Ex Parte HAYASHI et al - Page 5


                 Appeal No.  2001-0288                                                        Page 5                   
                 Application No.  08/277,031                                                                           
                 while Crespi expressly identifies IA2, IIEI and IIIA4, and suggests including other                   
                 P450 cytochromes, Crespi does not expressly teach cytochrome 2C9.                                     
                        To make up for this deficiency the examiner relies on Wolf, Sakaki,                            
                 Yasumori ‘87, and Yasumori ‘89.  According to the examiner (Answer, page 4)                           
                 Wolf teaches:                                                                                         
                        that Saccharomyces transformants may be alternatively and                                      
                        advantageously used for the recombinant expression of any                                      
                        mammalian cytochrome P450 in such assays so long as a suitable                                 
                        cytochrome P450 reductase is also expressed, preferably as “a                                  
                        hybrid, fusion protein comprising” both the cytochrome P450 and                                
                        the reductase, which may be a mammalian reductase or a host cell                               
                        reductase:  a “yeast reductase.”                                                               
                 To emphasize the teaching of cytochrome P450:NADPH-cytochrome P450                                    
                 reductase fusion polypeptides, the examiner finds (Answer, page 5) that Sakaki                        
                 teaches “the recombinant expression in Saccharomyces transformants of two                             
                 different fusion polypeptides comprising either of two mammalian cytochrome                           
                 P450s, each fused to a yeast NADPH-cytochrome P450 reductase….”                                       
                        The examiner finds (Answer, page 6) that Yasumori ‘89 teaches a human                          
                 cytochrome P450 “which they designate a ‘human-2’ cytochrome … [that is]                              
                 encoded by a cDNA having greatest similarity to the cDNA encoding human                               
                 cytochrome P450 IIC9, see footnote 1 at page 443….”  To further support this                          
                 teaching in Yasumori ‘89, the examiner finds (Answer, page 13) that footnote 1                        
                 of Yasumori ‘89:                                                                                      
                        indicates that Yasumori et al.[](‘89) had already aligned the DNA                              
                        sequence of Yasumori et al.[](‘87), which is SEQ ID NO:2 of the                                
                        specification, with cDNAs encoding cytochromes P450 known at                                   
                        that time and determined that it was a cytochrom[e] P450 IIC9                                  
                        cDNA, making it clear that the standard nomenclature for the                                   
                        “human-2” enzyme of [Yasumori ‘89] would be IIC9.                                              





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