Document:

Exhibit
10.6

 

Amendment to the Exclusive
License Agreement

for “Angiogenesis Gene Therapy”

 

This amendment (“Amendment”) to the Exclusive
License Agreement for Angiogenesis Gene Therapy, dated September 29, 1995
(the “License Agreement”) shall be effective as of the Transfer Date (as
described below), by and between The Regents of the University of California
(the “Regents”), a California corporation, having a principal administrative
office at 1111 Franklin Street, Fifth Floor, Oakland, CA 94607-5200, and Cardium
Therapeutics, Inc. (“Cardium” or “Licensee”), a Delaware corporation,
having a principal place of business at 11622 El Camino Real, Suite 300,
San Diego, CA 92130.

 

RECITALS

 

WHEREAS, Collateral Therapeutics, Inc. (“Collateral”)
and the Regents entered into a license agreement related to Angiogenic Gene
Therapy (AGT), effective on September 29, 1995, having U.C. Agreement
Control Numbers 96-04-0203 (“License Agreement”);

 

Whereas, Collateral Therapeutics subsequently
entered into a related license agreement, effective on June 18, 1997,
having U.C. Agreement Control Number 97-04-0664 (the “Related Agreement”);

 

WHEREAS, the License Agreement and The
Related Agreement contemplate one licensed product and, therefore, the parties
would like to terminate the Related Agreement and that the patent rights
formerly licensed thereunder will be governed by the terms and conditions of
the License Agreement, as amended herein;

 

WHEREAS, Collateral was acquired by a
corporation (Schering AG) which directly and through its affiliates made
considerable additional investments into the technology (including advancing a
product candidate termed Generx (Ad5-FGF4) into and through several human
clinical trials);

 

WHEREAS, Schering AG subsequently elected to
discontinue the AGT development program;

 

WHEREAS, Cardium was formed and financed in
order to acquire rights to the AGT technology, including the License Agreement,
license agreements and complementary rights from other institutions, as well as
know-how and biological

 

 

materials
developed by Collateral and its affiliates, and to reinitiate human clinical
trials of an AGT candidate based on Generx (Ad5-FGF4);

 

WHEREAS, Collateral, The Regents and Cardium
entered into a Transfer, Consent to Transfer, Amendment and Assumption of
License Agreement (the “Transfer & Assumption Agreement”), effective
on July     , 2005, under which all of Collateral’s
rights and obligations under the License Agreement are to be transferred to
Cardium in connection with the closing of a “Qualified Financing” on the “Transfer
Date” (each as defined in the Transfer & Assumption Agreement);

 

WHEREAS, despite considerable investments
into the AGT technology having been made by Collateral, Schering AG and their
affiliates, human gene therapy trials have been affected by numerous technical
difficulties and no significant gene therapy product has been successfully
commercialized to date;

 

WHEREAS, The Regents desires that the
invention be developed, utilized and marketed so that potential products therefrom
may be enjoyed by the general public, and desires to take advantage of the
considerable technological and other developments already made with respect to
the AGT technology, and of the complementary technologies and intellectual
property assets that have now been assembled by Cardium, and to facilitate
Cardium’s ongoing efforts to reinitiate and develop the AGT technology, and is,
therefore, willing to amend the License Agreement;

 

NOW, THEREFORE, in consideration of the
foregoing and the mutual promises and covenants contained herein, the parties
hereto agree to the following amendments to the License Agreement:

 

A.            Paragraph 1.1 (Patent Rights) of the License
Agreement is removed in its entirety and replaced with the following:

 

1.1           “Patent
Rights” means all United States patents and patent applications, corresponding
foreign patents and patent applications, and any reissues, extensions,
substitutions, continuations, divisions, and continuation-in-part applications
(but only those continuation-in-part applications that are entirely supported
in the specification and entitled to the priority date of the parent
application) based on the following:

 

 

1.1a         United States Patent
Application Serial Number 08/396,207, entitled “Gene Transfer-Mediated Angiogenesis
Therapy,” filed February 28, 1995, by Dr. Kirk Hammond et al, and
assigned to The Regents, and now abandoned (UC Case 1994-161-1);

 

1.1b         United States Patent
Number 5,792,453, entitled “Gene Transfer-Mediated Angiogenesis Therapy,”
issued August 11, 1998, to Dr. Kirk Hammond et al, and assigned to
The Regents (UC Case 1994-161-3);

