Exhibit 10.15


 


Exclusive
License Agreement


 


 


between


 


 


The
Regents of the University of California


 


 


and


 


 


Collateral
Therapeutics.


 


 


for


 


 


Angiogenesis
Gene Therapy


 


 


U.C. Case No. 94-161-1,-3


 


 


	
   

  	
  U.C. AGREEMENT

  
	
   

  	
  CONTROL NUMBER

  
	
   

  	
  96-04-0203

  



 





















 


Table
of Contents


 


	
  Article
  No.

  	
   

  	
  Title

  	
   

  	
  Page

  
	
   

  	
   

  	
   

  
	
   

  	
  Recitals

  	
  1

  
	
  1.

  	
  Definitions

  	
  4

  
	
  2.

  	
  Grant

  	
  7

  
	
  3.

  	
  License Issue Fee

  	
  9

  
	
  4.

  	
  Royalties

  	
  9

  
	
  5.

  	
  Due Diligence.

  	
  13

  
	
  6.

  	
  Progress and Royalty Reports

  	
  15

  
	
  7.

  	
  Books and Records

  	
  17

  
	
  8.

  	
  Life of the Agreement

  	
  18

  
	
  9.

  	
  Termination by The Regents

  	
  19

  
	
  10.

  	
  Termination by Licensee

  	
  20

  
	
  11.

  	
  Disposition of Patent Products on Hand Upon
  Termination

  	
  20

  
	
  12.

  	
  Use of Names and Trademarks

  	
  21

  
	
  13.

  	
  Limited Warranty

  	
  22

  
	
  14.

  	
  Patent Prosecution and Maintenance

  	
  23

  
	
  15.

  	
  Patent Marking

  	
  27

  
	
  16.

  	
  Patent Infringement

  	
  27

  
	
  17.

  	
  Indemnification

  	
  29

  
	
  18.

  	
  Notices

  	
  31

  
	
  19.

  	
  Assignability

  	
  32

  
	
  20.

  	
  Late Payments

  	
  32

  
	
  21.

  	
  Waiver

  	
  33

  
	
  22.

  	
  Failure to Perform

  	
  33

  
	
  23.

  	
  Governing Laws

  	
  33

  
	
  24.

  	
  Government Approval or Registration

  	
  34

  
	
  25.

  	
  Export Control Laws

  	
  34

  
	
  26.

  	
  Force Majeure

  	
  34

  
	
  27.

  	
  Confidentiality

  	
  35

  
	
  28.

  	
  Miscellaneous

  	
  37

  



 





















 


U.C.
Case No. 94-161-1,-3


Revised:
7/13/95 (SH)


Draft
date:  September 25, 1995


 


Exclusive
License Agreement


for


Angiogenesis
Gene Therapy


 


This license agreement (“Agreement”) is effective this 27th
day of September, 1995, by and
between The Regents of the University of California (“The Regents”), a
California corporation, having its statewide administrative offices at 300
Lakeside Drive, 22nd Floor, Oakland, California   94612-3550 and Collateral Therapeutics (“Licensee”),
a California corporation, having a principal place of business at 9360 Towne
Centre Drive, San Diego, California 
92121.


 


Recitals


 


Whereas, certain inventions, relating to “Angiogenesis Gene Therapy” (“Invention”),
useful for angiogenesis, were made at the University of California, San Diego (“UCSD”)
and are described and claimed in certain patent applications, naming Drs. H.
Kirk Hammond, Frank Giordano, and


 





















 


Wolfgang
Dillmann as co-inventors, identified in the below defined Patent Rights;


 


Whereas, Licensee entered into a Letter of Intent (“Letter of Intent”),
having U.C. Agreement Control No. 95-30-0891, effective March 27, 1995, that
provided the Licensee with a time-limited exclusive right to negotiate for a
license to the Patent Rights;


 


Whereas, under 35 USC 200-212, The Regents may elect to retain title to
any invention (including the Invention) made by it, in whole or in part, under
U.S. Government funding;


 


Whereas, if The Regents elects to retain title to the Invention, then
the law requires that The Regents grant to the U.S. Government a
nontransferable, paid-up, nonexclusive, irrevocable license to use the
Invention by or on behalf of the U.S. Government throughout the world;


 


Whereas, The Regents elected on September 19, 1995, to retain title to
the Invention and granted the required licenses to the U.S. Government;


 


Whereas, H. Kirk Hammond, M.D., is an employee of the Veterans
Administration Medical Center (“VA”);


 


Whereas, 37 CFR §501.6(a)(2) allows the VA to release the Invention to
Dr. Hammond, under certain conditions;


 


2





















 


Whereas, Dr. Hammond, also an employee of The Regents, is under
obligation to assign to The Regents the rights in the Invention that were
released to him by the VA;


 


Whereas, Licensee is a “small entity” as defined in 37 CFR Section 1.9
and a “small-business concern” defined at 15 U.S.C. §632;


 


Whereas, both parties recognize that royalties due under this Agreement
will be paid on issued patents and pending patent applications that are being
prosecuted diligently and in good faith;


 


Whereas, Licensee requested an exclusive license to the Patent Rights
from The Regents; and


 


Whereas, The
Regents wish to grant an exclusive license to the Patent Rights to Licensee so
that products and other benefits derived from the Invention can be enjoyed by
the general public.


 










The parties agree as follows:


 


3





















 


1.  Definitions


 


As used in this Agreement, the following terms will have the meaning
set forth below:


 


1.1        “Patent Rights” means all U.S. patents and
patent applications and foreign patents and patent applications assigned to The
Regents, and in the case of foreign patents and patent applications those
requested under Paragraph 14.4 herein, including any reissues, extensions,
substitutions, continuations, divisions, and continuations-in-part applications
(only to the extent, however, that claims in the continuations-in-part
applications are entitled to the priority filing date of the parent patent
application) based on and including the following:


 


1.1.1        any subject matter claimed in or described according to the
requirements of 35 USC Section 112 in U.S. Patent Application Serial Number
08/396,207, entitled “Gene Therapy for Myocardial Ischemia,” filed February 28,
1995, by Dr. H. Kirk Hammond, et al., and assigned to The Regents; and


 


1.1.2        any subject matter claimed in or described according to the
requirements of 35 USC Section 112 in U.S. Patent Application Serial Number
[ILLEGIBLE], entitled “Gene
Therapy for Myocardial Ischemia”, filed June 7, 1995, by Dr. H. Kirk Hammond,
et al., and assigned to The Regents.


 


1.2        “Patent Products” means:


 


1.2.1        any kit, composition of matter, material, or product;


 


4





















 


1.2.2        any kit, composition of matter, material, or product to be used in a
manner requiring the performance of the Patent Method; or


 


1.2.3        any kit, composition of matter, material, or product produced by the
Patent Method;


 


to the extent that the manufacture, use, or sale of such kit,
composition of matter, material, or product, in a particular country, would
fall within the scope of (1) an unexpired claim of a patent under Patent Rights
in that country or (2) a pending claim of a pending patent application that is
being prosecuted diligently and in good faith in that country, were it issued
as a claim in a patent under Patent Rights in that country in which such
application is pending.   This definition
of Patent Products also includes a service either used by Licensee or provided
by Licensee to its customers when such service requires the practice of the
Patent Method.


 


1.3        “Patent Method” means any process or method,
the use or practice of which in a country would fall within the scope of (1) an
unexpired claim of a patent under Patent Rights in that country or (2) a
pending claim of a pending application that is being prosecuted diligently and
in good faith in that country, were it issued as a claim in a patent under
Patent Rights in that country in which such application is pending.


 


1.4        “Net Sales” means the gross invoice prices
from the sale of Patent Products by Licensee, an Affiliate, a Joint Venture, or
a sublicensee


 


5





















 


to
independent third parties for cash or other forms of consideration in
accordance with Generally Accepted Accounting Principles limited to the
following deductions (if not already deducted from the gross invoice price and
at rates customary within the industry): 
(a) allowances (actually paid and limited to rejections, returns, and
prompt payment and volume discounts
granted to customers of Patent Products, whether in cash or Patent Products in
lieu of cash); (b) freight, transport packing, insurance charges associated
with transportation; and (c) taxes, tariff, or import/export duties based on
sales when included in gross sales, but not value-added taxes or taxes assessed
on income derived from such sales.


