Ex parte PAVLAKIS et al. - Page 8

              Appeal No. 1995-2723                                                                                            
              Application 07/858,747                                                                                          

              We find this combination of evidence sufficient to establish a case of prima facie                              
              unpatentability of the claimed method.                                                                          
                      Where, as here, a prima facie case of obviousness has been established, the                             
              burden of going forward shifts to the appellants.  In re Piasecki, 745 F.2d 1468, 1472, 223                     
              USPQ 785, 788 (Fed. Cir. 1984), In re Rinehart, 531 F.2d 1048, 1052, 189 USPQ 143,                              
              147, (CCPA 1976).                                                                                               
                      In rebuttal, the appellants initially argue (Principal Brief, page 7) that:                             
                      Schwartz et al. do not teach or suggest using multiple point mutations to                               
                      increase stability. . . Schwartz et al. do not suggest, contemplate, or teach                           
                      the use of anything other than the Rev regulatory protein to reduce the effect                          
                      of the INS present in HIV-1 gag gene.  There is no hint that would lead one                             
                      skilled in the art to know that multiple point mutations would reduce the                               
                      effects of INS.                                                                                         
              While we agree that Schwartz does not teach the use of multiple point mutations in the                          
              identification and study of INS regions in the HIV-1 gag gene, we do not read this                              
              disclosure to indicate that the Rev regulatory protein is the only factor important in reducing                 
              the effects of the INS region present in the gene.  Schwartz described the effect of a series                   
              of the deletion mutagenesis which evaluated the ability of the modified gene to express                         
              stable mRNA both in the presence and absence of Rev. (Note, for example, page 154,                              
              column 2, first full paragraph).  With regard to the use of multiple point mutations, we agree                  
              with he examiner that the combination of Wisdom and Kunkel, as discussed above, would                           
              have reasonably suggested the substitution of multiple point mutations for the deletion                         
              mutations used by Schwartz to determine whether a INS region was relevant to the stability                      
              of the mRNA being studied.                                                                                      


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