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EXHIBIT 10.9
FEASIBILITY EVALUATION/DEVELOPMENT OPTION AGREEMENT
This FEASIBILITY EVALUATION/DEVELOPMENT OPTION AGREEMENT, ("Agreement") is
entered into this 4th day of August, 1995, by and between VAXCEL, INC., having
its offices at 0000 Xxxxxxxxxx Xxxxxxx, Xxxxx 000, Xxxxxxxx, XX 00000 ("VAXCEL")
and CONNAUGHT LABORATORIES, INC., having its offices at X.X. Xxx 000, Xx. 000,
Xxxxxxxxxx, XX 00000 ("CLI").
RECITALS
A. VAXCEL and CLI have entered into discussions with respect to the
development of human vaccines utilizing antigen and vaccine development
technology of CLI and adjuvant technology of VAXCEL, and have signed a
Confidential Disclosure Agreement dated December 15, 1994 ("Confidentiality
Agreement") in that regard.
B. The parties wish to evaluate the feasibility of enhanced immune
responses to CLI's Antigen (as defined in Section 1.2) in VAXCEL's Optivax
System (as defined in Section 1.6). Following successful feasibility evaluation,
negotiation of definitive license and supply agreement covering the further
development, manufacture, and marketing of VAXCEL's Optivax System with CLI's
Antigen in a final vaccine formulation will be conducted.
NOW, THEREFORE, VAXCEL and CLI, in consideration of their mutual promises and
intending to be legally bound, do hereby agree that the following terms and
conditions shall govern the interim relationship between the parties:
1. DEFINITIONS
For purposes of this Agreement, the following terms shall have
the respective meanings set forth below:
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1.1 "Affiliate" shall mean a corporation or any other entity that
directly, or indirectly through one or more intermediaries, controls, is
controlled by, or is under common control with, the designated party, but only
for so long as the relationship exists. "Control" shall mean ownership of shares
of stock having at least fifty percent (50%) of the voting power entitled to
vote for the election of directors in the case of a corporation, and at least
fifty percent (50%) of the interests in profits in the case of a business entity
other than a corporation, or, in either case, the maximum allowed by law if less
than fifty percent (50%), on a country-by country basis, of the voting power or
percentage interest in profits.
1.2 "Antigen" shall mean CLI's recombinant lipidated outer surface
protein A (OspA) from Borrelia burgdorferi, the causative agent of Lyme Disease,
provided by CLI for the Program.
1.3 "Confidential Information" shall mean (i) in the case of CLI,
Technical Information concerning the Antigen as such (or the use or manufacture
thereof, except in the Product or with the Optivax System) owned by or licensed
to CLI prior to the date hereof or developed by CLI after the date hereof
outside the Program, and (ii) in the case of VAXCEL, Technical Information
concerning the Copolymer and/or Optivax System (or the use or manufacture
thereof exclusive of Antigen or its use in the Product), or otherwise useful to
the Program, owned by or licensed to VAXCEL prior to the date hereof or
developed by VAXCEL or its licensors after the date hereof outside the Program.
By way of illustration, but not limitation, Confidential Information may include
patents, patent applications, formulations, know-how, manufacturing processes,
inventions, products, processes, methods, techniques, formulas, compositions,
compounds, projects, plans, research or clinical data, development plans,
customers, suppliers, investors, etc.
1.4 "Copolymer" shall mean the polyoxyethylene/polyoxypropylene
copolymer adjuvant designated by VAXCEL as CRL-1005.
1.5 "Development Costs" shall mean the costs of the Program as incurred
by CLI and VAXCEL in conducting the Work Plan under this Agreement and
determined in accordance with Exhibit B hereof.
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1.6 "Optivax System" shall mean any technology or know-how which
utilizes, is based on or arises out of the use of the Copolymer or that uses
VAXCEL Technical Information. The term "System" shall include anything
incorporated in or used in conjunction with the Product, other than the Antigen,
which affects or may affect the stability, pharmacokinetics, pharmacodynamics or
absorption of Antigen. For this Agreement, the route of administration is by
parenteral injection.
1.7 "Product" shall mean the vaccine in which Antigen is incorporated
in or combined with VAXCEL Optivax System under the Program.
