issued in violation of or subject
to any preemptive rights or similar rights to subscribe for or purchase
securities. Except as disclosed in the SEC Documents (as defined in Section 3.6)
and the Financial Statements (as defined in Section 3.6) and related notes
thereto, the Company does not have outstanding any options or warrants to
purchase, or any preemptive rights or other rights to subscribe for or to
purchase any securities or obligations convertible into, or any contracts or
commitments to issue or sell, shares of its capital stock or any such options,
rights, convertible securities or obligations, except for options granted
subsequent to the date of information provided in the SEC Documents pursuant to
the Company's employee and stock option plans as disclosed in the SEC Documents.
(b) All outstanding shares of capital stock of each of the
Company's subsidiaries have been duly authorized and validly issued, and are
fully paid and nonassessable and are owned by the Company, directly or
indirectly through one or more wholly owned subsidiaries, free and clear of any
liens, encumbrances, equities or claims.
3.3 Corporate Power; Authorization. The Company has the full corporate
power and authority and has taken all requisite corporate action to (a) execute
and file the Certificate of Designations with the State of Delaware; (b) execute
and deliver each of the Transaction Agreements to which it is a party and all
other instruments and documents to be executed and delivered by the Company
under the Transaction Agreements; (c) sell and issue the Shares; and (d) perform
all of its obligations under each of the Transaction Agreements. Each of the
Transaction Agreements has been duly and validly authorized, executed and
delivered by the Company and is a valid and binding obligation of the Company,
enforceable against the Company in accordance with its respective terms, except
as the enforcement hereof may be limited by applicable bankruptcy, insolvency,
reorganization, liquidation, conservatorship, readjustment of debt, moratorium
or other similar laws affecting the rights of creditors or by general principles
of equity, or to the extent that rights to indemnity and contribution under the
Registration Rights Agreement may be limited by federal or state securities laws
or the public policy underlying such laws.
3.4 No Conflict. The execution, delivery and performance by the Company
of each of the Transaction Agreements and the consummation of the transactions
contemplated in each of the Transaction Agreements (i) will not result in any
violation of the provisions of the Restated Certificate, bylaws or other
organizational documents of the Company or its subsidiaries, or any law, order,
rule or regulation of any court or governmental agency or body having
jurisdiction over the Company or its subsidiaries or any of their properties or
assets; and (ii) will not conflict with or
-3-
77
result in a breach or violation of any of the terms or provisions of or
constitute a default under any indenture, mortgage, deed of trust, loan
agreement or other agreement or instrument to which the Company or any of its
subsidiaries is a party or by which it or any of its properties is or may be
bound or result in the creation of a lien (except for such violation of any such
law, order, rule or regulation or such conflict, breach, violation, default or
lien that would not cause a Material Adverse Change).
3.5 Issuance and Delivery of the Shares and Conversion Shares. The
Shares, when issued in compliance with the provisions of this Agreement, will be
duly and validly issued, fully paid and nonassessable. The shares of Common
Stock issuable upon conversion of the Shares (the "Conversion Shares") have been
duly reserved for issuance upon conversion of the Shares and, when issued in
compliance with the Certificate of Designations, will be duly and validly
issued, fully paid and nonassessable. Neither the issuance and delivery of the
Shares nor the issuance of the Conversion Shares are or will be at the time of
issuance subject to preemptive or any other similar rights of the stockholders
of the Company or any liens, encumbrances, equities or claims.
3.6 SEC Documents; Financial Statements. The Company has filed in a
timely manner all documents that the Company was required to file with the
Securities and Exchange Commission (the "Commission") under Sections 13, 14(a)
and 15(d) of the Securities Exchange Act of 1934, as amended (the "Exchange
Act") since October 12, 2000. As of their respective filing dates, all documents
filed by the Company with the Commission (the "SEC Documents") complied in all
material respects with the requirements of the Exchange Act or the Securities
Act of 1933, as amended (the "Securities Act"), as applicable. The SEC Documents
did not contain any untrue statement of material fact or omit to state a
material fact required to be stated therein or necessary to make the statements
made therein, in light of the circumstances under which they were made, not
misleading, except to the extent corrected in a subsequently filed SEC Document.
The financial statements of the Company and the notes thereto included in the
SEC Documents (the "Financial Statements") comply as to form in all material
respects with applicable accounting requirements and with the published rules
and regulations of the Commission with respect thereto. The Financial Statements
have been prepared in accordance with generally accepted accounting principles
consistently applied and fairly present the consolidated financial position of
the Company and any subsidiaries at the dates thereof and the consolidated
results of their operations and consolidated cash flows for the periods then
ended (subject, in the case of unaudited statements, to normal, recurring
adjustments).
3.7 Absence of Changes; Undisclosed Liabilities. Subsequent to the
respective dates as of which information is given in the SEC Documents, and
except as set forth or contemplated therein, neither the Company nor any of its
subsidiaries has sustained material loss or interference with its business from
fire, explosion, flood or other calamity, whether or not covered by insurance,
or from any labor dispute or court or governmental action, order or decree, nor
incurred any material liabilities or obligations, direct or contingent, nor
entered into any material transactions not in the ordinary course of business,
and there has not been any Material Adverse Change, or any change in the capital
stock, short-term or long-term debt of the Company and its subsidiaries
considered as a whole other than options granted pursuant to the Company's 1995
Stock Plan or 2000 Stock Option
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78
Plan, shares issued upon exercise of options granted pursuant to the 1995 Stock
Plan or 2000 Stock Option Plan, shares issued pursuant to the 2000 Employee
Stock Purchase Plan and shares issued upon exercise of outstanding warrants.
3.8 Litigation. Except as set forth in the SEC Documents, there are no
legal or governmental proceedings pending to which the Company or any of its
subsidiaries is a party or of which any property of the Company or any of its
subsidiaries is subject, which, if determined adversely to the Company or any
such subsidiary, might individually or in the aggregate, reasonably be expected
to (i) prevent or adversely affect the transactions contemplated by the
Transaction Agreements or the ability of the Company to perform its obligations
under any of the Transaction Agreements; or (ii) result in a Material Adverse
Change, and there is no valid basis for any such legal or governmental
proceeding; and to the Company's knowledge, no such proceedings are threatened
or contemplated against the Company or any subsidiary by governmental
authorities or others. The Company is not a party nor subject to the provisions
of any injunction, judgment, decree or order purporting to enjoin or restrain
the execution, delivery or performance of any of its obligations under any of
the Transaction Agreements.
3.9 Governmental Authorization; Third Party Consents. No approval,
consent, compliance, exemption, authorization, registration, declaration or
other filings or other action by, or notice to, or filing with (collectively,
"Approvals") (a) any governmental authority, (b) the National Association of
Securities Dealers, (c) the Nasdaq National Market or any other securities
exchange, or (d) any other individual, firm, corporation, partnership, trust,
incorporated or unincorporated association, joint venture, joint stock company,
limited liability company, governmental authority or other entity of any kind,
including any successor (by merger or otherwise) of such entity (collectively, a
"Person") (whether acting in an individual, fiduciary or other capacity), is
required in connection with the consummation of the transactions contemplated by
the Transaction Agreements, except for (i) the filing of the Certificate of
Designations with the Secretary of State for the State of Delaware, (ii) such
Approvals as may be required under applicable state securities laws in
connection with the sale of the Shares under this Agreement or under applicable
federal or state securities laws in connection with the exercise of rights
provided for in the Registration Rights Agreement, (iii) the filing of a
notification of listing of additional shares with the Nasdaq National Market
with respect to the Conversion Shares, (iv) any filings under the
Xxxx-Xxxxx-Xxxxxx Antitrust Improvements Act of 1976, as amended ("HSR Act") as
may be required with respect to the issuance of the Conversion Shares and (v)
any Approvals which, if not obtained or made, would not cause a Material Adverse
Change.
3.10 Compliance with Laws.(a) Neither the Company nor any of its
subsidiaries is in violation in any material respect of any applicable federal,
state, local and foreign laws, rules and regulations or any court or
governmental agency or body, including, without limitation, the United States
Food and Drug Administration; to the knowledge of the Company, otherwise than as
set forth in the SEC Documents, no prospective change in any of such federal or
state laws, rules or regulations has been adopted which, when made effective,
would cause a Material Adverse Change.
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79
(b) The Company has all licenses, permits and approvals of any
governmental authority (collectively, "Permits") that are necessary for the
conduct of the business of the Company; such Permits are in full force and
effect; and no violations are or have been recorded in respect of any Permit.
