THE INFORMATION MARKED BY * AND [ ] HAS BEEN OMITTED PURSUANT TO A REQUEST
FOR CONFIDENTIAL TREATMENT. THE OMITTED PORTIONS HAVE BEEN SEPARATELY FILED
WITH THE COMMISSION.
SPONSORED RESEARCH AGREEMENT
This Agreement is made and entered into this first day of May, 1997 by and
between the Board of Regents of the University of Nebraska doing business as the
University of Nebraska Medical Center, 000 X. 00xx Xxxxxx, Xxxxx, Xxxxxxxx,
00000 (hereinafter referred to as "Institution") and Progenitor, Inc. 0000
Xxxxxxxx Xxxx, Xxxxxxxx, Xxxx 0000-0000 (hereinafter referred to as "Sponsor").
WHEREAS, the research program contemplated by this Agreement is of mutual
interest and benefit to Institution and to the Sponsor, and will further the
research objectives of the Institution in a manner consistent with its status as
a non-profit, tax-exempt research institution,
NOW, THERFORE the parties agree as follows:
1. STATEMENT OF WORK. Institution agrees to use its best efforts to perform
the Research Plan outlined in the proposal dated March 21, 1997 and in
general conformance with the Proposal Budget and Research Plan which are
incorporated into this Agreement by reference and attached hereto as
Exhibit 1.
2. PRINCIPLE INVESTIGATOR. The research will be supervised by Xxxxx, X.
Xxxxxx, Ph.D. If for any reason Xx. Xxxxxx is unable to continue to serve
as principle investigator, and a successor acceptable to both Institute and
Sponsor is not available, this Agreement shall be terminated as mutually
agreed.
3. PERIOD OF PERFORMANCE. The research shall be conducted during the period
May 1, 1997 to April 30, 1998
4. CONSIDERATION. In consideration for the research to be conducted by the
Principle Investigator and Institution during the first year of this
Agreement, Sponsor will pay to Institution a total of [***]. Payment
shall be made to Institution in four installments. The first installment
shall equal [***] and shall be paid within thirty (30) days of the date of
execution of this Agreement. The second, third and fourth installments
shall each equal [***] and shall be paid on August 1, 1997, November 1,
1997 and February 1, 1998. Sponsor and Institution shall mutually agree
upon and determine in writing any extensions to this Agreement and any
associated research budget, no later than 60 days before the end of the
term of this Agreement. All payments by Sponsor in consideration for
research to be conducted by Principle Investigator and Center during
extensions of this Agreement shall be made in equal quarterly payments
on a quarterly basis beginning on the start date of each year and shall
be in accordance with the research budget corresponding to each year as
agreed between the Institution and Sponsor. Any equipment purchased
pursuant to this Agreement shall be and shall remain the property of
the Institution.
5. TERMINATION. Notwithstanding any other terms and conditions hereunder,
this Agreement may be terminated by either party by written notification to
the other party at least one-hundred eighty (180) days prior to the desired
effective date of the termination. In the event of early termination by
Sponsor for any reason except a material breach of this Agreement by
Institution and principle Investigator, the Institution shall be entitled
to payment of all expenditures or encumbrances that cannot be canceled and
which were incurred prior to the termination date. Further, upon early
termination of this Agreement, Institution shall return to Sponsor all data
and information obtained by Institution under this Agreement prior to the
date of termination shall be returned to Sponsor. In addition, any
materials provided to Institution by Sponsor under this Agreement shall be
destroyed or returned to Sponsor, at Sponsor's option.
6. PUBLICATIONS. Institution will be free to publish results under this
Agreement. A copy of
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each publication will be provided to the Sponsor forty-five (45) days prior
to submission for publication to allow adequate time for the parties to
identify and protect patentable subject matter. Notwithstanding the above,
publication will be delayed until patent applications have been filed in
the United States, provided the delay does not exceed sixty (60) days from
the date the publication is submitted to the Sponsor.
7. REPORTS. The Institution will provide Sponsor with annual written reports
within forty-five (45) days after (DATE) in each calendar year or after the
date of termination. Reports will include review of progress on the
Research Plan and a summary of activities during the preceding 12 months as
well as revisions to the Research Plan and the projected budget for the
next year. Institution and Principle Investigator will meet periodically
with Sponsor to review the Research Plan and discuss the research progress.
If the location of the meetings is outside of the Omaha, Nebraska area,
Sponsor will pay travel expenses of Institution and Principle Investigator.
8. INTELLECTUAL PROPERTY. Title to any invention conceived or first reduced
to practice in the performance of the Research Plan solely by any person(s)
employed or otherwise appointed by Institution, or at any time by any
person(s) at Institution whose salary and benefits are paid though
financial support provided by Sponsor, shall remain with Institution.