 


1.5        “Affiliate(s)” of Licensee means any entity
which, directly or indirectly, controls Licensee, is controlled by Licensee, or
is under common control with Licensee (“control” for these purposes being
defined as the actual, present capacity to elect a majority of the directors of
such affiliate, or if not, the capacity to elect the members that control fifty
percent (50%) of the outstanding stock or other voting rights entitled to elect
directors) provided, however, that in any country where the local law will not
permit foreign equity participation of a majority, then an “Affiliate” will
include any company in which Licensee will own or control, directly or
indirectly, the maximum percentage of such outstanding stock or voting rights
permitted by


 


6





















 


local
law.   Each reference to Licensee herein
will be meant to include its  Affiliates.


 


1.6        “Joint Venture” means any separate entity
established pursuant to an agreement between a third party and Licensee to
constitute a vehicle for commercializing patent products, in which the separate
entity manufactures, uses, purchases, sells, or acquires Patent Products from
Licensee.   Each reference to Licensee
herein will be meant to include its Joint Venture(s).


 


2.  Grant


 


2.1        Subject to the terms of this Agreement,
subject to the licenses granted to the U.S. Government as set forth in the
Recitals above, and subject to the obligations of Section 2.5 below, The
Regents hereby grants to Licensee exclusive licenses under Patent Rights to
make, use, sell, offer for sale, and import Patent Products and to practice the
Patent Method where Patent Rights exist.


 


2.2        The Regents also grants to Licensee the
exclusive right to issue sublicenses to third parties to make, use, sell, offer
for sale, and import Patent Products and to practice the Patent Method,
provided Licensee retains current exclusive rights thereto under this
Agreement.  To the extent applicable,
such sublicenses will include all of the rights of and obligations


 


7





















 


due
to The Regents (and, if applicable, the U.S. Government, including 35 USC
Sections 200-21 2 and the implementing regulations), including the payment of
royalties in Article 4, (Royalties) that are contained in this Agreement,


 


2.3        Licensee will notify The Regents of each
sublicense granted hereunder and provide The Regents with a copy of each
sublicense. Licensee will collect and pay all royalties due The Regents as set
forth in Paragraph  4.1 below (and
guarantee all such payments due from sublicensees).   Licensee will require sublicensees to
provide it with progress and royalty reports in accordance with the provisions
herein, and Licensee will collect and deliver to The Regents all such reports
due from sublicensees.


 


2.4        Upon termination of this Agreement for any
reason, The Regents, at its sole discretion, will determine whether any or all
sublicenses will be canceled or assigned to The Regents.


 


2.5        Nothing in this Agreement will be deemed to
limit the right of The Regents to publish any and all technical data resulting
from any research performed by The Regents relating to the Invention and to
make and use Patent Product(s), Patent Method(s), and associated technology
solely for educational and noncommercial research purposes.


 


8





















 


3.   License Issue Fee


 


3.1        As partial consideration for all the rights
and licenses granted to Licensee, Licensee will pay to The Regents a license
issue fee of Five Hundred and Fifty Thousand Dollars ($550,000) according to
the following schedule:


 


3.1.1        Seventy-Five Thousand Dollars ($75,000)
within thirty (30) days after the execution of this Agreement by both parties;


 


3.1.2        Seventy-Five Thousand Dollars ($75,000) on or
before June 30, 1997;


 


3.1.3        Fifty Thousand Dollars ($50,000) on or before
December 31, 1998;


 


3.1.4        One Hundred Thousand Dollars ($100,000) on orbefore June 30, 2000; and


 


3.1.5        Two Hundred and Fifty Thousand Dollars
($250,000) on or before December
31, 2001.


 


3.2        The fees set forth in Paragraph 3.1 above are
non-refundable, non-creditable, and not an advance against royalties.


 


4.   Royalties


 


4.1        As further consideration for all the rights
and licenses granted to Licensee, Licensee also will pay to The Regents an
earned royalty at the rate of two percent (2%) based on the Net Sales of Patent
Products.


 


9





















 


4.2        Paragraphs 1.1, 1.2, and 1.3 define Patent
Rights, Patent Product, and Patent Method so that royalties will be payable
only on Patent Products covered by either a pending patent application that is
being prosecuted diligently and in good faith in a relevant country or by an
issued patent in a relevant country.  
Earned royalties will accrue in each country for the duration of any
issued patent within Patent Rights in that country and wilt be payable to The
Regents when Patent Products are invoiced, or if not invoiced, when delivered
to a third party for the purpose of patient administration for purposes other
than clinical trials.   Licensee, its
Affiliates, Joint Ventures, and sublicensees will not use Patent Products or
Patent Methods for administration to patients in any business of the Licensee,
or of its Affiliates, Joint Ventures, and sublicensees without payment of
applicable royalty on Net Sales to be calculated on retail sales prices as if
the sales transaction had occurred at arm’s-length to an unrelated third party.


 


4.3        Royalties accruing to The Regents will be
paid to The Regents quarterly on or before the following dates of each calendar
year:


 


February 28 for the calendar
quarter ending December 31


 


May 31 for the calendar
quarter ending March 31


 


August 31 for the calendar
quarter ending June 30


 


November 30 for the calendar
quarter ending September 30


 


10





















 


Each such payment will be for royalties which
accrued up to the most recently completed calendar quarter of Licensee.


 


4.4        Beginning in the year 2003, Licensee will pay
to The Regents a minimum annual royalty in the amounts and at the times set
forth below:


 


	
  2003

  	
  -

  	
   

  	
  $

  	
  100,000

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  2004

  	
  -

  	
   

  	
  $

  	
  250,000

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  2005

  	
  -

  	
   

  	
  $

  	
  400,000

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  2006

  	
  -

  	
   

  	
  $

  	
  650,000

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  2007

  	
  -

  	
   

  	
  $

  	
  750,000

  	
   

  



 


In each succeeding calendar year after The year 2007, Licensee will pay a
minimum annual royalty of Seven Hundred and Fifty Thousand ($750,000) for the
life of this Agreement.  Each minimum
annual royalty payment must be paid to The Regents by February 28 of each year
fallowing the calendar year in which royalties accrued.   Royalties paid during the prior calendar
year will be credited against the minimal annual royalty payment due and owing
for the prior calendar year.


 


4.5        All monies due The Regents will be payable in
United States funds collectible at par in San Francisco, California.  When Patent Products are sold for monies
other than United States dollars, the earned royalties will first be determined
in the foreign currency of the country in which such Patent Products were sold
and then converted into equivalent United States


 


11





















 


funds.  The exchange rate will be that rate quoted in
the Wall Street Journal on the last business day of the reporting period.


 


4.6        Earned royalties on sales of Patent Products
occurring in any country outside the United States will not be reduced by any
taxes, fees, or other charges imposed by the government of such country except
those taxes, fees, and charges allowed under the provisions of Paragraph 1.4
(Net Sales).   Licensee will be
responsible for all bank transfer charges.


 


4.7        Notwithstanding the provisions of
Article 26. (Force Majeure), if at any time legal restrictions prevent
prompt remittance of part or all royalties owed to The Regents by Licensee with
respect to any country where a Patent Product is sold or distributed, Licensee
will convert the amount owed to The Regents into United States funds and will
pay The Regents directly from another source of funds for the amount impounded.


 


4.8        In the event that any patent or any claim
thereof included within the Patent Rights is held invalid or unenforceable in a
final decision by a court of competent jurisdiction and last resort and from
which no appeal has or can be taken, all obligation to pay royalties based on
such patent or claim or any claim patentably indistinct therefrom will cease as
of the date of such final decision.  
Licensee will not, however, be relieved from paying any royalties that
accrued before such decision or that are based on another patent or claim that
has not expired or that is not involved in such decision.


 


12





















 


4.9        No royalties will be collected or paid
hereunder to The Ragents on Patent Products sold to the account of the U.S.
Government.  Licensee and its sublicensee
will reduce the amount charged for Patent Products distributed to the United
Stares Government by an amount equal to the royalty for such Patent Products
otherwise due The Regents as provided herein.


 


5.   Due Diligence


 


5.1        Licensee, upon execution of this Agreement,
will diligently proceed with the development, manufacture and sale of Patent
Products.  In this regard, The Regents
acknowledges that the technology covered by this Agreement has only recently
been invented and that substantial additional effort, expense and time, as well
as regulatory approval, will be required before manufacture and sales of any
Patent Products will be possible. Meeting the requirements of Section 5.3
below shall be deemed to satisfy the due diligence requirements of this
Article 5.


