Ex Parte KLIPPEL et al - Page 12




             Appeal No. 2001-1378                                                                                    
             Application No. 08/832,571                                                                              

             that Kapeller, Varticovski and Aronheim teach that “other functional domains of p85,                    
             which are not components of the claimed polynucleotide fusion constructs (nor encoded                   
             by them), may be important for protein-protein interactions and required for PI 3-kinase                
             activity e.g., SH2 and SH3 domains.”   Brief, page 14.  Appellants argue that Aronheim                  
             teaches that localization to the plasma membrane alone may not be sufficient to                         
             produce catalytically active PI 3-kinase.   We find such arguments regarding the PI 3-                  
             kinase constructs disclosed by Klippel 93 and 94, which are not fusion constructs and                   
             which, when combined in vitro, fail to show PI 3-kinase activity, to be relevant with                   
             regard to the expectation of success of one of ordinary skill in the art at the time of the             
             present invention.   In our view, the cited references, as a whole, support appellants'                 
             argument that one of ordinary skill in the art at the time of the invention would perceive              
             that possibly other DNA sequences or conformational changes are necessary to provide                    
             for an active PI 3-kinase.                                                                              
                    The examiner responds, arguing that the problem of inactivity which occurs when                  
             the two subunits produced separately is “overcome when the two subunits are                             
             coexpressed and allowed to associate in vivo.   This is precisely what occurs when the                  
             two subunits are co-expressed as a fusion protein in vivo, and at the time the invention                
             was made the art of making a fusion protein with the desired activity is routine for one of             
             ordinary skill in the art.”   Answer, page 10.                                                          




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