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EXHIBIT 10.23
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COLLABORATION AGREEMENT
(K-ras PRODUCTS)
BY AND BETWEEN
XXXXX-XXXXXXX XXXXX PHARMACEUTICALS, INC.
AND
INTROGEN THERAPEUTICS, INC.
OCTOBER 7, 1994
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TABLE OF CONTENTS
PAGE
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1. DEFINITIONS....................................................... 1
2. NORTH AMERICAN DEVELOPMENT........................................ 5
2.1 Early Stage Development Program........................ 5
2.2 Collaboration Products................................. 5
2.3 Development Activities................................. 5
2.4 Reports and Records.................................... 6
2.5 Review of Publication.................................. 7
3. DEVELOPMENT COMMITTEE............................................. 8
3.1 Development Committee.................................. 8
3.2 Membership............................................. 8
3.3 Development Committee Meetings......................... 8
3.4 North American Plans and Budgets....................... 8
3.5 Plans for Later Stage Development...................... 9
3.6 Decision Making........................................ 9
4. EARLY STAGE DEVELOPMENT PROGRAM FUNDING........................... 10
4.1 Funding of Early Stage Development Program............. 10
4.2 Term of Early Stage Development Program................ 10
4.3 Excess Early Stage Development Program Costs........... 10
4.4 Capital Equipment...................................... 10
4.5 Payments............................................... 10
5.1 RPRP Territory......................................... 11
5.2 Co-Exclusive Territory................................. 11
5.3 Other Territory........................................ 11
5.4 Use of Clinical Data................................... 11
5.5 Development Committee Review........................... 12
5.6 Further Studies........................................ 12
6. EXCLUSIVITY....................................................... 12
6.1 Option to Commercialize................................ 12
6.2 Exclusivity............................................ 13
6.3 Right of First Discussion in Expanded Field............ 13
7. MARKETING RIGHTS.................................................. 13
7.1 RPRP Territory......................................... 13
7.2 Co-Exclusive Territory................................. 13
7.3 North America.......................................... 14
7.4 Other Territory........................................ 14
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TABLE OF CONTENTS
(CONTINUED)
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7.5 Sublicensees........................................... 15
7.6 Covenants.............................................. 15
8. ROYALTIES......................................................... 15
8.1 Running Royalties...................................... 15
8.2 Royalty Offset......................................... 15
9. THIRD PARTY ROYALTIES............................................. 17
9.1 RPRP Obligations....................................... 17
9.2 Introgen Obligations................................... 18
9.3 North America.......................................... 18
9.4 Efforts to Obtain Sublicense Rights.................... 18
10. PAYMENTS; BOOKS AND RECORDS....................................... 18
10.1 Royalty Reports and Payments........................... 18
10.2 Payment Method......................................... 19
10.3 Late Payment........................................... 19
10.4 Currency Conversion.................................... 19
10.5 No Withholding Taxes................................... 19
10.6 Records; Inspection.................................... 19
11. DUE DILIGENCE..................................................... 20
11.1 Due Diligence.......................................... 20
12. MANUFACTURING RIGHTS.............................................. 20
12.1 RPRP Territory......................................... 20
12.2 Co-Exclusive Territory................................. 20
12.3 North America.......................................... 20
12.4 Other Territory........................................ 21
12.5 Supply Agreements...................................... 21
13. LICENSE GRANTS.................................................... 21
13.1 Grant to RPRP.......................................... 21
13.2 Grant to Introgen...................................... 21
13.3 Grant to Joint Venture................................. 21
13.4 Sublicenses............................................ 21
13.5 Improvements by Introgen............................... 22
13.6 No Rights Beyond Collaboration Products................ 22
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TABLE OF CONTENTS
(CONTINUED)
PAGE
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14. INTELLECTUAL PROPERTY............................................. 22
14.1 Ownership of Inventions................................ 22
14.2 Patent Prosecution..................................... 23
14.3 Defense of Third Party Infringement Claims............. 24
14.4 Enforcement............................................ 24
15. REPRESENTATIONS AND WARRANTIES.................................... 25
15.1 Warranties............................................. 25
15.2 Disclaimer of Warranties............................... 25
15.3 Effect of Representations and Warranties............... 26
16. CONFIDENTIALITY................................................... 26
16.1 Confidential Information............................... 26
16.2 Permitted Disclosures.................................. 26
17. INDEMNIFICATION................................................... 27
17.1 Indemnification of Introgen............................ 27
17.2 Indemnification of RPRP................................ 27
17.3 Procedure.............................................. 28
18. TERM AND TERMINATION.............................................. 28
18.1 Term................................................... 28
18.2 Termination for Cause.................................. 28
18.3 Termination for Convenience by RPRP.................... 28
18.4 Effect of Breach or Termination........................ 29
18.5 Survival............................................... 30
19. MISCELLANEOUS..................................................... 30
19.1 Governing Law.......................................... 30
19.2 Force Majeure.......................................... 30
19.3 No Implied Waivers; Rights Cumulative.................. 30
19.4 Independent Research................................... 31
19.5 Independent Contractors................................ 31
19.6 Notices................................................ 31
19.7 Assignment............................................. 32
19.8 Modification........................................... 32
19.9 Severability........................................... 32
19.10 Non-Disclosure......................................... 32
19.11 Entire Agreement....................................... 32
19.12 Counterparts........................................... 33
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TABLE OF CONTENTS
(CONTINUED)
19.13 Headings............................................... 33
19.14 Patent Marking......................................... 33
19.15 Export Laws............................................ 33
EXHIBITS
A - Existing Introgen Licensed Patents
B - European Countries
C - Initial Program Plan and Budget
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COLLABORATION AGREEMENT
(K-Ras PRODUCTS)
This AGREEMENT (the "Agreement"), effective as of October 7, 1994 (the
"Effective Date"), is made by and between Xxxxx-Xxxxxxx Xxxxx Pharmaceuticals
Inc., a Pennsylvania corporation having offices at 000 Xxxxxx Xxxx, X.X. Xxx
0000, Xxxxxxxxxxxx, Xxxxxxxxxxxx 00000-0000 ("RPRP"), and Introgen Therapeutics,
Inc., a Delaware corporation having offices at 000 Xxxxxxxx Xxxxxx, Xxxxx 0000,
Xxxxxx, Xxxxx 00000 ("Introgen").
RECITALS
A. Introgen has established expertise related to gene therapy and RPRP
has established a major research program in the field of gene therapy for the
treatment of human cancer.
B. The parties desire to establish a collaborative relationship to
develop and commercialize novel gene therapy products as set forth below.
C. Introgen and RPRP's parent, Xxxxx-Xxxxxxx Xxxxx Inc., have also
entered into a Stock Purchase Agreement of even date herewith, pursuant to which
RPRP is acquiring Introgen Preferred Stock.
NOW THEREFORE, for and in consideration of the covenants, conditions,
and undertakings hereinafter set forth, it is agreed by and between the parties
as follows:
1. DEFINITIONS
1.1 "Affiliate" shall mean any entity which controls, is controlled or
is under common control with RPRP or Introgen. An entity shall be regarded as in
control of another entity if it owns or controls at least thirty-five percent
(35%) 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). A "Controlled Affiliate"
shall mean an entity that is controlled by a party wherein such percentage is at
least fifty percent (50%).
1.2 "Co-exclusive Territory" shall mean Japan, North and South Korea,
Taiwan, the People's Republic of China and India.
1.3 "Collaboration Products" shall mean the gene therapy products
within the Field which are being developed by Introgen and RPRP from time to
time pursuant to the Early Stage Development Program, as specified in the
Program Plan and Budget in effect at the time, and as further defined in Section
6.1 below.
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1.4 "Development Committee" shall have the meaning set forth in Article
3 herein.
1.5 "Early Stage Development" shall mean that part of the Early Stage
Development Program comprising the research, preclinical and clinical activities
with respect to approved Collaboration Products in North America through the
completion of Phase I clinical trials.
1.6 "Early Stage Development Program" shall have the meaning set forth
in Section 2.1 herein.
1.7 "Early Stage Development Program Costs" shall mean all direct and
indirect costs incurred by Introgen in conducting the Early Stage Development
Program in accordance with the applicable approved Program Plan and Budget.
1.8 "Expanded Field" shall mean gene therapy products which [*]
1.9 "Field" shall mean gene therapy products for the delivery of a gene
construct to patient cells via in vivo viral vectors or non-viral delivery
systems which expresses a molecule that [*] in each case for the treatment or
prevention of disease.
1.10 "FDA" means the U.S. Food and Drug Administration.
1.11 "IND" shall mean an investigational New Exemption for a
Collaboration Product, as defined in the U.S. Food, Drug and Cosmetic Act and
the regulations promulgated thereunder.
1.12 "Introgen Technology" shall mean Introgen Patents, Introgen
Licensed Patents and Introgen Know-how.
1.12.1 "Introgen Patents" shall mean all patents and
reissues, renewals and extensions thereof, and patent applications therefor, and
any divisions, continuations, in whole or in part, thereof, which claim a
process, composition of matter, or method of treatment used in the manufacture,
sale or use of a Collaboration Product and that are owned by Introgen or its
Controlled Affiliates during the term of this Agreement.
1.12.2 "Introgen Know-How" shall mean confidential
information and materials, including, but not limited to, pharmaceutical,
chemical, biological and biochemical products, technical and non-technical data,
and information relating to the results of tests, assays, methods and processes,
and drawings, plans, diagrams, specifications and/or other documents containing
said information and data, discovered, developed or acquired by Introgen or its
Controlled Affiliates during the term of this Agreement to the extent such
relates to the manufacture, sale or use of a Collaboration Product and to the
extent that Introgen or its Controlled Affiliates have the right to license or
sublicense the same.
1.12.3 "Introgen Licensed Patents" shall mean all patents
and reissues, renewals and extensions thereof, and patent applications therefor,
and any divisions, continuations, in whole or in part, thereof, which claim a
process, composition of matter, or method of treatment used in the
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manufacture, sale or use of a Collaboration Product, that are the subject of a
license or license option to Introgen or its Controlled Affiliates, in each case
to the extent that Introgen or its Controlled Affiliate has the right to license
or sublicense the same during the term of this Agreement. Introgen Licensed
Patents as of the Effective Date are listed on attached Exhibit A.
1.13 "Joint Venture" shall have the meaning set forth in Section 7.3.1
of this Agreement.
1.14 "Later Stage Clinical Development" shall mean all clinical
research and regulatory affairs necessary to obtain all governmental approvals
required to market each Collaboration Product for a particular indication in
North America following the Early Stage Development for such Collaboration
Product for such indication.