 


5.2        Licensee will be entitled to exercise prudent
and reasonable business judgment in the manner in which it meets its due
diligence obligations hereunder, including under Section 5.3 below.   In no case, however, will Licensee be wholly
relieved of its obligations to meet
each of the due diligence provisions of Paragraph 5.3 below.


 


13





















 


5.3        If Licensee is unable to
perform any of the following:


 


5.3.1        begin Phase I Clinical Trials in the United
States for Patent Products on or before June 30, 1997; and


 


5.3.2        enter pivotal clinical trials (a combination
of Phase II and Phase III Clinical Trials) in the United States for said Patent
Products on or before December 31, 1998; and


 


5.3.3        file far marketing approval in the United
States for said Patent Product on or before December 31, 2001; and


 


5.3.4        market Patent Products in the United States
within six (6) months after receiving marketing approval of such Patent
Products from the U.S. Food and Drug Administration; and


 


5.3.5        diligently and earnestly fill the market
demand for Patent Products following commencement of marketing at any time
during the exclusive period of this Agreement;


 


then The Regents will have the right and option to
terminate this Agreement or reduce the exclusive licenses granted to Licensee
to non-exclusive licenses in accordance with Paragraph 5.4 hereof.   The exercise of this right and option by The Regents supersedes the rights
granted in Article 2. (Grant).


 


5.4        To exercise either the right to terminate
this Agreement or reduce the exclusive licenses granted to Licensee to
non-exclusive licenses for lack of diligence required in this Article 5.
(Due Diligence), The Regents will give Licensee written notice of the
deficiency.   Licensee thereafter has


 


14





















 


60 (sixty) days to cure the deficiency. Licensee shall be entitled to a
one-time extension of each of the dates set forth in Subparagraphs 5.3.1
through 5.3.4 (which have not been met) by one (1) additional year to cure
the deficiency upon payment of One Hundred Thousand Dollars ($100,000) to The
Regents, provided that such payment is received by The Regents within sixty
(60) days of receipt of written notice by The Regents of Licensee’s
deficiency.  The One Hundred Thousand
Dollar ($100,000) payment has the effect of extending the subject date and all
subsequent dates by one (1) year.  
If The Regents has not received the One Hundred Thousand Dollar
($100,000) payment by the end of the sixty (60)-day period, or written tangible
evidence satisfactory to The Regents that the deficiency has been cured by the
end of the sixty (60)-day period, then The Regents may, at its option,
terminate this Agreement or reduce the exclusive licenses granted to Licensee
to non-exclusive licenses by giving written notice to Licensee. These notices
will be subject to Article 18, (Notices).


 


6. Progress and Royalty
Reports


 


6.1        Beginning February 28, 1996, and
semi-annually thereafter, Licensee will submit to The Regents a progress report
covering activities by Licensee related to the development, including clinical
trials and testing, of all Patent Products and the obtaining of the
governmental approvals necessary


 


15





















 


for marketing.  These progress
reports will be provided to The Regents to cover the progress of the research
and development of the Patent Products until their first commercial sale in the
United States.


 


6.2        The progress reports submitted under
Paragraph 6.1 will include, but
not be limited to, the following topics so that The Regents may be able to
determine the progress of the development of Patent Products:


 


•              summary of work completed;


 


•              summary of work in progress;


 


•              current schedule of anticipated events
or milestones specified in Paragraph 5.3 and the datas when said milestones
have been met or will be met, as of the time of the report;


 


•              market introduction date of Patent Products;
and


 


•              activities of sublicensees, if any.


 


6.3        Licensee will also report to The Regents in
its immediately subsequent progress and royalty report the date of first
commercial sale of a Patent Product(s) in each country where the Licensee has
sought marketing approval.


 


6.4        After the first commercial sale of a Patent
Product, Licensee will provide The Regents with quarterly royalty reports to
The Regents on or before each February 28, May 31, August 31,
and November 30 of each year.   Each
such royalty report will cover the most recently completed


 


16





















 


calendar quarter of Licensee (October through December, January through
March, April through June, and July through September) and will show:


 


6.4.1        the gross sales and Net Sales of Patent
Products sold by Licensee and reported to Licensee as sold by its sublicensees
during the most recently completed calendar quarter;


 


6.4.2        the number of Patent Products sold or
distributed by Licensee and reported to Licenses as sold or distributed by its
sublicensees;


 


6.4.3        the royalties, in U.S. dollars, payable
hereunder with respect to Net Sales; and


 


6.4.4        the exchange rates used, if any.


 


6.5        If no sales of Patent Products have been made
during any reporting period after the first commercial sale of a Patent
Product, then a statement to this effect is required.


 


7.   Books and Records


 


7.1        Licensee will keep books and records
accurately showing all Patent Products manufactured, used, and/or sold under
the terms of this Agreement.   Such books and records will be preserved for
at least four (4) years after the date of the royalty payment to which
they pertain and will be open to inspection by representatives or agents of The
Regents at reasonable times to determine the accuracy of the books and records
and to determine compliance by Licenses with the terms of this Agreement.


 


17





















 


7.2        The fees and expenses of representatives of
The Regents performing such an examination will be borne by The Regents.   However, if an error in royalties of more
than five percent (5%) of the total royalties due for any year is discovered,
then the fees and expenses of these representatives will be borne by Licensee.


 


8.   Life of the Agreement


 


8.1        Unless otherwise terminated by operation of
law or by acts of the parties in accordance with the terms of this Agreement,
this Agreement will be in force from the effective date recited on page one
and will remain in effect for the life of the last-to-expire patent licensed
under this Agreement, or until the last patent application licensed under this
Agreement is abandoned.


 


8.2        Any termination of this Agreement will not
affect the rights and obligations set forth in the following Articles:


 


	
  Article

  	
   

  	
  3

  	
   

  	
  License
  Issue Fee

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Article

  	
   

  	
  7

  	
   

  	
  Books
  and Records

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Article

  	
   

  	
  11

  	
   

  	
  Disposition
  of Patent Products on Hand Upon Termination

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Article

  	
   

  	
  12

  	
   

  	
  Use
  of Names and Trademarks

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Paragraph

  	
   

  	
  14.6

  	
   

  	
  Patent
  Prosecution and Maintenance

  



 


18





















 


	
  Article

  	
   

  	
  17

  	
   

  	
  Indemnification

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Article

  	
   

  	
  22

  	
   

  	
  Failure
  to Perform

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Article

  	
   

  	
  27

  	
   

  	
  Confidentiality

  



 


9.  Termination by The Regents


 


9.1        If Licensee should violate or fail to perform
any material term or covenant of this Agreement, then The Regents may give
written notice of such default (“Notice of Default”) to Licensee.   If Licensee should fail to repair such
default within sixty (60) days after the date of such notice takes effect, The
Regents will have the right to terminate this Agreement and the licenses herein
by a second written notice (“Notice of Termination”) to Licensee.   If a Notice of Termination is sent to
Licensee, this Agreement will automatically terminate on the date such notice
takes effect.   Such termination will not
relieve Licensee of its obligation to pay any royalty or license fees owing at
the time of such termination and will not impair any accrued right of The
Regents.  These notices will be subject
to Article 18. (Notices).


 


19





















 


10.   Termination by Licensee


 


10.1      Licensee will have the right at any time to
terminate this Agreement in whole or as to any portion of Patent Rights by
giving notice in writing to The Regents.  Such Notice of Termination will be subject to Article 18.
(Notices) and termination of this Agreement will be effective sixty (60) days
after the effective date thereof.


 


10.2      Any
termination pursuant to the above paragraph will not relieve The Regents or
Licensee of any obligation or liability accrued hereunder prior to such
termination or rescind anything done by The Regents or Licenses or any payments
made to The Regents hereunder prior to the time such termination becomes
effective, and such termination will not affect in any manner any rights of The
Regents or Licensee arising under this Agreement prior to such termination.


