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* Portions denoted with an asterisk have been omitted and filed separately with
the Securities and Exchange Commission pursuant to a request for confidential
treatment.
COLLABORATION AGREEMENT
This Collaboration Agreement (this "Agreement"), made as of July 1, 2004
(the "Effective Date"), is by and between Advanced Cardiovascular Systems, Inc.,
a corporation organized under the laws of California and having a place of
business at 3200 Lakeside Drive, Santa Clara, California 95054 (herein referred
to as "ACS"), and Miravant Medical Technologies, together with its subsidiary,
Miravant Cardiovascular, Inc., both corporations organized under the laws of
Delaware and having places of business at 336 Bollay Drive, Santa Barbara,
California 93117 (collectively referred to as "MMT"). ACS and MMT may each be
referred to as a "Party" or, collectively, as the "Parties" in this Agreement.
RECITALS
WHEREAS, ACS is engaged in the design, development, manufacture and
commercialization of medical devices for the diagnosis and treatment of
cardiovascular diseases, and ACS has patented and other proprietary medical
devices and systems for delivery of therapeutic compositions and drugs to
patients;
WHEREAS, MMT is developing photodynamic therapy ("PDT") products using
light activated compositions or drugs and related devices or systems for the
treatment of diseases, such as ophthalmology, dermatology, cardiovascular,
oncology and other conditions and diseases;
WHEREAS, the Parties wish to enter into a business alliance in which they
will collaborate on the development, pre-clinical and clinical investigations of
certain light activated compositions or drugs and related devices or systems for
use in the treatment of cardiovascular diseases, all on the terms and conditions
set forth below; and
WHEREAS, contemporaneously with the execution and delivery of this
Agreement, the Parties are executing and delivering a Securities Purchase
Agreement and a Registration Rights Agreement pursuant to which ACS has agreed
purchase certain MMT preferred stock and to provide certain registration rights
under the Securities Act, the rules and regulations promulgated thereunder and
applicable state securities laws.
AGREEMENT
NOW, THEREFORE, in consideration of the covenants and obligations expressed
herein, and intending to be legally bound, the Parties agree as follows:
ARTICLE 1: DEFINITIONS
1.1 "ACS Indemnitees" has the meaning ascribed to it in Section 11.1.
1.2 "ACS Inventions" has the meaning ascribed to it in Section 9.2.
1.3 "Affiliate" means, with respect to any Party, any corporation or other
business entity, which controls, is controlled by, or is under common control
with such Party. A corporation or other entity shall be regarded as in control
of another corporation or entity if it owns or directly or indirectly controls
at least fifty percent (50%) of the voting stock or other ownership interest of
the other corporation or entity (or alternatively, if not meeting the preceding
and with respect to foreign entities, if it owns the maximum such ownership
interest permitted by law), or if it possesses, directly or indirectly, the
power to direct or cause the direction of the management and policies of the
corporation or other entity or the power to elect or appoint at least fifty
percent (50%) of the members of the governing body of the corporation or other
entity.
1.4 "Agreement" has the meaning ascribed to it in the preamble hereof.
1.5 "Confidential Information" means all proprietary, non-public
information that has commercial value or other utility in a Party's business,
including but not limited to any information, inventions, know-how, biological
materials, chemical compounds, data, pre-clinical data, and materials provided
by one Party to the other pursuant to this Agreement, whether existing or
disclosed in oral, written, graphic, digital, optical, electronic or other form.
1.6 "Effective Date" has the meaning ascribed to it in the preamble hereof.
1.7 "FDA" means the United States Food and Drug Administration and any
successor agency thereto.
1.8 "INDA" means (a) an Investigational New Drug Application, as defined in
the United States Federal Food, Drug and Cosmetic Act, as amended, and the
regulations promulgated thereunder, that is required to be filed with the FDA
before beginning clinical testing of human subjects, or any successor
application or procedure, (b) any foreign counterpart of a United States
Investigational New Drug Application, and (c) all supplements and amendments,
including supplemental Investigational New Drug Applications and related foreign
counterparts, that may be filed with respect to the foregoing.
