Ex parte PERGOLIZZI et al. - Page 18




          Appeal No. 95-3606                                                          
          Application 07/827,691                                                      
          examiner engaged in hindsight reconstruction of the subject                 
          matter claimed is evident in this case because, while Kremer                
          routinely used 7-deaza-dGTP when sequencing by Sanger’s                     
          dideoxy method and with a TAQuence sequencing kit because of a              
          high GC content of the template DNA (Kremer, p. 1712, Fig. 1.               
          (A)), Kremer appears not to have considered the use of 7-                   
          deaza-dGTP in PCR analysis.  See Figs. 2 and 3.  Moreover,                  
          Kremer’s attempts to determine the sequence of fragile X by                 
          PCR analysis appears to have been foiled by unstable DNA                    
          (Kremer, p. 1713, col. 3):                                                  
               The fragile X genotype is characterized by an increased                
               amount of unstable DNA that maps to the repeat.  Most of               
               this unstable repeat and indeed most of the repeat in                  
          normal                                                                      
               chromosomes is lost during cloning and DNA amplification               
               by PCR; thus its exact nature must remain speculative.                 
          Thus we find no teaching in Kremer, which would have led                    
          persons having ordinary skill in the art to reasonably expect               
          success when amplifying unstable fragile X DNA by PCR with or               
          without the addition of 7-deaza-dGTP to the PCR reaction                    
          mixture. Nevertheless, even if persons having ordinary skill                
          in the art reasonably would have expected from the combined                 
          teachings of Kremer, Innis I, and Innis II that the process                 
          Innis I and Innis II describe would have been useful for                    

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