 


11.   Disposition of Patent Products on Hand Upon
Termination


 


11.1      Upon termination of this Agreement, Licensee
will have the privilege of disposing of all previously made or partially made
Patent Products, but no more, within a period of one hundred twenty (120) days,
provided, however, that the sale of such Patent Products will be subject to the
terms of this Agreement including, but not limited to the payment of fees and
reimbursement for patent costs and the payment of royalties based on


 


20





















 


the Net Sales of Patent Products at the rates and at the times provided
herein and the rendering of reports in connection therewith.


 


12.   Use of Names and Trademarks


 


12.1      Nothing contained in this Agreement will be
construed as conferring any right to use in advertising, publicity, or other
promotional activities any name, trade name, trademark, or other designation of
either party hereto by the other (including contraction, abbreviation or simulation
of any of the foregoing).   Unless
required by law, the use by Licensee of the name “The Regents of the University
of California” or the name of any campus of the University of California for
use in advertising, publicity, or other promotional activities is expressly
prohibited.


 


12.2      It is understood that The Regents will be
free to release to the inventors and senior administrative officials employed
by The Regents the terms of this Agreement upon their request.   If such release is made, The Regents will
request that such terms will be kept in confidence in accordance with the
provisions of Article 27. (Confidentiality) and not be disclosed to
others.   It is further understood that
should a third party inquire whether a license to Patent Rights is available,
The Regents may disclose the existence of this Agreement and the Extent of the
grant in Article 2. (Grant) to such third party, but will not disclose the
name of Licensee, except where The


 


21





















 


Regents is
required to release such information under either the California Public Records
Act or other applicable law.


 


13.  Limited
Warranty


 


13.1      The Regents warrants to Licensee that it has
the lawful right to grant this license, and that it has not granted any rights
or licenses to Patent Rights, other than to the U.S. Government, in derogation
of this Agreement.


 


13.2      This license and the associated Invention are
provided WITHOUT WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR
PURPOSE OR ANY OTHER WARRANTY, EXPRESSED OR IMPLIED.   THE REGENTS MAKES NO REPRESENTATION OR
WARRANTY THAT THE INVENTION, PATENT PRODUCTS, OR PATENT METHOD WILL NOT
INFRINGE ANY PATENT OR OTHER PROPRIETARY RIGHT.


 


13.3      IN NO EVENT WILL THE REGENTS BE LIABLE FOR
ANY INCIDENTAL, SPECIAL OR CONSEQUENTIAL DAMAGES RESULTING FROM EXERCISE OF
THIS LICENSE OR THE USE OF THE INVENTION, PATENT METHOD, OR PATENT PRODUCTS.


 


13.4      Nothing in this Agreement will be construed
as:


 


13.4.1      a
warranty or representation by The Regents as to the validity, enforceability,
or scope of any Patent Rights; or


 


22





















 


13.4.2      a warranty or representation that anything
made, used, sold or otherwise disposed of under any license granted in this
Agreement is or will be free from infringement of patents of third parties; or


 


13.4.3      an obligation to bring or prosecute actions
or suits against third parties for patent infringement except as provided in
Article 16. (Patent Infringement); or


 


13.4.4      conferring by implication, estoppel, or
otherwise any license or rights under any patents of The Regents other than
Patent Rights as defined herein, regardless of whether such patents are
dominant or subordinate to Patent Rights; or


 


13.4.5      an obligation to furnish any know-how not
provided in Patent Rights.


 


14.   Patent Prosecution and Maintenance


 


14.1      The Regents will diligently prosecute and
maintain the United States and foreign patents comprising Patent Rights using
counsel of its choice.   The Regents will
promptly provide Licensee with copies of all relevant documentation so that
Licensee may be currently and promptly informed and apprised of the continuing
prosecution, and may comment upon such documentation sufficiently in advance of
any initial deadline for filing a response, provided, however, that if Licensee
has not commented upon such documentation prior to the initial deadline for filing a
response with the relevant government patent office or The Regents must act to
preserve Patent Rights, The Regents will be free to respond appropriately


 


23





















 


without consideration of comments by Licensee, if any.  Both parties hereto will keep this
documentation in confidence in accordance with the provisions of Article 27.
(Confidentiality) herein.  The Regents’
counsel will take instructions only from The Regents.


 


14.2      The Regents will use all reasonable efforts
to amend any patent application to include claims requested by Licensee and
required to protect the Patent Products contemplated to be sold or Patent
Method to be practiced under this Agreement.


 


14.3      The Regents and Licensee will cooperate in
applying for an extension of the term of any patent included within Patent
Rights, if appropriate, under the Drug Price Competition and Patent Term
Restoration Act of 1 984, Licensee will prepare all such documents, and The
Regents will execute such documents and will take such additional action as
Licensee may reasonably request in connection therewith.


 


14.4      The Regents will, at the request of Licensee,
file, prosecute, and maintain patent applications and patents covered by Patent
Rights in foreign countries if available. 
Licensee must notify The Regents within nine (9) months of the
filing of the corresponding United States application of its decision to
request The Regents to file foreign counterpart patent applications.  This notice concerning foreign filing must be
in writing and must identify the countries desired.   The absence of such a notice from


 


24





















 


Licensee to The Regents within the nine (9)-month period will be
considered an election by Licensee not to request The Regents to secure foreign
patent rights an behalf of Licensee.  The
Regents wilt have the right to file patent applications at its own expense in
any country Licensee has not included in its list of desired countries, and
such applications and resultant patents, if any, will not be included in the
licenses granted under this Agreement unless Licensee agrees in writing to pay
all costs associated with any such patent application(s) and provided the
rights of said patent application(s) are available at the time Licensee agrees
to pay the associated costs.


 


14.5      All past, present and future costs of
preparing, filing, prosecuting and maintaining all United States and foreign
patent applications and all costs and fees relating to the preparation and
filing of patents covered by Patent Rights in Paragraph 1.1 will be borne by
Licensee.   This includes all patent preparation
and prosecution costs incurred by The Regents prior to the execution of this
Agreement.  Such costs will be due upon
execution of this Agreement and will be payable at the time that the license
issue fee is payable.   The costs of all
interferences and oppositions will be considered prosecution expenses and also
will be borne by Licensee.   Licensee
will reimburse The Regents for all costs and charges within thirty (30) days
following receipt of an itemized invoice from The Regents for same.


 


25





















 


14.6      The obligation of Licenses to underwrite and
to pay patent preparation, filing, prosecution, maintenance, and related costs
will continue for such costs as may be incurred during the three (3)-month period
after receipt by either party of a Notice of Termination for ail non-cancelable
obligations made prior to the receipt of said Notice of Termination,  Licensee will reimburse The Regents for all
patent costs incurred during the term of the Agreement and for three (3) months
thereafter whether or not invoices for such costs are received during the three
(3)-month period after receipt of a Notice of Termination.   Licensee may with respect to any particular
patent application or patent terminate its obligations with the patent
application or patent in any or ail designated countries upon three months
written notice to The Regents.  The
Regents may continue prosecution and/or maintenance of such application(s) or
patent(s) at its sole discretion and expense, provided, however, that Licensee
will have no further right or licenses thereunder.


 


14.7      Licensee will have a continuing
responsibility to keep The Regents informed of its large/small entity status
(as defined by the United States Patent and Trademark Office) of itself and its
sublicensees.


 


26





















 


15.  Patent
Marking


 


15.1   Licensee will mark all Patent Products made,
used or sold under the terms of this Agreement, or their containers, in
accordance with the applicable patent marking laws.


 


16.  Patent
Infringement.


 


16.1   In the event that Licensee learns of the
substantial infringement of any patent licensed under this Agreement, Licensee
will call the attention of The Regents thereto in writing and will provide The
Regents with reasonable evidence of such infringement.  Both parties to this Agreement acknowledge
that during the period and in a jurisdiction where Licensee has exclusive
rights under this Agreement, neither will notify a third party of the
infringement of any of Patent Rights without first obtaining consent of the
other party, which consent will not be unreasonably withheld.   Both parties will use their best efforts in
cooperation with each other to terminate such infringement without litigation.


