Ex Parte Crea - Page 9

                Appeal  2007-2400                                                                            
                Application  10/418,182                                                                      

                (Answer 5.)  The Examiner acknowledges that “Crea . . . does not positively                  
                recite the total subset of the possible subsets that can be formed from the                  
                combined mutations in the CDRs library” (id. at 8).  However, the Examiner                   
                concludes that it would have been obvious                                                    
                      to determine the total number of subset[s] that can be obtained                        
                      from  the  possible  combinations  of  mutations  in  the  CDR                         
                      regions of a library.  The motivation to make such mutations is                        
                      provided by Crea above in reciting the advantages derived in                           
                      said mutations e.g., providing a means for systematic insertion                        
                      of  an  amino  acid  into  a  region  of  a  protein,  this  method                    
                      provides a way to enrich a region of a protein with a particular                       
                      amino acid.                                                                            
                (Id.)                                                                                        
                      We agree with the Examiner that the library of claim 1 would have                      
                been obvious to a person of ordinary skill in the art based on Crea.  Crea                   
                teaches the method of walk-through mutagenesis:  “[T]he method comprises                     
                introducing a predetermined amino acid into each and every position in a                     
                predefined region (or several different regions) of the amino acid sequence                  
                of a protein. . . . The method can be referred to as ‘walk-through’                          
                mutagenesis.”  (Crea, col. 2, ll. 45-65).                                                    
                      Crea teaches that “[u]sually, the region studied will be a functional                  
                domain of a protein such as a binding or catalytic domain.  For example, the                 
                region can be the hypervariable region (complementarity-determining region                   
                or CDR) of an immunoglobulin.”  (Id. at col. 10, ll. 1-5.)  Crea also teaches                
                that “several different regions or domains of a protein can be mutagenized                   
                simultaneously.  The same or a different amino acid can be ‘walked-                          
                through’ each region.”  (Id. at col. 11, ll. 1-3.)  Crea specifically suggests               
                that “the six hypervariable regions of an immunoglobulin, which make up                      

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