Title to any invention conceived or first reduced to practice jointly by
Institution and by any employee(s) of Sponsor in the performance of the
Research Plan shall be jointly owned by Institution and Sponsor. Sponsor
shall have, and Institution hereby grants to Sponsor, a right of first
refusal to acquire an exclusive license to Institution's rights in any
invention conceived or first reduced to practice either (I) in the
performance of the Research Plan by any person(s) employed or otherwise
appointed by Institution, or (II) at any time by any person(s) whose salary
and benefits are paid through financial support provided by Sponsor. The
terms and condition of such license shall be negotiated in good faith
between the parties and shall be consistent with the terms of license and
consideration which are incorporated into this Agreement by reference and
attached hereto as Exhibit 2. Sponsor may exercise such right of first
refusal at any time during a period of ninety (90) days after the date of
Sponsor's receipt of Institution's written notice describing an invention
in detail. After such ninety (90) day period, the right of first refusal
granted to Sponsor shall expire and Institution may grant rights to a third
party under Institution's rights in any such invention without obligation
to Sponsor.
9. USE OF NAMES. Neither party will use the name of the other in any
advertising or other form of publicity without the prior written permission
of the other.
10. CONFIDENTIAL INFORMATION. During the term of this Agreement both parties
will exchange certain proprietary Confidential Information in connection
therewith, either written or orally ("Information"). Both Sponsor and
Institution agree to keep such Information strictly confidential; will not
use such Information to reverse engineer or design around proprietary
projects or products; and will not disclose Information to others without
the express written permission of the other party; provided, however, they
will not be prevented from using or disclosing information which:
a) is now, or which hereafter, through no act or failure of the other
party, becomes generally known or available;
b) is known by the other party at the time of receiving such Information
c) is hereafter furnished to the other party by a third party who did not
acquire such Information directly or indirectly form the other party; or
d) is independently developed by the other party without knowledge of
Information, and the recipient party can demonstrate or prove truth
thereof.
11. NOTICES. Any notice required to be given or which shall be given under
this Agreement shall be in writing delivered by first class mail addressed
to the parties as follows:
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Progenitor, Inc.
Vice President, Corporate Development
0000 Xxxxxxxx Xxxx
Xxxxxxxx, Xxxx 00000-0000
Office of the Vice Chancellor for Academic Affairs
University of Nebraska Medical Center
0000 Xxxxxx Xxxxxxx Xxxx
Xxxxx, XX 00000-0000
In the event notices, statements and payments required under this Agreement
are sent by certified or registered mail by one party to the other party at
its above address, they shall be deemed to have been given or made as of
the date so mailed, otherwise as of the date received.
12. ASSIGNMENT. This Agreement shall be binding upon and inure to the benefit
of the parties hereto and the successors to substantially the entire
business and assets hereto, provided the successor entity agrees in writing
to abide by all the terms of this Agreement.
13. GOVERNING LAW. The validity and interpretation of the Agreement and the
legal relation of the parties to it shall be governed by the laws of the
State of Nebraska and the United States.
14. FORCE MAJEURE. Institution shall not be responsible to the Sponsor for
failure to perform any of the obligations imposed by the Agreement,
provided such failure shall be occasioned by fire, flood, explosion,
lightning, windstorm, earthquake, subsidence of soil, failure or
destruction, in whole or in part, of machinery or equipment failure or
supply of materials, discontinuity in supply of power, governmental
interference, civil commotion, riot, war, labor disturbance, transportation
difficulties, labor shortage or any cause beyond the reasonable control of
Institution
15. ENTIRE AGREEMENT. Unless otherwise specified, this Agreement embodies the
entire understanding between Institution and Sponsor for this project, and
any prior or contemporaneous representations, either written or oral are
hereby superseded. No amendment or changes to this Agreement, including
without limitation, change in the statement of work, total estimated cost,
and period of performance, shall be effective unless made in writing and
signed by authorized representative of the parties.
For Institution For Progenitor, Inc.
