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EXHIBIT 10.3  

  
 

    FIRST AMENDMENT TO COLLABORATION AGREEMENT
  DATED AUGUST 1, 1997, BETWEEN VYREX CORPORATION
  AND THE IMMUNE RESPONSE CORPORATION    
  

 
  RECITALS    
  

    WHEREAS, Vyrex Corporation (hereinafter "Vyrex") and The Immune Response Corporation (hereinafter "IRC") entered in a Collaboration Agreement effective as of
August 1, 1997 (hereinafter "Agreement"), pursuant to which, inter alia, the parties agreed to conduct a collaborative research program and Vyrex, as the exclusive worldwide licensee of patent
rights and know-how relating to CD-TaggingTM technology, granted to IRC certain exclusive worldwide rights to develop, make, use, offer for sale, sell and import
Products (as defined in the Agreement), and to conduct the Program (as defined in the Agreement). 

    WHEREAS,
Vyrex is the owner and assignee of all right, title and interest in certain antioxidant compounds, methods, processes, procedures and uses specifically set forth in
Appendix I hereto and thereby incorporated by reference herein (hereinafter collectively referred to as "VANTOX-N"). 

    WHEREAS,
Vyrex and IRC desire to evaluate VANTOX-N for potential applications within the Field and Scope of the Program. 

    WHEREAS,
Vyrex agrees to grant IRC an exclusive world-wide license to VANTOX-N under the terms and conditions
set forth below. 

    NOW
THEREFORE, in consideration of the foregoing recitals and the mutual covenants contained herein, Vyrex and IRC agree to amend the Agreement, and otherwise agree, as follows: 

 
 

1. DEFINITIONS

    Article 1
of the Agreement is hereby amended to add the following new definitions, and to amend the definition of "Product" as follows: 

	1.1
	"VANTOX-N" shall mean the compounds, methods, processes, procedures and uses described in Appendix I hereto,
which, based upon testing conducted by or on behalf of the parties during and in the performance of the Program, have demonstrated, in the reasonable discretion of the Steering Committee (as defined
in the Agreement), potential utility in the Field and within the Scope (as defined in the Agreement).

	1.2
	"VANTOX-N Improvement" shall mean any compound, process, method, procedure, derivative or use (a) which
constitutes an improvement to VANTOX-N conceived by or on behalf of, Vyrex or IRC during the performance of the Program; (b) which
based upon testing conducted by or on behalf of the parties during and in the performance of the Program, has demonstrated, in the reasonable discretion of the Steering Committee (as defined in the
Agreement), potential utility in the Field (as defined in the Agreement); and (c) which, if patentable, claims priority of U.S. Patent Application Serial No. 09/075,356 filed
May 8, 1998, entitled "Water-Soluble Pro-Drugs of Propofol".

	1.3
	"VANTOX-N Know-How"shall mean all information and data, which is not generally known including, but not
limited to, syntheses, formulae, procedures, protocols, techniques and results of experimentation and testing, which are necessary or useful to develop, synthesize, manufacture, use, practice or sell  VANTOX-N
or any VANTOX-N Improvement.

	1.4
	"First
Amendment Commencement Date" shall mean June 24, 1998.

	1.5
	"VANTOX-N Patent Rights" shall mean, collectively, (a) the patent rights specifically described in
Appendix I; and (b)(i) any and all patent applications heretofore or hereafter filed or having legal force in any country, which claim a  VANTOX-N Improvement and/or VANTOX-N Know-How; (ii) all
patents that issue therefrom, including utility, model and design patents and certificates of 

invention;
and (iii) all divisionals, continuations, continuations-in-part, reissues, renewals, extensions of additions to any such patent applications and patents.  VANTOX-N Patent Rights shall be excluded from
Program Patent Rights as defined in Paragraph 1.22 of the Agreement. 

