EXHIBIT 10(i)
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RESEARCH SUPPORT AGREEMENT
This AGREEMENT (this "Agreement") is made as of the 1st day of February,
1996 by and between VIROLOGIX CORPORATION (the "Sponsor"), a corporation
organized and existing under the laws of the State of Delaware, having an office
at 000 Xxxxx Xxxxxx, 00xx Xxxxx, Xxx Xxxx, Xxx Xxxx, 00000 and UNIVERSITY
COLLEGE DUBLIN, an institution of higher education in Ireland located in Dublin,
Ireland (the "University").
I. Scope of Work
The Sponsor grants to the University and the University accepts
support for research under the direction of Xxxxxxx X. Xxxx, Ph.D., as
described in the attached Statement of Work (Attachment A).
II. Compensation
In consideration of the University's exerting its good faith efforts
to carry out the research described in Attachment A ("Research"), the
Sponsor will pay the University $53,625 quarterly. Checks should be made
payable to "University College Dublin" and should identify the Sponsor and
the Principal Investigator and be sent to the address set forth for the
University in Paragraph 12.
III. Technical Representatives
The Sponsor's Technical Representative shall be Xxxxxx X. Xxxxxx,
Ph.D., or other such representative as the Sponsor may subsequently
designate in writing. The University's Principal Investigator shall be
Xxxxxxx X. Xxxx, Ph.D., who shall be responsible for the direction and
conduct of the Research.
IV. Consultation with Sponsor's Representatives
During the period of this Agreement, the Sponsor's Technical
Representative and other representatives will have reasonable access to
visit and consult informally with the University's Principal Investigator
regarding the Research both personally and by telephone. Access to work
carried on in the University's laboratories in the course of the Research
shall be entirely under the control of the University's personnel; the
Sponsor's representatives shall be permitted to visit such laboratories
only during usual hours of operation as is mutually agreeable.
V. Technical Reports
The Principal Investigator shall make quarterly oral reports and a
detailed, written annual report regarding the Research to the Sponsor's
Technical Representative. Within sixty (60) days after the expiration of
this Agreement, the Principal Investigator shall submit a comprehensive
written final report to the Sponsor.
VI. Publicity
Neither party shall use the name of the other in any form of
advertising or promotion without the prior written approval of the other;
provided, however, that it is expressly agreed that the Sponsor may reveal
or identify the University or any member of its faculty or staff as the
inventor, source or origin of any technology, technical information or any
product or process arising from the Research for the purpose of soliciting
third parties to invest or enter into other commercial arrangements with
the Sponsor, or to acquire a sublicense, assignment or other transfer of
rights in such technology from the Sponsor and provided further that the
Sponsor may use and disclose the University's name and the name of any
member of its faculty or its staff
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in its internal communications or, upon prior disclosure and consultation
with the University, in making any required governmental reports and
filings. In addition, the parties may acknowledge the Sponsor's support
for, and the nature of, the investigations being pursued under this
Agreement. In any such statement, the relationship of the parties shall be
accurately and appropriately described.
VII. Publication
The Parties recognize the traditional freedom of all scientists to
publish and present promptly the results of their research. The Parties
also recognize that patent rights can be jeopardized by public disclosure
prior to the filing of suitable patent applications. Therefore, the
University will assure that each proposed publication concerning the
Research, whether oral or written, before submission to a publisher (or
other entity), will be submitted to the Sponsor for review in connection
with preservation of patent rights. The Sponsor shall have thirty (30) days
in which to review the publication, which may be extended for an additional
thirty (30) days when the Sponsor provides the University with a reasonable
need for such extension. By mutual agreement, this period may be further
extended for not more than an additional three (3) months. The Sponsor will
allow for simultaneous submission of the publication to the publisher (or
other entity) and the Sponsor, where appropriate. All employees of the
University and persons otherwise acting on behalf of both the University
and the Sponsor will be expected to treat matters of authorship in a proper
collaborative spirit, giving credit where it is due and proceeding in a
manner which fosters cooperation and communication.