1.9 "Intellectual Property" means all of the following or their substantial
equivalents or counterparts in any jurisdiction throughout the world: (i)
patents, patent applications and invention disclosures, (ii) trademarks, service
marks, trade dress, trade names, corporate names, logos and Internet domain
names, (iii) copyrights, software and source code and copyrightable works, (iv)
registrations and applications for any registration for any of the foregoing and
(v) trade secrets, know-how, confidential information and inventions.
1.10 "Joint Inventions" has the meaning ascribed to it in Section 9.2.
1.11 "JSC" has the meaning ascribed to it in Section 2.1.
1.12 "Lead Drug" means that certain MMT compound designated as MV0633, or
such other PDT Drug, as the Parties may mutually agree to in writing.
1.13 "MMT Indemnitees" has the meaning ascribed to it in Section 11.2.
1.14 "MMT Inventions" has the meaning ascribed to it in Section 9.2.
1.15 "PDT" has the meaning ascribed to it in the recitals hereof.
1.16 "PDT Device" means those certain non-thermal medical laser devices,
including catheters, that have light sources of any wavelength and associated
equipment designed by MMT to activate the Lead Drug or PDT Drug for the
treatment of cardiovascular disease in the Therapeutic Field.
1.17 "PDT Drug" means those certain light activated compositions or drugs
that are designated as MV0633 and MV0611, including compounds and derivatives of
these compounds that have been, are being, or will be evaluated during the term
of this Agreement by MMT for the treatment of patients within the Therapeutic
Field or that are being developed by MMT during the Term and activated with a
PDT Device for the treatment of patients within the Therapeutic Field. For
clarity, the MMT compound designated as SnET2 is not a PDT Drug under this
Agreement.
1.18 "PDT Technology" means existing and future technology owned or
controlled by MMT that is specifically directed to treating cardiovascular
indications within the Therapeutic Field and necessary for the manufacture, use
or sale of PDT Drug, PDT Device or PDT Therapy, including, without limitation,
materials and processes utilized in production or processing of such PDT Drug,
PDT Device or PDT Therapy, and trade secret information or know-how relating to
such materials and processes.
1.19 "PDT Therapy" means a PDT Drug, its related delivery product or
system, and its related light activation product or system that are owned or
controlled by MMT and used for the treatment of a patient within the Therapeutic
Field.
1.20 "Party" and/or "Parties" has the meaning ascribed to it in the
preamble hereof.
1.21 "Patent Prosecution" has the meaning ascribed to it in Section 9.3.
1.22 "Patent Rights" means all existing patents and patent applications and
all patent applications disclosing or claiming any Lead Drug, PDT Drug, PDT
Device or PDT Therapy conceived by a Party during the Term, including any
continuations, continuations-in-part, divisions, provisionals or any substitute
applications, any patent issued with respect to any such patent applications,
any reissue, reexamination, renewal or extension (including any supplemental
patent certificate) of any such patent, and any confirmation patent or
registration patent or patent of addition based on any such patent, and all
foreign counterparts of any of the foregoing.
1.23 "Phase I Trial" means a complete program of one or more human
clinical trials in the United States wherein such program is intended to
initially evaluate the safety and/or pharmacological effect of, or otherwise to
satisfy the requirements of 21 ss.CFR 312.21(a), with respect to a Lead Drug,
PDT Drug, PDT Device or PDT Therapy for a particular condition in patients under
study within the Therapeutic Field.
1.24 "Phase II Trial" means a complete program of one or more human
clinical trials in the United States wherein such program is intended to
initially evaluate the appropriate dose of a drug for effectiveness of, or
otherwise satisfy the requirements of 21 CFR ss.312.21(b), with respect to a
Lead Drug, PDT Drug, PDT Device or PDT Therapy for a particular condition in
patients under study within the Therapeutic Field.
