Confidential

Exhibit 10.49

Amendment No. 1 to Manufacturing Services Agreement relating to rhThrombin

This Amendment No. 1 to Manufacturing Services Agreement relating to rhThrombin, dated as of December 3, 2007
(Effective Date), is entered into by and between Patheon Italia S.p.A. (Patheon) and ZymoGenetics, Inc., a Washington corporation (ZGEN).

The parties hereby agree that the Manufacturing Services Agreement relating to rhThrombin, dated January 1, 2006 (the
Agreement) shall be amended as follows:



|1. | Territory
|-- | ---------

Schedule H shall be replaced by the
updated Schedule H attached hereto.



|2. | Ratification of Agreement
|-- | -------------------------

All other terms and
obligations of the Agreement shall remain in full force and effect.

IN WITNESS WHEREOF, ZGEN
and Patheon have executed this Amendment No. 1 to Manufacturing Services Agreement relating to rhThrombin as of the Effective Date.



|                                                                  |  |  |  |                                           
|----------------------------------------------------------------- |  |  |  | ------------------------------------------
|Patheon Italia S.p.A.                                             |  |  |  | ZymoGenetics, Inc.                        
|                                                                  |  | 
|/s/ Aldo Braca                                                    |  |  |  | /s/ Vaughn B. Himes                       
|Aldo Braca                                                        |  |  |  | Vaughn B. Himes, Ph.D.                    
|Managing Director Patheon Italia S.p.A. President Patheon Europe |  |  |  | Senior Vice President, TechnicalOperations
|Date: December 3, 2007                                            |  |  |  | Date: December 5, 2007                    



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Confidential

SCHEDULE H

TERRITORY

United States of America

Countries
within Europe



|                        |  |                                 |  |                        
|----------------------- |  | ------------------------------- |  | -----------------------
|        Albania        |  |         Andorra                |  |         Armenia       
|                        |  |                                
|        Austria        |  |         Azerbaijan             |  |         Belarus       
|                        |  |                                
|        Belgium        |  |         Bosnia and Herzegovina |  |         Bulgaria      
|                        |  |                                
|        Croatia        |  |         Cyprus                 |  |         Czech Republic
|                        |  |                                
|        Denmark        |  |         Estonia                |  |         Finland       
|                        |  |                                
|        France         |  |         Georgia                |  |         Germany       
|                        |  |                                
|        Greece         |  |         Hungary                |  |         Iceland       
|                        |  |                                
|        Ireland        |  |         Italy                  |  |         Kazakhstan    
|                        |  |                                
|        Kyrgyzstan     |  |         Latvia                 |  |         Liechtenstein 
|                        |  |                                
|        Lithuania      |  |         Luxembourg             |  |         Macedonia     
|                        |  |                                
|        Malta          |  |         Moldova                |  |         Monaco        
|                        |  |                                
|        Montenegro     |  |         Netherlands            |  |         Norway        
|                        |  |                                
|        Poland         |  |         Portugal               |  |         Romania       
|                        |  |                                
|        Russia         |  |         San Marino             |  |         Serbia        
|                        |  |                                
|        Slovakia       |  |         Slovenia               |  |         Spain         
|                        |  |                                
|        Sweden         |  |         Switzerland            |  |         Tajikistan    
|                        |  |                                
|        Turkey         |  |         Turkmenistan           |  |         Ukraine       
|                        |  |                                
|        United Kingdom |  |         Uzbekistan             |  |         Vatican City  



---

Countries within Canada/Latin America Region



|                       |  |                             |  |                   
|---------------------- |  | --------------------------- |  | ------------------
|        Canada        |  |         Mexico             |  |         Argentina
|                       |  |                            
|        Bolivia       |  |         Brazil             |  |         Chile    
|                       |  |                            
|        Colombia      |  |         Dominican Republic |  |         Ecuador  
|                       |  |                            
|        El Salvador   |  |         Guatemala          |  |         Nicaragua
|                       |  |                            
|        Paraguay      |  |         Peru               |  |         Uruguay  
|                       |  |                            
|        Venezuela     |  |         Costa Rica         |  |         Honduras 
|                       |  |                            
|        Panama        |  |         Belize             |  |         Cuba     
|                       |  |                            
|        French Guiana |  |         Guadeloupe         |  |         Guyana   
|                       |  |                            
|        Haiti         |  |         Suriname           |  |                   

Countries within Asia/Pacific Region



|                      |  |                               |  |                     
|--------------------- |  | ----------------------------- |  | --------------------
|        Australia    |  |         Cambodia             |  |         China      
|                      |  |                              
|        Hong Kong    |  |         Indonesia            |  |         India      
|                      |  |                              
|        Malaysia     |  |         New Zealand          |  |         Pakistan   
|                      |  |                              
|        Philippines  |  |         Singapore            |  |         South Korea
|                      |  |                              
|        Vietnam      |  |         Taiwan               |  |         Thailand   
|                      |  |                              
|        Bahrain      |  |         Bangladesh           |  |         Bhutan     
|                      |  |                              
|        Brunei       |  |         Israel               |  |         Jordan     
|                      |  |                              
|        Kuwait       |  |         Oman                 |  |         Qatar      
|                      |  |                              
|        Saudi Arabia |  |         United Arab Emirates |  |                     

Countries within Japan Region



|              
|--------------
|        Japan