 

1.1c         United States Patent No. 6,100,242,
entitled “Gene Therapies for Enhancing Cardiac Function,” issued August 8,
2000, to Dr. Kirk Hammond et al, and assigned to The Regents (UC Case 1994-161-4);

 

1.1d         United States Patent
Application Serial Number 09/021,773, entitled “Myocardial Gene Therapy,” filed
February 11, 1998, by Dr. Kirk Hammond et al and assigned to The
Regents, and now abandoned (UC Case 1994-161-5);

 

1.1e         United States Patent
Number 6,174,871, entitled “Gene Therapies for Enhancing Cardiac Function,”
issued January 16, 2001, to Dr. Kirk Hammond et al, and assigned to
The Regents (1994-161-6);

 

1.1f          United States Patent
Application Serial Number 09/435,156, entitled “Myocardial
Gene Therapy,” filed November 5, 1999, by Dr. Kirk Hammond et al, and
assigned to The Regents, and now abandoned (UC Case 1994-161-7).

 

1.1g         United States Patent
Application Serial Number 09/609,080, entitled “Myocardial Gene Therapy,” filed
November June 30, 2000, by Dr. Kirk Hammond et al, and assigned
to The Regents, and now abandoned (UC Case 1994-161-8).

 

1.1h         United States Patent
Application Serial Number 09/847,936, entitled “Myocardial Gene Therapy,” filed
May 3, 2001, by Dr. Kirk Hammond et al, and assigned to The Regents
(UC Case 1994-161-9).

 

1.1i          United States Patent
Application Serial Number 08/852,779, entitled “Gene Therapy for Heart Failure,”
filed May 6, 1997, by Dr. Kirk Hammond et al, and assigned to The
Regents, and now abandoned (UC Case 1997-119).

 

B.            Paragraph 4.4 (Minimum Annual Royalties) is
replaced in its entirety by the following:

 

4.4           Beginning
in the year 2010, the Licensee will pay to The Regents a minimum earned royalty
as follows

 

 

	
  2009

  	
   

  	
  $

  	
  150,000;

  	
   

  
	
  2010

  	
   

  	
  $

  	
   200,000;

  	
   

  
	
  2011

  	
   

  	
  $

  	
   250,000;

  	
   

  
	
  2012

  	
   

  	
  $

  	
   300,000;

  	
   

  
	
  2013

  	
   

  	
  $

  	
   400,000;

  	
   

  
	
  2014

  	
   

  	
  $

  	
   500,000;

  	
   

  

 

In each succeeding year after the year 2014,
the Licensee will pay a minimum annual royalty of Five Hundred Thousand Dollars
($500,000.) for the life of this Agreement.  
Minimum annual royalties are creditable against earned royalties, and if
the earned royalty owed for any calendar year is less than the minimum annual
royalty due for that same calendar year, then, in addition to the earned
royalty owed, Licensee will pay to The Regents an amount equal to the
difference between them by February 28 of the following year.

 

C.            Paragraph 5.3 (Due Diligence) of the License
Agreement is replaced in its entirety by the following:

 

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

 

5.3.1  begin new Phase
II Clinical Trials in the United States (or an equivalent phase of clinical
trials conducted in another country) for Patent Products on or before June 30,
2006;

 

5.3.2 
begin new pivotal Clinical Trials (Phase III Clinical Trials or a
combination of Phase II and Phase III Clinical Trials) in the United States (or
an equivalent phase of clinical trials conducted in another country) for Patent
Products within eighteen (18) months of completing successful Phase II Clinical
Trials, but not later than June 30, 2009;

 

5.3.3 
file for marketing approval in the United States for said Patent Product
within eighteen (18) months of completing successful pivotal Clinical Trials,
but not later than December 31, 2010;

 

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.  The exercise of this
right and option by the Regents supersedes the rights granted in Article 2.
(Grant).