1.8 "Program" shall mean the collaboration between VAXCEL and CLI for
the feasibility evaluation and interim development of Product as provided in
this Agreement, including the work to be conducted by each of the parties as set
forth in the work plan attached as Exhibit A ("Work Plan").
1.9 "Program Information" shall mean any Technical Information
developed or acquired by either party under or in connection with the Program.
Program Information shall include any methods for Product development,
formulation or manufacturing developed for, under or as a result of the Program,
or using or resulting from any Program Information. Program Information shall
not include CLI's or VAXCEL's Confidential Information.
1.10 "Technical Information" shall mean technology and information,
know-how, trade secrets, data, including improvements and modifications to any
thereof, relating to the Antigen, Copolymer, Optivax System, or Product or
otherwise necessary or useful to the Program, which a party hereto has the
lawful and contractual right to disclose to the other party. Technical
Information shall include, without limitation, processes and analytical
methodology used in development, testing, analysis and manufacture, and medical,
clinical, toxicological and other scientific data. Notwithstanding the
foregoing, Technical Information shall not include patents or trademarks.
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2. PRODUCT DEVELOPMENT PROGRAM
2.1 Upon execution of this Agreement, VAXCEL and CLI shall commence the
Program pursuant to the initial Work Plan attached hereto as Exhibit A. CLI
shall ensure that any Product feasibility evaluation and/or development shall be
performed in accordance with U.S. Food and Drug Administration and cGLP
regulations. Within thirty (30) days following completion of pre-clinical
studies, CLI shall provide VAXCEL with a written report of the results, and such
report and the data shall be deemed Program Information and shall be jointly
owned by CLI and VAXCEL in accordance with Section 3.1.
After completion of the feasibility work contemplated by the
initial Work Plan, VAXCEL and CLI agree to cooperate in devising mutually
agreeable Work Plans and cost estimates for further development of the Product;
such Work Plans may include but are not limited to times for mutual reporting of
results and times when crucial decisions are to be made. Each party agrees to
use its reasonable efforts to review, execute and proceed diligently under the
agreed-upon initial Work Plan and any additional or amended agreed-upon Work
Plans and to report significant deviations therefrom, in a timely fashion. Each
party agrees to revise such Work Plans from time to time so that the Work Plans
may remain a good faith estimate of the work to be done and of Development
Costs. The parties shall participate in periodic conferences to review the
current Work Plan and the status of the Program. These conferences will be held
on an "as needed" basis in the spirit of collaboration, but at least every sixty
(60) days. Notwithstanding the foregoing, (i) all Work Plans, cost estimates and
any major deviations therefrom shall be submitted in writing by the responsible
party for the other party's approval and (ii) neither party shall be required to
perform any work which would result in Development Costs exceeding approved cost
estimates.
2.2 CLI and VAXCEL shall each pay for their respective Development
Costs incurred in the performance of the Work Plan(s) under the Program. The
approved guidelines for their respective Development Costs for both CLI and
VAXCEL are attached hereto as Exhibit B. CLI shall pay Vaxcel a sum of
twenty-five thousand dollars ($25,000) upon signing this Agreement. This payment
is for exclusive rights to evaluate the Product according to the initial Work
Plan and any additional or amended agreed-upon Work Plans.
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In the event preclinical evaluation of the Product is
successful, based on CLI's sole judgment, CLI will proceed to file an IND and
initiate Phase I clinical trials on a timely basis and will pay VAXCEL a sum of
twenty thousand dollars ($20,000), within thirty (30) days of the filing of an
IND, for exclusive development rights to Product through Phase I clinical
trials.
2.3 Except as specifically authorized by this Agreement, each party
shall, for the term of this Agreement and after its expiration or termination
for any reason, keep confidential and not disclose to others, and use only for
the purposes authorized herein, all of the other party's Confidential
Information and Program Information owned by the other party; provided, however,
that the foregoing obligations shall not apply to the extent that any such
information is:
(i) already known to the other party at the time of
disclosure, as evidenced by such party's written records made prior to
the date of the Confidentiality Agreement; or
(ii) publicly known prior to or after disclosure, other than
through unauthorized acts or omissions of the other party; or
(iii) disclosed in good faith to the other party by a third
party, lawfully and contractually entitled to make such disclosure; or
(iv) the subject of a written consent of the parties which
supplied such information, authorizing disclosure; or
(v) disclosed to a licensee, distributor or agent in
accordance with the Work Plan under a secrecy agreement, provided that
the material provisions of such secrecy agreement as to confidentiality
are the same as those in this Agreement; or
(vi) developed by the recipient independent of information
received, or performed, under this Agreement and evidenced by such
parties written records.
