Ex parte DE LA BROUSSE et al. - Page 8


                  Appeal No. 2001-1148                                                              Page 8                     
                  Application No. 09/114,552                                                                                   

                  We can find nothing in the prior art that would lead one of ordinary skill to select                         
                  Kitamoto’s technique as the means for inserting Kress’ reporter gene in the mouse                            
                  chromosome.                                                                                                  
                          We now turn to Sista which, like Kress, examiner has cited for its teaching                          
                  of a reporter gene. According to the examiner5, Sista teaches mouse fibroblast cells                         

                  transfected with a construct “containing a triplet repeat of the TPA response element                        
                  (TRE) upstream of a thymidine kinase promoter fused to the human growth hormone                              
                  (hGH) gene” (lines 6-8). Therefore, Sista is directed to inserting a particular reporter                     
                  gene within the chromosome of a mouse cell. While we recognize that Sista                                    
                  indicates that the mouse fibroblast cell line “has been stably transfected”, how the                         
                  “stably transfected” cell line has been produced is not explained. It is a matter of                         
                  speculation whether Sista employed a homologous recombination technique, like                                
                  the one claimed, to insert the disclosed construct in the mouse chromosome.                                  
                  Accordingly, Sista is relevant only to the extent that it teaches a particular reporter                      
                  construct. In that regard, modifying Tartaglia in view of Sista would result in Sista’s                      
                  particular reporter-containing construct residing somewhere on the mouse                                     
                  chromosome. This combination of references, however, fails to lead one of ordinary                           
                  skill to locate the construct on the chromosome such that “the expression of the                             
                                                                                                                               
                  5 Examiner (Examiner’s Answer, p. 6) states that                                                             
                          Sista teaches a cell-based assay for identifying modulators of gene expression. In this              
                      system, cells were stably transfected with a reporter gene operably linked to TPA response               
                      elements (TREs). TREs are DNA segments which stimulate RNA transcription in response to                  
                      protein kinase C (PKC) activity, so modulation of PKC activity is reflected in modulation of             
                      reporter gene expression. The reporter gene in this assay encoded human growth hormone                   
                      (hGH). Modulators of gene expression were identified by incubation of candidate compounds                
                      with cells containing the reporter construct, and subsequent measurement of hGH expression.              






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