 


1 6.2  Licensee may request that The Regents take
legal action against the infringement of Patent Rights.  Such request must be made in writing and must
include reasonable evidence of such infringement and damages to Licensee.   If the infringing activity has not been
abated within ninety (90)


 


27





















 


days
following the effective date of such request, The Regents will have the right
to elect to:


 


16.2.1      commence suit on its own account; or


 


16.2.2      refuse to participate in such suit


 


and
The Regents will give notice of its election in writing to Licensee by the end
of the one hundredth (100th) day after receiving notice of such request from
Licensee.  Licensee may thereafter bring
suit for patent infringement if and only if The Regents elects not to commence
suit and if the infringement occurred during the period and in a jurisdiction
where Licensee had exclusive rights under this Agreement.  However, in the event Licensee elects to
bring suit in accordance with this paragraph, The Regents may thereafter join
such suit at its own expense, but the Licensee will control the lawsuit.


 


16.3   Such
legal action as is decided upon will be at the expense of the party on account
of whom suit is brought and all recoveries recovered thereby will belong to
such party, provided, however, that legal action brought jointly by The Regents
and Licensee and participated in by both will be at the joint expense of the
parties and all recoveries will be allocated in the following order:  a) to each party reimbursement in equal
amounts of the attorney’s costs, fees, and other related expenses to the extent
each party paid for such costs, fees, and expenses until all such costs, fees,
and


 


28





















 


expenses
are consumed for each party; and b) any remaining amount shared jointly by them
in proportion to the share of expenses paid by each party.


 


16.4   Each party will cooperate with the other in
litigation proceedings instituted hereunder but at the expense of the party on
account of whom suit is brought.   Such
litigation will be controlled by the party bringing the suit, provided,
however, that The Regents may be represented by counsel of its choice in any
suit brought by Licensee.


 


17.  
Indemnification


 


17.1   Licensee will (and will require its
sublicensees to) indemnify, hold harmless, and defend The Regents, its
officers, employees, and agents; the sponsors of the research that led to the
Invention; the inventors of any invention covered by Patent Rights (including
the Patent Products and Patent Method contemplated thereunder) and their
employers against any and all claims, suits, losses, damage, costs, fees, and
expenses resulting from or arising out of exercise of this license or any
sublicense.   This indemnification will
include, but will not be limited to, any product liability.


 


17.2   Licensee, at its sole cost and expense, will
insure its activities in connection with the work under this Agreement and
obtain, keep in force, and maintain insurance as follows: (or an equivalent
program of self insurance)


 


29





















 


At the initiation of
clinical trials, Comprehensive or Commercial Form General Liability
Insurance (contractual liability included) with limits as follows up to and
until Licensee enters Phase III Clinical Trials:


 


	
  (a)

  	
   

  	
  Each
  Occurrence

  	
   

  	
  $

  	
  3,000,000

  	
   

  
	
  (b)

  	
   

  	
  Products/Completed
  Operations Aggregate

  	
   

  	
  $

  	
  3,000,000

  	
   

  
	
  (c)

  	
   

  	
  Personal and
  Advertising injury

  	
   

  	
  $

  	
  3,000,000

  	
   

  
	
  (d)

  	
   

  	
  General
  Aggregate (commercial form only)

  	
   

  	
  $

  	
  3,000,000

  	
   

  



 


Comprehensive or Commercial Form General
Liability Insurance (contractual liability included) with limits as follows
after Licensee enters


 


Phase
III Clinical Trials:


 


	
  (a)

  	
   

  	
  Each Occurrence

  	
   

  	
  $

  	
  5,000,000

  	
   

  
	
  (b)

  	
   

  	
  Products/Completed
  Operations Aggregate

  	
   

  	
  $

  	
  5,000,000

  	
   

  
	
  (c)

  	
   

  	
  Personal and Advertising
  Injury

  	
   

  	
  $

  	
  5,000,000

  	
   

  
	
  (d)

  	
   

  	
  General Aggregate
  (commercial form only)

  	
   

  	
  $

  	
  5,000,000

  	
   

  



 


It should be expressly
understood, however, that the coverages and limits referred to under the above
will not in any way limit the liability of Licensee.   Licensee will furnish The Regents with
certificates of insurance evidencing compliance with all requirements.  Such certificates will:


 


(a)           Provide for thirty (30)-day advance written
notice to The Regents of any modification;


 


(b)           Indicate that The Regents has been endorsed
as an additional Insured under the coverages referred to under the above; and


 


(c)           Include a provision that the coverages will
be primary and will not participate with nor will be excess over any valid and
collectable insurance or program of self-insurance carried or maintained by The
Regents.


 


30





















 


17.3 The Regents will
immediately notify Licensee in writing of any claim or suit brought against The
Regents in respect of which The Regents intends to invoke the provisions of
this Article 17. (Indemnification). 
Licensee will keep The Regents informed as appropriate and necessary on
a current basis of its defense of any claims pursuant to this Article 17.
(Indemnification).


 


18.  Notices


 


18.1   Any notice or payment required to be given
to either party will be deemed to have been properly given and to be effective (a) on
the date of delivery if delivered in person or (b) five days after mailing
if mailed by first-class certified mail, postage paid, to the respective addresses
given below, or to another address as it may designate by written notice given
to the other party.


 


	
  In the case of Licensee:

  	
   

  	
  COLLATERAL THERAPEUTICS

  
	
   

  	
   

  	
  9360 Towne Centre Drive

  
	
   

  	
   

  	
  San Diego, CA  92121

  
	
   

  	
   

  	
  Tel:  (619) 622-4100

  
	
   

  	
   

  	
  Fax:  (619) 587-3518

  
	
   

  	
   

  	
  Attention: Jack Reich,
  Ph.D.

  



 


31





















 


	
  In the case of The
  Regents:

  	
   

  	
  THE REGENTS OF THE
  UNIVERSITY

  	
   

  	
   

  
	
   

  	
   

  	
  OF CALIFORNIA

  	
   

  	
   

  
	
   

  	
   

  	
  1320 Harbor Bay Parkway,
  Suite 150

  	
   

  	
   

  
	
   

  	
   

  	
  Alameda, California 94502

  	
   

  	
   

  
	
   

  	
   

  	
  Tel: (510) 743-6600

  	
   

  	
   

  
	
   

  	
   

  	
  Fax: (510) 748-6639

  
	
   

  	
   

  	
  Attention:

  	
   

  	
  Terence A. Feuerborn

  
	
   

  	
   

  	
   

  	
   

  	
  Executive Director

  
	
   

  	
   

  	
   

  	
   

  	
  Research Administration
  and

  
	
   

  	
   

  	
   

  	
   

  	
  Technology Transfer

  
	
   

  	
   

  	
  Referring to: U.C. Case No.
  94-161-1,-3

  
							



 


19.  Assignability


 


19.1   This Agreement is binding upon and will
inure to the benefit of The Regents, its successors and assigns, but will be
personal to Licensee and assignable by Licensee only with the written consent
of The Regents, which consent shall not be unreasonably withheld.


 


20.   Late
Payments


 


20.1   In the event royalty payments or fees or
patent prosecution costs are not received by The Regents when due, Licensee
will pay to The Regents interest charges at a rate of ten percent (10%) simple
interest per annum. Such interest will be calculated from the date payment was
due until actually received by The Regents. 
Acceptance by The Regents of any late payment interest from Licensee
under this Paragraph 20 will in no way affect the provision of Article 21.
(Waiver) herein.


 


32





















 


21.   Waiver


 


21.1  It is agreed that no waiver by either party
hereto of any breach or default of any of the covenants or agreements herein
set forth will be deemed a waiver as
to any subsequent and/or similar breach or default.


 


22.   Failure to Perform


 


22.1   In the event of a failure of performance due
under the terms of this Agreement and if it becomes necessary for either party
to undertake legal action against the other on account thereof, then the
prevailing party will be entitled to reasonable attorney’s fees in addition to
casts and necessary disbursements.


 


23.   Governing Laws


 


23.1   THIS AGREEMENT WILL BE INTERPRETED AND
CONSTRUED IN ACCORDANCE WITH THE LAWS OF THE STATE OF CALIFORNIA, excluding any
choice of law rules that would direct the application of the laws of
another jurisdiction, but the scope and validity of any patent or patent
application will be governed by the applicable laws of the country of such
patent or patent application.


 


33





















 


24.  
Government Approval or Registration


 


24.1  If this Agreement or any associated
transaction is required by the law of any nation to be either approved or
registered with any governmental agency, Licensee will assume all legal obligations
to do so.   Licensee will notify The
Regents if it becomes aware that this Agreement is subject to a United States
or foreign government reporting or approval requirement. Licensee will make all
necessary filings and pay all costs including fees, penalties, and all other
out-of-pocket costs associated with such reporting or approval process.