	1.6
	"Product"
shall mean, collectively, (a) a product which incorporates or contains a Program Compound (as defined in the Agreement), and/or (b) a product which
incorporates, contains, uses, is based on or results from VANTOX-N or a VANTOX-N
Improvement. 

 
 

2. REPRESENTATIONS AND WARRANTIES

    Each
party hereby represents and warrants to the other party as follows: 

	2.1
	Each
party has the corporate power, authority and the legal right to enter into this Amendment and to perform its obligations hereunder, and has taken all necessary corporate action
on its part to authorize the execution and delivery of the Amendment and the performance of its obligations hereunder. The Amendment has been duly executed and delivered on behalf of such party, and
constitutes a legal, valid and binding obligation, enforceable against such party in accordance with its terms

	2.2
	All
necessary consents, approvals and authorizations of all governmental authorities and other Persons (as defined in the Agreement) required to be obtained by such party in
connection with the Amendment have been obtained.

	2.3
	The
execution and delivery of the Amendment, and the performance of such party's obligations hereunder, do not conflict with or violate any requirement of applicable laws or
regulations, and do not conflict with, or constitute a default under, any contractual obligations of such party.

	2.4
	Nothing in this Amendment shall be construed as a representation made, or warranty given, by either party that any patent will issue based upon any pending
patent application within the VANTOX-NPatent Rights, that any patent issued with respect thereto will be valid, or
that the use of any license granted hereunder, or the use of any VANTOX-NPatent Rights or  VANTOX-N Know-How will not infringe the patent or
intellectual patent rights of any other Person. Furthermore, neither party
makes any representations or warranties, express or implied, with respect to VANTOX-N Patent Rights or  VANTOX-N Know-How, including without
limitation, merchantability or fitness for a particularpurpose.

 
 

3. LICENSE GRANTS    
  

    Article 6 of the Agreement is hereby amended to add the following new provision: 

	3.1
	Vyrex
hereby grants to IRC an exclusive worldwide license (with the exclusive right to grant sublicenses) under Vyrex' rights in the  VANTOX-N Patent Rights and VANTOX-N
Know-How (a) to conduct
the Program, and (b) to develop, make, use, offer for sale, sell and import Products. 

 
 

4. PROGRAM INVENTIONS AND PATENT RIGHTS

    Article 10
of the Agreement is hereby amended to add the following new provisions: 

	4.1
	Vyrex
shall solely own the entire right, title and interest in all VANTOX-N, VANTOX-N Improvements,  VANTOX-N Patent Rights and VANTOX-N
Know-How.

	4.2
	Vyrex,
at its sole cost, shall be responsible for and shall have the sole right to control the preparation, filing, prosecution and maintenance of  VANTOX-N Patent Rights. The provisions of Section 10.3 of the
Agreement additionally shall apply to the  VANTOX-N Patent Rights.

	4.3
	Upon
expiration of the Agreement under Section 11.1 of the Agreement, the license under the VANTOX-N
Know-How granted to IRC pursuant to Section 3.1 of this Amendment shall continue and become a perpetual and fully-paid license. 

 
 

5. RELATION TO OTHER DOCUMENTS

	5.1
	The
Program Workplan (as defined in the Agreement), when drafted, shall include reference to VANTOX-N.

	5.2
	Vyrex
and IRC agree that, except as specifically provided in this Amendment, all other terms and conditions set forth in the Agreement shall remain in full force and effect and
shall govern the rights and obligations of the parties hereto.

	5.3
	The
parties agree that in the event of any conflict or inconsistency between the Agreement and the specific provisions of this Amendment, the provisions of this Amendment shall
control in all respects. 

    IN
WITNESS WHEREOF, the parties have executed this amendment effective as of the First Amendment Commencement Date at La Jolla, California. 

	For VYREX CORPORATION:	 
	

By:	
 	

/s/ SHELDON S. HENDLER   
 Sheldon S. Hendler, PhD., M.D.