Notwithstanding the foregoing, such information may be (a)
disclosed to government agencies and others where such information may be
required to be included in patent applications or regulatory filings not
prohibited by the terms of this Agreement; or (b) disclosed to the extent
required by applicable laws or regulations or as ordered by a court or other
regulatory body having competent jurisdiction.
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Notwithstanding anything herein to the contrary, if no further
agreement between the parties is reached, Vaxcel may use or disclose to others
the information in the evaluation report, though not the report itself,
provided: (a) all Confidential Information and Program Information related
solely to the Antigen are deleted (except with respect to which vaccines were
used in the Program); and (b) CLI is not identified by name as the collaborator.
Further, notwithstanding anything herein to the contrary, it is
understood and agreed by the parties that Confidential Information and Program
Information may be disclosed to and used by any Affiliate of the parties
provided such Affiliate is bound by non-use and non-disclosure obligations
consistent with the terms of this Agreement. In each of the foregoing cases, the
other party will use its best efforts to limit the disclosure and maintain
confidentiality to the extent possible.
Further, notwithstanding anything herein to the contrary, it is
understood and agreed by the parties that VAXCEL may make public the existence
of this Agreement, contingent upon CLI's prior written approval of any
publication or announcement revealing the existence of this Agreement.
2.4 If any party desires to publish the results and/or evaluation of the
Program, the publishing party shall provide the non-publishing party a copy of
the manuscript of any proposed publication. The non-publishing party shall then
have thirty (30) days to review and comment on the manuscript, and the
publishing party agrees to delete any information identified by the
non-publishing party as its Confidential Information and/or Program Information.
2.5 CLI shall indemnify, defend and hold harmless VAXCEL, its Affiliates,
employees, directors and agents from and against any and all claims, liability,
loss or expense incurred by any such person which arises out of the Program,
unless such liability is due solely to such person's negligence or misconduct.
VAXCEL shall indemnify, defend and hold harmless CLI, its Affiliates, employees,
directors and agents from and against any and all claims, liability, loss or
expense incurred by any such person which arises from VAXCEL's negligence or
misconduct in its performance and/or obligations under the Program.
2.6 The Antigen by CLI and the Optivax System by VAXCEL are provided for
this Program without warranty of title, noninfringement, merchantability or
fitness for a particular use, purpose, or any other warranty, expressed or
implied.
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3. OWNERSHIP
3.1 Inventions and Program Information which are conceived, generated
or first reduced to practice by either party or both parties under or as a
result of the Program shall be jointly owned with undivided interest by the
parties ("Joint Inventions"); provided, however, that inventions and Technical
Information shall be: (i) the sole property of CLI, and not deemed to be Joint
Inventions, if and to the extent related to the Antigen itself (exclusive of the
Copolymer and/or Optivax System or its use with the Copolymer and/or Optivax
System or the Product); or (ii) the sole property of VAXCEL, and not deemed to
be Joint Inventions, if and to the extent related to the Copolymer and/or
Optivax System itself (exclusive of the Antigen or its use in the Product). Each
party shall promptly notify the other in writing of all Joint Inventions. Upon
the reasonable request of either party, the other party shall execute any
reasonable document necessary to evidence or confirm the sole property rights of
the other under this Section 3.1. Unless either party provides written notice to
the other party that the invention and/or Program Information relates solely to
the Antigen or Copolymer and/or Optivax System, the inventions and Program
Information shall be considered Joint Inventions. In the event that a party
notifies the other party that it is claiming sole property rights by asserting
that the invention or Program Information are related solely to Antigen or
Copolymer and/or Optivax System, and the other party disagrees with such request
for sole property rights, the parties agree that inventorship shall be
determined in accordance with U.S. law and that ownership shall be determined by
the inventors obligations to assign such property rights. Nothing herein shall
be construed to constitute a grant by CLI of any of its rights with respect to
its Confidential Information and Technical Information (including patent rights
and trademarks) related to the Antigen nor a grant by VAXCEL of any of its
rights with respect to its Confidential Information and Technical Information
(including patent rights and trademarks) related to the Copolymer and/or Optivax
System.