 


25.   Export
Control Laws


 


25.1   Licensee will observe all applicable United
States and foreign laws with respect to the transfer of Patent Products and
related technical data to foreign countries, including, without limitation, the
International Traffic in Arms Regulations (1TAR) and the Export Administration
Regulations.


 


26.   Force Majeure


 


26.1  The parties to this Agreement will be excused
from any performance required hereunder if such performance is rendered
impossible or unfeasible due to any acts of God, catastrophes, or other major
events


 


34





















 


beyond
their reasonable control, including, without limitation, war, riot, and
insurrection; laws, proclamations, edicts, ordinances, or regulations; strikes,
lock-outs, or other serious labor disputes; and floods, fires, explosions, or
other natural disasters.  However, any
party to this Agreement will have the right to terminate this Agreement upon
thirty (30) days’ prior written notice if either party is unable to fulfill its
obligations under this Agreement due to any of the causes mentioned above and
such inability continues for a period of one year.   Notices will be subject to Article 18.
(Notices).


 


27.  
Confidentiality


 


27.1   Licensee and The Regents respectively will
treat and maintain the proprietary business, patent prosecution, software,
engineering drawings, process and technical information, and other proprietary
information of the other party (“Proprietary Information”) in confidence using
at least the same degree of care as that party uses to protect its own
proprietary information of a like nature for a period from the date of
disclosure until five (5) years after the date of termination of this
Agreement.


 


27.2   Proprietary Information will be labeled or
marked confidential or as otherwise similarly appropriate by the disclosing
party, or if the Proprietary Information is orally disclosed, it will be reduced
to writing or some other physically tangible form, marked and labeled as set
forth above


 


35





















 


by
the disclosing party and delivered to the receiving party within thirty (30)
days after the oral disclosure as a record of the disclosure and the
confidential nature thereof. 
Notwithstanding the foregoing, Licensee and The Regents may use and
disclose Proprietary Information to its employees, agents, consultants, and
contractors having a need to know the Proprietary Information and, in the case
of Licensee, its sublicensees, provided that any such parties are bound by a
like duty of confidentiality.


 


27.3  Nothing contained herein will in any way
restrict or impair the right of Licensee or The Regents to use, disclose, or
otherwise deal with any Proprietary Information:


 


27.3.1      that recipient can demonstrate by written
records was previously known to it;


 


27.3.2      that is now, or becomes in the future, public
knowledge other than through acts or omissions of recipient;


 


27.3.3      that is lawfully obtained without
restrictions by recipient from sources independent of the disclosing party;


 


27.3.4      that is required to be disclosed to a
governmental entity or agency in connection with seeking any governmental or
regulatory approval, or pursuant to the lawful requirement or request of a
governmental entity or agency;


 


27.3.5      that is furnished to a third party by the
recipient with a need to know and with similar confidentiality restrictions
imposed on such third party, as evidenced in writing, or


 


36





















 


27.3.6      that The Regents is required to disclose
pursuant to the California Public Records Act or other applicable law.


 


27.4   Upon termination of this Agreement, Licensee
and The Regents will destroy or return to the disclosing party proprietary
information received from the other in its possession within fifteen (15) days
following the effective date of termination. 
Licensee and The Regents will provide each other, within thirty (30)
days following termination, with a written notice that Proprietary Information
has been returned or destroyed.  Each
party may, however, retain one copy of Proprietary Information for archival
purposes in nonworking files.


 


28.  
Miscellaneous


 


28.1   The headings of the several sections are
inserted for convenience of reference only and are not intended to be a part of
or to affect the meaning or interpretation of this Agreement.


 


28.2   The licenses and any sublicenses granted
hereunder will be subject to any legal obligations to the U.S. Government
including those set forth in 35 U.S.C. 200-212 and applicable governmental
implementing regulations.   Because this
Agreement grants the exclusive right to use or sell the Patent Products in the
United States, Licensee acknowledges that


 


37





















 


Patent
Products will be manufactured substantially in the United States as required
under 35 USC Section 204.


 


28.3   The manufacture of Patent Products will be
in accordance with any applicable government importation laws and regulations
of a particular country on Patent Products made outside the particular country
in which such Patent Products are to be used or sold.


 


28.4  Licensee will obtain all necessary governmental
approvals in each country where it intends to sell or manufacture and use
Patent Products or permit others to manufacture, use, or sell Patent Products.


 


28.5  This Agreement will not be binding upon the
parties until it has been signed below on behalf of each party, in which event,
it will be effective as of the date recited on page one.


 


28.6  No amendment or modification hereof will be
valid or binding upon the parties unless made in writing and signed on behalf
of each party.


 


28.7  This Agreement embodies the entire
understanding of the parties and will supersede all previous communications,
representations or understandings, either oral or written, between the parties
relating to the subject matter hereof.  The
Letter of intent specified in the Recitals in this Agreement is hereby
terminated.


 


28.8  In case any of the provisions contained in
this Agreement are held to be invalid, illegal, or unenforceable in any
respect, such invalidity,


 


38





















 


illegality,
or unenforceability will not affect any other provisions hereof, but this
Agreement will be construed as if such invalid or illegal or unenforceable
provisions had never been contained herein.


 


The Regents and Licensee
execute this Agreement in duplicate originals by their respective, authorized
officers on the date indicated.


 


 


	
  Collateral Therapeutics:

  	
  The Regents of the University 

  of California:

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  By

  	
  /s/ Jack W.
  Reich Ph.D.

  	
   

  	
  By

  	
  /s/ Terence
  A. Feuerborn

  	
   

  	
   

  
	
   

  	
  (Signature)

  	
   

  	
   

  	
  (Signature)

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Name

  	
    JACK
  W. REICH, Ph.D.

  	
   

  	
  Name 

  	
  Terence A. Feuerborn

  	
   

  
	
   

  	
  (Please Print)

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Title

  	
    PRESIDENT AND C.E.O.

  	
   

  	
  Title

  	
  Executive Director

  	
   

  
	
   

  	
   

  	
   

  	
  Research Administration
  and

  	
   

  
	
   

  	
   

  	
   

  	
  Technology Transfer

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Date

  	
      Sept.
  27, 1995

  	
   

  	
  Date

  	
       9-28-95

  	
   

  	
   

  
										



 


 


	
  Approval as to legal form:

  	
  /s/ ILLEGIBLE

  	
   

  	
  9//24/95

  	
   

  
	
   

  	
  [SEAL]

  	
   

  	
  Date

  	
   

  
	
   

  	
   

  	
   

  	
   

  



 


39





















 


1st Amendment


to the Exclusive License Agreement


 


between


 


The Regents of the University of California


 


and


 


Collateral Therapeutics, Inc.


 


for


 


“Angiogenesis Gene Therapy”


 


UC Case No. 94-161-1, -3


 


 





















 


1st Amendment to the Exclusive License Agreement


for “Angiogenesis Gene Therapy”


 


This Amendment is made and
is effective this 19th day of Sept.,1996, by and between The Regents
of the University of California (“The Regents”), a California corporation,
having its statewide administrative offices at 300 Lakeside Drive, 22nd Floor,
Oakland, California 94612-3550, and Collateral Therapeutics, Inc. (“Licensee”),
a California corporation, have a principal place of business at 9360 Towne
Centre Drive, San Diego, California 92121.