1.15 "Manufacturing Costs" with respect to units of a Collaboration
Product means (i) those costs associated with manufacture of such units which
would be viewed by the manufacturing party's independent auditor as costs that
could be capitalized on the balance sheet as inventory and would include all raw
material (including normal scrap) and actual direct labor costs and a proper
accounting of actual manufacturing overhead allocated to such units. It would
exclude any excess capacity, excess direct labor inefficiencies, unusable
material, or any other costs related to such units not deemed to add value or
not deemed to be ongoing in the production process for such product; and (ii)
with respect to portions acquired from a non-Affiliate vendor, the amounts paid
to the vendor.
1.16 "Net Sales" shall mean the total amount invoiced to third parties
in connection with sales or use of Collaboration Products by RPRP, its
Affiliates or its permitted Sublicensees, less the following reasonable and
customary accrual-basis deductions to the extent applicable to such invoiced
amounts in accordance with U.S. generally accepted accounting practices, as
consistently applied by both RPRP and RPR Inc. for financial reporting purposes:
(i) all trade, cash and quantity credits, discounts, refunds or rebates
(including without limitation Medicaid rebates); (ii) amounts for claims,
allowances or credits for returns; retroactive price reductions; chargebacks;
and (iii) packaging, handling fees and prepaid freight, sales taxes, duties and
other governmental charges (including value added tax), but excluding what is
commonly known as income taxes), in each case if charged separately on the
invoice and paid by the customer. For the removal of doubt, Net Sales shall not
include sales by RPRP to its Affiliate or its permitted Sublicensees for resale.
A "sale" shall also include a transfer or other disposition for consideration
other than cash, in which case such consideration shall be valued at the fair
market value thereof. Transfers or dispositions for charitable or promotional
purposes or for pre-clinical, clinical, regulatory or governmental purposes
prior to receiving marketing approval are not considered a "sale;" provided that
such transfers or dispositions are at a price less than [*] RPRP's Manufacturing
Cost for the units so transferred or disposed.
1.17 "North America" shall mean Canada, the United States (and its
territories and possessions including the commonwealth of Puerto Rico) and
Mexico.
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1.18 "PLA" and "ELA" means a Product License Application and an
Establishment License Application, respectively, as defined in the Public Health
Service Act, Biological Products and the regulations promulgated thereunder,
viz. 21 CFR Part 600, or its foreign equivalents.
1.19 "Phase I" means Phase I clinical trials as prescribed by
applicable FDA Regulations.
1.20 "Product Plan and Budget" shall have the meaning set forth in
Section 3.4.2 below.
1.21 "Program Plan and Budget" shall have the meaning set forth in
Section 3.4.1 hereof.
1.22 "RPR Inc." shall mean Xxxxx-Xxxxxxx Xxxxx, Inc., a Pennsylvania
Corporation.
1.23 "RPRP Development Costs" shall have the meaning set forth in
Section 7.3.3 below.
1.24 "RPRP Technology" shall mean RPRP Patents, RPRP Licensed Patents
and RPRP know-how.
1.24.1 "RPRP Patents" shall mean all patents and reissues,
renewals and extensions thereof, and patent applications therefor, and any
divisions, continuations, in whole or in part, thereof, which claim a process,
composition of matter, or method of treatment used in the manufacture, sale or
use of a Collaboration Product and that are owned by RPRP, RPR Inc. or their
Controlled Affiliates during the term of this Agreement.
1.24.2 "RPRP Know-How" shall mean confidential information
and materials, including, but not limited to, pharmaceutical, chemical,
biological and biochemical products, technical and non-technical data, and
information relating to the results of tests, assays, methods and processes, and
drawings, plans, diagrams, specifications and/or other documents containing said
information and data, discovered, developed or acquired by RPRP or its
Controlled Affiliates during the term of this Agreement to the extent such
relates to the manufacture, sale or use of a Collaboration Product and to the
extent that RPRP, RPR Inc. or their Controlled Affiliates have the right to
license or sublicense the same.
1.24.3 "RPRP Licensed Patents" shall mean all patents and
reissues, renewals and extensions thereof, and patent applications therefor, and
any divisions, continuations, in whole or in part, thereof, which claim a
process, a composition of matter, or method of treatment used in the
manufacture, sale or use of a Collaboration Product, that are the subject of a
license or license option to RPRP, RPR Inc. or their Controlled Affiliates and
to the extent that RPRP, RPR Inc. or their Controlled Affiliates have the right
to license or sublicense the same during the term of this Agreement.
1.25 "RPRP Territory" means those Eastern and Western European
countries set forth on Exhibit B hereto.
1.26 "Other Territory" shall mean [*]
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1.27 "Sublicensee" shall mean, with respect to a particular
Collaboration Product, a third party to whom Introgen or RPRP has granted a
license or sublicense under the RPRP Technology and/or Introgen Technology to
make, use and sell such Collaboration Product. As used in this Agreement,
"Sublicensee" shall also include a third party to whom Introgen or RPRP has
granted the right to distribute such Collaboration Product, provided that such
third party is responsible for the marketing and promotion of such products
within the applicable territory.
1.28 "Term of the Early Stage Development Program" shall be that period
of time described in Section 4.2 below.
2. NORTH AMERICAN DEVELOPMENT
2.1 Early Stage Development Program. Subject to the terms and
conditions set forth herein, RPRP and Introgen shall cooperate with respect to
the Early Stage Development of Collaboration Products in accordance with an
"Early Stage Development Program" for North America which shall be carried out
in accordance with a Program Plan and Budget prepared and approved on an annual
basis in accordance with Article 3.4 hereof. The Early Stage Development Program
shall include all of the approved Program Plans and Budgets in effect from time
to time. The activities conducted in connection with the Early Stage Development
Program will be overseen and administered by the Development Committee, pursuant
to Article 3 below. Introgen shall use its best efforts to conduct the Early
Stage Development in accordance with such Program Plan and Budget and within the
time schedules contemplated therein.
2.2 Collaboration Products. The Initial Collaboration Products to be
developed hereunder will contain or employ Introgen's Retroviral K-ras related
Transduction Vector and/or its Adenoviral K-ras related Transduction Vector.
From time to time, upon agreement of RPRP and Introgen, new projects may be
added to the Early Stage Development Program to be developed as Collaboration
Products. Such projects may include RPRP or Introgen products. It is understood
that RPRP may terminate its support for the development for any Collaboration
Product as provided in Section 18.3.2 below or as otherwise agreed by the
parties.
2.3 Development Activities.
2.3.1 Early Stage Development Program. Introgen will be
responsible for conducting, directly or through third parties, all development
of each new project and each Collaboration Product in North America through the
completion of Early Stage Development in accordance with the Program Plan and
Budget in effect from time to time. As soon as possible after completion of the
necessary preclinical studies required by the applicable Product Plan and Budget
for a Collaboration Product, Introgen shall be responsible for preparing, with
the cooperation of RPRP, a data package for each Collaboration Product
sufficient to meet IND requirements of the FDA.
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2.3.2 Later Stage Clinical Development.
(a) In addition to the Early Stage Development
Program, RPRP and Introgen will cooperate in the Later Stage Clinical
Development of each Collaboration Product; provided, RPRP will be primarily
responsible for conducting all such Later Stage Clinical Development, at RPRP's
expense. Introgen shall be consulted and fully informed with respect to such
Later Stage Clinical Development at all times through its representatives on the
Development Committee. All Later Stage Clinical Development shall be monitored
and managed by the Development Committee; [*].
(b) It is anticipated that RPRP will establish a
committee of independent experts (the "External Review Committee") to provide
advice with respect to Later Stage Clinical Development. The Chief Scientific
Officer of Introgen, or other designee of Introgen, if a clinician of recognized
stature, shall serve on and chair the External Review Committee; otherwise, RPRP
and Introgen shall agree on the chair of such External Review Committee. In any
event, Introgen shall have a representative on such External Review Committee.
(c) It is understood that additional preclinical
studies may be required following the completion of Early Stage Development with
respect to a Collaboration Product. The parties anticipate that, where
appropriate, such work will be performed by Introgen and reimbursed by RPRP, as
agreed from time to time by the Development Committee.
2.3.3 FDA Filings. Introgen shall be responsible for the
preparation and filing of all IND's in North America with respect to the
Collaboration Products, which shall be filed in Introgen's name; provided RPRP
shall have a reasonable opportunity to review and comment upon such filings in
advance of their filing. RPRP shall be responsible for all further submissions
to existing INDs once Later Stage Clinical Development has begun, provided that
Introgen is given a reasonable opportunity to review and comment upon such
submissions prior to the filing of such submissions. Introgen shall cooperate in
transferring to RPRP authority for such correspondence. RPRP, at its expense,
shall prepare all PLAs and ELA's for filing in North America with respect to
each Collaboration Product. All such PLA's and ELA's shall be filed in the names
of RPRP and Introgen, to the extent permitted by applicable FDA regulations
(taking into account the supply arrangements under Section 12.3. below), or in
such other manner as the Development Committee approves. In addition, RPRP shall
in all events have the right to file separately a PLA/ELA in its own name to
qualify, as a permitted supply source for the United States, its manufacturing
facility for the RPRP Territory (consistent with Section 12.3. below).
2.4 Reports and Records.
2.4.1 Records. Introgen and RPRP shall maintain records of the
Early Stage Development Program (or cause such records to be maintained) in
sufficient detail and in good scientific manner as will properly reflect all
work done and results achieved in the performance of the Early Stage Development
Program (including all data in the form required under any applicable
governmental regulations). Each party shall allow the other to have prompt
access to all materials
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and data generated on behalf of such party with respect to each Collaboration
Product at reasonable times and in a reasonable manner.
2.4.2 Introgen Reports. Introgen shall periodically, and not
less often than semi-annually during the term of this Agreement, provide the
Development Committee with a written report summarizing the progress of the
Early Stage Development performed by Introgen with respect to each Collaboration
Product during the preceding calendar half-year. Unless otherwise agreed, such
reports shall be due on 28 February and 30 August of each calendar year during
the Early Stage Development Program.
2.4.3 RPRP Reports. RPRP shall periodically, and not less
often than semi-annually during the term of this Agreement, provide the
Development Committee with a written report summarizing the progress of the
Later Stage Clinical Development performed by RPRP with respect to each
Collaboration Product during the preceding calendar half-year. Unless otherwise
agreed, such reports shall be due on 28 February and 30 August of each calendar
year during the term of this Agreement.
2.5 Review of Publication. As soon as is practicable prior to the oral
public disclosure, and prior to the submission to any outside person for
publication of a manuscript describing the scientific data resulting from any
stage of the Early Stage Development Program or Later Stage Clinical
Development, Introgen or RPRP, as the case may be, shall disclose to the
Development Committee the disclosure or manuscript to be made or submitted, and
shall allow the Development Committee at least thirty (30) days to determine
whether such disclosure or manuscript contains subject matter for which patent
protection should be sought prior to publication or which the other believes
should be modified to avoid necessary regulatory or commercial difficulties.
With respect to publications by investigators or other third parties, such
publications shall be subject to review by the Development Committee under this
Section 2.5 to the extent that Introgen or RPRP (as the case may be) has the
right to do so.
