Ex Parte Rubin et al - Page 8




               Appeal No. 2004-1106                                                                   July 2004                       
               Application 09/871,388                                                                 Page 8                          
               (Answer, p. 4).7                                                                                                       
               22.     The last paragraph on specification page 5 (i.e., ll. 14-31) reads:                                            
                               The subject domains provide KUZ domain specific activity or                                            
                       function, such as KUZ-specific protease or protease inhibitory activity,                                       
                       disintegrin or disintegrin inhibitory activity, ligand/antibody binding or                                     
                       binding inhibitory [sic], immunogenicity, etc.; see, e.g. domains identified                                   
                       in Fig. 1A-C.  Preferred domains cleave a NOTCH protein.  KUZ-specific                                         
                       activity or function may be determined by convenient in vitro, cell-based,                                     
                       or in vivo assays: e.g. in vitro binding assays, cell culture assays, in                                       
                       animals (e.g. gene therapy, transgenics, etc.), etc.  Binding assays                                           
                       encompass any assay where the molecular interaction of an KUZ                                                  
                       polypeptide with a binding target is evaluated.  The binding target may be                                     
                       a natural intracellular binding target such as an KUZ substrate, a KUZ                                         
                       regulating protein or other regulator that directly modulates KUZ activity or                                  
                       its localization; or non-natural binding target such [sic] a specific immune                                   
                       protein such as an antibody, or an KUZ specific agent such as those                                            
                       identified in screening assays such as described below.  KUZ-binding                                           
                       specificity may [sic] assayed by protease activity or binding                                                  
                       equilibrium constants (usually at least about 10          7 M-1, preferably at least                           
                       about 108 M-1, more preferably at least about 109 M-1), by the ability of                                      
                       the subject polypeptide to function as negative mutants in KUZ-                                                
                       expressing cells, to elicit KUZ specific antibody in a heterologous                                            
                       host (e.g [sic] a rodent or rabbit), etc.  The KUZ binding specificity of                                      
                       preferred KUZ polypeptides necessarily distinguishes that of the                                               
                       bovine protein of Howard, L., et al. (1996).  Biochem. J. 317, 45-50.                                          
                       [Emphasis added.]                                                                                              
               23.     In essence, appellants' position is that since "KUZ, by definition, must have a                                
               binding specificity that distinguishes MADM [... and] KUZ binding specificity by definition                            
               includes binding of a KUZ-specific antibody, a KUZ-specific antibody must necessarily                                  
               [i.e., inherently] distinguish KUZ from MADM" (Brief, p. 3).                                                           
                       C.      The examiner's position                                                                                
               24.     According to the examiner, "the actual enzymes, the KUZ polypeptides, are                                      

                       7 The pages of the Answer are not numbered.  We have considered the cover sheet of the                         
               Answer as page 1 and subsequently numbered the remaining pages.                                                        





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