3.11 Investment Company. Neither the Company nor any of its
subsidiaries is or, after application of the net proceeds from the sale of the
Shares under this Agreement will become an "investment company" or an entity
"controlled" by an "investment company" as such terms are defined in the
Investment Company Act of 1940, as amended, assuming that neither the Purchaser
nor RPRIH is such an investment company.
SECTION 4
Representations and Warranties of the Purchaser
The Purchaser hereby represents and warrants to the Company with
respect to its purchase of the Shares, as of the Closing Date, as follows:
4.1 Authorization. The Purchaser has the full corporate power and
authority and has taken all requisite corporate action to execute and deliver
each of the Transaction Agreements to which it is a party and to perform its
obligations hereunder and thereunder. Each of the Transaction Agreements has
been duly and validly authorized, executed and delivered by the Purchaser and is
a valid and binding obligation of the Purchaser, enforceable against the
Purchaser in accordance with its respective terms, except as the enforcement
thereof may be limited by applicable bankruptcy, insolvency, reorganization,
liquidation, conservatorship, readjustment of debt, moratorium or other similar
laws affecting the rights of creditors or by general principles of equity, or to
the extent that rights to indemnity and contribution under the Registration
Rights Agreement may be limited by federal or state securities laws or the
public policy underlying such laws.
4.2 Investment Representations and Covenants of the Purchaser
(a) The Purchaser understands that the Shares are not, and the
Conversion Shares may not be, registered under the Securities Act on the ground
that the sale provided for in this Agreement and the issuance of the Shares
hereunder is exempt from registration under the Securities Act pursuant to
Section 4(2) thereof, and that the Company's reliance on such exemption is
predicated on the Purchaser's representations set forth herein.
(b) The Purchaser represents that the Shares and Conversion Shares
will be acquired for investment for its own account, not as a nominee or agent,
and not with a view to the distribution of any part thereof, and that it has no
present intention of selling, granting any participation in or otherwise
distributing the same in violation of the Securities Act or the securities laws
of any state in the United States.
(c) The Purchaser represents that it is experienced in evaluating
investments in companies similar to the Company, is able to fend for itself in
transactions such as the one contemplated by this Agreement, has such knowledge
and experience in financial and business
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matters that it is capable of evaluating the merits and risks of its prospective
investment in the Company, has the ability to bear the economic risks of the
investment and is an "accredited investor" as defined by Regulation D,
promulgated under the Securities Act.
(d) The Purchaser acknowledges and understands that the Shares and
the Conversion Shares, must be held indefinitely unless it is subsequently
registered under the Securities Act or an exemption from such registration is
available, and that, except as otherwise provided in the Registration Rights
Agreement, the Company is under no obligation to register either the Shares or
the Conversion Shares.
4.3 Receipt of Information. The Purchaser has reviewed the Transaction
Agreements and all exhibits thereto and the SEC Documents. The Purchaser and its
counsel have had access to and an opportunity to review all documents and other
materials requested of the Company; the Purchaser and its counsel have been
given an opportunity to ask any and all questions of the Company concerning the
terms of the offering and to obtain all information it or they believe necessary
or appropriate to evaluate the suitability of an investment in the Shares.
4.4 Further Limitations on Disposition. Without in any way limiting the
representations set forth above, the Purchaser further agrees not to make any
disposition of all or any portion of the Shares or the Conversion Shares unless
and until (x) there is then in effect a registration statement under the
Securities Act covering such proposed disposition and such disposition is made
in accordance with such registration statement or (y) the Purchaser shall have
notified the Company of the proposed disposition and shall have furnished the
Company with a statement of the circumstances surrounding the proposed
disposition, and if reasonably requested by the Company, the Purchaser shall
have furnished the Company with an opinion of counsel (who may be Purchaser's
in-house counsel), reasonably satisfactory to the Company, that such disposition
will be exempt from registration under the Securities Act.
4.5 Legends. The Purchaser understands and agrees that the certificates
evidencing the Shares and the Conversion Shares shall bear a legend
substantially as follows:
"THE SHARES REPRESENTED BY THIS CERTIFICATE HAVE NOT BEEN
REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED, OR
THE SECURITIES LAWS OF ANY STATE, AND MAY NOT BE SOLD,
TRANSFERRED, ASSIGNED, PLEDGED OR HYPOTHECATED UNLESS AND
UNTIL REGISTERED UNDER SUCH ACT AND/OR APPLICABLE STATE
SECURITIES LAWS, OR UNLESS THE CORPORATION HAS RECEIVED AN
OPINION OF COUNSEL (WHO MAY BE IN-HOUSE COUNSEL TO THE HOLDER)
OR OTHER EVIDENCE, REASONABLY SATISFACTORY TO THE CORPORATION
AND ITS COUNSEL, THAT SUCH REGISTRATION IS NOT REQUIRED."
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SECTION 5
Covenants of the Company
The Company covenants and agrees with the Purchaser as follows:
5.1 Use of Proceeds. Introgen intends to use the proceeds from the sale
of the Shares to fund the commercialization of INGN 201, to begin building its
internal sales and marketing division to support INGN 201's anticipated market
introduction and for general working capital.
5.2 Listing on The Nasdaq National Market. The Company will list the
Conversion Shares, subject to official notice of issuance, on the Nasdaq
National Market at or before any sale of such shares by the Purchaser.
SECTION 6
Documents to be Delivered and Actions to be Taken Prior to the Closing
The respective obligations of the parties hereto to effect the sale and
purchase of the Shares shall be subject to the satisfaction or waiver prior to
the Closing, of all of the following conditions and only the following
conditions:
6.1 Execution and Delivery of Registration Rights Agreement. The
Purchaser and the Company shall have executed and delivered the Registration
Rights Agreement.
6.2 Execution and Delivery of Voting Agreement. The Purchaser and the
Company shall have executed and delivered the Voting Agreement.
6.3 Filing and Delivery of Certificate of Designations. The Company
shall have executed and filed the Certificate of Designations with the Secretary
of State of the State of Delaware in accordance with the General Corporation Law
of the State of Delaware. The Company shall have delivered to the Purchaser a
copy of the executed Certificate of Designations as certified by the office of
the Secretary of State of the State of Delaware.
6.4 Execution and Delivery of Compliance Certificate. The Company shall
have delivered to the Purchaser a certificate, executed by the President of the
Company, dated the Closing Date, and certifying, among other things, that (i)
the representations and warranties of the Company set forth in Section 3 hereof
are true and correct in all respects on the Closing Date; and (ii) that all
covenants and agreements contained in this Agreement to be performed by the
Company on or prior to the Closing Date have been performed or complied with.
6.5 Execution and Delivery of Secretary's Certificate. The Company
shall have delivered to the Purchaser a certificate, in form and substance
satisfactory to the Purchaser, dated the Closing Date and signed by the
Secretary or an Assistant Secretary of the Company, certifying (i) that the
attached copies of the Restated Certificate, Certificate of Designations, the
Bylaws and resolutions of the Board of Directors of the Company approving each
of the Transaction Agreements are true, complete and correct and remain
unattended and in full force and effect; and (ii) as to the
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incumbency and specimen signature of each officer of the Company executing each
Transaction Agreement and any other document or instrument delivered at the
Closing on behalf of the Company.
6.6 Delivery of Additional Documents. The Company shall have delivered
to Purchaser true, complete and correct copies of such documents as Purchaser
may have reasonably requested in connection with or relating to the sale of the
Shares and the transactions contemplated hereby, all in form and substance
reasonably satisfactory to the Purchaser.
SECTION 7
Termination of Aventis Board Representation
Effective as of the Closing Date, Section 23 of that certain Series B
Preferred Stock Purchase Agreement, dated as of October 7, 1994, shall be
terminated in its entirety and be of no further force or effect.
SECTION 8
Miscellaneous
8.1 Governing Law. This Agreement shall be governed in all respects by
and in accordance with the laws of the State of Delaware, without regard to the
principles of conflicts of law thereof.
8.2 Survival. The representations, warranties, covenants and agreements
made herein shall survive any investigation made by the Purchaser and the
Closing.
8.3 Successors and Assigns. Except as otherwise provided herein, the
provisions hereof shall inure to the benefit of, and be binding upon, the
successors, assigns, heirs, executors and administrators of the parties hereto.
8.4 Entire Agreement; Amendment. This Agreement and the other documents
delivered pursuant hereto at the Closing constitute the full and entire
understanding and agreement between the parties with regard to the subjects
hereof and thereof, and no party shall be liable or bound to any other party in
any manner by any warranties, representations or covenants except as
specifically set forth herein or therein. Except as expressly provided herein,
neither this Agreement nor any term hereof may be amended, waived, discharged or
terminated other than by a written instrument signed by the party against whom
enforcement of any such amendment, waiver, discharge or termination is sought.