2.5.1 Publication Rights. After the expiration of thirty (30)
days from the date of mailing such disclosure or manuscript, unless Introgen or
RPRP has received from the other the written notice specified below, the
authoring party shall be free to submit such manuscript for publication or to
publish the disclosed research results in any manner consistent with academic
standards.
2.5.2 Delay of Publication. Prior to the expiration of the
thirty (30) day period specified in this Section 2.5, the Development Committee
may notify the submitting party of its determination that such oral presentation
or manuscript contains objectionable material or material that consists of
patentable subject matter for which patent protection should be sought. The
notified party shall withhold its proposed public disclosure and confer with the
Development Committee to determine the best course of action to take in order to
modify the disclosure or to obtain patent protection. After resolution of the
regulatory or commercial issues, or the filing of a patent application or due
consideration as to whether a patent application can reasonably be filed, the
submitting party shall be free to submit the manuscript and/or make its public
oral disclosure. If the
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submitting party declines to file an appropriate patent application pursuant to
the request of the Development Committee, then either Introgen or RPRP may
undertake to file such application in accordance with Article 14 below.
3. DEVELOPMENT COMMITTEE
3.1 Development Committee. RPRP and Introgen will establish a
Development Committee to oversee, review and coordinate the development of
Collaboration Products worldwide, including the conduct of the Early Stage
Development Program and Later Stage Clinical Development in North America.
3.2 Membership. The Development Committee shall be comprised of an
equal number of representatives from each of RPRP and Introgen, selected by such
parties. The exact number of such representatives shall be three (3) for each of
RPRP and Introgen, or such greater number as the parties may agree. Introgen and
RPRP may replace its Development Committee representatives at any time, with
written notice to the other party. From time to time, the Development Committee
may establish subcommittees to oversee particular projects or activities, and
such subcommittees will be constituted as the Development Committee agrees.
3.3 Development Committee Meetings. During the term of this Agreement,
the Development Committee shall meet every two months, or more often as agreed
by the parties, in Houston, Texas, or such other location as the parties agree.
The parties agree that at least two (2) meetings of the Development Committee
per full calendar year will be held at RPRP's facilities. At its meetings, the
Development Committee will (i) formulate and review the Early Stage Development
Program objectives, (ii) monitor the progress of the Early Stage Development
Program toward those objectives, (iii) review and approve the Program Plan and
Budget, and Product Plans and Budgets, pursuant to Section 3.4 of this
Agreement, and (iv) monitor the progress of both Early Stage Development and
Later Stage Clinical Development. With the consent of the parties, other
representatives of Introgen or RPRP or their Affiliates or Sublicensees, may
attend Development Committee meetings as non-voting observers. With respect to
matters relating to Early Stage Development, Introgen's lead representative
shall chair meetings of the Development Committee, and with respect to matters
relating to Later Stage Clinical Development, RPRP's lead representative shall
chair such meetings. The party whose representatives chair a meeting with
respect to particular matters shall be responsible for preparing the agenda and
minutes for such meetings.
3.4 North American Plans and Budgets.
3.4.1 Program Plan and Budget. Introgen shall be responsible
for preparing reasonably detailed plans and budgets on an annual basis for the
"Program Plan and Budget" through which the Early Stage Development Program will
be carried out. The Program Plan and Budget shall specify the research
objectives and work plan activities of the Early Stage Development Program
research of both parties, and the headcounts and other costs and expenses of
Introgen, including consultants and third party contractors, in connection with
the Early Stage Development Program.
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3.4.2 Product Plans and Budgets. In connection with the
Program Plan and Budget, Introgen shall be responsible for developing individual
Product Plans and Budgets with respect to Early Stage Development for each
particular Collaboration Product, which shall contain the research objectives
and work plan activities, headcounts and other costs and expenses with respect
to each such Collaboration Product (each a "Product Plan and Budget"). Such
individual Product Plans and Budgets shall be incorporated into and be a part of
the annual Program Plan and Budget. Following Early Stage Development with
respect to a Collaboration Product, RPRP will be responsible for developing
individual Product Plans and Budgets for Later Stage Clinical Development
pursuant to Section 2.3.2 and 3.5 below.
3.4.3 Annual Review. Attached hereto as Exhibit C is the
initial Program Plan and Budget, which shall be fixed for the period from the
Effective Date through 30 December 1995, unless otherwise agreed. Beginning in
1995, by August 1 of each year during the Early Stage Development Program,
Introgen shall submit to the Development Committee a proposed Program Plan and
Budget for the Early Stage Development Program for the following calendar year.
The Development Committee shall review such proposal as soon as possible and
shall establish and approve no later than October 31 of such year the final
Program Plan and Budget for the next succeeding year.
3.4.4 Periodic Reviews. The Development Committee shall review
the Program Plan and Budget on an ongoing basis and may make changes to the
Program Plan and Budget then in effect; provided, however, the Program Plan and
Budget in effect for a year shall not be modified except as approved by the
Development Committee.
3.5 Plans for Later Stage Development. Concurrently with the submission
and establishment of Product Plans and Budgets for the Early Stage Development
to be conducted under the Early Stage Development Program in accordance with
Section 3.4 above, RPRP shall submit to the Development Committee an outline of
the Product Plan and Budget for Later Stage Clinical Development for each
Collaboration Product in North America. Following RPRP's election to proceed
with Later Stage Clinical Development of a Collaboration Product under Section
6.1 below, RPRP shall submit a reasonably detailed Product Plan and Budget for
such Later Stage Development, and shall keep the Development Committee
reasonably informed as to any material changes to such Product Plan and Budget.
The Development Committee shall review and discuss such Product Plans and
Budgets; [*].
3.6 Decision Making. Except as set forth in Section 2.3.2(a) and 3.5
above, decisions of the Development Committee shall be made by majority
approval. In the event that a deadlock arises within the Development Committee,
the dispute will be referred to Introgen's president and RPRP's Biotech Division
President, who shall meet to resolve the dispute. If such dispute remains
deadlocked, the parties may submit such dispute to arbitration, on mutually
agreed terms.
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4. EARLY STAGE DEVELOPMENT PROGRAM FUNDING
4.1 Funding of Early Stage Development Program. During the Term of the
Early Stage Development Program, subject to Section 4.3 and 4.5 below, RPRP
shall pay to Introgen the budgeted Early Stage Development Program Costs set
forth in the applicable Program Plan and Budget. RPRP may elect to pay for Early
Stage Development Program Costs paid or accrued by Introgen in connection with
the Early Stage Development Program in excess of that provided for in the
Program Plan and Budget, as approved by the Development Committee. Introgen
shall apply all such funds paid by RPRP toward the Early Stage Development
Program in accordance with the Program Plan and Budget.
4.2 Term of Early Stage Development Program. Subject to Section 18.3
below, the Term of the Early Stage Development Program shall continue from the
Effective Date until October 1, 1997 or such later date as the parties may
agree.
4.3 Excess Early Stage Development Program Costs. Unless otherwise
agreed by the parties, Introgen shall not be obligated to incur nor shall RPRP
be obligated to pay Early Stage Development Program Costs in connection with the
Early Stage Development Program beyond amounts provided for in the approved
Program Plan and Budget.
4.4 Capital Equipment. The Program Plan and Budget may include
reasonable depreciation charges or lease expenses for certain capital equipment
to be purchased or leased by Introgen for use in connection with the Early Stage
Development Program. It is understood that Introgen will be the owner of all
capital equipment purchased by Introgen in connection with the Early Stage
Development Program, whether or not separately identified in the Program Plan
and Budget.
4.5 Payments. Promptly following the Effective Date, and prior to the
beginning of each calendar quarter during the Term of the Early Stage
Development Program, the Development Committee shall approve a spending forecast
for the next quarter, consistent with the Program Plan and Budget then in
effect. On or before October 15, 1994, and the first day of each subsequent
calendar quarter during the Term of the Early Stage Development Program, RPRP
shall pay to Introgen the amount of the approved forecasted amount; provided
that if for any reason the Development Committee does not approve a forecasted
amount prior to the due date, RPRP shall pay to Introgen the amount budgeted for
the quarter in the Program Plan and Budget them in effect. Within thirty (30)
days following the end of each quarter during the Term of the Early Stage
Development Program, Introgen shall provide to RPRP a summary of the Early Stage
Development Program Costs actually incurred by Introgen during such quarter. If
the actual development expenses incurred by Introgen in such quarter are less
than the amounts advanced by RPRP, then the difference will be carried forward
and credited to the next quarterly payment to be advanced. If such Early Stage
Development Program Costs were greater than the amount advanced by RPRP, then
RPRP agrees to pay the difference within thirty (30) days of receiving
Introgen's invoice, provided that in no event shall RPRP be obligated to
reimburse aggregate Program Development Costs in any calendar
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year in excess of the aggregate Program Development Costs reflected in the
Program Plan and Budget for such year then in effect.
5. COLLABORATION PRODUCT DEVELOPMENT OUTSIDE THE EARLY STAGE
DEVELOPMENT PROGRAM
5.1 RPRP Territory. RPRP shall be responsible for, and shall have the
exclusive right to conduct, all clinical development of Collaboration Products
within the Field in the RPRP Territory, at RPRP's own expense.
5.2 Co-Exclusive Territory. RPRP and Introgen shall each have the right
to develop the Collaboration Products within the Field in the Co-Exclusive
Territory, at their own expense, including the right to authorize Sublicensees
permitted under Section 7.5 and 13.4 below to conduct such development.
5.3 Other Territory. [*]
5.4 Use of Clinical Data.
5.4.1 Exchange. RPRP and Introgen shall each have access to
and the right to use for any purpose, including incorporation in any regulatory
filing, any preclinical and/or clinical data with respect to the Collaboration
Product developed by Introgen or RPRP in the course of the Early Stage
Development Program or otherwise (including in the Co-Exclusive Territory or the
RPRP Territory). Introgen and RPRP will provide to the other access to all
regulatory fillings made for clinical trial and marketing approval by Introgen
or RPRP or on their behalf in any country with respect to each Collaboration
Product, together with the underlying pre-clinical and clinical data, at
reasonable times and on reasonable notice, to the extent each has the right to
do so.
5.4.2 Sublicensees. Either Party may provide the IND package
prepared pursuant to Section 2.3.1, or any other clinical or preclinical data
provided under Section 5.4.1, to Sublicensees permitted under Section 7.5 and
13.4 below, except as set forth in this Section 5.4.2 and 5.4.3 below. Introgen
and RPRP shall each use commercially reasonable efforts to obtain from its
permitted Sublicensees reasonable, prompt access to all regulatory filings and
underlying data prepared by or for such Sublicensee with respect to a
Collaboration Product at reasonable times and in a reasonable manner, with the
right to provide such filings and/or access to the other of Introgen and RPRP
and their respective Sublicensees. However, if a prospective licensee is
unwilling to provide such access, the party hereto proposing to enter into the
sublicense (the "Sublicensing Party") may grant the sublicense, but the
Sublicensee shall not have access to clinical data or regulatory filings
provided by the other of Introgen or RPRP (or such other party's Sublicensees).