1.25 "Pre-Clinical Development Program" means the collection of
pre-clinical development activities including, without limitation, conducting
all animal studies, good laboratory practices (GLP) animal studies, or other
studies and gathering all data required with respect to non-safety research
studies, early stage drug development, drug metabolism, mechanism of action
analyses, pharmacokinetics, potency, selectivity, safety/toxicology and
manufacturing scale up, which are to be conducted by MMT as it deems necessary
with input from the JSC in order to file an INDA submission with the FDA for a
Lead Drug, PDT Drug, PDT Device or PDT Therapy in the Therapeutic Field.
1.26 "Term" has the meaning ascribed to it in Section 12.1.
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1.27 "Therapeutic Field" means the use of a Lead Drug, PDT Drug, PDT
Device or PDT Therapy for PDT treatment of human cardiovascular diseases
including but not limited to treatment of atherosclerotic vascular disease and
prevention of restenosis as well as other cardiovascular diseases or indications
designated by mutual written agreement of MMT and ACS from time to time in
accordance with the terms of this Agreement. Notwithstanding the foregoing,
Therapeutic Field shall not in any case include hemodialysis graft applications,
arterio-venous access disease, or diseases requiring local (non-intravenous)
SnET2 PDT drug delivery.
1.28 "Third Party" means a person or party other than ACS and MMT.
ARTICLE 2: JOINT COMMITTEE
2.1 Joint Steering Committee. Promptly following the Effective Date,
the Parties shall establish a Joint Steering Committee ("JSC") for the purposes
of collaborating on the development of MMT's Lead Drug, PDT Drug, PDT Device or
PDT Therapy within the Therapeutic Field pursuant to the preliminary development
plan that is attached to this Agreement as Exhibit A, in the manner and to the
extent provided herein. The JSC will be staffed by ACS and MMT employee
appointees, and the total number of JSC members will be eight (8), with four (4)
appointees for each Party, but the number may be adjusted upward or downward by
mutual agreement of the Parties. ACS initial JSC appointees will include one
business development manager, one new ventures research fellow, one new ventures
director and one clinical-regulatory research fellow. MMT's initial JSC
appointees will include one Endovascular Product Team Leader, one
Atherosclerosis Program Manager, one Cardiovascular Program Manager, and one
Director of Corporate Development & Strategic Planning. Either Party may replace
any of one or more of its appointees to the JSC at-will by giving written notice
thereof to the other Party.
2.2 Chairperson. The chairperson of the JSC shall be selected initially
by MMT from among the MMT employee appointees serving on the JSC and shall serve
in such role for one (1) year. After such one year period, the chairperson of
the JSC shall be selected from among the ACS employee appointees then serving on
the JSC, and that person will then serve in such role for one (1) year.
Thereafter, ACS and MMT shall alternate annually in selecting the chairperson of
the JSC from their respective appointees throughout the Term. The Chairperson of
the JSC will be responsible for calling and chairing meetings, developing
meeting agendas, and recording and distributing meeting minutes and directing
future actions of the JSC. The Chairperson of the JSC shall call one (1)
meeting, either face-to-face, video conference, or telephone conference, as
appropriate, for every calendar quarter during the Term or more frequently as
mutually agreed by the Parties.
2.3 Responsibilities of the Joint Steering Committee.
(a) In general, the responsibilities of the JSC will be to
analyze, consult, review and advise MMT, solely on a non-binding, advisory
basis, concerning the research, development, record keeping and other activities
related to any Lead Drug, PDT Drug, PDT Device, PDT Therapy or the Pre-Clinical
Development Program. As part of its responsibilities, the JSC will review and
make non-binding recommendations as necessary from time to time concerning MMT's
Pre-Clinical Development Program and Phase I Trial. Specific review and
consulting activities for JSC include, but are not limited to, (i) recommending
guidelines for staffing physician advisory groups, Pre-clinical Development
Program Plans, and Phase I Trial plans, (ii) discussing project projections,
budgets, tracking reports, and timelines, (iii) reviewing and discussing data
from pre-clinical studies and clinical trials, (iv) recommending additional
research studies beyond Pre-clinical Development Program Plans, (v) recommending
timing of and content for the INDA submission program with respect to any Lead
Drug, PDT Drug, PDT Device or PDT Therapy in the Therapeutic Field, (vi)
recommending content for the clinical readiness review, (vii) analysis of the
Phase I Trial Report, and (viii) recommending how to amend, as needed, the
Pre-clinical Development Program and Phase I Trial plans.