 

D.            Paragraph 5.4 (Due Diligence) of the License
Agreement is replaced in its entirety by the following:

 

5.4           To exercise either the
right to terminate this Agreement or reduce the exclusive licenses granted to
the Licensee to non-exclusive licenses for lack of diligence required in this Article 5
(Due Diligence), The Regents will give the Licensee written notice of the
deficiency.  The Licensee has sixty (60)
days from the date of written notice to cure the deficiency.  If The Regents has not received written
evidence that the deficiency has been cured, then The Regents may, at its
option, terminate this Agreement or reduce the exclusive licenses granted to
the Licensee to non-exclusive licenses by giving written notice to the
Licensee.  These notices are subject to Article 18
(Notices).  Notwithstanding the
foregoing, if the Licensee can demonstrate that it is diligently developing
Patent Products but market or regulatory circumstances beyond the Licensee’s
control necessitate a first one-year extension of one or all of the provisions
5.3.2 through 5.3.4, then the License may extend the timeline of these
provisions by one (1) year upon payment of an first extension fee of Fifty
Thousand Dollars ($50,000).  The Licensee
may obtain two (2) additional one-year extensions of one or all of the
provisions of 5.3.2 through 5.3.4, subject to (a) payment of One Hundred
Thousand Dollars ($100,000) for the second one-year extension and One Hundred
and Fifty Thousand Dollars ($150,000) for the third one-year extension, and (b) the
Licensee’s written demonstration that failure to meet the development deadlines
are due to market and regulatory circumstances beyond the Licensee’s control.

 

E.             Paragraph 18.1 (Notice) of the License Agreement
is replaced in its entirety by the following:

 

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 by FedEx, UPS or other courier) or (b) five days
after mailing if mailed by first-class certified mail, postage paid, to the
party’s respective address as given below, or to another address as it may
designate by written notice to the other party:

 

 

	
  In the case of Licensee:

  
	
   

  	
  Cardium Therapeutics, Inc.

  
	
   

  	
  11622 El Camino Real, Suite 300

  
	
   

  	
  San Diego, CA 92130

  
	
   

  	
  Tel. (858) 794-3428

  
	
   

  	
  Fax (858) 794-3430

  
	
   

  	
  Attn: General Counsel

  
	
   

  	
   

  
	
  In the case of The Regents:

  
	
   

  	
  The Regents of the University of California

  
	
   

  	
  Office of Technology Transfer

  
	
   

  	
  1111 Franklin Street,

  
	
   

  	
  5th Floor

  
	
   

  	
  Oakland, CA 94607-5200

  
	
   

  	
  Tel: (510) 587-6000

  
	
   

  	
  Fax: (510) 587-6090

  
	
   

  	
  Attn: Executive Director

  
	
   

  	
   

  	
  Research Administration and

  
	
   

  	
   

  	
  Technology Transfer

  
	
   

  	
  Referring to: U.C. case No. 94-161 and
  97-119

  

 

F.             In consideration of this Amendment and the
rights granted under the License Agreement, the Licensee will pay the following
milestone payments:

 

One Hundred Thousand Dollars ($100,000) upon
beginning a new Phase II Clinical Trial in the United States (or an equivalent
phase of clinical trials conducted in another country) for Patent Products on
or June 30, 2006; 
whichever is earlier; and

 

Two Hundred Thousand Dollars ($200,000) upon
beginning Phase II/III Clinical Trials in the United States for Patent Products
or on December 31, 2008, whichever is earlier.

 

 

G.            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 License Agreement, which are
intended to remain in full force and effect. FURTHERMORE, by virtue of this
agreement, and given that the subject matter of the Related Agreement is hereby
incorporated into the License Agreement, the Related Agreement is hereby
terminated by mutual agreement of the Parties hereto.

 

H.            IN WITNESS WHEREOF,
both The Regents and Licensee have executed this Amendment, in duplicate
originals, by their respective officers hereunto duly authorized, effective as
of the date noted above.

 

 

	
  CARDIUM THERAPEUTICS, INC.

  	
  THE REGENTS OF THE UNIVERSITY

  
	
   

  	
  OF CALIFORNIA

  
	
   

  	
   

  
	
  By 

  	
     / S / Christopher J.
  Reinhard

  	
   

  	
  By 

  	
     / S / Candace L. Voelker

  	
   

  
	
   

  	
  for

  
	
  Name   Christopher J.
  Reinhard

  	
  Name   William T. Tucker

  
	
   

  	
   

  
	
  Title CEO

  	
  Title  Interim Executive Director

  
	
   

  	
             Research
  Administration and

  
	
   

  	
             Technology
  Transfer

  
	
   

  	
   

  
	
  Date 

  	
     October 3, 2005

  	
   

  	
  Date 

  	
     October 1, 2005

  	
   

  
	
   

  	
   

  
	
   

  	
   

  
	
   

  	
  Approved as to legal form:

  
	
   

  	
  / S / P. Martin Simpson, Jr.