VIII. Intellectual Property and Patent Rights
All rights in inventions, discoveries, biological material or software
created in the course of the Research (collectively, the "Inventions")
shall be assigned to and the property of the Sponsor. The University shall
promptly report in writing to the Sponsor the existence and nature of any
Inventions. The Sponsor shall select qualified independent patent counsel,
to file, prosecute and maintain all patent applications arising from the
Research, at the expense of the Sponsor, including divisionals,
continuations, continuations-in-part, reissues, renewals, foreign
counterparts or extensions. The Sponsor shall be entitled to determine the
countries in which it wishes to obtain and maintain patent protection under
this Agreement, if any, and shall be free, at any time and at its sole
option and upon notice to the University, to abandon patent prosecution or
maintenance in any country. Should the Sponsor decide not to finance the
preparation, filing, prosecution, or maintenance of any patent application,
the Sponsor will give notice to the University of such decision in writing
in adequate time to allow the University, at its own cost, to effectuate
such preparation, filing, prosecution, or maintenance if it desires to do
so. The University agrees to cooperate with the Sponsor in its activity in
applying for U.S. or foreign patents or in the defense or enforcement of
any patent rights, and will cause the University's employees to execute and
deliver to the Sponsor such documents and instruments as the Sponsor may
request in order to assist the Sponsor in the preparation, filing,
prosecution or maintenance of any patent application. Nothing herein is
intended or shall be construed as obligating the Sponsor to finance the
preparation, filing, prosecution or maintenance of any patent application
in any country or jurisdiction in which it believes it is not in the best
business interest of the Sponsor to do so.
IX. Confidentiality
Subject only to publication rights set forth in Paragraph 7, the
University represents that the University and its employees, faculty and
students are obligated to keep all information concerning the Research
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confidential and agrees that the University and its employees, faculty and
students will not disclose any information related to the Research to any
third party without the express written consent of the Sponsor.
X. Independent Contractor
For the purposes of this Agreement and all services to be provided
hereunder, each party shall be, and shall be deemed to be, an independent
contractor and not an agent or employee of the other party. Neither party
shall have authority to make any statements, representations or commitments
or any kind, or to take any action, which shall be binding on the other
party, except as may be explicitly provided for herein or authorized by the
other party in writing.
XI. Assignment
Neither party may assign this Agreement without the prior written
consent of the other party; except, however, Sponsor may assign its rights
to any of its affiliates, successors, or strategic partners. Any and all
assignments not made in accordance with this section shall be void.
XII. Notices
Any notice required to be given pursuant to this Agreement shall be
made by personal delivery or, if by mail, then by registered or certified
mail, return receipt requested, with postage and fees prepaid, by one party
to the other party at the addresses noted below, or to such other address
as such party may designate in writing from time to time to the other
party.
In the case of Sponsor, notice should be sent to:
Virologix Corporation
000 Xxxxx Xxxxxx, 00xx Xxxxx
Xxx Xxxx, XX 00000
Attention: Xxxxxx X. Xxxxxx
In the case of the University, notice should be sent to:
University College Dublin
Department of Microbiology
Xxxxxxxx, Xxxxxx 0
Xxxxxxx
Attention: Xx. Xxxxxxx X. Xxxx
XIII. No Oral Modification
No change, modification, extension, termination or waiver of this
Agreement, or any of the provisions herein contained, shall be valid unless
made in writing and signed by duly authorized representatives of the
parties hereto.
XIV. Survivorship
The provisions of Paragraphs 6, 8, 9, 10, 14, 15, 16, 17 and 18 shall
survive any expiration or termination of this Agreement.