Chairman and Chief Executive Officer	

 
	

For THE IMMUNE RESPONSE CORPORATION:	

 
	

By:	
 	

/s/ DENNIS J. CARLO   
 Dennis J. Carlo, Ph.D.

Chief Executive Officer	

 

 
 

APPENDIX I    
  

VANTOX-N shall mean any compound, method, process, procedure or use claimed in U.S. Patent Application Serial No. 09/075,356, filed
May 8, 1998, entitled "Water-Soluble Pro-Drugs of Propofol"and any United States and foreign patent applications that claim priority thereof; all patents that have issued or in the
future issue therefrom, including utility, model and design patents and certificates of invention; and all divisionals, continuations, continuations-in-part, reissues,
renewals, extensions or additions to any such patent applications and patents. 

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FIRST AMENDMENT TO COLLABORATION AGREEMENT DATED AUGUST 1, 1997, BETWEEN VYREX CORPORATION AND THE IMMUNE RESPONSE CORPORATION

RECITALS

1. DEFINITIONS

2. REPRESENTATIONS AND WARRANTIES

3. LICENSE GRANTS

4. PROGRAM INVENTIONS AND PATENT RIGHTS

5. RELATION TO OTHER DOCUMENTS

APPENDIX IPrepared by MERRILL CORPORATION www.edgaradvantage.com

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EXHIBIT 10.4  

 
 

SECOND AMENDMENT TO COLLABORATION AGREEMENT
  DATED AUGUST 1, 1997, BETWEEN VYREX CORPORATION
  AND THE IMMUNE RESPONSE CORPORATION    
  

RECITALS  

    WHEREAS, Vyrex Corporation (hereinafter "Vyrex") and The Immune Response Corporation (hereinafter "IRC") entered into a Collaboration Agreement dated
August 1, 1997 (hereinafter "Agreement"), wherein Vyrex, as the exclusive worldwide licensee of patent rights and know-how relating to CD-TaggingTM
technology, granted to IRC certain exclusive worldwide rights, as limited by Field and Scope (as defined in the Agreement), to use its CD-Tagging technology in furtherance of the Program
(as defined in the Agreement). 

    WHEREAS,
Vyrex and IRC executed a First Amendment to the Agreement, effective June 24, 1998, wherein Vyrex granted to IRC an exclusive world-wide license to
Vantox-N compounds, limited by Field and Scope, to develop and use Vyrex's Vantox-N compounds in furtherance of the Program. 

    WHEREAS,
Vyrex and IRC, pursuant to an agreement reached between the companies on or about April 26, 1999, now wish to formalize the termination of the exclusive worldwide
sub-license of patent rights and know-how relating to CD-Tagging technology granted in the Agreement. 

    WHEREAS,
Vyrex and IRC now desire to further amend the Agreement by incorporating the license grant of specific Vyrex proprietary technology, limited by Field and Scope, as more fully
set forth below. 

    NOW
THEREFORE, in consideration of the foregoing promises and the mutual covenants set forth below, the parties hereby agree to amend the Agreement as follows: 

 
 

ARTICLE 1
  AMENDMENT    
  

    1.1 Section 1.9
of the Agreement is restated in its entirety to read as follows: 

    "Field" shall mean the treatment of diseases, states or conditions associated with central or peripheral nervous systems, including but
not limited to migraine and anesthesia. 

    1.2 Section 1.25
of the Agreement is restated in its entirety to read as follows: 

    "Scope" shall mean the discovery, research and development of (a) proteins, small molecules and compounds involved in nerve
growth and repair, and (b) propofol pro-drugs described in U.S. Patent WO 99/58555, owned by Vyrex, as limited by the Field. 

    1.3 Section 3.6
of the Agreement is restated in its entirety to read as follows: 

     Term of the Program.  Except as provided in Article 11 below, the term of the Program shall commence on the Commencement Date and
terminate on the sixth anniversary thereof. Termination of the Program pursuant to this paragraph shall not serve to terminate or otherwise affect the rights and obligations of the parties pursuant to
any other Article under this Agreement. 

