Ex Parte PEOPLES et al - Page 12


              Appeal No. 2005-1383                                                                                       
              Application No. 09/364,847                                                                                 

              lines 16-18).”  Id.  The examiner states that Peoples does “not teach a fusion of                          
              enzymes catalyzing successive enzymatic reactions [emphasis added].”  To that end,                         
              the examiner relies on the teachings of Bülow that the (i) “preparation of a bifunctional                  
              enzyme can be accomplished by joining the genes of two enzymes by removing the                             
              translational stop signal at the 3’-end of the first gene and ligating the ATG-start codon                 
              of the second gene in-frame with the first gene”; (ii) “the enzyme selected to be at the                   
              N-terminal end [of a bifunctional enzyme] is arbitrary and that the native tertiary                        
              structure of the fused enzymes remains almost intact”; (iii) “if the entire primary                        
              sequences of the [] native enzymes are maintained in [a] fusion, the enzymes usually                       
              retain most of their native specific activities despite being fused together;” and                         
              (iv) “a linker peptide of two to ten amino acids separating the fused native enzymes                       
              [of a bifunctional enzyme] is optimal.”  Id., p. 8.                                                        
                     The examiner concludes that                                                                         
                     . . . it would have been obvious to one of ordinary skill in the art to                             
                     combine the teachings of Peoples [] and Bulow [] for a beta-ketothiolase                            
                     and acetoacetyl-CoA reductase or acetoacetyl-CoA reductase and PHB                                  
                     polymerase fusion protein having a linker of between two and ten amino                              
                     acids expressed in E. coli or a plant.  One would have been motivated to                            
                     make a beta-ketothiolase and acetoacetyl-CoA reductase or acetoacetyl-                              
                     CoA reductase and PHB polymerase fusion protein having a linker of                                  
                     between two and ten amino acids for expression in E. coli or a plant                                
                     because of the teachings of Peoples [] who teach PHB is a commercially                              
                     useful biopolymer that can be expressed in bacteria or plants as described                          
                     above and Bulow [] who teach the advantages of fusion proteins,                                     
                     particularly those catalyzing sequential enzymatic reactions and that a                             
                     linker of two to ten amino acids separating the native enzymes is optimal                           
                     as described above [Answer, pp. 8-9].                                                               
                     In response, the appellants argue that Peoples “teaches the construction of                         
              polymerase fusions for the purpose of ‘altering the enzyme’s specificity to create novel                   
              polymerases’ (see column 23, lines 14-24).”  Brief, p. 16.  The appellants further argue                   


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