 


RECITALS


 


WHEREAS, Licensee and The
Regents entered into a license agreement entitled “Exclusive License Agreement
for Angiogenesis Gene Therapy,” effective on September 27, 1995, having
U.C. Agreement Control Number 96-04-0203 (“License Agreement”), and covering
licensure to Licensee by The Regents of rights in certain inventions developed
by Dr. H. Kirk Hammond, et al. (“Inventor”) at the University of
California, San Diego (“UCSD”) and claimed in U.S. Patent Application Serial
Nos. 08/396,207 and 08/485,472;


 


	
   

  	
  U.C. AGREEMENT

  
	
   

  	
  CONTROL NUMBER

  
	
   

  	
  96-04-0203 B

  



 


1





















 


Whereas, in accordance with
Paragraph 2.3 of the License Agreement, Licensee has notified The Regents of
its intent to enter into a sublicense agreement with Schering
Aktiengesellschaft (“Schering AG”);


 


Whereas, Schering AG will
use its resources to further develop the Patent Products so that the technology
licensed under the sublicense agreement may be developed, utilized, and
marketed and the products therefrom and other benefits may be enjoyed by the
general public;


 


Whereas, Licensee desires to
amend the License Agreement to reflect that, upon termination of the License
Agreement, any sublicenses to Schering AG will be assigned to The Regents;


 


Whereas, Licensee and The
Regents desire to amend the License Agreement to redefine Patent Rights to
exclude two continuing patent applications entitled “Gene Therapy for
Myocardial Ischemia” filed in the names of Dr. Wolfgang Dillmann, Dr. Ruben
Mestril, and Dr. Frank Giordano and any continuing patent applications
thereof;


 


Whereas, Licensee and The
Regents desire to amend the License Agreement to reflect the above changes;


 


Now, Therefore, in
consideration of the foregoing and the mutual promises and covenants contained
herein, the parties hereto agree as follows:


 


2





























 


1.             Paragraph 1.1 (Definitions) of the License Agreement
shall be replaced in its entirety with the following Paragraphs 1.1a and 1.1b: 


 


1.1a   “Patent
Rights” means all U.S. patents and patent applications and foreign patents and
patent applications assigned to The Regents, and in the case of foreign patents
and patent applications those requested under Paragraph 14.4 herein, including
any reissues, extensions, substitutions, continuations, divisions, and
continuations-in-part applications (only to the extent, however, that claims in
the continuations-in-part applications are entitled to the priority filing date
of the parent patent application) based on and including the following:


 


1.1.1.       any subject matter claimed in or described
according to the requirements of 35 USC Section 112 in U.S. Patent Application
Serial Number 08/396,207, entitled “Gene Therapy for Myocardial Ischemia,”
filed February 28, 1995, by Dr. H. Kirk Hammond, et al., and assigned
to The Regents; and


 


1.1.2.       any subject matter claimed in or described
according to the requirements of 35 USC Section 112 in U.S. Patent
Application Serial Number 08/485,472, entitled “Gene Therapy for Myocardial
Ischemia,” filed June 7, 1995, by Dr. H. Kirk Hammond, Dr. Wolfgang


 


3





















 


Dillmann, and Dr. Frank Giordano, and assigned to The Regents.


 


1.1b         The subject matter relating to the use of
heat-shock proteins described and claimed in U.S. Patent Application Serial
Number 08/481,122 entitled “Gene Therapy for Myocardial Ischemia,” filed June 7,
1995, by Dr. Wolfgang Dillmann, Dr. Ruben Mestril, and Dr. Frank
Giordano and U.S. Patent Application Serial Number 08/660,387 entitled “Gene
Therapy for Myocardial Ischemia,” filed June 7, 1996, by Dr. Wolfgang
Dillmann, Dr. Ruben Mestril, and Dr. Frank Giordano and any
continuing applications thereof are expressly excluded from this
Agreement.   The excluded patent
applications specified in this Paragraph 1.1b do not and will not claim any
angiogenesis gene therapy or gene therapy delivery subject matter that is described
and/or claimed in any of the patent applications referred to in Paragraph 1.1a
above.


 


2.             Paragraph 2.4 (Grant) of the License
Agreement shall be replaced in its entirety with the following:


 


2.4           Except as provided below, upon termination of
this Agreement for any reason, The Regents, at its sole discretion, will
determine whether any or all sublicenses will be canceled or assigned to The
Regents.   Notwithstanding the foregoing,
any sublicenses to


 


4





















 


Schering AG will be assigned to The Regents.   The Regents will not be bound by any duties
or obligations contained in any sublicense that extend beyond the duties and
obligations of The Regents in this Agreement.


 


In Witness Whereof, both The
Regents and Licensee have executed this Amendments, in duplicate originals, by
their respective officers hereunto duly authorized, on the day and year
hereinafter written.


 


 


	
  COLLATERAL THERAPEUTICS,
  INC.

  	
  THE REGENTS OF THE UNIVERSITY

  OF CALIFORNIA

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  By

  	
  /s/ Jack W.
  Reich, Ph.D.

  	
   

  	
  By

  	
  /s/ Candace
  L. Voelker

  	
   

  	
   

  
	
   

  	
  (Signature)

  	
   

  	
   

  	
  (Signature)

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Name

  	
  JACK W.
  REICH, Ph.D.

  	
   

  	
  Name

  	
  Candace L. Voelker

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Title

  	
    PRESIDENT & C.E.O.

  	
   

  	
  Title

  	
  Associate Director

  	
   

  
	
   

  	
   

  	
   

  	
  Office of Technology
  Transfer

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Date

  	
    Sept. 19, 1996

  	
   

  	
  Date

  	
  9/19/96

  	
   

  	
   

  
										



 


 


	
  Approval as to legal form:

  	
  /s/ ILLEGIBLE

  	
   

  	
  9-19-96

  
	
   

  	
  [SEAL]

  	
   

  	
  Date

  
	
   

  	
   

  	
   

  	
   

  



 


5





















 


2nd Amendment


to the Exclusive License Agreement


 


between


 


The Regents of the University of California


 


and


 


Collateral Therapeutics, Inc.


 


for


 


“Angiogenesis Gene Therapy’


 


UC Case No. 94-161-1,-3


 


 


	
   

  	
  U.C. AGREEMENT

  
	
   

  	
  CONTROL NUMBER

  
	
   

  	
  96-04-0203C

  



 





















 


2nd Amendment to the Exclusive License Agreement 

for “Angiogenesis Gene Therapy”


 


This amendment (‘“Amendment’”)
is effective this 30th day of June, 1997, by and between The Regents
of the University of California (“The Regents”), a California corporation,
having its statewide administrative offices at 300 Lakeside Drive, 22nd Floor,
Oakland, California 94612-3550, and Collateral Therapeutics, Inc. (“Licensee”),
a California corporation, having a principal place of business at 9360 Towne
Centre Drive, San Diego, California 92121.


 


RECITALS


 


WHEREAS, Licensee and The
Regents entered into a license agreement entitled “Exclusive License Agreement
for Angiogenesis Gene Therapy,” effective on September 29, 1995, having
U.C. Agreement Control Number 96-04-0203 (“License Agreement”), and covering
licensure to Licensee by The Regents of rights in certain inventions developed
by Dr. H. Kirk Hammond, et al. (“Inventor”) at the University of
California, San Diego (“UCSD”) and claimed in Patent Rights (as defined in the
License Agreement);


 


Whereas, Licensee and The
Regents amended the License Agreement on September 19, 1996, to redefine
Patent Rights and to grant Licensee rights to enter into a sublicense agreement
with Schering Aktiengesellschaft;


 


Whereas, Licensee has
experienced unforeseen difficulties in obtaining rights in materials desired
for the development of the invention:


 


1





















 


Whereas, Licensee desires to
amend the License Agreement to extend the diligence provisions provided in
Paragraph 5.3 in order to accommodate the above-cited unforeseen difficulties
so that it can continue development of the invention; and


 


Whereas, The Regents desires
that the invention be developed, utilized, and marketed to the fullest extent
so that the products therefrom may be enjoyed by the general public and,
therefore, is willing to amend the Agreement;


 


Now, Therefore, in
consideration of the foregoing and the mutual promises and covenants contained
herein, the parties hereto agree as follows:


 


1.             Paragraph 5.3 (Due Diligence) of the License
Agreement shall be replaced in its entirety with the following:


 


“5.3         If Licensee is unable
to perform any of the following:


 


5.3.1        begin Phase I Clinical Trials in the United
States for Patent Products on or before June 30, 1998; and


 


5.3.2        enter pivotal clinical trials (a combination
of Phase II and Phase III Clinical Trials) in the United States for said Patent
Products on or before December 31, 1999; and


 


5.3.3        file for marketing approval in the United
States for said Patent Product on or before December 31, 2002; and


 


5.3.4        market Patent Products in the United States
within six (6) months after receiving marketing approval of such Patent
Products from the U.S. Food and Drug Administration; and


 


5.3.5        diligently and earnestly fill the market
demand for Patent Products following commencement of marketing


 


2





















 


at any time during the exclusive period of this Agreement;


 


then
The Regents will have the right and option to terminate this Agreement or
reduce the exclusive licenses granted to Licensee to non-exclusive licenses in
accordance with Paragraph 5.4 hereof. The exercise of this right and option by
The Regents supersedes the rights granted in Article 2. (Grant).”


