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

 

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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:

 

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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

 

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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;

 

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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:

 

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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.

 

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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

 

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