Fourth Amendment to Amended and Restated License Agreement



 Exhibit 10.28 
 FOURTH AMENDMENT TO THE 
 AMENDED AND RESTATED LICENSE AGREEMENT 
 THIS FOURTH AMENDMENT TO THE AMENDED AND RESTATED LICENSE AGREEMENT (“Amendment”) made as of the 31st day of January, 2006, by and
between VASCULAR GENETICS INC., a Delaware corporation (the “Licensee”) and HUMAN GENOME SCIENCES, INC., a Delaware corporation (“HGS”). 
 WHEREAS, HGS and the Licensee entered into that certain License Agreement, dated as of October 31, 1997 (“Original License Agreement”), whereunder HGS granted to the Licensee an exclusive license
to use the gene Vascular Endothelial Growth Factor 2 in gene therapy treatment of vascular diseases; and 
 WHEREAS, the parties
amended the Original License Agreement in its entirety with that certain Amended and Restated License Agreement, dated February 28, 2001, and further amended such document by a First Amendment to Amended and Restated License Agreement dated
October 10, 2002 and a Second Amendment to Amended and Restated License Agreement dated April 26, 2004, and a Third Amendment to Amended and Restated License Agreement dated March 21, 2005 (collectively “Amended License
Agreement”); and 
 WHEREAS, the parties desire to herein amend the Amended License Agreement. 
 NOW, THEREFORE, for and in consideration of the premises and mutual promises herein contained, and for other good and valuable consideration, the
receipt and sufficiency of which are hereby acknowledged, the parties agree as follows: 
  

	1.	The Parties acknowledge that all capitalized terms not otherwise defined herein shall have the meaning ascribed to such terms in the Amended License Agreement.


  

	2.	Section 3.2. Section 3.2 of the Amended License Agreement (minimum use standards) is hereby deleted in its entirety and replaced with the following:


 LICENSEE agrees that it will meet the following minimum use standards either by its own performance or through or in
combination with an affiliate or sublicensee. 
 (a) LICENSEE shall have initiated a Phase IIb or Phase III clinical trial no
later than December 31, 2004. 
 (b) If both a Phase II and Phase III clinical trial are required by FDA, LICENSEE shall
have initiated the Phase III clinical trial no later than six (6) months after the end of the Phase II meeting, but no later than June 30, 2007. 







 (c) LICENSEE shall have filed a BLA for at least one LICENSED PRODUCT no later than
December 31, 2009. 
 LICENSEE will give notice of meeting each milestone within ten (10) business days of its
occurrence. LICENSEE will provide semi-annual updates to HGS on the clinical trial progress. For purposes of the above milestone, initiate shall mean when the first patient is dosed with CLINICAL TRIAL MATERIAL. If FDA imposes unexpected
requirements unrelated to actions by LICENSEE, LICENSEE and HGS will negotiate in good faith extension of these milestones. 
  

	3.	Appendix A of the Amended License Agreement is hereby deleted in its entirety and replaced with Schedule A attached hereto. 

  

	4.	Except as otherwise expressly stated herein, all provisions of the Amended License Agreement remain in full force and effect. 

  

	5.	This Amendment may be signed in one or more counterparts, which when taken together shall constitute one and the same Amendment. 

 IN WITNESS WHEREOF, the parties have executed and delivered this Amendment as of the date first written above. 
  

			
	HGS:
	
	HUMAN GENOME SCIENCES, INC.
		
	By:	 	 /s/ James H. Davis, Ph.D.
  

	Name:	 	 James H. Davis, Ph.D.

	Title:	 	 Executive Vice President

	
	LICENSEE:
	
	VASCULAR GENETICS INC.
		
	By:	 	 /s/ Richard E. Otto
  

	Name:	 	 Richard E. Otto

	Title:	 	 Chief Executive Officer










 Schedule A 
  

					
	 Application Title
	  	U.S. Serial No.	  	Patent No.
	Vascular Endothelial Growth Factor 2	  	08/207,550	  	
			
		  	08/824,996	  	5,935,820
			
		  	09/257,918	  	
			
		  	09/618,451	  	
			
		  	10/060,523	  	
			
		  	10/853,232	  	
			
	Vascular Endothelial Growth Factor 2	  	08/465,968	  	6,608,182
			
		  	10/127,551	  	
			
		  	10/023,584	  	
			
	Vascular Endothelial Growth Factor 2	  	11/211,724	  	
			
	Vascular Endothelial Growth Factor 2	  	08/999,811	  	5,932,540
			
	Vascular Endothelial Growth Factor 2	  	09/219,442	  	
			
	Vascular Endothelial Growth Factor 2	  	09/257,272	  	
			
	Vascular Endothelial Growth Factor 2	  	11/153,880	  	
			
	Vascular Endothelial Growth Factor 2	  	09/042,105	  	6,040,157
			
		  	09/935,726	  	
			
		  	09/438,538	  	
			
		  	11/067,015	  	
			
	Vascular Endothelial Growth Factor 2 and Compositions	  	09/623,725	  	
			
		  	10/084,488	  	6,734,285
			
		  	10/696,002	  	
			
	Vascular Endothelial Growth Factor 2	  	09/107,997	  	
			
	Vascular Endothelial Growth Factor 2	  	11/233,119	  	
			
	Vascular Endothelial Growth Factor 2	  	09/921,143	  	
			
	Vascular Endothelial Growth Factor 2	  	11/249,422	  	
			
	Vascular Endothelial Growth Factor 2	  	09/499,468	  	
			
	Vascular Endothelial Growth Factor 2	  	11/078,507