8.5 Notices. All notices and other communications required or permitted
hereunder shall be in writing and shall be deemed to have been duly given if (i)
personally delivered (by courier service or otherwise) or sent by registered or
certified mail (return receipt requested and postage prepaid), in each case to
the respective address specified below, or such other addresses as may be
specified in writing by such party to the other party hereto, or sent by
confirmed telecopier, as follows:
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Purchaser: Xxxxx 000-000
Xxxxxxxxxxx, Xxx Xxxxxx 00000-0000
Facsimile: (000) 000-0000
Attn: Senior Vice President - Corporate
Development
with copies to (which shall not constitute
notice):
Xxxxxxx X. Xxxxxx
Vice President, Legal - Corporate Development
Xxxxx 000-000
Xxxxxxxxxxx, Xxx Xxxxxx 00000-0000
Facsimile: (000) 000-0000
and
Xxx X. Xxxx
Xxxxx Xxxxx L.L.P.
Xxx Xxxxx Xxxxx
Xxxxxxx, Xxxxx 00000
Facsimile: (000) 000-0000
Company: Introgen Therapeutics, Inc.
000 Xxxxxxxx Xxx., Xxxxx 0000
Xxxxxx, Xxxxx 00000
Facsimile: (000) 000-0000
Attn: Xxxxx X. Xxxxx
with copies to (which shall not constitute
notice):
Xxxxxx Xxxxxx, Esq.
Xxxxxx & Xxxxxx, L.L.P.
000 Xxxxxxxx Xxxxxx
Xxxxxx, Xxxxx 00000
Facsimile: (000) 000-0000
Xxxxxx Xxxxxxx Xxxxxxxx & Xxxxxx
Professional Corporation
0000 Xxxxxxx xx Xxxxx Xxxxxxx, Xxxxx 0000
Xxxxxx, Xxxxx 00000
Facsimile: (000) 000-0000
Attn: Xxxxxxxxxxx X. Xxxxxx, Esq.
8.6 Delays or Omissions. Except as expressly provided herein, no delay
or omission to exercise any right, power or remedy accruing to any holder of any
Shares, upon any breach or default of the Company under this Agreement, shall
impair any such right, power or remedy of such
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84
holder nor shall it be construed to be a waiver of any such breach or default,
or an acquiescence therein, or of or in any similar breach or default thereafter
occurring; nor shall any waiver of any single breach or default be deemed a
waiver of any other breach or default theretofore or thereafter occurring. Any
waiver, permit, consent or approval of any kind or character on the part of any
holder of any breach or default under this Agreement or any waiver on the part
of any holder of any provisions or conditions of this Agreement, must be in
writing and shall be effective only to the extent specifically set forth in such
writing. All remedies, either under this Agreement or by law or otherwise
afforded to any holder, shall be cumulative and not alternative.
8.7 Expenses. Each of the Company and the Purchaser shall bear its own
expenses and legal fees incurred with respect to this Agreement and the
transactions contemplated hereby.
8.8 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 and the same instrument.
8.9 Telecopy Execution and Delivery. A facsimile, telecopy or other
reproduction of this Agreement may be executed by one or more parties hereto,
and an executed copy of this Agreement may be delivered by one or more parties
hereto by facsimile or similar electronic transmission device pursuant to which
the signature of or on behalf of such party can be seen, and such execution and
delivery shall be considered valid, binding and effective for all purposes. At
the request of any party hereto, all parties hereto agree to execute an original
of this Agreement as well as any facsimile, telecopy or other reproduction
hereof.
8.10 Severability. If any provision of this Agreement should be held
invalid, illegal or unenforceable in any jurisdiction, all other provisions
hereof shall remain in full force and effect in such jurisdiction and shall be
liberally construed in order to carry out the intentions of the parties as
nearly as may be possible. Such invalidity, illegality or unenforceability shall
not affect the validity, legality or enforceability of such provision in any
other jurisdiction.
8.11 Further Assurances. Each of the parties shall execute such
documents and perform such further acts (including, without limitation,
obtaining any consents, exemptions, authorizations or other actions by, or
giving any notices to, or making any filings with, any governmental authority or
any other Person) as may be reasonably required or desirable to carry out or to
perform the provisions of this Agreement.
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IN WITNESS WHEREOF, the foregoing Agreement is hereby executed as of
the date first above written.
Introgen Therapeutics, Inc.
By:
---------------------------------------------
Xxxxx X. Xxxxx
President and Chief Executive Officer
Aventis Pharmaceuticals Products Inc.
By:
---------------------------------------------
Name: Xx. Xxxxxx Xxxxxxxxxxx
-------------------------------------------
Title: Senior Vice President
------------------------------------------
Xxxxx-Xxxxxxx Xxxxx International (Holdings), Inc.
By:
-----------------------------------------------
Name: Xxxxxxx X. Xxxxxxx
--------------------------------------------
Title: President
--------------------------------------------
[Signature page for Series A Non-Voting Convertible Preferred
Stock Purchase Agreement]
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EXHIBIT 1.50
THIRD PARTY AGREEMENTS
o License Agreement effective September 1, 1999, between [*] and Xxxxx-
Xxxxxxx Xxxxx Pharmaceuticals Inc.
o Patent License Agreement effective September 10, 1996, between [*] and
Xxxxx-Xxxxxxx Xxxxx Pharmaceuticals Inc.
o Research Support and License Agreement effective December 1, 1998,
between [*] and Xxxxx-Xxxxxxx Xxxxx Pharmaceuticals Inc.
o Other third party agreements pursuant to the Third Party Involvement
referenced in Exhibits 1.6, 1.8 and 1.10 and as further described in
Exhibit 7.2.
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
87
EXHIBIT 1.55
VOTING AGREEMENT
88
VOTING AGREEMENT
This VOTING AGREEMENT (this "Voting Agreement") is made and entered
into as of June 30, 2001, by and among Introgen Therapeutics, Inc., a Delaware
corporation ("Introgen"), Xxxxx-Xxxxxxx Xxxxx International (Holdings), Inc., a
Delaware corporation ("RPRIH"), and Aventis Pharmaceuticals Products Inc., a
Pennsylvania corporation ("APPI", and together with RPRIH, the "Aventis
Holders"), each of whom is sometimes referred to herein as a "Party" and
collectively as the "Parties."
RECITALS
WHEREAS, Introgen and APPI are each a party to that certain Restated
p53 and K-ras Agreement of even date herewith, whereby each has agreed, among
other things, to enter into this Voting Agreement; and
WHEREAS, as of the date hereof, the RPRIH is the holder of record of
3,968,893 shares of Introgen's Common Stock, par value $0.001 per share (the
"Existing Introgen Shares"); and
WHEREAS, pursuant to that certain Series A Non-Voting Convertible
Preferred Stock Purchase Agreement of even date herewith by and among Introgen,
APPI and RPRIH (the "Stock Purchase Agreement"), Introgen has agreed to sell,
and APPI has agreed to purchase, at the Closing (as defined in the Stock
Purchase Agreement) 100,000 shares of Introgen's Series A Non-Voting Convertible
Preferred Stock, par value $0.001 per share (the "Series A Shares"), which
Series A Shares are convertible into shares of Introgen common stock. The
Existing Introgen Shares and the shares of common stock of Introgen actually
issued upon the conversion of the Series A Shares (the "Conversion Shares") are
collectively referred to herein as the "Introgen Shares;" and
WHEREAS, APPI contemplates the formation of an affiliated or otherwise
related company ("Gencell") and may wish to transfer some or all of the Series A
Shares or Conversion Shares to Gencell; and
WHEREAS, the Stock Purchase Agreement contemplates, among other things,
that the Company, APPI and RPRIH enter into this Voting Agreement and that this
Voting Agreement become effective upon the Closing of the purchase and sale of
the Series A Shares under the Stock Purchase Agreement (the "Effective Date");
AGREEMENT
NOW, THEREFORE, in consideration of the premises and the mutual
covenants contained herein, and for other good and valuable consideration, the
receipt and sufficiency of which are hereby acknowledged, the Parties, intending
to be legally bound, hereby agree as follows:
89
1. Voting on Corporate Action.
(a) Voting Agreement.
(i) In the event that, following the Effective Date,
a Corporate Action (i) is approved by Introgen's Board of Directors or other
governing body and (ii) receives approval of the holders of not less than a
majority of Introgen's outstanding Voting Securities without taking into account
any such securities held by any of the Aventis Holders, each of the Aventis
Holders shall consent to and vote all of the Introgen Shares held by it in favor
of such Corporate Action at any meeting of stockholders (or by any action by
written consent) called to consider the approval of such Corporate Action.
