Ex Parte PEOPLES et al - Page 16


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

              pp. 226-27.  As pointed out by the examiner, Bülow still further discloses different                       
              methods of “creating proximity between the enzymes” (p. 227, col. 1, first complete                        
              para.) which include gene fusions which “maintain the monomeric character of the                           
              native enzymes” (id., col. 2, first complete para.) by “joining the structural genes of two                
              enzymes: the translational stop signal at the 3’ end of the first gene is removed and                      
              ligated in-frame to the ATG start codon of the second gene” (id., col. 1, para. 3).  Bülow                 
              still further discloses that through experience, it has “found that fairly short linkers (two              
              to ten amino acid residues) [between the fused enzymes] are optimal.”  Id., p. 230,                        
              col. 1, first complete para.; see also, Figure 1c and Figure 3.  Bülow exemplifies several                 
              fusion proteins consisting of catalytically active enzymes which act on substrate in                       
              successive reactions.  See, the β-galactosidase-galactokinase fusion protein                               
              (pp. 227-228), the β-galactosidase-galactose dehydrogenase fusion protein (p. 228,                         
              cols. 1-2), and the bovine P-450s and yeast reductase fusion protein (p. 229, col. 2).                     
              Not only does Bülow exemplify several fusion proteins, but the publication reports that                    
              “[o]ver the past few years a variety of artificial bifunctional enzymes have been prepared                 
              by gene fusion in vitro.”  Id., p. 227, col. 2, last para.                                                 
                     Accordingly, in view of the teachings of Peoples with respect to the construction                   
              of (i) plasmids comprising two catalytically active enzymes in the PHA biosynthetic                        
              pathway which act on a substrate in successive reactions (see, e.g., col. 22,                              
              lines 26-30; Figure 3); and (ii) protein fusions comprising catalytically active enzymes                   
              involved in the PHA biosynthetic pathway (col. 23, lines 14-24), and the teachings of                      
              Bülow as to the construction of bifunctional enzymes comprising two enzymes involved                       
              in successive reactions, the advantages of said constructions, and that said                               



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