If the Sublicensee does not allow the Sublicensing Party to provide to the other
of Introgen or RPRP (and their Sublicensees) all clinical data and regulatory
filings made by or on behalf of the Sublicensee with respect to the sublicensed
Collaboration Product, the Sublicensing Party shall not provide to the
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Sublicensee access to any such clinical data or regulatory filings of the other
of Introgen or RPRP (or its respective Sublicensees).
5.4.3 Japanese Data. [*]
5.4.4 Regulatory Requirements. In all agreements with third
parties or Affiliates involving the development of clinical data for a
Collaboration Product, RPRP and Introgen shall require that such third parties
and Affiliates provide RPRP or Introgen (respectively) access to all such data,
to the extent that such data is required to be obtained from such third parties
by the FDA and/or the Commission of Proprietary Medicines of the European
Community or the European Medicines Evaluation Agency.
5.5 Development Committee Review. Notwithstanding Sections 5.1 or 5.2,
all protocols for clinical trials to be conducted for Collaboration Products in
any territory shall be submitted for review by the Development Committee prior
to the initiation of such trials and filing such protocols with any health
regulatory agency; and RPRP and Introgen will be bound by the recommendations of
the Development Committee with respect to such protocols. In addition, Introgen
and RPRP shall submit their product registration plans to the Development
Committee for review and comment, and the recommendations of the Development
Committee with respect to such plans shall be binding on Introgen and RPRP. It
is understood, however, that this Section 5.5 only requires that each party
abide by such recommendations as are agreed by the Development Committee, and
does not require that the Development Committee approve protocols or
registration plans.
5.6 Further Studies. In the event that RPRP and Introgen agree that
there are preclinical and/or clinical studies that may be mutually beneficial
with respect to obtaining approval for any Collaboration Products outside North
America. Introgen and RPRP may agree to conduct such studies jointly, on
mutually agreed terms.
6. EXCLUSIVITY
6.1 Option to Commercialize. Following completion of Phase I clinical
trials for a Collaboration Product during the Term of the Early Stage
Development Program, Introgen shall provide to RPRP a report summarizing the
results of such Phase I trials. Within one hundred eighty (180) days following
its receipt of such report, RPRP shall notify Introgen whether RPRP wishes to
proceed with the Later Stage Clinical Development and commercialization of such
Collaboration Product as provided in this Agreement, taking into consideration
the recommendation of the Development Committee. In the event that RPRP does not
so notify Introgen within the one hundred eighty (180) day period, such product
shall cease to be a "Collaboration Product" for all purposes of this Agreement
(but such unelected product shall continue to be subject to Section 6.2 below).
As used in this Section 6.1, "completion of Phase I clinical trials" for a
particular Collaboration Product shall be deemed to occur when Introgen has
dosed all patients called for in the protocol for Phase I clinical trials filed
in the applicable IND, and has either completed all patient follow-up as defined
in such protocol or initiated the next phase of clinical trials. Following
RPRP's election to proceed with
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the further development and commercialization of a Collaboration Product under
this Section 6.1, the particular Collaboration Product shall be as defined in
the IND therefor filed with the FDA pursuant to the Early Stage Development
Program. After the Term of the Early Stage Development Program, "Collaboration
Products" shall include only those Collaboration Products that completed Phase I
clinical trials during the Term of the Early Stage Development Program and with
respect to which RPRP has exercised its right to further develop and
commercialize the same pursuant to this Section 6.1.
6.2 Exclusivity. During the period from the Effective Date until the
tenth anniversary thereof, neither Introgen nor RPRP, RPR Inc. or their
Controlled Affiliates, shall develop or commercialize a product within the
Field, except as a Collaboration Product pursuant to this Agreement.
Notwithstanding the foregoing, it is understood that Introgen may conduct
research and development work on potential products and technologies for use
within the Field outside the Early Stage Development Program; provided that
Introgen may not license to third parties or market any product within the Field
during the ten (10) year period specified in this Section 6.2, without RPRP's
prior approval.
6.3 Right of First Discussion in Expanded Field. At least one hundred
eighty (180) days prior to commercializing, or granting to any third party a
right or license to commercialize, a product specifically directed for use
within the Expanded Field, Introgen and its Controlled Affiliates shall notify
RPRP, and upon written request by RPRP within thirty (30) days after receiving
such notice, the parties will discuss as mutually convenient a potential
agreement to collaborate with respect to such product, on such terms as may be
agreed. Similarly, at least one (180) days prior to commercializing, or granting
to a third party a right or license to market, a product specifically directed
for use within the Expanded Field, or acquiring a right or license from a third
party with respect to such a product, RPRP shall notify Introgen, and upon
written request by Introgen within thirty (30) days after receiving such notice,
the parties will discuss as mutually convenient a potential agreement to
collaborate with respect to such product, on such terms as may be agreed. RPRP
shall cause RPR, Inc. and their Controlled Affiliates to comply with this
Section 6.3 to the same extent as RPRP is bound by this Section. Each party's
obligations under this Section 6.3 shall terminate on the tenth anniversary of
the Effective Date. If either Introgen or RPRP (as the case may be) does not
request further discussions within thirty (30) days after receiving a notice
from the other party under this Section 6.3, or if after such a request the
parties do not enter into an agreement within the one hundred eighty (180) day
period described above for any reason, the other party shall have no further
obligations under this Section 6.3 with respect to the product or other subject
matter described in its notice.
7. MARKETING RIGHTS
7.1 RPRP Territory. RPRP shall have the exclusive right to market, sell
and distribute the Collaboration Products in the RPRP Territory for use within
the Field.
7.2 Co-Exclusive Territory. RPRP and Introgen shall each have the
co-exclusive right to market, sell and distribute Collaboration Products in the
Co-Exclusive Territory for use within the
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Field, and subject to Article 9, each may retain any revenues it obtains in the
Co-Exclusive Territory as the result of such activities, without accounting to
the other. Each of RPRP and Introgen may market the Collaboration Product in the
Co-Exclusive Territory under such labels and tradenames as it may elect;
provided that neither party shall have any right to use tradenames or trademarks
owned by the other party or by the Joint Venture described in Section 7.3.
7.3 North America. Rights to market, sell and distribute the
Collaboration Products in North America shall be as follows:
7.3.1 Election to Form Joint Venture. Within [*] after the
filing of a PLA for a Collaboration Product in the United States, on request by
Introgen, the parties shall establish a joint commercial operation to market
such Collaboration Product within the Field throughout North America. Such
operation may be a joint venture company or such other arrangement as the
parties mutually agree (the "Joint Venture"). No later than ninety (90) days
after filing of a PLA for a Collaboration Product in the United States, Introgen
and RPRP shall meet to discuss RPRP's preliminary launch, marketing and sales
plans, launch budget projections, Introgen's possible contributions and RPRP's
Development Costs for such Collaboration Product.
7.3.2 Responsibilities and Profit. Introgen and RPRP will
equally share the costs and responsibilities for marketing the Collaboration
Product in North America through the Joint Venture, and will share any profits
from sales of such Collaboration Product in North America [*] basis; provided,
however that [*]. At the time Introgen elects to establish the Joint Venture,
the parties will agree upon the form of each party's contribution (whether
physical resources, funding or otherwise), and each party shall thereafter
provide the agreed contribution.
7.3.3 RPRP Development Costs. As used in this Section 7.3,
"RPRP Development Costs" shall mean: (i) amounts [*] of such Collaboration
Product [*]; and (II) [*] to such Later Stage Clinical Development [*] (on a
proportionate basis based on the percentage of total [*]; and (iii) [*] of the
amounts [*] the Collaboration Product outside North America, and [*],
Development Costs shall include [*] the amounts set forth in (i) and (ii) above.
As used herein, a "pivotal study" shall mean a clinical trial conducted outside
North America that is required to be filed with the FDA in order to obtain
marketing approval in the United States and that is designated as a "pivotal
study" for such purposes by the Development Committee. RPRP Development Costs
("Costs") shall be adjusted to then-current dollars using the change in the
Consumer Price Index, U.S. Cities Average for All Urban Consumers, as published
by the U.S. Department of Labor, Bureau of Labor Statistics from the date the
Costs are incurred until the date such costs are recouped.
7.3.4 RPRP Exclusive. In the event that Introgen does not
elect to enter into a Joint Venture for marketing of a Collaboration Product in
North America in accordance with 7.3.1 above, or subsequently elects not to
proceed with such Joint Venture, RPRP shall have the exclusive right to market,
sell and distribute such Collaboration Product in North America, subject to the
payment of the amounts set forth in Section 8.1 and Article 9.
7.4 Other Territory. [*]
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7.5 Sublicensees. Introgen may authorize Sublicensees to market, sell
and distribute Collaboration Products in the Co-Exclusive Territory and other
territories in which Introgen has the right to market Collaboration Products
under this Agreement; provided that Introgen shall notify RPRP of any
prospective Sublicensee and consult with RPRP prior to so authorizing any such
Sublicensee. Introgen shall not authorize any such Sublicensee to authorize
further Sublicensees to market and sell a Collaboration Product. Unless
otherwise agreed by RPRP and Introgen, RPRP and the Joint Venture shall not
authorize any Sublicensee to market, sell or distribute any Collaboration
Product, provided, however, that either party may market, sell or distribute
through an Affiliate.
7.6 Covenants. It is understood that, with respect to any particular
Collaboration Product, the manufacture, use and sale of such Collaboration
Products by Introgen and/or RPRP in any country may not require a license under
intellectual property rights of the other. Accordingly, notwithstanding that
such a license may not be required, neither Introgen nor RPRP shall market, sell
or distribute a Collaboration Product anywhere in the world except in accordance
with this Agreement, including this Article 7.
8. ROYALTIES
8.1 Running Royalties. RPRP shall pay running royalties to Introgen [*]
of Net Sales by RPRP and its Affiliates (and its Sublicensees permitted under
Sections 7.5 above and 13.4 below) of Collaboration Products [*].
Notwithstanding the above, no royalty will be due to Introgen under this Article
8 with respect to such sales of a Collaboration Product in North America if a
Joint Venture is formed for such Collaboration Products pursuant to Section 7.3
above and such Joint Venture has not terminated.
8.2 Royalty Offset. RPRP and Introgen understand and recognize that
RPRP is a party to consulting, license and/or research funding agreements (but
not agreements where third party non-government investors finance the research
or development of technology for RPRP) with other commercial and research
institutions ("collaborators") which agreements provide for RPRP's payment of
royalties on products manufactured, used or sold by RPRP based on the
contribution of said collaborators to the discovery and development of said
products. Consequently, it is foreseeable that a Collaboration Product developed
with Introgen may become subject to multiple royalty obligations as the result
of more than one collaborator's contribution to the development of, or ownership
of patent rights covering, the Collaboration Product. In order to avoid the
development of a dispute over royalty entitlements and to provide RPRP with the
incentive to invest in and commercialize products which might otherwise not be
commercialized due to excess royalty obligations, RPRP and Introgen agree that
the royalty rates applicable to any specific Collaboration Product pursuant to
the first sentence of Section 8.1 (the "Introgen Royalty") or pursuant to an
agreement with a third party collaborator not an Affiliate at the time of
agreement or the payment of a royalty (the "Third Party Royalties") may be
reduced to provide reasonable royalty income to each contributing collaborator.