(ii) In the event that, following the Effective Date,
a Corporate Action (i) is approved by Introgen's Board of Directors or other
governing body and (ii) is rejected by the holders of not less than a majority
of Introgen's outstanding Voting Securities without taking into account any such
securities held by any of the Aventis Holders, each of the Aventis Holders shall
consent to and vote all of the Introgen Shares held by it against such Corporate
Action at any meeting of stockholders (or by any action by written consent)
called to consider the approval of such Corporate Action.
(iii) A "Corporate Action" shall mean any matter put
to a vote of the stockholders of Introgen. "Voting Securities" shall mean, with
respect to any specified person, any class or classes of Capital Stock of the
specified person pursuant to which the holders thereof have the general voting
power under ordinary circumstances to elect at least a majority of the board of
directors, supervisory board, managers or trustees of the specified person
(irrespective of whether or not, at the time, stock of any other class or
classes have, or might have, voting power by reason of the happening of any
contingency). "Capital Stock" shall mean, with respect to any person, any and
all shares, interests, participation, rights or other equivalents in the equity
interests (however designated) in that person.
(b) Power of Attorney. If any of the Aventis Holders fails or refuses
to vote the Introgen Shares held by it as required by, or votes the Introgen
Shares held by it in contravention of this Section 1, then Introgen's Chairman
of the Board or Chief Executive Officer shall have an irrevocable proxy, coupled
with an interest, to vote such Introgen Shares in accordance with this Section
1. Each of the Aventis Holders hereby grants to Introgen's Chairman of the Board
and Chief Executive Officer such an irrevocable proxy and hereby appoints
Introgen's Chairman of the Board and Chief Executive Officer, and each of them
acting singly, its attorney-in-fact to vote the Introgen Shares held by it in
accordance with the terms of this Section 1. In the event that any of the
Aventis Holders fails or refuses to comply for any reason with the provisions of
this Section 1, Introgen, at its option, may elect to proceed with the Corporate
Action notwithstanding such failure or refusal. The voting of shares pursuant to
this Voting Agreement may be effected in person, by proxy, by written consent or
in any other manner permitted by applicable law.
(c) The proxies granted pursuant to this Section 1 shall be deemed
coupled with an interest and are irrevocable for the term of this Voting
Agreement. It is agreed and understood that (i) monetary damages would not
adequately compensate an injured Party for the
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breach of this Section 1 by any Party, (ii) this Section 1 shall be specifically
enforceable, and (iii) any breach or threatened breach of this Section 1 shall
be the proper subject of a temporary or permanent injunction or restraining
order. Further, each Party waives any claim or defense that there is an adequate
remedy at law for such any breach or threatened breach.
(d) After receiving proper notice, one or more representatives of each
Aventis Holder, as a holder of Introgen Shares, shall be present, in person or
by proxy, at all meetings of stockholders of Introgen, as appropriate, to vote
upon a proposed Corporate Action so that all of the Introgen Shares beneficially
owned by the Aventis Holders and/or their respective affiliated entities may be
counted for the purposes of determining the presence of a quorum at such
meetings.
(e) The Aventis Holders shall not deposit any of the Introgen Shares
beneficially owned by either of them in a voting trust or subject any such
securities to any arrangement or agreement with respect to the voting of such
securities provided that this provision will not restrict the right of APPI to
transfer any Series A Shares or Conversion Shares to Gencell as contemplated by
Section 2.
(f) This Voting Agreement shall extend to any national or state
statutory approval rights for any Corporate Action that either Aventis Holder
may have by virtue of beneficially holding Introgen Shares.
2. Gencell as a Party.
(a) APPI shall have the right to transfer some or all of its Series A
Shares or Conversion Shares to Gencell in accordance with the terms of the Stock
Purchase Agreement. In connection with any such transfer, APPI shall cause
Gencell to agree to be bound by the obligations of this Voting Agreement as a
Party with respect to such transferred shares and to execute and deliver to
Introgen a counterpart signature page to this Voting Agreement.
3. Termination.
(a) This Voting Agreement, except for the obligation of Introgen set
forth in the last sentence of Section 4, shall terminate as to any Introgen
Shares on the earliest to occur of: (i) the date upon which such shares are sold
into an established trading market for such shares in accordance with applicable
securities laws, including sales made under Rule 144 under the Securities Act of
1933, as amended; (ii) the date upon which such shares are sold under an
effective registration statement covering such shares filed with the United
States Securities and Exchange Commission under the Securities Act of 1933, as
amended; (iii) the date upon which such shares are sold by either of the Aventis
Holders in a private sale to a non-affiliate (as such term "affiliate" is
defined in Rule 12b-2 of the General Rules and Regulations under the Securities
Exchange Act of 1934, as amended) of such Aventis Holder that is not either (x)
a direct competitor of Introgen whose main line of activity (based on
publicly-available information or, in the case of a privately-held company,
otherwise commonly known information regarding such competitor) is the
development of gene therapy products or (y) a pharmaceutical company; or (iv)
the date indicated in paragraph (b) below.
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91
(b) In any event, this Voting Agreement shall terminate on the date
corresponding to the tenth anniversary of the Effective Date of this Voting
Agreement.
4. Legend. Concurrently with (i) the execution of this Voting
Agreement, with respect to the Existing Introgen Shares outstanding on the date
of this Voting Agreement; and (ii) the issuance of the Conversion Shares, with
respect to such shares, there shall be imprinted or otherwise placed, on
certificates representing such shares a restrictive legend substantially to the
following effect (the "Legend"):
THE SECURITIES REPRESENTED BY THIS CERTIFICATE ARE SUBJECT TO THE TERMS
AND CONDITIONS OF A CERTAIN VOTING AGREEMENT DATED AS OF JUNE 30, 2001
AMONG THE CORPORATION, THE ORIGINAL HOLDER OF THESE SECURITIES AND
CERTAIN OTHER PARTIES. COPIES OF SUCH AGREEMENT MAY BE OBTAINED UPON
WRITTEN REQUEST TO THE SECRETARY OF THE CORPORATION.
If such shares are not certificated, then a substantially similar notification
shall be placed in an appropriate fashion with the person charged with
maintaining registration of the ownership of such shares so as to put on notice
of the terms and conditions of this Voting Agreement any transferee of such
shares. Following the termination of this Voting Agreement with respect to any
Introgen Shares, upon the request of the Aventis Holder that holds or held such
shares, Introgen shall issue to or as directed by such Aventis Holder a new
certificate or certificates representing such Introgen Shares that does not or
do not contain the Legend.
5. Miscellaneous
(a) Governing Law. This Voting Agreement shall be governed in all
respects by and in accordance with the laws of the State of Delaware, without
regard to the principles of conflicts of law thereof.
(b) Equitable Relief. The Parties hereby agree that it would be
impossible to measure in money the damages that may accrue to a Party by reason
of a failure of another Party to perform any of the obligations under this
Voting Agreement, and further agree that the terms of this Voting Agreement
shall be specifically enforceable. If any Party institutes any action or
proceeding to specifically enforce the provisions hereof, any other Party
against whom such action or proceeding is brought hereby waives the claim or
defense therein that the instituting Party has an adequate remedy at law, and
such other Party shall not offer in any such action or proceeding the claim or
defense that such remedy at law exists.
(c) Successors and Assigns; Assignment. The provisions of this Voting
Agreement shall be binding on and inure to the benefit of the Parties and their
respective successors and permitted assigns. APPI shall have the right to have
Gencell assume those obligations of APPI under this Voting Agreement that relate
to any Introgen Shares transferred by APPI to Gencell in accordance with Section
2. APPI shall cause Gencell to assume the those obligations of APPI under this
Voting Agreement that relate to any Introgen Shares transferred by APPI to
Gencell in accordance with Section 2.
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(d) Entire Agreement. This Voting Agreement constitutes the entire
agreement among the Parties with respect to the subject matter hereof, and
supersedes all prior or contemporaneous agreements and understandings, whether
written or oral, among the Parties with respect to such subject matter.
(e) Amendment. Except for the addition of Gencell as a Party hereto in
accordance with Section 2, no amendment or modification of any provision of this
Voting Agreement shall be effective unless in writing signed by all of the
Parties. No provision of this Voting Agreement shall be varied, contradicted or
explained by any oral agreement, course of dealing or performance, or any other
matter not set forth in an agreement in writing and signed by all of the
Parties.
