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 Counsel