RPRP shall make reasonable and diligent efforts to establish agreements and
amend its existing royalty-bearing agreements with said collaborators so as to
ensure the fair distribution of royalty income based on Collaboration Products
for which more than one royalty claim is made, provided the Introgen Royalty
paid to Introgen shall in no event be adjusted to [*] on a country by country
basis
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(notwithstanding any other provision of this Agreement). It is understood that
this Section shall not be invoked by RPRP as regards Introgen until the sum of
the Introgen Royalty and Third Party Royalties payable by RPRP for a
Collaboration Product ("Total Royalty") is greater than [*] on a country by
country basis. Thereafter, royalty reduction shall be applied equitably in
accordance with the formula in this Section 8.2, taking into account each
collaborator's minimum royalty rate, to reduce on a percentage basis the royalty
rates specified in all collaborator agreements having an applicable royalty
adjustment provision therein and thereby adjust, to the extent possible, RPRP's
Total Royalty burden to no more than [*] on a country by country basis.
(a) Royalty payment reductions shall be calculated
quarterly, based on the Total Royalties payable by RPRP with respect to Net
Sales for such quarter. Within ninety (90) days after the end of each calendar
year, RPRP and Introgen shall reconcile the calculation of royalty reductions
under this Section 8.2 for the preceding calendar year, based upon the total Net
Sales for such year and the Total Royalties with respect to such Net Sales. If
the amount deducted from the Introgen Royalty exceed the amount of such
reconciled reduction, the difference shall be paid to Introgen within thirty
(30) days; if the amount actually deducted from the Introgen Royalty is less
than the amount of such reconciled reduction, the difference may be applied by
RPRP as a credit against royalties owed to Introgen in the then-current calendar
year, in equal quarterly installments.
(b) Unless a more equitable procedure is agreed to by
all participating parties to whom RPRP owes a royalty on a Collaboration
Product, the reduction in the Introgen Royalty and each of the other Third Party
Royalties shall be calculated and applied to royalty payment obligations on a
country by country basis as follows:
(i) Calculate the effective overall Royalty
rate for each collaborator (i.e., Introgen and each of the
other collaborators receiving Third Party Royalties) based on
total worldwide Net Sales for the quarter or year, as
applicable ("EFF RATE");
(ii) On a country by country basis, total
the EFF RATE of all collaborators ("TOTAL RATE");
(iii) On a country by country basis, [*];
If [*] is greater than [*]:
(iv) Calculate the adjustable portions of
[*];
(v) Calculate [*];
(vi) Multiply the [*] for each collaborator
by the [*];
(vii) Subtract the product obtained in (vi)
from the [*] for each collaborator [*]; and
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(viii) Calculate for each collaborator their
reduced royalty rate by [*] on a country by country basis.
(c) Notwithstanding the foregoing calculation, in no
event shall the Introgen Royalty with respect to a Collaboration Product in any
country be reduced by an amount greater than [*] of the amount by which the
Total Royalty for such Collaboration Product in such country exceeds [*] (prior
to any reduction under a provision substantially identical to Section 8.2(b)
above). However, it is understood that at such time as third parties have agreed
to be bound by the calculation in this Section 8.2, and Introgen approves the
resulting impact on the Introgen Royalty, Introgen may agree to waive this
paragraph (c).
(d) At least ninety (90) days prior to entering into
any agreement that would require the payment of any royalty to a third party
with respect to a patent right or technology specifically intended for use in a
Collaboration Product, RPRP or Introgen (as the case may be) agrees to notify
the other of such fact and the party with whom it proposes to enter into such
agreement. Following such notice, RPRP and Introgen (respectively) agree to keep
the other reasonably informed as to the progress of its negotiations with such
third party, including the proposed principal terms of the agreement, as they
reasonably progress. It is understood that the terms of the agreement will not
have been finalized at the time of the initial notice under this Section 8.2(c),
and that such notice is only to inform the other party of an intention to enter
into such an agreement.
9. THIRD PARTY ROYALTIES
9.1 RPRP Obligations. RPRP shall be solely responsible for the payment
of any royalties, license fees and milestone or other payments due to third
parties under licenses or similar agreements necessary to allow the manufacture,
use or sale of any Collaboration Product worldwide, except as set forth in 9.3
below and except for royalties due as a result of sales of Collaboration
Products in the Co-Exclusive Territory or the Undesignated Territory by
Introgen, its Affiliates or Sublicensees (other than RPRP). RPRP's
responsibilities hereunder shall include the reimbursement of Introgen for
royalties owed by Introgen on sales of Collaboration Products pursuant to that
certain Patent and Technology License Agreement executed as of April 21, 1994,
between Introgen and the Board of Regents of the University of Texas System (the
"UT Agreement"). It is understood that Introgen intends to have in effect a
subsequent Patent and Technology License Agreement with the University of Texas,
dated as of July 20, 1994 (the "Restated UT Agreement"), which will supersede
the existing UT Agreement, and that when the Restated UT Agreement becomes
effective, the reference in the preceding sentence to the Patent and Technology
Agreement shall mean the Restated UT Agreement. In the event that Introgen
enters into any other license or agreement during the term of this Agreement for
which royalties, license fees or milestone or other payments would be due with
respect to a Collaboration Product, RPRP shall not be obligated to pay any
amounts due with respect to such license or agreement unless RPRP approves such
agreement or license and agrees to pay the same to the extent such relates to
the commercialization of Collaboration Products by RPRP, its Affiliates and
permitted Sublicensees. If RPRP does not so approve any such license or
agreement
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and agree to pay such amounts, the subject matter covered by such license or
agreement shall not be within the Introgen Technology for purposes of this
Agreement.
9.2 Introgen Obligations. If RPRP enters into a license or agreement
during the term of this Agreement for which royalties would be due with respect
to a Collaboration Product, Introgen shall not be obligated to pay any royalties
due with respect to such license or agreement unless Introgen approves such
license or agreement and agrees to pay the same to the extent such relates to
the commercialization of Collaboration Products by Introgen, its Affiliates and
Sublicensees (other than RPRP), and agrees to pay [*] with respect to the
Collaboration Products that are sold by Introgen, its Affiliates and
Sublicensees in the Co-Exclusive Territory. If Introgen does not so approve any
such license or agreement and agree to pay such the amounts, the subject matter
covered by such license or agreement shall not be within the RPRP Technology for
purposes of this Agreement. Introgen's portion of any such license fees,
milestone payments and other amounts (other than royalties) shall be payable on
the later of the date the amounts are payable by RPRP to the third party or the
first commercial sale of the Collaboration Product by Introgen, its Affiliate or
Sublicensee in the Co-Exclusive Territory.
9.3 North America. In the event that a Joint Venture is formed for a
Collaboration Product in North America pursuant to Section 7.3.1, all royalties
due third parties for the manufacture, use or sale of Collaboration Products in
North America, and [*] of all license fees, milestone payments and other
payments made to third parties under licenses or agreements with respect to
patent rights or technologies incorporated in the Collaboration Products, shall
be deducted from the resulting revenues to the Joint Venture prior to
determining the profits to be shared by Introgen and RPRP from such North
American sales as set forth in Section 7.3.2; provided that both RPRP and
Introgen approved such license or agreement. If both RPRP and Introgen do not
approve such license or agreement, the patent rights or technologies covered
thereby shall not be included within the Introgen Technology or RPRP Technology
licensed to the Joint Venture.
9.4 Efforts to Obtain Sublicense Rights. If RPRP or Introgen undertakes
to acquire from a third party a technology or patent rights that are intended
for use or application with respect to a Collaboration Product, RPRP and
Introgen (as the case may be) shall use good faith efforts to acquire from such
third party the right to sublicense or otherwise make available to the other
party hereto, such technology or patent rights to the extent the same are to be
used in or applied to Collaboration Products. It is understood, however, that
neither party will be obligated to incur additional costs or hardship in
connection with such efforts to acquire such sublicensing or other rights in
accordance with this Section 9.4.
10. PAYMENTS; BOOKS AND RECORDS
10.1 Royalty Reports and Payments. After the first commercial sale of a
Collaboration Product on which royalties are required, RPRP agrees to make
quarterly written reports to Introgen within [*] after the end of each calendar
quarter, stating in each such report the number, description, and aggregate Net
Sales of the Collaboration Product sold during the calendar quarter upon which a
royalty is payable under Section 8.2 above. Concurrently with the making of such
reports, RPRP shall
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pay to Introgen royalties at the rate specified in Article 8. In addition, RPRP
and Introgen each agree to submit to the other such reports and payments as are
payable to third parties and for which RPRP or Introgen (as the case may be) are
responsible under Article 9 above, at least ten (10) days prior to the date such
reports and payments are due to the third party.
10.2 Payment Method. All payments due under this Agreement shall be
made by bank wire transfer in immediately available funds to an account
designated by the recipient. All payments hereunder shall be made in U.S.
dollars.
10.3 Late Payment. Any payments due under this Agreement which 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 the prime rate as reported by the
Chase Manhattan Bank, New York, New York, on the date such payment is due, plus
an additional two percent (2%), calculated on the number of days such payment is
delinquent. This Section 10.3 shall in no way limit any other remedies available
to any party.
10.4 Currency Conversion. If any currency conversion shall be required
in connection with the calculation of royalties hereunder, such conversion shall
be made using the selling exchange rate for conversion of the foreign currency
into U.S. Dollars, quoted for current transactions reported in The Wall Street
Journal for the last business day of the calendar quarter to which such payment
pertains.
10.5 No Withholding Taxes. So that there will be no withholding taxes
applicable to payments by RPRP to Introgen under this Agreement, RPRP agrees
that all amounts to be paid to Introgen hereunder shall be paid directly by RPRP
from accounts of RPRP in the United States to the accounts of Introgen
designated under Section 10.3 above.
10.6 Records; Inspection. Each party and its Affiliates shall keep
complete, true and accurate books of account and records for the purpose of
determining the royalty amounts payable under this Agreement. Such books and
records shall be kept at the principal place of business of such party or its
Affiliate, as the case may be, for at least [*] following the end of the
calendar quarter to which they pertain. Such records will be open for inspection
during such [*] period by a representative or agent of the other party for the
purpose of verifying the royalty statements. Such inspections may be made no
more than once each calendar year, at reasonable times mutually agreed by
Introgen and RPRP. The auditing party's representative or agent will be obliged
to execute a reasonable confidentiality agreement prior to commencing any such
inspection. Inspections conducted under this Section 10.7 shall be at the
expense of the auditing party, unless a variation or error producing an increase
exceeding [*] of the amount stated for any period covered by the inspection is
established in the course of any such inspection, whereupon all costs relating
to the inspection for such period will be paid the party being audited.