(f) Notices. All notices and other communications required or permitted
hereunder shall be in writing and shall be deemed to have been duly given if
personally delivered (by courier service or otherwise) or sent by registered or
certified mail (return receipt requested and postage prepaid), in each case to
the respective address specified below, or such other addresses as may be
specified in writing by such party to the other party hereto, or sent by
confirmed telecopier, as follows:
Aventis Holders:
Aventis Pharmaceuticals Products Inc.
Xxxxx 000-000
Xxxxxxxxxxx, Xxx Xxxxxx 00000-0000
Facsimile: (000) 000-0000
Attn: Senior Vice President - Corporate Development
and
Xxxxx-Xxxxxxx Xxxxx International (Holdings), Inc.
0000 Xxxxxxx Xxxx, Xxxxx 000
Xxxxxxxxxx, Xxxxxxxx 00000
Facsimile: (000) 000-0000
Attn: Xxxxxxx Xxxxxxx, President
with copies to (which shall not constitute notice):
Xxxxxxx X. Xxxxxx
Vice President, Legal - Corporate Development
Xxxxx 000-000
Xxxxxxxxxxx, Xxx Xxxxxx 00000-0000
Facsimile: (000) 000-0000
and
X-0
00
Xxx X. Xxxx
Xxxxx Xxxxx L.L.P.
Xxx Xxxxx Xxxxx
Xxxxxxx, Xxxxx 00000
Facsimile: (000) 000-0000
Introgen:
Introgen Therapeutics, Inc.
000 Xxxxxxxx Xxx., Xxxxx 0000
Xxxxxx, Xxxxx 00000
Facsimile: (000) 000-0000
Attn: Xxxxx X. Xxxxx
with a copies to (which shall not constitute notice):
Xxxxxx Xxxxxx, Esq.
Xxxxxx & Xxxxxx, L.L.P.
000 Xxxxxxxx Xxxxxx
Xxxxxx, Xxxxx 00000
Facsimile: (000) 000-0000
and
Xxxxxx Xxxxxxx Xxxxxxxx & Xxxxxx
Professional Corporation
0000 Xxxxxxx xx Xxxxx Xxxxxxx, Xxxxx 0000
Xxxxxx, Xxxxx 00000
Facsimile: (512) 338- 5499
Attn: Xxxxxxxxxxx X. Xxxxxx, Esq.
(g) Delays or Omissions; Waiver. Except as expressly provided in this
Voting Agreement, no delay or omission to exercise any right, power or remedy
accruing to any Party, upon any breach or default of this Voting Agreement by
another Party, shall impair any such right, power or remedy of the non-breaching
Party, nor shall it be construed to be a waiver of any such breach or default,
or an acquiescence therein, or of or in any similar breach or default thereafter
occurring; nor shall any waiver of any single breach or default be deemed a
waiver of any other breach or default theretofore or thereafter occurring. Any
waiver, permit, consent or approval of any kind or character on the part of any
Party of any breach or default under this Voting Agreement or any waiver on the
part of any Party of any provisions or conditions of this Voting Agreement must
be in writing and shall be effective only to the extent specifically set forth
in such writing.
(h) Counterparts. This Voting 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 and the same instrument.
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94
(i) Titles and Subtitles. The titles and subtitles used in this Voting
Agreement are used for convenience only and are not to be considered in
construing or interpreting this Voting Agreement.
(j) Telecopy Execution and Delivery. A facsimile, telecopy or other
reproduction of this Voting Agreement may be executed by one or more Parties,
and an executed copy of this Voting Agreement may be delivered by one or more
Parties by facsimile or similar electronic transmission device pursuant to which
the signature of or on behalf of such Party can be seen, and such execution and
delivery shall be considered valid, binding and effective for all purposes. At
the request of any Party hereto, all Parties shall execute an original of this
Voting Agreement as well as any facsimile, telecopy or other reproduction
hereof.
(k) Severability. If any provision of this Voting Agreement should be
held invalid, illegal or unenforceable in any jurisdiction, all other provisions
hereof shall remain in full force and effect in such jurisdiction and shall be
liberally construed in order to carry out the intentions of the Parties as
nearly as may be possible. Such invalidity, illegality or unenforceability shall
not affect the validity, legality or enforceability of such provision in any
other jurisdiction.
(l) Further Assurances. Each of the Parties shall execute such
documents and perform such further acts as may be reasonably required or
desirable to carry out or to perform the provisions of this Voting Agreement.
B-7
95
VOTING AGREEMENT SIGNATURE PAGE
IN WITNESS WHEREOF, the Parties have executed this Voting Agreement as
of the date first written above.
Introgen Therapeutics, Inc.
By:
-------------------------------------------------
Xxxxx X. Xxxxx
President and Chief Executive Officer
Aventis Pharmaceuticals Products Inc.
By:
---------------------------------------------
Name: Xx. Xxxxxx Xxxxxxxxxxx
---------------------------------------------
Title: Senior Vice President
---------------------------------------------
Xxxxx-Xxxxxxx Xxxxx International (Holdings), Inc.
By:
---------------------------------------------
Name: Xxxxxxx X. Xxxxxxx
---------------------------------------------
Title: President
---------------------------------------------
B-8
96
EXHIBIT 2.2.1(c)
FORM OF ASSIGNMENT AND ASSUMPTION INSTRUMENT
ASSIGNMENT AND ASSUMPTION AGREEMENT
ASSIGNMENT AND ASSUMPTION AGREEMENT, effective as of July 2, 2001, among Aventis
Pharmaceuticals Products Inc. (formerly Xxxxx-Xxxxxxx Xxxxx Pharmaceuticals
Inc.), a Pennsylvania corporation ("APPI" or "Assignor") [SHOULD AN AVENTIS
ENTITY OTHER THAN OR IN ADDITION TO APPI BE THE ACTUAL PARTY TO ANY CLINICAL
TRIAL AGREEMENT, THAT PARTY SHALL BE SUBSTITUTED OR ADDED TO THIS AGREEMENT AS
APPROPRIATE], and
Introgen Therapeutics Inc., a Delaware corporation ("Introgen
Therapeutics" or "Assigne
WITNESSETH
WHEREAS, Assignor and Assignee have entered into a Restated
p53 and K-ras
Agreement, dated as of June 30, 2001 (the "Restated Agreement"; capitalized
terms used herein and not otherwise defined herein having the respective
meanings given in the Restated Agreement), providing for the restructuring of
the Original p53 Agreement and the Original K-ras Agreement so that Introgen
Therapeutics takes over from the Aventis Parties the further development and
commercialization of the gene therapy products for the delivery of the p53 and
K-ras inhibition genes, including the INGN 201 product, and that Aventis retain
a potential economic upside in those products by making an additional equity
investment in Introgen Therapeutics; and
WHEREAS, pursuant to Section 2.2. 1 (c) of the Restated Agreement, Assignor has
agreed to enter into this Assignment and Assumption Agreement providing for the
assumption by Assignee of the agreement listed on Schedule - attached hereto
(the "Clinical Trial Agreement");
NOW, THEREFORE, for and in consideration of the mutual consideration provided
for in the Restated Agreement, and for other good and valuable consideration,
the receipt and sufficiency of which is hereby acknowledged, and pursuant to the
terms and conditions of the Restated Agreement, the parties hereto agree as
follows:
1. Assignment of Rights. The Assignor hereby assigns and relinquishes all rights
of any kind, whether fixed, contingent, accrued or otherwise, that either the
Assignor or any Affiliate of the Assignor may have under, with respect to or in
connection with the Clinical Trial Agreement unless otherwise required to retain
such rights and obligations under the such contract or by law.
2. Assumption of Liabilities. Assignee hereby assumes all obligations and
liabilities of any kind, whether fixed, contingent, accrued or otherwise, that
the Assignor or any Affiliate of the Assignor may have under, with respect to or
in connection with the Clinical Trial Agreement.
3. Representations and Warranties. The Assignor is not making any
representations or warranties of any nature or kind with respect to the
Clinical Trial Agreement, except as expressly made and contained in the Restated
Agreement.
97
4. Conflicts with Restated Agreement. In the event that any provision of this
Agreement is construed to conflict with a provision of the Restated Agreement,
the provision in the Restated Agreement shall be deemed controlling.
5. Governing Law. This Agreement shall be construed and enforced in accordance
with the laws of the State of
New York without giving effect to the choice of
law principles thereof which would require the application of the laws of a
jurisdiction other than
New York.
IN WITNESS WHEREOF, each party hereto has caused this Assignment and Assumption
AgFeement to be duly executed by its duly authorized officer and to be effective
as of the date indicated above.
INTROGEN THERAPEUTICS, INC. AVENTIS PHARMACEUTICALS
PRODUCTS INC.