XV. Term and Termination
This Agreement shall expire on February 27, 1998 unless otherwise
agreed to in writing by the Parties no less than 40 days prior to such
expiration date. or the Agreement is sooner terminated in accordance with
the provisions of this Paragraph. In the event the University's
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Principal Investigator is unavailable or unable to continue direction of
the Research for a period of thirty (30) days, the Sponsor may immediately
terminate this Agreement. Either party may terminate this Agreement in the
event of a material breach by the other party, provided only that the
breaching party is given notice of the breach and a reasonable time, not to
exceed thirty (30) days, in which to cure such breach. Termination or
expiration of this Agreement for reasons other than an unremedied failure
to meet the material obligations under this Agreement shall not affect the
rights and obligations of the parties accrued prior to termination.
XVI. Governing Law
This Agreement shall be governed by and construed in accordance with,
the laws of the State of New York, without giving effect to its conflicts
of law principles.
XVII. Arbitration
In the event of any dispute under this Agreement, such dispute shall
be submitted to arbitration in accordance with the terms of this Section.
The party who is alleging that a dispute exists shall send a notice of such
dispute to all other parties, which notice shall set forth in detail the
dispute, the parties involved and the position of such party with respect
thereto. Within ten (10) business days after the delivery of such a notice,
counsel for the parties shall mutually select as an arbitrator an attorney
practicing in New York, New York, who is experienced in commercial
arbitration. If counsel for the parties are unable to agree upon the
selection of the arbitrator, an arbitrator residing in or about New York,
New York shall be selected by the New York office of the American
Arbitration Association. The arbitrator so selected shall schedule a
hearing in New York, New York on the disputed issues within forty-five (45)
days after his/her appointment and the arbitrator shall render a decision
after the hearing, in writing, as expeditiously as is possible, which shall
be delivered to the parties. The arbitrator shall render a decision based
on written materials supplied by the parties to the arbitration in support
of their respective oral presentations at the hearing, and no party shall
be entitled to discovery in such matter. The parties shall supply a copy of
any written materials to be submitted to the arbitrator at least fifteen
(15) days prior to the scheduled hearing. A default judgment may be entered
against a party who fails to appear at the arbitration hearing. Such
decision and determination shall be final and unappealable and shall be
filed as a judgment of record in any jurisdiction designated by the
successful party. The parties to this Agreement agree that this paragraph
has been included to rapidly and inexpensively resolve any disputes between
them with respect to the matters described above, and that this paragraph
shall be grounds for dismissal of any court action commenced by any party
with respect to a dispute arising out of such matters. For purposes of this
Section, the Parties may participate in any arbitration either jointly or
severally, in their sole discretion.
XVIII. Entire Agreement
This instrument contains the entire Agreement between parties hereto.
No verbal agreement, conversation or representation between any officers,
agents, or employees of the parties hereto either before or after the
execution of this Agreement, shall affect or modify any of the terms or
obligations herein contained.
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XIX. Counterparts
This Agreement may be executed in any number of counterparts, each of
which shall be deemed an original, but all of which together shall
constitute one and the same instrument.
IN WITNESS WHEREOF, the parties have caused this Agreement to be executed as of
the date first set forth above.
VIROLOGIX CORPORATION
By: /s/ Xxxxxx X. Xxxxxx
------------------------
Its: President and Secretary
UNIVERSITY COLLEGE DUBLIN
By: /s/ T.J.G. Xxxxxxxxx
------------------------
Its: Finance Officer
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Exhibit A
The funds received from VIROLOGIX CORPORATION will be used to support research
activities in the laboratory of Xxxxxxx X. Xxxx, Ph.D. at University College
Dublin. The research activities are described below:
Core Technology
1. Transgenic Animals Permissive for HIV infection
2. Inhibitor of HIV Activator of Topoisomerase/Transcription
3. High Efficiency Retrovirus-Mediated Gene Therapy
4. Vaccine for HTLV-I and II
HUMAN RETROVIROLOGY: XXXXXXX X. XXXX, M.D. Ph.D.
