Ex Parte MCWHERTER et al - Page 5


               Appeal No. 2001-1580                                                  Page 5                 
               Application No. 08/955,090                                                                   

                      The examiner concluded that                                                           
                      [i]t would have been obvious to the person of ordinary skill in the art               
                      at the time the invention was made to modify the fusion proteins of                   
                      Pastan et al. . . . by substituting for the cytokines disclosed therein               
                      the soluble flt3 ligand disclosed by Lyman et al.  One of ordinary                    
                      skill in the art would have been motivated to make circularly                         
                      permuted forms of the soluble flt3 ligand disclosed by Lyman et al.                   
                      by the disclosure of Pastan et al. that such circularly permuted                      
                      proteins are expected to retain or have improved binding properties                   
                      to the receptor to which they bind, as compared to the non-                           
                      permuted forms.  The particular termini recited in claim 1 are                        
                      considered to be obvious in view of Hannum et al., which discloses                    
                      . . . that such sites occur in regions between alpha helices, given                   
                      that Pastan et al. teach that regions that do not show a highly                       
                      regular three-dimensional structure are desirable for introducing the                 
                      new termini to the circularly permuted protein.                                       
               Id., page 6.                                                                                 
                      Appellants argue that the examiner has not shown prima facie                          
               obviousness, because, inter alia, the cited references at best would have made               
               the claimed invention “obvious to try.”  See the Appeal Brief, pages 12-17.                  
               Appellants argue that the cited references would not have led those of skill in the          
               art to reasonably expect that a circularly permuted flt3 ligand would retain the             
               binding activity of the native ligand, much less have improved binding properties,           
               because the record shows that circular permutation produces unpredictable                    
               effects.  In support, Appellants refer to the prior art cited in the present                 
               specification (pages 3-7), which lists sixteen proteins which have been circularly           
               permuted, and which concludes that                                                           
                      [t]he results of these studies have been highly variable.  In many                    
                      cases substantially lower activity, solubility or thermodynamic                       
                      stability were observed [listing seven proteins]. . . .  In other cases,              
                      the sequence rearranged protein appeared to have many nearly                          
                      identical properties as its natural counterpart [listing eight                        





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