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3.2 In the event of the expiration or termination for any reason of
this Agreement and if no further definitive agreement with respect to Product
has been executed by the parties, each party shall grant to the other party an
irrevocable, royalty-free, worldwide, non-exclusive license, with the right to
sub-license, to any inventions and Program Information jointly owned by the
parties under Section 3.1 above. Upon the reasonable request of either party,
the other party shall execute any documents to evidence or confirm the foregoing
license. Nothing herein shall be construed to constitute a grant by CLI of any
rights of CLI relating to the Antigen or a grant by VAXCEL of any rights of
VAXCEL relating to the Copolymer an/or Optivax System existing prior to the date
of this Agreement, or developed outside the Program and without reference
thereto or the use of any information therefrom.
3.3 Each party shall have the right, with respect to all inventions and
Program Information jointly owned under Section 3.1 or licensed to it under
Section 3.2 hereof, to disclose and to license such inventions and Program
Information to third parties, provided that such disclosure and/or license shall
not be inconsistent with the terms of this Agreement.
3.4 Both parties or either party shall have the right to decide whether
or not to seek or maintain patent protection in any country on any Joint
Invention; provided, however, that a party shall agree to proceed with patent
prosecution, filing and maintenance for a Joint Invention upon the reasonable
request of the other party. Should a party decide to pursue patent protection,
it shall inform the other party in writing of its intention to do so. The patent
application shall be filed and prosecuted in the names of both parties. In the
event that both parties decide to seek or maintain patent protection, the
following will apply:
(i) CLI shall decide on patent counsel;
(ii) CLI shall consult with VAXCEL regarding preparation,
filing, prosecution and maintenance of such patent applications and
shall furnish VAXCEL with copies of all documents relating thereto in
sufficient time to enable VAXCEL to comment on them prior to filing;
provided, however, that CLI shall make all final decisions; and
(iii) CLI shall pay all out-of-pocket expenses incurred in
filing for, prosecuting and maintaining patents with respect to any
Joint Inventions.
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VAXCEL shall make available to CLI or its authorized attorneys,
agents, or representatives, such of its employees or consultants whom CLI in its
reasonable judgment deems necessary in order to assist it in obtaining patent
protection for the Joint Inventions. VAXCEL shall sign all legal documents
necessary to file and prosecute patent applications or to obtain or maintain
patents at no charge to VAXCEL.
If at any time, VAXCEL licenses its rights or gains any other
form of economic benefit, including but not limited to, practice of the patent
by VAXCEL, under any patent on any Joint Inventions, it shall: (i) notify CLI of
such action; (ii) reimburse CLI for one-half of all out-of-pocket patent costs
incurred by CLI for any such patent(s) on Joint Invention(s) within forty-five
(45) days of receiving an invoice with accompanying documentation for such costs
from CLI; and (iii) pay for one-half of all subsequent patent maintenance costs
for such patent(s).
4. DEFINITIVE AGREEMENT
Both parties enter this Agreement with the intention of
completing the Program then negotiating definitive license and supply agreements
if, in CLI's sole judgment, the safety and immunogenicity results of the Product
are favorable. Within sixty (60) days after completion of the Program, CLI shall
advise VAXCEL in writing whether CLI wishes to pursue further development of the
Product pursuant to a definitive agreement relating to further development and
subsequent marketing rights. If CLI so notifies VAXCEL, each party agrees to
enter good faith negotiations with the other party for such a definitive
agreement covering the Product. Such good faith negotiations shall be completed
within ninety (90) days after CLI notifies VAXCEL that CLI wishes to pursue
further development of the Product. The following terms are non-binding upon the
parties, but shall serve as guidelines for the terms of the definitive
agreements relating to further development of the Product under which CLI shall
receive world-wide exclusive manufacturing and marketing rights to the Product,
with the right to sub-license, for fifteen years or for the life of any patent
covering the Copolymer and/or Optivax System, on a country by country basis,
whichever is later, further provided that VAXCEL shall supply CLI with the
Copolymer at a fixed supply price, bearing a relationship to cost, not to exceed
twenty dollars and seventy-five cents ($20.75) per gram in 1995 dollars:
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License Issue Fee $ 500,000
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Performance Milestone Payments*
- Beginning of Phase 1I $ 250,000
- Beginning of Phase III $ 250,000
- PLA Filing $ 500,000
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U.S. FDA/CBER Product Approval $1,000,000
Payments
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Per Country Regulatory Approval $ 100,000 (Maximum $500,000)
Payments
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Royalty on Sale 6-8% on Net Sales (to be defined)
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* If no development milestone is achieved within a 12-month calendar period, CLI
will pay VAXCEL $100,000 provided such payment shall be fully creditable against
the next Performance Milestone Payment.