By: By:
------------------------------ ---------------------------------
Name: Name:
---------------------------- -------------------------------
Title: Title:
--------------------------- ------------------------------
SHOULD ANY CLINICAL TRIAL AGREEMENT REQUIRE THE ADDITION OF ANY ADDITIONAL
LANGUAGE OR TERMS TO THIS ASSIGNMENT AND ASSUMPTION AGREEMENT, AVENTIS RESERVES
THE RIGHT TO ADD SUCH LANGUAGE OR TERMS. ADDITIONALLY, SHOULD ANY CLINICAL TRIAL
AGREEMENT REQUIRE THAT THE NON-AVENTIS PARTY TO SUCH CLINICAL TRIAL AGREEMENT
ALSO BE A PARTY TO THIS AGREEMENT, SUCH PARTY SHALL BE ADDED.
98
EXHIBIT 2.2.2
LATER STAGE CLINICAL DEVELOPMENT ACTIVITIES
Point of transfer of late stage clinical studies from Aventis to Introgen:
- [*]: Final Study Reports
- [*]: Close study sites for enrollment and transfer of safety data.
- [*]:
o Transfer current clinical database
o Completion of therapy in [*] patients currently treated. If
therapy/monitoring extended beyond [*], Introgen will pay
for all services (including internal costs) provided by
[*], as well.
o Transition to Clinical Research status, as appropriate.
- [*]: Transfer of current clinical database.
- [*]: Aventis to complete database lock.
- [*] & Bio-safety Report: Draft Final Study Reports.
- [*]: Transfer of current clinical database.
- [*]: Clinical responsibility transferred in May in the US. Outside
the United States, the clinical responsibility will be transferred to
Introgen within [*] days of signature of the Agreement.
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
99
EXHIBIT 2.3.1
DOCUMENTATION AND P53 MATERIALS
If additional documents fall within the definition of p53 or K-Ras related
material, Introgen shall have until the end of the Transition Period to make
photocopies.
EFFICACY STUDIES
[*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
[*]
o [*]
[*]
o [*]
o [*]
BIODISTRIBUTION
Preclinical study : local and general biodistribution of Ad5CMV-p53 construct in
mice
[*]
[*]
[*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
100
[*]
o [*]
o [*]
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o [*]
o [*]
o [*]
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o [*]
TOXICOLOGY
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
101
o [*]
o [*]
o [*]
o [*]
o [*]
MOLECULAR ANALYSIS
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
102
EXPERIMENTAL REPORTS
[*]
[*]
[*]
[*]
[*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
HCC - BRECHOT'S STUDIES
o [*]
o [*]
o [*]
o [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
103
o [*]
[*]
o [*]
o [*]
PUBLICATIONS RELATED TO RPR/INGN 201 (RESEARCH)
o [*]
o [*]
o [*]
o [*]
CLINICAL/REGULATORY
o [*]
o [*]
o Copy of all CROs contracts
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
104
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o List of additional institutions and ethics committees
expecting Finalized Biosafety report
o Material Tracking Documentation for Materials used at clinical
sites in the EU
o Material Tracking Documentation for Materials used at clinical
sites in the US
o Material Tracking Documentation for Materials used at clinical
sites in the US; completed [*]
o Tracking Documentation for Materials used at clinical
sites in the US collected between [*] and hand over of
responsibility to Introgen
o Material Tracking Documentation for Materials used at clinical
sites in [*]
o US - Investigational Materials Request Form (IMRF) Database
(Access Material Tracking)
o US drug request form
o Aventis Clinical procedures document for US IMRF process -
electronic version
o Aventis Regulatory procedure document for US IMRF process
o Identify Authorities needing to get Biosafety report (when
complete)
CMC/REGULATORY
o Regulatory Submissions to US, EU (eg: CMC & protocol &
biosafety submissions to various regulatory agencies in EU)
o Regulatory communications to all agencies.
o Current status of submissions
o Addresses/contact information for various agencies
o List of reporting responsibilities that will have to be
carried out for each agency
o CMC dossiers for support of EU trials
o Electronic copies of documents prepared by Aventis & submitted
to US
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
105
o Electronic copies of documents prepared by Aventis & submitted
to [*]
o Electronic copies of documents prepared by Aventis & submitted
to [*]
o Aventis R SAs concerning regulatory strategies for dealing
with regulatory agencies
o Import information used to release previous Introgen material
for use in EU/JP/Canada
o Text provided for submission to [*] including immunological
reaction and hepatotoxicity
o Send package to [*] for [*] submission
o Dossier in progress for [*] submission of [*]
o Dossier in progress for [*] Submission of [*] - Introgen
input needed for SKBS form - complaints and recalls procedure
DATABASES
Only when Introgen is ready to receive (Safe Harbor, Section 7.5)
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
106
TECHNICAL
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
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o [*]
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o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
107
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
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o [*]
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o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
108
RELEASE ASSAYS - INFORMATION AND TRAINING AS LISTED BELOW
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
109
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
CLINICAL SUPPLY INFORMATION
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
o [*]
QUALITY ASSURANCE
Summary of audit reports of vendors for p53 program
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
110
TECHNICAL MATERIALS
[*] [*]
--------- ------
[*]
[*] [*]
[*] [*]
[*] [*]
[*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*]
[*] [*]
[*] [*]
VENDORS
o Authorization for Introgen to directly communicate with Aventis vendors
concerning p53
[*]
[*]
[*]
[*]
[*]
o [*]
[*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
111
o [*]
o [*]
o [*]
o [*]
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o [*]
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[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
112
o [*]
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o [*]
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[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
113
o [*]
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[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
114
o [*]
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[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
115
o [*]
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[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
116
o [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
117
o [*]
OTHER TECHNOLOGIES
(NON-p53)
AV1Y28
o [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
118
o [*]
LIPIDS
o [*]
MARKETING AND COMMUNICATIONS
o p53 business plans (initial/current)
o p53 worldwide marketing analysis/studies (broken down by
country/other geography)
o p53 European marketing analysis/studies (broken down by
country/other geography)
o p53 worldwide forecasted revenue by application (head & heck,
lung, etc..) & geography
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
119
o p53 European forecasted revenue by application (head & heck,
lung, etc..) & geography
o p53 worldwide marketing plans
o p53 European marketing plans
o p53 product pricing/gross margin analysis
o p53 marketing materials (planned brochures, flyers,
photographs)
o p53 targeted customers contact list (hospitals, cancer
clinics, etc.)
o p53 press releases (released and planned - including Phase III
program)
o p53 sales training material/plans
o p53 sales & marketing presentations
o Marketing Subteam meeting minutes
o Planned press releases for p53
o Competitive information on p53 programs [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
120
EXHIBIT 2.3.1.a
SCHEDULE FOR TRANSFER OF MATERIALS AND DOCUMENTATION IN EXHIBIT 2.3.1
IF ANY ITEM APPEARS ON EXHIBIT 2.3.1(a) THAT DOES NOT ALSO APPEAR ON
EXHIBIT 2.3.1, THE AVENTIS PARTIES SHALL HAVE NO OBLIGATION TO PROVIDE SUCH ITEM
TO INTROGEN THERAPEUTICS. THE CONTENT OF EXHIBIT 2.3.1 SHALL CONTROL AS TO
DOCUMENTS TO BE DELIVERED BY THE AVENTIS PARTIES TO INTROGEN THERAPEUTICS.
121
EXHIBIT 2.3.2
P53 ASSIGNMENT AGREEMENT
p53 ASSIGNMENT AGREEMENT, effective as of July 2, 2001, among Aventis
Pharmaceuticals Products Inc. (formerly Xxxxx-Xxxxxxx Xxxxx Pharmaceuticals
Inc.), a Pennsylvania corporation ("APPI"), Aventis Pharma S.A., a company
organized under the laws of France ("APSA" and, together with APPI, the "Aventis
Parties") ("Assignors"), having an office for the transaction of business at
Xxxxx 000-000, Xxxxxxxxxxx, XX, and
Introgen Therapeutics Inc., a Delaware
corporation ("Introgen Therapeutics"), ("Assignee"), having an office for the
transaction of business at 000 Xxxxxxxx Xxxxxx, Xxxxxx, Xxxxx.