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11. DUE DILIGENCE
11.1 Due Diligence. RPRP shall use its best efforts to diligently
conduct the Later Stage Clinical Development with respect to at least one
Collaboration Product and to obtain regulatory approvals to market such
Collaboration Product in North America and the RPRP Territory. In addition, RPRP
shall use no less the reasonable efforts to complete Later Stage Clinical Trials
and obtain such approvals for all other Collaboration Products. After obtaining
regulatory approvals for any Collaboration Products in a county within the RPRP
Territory (and if a Joint Venture is not formed with respect to such
Collaboration Product, in a county within North America), RPRP shall launch such
Collaboration Product and use no less than reasonable efforts to promote and
meet the market demand therefor in such county.
12. MANUFACTURING RIGHTS
12.1 RPRP Territory. Except as otherwise provided herein, RPRP shall
have the exclusive right to manufacture Collaboration Products for sale within
the Field in the RPRP Territory.
12.2 Co-Exclusive Territory. Except as provided herein, RPRP and
Introgen shall each have the right to manufacture its respective requirements
for the Collaboration Products distributed in the Co-Exclusive Territory. At
Introgen's option and request, Introgen shall have the right to purchase
Collaboration Products from RPRP for sale in the Co-Exclusive Territory, at a
price equal to [*], such right being subject to RPRP's manufacturing capacity
after providing for RPRP's reasonably anticipated supply requirements. However,
in no case shall the [*] the average selling price of the Collaboration Products
in the country for which Introgen resells such Collaboration Products.
12.3 North America. Subject to Section 12.3.3 below, Introgen shall
have the exclusive right to supply Collaboration Products for sale in North
America.
12.3.1 Manufacture and Supply. In the event that a Joint
Venture is formed under 7.3.1 above to market a Collaboration Product in North
America, Introgen shall have the exclusive right to supply such Collaboration
Product to the Joint Venture, and except as set forth below, the Joint Venture
shall purchase such Collaboration Product exclusively from Introgen. In the
event that a Joint Venture is not so formed with respect to a Collaboration
Product, Introgen shall have the exclusive right to supply such Collaboration
Product to RPRP for sale in North America, and RPRP shall purchase such
Collaboration Product exclusively from Introgen for sale in North America. At
its option, however, Introgen may forego such rights to manufacture for North
America, in which case RPRP may do so as provided in 12.3.3 below. It is
understood that Introgen may engage subcontractors with respect to the
manufacture of Collaboration Products for supply to the Joint Venture or RPRP.
12.3.2 Transfer Price. Introgen will supply Collaboration
Products to the Joint Venture or RPRP (as the case may be) for sale in North
America at a price equal to [*]; provided, however, that in no case shall the
margin portion of Introgen's transfer price [*] the average selling
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price of the Collaboration Products in North America. For purpose of
Collaboration Products used for Later Stage Clinical Development the price will
be equal to [*].
12.3.3 [*] In the event that [*] in North America, or [*]
quantities for sale in North America. With respect to the supply of the [*] to
the Joint Venture in such case, [*] receive a price equal to [*] provided,
however, that in no case shall the [*]. For the purpose of [*] used for Later
Stage Clinical Development the [*] be equal to [*].
12.4 Other Territory. For countries within the Other Territory, the
party having exclusive marketing rights in any such country shall also have
rights to manufacture Collaboration Products for sale in such country, unless
otherwise agreed by the parties.
12.5 Supply Agreements. Upon request by RPRP or Introgen, the parties
shall enter into a supply agreement on reasonable and customary terms with
respect to the supply arrangements contemplated in 12.2 and 12.3 above.
13. LICENSE GRANTS
13.1 Grant to RPRP. Subject to the terms and conditions of this
Agreement, Introgen hereby grants to RPRP the following licenses and
sublicenses, as the case may be, under the Introgen Technology: (i) to use and
sell Collaboration Products in the Field within the RPRP Territory and the
Co-Exclusive Territory; (ii) to make and have made the Collaboration Products
anywhere in the world solely for sale and use in the Field within the RPRP
Territory and the Co-Exclusive Territory, and subject to Section 12.3.3 above,
in North America; and (iii) subject to Sections 7.3 and 12.3, to use and sell
Collaboration Products in the Field in North America. The foregoing licenses to
use and sell Collaboration Products under (i) and (iii) shall be: (a)
royalty-bearing and exclusive as to the RPRP Territory and North America, and
(b) royalty-free (except as provided in Article 9) and non-exclusive as to the
Co-Exclusive Territory. The license under (ii) to make Collaboration Products
shall be non-exclusive.
13.2 Grant to Introgen. Subject to the terms and conditions of this
Agreement, RPRP hereby grants to Introgen the following licenses and
sublicenses, as the case may be, under the RPRP Technology: (i) to use and sell
the Collaboration Products in the Field in the Co-Exclusive Territory; (ii) to
make and have made the Collaboration Products anywhere in the world for use and
sale in the Field solely within North America and the Co-Exclusive Territory.
The licenses under (i) above shall be royalty-free and co-exclusive (with RPRP),
and the license under (ii) above shall be royalty-free (except as provided in
Article 9) and non-exclusive.
13.3 Grant to Joint Venture. In the event that a Joint Venture is
formed under Section 7.3 above to market a Collaboration Product in North
America and a license grant is required to operate, Introgen and RPRP shall each
grant and hereby grant to the Joint Venture an exclusive, royalty-free (except
as provided in Article 9) license under the Introgen Technology and the RPRP
Technology (respectively) to use and sell such Collaboration Product in North
America.
13.4 Sublicenses. Introgen shall have the right to grant sublicenses to
third parties of the rights granted by RPRP in Section 13.2 above (including the
co-exclusive rights granted to Introgen under 13.2(i)), provided, however,
Introgen will notify RPRP of any prospective Sublicensee and
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consult with RPRP prior to granting any such sublicense. Introgen may not
authorize any such Sublicensee in the Co-Exclusive Territory to grant further
sublicenses. Unless agreed in writing by Introgen and RPRP, neither RPRP nor the
Joint Venture may sublicense the rights granted in Section 13.1 or 13.3 above or
otherwise authorize any Sublicensees to sell or market Collaboration Products.
13.5 Improvements by Introgen.
13.5.1 [*] to make, use and sell products incorporating a [*]
then following such [*] at least [*] shall notify [*] in reasonable detail of
the [*] is to be licensed. Upon request by [*] receipt of such a notice,
Introgen and RPRP shall meet as mutually agreed to [*] with respect to [*]
described in [*]. If the parties so agree, [*] for the mutually agreed [*] as
are agreed. Otherwise, [*] may proceed to [*] with respect to any [*] for the
[*] summarized in the notice [*] no further obligation under this Section 13.5.
13.5.2 "Program Inventions." As used in 13.5.1 above, a
"Program Invention" shall mean any invention that is first conceived and reduced
to practice by employees or contractors of Introgen in the course of performing
the Early Stage Development Program (i.e. as a part of work specifically
identified in a Program Plan and Budget), and for which RPRP has funded under
the Early Stage Development Program a substantial portion of the in vitro and in
vivo testing of such invention under the Development Program.
13.5.3 Period. Introgen's obligations under this Section 13.5
shall terminate five (5) years after the end of the Term of the Early Stage
Development Program.
13.6 No Rights Beyond Collaboration Products. Except as may be agreed
by RPRP and Introgen after the Effective Date, this Article 13, and Articles 7
and 12 above, shall not be deemed to grant to RPRP rights with respect to the
use, in products other than the Collaboration Products, of Introgen Technology
incorporated in such Collaboration Products; nor shall such provisions of this
Agreement be deemed to restrict Introgen's right to exploit any Introgen
Technology in products other than Collaboration Products (subject to Sections
13.5 and 6.2 above).
14. INTELLECTUAL PROPERTY
14.1 Ownership of Inventions. Inventorship of inventions and other
intellectual property rights conceived and/or reduced to practice in connection
with the Early Stage Development Program shall be determined in accordance with
the patent and other intellectual property laws of the United States. Title to
all inventions and other intellectual property made solely by an Introgen
employee in connection with the Early Stage Development Program shall be owned
by Introgen. Title to all inventions and other intellectual property made solely
by an RPRP employee in connection with the Early Stage Development Program shall
be owned by RPRP. Title to all inventions and other intellectual property made
jointly by employees of Introgen and RPRP in connection the Early Stage
Development Program shall be jointly owned by RPRP and Introgen. Except as
expressly provided in this Agreement, it is understood that neither party shall
have any obligation to account to the other for profits, or to obtain any
approval of the other party to license or exploit a joint invention, by reason
of joint ownership of any such intellectual property.
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14.2 Patent Prosecution.
14.2.1 Sole Inventions. Introgen or RPRP, as the case may be,
shall, at its expense, control the preparing, filing, prosecuting and
maintaining the patent applications and patents within the Introgen Technology
and RPRP Technology (respectively) worldwide, in such countries as it deems
appropriate, and conducting any interferences, re-examinations, reissues,
oppositions or requests for patent term extensions relating to the Introgen
Technology and RPRP Technology (respectively) using counsel of its choice.
14.2.2 Joint Inventions. To provide for the most sensible,
efficient and cost effective means to protect inventions that are owned jointly
by RPRP and Introgen under Section 14.1 above, patent counsel for Introgen and
RPRP shall consult with each other. As a result of such consultation, patent
counsel will be chosen to prepare, file, prosecute and maintain patent
applications and patents worldwide on such joint inventions, and the parties
shall share the costs thereof as reasonably agreed, based upon the relative
benefits thereof to each party.
14.2.3 Prosecution by Other Party. In the event that Introgen
or RPRP, as the case may be (the "Owner"), declines to file or, having filed,
declines to further prosecute and maintain any such patent applications or
patents in accordance with 14.2.1 above, or conduct any interferences or
oppositions, or request any re-examinations, reissues or extensions of patent
term with respect to the Technology it owns in accordance with 14.2.1 above, the
other party shall have the right to file, prosecute and maintain such patent
applications or patents or conduct such interferences, at its own expense, in
the name of the Owner in any country, in which event the Owner of such
Technology shall provide, at the other party's request and expense, all
reasonable assistance. If the Owner of such Technology declines or fails to take
any such actions, such Owner shall notify the other party hereto at least sixty
(60) days prior to the date the next action or filing is due to be taken with
respect to the subject patent application or patent. One-half of all such
expenses shall be deducted from the royalties or profits due to the Owner with
respect to the country in which the patent issues.
