Ex parte PAVLAKIS et al. - Page 6

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

              The examiner acknowledges that Schwartz does not teach (Answer, page 5):                                        
                      [m]utating said instability/inhibitory sequences within said gene by making                             
                      multiple point mutations such that the amino acid sequence encoded by                                   
                      mRNA is unchanged.                                                                                      
              The examiner relies on Wisdom as teaching (Answer, page 6):                                                     
                      [i]nstability/inhibitory sequences coding for 4 amino acids of c-myc mRNA                               
                      and disruption of the initiation codon by a single point mutation effects                               
                      mRNA stability and rapid turnover of the mRNA . . . .                                                   
              The examiner relies on Kunkel as teaching (Answer, page 6):                                                     
                      [a] method of producing several single base substitution mutations                                      
                      introduced within a DNA template region as a way of generating a high                                   
                      frequency of desired nucleotide changes of a genotype by using a uracil-                                
                      containing DNA template, prepared by standard procedures after growth on                                
                                               -    -                                                                         
                      an Escherichia coli dut ung  strain (see page 488, column 1).  Kunkel also                              
                      teaches site specific misincorporation mutagenesis which is used to change                              
                      single codons from C to A and C to T (see page 490, column 2).                                          
              Finally, Hatfield is said to disclose (Answer, paragraph bridging pages 6-7):                                   
                      [a]nalyzing the frequency of at least some codon pairs (encoding the same                               
                      amino acid) from organism to organism, this information is used to construct                            
                      and express altered or synthetic genes having greater translational efficiency                          
                      for highly expressed genes (see abstract).  Hatfield et al. also discloses that                         
                      by replacing from 10% to 20% or more of the codons may be designed to                                   
                      either increase or decrease the translational efficiency of the codon pairs                             
                      (see column 5, lines 34-40).                                                                            
                      The examiner concludes (Answer page 7):                                                                 
                      [I]t would have been prima facie obvious to one of ordinary skill in the art at                         
                      the time the invention was made to identify RNA sequences in the gag                                    
                      region of HIV-1 which decrease RNA stability or inhibit expression as taught                            
                      by Schwartz et al, in view of other known instability/inhibitory sequences and                          


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