Further, CLI will be responsible for all further development activities and
costs associated with the Product, including, but not limited to human clinical
testing, laboratory testing, pursuing regulatory approval, final manufacturing,
distribution, and marketing. VAXCEL will provide reasonable technical support to
CLI during further development of the Product as requested by CLI. For any such
work performed by VAXCEL, CLI will pay VAXCEL for any and all reasonable
expenses associated with this effort.
Further, if requested by CLI, VAXCEL will allow the definition of Antigen
contained in this Agreement to be expanded under the license and supply
agreements to include Lyme Disease antigens other than OspA.
5. THIRD PARTY ACTIVITIES
During the Program and for a period of up to sixty (60) days
after completion of the Program, if CLI has notified VAXCEL in writing of CLI's
wish to pursue further development of the Product, to be specifically identified
in such notice, each party agrees to enter into good faith negotiations with the
other party for a definitive agreement covering the further development, and if
successful, the manufacturing and marketing of the Product on such terms and
conditions as the parties shall agree. During such time and during the
additional ninety (90) day period that the parties are negotiating a definitive
agreement, VAXCEL agrees not to conduct any vaccine product development
discussions or activities with any third party related to the Product under the
Work Plan. This additional negotiating period may extend beyond ninety (90) days
by mutual agreement of the parties.
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6. TERM AND TERMINATION
6.1 This Agreement shall remain in effect until the earlier of (i) two
(2) years from the effective date of this Agreement; or 2) such time as work is
no longer being carried out under the Program in accordance with mutually
approved Work Plans and cost estimates.
6.2 In the event that the Product does not appear viable during
preclinical testing, CLI shall have the option to terminate this Agreement by
written notice to VAXCEL.
6.3 Either party may terminate this Agreement in its sole discretion,
at any time, by giving not less than sixty (60) days prior written notice to the
other party, if the other party is not proceeding diligently with the Program in
accordance with Section 2.1 hereof.
6.4 Either party may terminate this Agreement if the other party has
failed to pay any amount payable hereunder, and such failure is continuing for
thirty (30) days after receiving proper notification of such nonpayment.
6.5 Either party may terminate this Agreement if the parties cannot
successfully negotiate a definitive license and supply agreement within the time
limits outlined in Sections 4 and 5 above.
6.6 Termination of this Agreement shall be without prejudice to either
party's right to receive any and all payments accrued under Section 2.2 prior to
the effective date of the termination. After termination of this Agreement by
either party or in the event of a breach by either party of this Agreement, each
party shall reimburse the other party, within forty five (45) days after
invoice, for any uncancellable obligations and expenses incurred by such party
prior to termination in connection with the Program, and all reasonable costs
incurred by such party in terminating the Program, if the paying party would
have been responsible for such obligations, expenses or costs under Section 2.2
and Exhibit B; provided, however, that no payments for such obligations or
expenses shall be due to the party in breach of this Agreement.
6.7 If this Agreement is terminated by CLI for any reason, VAXCEL shall
be free to license the Optivax System to other third parties for any Lyme
Disease antigens other than the Antigen.
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7. MISCELLANEOUS
7.1 This Agreement shall be governed by and construed in accordance
with the laws of the Commonwealth of Pennsylvania and each party submits to the
jurisdiction of any state or federal court of the Commonwealth of Pennsylvania.
7.2 This Agreement shall not be amended or modified except in writing
signed by each of the parties hereto.