(b) The JSC shall have such other responsibilities as are
expressly set forth elsewhere in this Agreement or as are assigned to it as
mutually agreed upon by the Parties in writing.
(c) For clarity, MMT shall have the sole and exclusive right
to determine and control all research, development, commercialization and other
activities with respect to any Lead Drug, PDT Drug, PDT Device, PDT Therapy and
PDT Technology.
ARTICLE 3: MMT AND ACS OBLIGATIONS AND RESPONSIBILITIES
3.1 MMT Obligations and Responsibilities.
(a) MMT, through its Pre-Clinical Development Program, will
use commercially reasonable efforts to develop sufficient data concerning the
Lead Drug, PDT Drug, PDT Device, or PDT Therapy to enable MMT to file an INDA
submission with the FDA for such Lead Drug, PDT Drug, PDT Device, or PDT Therapy
in an expeditious and efficient manner.
(b) MMT agrees, in order for the JSC to undertake its
responsibilities, to provide the JSC with its information, data, records and
other documents including but not limited to MMT's comprehensive project plans
and tracking reports related to the Lead Drug, PDT Drug, PDT Device, PDT
Therapy, Pre-Clinical Development Program, and the Phase I Trial.
(c) MMT will use commercially reasonable efforts to i) provide
technical expertise concerning PDT Technology, ii) conduct its activities for
the Pre-Clinical Development Program and Phase I Trial, and (iii) provide data,
results and other related information generated in the course of the
Pre-Clinical Development Program and Phase I Trial to the JSC for review and
comment.
(d) MMT agrees to provide ACS with exclusive access to its
records reflecting inventions, ideas, information or data related to any Lead
Drug, PDT Drug, PDT Device, PDT Therapy or PDT Technology developed in the
course of work done under a Pre-Clinical Development Program and Phase I Trial
and to its records and data that existed prior to this Agreement related to any
PDT Drug. ACS acknowledges that MMT may share such records with its third party
contractors who are performing services for MMT in connection with the Phase I
Trial and who are under a confidentiality obligation with MMT without violating
the exclusive access granted to ACS herein. MMT also agrees to provide ACS with
written quarterly research and development updates as well as pre-clinical
research and clinical research updates in a format that is mutually agreed upon
by the Parties.
3.2 ACS Obligations and Responsibilities. ACS agrees, through its
appointees to the JSC, to (i) provide pre-clinical, clinical and regulatory
advice and consultation to MMT, (ii) offer its business and strategic
perspectives concerning treatment of atherosclerotic vascular disease, and (iii)
provide, in its sole discretion, reasonable advice and consultation concerning
catheter devices and systems for use in, or as used for, PDT Therapy.
ARTICLE 4: EXCLUSIVITY
4.1 Exclusive Collaboration Within The Therapeutic Field. Subject to
any obligations of the Parties herein, each Party agrees that it will not
commence a research, development, or commercialization plan or program, directly
or indirectly in collaboration with any Third Party, for the purpose of
researching, developing, delivering, administering, commercializing or otherwise
exploiting any Lead Drug, PDT Drug, PDT Device or PDT Therapy in the Therapeutic
Field during the Term, unless otherwise mutually agreed to by the Parties in
writing. The Parties acknowledge that this exclusivity obligation does not
prevent ACS or its Affiliates from making equity investments in, licensing or
acquiring PDT technology of any Third Party in the Therapeutic Field.
Notwithstanding the foregoing, MMT shall have the right to have any of the
activities under the Pre-Clinical Development Program and Phase I Trial
conducted on its behalf by Third Party contractors, and except as provided
herein nothing contained herein shall restrict either party's right to research,
discover, develop, manufacture and/or commercialize PDT products and technology
outside the Therapeutic Field.