14.2.4 Cooperation. Each of Introgen and RPRP shall keep the
other reasonably informed as to the status of such patent matters, including,
without limitation, by providing the other the opportunity to review and comment
on any documents which will be filed in any patent office, and providing the
other copies of any documents that such party receives from such patent offices,
including notice of all interferences, re-examinations, oppositions or requests
for patent term extensions. Introgen and RPRP shall each cooperate with and
assist the other in connection with such activities, at the others' request and
expense.
14.2.5 Third Party Rights. The foregoing provisions of this
Article 14 shall be subject to and limited by any agreements pursuant to which
Introgen and RPRP, as the case may be, acquired any particular Introgen
Technology or RPRP Technology. It is understood that such agreements may
require, for example, that the licensor party from whom Introgen or RPRP
acquired a license to such Technology control the prosecution of particular
patents and patent applications and does not permit access or an opportunity to
comment on the any documents filed in patent offices.
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14.3 Defense of Third Party Infringement Claims.
14.3.1 Infringement Claims. If the production, sale or use of
any Collaboration Product pursuant to this Agreement results in a claim, suit or
proceeding alleging patent infringement against Introgen or RPRP (or their
respective Affiliates or Sublicensees), such party shall promptly notify the
other party hereto in writing setting forth the facts of such claim in
reasonable detail. The party subject to such claim shall have the exclusive
right to defend and control the defense of any such claim, suit or proceeding,
at its own expense, using counsel of its own choice, provided, however, it shall
not enter into any settlement which admits or concedes that any aspect of the
Technology of the other party hereto is invalid or unenforceable without the
prior written consent of such other party. Such party shall keep the other party
hereto reasonably informed of all material developments in connection with any
such claim, suit or proceeding.
14.3.2 Third Party Blocking Patent. If an unexpired third
party patent(s) covering the manufacture, use or sale of a Collaboration Product
exist(s) in a country where the Collaboration Product is being manufactured,
used or sold during the term of this Agreement, and if it should prove in RPRP's
judgment impractical or impossible for it or its sublicensees to continue the
manufacture, use or sale of Collaboration Product in such country without
obtaining a royalty-bearing patent license from such third party, then RPRP
shall have the following options:
(a) RPRP may terminate the continued manufacture
and/or sale of the Collaboration Product in such country upon sixty (60) days'
written notice to Introgen, with Introgen's written consent, whereupon RPRP
shall have no further rights in such country; or
(b) RPRP may obtain a license from such third party
and treat such third party as a "collaborator" for purposes of Section 8 and 9
for such country.
14.4 Enforcement.
14.4.1 Solely Owned Technology. Subject to 14.4.2 below, in
the event that any Introgen Technology or RPRP Technology necessary for
manufacture, use and sale of a Collaboration Product is infringed or
misappropriated by a third-party in any country in which Introgen or RPRP has
rights to market such Collaboration Product, or is subject to a declaratory
judgment action arising from such infringement in such country, Introgen or RPRP
(respectively) shall promptly notify the other party hereto. The owner of such
Technology shall have the initial right (but not the obligation) to enforce the
Technology it owns, or defend any declaratory judgment action with respect
thereto, at its expense. In the event that the owner of such Technology fails to
initiate a suit to enforce such Technology against a commercially significant
infringement in the Field by a third party within one hundred eighty (180) days
of a request by the other party to do so if such infringement is occurring in a
territory in which the other party (the "Licensee") has the right to market the
subject Collaboration Product, such Licensee may initiate such suit in the name
of the owner of such Technology against such infringement, at the expense of
such Licensee. 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
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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. If the Party initiating the suit
was the owner of the subject Technology, all of the remainder shall be retained
by such owner, and if applicable, included in Net Sales for purposes of Article
8 if the infringing activities were in a country in which royalties would be due
on sales of a Collaboration Product. If the party initiating the suit is the
Licensee, twenty percent (20%) of the remainder shall be paid to the owner of
the subject Technology and eighty percent (80%) to the Licensee.
14.4.2 Jointly Owned Technology. Notwithstanding 14.4.1 above,
in the event that any Technology that is jointly owned by RPRP and Introgen
under Section 14.1 of this Agreement is infringed or misappropriated by a third
party, Introgen and RPRP shall mutually agree upon whether, and, if so, how, to
enforce such Joint Technology or defend such Joint Technology in a declaratory
judgment or similar proceeding.
15. REPRESENTATIONS AND WARRANTIES
15.1 Warranties. Each party warrants and represents to the other that
(i) it has the full right and authority to enter into this Agreement and grant
the rights and licenses granted herein; (ii) it has not previously granted and
will not grant any rights in conflict with the rights and licenses granted
herein; (iii) and there are no existing or threatened actions, suits or claims
pending against it with respect to its Technology or its right to enter into and
perform its obligations under this Agreement and (iv) it has not previously
granted, and will not grant during the term of this Agreement, any right,
license or interest in or to its Technology, or any portion thereof, to
manufacture, sell or use a Collaboration Product that is in conflict with the
rights or licenses granted under this Agreement. RPRP further represents and
warrants that, as of the Effective Date, it is a wholly owned subsidiary of RPR
Inc., and that no other "person" (as defined in the Securities Exchange Act of
1934) owns beneficially more than eighty percent (80%) of the outstanding
capital stock of RPR Inc. Introgen further represents and warrants that a true
and correct copy of the UT Agreement and the Restated UT Agreement (as defined
in Section 9.1 above) were provided to RPRP by facsimile from Wilson, Sonsini,
Xxxxxxxx & Xxxxxx on September 28, 1994.
15.2 Disclaimer of Warranties. Introgen and RPRP specifically disclaim
any guarantee that the Early Stage or Later Stage Development Program will be
successful, in whole or in part. To the extent that Introgen and RPRP have
complied with Articles 2, 3, 4 and 14.2 hereof, the failure of the parties to
successfully develop Collaboration Products will not constitute a breach of any
representation or warranty or other obligation under this Agreement. Neither
Introgen nor RPRP makes any representation or warranty or guaranty that the
Program Plan and Budget will be sufficient for the successful completion of the
Early Stage Development Program. INTROGEN AND RPRP EXPRESSLY DISCLAIM ANY
WARRANTIES OR CONDITIONS, EXPRESS, IMPLIED, STATUTORY OR OTHERWISE, WITH RESPECT
TO THE EARLY STAGE OR LATER STAGE DEVELOPMENT PROGRAM AND THE INTROGEN AND RPRP
INTELLECTUAL PROPERTY, INCLUDING, WITHOUT LIMITATION, ANY WARRANTY OF
MERCHANTABILITY, NONINFRINGEMENT, OR FITNESS FOR A PARTICULAR PURPOSE,
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VALIDITY OF INTROGEN OR RPRP TECHNOLOGY, PATENTED OR UNPATENTED, AND
NON-INFRINGEMENT OF THE INTELLECTUAL PROPERTY RIGHTS OF THIRD PARTIES.
15.3 Effect of Representations and Warranties. It is understood that if
the representations and warranties under this Article are not true and accurate
and Introgen or RPRP incurs liabilities, costs or other expenses as a result of
such falsity, Introgen or RPRP, 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 or RPRP, as the case maybe, resulting from or
related to such falsity, the cooperation of the indemnified party, as requested
in connection with any such claim, and the sole right to control the defense or
settlement thereof.
16. CONFIDENTIALITY
16.1 Confidential Information. Except as expressly provided herein, the
parties agree that, for the term of this Agreement and for five (5) years
thereafter, the receiving party shall keep completely confidential and shall not
publish or otherwise disclose and shall not use for any purpose any information
furnished to it by the other party hereto pursuant to this Agreement except to
the extent that it can be established by the receiving party by competent proof
that such information:
(a) was already known to the receiving party, other
than under an obligation of confidentiality, at the time of disclosure;
(b) was generally available to the public or
otherwise part of the public domain at the time of its disclosure to the
receiving party;
(c) became generally available to the public or
otherwise part of the public domain after its disclosure and other than through
any act or omission of the receiving party in breach of this Agreement; or
(d) was subsequently lawfully disclosed to the
receiving party by a person other than a party or developed by the receiving
party without reference to any information or materials disclosed by the
disclosing party.
16.2 Permitted Disclosures. Each party hereto may disclose another's
information to the extent such disclosure is reasonably necessary in filing or
prosecuting patent applications, prosecuting or defending litigation, complying
with applicable governmental regulations or otherwise submitting information to
tax or other governmental authorities, making a permitted sublicense or other
exercise of its rights hereunder or conducting clinical trials, 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 give
reasonable advance notice to the latter party of such disclosure and, save to
the extent inappropriate in the case of patent applications, will use its best
efforts to secure confidential treatment of such information prior to its
disclosure (whether through protective orders or
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otherwise). Notwithstanding the foregoing, neither party shall disclose to third
parties, clinical data or regulatory filings received from Introgen or RPRP,
except as permitted under section 5.4 above.
17. INDEMNIFICATION
17.1 Indemnification of Introgen. RPRP shall indemnify each of Introgen
and its Affiliates and the directors, officers, employees, and counsel of
Introgen and such Affiliates and the successors and assigns of any of the
foregoing (the "Introgen Indemnitees"), pay on demand and protect, defend, save
and hold each Introgen 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 Indemnitee, arising from or occurring as a result of
(a) activities performed by or on behalf of RPRP in connection with the Later
Stage Clinical Development, (b) activities performed by RPRP in connection with
the development of any Collaboration Product for commercialization outside North
America, (c) third party claims, including without limitation, product liability
claims relating to any Collaboration Products used, sold or otherwise
distributed by RPRP, its Affiliates or Sublicensees, (d) third party claims
relating to any Collaboration Products supplied by Introgen to the Joint
Venture; except in each case to the extent such claim is caused by the
negligence or intentional misconduct of an Introgen Indemnitee. For purposes of
this Section 17.1, it is understood that product liability claims that arise out
of the marketing or use of a Collaboration Product in a country after obtaining
governmental approval to market such Collaboration Product shall not be deemed
to "arise from or occur as a result of" the activities of RPRP described in (a)
above.
17.2 Indemnification of RPRP. Introgen shall indemnify each of RPRP and
its Affiliates and the directors, officers, employees, and counsel of RPRP and
such Affiliates and the successors and assigns of any of the foregoing (the
"RPRP Indemnitees"), pay on demand and protect, defend, save and hold each RPRP
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 RPRP Indemnitee,
arising from or occurring as a result of (a) activities performed by or on
behalf of Introgen in connection with Early Stage Development, (b) activities
performed by Introgen in connection with the development of any Collaboration
Product for commercialization outside North America, and (c) third party claims,
including without limitation, product liability claims, relating to any
Collaboration Products used, sold or otherwise distributed by Introgen, its
Affiliates or Sublicensees (other than RPRP), or (d) third party claims relating
to any Collaboration Products supplied by RPRP to Introgen for sale or use by
Introgen, its Affiliates or Sublicensees outside North America, except in each
case to the extent such claim is caused by the negligence or intentional
misconduct by an RPRP Indemnitee. For purposes of this Section 17.2, it is
understood that product liability claims that arise out of the marketing or use
of a Collaboration Product in a country after obtaining governmental approval to
market such Collaboration Product shall not be deemed to "arise from or occur as
a result of" the activities of Introgen described in (a) above.