7.3 Nothing in this Agreement shall be construed to constitute a grant
to CLI of any rights other than those expressly granted herein. Specifically,
CLI shall not have the right to use: (a) the Copolymer or Optivax System with
antigens other than the Antigen, without VAXCEL's prior written approval; (b)
the Copolymer or Optivax System to immunize individuals for the purpose of
producing antibodies which will subsequently be purified and concentrated to
make a high-titer, human immune globulin for commercial sale; or (c) the
Copolymer or Optivax System in any testing or analysis that would reverse
engineer or otherwise reveal the chemical or structural composition of the
Copolymer or the Optivax System. In addition, VAXCEL shall supply all of CLI's
requirements of the Copolymer and nothing in this Agreement shall be construed
to constitute a grant to CLI the right to manufacture the Copolymer either
directly or through a third party.
7.4 Any notice required or permitted under this Agreement shall be in
writing and addressed as follows:
If to VAXCEL: If to CLI:
Vaxcel, Inc. Connaught Laboratories, Inc.
0000 Xxxxxxxxxx Xxxxxxx, Xxxxx 000 X.X. Xxx 000, Xxxxx 000
Xxxxxxxx, XX 00000 Xxxxxxxxxx, XX 00000
Attention: President Attention: Vice President
Business Development
All notices given in accordance with this Section 7.4 shall be
deemed to be effective five (5) days after the date of mailing, if mailed by
registered or certified mail, postage prepaid and return receipt requested or,
upon delivery, if delivered by hand. Any party may change its address at which
notice is to be received by written notice provided pursuant to this Section
7.4.
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7.5 This Agreement, together with the Confidentiality Agreement and the
exhibits hereto, sets forth the entire agreement and understanding between the
parties as to the subject matter hereof and supersedes all agreements and
understandings between the parties with respect to the subject matter, whether
oral or in writing.
7.6 The provisions of Sections 2.3, 2.5, 3.1,3.2, 3.3, 3.4, 5, 6.6,
7.1, 7.7, 7.14 and this Section 7.6 shall survive termination for any reason of
this Agreement.
7.7 All disputes arising in connection with this Agreement shall be
finally settled under the rules of the American Arbitration Association by one
(1) independent arbitrator experienced in the matter at issue and appointed in
accordance with said rules. The place of arbitration shall be New York City, New
York. The Arbitrator shall determine the matters in dispute in accordance with
the laws of the Commonwealth of Pennsylvania. All costs and expenses incurred in
connection with the arbitration (including reasonable attorney fees) shall be
borne by the party against whom the decision is rendered or, if no decision is
rendered, such costs and expenses shall be borne equally by the parties (except
that each party shall pay its own legal fees and expenses). If the arbitrator's
decision is a compromise, the determination of which party or parties bears the
costs and expenses incurred in connection with any such arbitration proceeding
shall be made by the arbitrator on the basis of the arbitrator's assessment of
the relative merits of the parties' positions. Notwithstanding the above, either
party has the right to bring suit in a court of competent jurisdiction against
the other party for (i) any breach of the duties of confidentiality pursuant to
this Agreement or the Confidentiality Agreement, or (ii) any infringement by a
third party of the other party's proprietary rights.
7.8 Except as permitted under Section 2.3, each party agrees not to
disclose to any third party the existence of the arrangements between the
parties contemplated by this Agreement, without the written consent of the other
party.
7.9 The respective rights of the parties hereto may be assigned by each
party to any Affiliate of such party. No other assignment or delegation of the
rights or obligations of either party may be made, without the express written
consent of the other party.
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7.10 Each party represents and warrants that it has the power and
authority to execute, deliver, and perform its obligations under this Agreement,
and that neither the execution nor delivery of this Agreement nor the
performance of its obligations hereunder will constitute a breach of the terms
or provisions of any contract or violate the rights of any third party.
7.11 No party hereto shall be liable for failure to perform or delay in
performing obligations set forth in this Agreement and no party shall be deemed
in breach of its obligations, if, to the extent and for so long as such failure,
delay, or breach is due to natural disasters or any causes beyond reasonable
control of that party. Any party desiring to invoke this section 7.11 shall
notify the other party promptly of such desire and shall use reasonable efforts
to resume performance of its obligations.
7.12 No waiver of any term or condition of this Agreement shall be
valid except by an instrument in writing expressly waiving such term or
condition signed by the waiving party.