    1.4  Termination of License Rights.  Vyrex and IRC hereby agree that this Second Amendment terminates all
rights of IRC under the sub-license covering CD-Tagging patent rights granted by Vyrex to IRC in the Agreement. IRC acknowledges and represents hereby that it has not, pursuant
to the Agreement, granted any sub-license or conveyed any rights to any affiliate or third party with respect to CD-Tagging. 

Vyrex/IRC Collaboration - Page 1 of 3 

 

    1.5 Section 6.1 of the Agreement is restated in its entirety to read as follows: 

     Licenses to IRC.  Vyrex hereby grants to IRC an exclusive worldwide license (with the exclusive right to grant sub-licenses) under
Vyrex's rights in the VANTOX-N Patent Rights and VANTOX-N Know-How (including without limitation the propofol pro-drugs described in U.S. Patent WO
99/58555), and as limited by the Field and Scope, to conduct the Program, and to develop, make, use, offer for sale, sell and import Products. 

    1.6 Section 6.3
of the Agreement is restated in its entirety to read as follows: 

     Sublicenses.  

    6.3.1.  IRC
shall provide to Vyrex a written summary of the general financial terms of any proposed sublicense under the licenses granted to IRC under
the Agreement prior to execution thereof. Such summary shall be Confidential Information of IRC. Vyrex shall have ten (10) days after the date of such written summary to provide IRC with
comments on such proposed sublicense. IRC may enter into an agreement with a sublicensee on terms that are substantially similar to or more favorable to IRC than the proposed terms, provided, if Vyrex
reasonably demonstrates that the proposed terms are not arms length terms, negotiated in good faith, under the circumstances, IRC shall consider in good faith any reasonable comments provided by Vyrex
during such ten (10) day period. 

    6.3.2.  IRC
and Vyrex shall provide to the other party a copy of any sublicense under the licenses granted under the Agreement promptly upon execution
of the same. Any such sublicense shall be subject to the provisions of the Agreement. 

 
 

ARTICLE 2
  MISCELLANEOUS    
  

    2.1  Defined Terms.  All terms used, but not defined, in this Second Amendment shall have the respective
meanings set forth in the Agreement. 

    2.2  Continuing Effect.  This Second Amendment shall be effective for all purposes as of the Effective
Date. Except as otherwise expressly modified by this Second Amendment, the Agreement shall remain in full force and effect in accordance with its terms. 

    2.3  Governing Law.  This Second Amendment shall by governed by and construed in accordance with the laws
of the State of California without regard to the conflicts of law principles hereof. 

    2.4  Counterparts.  This Amendment may be executed in counterparts, each of which shall be deemed to be
an original and together shall be deemed to be one and the same document. 

Vyrex/IRC Collaboration - Page 2 of 3 

 

    IN WITNESS WHEREOF, the undersigned have duly executed and delivered this Second Amendment effective as of the date of the last signed below. 

	THE IMMUNE RESPONSE CORPORATION	 	 	 	 
	

By:	
 	

/s/ Dennis J. Carlo
 Dennis J. Carlo, Ph.D.

Chief Executive Officer	
 	

Date:	
 	

  

	

VYREX CORPORATION	
 	

 	
 	

 
	

By:	
 	

/s/ G. Dale Garlow
 G. Dale Garlow

Chief Executive Officer	
 	

Date:	
 	

  

Vyrex/IRC Collaboration - Page 3 of 3 

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SECOND AMENDMENT TO COLLABORATION AGREEMENT DATED AUGUST 1, 1997, BETWEEN VYREX CORPORATION AND THE IMMUNE RESPONSE CORPORATION

ARTICLE 1 AMENDMENT

ARTICLE 2 MISCELLANEOUS

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