 


This Amendment is not
intended to, and it is agreed that it does not, expressly or by implication,
affect in any way, any other provisions of the Exclusive License Agreement for
Angiogenesis Gene Therapy, dated September 29, 1995, which are intended to
remain in full force and effect.


 


In Witness Whereof, both The
Regents and Licensee have executed this Amendments, in duplicate originals, by
their respective officers hereunto duly authorized, on the day and year
hereinafter written.


 


 


	
  COLLATERAL THERAPEUTICS, INC.

   

  	
  THE REGENTS OF THE UNIVERSITY
OF CALIFORNIA

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  By

  	
  /s/ Jack W.
  Reich, Ph.D.

  	
   

  	
  By

  	
  /s/ Candace
  L. Voelker

  	
   

  	
   

  
	
   

  	
  (Signature)

  	
   

  	
   

  	
  (Signature)

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Name

  	
  JACK W.
  REICH, Ph.D.

  	
   

  	
  Name

  	
  Candace L. Voelker

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Title

  	
  President & CEO

  	
   

  	
  Title

  	
  Associate Director

  	
   

  
	
   

  	
   

  	
   

  	
  Office of Technology
  Transfer

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Date

  	
     6-24-97

  	
   

  	
  Date

  	
  6/30/97

  	
   

  	
   

  
										



 


 


	
  Approval as to legal form:

  	
  /s/ [ILLEGIBLE]

  	
   

  	
  [ILLEGIBLE]

  
	
   

  	
  [SEAL]

  	
   

  	
  Date

  
	
   

  	
   

  	
   

  	
   

  



 


3





















 


3rd Amendment to 

the Exclusive License Agreement


 


between


 


The Regents of the University of California


 


and


 


Collateral Therapeutics


 


UC Case No. 94-161


Agreement No. 96-04-0203


 





















 


3rd AMENDMENT TO THE EXCLUSIVE LICENSE AGREEMENT FOR 


ANGIOGENESIS GENE THERAPY


 


This
amendment (Amendment) is effective this 11th day of March 1999
between The Regents of the University of California (“The Regents’’), a
California corporation having its statewide administrative offices at 1111
Franklin Street, 12th Floor, Oakland, California 94607-5200, and
Collateral Therapeutics (“Licensee”), a Delaware corporation having a principal
place of business at 11622 El Camino Real, San Diego California 92130.


 


RECITALS


 


Licensee
and The Regents entered into a license agreement entitled “Exclusive License
Agreement for Angiogenesis Gene Therapy,” effective on September 27, 1995
(UC Agreement Control Number 96-04-0203). The above described license agreement
(the “Agreement”) was amended by mutual agreement of the parties on September 19,
1996 and again on June 30, 1997;


 


Licensee
has requested that some provisions of Article 5 (Due Diligence) be amended
and extended so that Licensee can remain in compliance with the Agreement and
achieve product approval under feasible diligence provisions. The Regents has
agreed to this Third Amendment so that the products licensed under the
Agreement may be developed for the benefit of the general public. 


 


The Regents and the Licensee
agree as follows:


 


Subparagraph
5.3.2 of Article 5 (Diligence) is removed in its entirely from the
Agreement and replaced with the following:


 


5.3.2    Submit a Phase III
(large scale) clinical trial protocol to the U.S. Food and Drug Administration
on or before December 31, 1999; and


 


This
Third Amendment does not, expressly or by implication, affects any other
provision of the Agreement in any way.


 





















 


The
Regents and Licensee have executed this Third Amendment in duplicate originals,
by their respective and duly authorized officers on the day and year written
below.


 


 


 


	
  COLLATERAL THERAPUETICS

  	
  THE REGENTS OF THE UNIVERSITY

  OF CALIFORNIA

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  By

  	
  /s/ Jack W.
  Reich, Ph.D.

  	
   

  	
  By

  	
  /s/ Candace
  L. Voelker

  	
   

  	
   

  
	
   

  	
  (Signature)

  	
   

  	
   

  	
  (Signature)

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Name

  	
  Jack W.
  Reich

  	
   

  	
  Name

  	
  Candace L. Voelker

  	
   

  
	
  Title

  	
  President and CEO

  	
   

  	
  Title

  	
  Associate Director

  	
   

  
	
   

  	
   

  	
   

  	
  Office of Technology
  Transfer

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Date

  	
    April 8, 1999

  	
   

  	
  Date

  	
  4/23/99

  	
   

  	
   

  
										



 





















 


4th Amendment to


 


the Exclusive License Agreement


 


between


 


The Regents of the University of California


 


and


 


Collateral Therapeutics


 


UC Case No. 94-161


 


Agreement Control No. 96-04-0203


 


 


	
   

  	
  U.C. AGREEMENT

  
	
   

  	
  CONTROL NUMBER

  
	
   

  	
  96-04-0203 RevH

  



 





















 


4th AMENDMENT TO THE EXCLUSIVE LICENSE AGREEMENT FOR


ANGIOGENESIS GENE THERAPY


 


This amendment (Amendment)
is effective this 8th day
of February, 2000 between The Regents of the University of California (“The
Regents”), a California corporation, having its statewide administrative
offices at 1111 Franklin Street, 12’h Floor, Oakland, California
94607-5200, and Collateral Therapeutics (“Licensee”), a Delaware corporation,
having a principal place of business at 11622 El Camino Real. San Diego,
California 92130.


 


RECITALS


 


Licensee and The Regents
entered into a license agreement entitled “Exclusive License Agreement for
Angiogenesis Gene Therapy,” effective an September 27, 1995 (U.C. Agreement Control Number 96-04-0203).
The above described license agreement (the ‘‘Agreement”) was amended by mutual
agreement of the parties on September 19, 1996, on June 30, 1997, and
on March 11, 1999;


 


In response to an unforeseen
and unavoidable delay in the regulatory approval process, Licensee has asked
The Regents to extend the term of a diligence provision (Article 5) in the
Agreement;


 


Licensee so requests and the
Regents accedes to the Licensee’s request so that the Licensee can remain in
compliance with the Agreement and achieve product approval within a feasible
time period;


 


In consideration for this
Fourth Amendment, Licensee will make an early payment of the License Issue Fee
due under Subparagraph 3.1.4 of the Agreement.


 


The parties therefore agree
to amend the Agreement as follows:


 





















 


1.             Subparagraph 3.1.4 of Article 3 (License
Issue Fee) is removed in its entirety and replaced with the following:


 


3.1.4        One Hundred Thousand Dollars ($100,000) on or
before January 20, 2000; and


 


2.             Subparagraph 5.3.2 of Article 5
(Diligence) is removed in its entirety from the Agreement and replaced with the
following;


 


5.3.2        Submit a Phase III (large scale) clinical
trial protocol to the U.S. Food and Drug Administration on or before July 31,
2000; and


 


This
Fourth Amendment does not, expressly or by implication, affect any other
provision of the Agreement in any way.


 


The
Regents and Licensee have executed this Fourth Amendment, in duplicate
originals, by their respective and duly authorized officers on the day and year
written below.


 


 


	
  COLLATERAL THERAPUETICS

  	
  THE REGENTS OF THE UNIVERSITY

  

  OF CALIFORNIA

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  By

  	
  /s/ Jack W.
  Reich, Ph.D.

  	
   

  	
  By

  	
  /s/ Candace
  Voelker

  	
   

  	
   

  
	
   

  	
  (Signature)

  	
   

  	
   

  	
  (Signature)

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Name

  	
  Jack W.
  Reich

  	
   

  	
  Name

  	
  Candace L. Voelker

  	
   

  
	
  Title

  	
  Chief Executive Officer

  	
   

  	
  Title

  	
  Associate Director,

  	
   

  
	
   

  	
   

  	
   

  	
   Office of Technology
  Transfer

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Date

  	
    Feb. 8, 2000

  	
   

  	
  Date

  	
  2/9/00

  	
   

  	
   

  
										



 


 


	
  Approved as to legal form:

  	
  /s/ P. Martin Simpson, Jr.

  	
   

  	
  2/7/96

  
	
   

  	
  [SEAL]

  	
   

  	
  Date