By: /s/ Xxxxx X. Xxxxxx, Ph.D. By: /s/ Xxxxxxx X. Xxxxxxxx
-----------------------------
Title: Int. X. Xxxxxxxxxx for
Academic Affairs, UNMC Title: V.P. Corporate Development
---------------------------
Date: 4/16/97 Date: 4/14/97
--------------
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EXHIBIT 1 - BUDGET AND RESEARCH PLAN
USING XENOPUS TO IDENTIFY NOVEL GENES IMPORTANT IN EARLY
HEMATOPOIETIC DEVELOPMENT
BUDGET PROPOSAL
PERSONNEL SALARY BENEFITS TOTAL
--------- ------ -------- -----
Xxxxx Xxxxxx, Ph.D. (.25 FTE)
Principal Investigator [***] [***] [***]
TBA (1.00 FTE) [***] [***] [***]
Research Technologist II
Equipment
Pipette Grinder [***]
Micromanipulators and stands (2) [***] [***]
Supplies [***]
Total Direct Costs [***]
Indirect Costs (15% of salaries) [***]
----------
Total Costs [***]
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PROPOSAL FOR USING XENOPUS TO IDENTIFY NOVEL GENES
IMPORTANT IN EARLY HEMATOPOIETIC DEVELOPMENT
Early hematopoietic development in Xenopus involves the induction of
ventral mesoderm and the subsequent proliferation and differentiation of
progenitor populations to yield the blood cell lineages. Although the growth
requirements for definitive (fetal/adult) progenitors is regulated by
hematopoietic cytokines, conditions that yield abundant primitive (embryonic)
colonies have not been adequately defined.
Bone morphogenetic protein-4 (BMP-4) has been shown to be necessary for
ventral mesoderm induction in Xenopus and injection of BMP-4 RNA into fertilized
eggs ventralizes the embryos. Overexpression of BMP-4 partially induces the
erythroid program in isolated animal cap explant assays and this induction is
enhanced in explants treated with mesoderm inducing factors such as activin or
FGF. Expression of a dominant negative BMP-4 receptor (-BMP-4R) inhibits the
erythroid program in explant assays and results in tadpoles lacking primitive
blood cells. These data suggest that activin and FGF induce mesodermal
differentiation and that BMP-4 stimulates hematopoietic development by
patterning ventral mesoderm.
We have used these insights to develop a rapid, reproducible and sensitive
functional assay for identifying genes that play a role in early hematopoietic
development in the Xenopus system. Furthermore, it has been shown that a
several mammalian gene products (e.g. stem cell factor, bFGF, activin, TGF-6)
function in this system. We propose to collaborate with Progenitor to use this
system as a high throughput functional assay for genes important in early
hematopoietic development.
GOALS
To collaborate with Progenitor to develop the Xenopus system as a high
through-put functional screen for genes from stage-specific cDNA expression
libraries. The libraries and screens will focus on genes important to mesoderm
and early hematopoietic development.
APPROACH
Progenitor will prepare, or have prepared, these stage-specific cDNA
libraries in the pcDNA3 expression vector. My laboratory will test interesting
cDNA clones from these libraries in three functional Xenopus assays (e.g.
developmental phenotype, animal cap cell morphology, animal cap gene
expression). The assays will include testing the gene by itself, testing the
gene in conjunction with BMP-4 and testing the gene in conjunction with activin
or FGF. Any gene that induces a significant increase in erythroid development
in these screens will be selected for further functional characterization and
development by mutual agreement.
BUDGET (direct costs only):
[***] (~2FTEs). 2 years
Progenitor contributes the resources for generation of stage-specific
libraries and all necessary sequencing (~4 FTEs)
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EXHIBIT 2 TERM SHEET
LICENSE TERMS:
Grant: Worldwide, exclusive right and
license, with the right to grant
sub-licenses, under any and all
intellectual property conceived
and/or reduced to practice to make,
use, offer to sell, sell and import
inventions made under inventions
relating to products and uses of gene
sequences (full or partial), protein
sequences (full or partial),
antibodies, expression systems, DNA,
RNA and anti-sense.
Field: All fields without restriction
Term: Expires on last to expire of valid
patent claims
Intellectual Property: Filing, prosecution, enforcement, and
defense responsibility of Progenitor.
Patents to be filed in major market
countries and prosecuted to obtain
broad protection consistent with
sound, prudent patent practice.
Progenitor will provide Institution
with copies of filings and
correspondence relating to, and will
consult with Institution on,
prosecution activities.
Diligence: Commercially reasonable efforts to
achieve objective milestones leading
to commercialization
Termination: By Institution: For breach by
Progenitor
By Progenitor: For breach by
Institution or upon 30-day notice
Grant-back: Patent applications and data revert
to Institution upon termination of
the license agreement by Progenitor
For a period of one (1) year after
the date of reversion of rights to
Institution, Progenitor shall have a
right of first refusal on third-party
grant-backs of joint intellectual
property to Institution
FINANCIAL TERMS:
Intellectual property costs and expenses: Borne by Progenitor
Consideration: Joint Intellectual Property:
Progenitor to pay to Institution
[***] of any fees, royalties or
other cash consideration actually
received by Progenitor, excluding
research and development support and
equity investments.
Institutional Intellectual Property:
Progenitor to pay to Institution
[***] of any fees, royalties or other
cash consideration actually received
by Progenitor, excluding research and
development support and equity
investments.
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