  	
    August 1, 2005

  
	
   

  	
  University Counsel

  
	
   

  	
  Office of General CounselExhibit
10.7

 

Amendment
to License Agreement

 

This amendment (“Amendment”) to the License
Agreement with respect to certain technology related to FGF-4 dated as of March 24,
1997 (the “License Agreement”), is entered into by and among New York
University, a corporation organized and existing under the laws of the State of
New York (“NYU”), and Cardium Therapeutics, Inc., a Delaware Corporation (“CORPORATION”),
and shall be effective on the date (the “Effective Date”) upon which
CORPORATION becomes licensee under the License Agreement (pursuant to a
separate Transfer, Consent to Transfer, Amendment and Assumption of License
Agreement between NYU, CORPORATION and Collateral Therapeutics, Inc.).  NYU and CORPORATION are each a Party,
collectively Parties hereto.

 

RECITALS

 

Whereas, NYU and CORPORATION are now the
parties to the License Agreement;

 

Whereas, CORPORATION and its
predecessors-in-interest (and affiliates thereof) have pursued and/or are
expected to pursue product development efforts related to DNA-based product
candidates under the License Agreement, including in particular the original
Field of gene therapy for coronary artery disease, congestive heart failure and
peripheral vascular disease (the “Original Field”);

 

Whereas, NYU had previously licensed certain
other rights in the Research Technology to a third-party licensee (including
without limitation certain rights to the use of FGF-4 proteins) which third
party was also responsible for bearing three quarters (3/4) of the costs of the
associated patent expenses, but which third-party licensee subsequently
terminated its interests in the Research Technology and no other party has
since assumed such interests;

 

Whereas, CORPORATION intends to continue to
focus efforts on the development of DNA-based FGF-4 products but might if
technological aspects warrant also develop additional FGF-4 related products
including FGF-4 protein products;

 

Whereas, NYU desires to enable CORPORATION to
commercialize any and all aspects of the Research Technology;

 

Whereas, CORPORATION is willing to assume all
rights under the Research Technology in order to potentially develop products
beyond those of the Original Field and for as long as CORPORATION continues to
maintain all such rights, CORPORATION is willing to pay twice the original
license maintenance fee and to assume all ongoing patent costs associated with
the Research Technology;

 

AGREEMENT

 

Now, therefore, in consideration of the
foregoing and the promises and covenants contained herein, and other good and
valuable consideration, the receipt of which is hereby acknowledged, and
intending to be legally bound, the Parties agree as follows:

 

1.             Amendment.
The License Agreement is amended as follows, effective as of the Effective
Date:

 

(i) in Section 1(e), the definition
of Field is replaced in its entirety by the following:  “‘Field’ shall mean any and all uses of the
Research Technology.”;

 

 

(ii) in Section 1(f), the following
is added as the last sentence: “NYU represents and warrants that the Research and Licensing Agreement
with GI (i.e. the agreement dated February 6, 1989 as subsequently
amended) has been terminated and that all rights in the Research Technology for
use in the Field that were previously licensed to GI or any other third party
are immediately prior to the Effective Date of this Amendment the rights of
NYU, which rights NYU is as of the Effective Date free to transfer to
CORPORATION.”;

 

(iii) in Section 1(h), the
definition of “Licensed Products” is replaced in its entirety by the following:
“‘LIcensed Products’ shall mean any products which are covered by a claim of
any unexpired patent within the NYU Patents (as hereinafter defined) which has
not been disclaimed or held invalid, revoked or unenforceable by a court or
other governmental agency of competent jurisdiction from which no appeal can be
taken.”;

 

(iv) in Section 4, the following
paragraph (c) is added: “The Parties acknowledge and agree that, as of June 1,
2005, the NYU Research Project had been completely performed and funded as
contemplated by Sections 3 and 4.”;

 

(v) in Section 6(b), the phrase “excluding
any Pre-Existing Invention” shall be replaced by the phrase “including any
Pre-Existing Invention”;

 