ARTICLE 5: RIGHT OF FIRST REFUSAL
5.1 ACS's Right Of First Refusal. Upon (i) the completion of the Phase
I Trial as that event is defined in Section 12.1, or (ii) receipt by either
party of notice of termination of this Agreement pursuant to Section 12.2(a),
(b), (c) or (e), ACS shall have a right of first refusal ("ROFR") for a period
of 12 months to participate in any Phase II Trial. ACS participation may
include, but is not limited to, consultation regarding the design, manufacture
or use of light activation catheters or products, providing clinical and
regulatory consultation to MMT, providing funding to MMT for access to the Phase
II Trial data and results, or conducting the Phase II Trial in collaboration
with MMT or independently in the event that MMT would transfer or assign the
INDA to ACS, in each case as mutually agreed in writing by the Parties in
accordance with the process set forth in Section 5.1. ACS shall have thirty (30)
days to decide to exercise its ROFR after receiving written notice from MMT that
it has a bona-fide intention to begin, or that it has a bona-fide intention to
have a third party begin, any Phase II Trial. If ACS exercises its ROFR it shall
notify MMT in writing within such 30 day period. Then, the Parties will have an
additional thirty (30) days from the date of ACS's notice to MMT to exclusively
negotiate and enter into a term sheet concerning ACS participation in the Phase
II Trial. If the Parties execute a term sheet, they agree for a period of at
least sixty (60) days following the date of ACS's notice to MMT to negotiate in
good faith to reach a definitive agreement. In the event that MMT and ACS enter
into a definitive agreement, that agreement shall provide ACS with an option to
obtain a license from MMT to develop and commercialize, or otherwise exploit any
Lead Drug, PDT Drug, PDT Device or PDT Therapy within the Therapeutic Field on
terms to be mutually agreed upon by the Parties. If with respect to the subject
of a particular written notice received by ACS pursuant to this Section 5.1, the
Parties do not execute either the term sheet or the definitive agreement within
the foregoing time periods, then ACS's rights and MMT's obligations under this
Section 5.1 shall terminate, unless extended by mutual agreement or in the event
a delay is caused by the other Party's action or inaction, and MMT may proceed
with its plans for a Phase II Trial as set forth in the notice to ACS.
This Article 5 shall survive expiration or termination of this
Agreement except in the event of termination pursuant to Section 12.2(d) hereof.
ARTICLE 6: COSTS
6.1 Pre-Clinical Development Program and Phase I Trial Costs. All costs
and expenses related to research and development of PDT Therapy, MMT's
Pre-Clinical Development Program and Phase I Trial during the Term will be borne
by MMT.
ARTICLE 7: MMT RECORD KEEPING
7.1 Documentation. All tasks conducted by MMT in the course of its
performance under this Agreement shall be completely and accurately recorded,
recorded in reasonably sufficient detail and, where applicable, in good
scientific manner.
7.2 Policies for Maintaining Records. In order to protect the Parties'
Patent Rights under United States law in any inventions conceived or reduced
to practice during or as a result of any work performed by the Parties under
this Agreement, each Party agrees to require, consistent with its existing
policies, its employees to record and maintain all data and information
developed during this Agreement in such a manner as to enable the Parties to
use such records to establish the earliest date of invention and/or diligence
to reduction to practice. At a minimum, such individuals will record all
inventions generated by them in standard laboratory notebooks which are dated
and corroborated by non-inventors on a regular, contemporaneous basis.
ARTICLE 8: CONFIDENTIAL INFORMATION
8.1 Confidentiality Obligations. The Parties agree that, for the Term
and for three (3) years thereafter, either Party that receives Confidential
Information (a "Receiving Party") from the other Party (a "Disclosing Party")
shall keep completely confidential and shall not publish or otherwise disclose
and shall not use for any purpose (except as expressly permitted hereunder)
any Confidential