WITNESSETH
WHEREAS, Assignors and Assignee have entered into a Restated
p53 and K-ras
Agreement, dated as of June 30, 2001 (the "Restated Agreement"; capitalized
terms used herein and not otherwise defined herein having the respective
meanings given in the Restated Agreement), providing for the restructuring of
the Original p53 Agreement and the Original K-ras Agreement, so that Introgen
Therapeutics takes over from the Aventis Parties the further development and
commercialization of the gene therapy products for the delivery of the p53 and
K-ras inhibition genes, including the INGN 201 product, and that Aventis retain
a potential economic upside in those products by making an additional equity
investment in Introgen Therapeutics; and
WHEREAS, pursuant to Section 2.3.2 of the Restated Agreement, Assignors have
agreed to enter into this Assignment Agreement providing for the assignment of
Assignor of the (i) p53 Materials; (ii) p53 Documentation; and (iii) INDs with
respect to INGN 201 ("Assigned Matter") as provided under Section 2.3.1 of the
Restated Agreement;
NOW, THEREFORE, for and in consideration of the mutual consideration provided
for in the Restated Agreement, and for other good and valuable consideration,
the receipt and sufficiency of which is hereby acknowledged, and pursuant to the
terms and conditions of the Restated Agreement, the parties hereto agree as
follows:
1. Assignment of Rights. Each Assignor hereby assigns and relinquishes its
right, title and interest, that any Assignor may have with respect to or in
connection with the (i) p53 Materials; (ii) p53 Documentation; and (iii) INDs
with respect to INGN 201 under Section 2.3.2 of the Restated Agreement unless
otherwise required to retain such rights and obligations under a Third Party
Agreement or by law and as further limited in Sections 2.3.1. 2.3.4. 7.2 and
7.3 of the Restated Agreement.
3. Representations and Warranties. The Assignors are not making any
representations or warranties of any nature or kind with respect to the Assigned
Materials, except as expressly made and contained in the Restated Agreement.
4. Conflicts with Restated Agreement. In the event that any provision of this
Agreement is construed to conflict with a provision of the Restated Agreement,
the provision in the Restated Agreement shall be deemed controlling.
122
5. Governing-Law. This Agreement shall be construed and enforced in accordance
with the laws of the State of
New York without giving effect to the choice of
law principles thereof which would require the application of the laws of a
jurisdiction other than
New York.
IN WITNESS WHEREOF, each party hereto has caused this Assignment and Assumption
Agreement to be duly executed by its duly authorized officer effective as of the
date indicated above.
INTROGEN THERAPEUTICS, INC. AVENTIS PHARMACEUTICALS
PRODUCTS INC.
By: By:
-------------------------------- --------------------------------
Name: Name:
------------------------------ ------------------------------
Title: Title:
----------------------------- -----------------------------
AVENTIS PHARMA S.A..
By:
--------------------------------
Name:
------------------------------
Title:
-----------------------------
(SIGNATURE PAGE TO p53 ASSIGNMENT AGREEMENT]
123
EXHIBIT 4.1.2
K-RAS ASSIGNMENT AGREEMENT
K-ras ASSIGNMENT AGREEMENT, effective as of July 2, 2001, among Aventis
Pharmaceuticals Products Inc. (formerly Xxxxx-Xxxxxxx Xxxxx Pharmaceuticals
Inc.), a Pennsylvania corporation ("APPI"), Aventis Pharma S.A., a company
organized under the laws of France ("APSA" and, together with APPI, the "Aventis
Parties") ("Assignors"), having an office for the transaction of business at
Xxxxx 000-000, Xxxxxxxxxxx, XX, and
Introgen Therapeutics Inc., a Delaware
corporation ("Introgen Therapeutics"), ("Assignee"), having an office for the
transaction of business at 000 Xxxxxxxx Xxxxxx, Xxxxxx, Xxxxx.
WITNESSETH
WHEREAS, Assignors and Assignee have entered into a Restated
p53 and K-ras
Agreement, dated as of June 30, 2001 (the "Restated Agreement"; capitalized
terms used herein and not otherwise defined herein having the respective
meanings given in the Restated Agreement), providing for the restructuring of
the Original p53 Agreement and the Original K-ras Agreement, so that Introgen
Therapeutics takes over from the Aventis Parties the further development and
commercialization of the gene therapy products for the delivery of the p53 and
K-ras inhibition genes, including the INGN 201 product, and that Aventis retain
a potential economic upside in those products by making an additional equity
investment in Introgen Therapeutics; and
WHEREAS, pursuant to Section 4.2.2 of the Restated Agreement, Assignors have
agreed to enter into this Assignment Agreement providing for the assignment of
Assignor of the K-ras Materials and K-ras Documentation ("Assigned Matter")
under Section 4.2.1 of the Restated Agreement;
NOW, THEREFORE, for and in consideration of the mutual consideration provided
for in the Restated Agreement, and for other good and valuable consideration,
the receipt and sufficiency of which is hereby acknowledged, and pursuant to the
terms and conditions of the Restated Agreement, the parties hereto agree as
follows:
1. Assignment of Rights. Each Assignor hereby assigns and relinquishes its
right, title and interest, that any Assignor may have with respect to or in
connection with the K-ras Materials and K-ras Documentation under Section 4.2.2
of the Restated Agreement unless otherwise required to retain such rights and
obligations under a Third Party Agreement or by law and as further limited in
Sections 4.2.1, 7.2 and 7.3 of the Restated Agreement. .
3. Representations and Warranties. The Assignors are not making any
representations or warranties of any nature or kind with respect to the Assigned
Materials, except as expressly made and contained in the Restated Agreement.
4. Conflicts with Restated Agreement. In the event that any provision of this
Agreement is construed to conflict with a provision of the Restated Agreement,
the provision in the Restated Agreement shall be deemed controlling.
124
5. Governing Law. This Agreement shall be construed and enforced in accordance
with the laws of the State of
New York without giving effect to the choice of
law principles thereof which would require the application of the laws of a
jurisdiction other than New York.
IN WITNESS WHEREOF, each party hereto has caused this Assignment and Assumption
Agreement to be duly executed by its duly authorized officer effective as of the
date indicated above.
INTROGEN THERAPEUTICS, INC. AVENTIS PHARMACEUTICALS PRODUCTS INC.
By: By:
----------------------------------- --------------------------------
Name: Name:
--------------------------------- ------------------------------
Title: Title:
-------------------------------- -----------------------------
AVENTIS PHARMA S.A..
By:
--------------------------------
Name:
------------------------------
Title:
-----------------------------
[SIGNATURE PAGE TO K-ras ASSIGNMENT AGREEMENT]
125
EXHIBIT 7.2
CONSENT REPORTS
126
INTROGEN/AVENTIS
IP/COLLABORATION UPDATE
EXHIBIT 1 FROM LOI
THIRD PARTY PROPOSAL TO
FILE PCT NUMBER INVOLVEMENT TITLE OWNERSHIP ASSIGN OR LICENSE ACTIONS DONE
---- ---------- ----------- ----- --------- ----------------- ------------
[*] [*] [*] [*] [*] [*] [*]
LICENSING
FILE PCT NUMBER DATA ACTION NEXT STEP NOTES
---- ---------- ----------- --------- ---------
[*] [*] [*] [*] [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
Page 1
127
INTROGEN/AVENTIS
IP/COLLABORATION UPDATE
EXHIBIT 1 FROM LOI
THIRD PARTY PROPOSAL TO
FILE PCT NUMBER INVOLVEMENT TITLE OWNERSHIP ASSIGN OR LICENSE ACTIONS DONE
---- ---------- ----------- ----- --------- ----------------- ------------
[*] [*] [*] [*] [*] [*] [*]
LICENSING
FILE PCT NUMBER DATA ACTION NEXT STEP NOTES
---- ---------- ----------- --------- ---------
[*] [*] [*] [*] [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
Page 2
128
INTROGEN/AVENTIS
IP/COLLABORATION UPDATE
EXHIBIT 2 FROM LOI
AVENTIS PHARMACEUTICALS' ADENOVIRAL DELIVERY IP
THIRD PARTY PROPOSAL TO
FILE PCT NUMBER INVOLVEMENT TITLE OWNERSHIP ASSIGN OR LICENSE ACTIONS DONE
---- ---------- ----------- ----- --------- ----------------- ------------
[*] [*] [*] [*] [*] [*] [*]
LICENSING
FILE PCT NUMBER DATA ACTION NEXT STEP NOTES
---- ---------- ----------- --------- ---------
[*] [*] [*] [*] [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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EXHIBIT 2 FROM LOI
AVENTIS PHARMACEUTICALS' ADENOVIRAL DELIVERY IP
THIRD PARTY PROPOSAL TO
FILE PCT NUMBER INVOLVEMENT TITLE OWNERSHIP ASSIGN OR LICENSE ACTIONS DONE
---- ---------- ----------- ----- --------- ----------------- ------------
[*] [*] [*] [*] [*] [*] [*]
LICENSING
FILE PCT NUMBER DATA ACTION NEXT STEP NOTES
---- ---------- ----------- --------- ---------
[*] [*] [*] [*] [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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EXHIBIT 2 FROM LOI
AVENTIS PHARMACEUTICALS' ADENOVIRAL DELIVERY IP
THIRD PARTY PROPOSAL TO
FILE PCT NUMBER INVOLVEMENT TITLE OWNERSHIP ASSIGN OR LICENSE ACTIONS DONE
---- ---------- ----------- ----- --------- ----------------- ------------
[*] [*] [*] [*] [*] [*] [*]
LICENSING
FILE PCT NUMBER DATA ACTION NEXT STEP NOTES
