Amendment No. 1 to Royalty Agreement



 Exhibit 4.8 
 AMENDMENT NO. 1 TO ROYALTY AGREEMENT 
 This AMENDMENT NO. 1 TO ROYALTY AGREEMENT (this
“Amendment No. 1”), dated as of October 22, 2008, is made by and among Deerfield Private Design Fund, L.P., a Delaware limited partnership (“Design Fund”), Deerfield Private Design International, L.P., a
British Virgin Islands limited partnership (“Design International”), Deerfield ZG Corporation, a Delaware corporation (“Deerfield ZG”) and ZymoGenetics, Inc., a Washington corporation
(“ZymoGenetics”). 
 WHEREAS, Design Fund, Design International and ZymoGenetics are parties to a Royalty Agreement
dated June 26, 2008 (the “Royalty Agreement”); and 
 WHEREAS, the parties to this Amendment No. 1 desire
to amend the Royalty Agreement to substitute Deerfield ZG as a party thereto in place of Design International; 
 NOW, THEREFORE, the
parties hereto agree as follows: 
 1. Substitution of Deerfield ZG for Design International. Design International shall cease to be a
party to the Royalty Agreement, and Deerfield ZG shall become a party to the Royalty Agreement in the place of Design International. The term “Deerfield” shall mean Design Fund and Deerfield ZG together, and references to “Design
International” appearing in Sections 1 through 7 of the Royalty Agreement shall be replaced by references to “Deerfield ZG.” 
 2. Representations and Warranties. The first sentence of Section 5(a) shall be deleted and replaced with the following: 
 Design Fund is a limited partnership duly organized, validly existing and in good standing under the laws of Delaware. Deerfield ZG is a corporation duly organized, validly existing and in good standing under the laws of Delaware.

 For the sake of clarity, Deerfield ZG will make the remaining representations and warranties in Section 5 pursuant to Section 1
of this Amendment No. 1. 
 3. Definition of Facility Units. The last sentence of the definition of “Facility Units” in
Section 1(j) of the Royalty Agreement is deleted and replaced in its entirety by the following: 
 Notwithstanding the foregoing, and
solely for purposes of the determination of the Facility Units, the number of Facility Units shall be deemed to be equal to zero (0) for each day within the Royalty Term during which Deerfield or Design International is in breach of its
obligation to make a Disbursement under the Facility Agreement. 
 4. Deletion of Section 2(i). Section 2(i) of the Royalty
Agreement, and all references thereto, are deleted. 







 5. Royalty Agreement in Full Force and Effect. Except as amended by this Amendment No. 1, the
Royalty Agreement shall remain in full force and effect. 
 IN WITNESS WHEREOF, the Parties have caused this Amendment No. 1 to
be executed by their duly authorized representatives as of the date first set forth above. 
  

			
	DEERFIELD PRIVATE DESIGN FUND, L.P.
		
	By:	 	 /s/    James Flynn

	Name:	 	James Flynn
	Title:	 	General Partner
	
	DEERFIELD PRIVATE DESIGN INTERNATIONAL, L.P.
		
	By:	 	 /s/    James Flynn

	Name:	 	James Flynn
	Title:	 	General Partner
	
	DEERFIELD ZG CORPORATION
		
	By:	 	 /s/    James Flynn

	Name:	 	James Flynn
	Title:	 	General Partner
	
	ZYMOGENETICS, INC.
		
	By:	 	 /s/    James A. Johnson

	Name:	 	James A. Johnson
	Title:	 	Executive Vice President and Chief Financial Officer