7.13 If any provision of this Agreement is ultimately held to be
invalid, illegal or unenforceable, the validity, legality, and enforceability of
the remaining provisions hereof shall not in any way be affected or impaired
thereby, unless the absence of the invalidated provision materially affects the
substantive rights of the parties hereto.
7.14 Notwithstanding anything to the contrary set forth in this
Agreement, (a) neither party will be liable to the other for any incidental,
special, consequential, punitive, or exemplary damages of any kind and (b) if
arbitration, litigation or other action is commenced between the parties
concerning any dispute arising out of or relating to this Agreement, the
prevailing party in any contested ancillary proceeding related to the action
(e.g., motions to transfer, to compel discovery, etc.) and the prevailing party
in the action itself will be entitled, in addition to any other award that may
be made, to recover all court costs or other official costs and all reasonable
expenses associated with the ancillary proceeding or action, including without
limitation reasonable attorney's fees and expenses.
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IN WITNESS WHEREOF, the parties have executed this Agreement as of the date
first set forth above.
VAXCEL, INC. CONNAUGHT LABORATORIES, INC.
By By
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Title Title
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EXHIBIT A
WORK PLAN
TITLE: EVALUATION OF OspA SPECIFIC ANTIBODY RESPONSES INDUCED USING
FORMULATIONS CONTAINING OPTIVAX ADJUVANT
1. PURPOSE AND LOGIC
A. PURPOSE: To compare immune responses induced using experimental subunit
vaccine formulations based on Connaught's recombinant OspA and containing the
nonionic block copolymer P1005, the Optivax adjuvant. The experimental endpoint
will be the production of specific antibodies that are high titered and
long-lived. Experimental challenge experiments will not be done in this study
but rather in subsequent studies.
B. LOGIC: The Optivax adjuvant system is based on the nonionic block
copolymer, P1005, which can be used in both aqueous and oil-containing vaccine
formulations. The Optivax adjuvant routinely augments immune responses and could
induce additional or different effector mechanisms. Mechanisms of action are not
known but could include:
1. When correctly formulated in aqueous solutions the polymer will form
1-5[mu]m particles in association with the vaccine immunogen. Particulate based
delivery of protein immunogens is known to augment both antibody and cellular
immune responses through depot effects.
2. When Optivax is used in oil-in-water (O/W) emulsions, the emulsion
is stabilized.
3. Particles may preferentially deliver immunogens to phagocytic
macrophages, and potentially to phagocytic immature dendritic cells, which would
increase antigen processing and presentation.
4. Optivax polymer may activate antigen presenting cells directly.
II. TEST REAGENTS, ANIMAL REQUIREMENTS AND TEST GROUP ORGANIZATION
A. IMMUNOGENS AND VACCINE FORMULATIONS:
1. The subunit vaccines will be based on recombinant OspA protein, 0.2
or 2[mu]g/dose in a dose volume of 100[mu]l.
a. Amount of recombinant OspA protein required for the actual
experimental vaccine formulations is 176[mu]g. Because of technical
limitations, a minimum of 500[mu]g will be needed.
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2. The poloxamer P1005 (Optivax) will be used as the experimental
adjuvant, 2.5-7.5mg/dose.
a. Amount of P1005 polymer required for actual experimental
vaccine formulations is 600mg. Additional material will be available as
needed to address formulation issues.
3. All formulations will be prepared at laboratory scale at Vaxcel.
B. ASSAY PROTEINS OR PEPTIDES:
1. The recombinant OspA will be used to measure antibodies in a
standard ELISA. All serological testing will be done at Connaught.
C. ANIMAL TYPE AND NUMBERS
The initial experiment will require the use of 80 C3H mice, ten mice / group,
eight groups. Mice will be age and gender matched, purchased from a standard
supplier and housed and maintained at the Vaxcel/CytRx animal facility. Mice
will be immunized two times, 21 days between immunizations. All immunizations
will be done using the CytRx facility. The vaccines will be administered by
needle injection, subcutaneously (s.c.) at one site, total volume of
100[mu]l/dose. The groups will be immunized using the following format:
1. Group 1 mice will receive 0.2[mu]g/dose of OspA, without Optivax
adjuvant.