(vi) in Section 6(c), the phrase “other
than those relating to any Pre-Existing Invention” shall be replaced by the
phrase “including those relating to any Pre-Existing Invention”;

 

(vii) in Section 6(e), the phrase “other
than those relating to any Pre-Existing Invention” shall be replaced by the
phrase “including those relating to any Pre-Existing Invention”;

 

(viii) Section 6(f) is
replaced in its entirety by the following: “Copies of all patents, patent
applications, official actions and associated documents with respect to the
Research Technology shall be forwarded to CORPORATION who may consult with NYU
with regard thereto.  CORPORATION agrees
that upon presentation of supporting documentation to CORPORATION, CORPORATION
shall be obligated to reimburse NYU for one hundred percent (100%) of the patent
expenses accruing on or after the Effective Date that are incurred by NYU in
connection with procuring or maintaining the NYU Patents.”;

 

(ix) in Section 8(a)(2) the
annual license maintenance fee of twenty-five thousand dollars ($25,000) shall
be increased to fifty thousand dollars ($50,000) (beginning with the first
annual license maintenance fee that becomes due following the Effective Date of
this Amendment);

 

(x) in Section 8(a)(3), the following is
added to the end of the last sentence: “provided further that in the event that
a given milestone has been met and paid for a DNA-based FGF-4 product (such as
an Ad5-FGF-4 gene therapy product candidate) and CORPORATION elects to pursue
development of a related version of the product (a “Protein Added Version of a
Product”) in which FGF-4 protein is added to or administered with a DNA-based
FGF-4 product (i.e. to the same patient before, at the same time or following
administration of the DNA-based FGF-4 product), no separate milestone payments
shall be paid in connection with the Protein Added Version of a Product;

 

(xi) in Section 14(b) the phrase “without
notice or any additional waiting periods” is replaced by “upon thirty (30) days
prior written notice in the event that CORPORATION has not completely cured
such deficiency within such thirty-day period (including obtaining insurance or
providing evidence of self-insurance adequate to cover any period of
deficiency)”.

 

2.             Authority.  Each
Party represents and warrants to the other that, as of the Effective Date, it: (1) has
the corporate power and authority and the legal right to enter into this
Amendment and to perform its obligations under the License Agreement as so
amended; (2) has taken all necessary corporate action on its part required
to authorize the execution and delivery of this Amendment and the performance
of its obligations under the License Agreement as so amended; (3) has not
taken and will not take any action that is inconsistent with the terms of the
License Agreement as so amended; (4) this Amendment has been duly executed
and delivered on behalf of such Party, and constitutes a legal, valid and
binding obligation of such

 

2

 

Party and is enforceable against it in
accordance with its terms; and (5) all necessary consents, approvals and
authorizations of all governmental authorities and other persons or entities
required to be obtained by such Party in connection with this Amendment of the
Agreement have been obtained.

 

3.             Further
Assurances.  Each Party agrees to execute, acknowledge and deliver such further
instruments, and to do all such other acts as may be necessary or appropriate
in order to carry out the purposes and intent of the License Agreement as
amended.

 

4.             Successors.
This Amendment and the License Agreement as amended shall be binding upon and
inure to the benefit of the Parties hereto and their respective successors and
permitted assigns.

 

5.             Counterparts.  This Amendment may be signed in counterparts,
each of which shall be deemed an original and which shall together constitute
an Amendment to the License Agreement.

 

IN WITNESS WHEREOF, each of the Parties, intending to be legally bound,
have caused the execution of this Amendment by their respective duly-authorized
officers who have signed below, to be effective as of the date noted above.

 

 

	
  NEW YORK UNIVERSITY

  	
  CARDIUM THERAPEUTICS, INC.

  
	
   

  	
   

  
	
  By:

  	
     / S / Abram M. Goldfinger

  	
   

  	
  By:

  	
      / S / Christopher
  J. Reinhard

  	
   

  
	
   

  	
   

  
	
  Name: Abram M. Goldfinger

  	
  Name:

  	
  Christopher J. Reinhard

  
	
   

  	
   

  	
   

  
	
  Title:   Executive Director,

  	
  Title:

  	
  CEO

  
	
              Industrial
  Liaison/Technology Transfer

  	
   

  	
   

  
	
  Date:   August 2, 2005

  	
  Date:

  	
  September 30, 2005

  
							

 

3

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