---- ---------- ----------- --------- ---------
[*] [*] [*] [*] [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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EXHIBIT 2 FROM LOI
AVENTIS PHARMACEUTICALS' ADENOVIRAL DELIVERY IP
THIRD PARTY PROPOSAL TO
FILE PCT NUMBER INVOLVEMENT TITLE OWNERSHIP ASSIGN OR LICENSE ACTIONS DONE
---- ---------- ----------- ----- --------- ----------------- ------------
[*] [*] [*] [*] [*] [*] [*]
LICENSING
FILE PCT NUMBER DATA ACTION NEXT STEP NOTES
---- ---------- ----------- --------- ---------
[*] [*] [*] [*] [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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EXHIBIT 2 FROM LOI
AVENTIS PHARMACEUTICALS' ADENOVIRAL DELIVERY IP
THIRD PARTY PROPOSAL TO
FILE PCT NUMBER INVOLVEMENT TITLE OWNERSHIP ASSIGN OR LICENSE ACTIONS DONE
---- ---------- ----------- ----- --------- ----------------- ------------
[*] [*] [*] [*] [*] [*] [*]
LICENSING
FILE PCT NUMBER DATA ACTION NEXT STEP NOTES
---- ---------- ----------- --------- ---------
[*] [*] [*] [*] [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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EXHIBIT 2 FROM LOI
AVENTIS PHARMACEUTICALS' ADENOVIRAL DELIVERY IP
THIRD PARTY PROPOSAL TO
FILE PCT NUMBER INVOLVEMENT TITLE OWNERSHIP ASSIGN OR LICENSE ACTIONS DONE
---- ---------- ----------- ----- --------- ----------------- ------------
[*] [*] [*] [*] [*] [*] [*]
LICENSING
FILE PCT NUMBER DATA ACTION NEXT STEP NOTES
---- ---------- ----------- --------- ---------
[*] [*] [*] [*] [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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EXHIBIT 7 FROM LOI
AVENTIS PHARMACEUTICALS' NON-VIRAL TECHNOLOGY AND LICENSES.
[*]
THIRD PARTY PROPOSAL TO
FILE PCT NUMBER INVOLVEMENT TITLE OWNERSHIP ASSIGN OR LICENSE ACTIONS DONE
---- ---------- ----------- ----- --------- ----------------- ------------
[*] [*] [*] [*] [*] [*] [*]
LICENSING
FILE PCT NUMBER DATA ACTION NEXT STEP NOTES
---- ---------- ----------- --------- ---------
[*] [*] [*] [*] [*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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LICENSING NOTES
(1) [*] FUNDING: In general, funding for these patents came under [*]
agreements with the [*]. Although the exact agreement has not been
identified with the specific IP item, Aventis anticipates (based on contract
terms) that the license granted to Introgen will have the following
parameters:
Generally, there is a royalty of [*] of sales generated by the results of
the funded research program (not to exceed the total amount of the advance,
[*], for the gene therapy agreement). There are two measurement dates for
determining royalty (reimbursement of funding) amounts:
[*]
The provisions of the other four agreements are similar with the longest
reimbursement date of [*], for sales made between [*], thus making it
unlikely that royalties or reimbursement is due for a p53 product under the
other [*] agreements. No royalties or funding reimbursement is required if
sales occur outside of the reimbursement dates.
May not be licensed nor assigned to third party without prior consent of
French government. Request for license or transfer will be made the first
week of [*].
For those properties that may be assigned to Introgen, the current [*]
grants are silent as to the specific question of patent abandonment.
However, there is a general requirement in the funding grant that any change
in the status of the cases, such as transfer to a third party requires
notification of the [*] and consent. Therefore, it is likely that there is a
requirement that Introgen notify the [*] and obtain its consent if Introgen
wanted to abandon any of the properties tied to [*] funding. Aventis, in the
next contacts with the [*] about the properties licensed or assigned under
[*], will seek clarification of this point.
(2) [*]:
Research Collaboration Agreement [*]
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Aventis Pharma has the right to exploit directly or indirectly the results
arising out the performance of the research program conducted under this
agreement.
If Aventis Pharma commercializes such results, agreement provides for the
signature of a specific license arrangement which will mention the royalty
rate (no more than [*] of the sales of products including a recombinant
adenovirus). However, if these patents require the patents licensed under
the co-exclusive license agreement [*], then the maximum royalty can reach
[*]. This rate could be reduced in case Aventis Pharma should have to pay
royalties to another third party for the exploitation of such products.
Aventis Pharma can't transfer rights of exploitation and ownership of the
patents to a third party without the prior approval of Organization.
For those properties that may be assigned to Introgen, all of the [*]
agreements require notification to the [*] and the [*] must be provided the
opportunity to take over the prosecution and maintenance of the properties
on its own behalf.
(3) [*]
Requires Prior consent of [*]. Royalty rate as noted under [*] agreement
(note #2)
(4) [*]
[*]
Since Aventis Pharma has to exploit, the results arising out the performance
of research programs in the [*], we can consider that Aventis Pharma has the
right to license such results to a third party.
CONDITIONS:
The [*] agreement provides that:
- the royalty rate shall not be less than [*] of the sales of specialties
including one or more products or processes arising out the results
- such rate shall be determined based on the intellectual and financial
contributions of each party to the results
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-before commercialization of the results, directly or indirectly, a
specific agreement has to be concluded
Aventis needs to negotiate with [*] and [*] a specific agreement which
determines the royalty rate before a license is granted to Introgen.
(5) AVENTIS PHARMACEUTICALS: These IP items are free and clear of any third
party association.
(6) [*]:
No agreement is in place regarding the IP rights and obligations with this
institution. First meeting with [*] was on May 29th and a written proposal
is to follow shortly.
Relative proportions of co-ownership have yet to be determined between
Aventis and [*]. Although prior written consent for licensing,
sub-licensing and assignment is not necessary, Aventis has the obligation
to keep [*] informed of any licensing activities.
(7) [*]
[*]
Aventis Pharma has the right to exploit directly or indirectly the results
arising out the performance of the research program conducted under this
agreement.
Aventis needs to negotiate a specific agreement to precise the royalty
rate. Prior approval before transfer of the ownership of the patents.
(8) [*]
Aventis has an agreement with [*] that covers a research program from [*]
with minimum funding requirement for the each year (about [*] remains on
minimum research funding, in which Introgen would fund if the contract is
assigned) and also covers a license for [*]. There is no provision in the
agreement to just terminate the research program and continue with the
license portion of the agreement. We [*] to make a modification to the
agreement to terminate the research program and maintain the license and
option rights under the agreement. Also, we asked for their consent to
assign the license agreement to a third party [Introgen was specifically
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named]. [*] is firm on keeping the research program and license together and
would not terminate only a part of it. In other words, if we terminate the
research program the complete agreement will terminate. On the assignability
issue, [*] is willing to discuss, but would like the new partner focused on
similar scientific interests. [*] would like to meet with Introgen in early [*]
to discuss Introgen's interest in the technology and research.
(8) [*]:
o [*]
o [*]
o [*]
o [*]
o [*]
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[*]
(9) [*]:
Aventis has a license agreement with [*] that grants Aventis exclusive
option to select up to [*] genes for [*] homing peptide technology. Aventis
has already exercised its option for all [*] genes [*] and has named [*]
genes. We approached [*] to name the 4th gene as p53. BI has confirmed that
this gene is available for license in their [*] Fax. We are in the process
of preparing a license agreement for p53 gene on predetermined terms as
noted below. [*] is O.K. with the assignment of p53 gene license to Introgen
pending due diligence of development timelines and commitment of Introgen.
This will happen in two different steps:
1) Aventis will execute a license agreement with [*] for p53 gene.
2) When the p53 agreement is executed we will proceed with the assignment of
this agreement to Introgen. [*] would like to do their due diligence on
Introgen before giving Aventis permission to assign p53 license to Introgen.
We will have the p53 license document ready to send to [*] by [*] and
soon after discuss the assignment issue with [*].
MAIN TERMS:
[*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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[*]
[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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