2. Group 2 mice will receive 0.2[mu]g/dose of OspA + 2.5% (2.5mg/dose)
P1005 (Optivax).
3. Group 3 mice will receive 0.2[mu]g/dose of OspA + 5.0% (5.0mg/dose)
P1005 (Optivax).
4. Group 4 mice will receive 0.2[mu]g/dose of OspA + 7.5% (7.5mg/dose)
P1005 (Optivax).
5. Group 5 mice will receive 2[mu]g/dose of OspA, without Optivax
adjuvant.
6. Group 6 mice will receive 2[mu]g/dose of OspA + 2.5% (2.5mg/dose)
P1005 (Optivax).
7. Group 7 mice will receive 2[mu]g/dose of OspA + 5.0% (5.0mg/dose)
P1005 (Optivax).
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8. Group 8 mice will receive 2[mu]g/dose of OspA + 7.5% (7.5mg/dose)
P1005 (Optivax).
NOTE: The option of giving a third immunization will be considered if
high-titered antibody responses are not raised following the two
immunizations.
III. MEASUREMENT OF ANTIGEN - SPECIFIC IMMUNE RESPONSES
A. ANTIBODY RESPONSES: On the day of the first immunization, day 0, but
prior to the vaccine administration and on days 14 and 35, blood will be
collected from all mice. Sera will be recovered for serological assays,
specifically the measurement of antibody titers by ELISA. Selected antibody
positive samples will be further tested to measure bacterial growth inhibition
activity. Additional blood sampling will be done if needed or if a third
immunization is given.
IV. EXPERIMENTAL SCHEDULE
A. AVAILABILITY OF VACCINE COMPONENTS: The recombinant OspA protein and
the P1005 Optivax polymer are available currently so no delays are anticipated
regarding formulation of experimental OspA vaccines.
B. ANIMALS, PURCHASE, HOUSING AND IMMUNIZATIONS: Capacity for housing 80
mice is currently available and animals were ordered for delivery during the
week of June 26, 1995. One week quarantine at the Vaxcel/CytRx animal facility
was required which means the immunizations were done during the week of July 3,
1995. The 'in-life' animal portion of the experiments will be completed by
August 7, 1995.
C. ANIMAL MATERIALS FOR TESTING: All serum samples will be shipped
together upon completion of the 'in-life' portion of the experiments during the
week of August 7, 1995. Testing schedule, for CLI, to be determined by Dr. Xxxx
Xxxx.
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EXHIBIT B
GUIDELINES FOR DEVELOPMENT COSTS
LYME DISEASE VACCINE
VAXCEL DEVELOPMENT COSTS
1. VAXCEL will select an appropriate Optivax System formulation(s) as an
adjuvant for the Antigen.
2. VAXCEL will provide CLI with sufficient quantities of Copolymer to
conduct toxicology and other preclinical studies to determine
feasibility.
3. VAXCEL will provide technical support during Product formulation,
manufacturing, preclinical evaluation, IND submission, and Phase I
clinical trials, as requested by CLI.
4. VAXCEL will perform toxicology study on the Copolymer alone in a manner
to support an IND, submit this data to the U.S. Food and Drug
Administration, and allow CLI to access this information for
confidential regulatory purposes.
5. VAXCEL and its current parent, CytRx Corporation, will prepare and
CytRx will submit a Drug Master File on the Copolymer to the U.S. Food
and Drug Administration and allow CLI to access this information for
confidential regulatory purposes.
CLI DEVELOPMENT COSTS
1. CLI will perform all preclinical studies on the Product to determine
feasibility.
2. CLI will perform toxicology and other necessary preclinical studies on
the Product to support an IND
3. CLI will prepare and submit the IND for the Product.
4. CLI will be responsible for all manufacturing of the Product for
preclinical testing and Phase I clinical trials.
5. CLI will pay VAXCEL reasonable expenses for VAXCEL scientific personnel
to assist with formulations and manufacturing, at CLI's facility in
Swiftwater, if necessary.
6. Vaxcel will charge CLI $20.75 per gram for Phase I clinical material.
7. CLI will conduct the Phase I clinical trial on the Product.
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8. CLI will reimburse VAXCEL for any VAXCEL activities performed under the
Work Plan beyond those specifically described above under "VAXCEL
Development Costs".
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