(A) HIV-I: Development of Mouse Models for HIV-I Replication.
Preliminary studies from our laboratory have shown that in addition to
the virus receptor (CD4 molecule) HIV replication requires specific interactions
with several cellular proteins and these interactions appear to be
species-specific. In particular the studies have shown that HIV requires the
involvement of the human enzyme topoisomerase I (topo I). Importantly the
interaction of the virus with topo I of other species is extremely inefficient.
With this information we have begun to investigate if this enzyme may be
involved in the host restriction of virus replication, and in fact this would
appear to be the case. In recent studies we have shown that HIV infection of
mouse fibroblasts is possible if both the CD4 molecule and human topo I are
expressed in these cells. As part of our plans to develop a mouse model for
HIV-replication: 1) we intend to produce transgenic mice with expression of both
of these molecules in peripheral blood mononuclear cells. If these can
successfully support HIV replication, they will be extremely useful for studies
of virus replication, drug inhibition studies and possibly tests of vaccine
efficacy. 2) To further optimize the mouse model for HIV replication we also
intend to produce chimeric or pseudotype retroviruses containing the HIV core
and the surface molecules (receptor binding molecules) of mouse retroviruses.
These will then be tested for their ability to infect transgenic mice only
expressing human topo I. Preliminary in vitro studies have indicated a high
probability of success with the latter approach.
Research Plan
1. Transgenic Mice: The studies to produce transgenic mice are underway and
this involves the introduction of human CD4 and human topo I genes. The
latter are prepared by a combination of PCR and cloning methods, and the
fidelity of the constructs are analyzed by nucleotide sequencing analysis.
It is hoped to establish a line of double transgenic males and use these to
mate normal females. The offspring are checked for double gene expression
by Southern hybridization methods. To determine if they can be infected
with HIV initial studies will involve the establishment of spleen cell
cultures in vitro and assaying the ability of virus (both laboratory and
wild type strains) to replicate in these cells and to compare the
efficiencies of replication.
If efficient replication can be demonstrated conditions will be established
for in vivo infection. It should be appreciated that this project is extremely
labor-intensive and very expensive as this will involve the maintenance and care
of a large number of animals.
As noted above to optimize virus replication in the mouse we are also
intending to prepare chimeric murine/HIV retroviruses as this will overcome what
we feel is the rate limiting step of infection, namely virus entry.
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Using murine retrovirus glycoproteins to permit virus entry we will not need to
include human CD4 in our system. Chimeric virus production will require
sophisticated molecular biological manipulation of infectious clones of HIV and
murine leukemia virus and at least one year will be required to produce a
chimeric clone. This will require the expertise of an individual with extensive
experience in molecular biology. Once established this "virus" should be able to
repliate very effectively in vivo in the mouse and will permit an analysis of
almost all stages of HIV repliation.
(B) HTLV-I Vaccine Production
Previous studies in our laboratory have resulted in the successful cloning
and expression of a truncated form of the precursor glycoproteins (gp 63) of
HTLV-I and HTLV-II. Initial studies in a rabbit model have shown that when used
as a vaccine (employing complete Xxxxxx'x as adjuvant), these can effectively
prevent infection in a rabbit model. We now intend to continue these studies and
(a) analyze the effectiveness of the vaccine in rabbits using alum and other
adjuvants which would be more suitable for human use. (b) Establish a phase I
(safety) trial of the HTLV-I vaccine in humans. This will be carried out in
Brazil where a suitable population has been identified.
The studies planned will involve vaccine production under conditions
approved by the FDA in terms of product safety and lack of toxicity. The trial
which will be carried out in Brazil should begin within one year. The rabbit
studies will take approximately 12 months to study different dosages and
adjuvant conditions. These will be also expensive due to high maintenance and
procedure cost. Immunological studies will also be carried out on certain
animals to determine the mechanisms of vaccine protection.
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