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17.3 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 shall not apply to amounts
paid in settlement of any loss, claim, damage, liability or action if such
settlement is effected without the consent of the Indemnitor, which consent
shall not be withheld unreasonably. The failure to deliver written notice to the
Indemnitor within a reasonable time after the commencement of any such action,
if prejudicial to its ability to defend such action, shall relieve such
Indemnitor of any liability to the Indemnitee under this Article 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.
18. TERM AND TERMINATION
18.1 Term. This Agreement shall become effective as of the Effective
Date and, unless earlier terminated pursuant to the other provisions of this
Article, shall continue in full force and effect on a product-by-product and
country-by-country basis, until twelve and one-half years after the first
commercial sale of each Collaboration Product in such country.
18.2 Termination for Cause. Either party to this Agreement may
terminate this Agreement in the event the other party shall have materially
breached or defaulted in the performance of any of its material obligations
hereunder, and such default shall have continued for sixty (60) days after
written notice thereof was provided to the breaching party by the non-breaching
party. Any termination shall become effective at the end of such sixty (60) 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 sixty (60) day period.
18.3 Termination for Convenience by RPRP.
18.3.1 Entire Agreement. RPRP shall have the right to
terminate this Agreement on one hundred eighty (180) days prior written notice
to Introgen, provided such notice of termination may not be given prior to
December 15, 1995.
18.3.2 Individual Products. Upon one hundred eighty (180) days
prior notice to Introgen, RPRP may terminate the development of any particular
Collaboration Product, and RPRP shall have no further payment obligations with
respect to the development of such Collaboration
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Product following the effective date of such termination, except as set forth in
18.4.2(b) below. In such event, such product will cease to be a Collaboration
Product for all purposes of this Agreement, and RPRP shall have no further
rights with respect thereto; provided, however, that unless there is at least
one Collaboration Product remaining, such termination shall also be deemed a
termination of this Agreement under 18.3.1 above.
18.4 Effect of Breach or Termination.
18.4.1 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.
18.4.2 Wind-Down Expenses.
(a) Following any termination pursuant to Section
18.3.1, RPRP shall reimburse Introgen for all non-cancelable obligations or
commitments incurred by Introgen prior to RPRP's notice of such termination in
the course of performing the Early Stage Development Program, and expenses of
Introgen employees who had been engaged in the performance of the Early Stage
Development Program, which employee expenses are incurred by Introgen during the
six (6) months following the effective date of such termination (including
benefits, a reasonable allocation of overhead, and/or if the employees are
terminated by Introgen, reasonable severance pay); provided that RPRP shall be
responsible only for that portion of such employee expenses equal to the
percentage of such employees' time that was dedicated towards work under the
Early Stage Development Program during the six (6) months prior to RPRP's notice
of termination ("Employee Expenses").
(b) Following any termination of development of any
particular Collaboration Product pursuant to Section 18.3.2, RPRP shall
reimburse Introgen for all non-cancelable obligations and commitments incurred
by Introgen with respect to such Collaboration Product prior to RPRP's notice of
such termination, and Employee Expenses (as described in 18.3.2(a) above)
incurred by Introgen during the six (6) months following the effective date of
such termination, to the extent that such employees are not reassigned to other
work to be performed under the Early Stage Development Program and funded by
RPRP. Introgen shall use reasonable efforts to mitigate these "wind-down"
expenses by redirecting such obligations and commitments, and employees, to the
furtherance of the continuing Early Stage Development Program and the
development of other Collaboration Products.
18.4.3 Return of Materials. Upon any termination of this
Agreement, Introgen and RPRP shall promptly return to the other all Confidential
Information received from the other (except one copy of which may be retained
for archival purposes).
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18.4.4 Stock on Hand. In the event this Agreement is
terminated with respect to Introgen or RPRP for any reason, subject to Articles
8, 9 and Article 10, the terminated party and their respective Affiliates and
Sublicensees, shall have the right to sell or otherwise dispose of the stock of
any Collaboration Product subject to this Agreement then on hand.
18.5 Survival. Section 14.1 and Articles 10, 15, 16, 17, 18 and 19 of
this Agreement shall survive expiration or termination of this Agreement for any
reason. In addition, for a period of three (3) years following any termination
of this Agreement prior to the end of the term specified in 18.1 above (other
than pursuant to Section 18.2 for material breach by Introgen), RPRP shall not
develop or commercialize directly or through third parties a product within the
Field. In addition:
(a) In the event of a termination under 18.2 above by
reason of a material breach by Introgen, RPRP shall have an exclusive, worldwide
license, with the right to grant sublicenses, under the Introgen Technology to
make, have made, use and sell the Collaboration Products within the Field, and
in addition to the other Articles surviving as set for the above, Article 9 and
Sections 14.3 and 14.4 shall also survive.
(b) In the event of a termination under 18.2 above by
reason of a material breach by RPRP, or by reason of a termination of this
Agreement by RPRP under Section 18.3.1 hereof, Introgen shall have an exclusive,
worldwide license, with the right to grant sublicenses, under the RPRP
Technology to make, have made, use and sell the Collaboration Products, and in
addition to the other Articles surviving as set forth above, Article 9 and
Sections 14.3 and 14.4 shall also survive.
(c) In the event of a termination contemplated under
18.5(a) or (b), the term "Collaboration Products" shall be deemed to also
include any product within the Field for which an IND was filed under the Early
Stage Development Program but for which Phase I was continuing and not completed
prior to the date of such termination.
19. MISCELLANEOUS
19.1 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.
19.2 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.
19.3 No Implied Waivers; Rights Cumulative. No failure on the part of
Introgen or RPRP to exercise 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
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shall any partial exercise of any such right preclude any other or further
exercise thereof or the exercise of any other right.
19.4 Independent Research. Each party acknowledges and agrees that
Introgen and RPRP shall have the right to engage in their own research and
development activities outside the Field. Neither party shall, by virtue of this
Agreement, have any right, title or interest in or to such independent
activities or to the income or profits derived therefrom.
19.5 Independent Contractors. Nothing contained in this Agreement is
intended implicitly, or is to be construed, to constitute Introgen or RPRP 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.
19.6 Notices. All notices, requests and other communications hereunder
shall be in writing and shall be personally delivered or sent by registered or
certified mail, return receipt requested, postage prepaid, in each case to the
respective address specified below, or such other address as may be specified in
writing to the other parties hereto:
RPRP: Xxxxx-Xxxxxxx Xxxxx Pharmaceuticals, Inc.
000 Xxxxxx Xxxx
X.X. Xxx 0000
Xxxxxxxxxxxx, Xxxxxxxxxxxx 00000-0000
Attn: President, Cell and Gene Therapy
Division
with a copy to: Xxxxx-Xxxxxxx Xxxxx, Inc.
000 Xxxxxx Xxxx
X.X. Xxx 0000
Xxxxxxxxxxxx, Xxxxxxxxxxxx 00000-0000
Attn: General Counsel
Introgen: Introgen Therapeutics, Inc.
000 Xxxxxxxx Xxx.
Xxxxx 0000
Xxxxxx, Xxxxx 00000
Attn: President
with a copy to: Xxxxxx Xxxxxx, Esq.
Xxxxxx & Xxxxxx, L.L.P.
000 Xxxxxxxx Xxxxxx
Xxxxxx, Xxxxx 00000
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Xxxxxx Xxxxxxx Xxxxxxxx & Xxxxxx
Professional Corporation
000 Xxxx Xxxx Xxxx
Xxxx Xxxx, Xxxxxxxxxx 00000-0000
Attention: Xxxxxxx X. Xxxxx, Esq.
19.7 Assignment. This Agreement shall not be assignable by either party
to any third party hereto without the written consent of the other party hereto;
except Introgen may assign this Agreement without RPRP's consent to an entity
that acquires substantially all of the business or assets of Introgen, and RPRP
may assign this Agreement without Introgen's consent to an entity that acquires
substantially all of the business or assets of RPR Inc., in each case whether by
merger, acquisition or sale. The terms and conditions of this Agreement shall be
binding on and inure to the benefit of the permitted successors and assigns of
the parties.
19.8 Modification. No amendment or modification of any provision of
this Agreement shall be effective unless in writing signed by all parties
hereto. 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 parties.
19.9 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 hereto 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.
19.10 Non-Disclosure. Each of the parties hereto agrees: (i) not to
disclose to any third party the financial terms of this Agreement without the
prior written consent of each other party hereto, 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 hereto
shall be responsible for the observance by its employees of the foregoing
confidentiality obligations. Notwithstanding the foregoing, the parties shall
agree upon a press release to announce the execution of this Agreement, together
with a corresponding Q&A outline for use in responding to inquiries about the
Agreement; thereafter, RPRP and Introgen may each disclose to third parties the
information contained in such press release and Q&A without the need for further
approval by the other.
19.11 Entire Agreement. This Agreement together with the Stock Purchase
Agreement entered by the parties of even date herewith, constitute the entire
agreement, both written or oral, with respect to the subject matter hereof, and
supersede all prior or contemporaneous understandings or agreements, whether
written or oral, between Introgen and RPRP with respect to such subject matter.
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19.12 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.
19.13 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.
19.14 Patent Marking. Introgen and RPRP agree to xxxx and have their
Affiliates and Sublicensees xxxx all Collaboration Products 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.
19.15 Export Laws. Notwithstanding anything to the contrary contained
herein, all obligations of Introgen and RPRP 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 and RPRP shall cooperate with each other and shall provide assistance
to the other as reasonably necessary to obtain any required approvals.
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IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be
duly executed and delivered in duplicate originals as of the date first above
written.
INTROGEN THERAPEUTICS, INC. XXXXX-XXXXXXX XXXXX
PHARMACEUTICALS INC.
By: /s/ XXXXX X. XXXXX By: /s/ XXXXXX XX XXXXX
------------------------------------ --------------------------------
Name: Xxxxx X. Xxxxx Name: Xxxxxx xx Xxxxx
---------------------------------- ------------------------------
Title: President Title: President
--------------------------------- -----------------------------
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EXHIBIT A
Existing Introgen Licensed Patents
[*]
41
EXHIBIT B
European Countries
Albania Macedonia
Andorra Malta
Austria Moldavia
Belgium Monaco
Bosnia Montenegro
Bulgaria Netherlands
Croatia Norway
Czech Republic Poland
Denmark Portugal
Finland Rumania
France San Marino
Germany Slovakia
Greece Slovenia
Hungary Spain
Iceland Sweden
Ireland Switzerland
Italy Turkey
Liechtenstein United Kingdom
Luxembourg Vatican City
42
EXHIBIT C
Initial Program Plan and Budget
[*]
