Ex Parte BERG et al - Page 5


                  Appeal No.  1999-2231                                                                                    
                  Application No.  08/278,774                                                                              
                  propeptide or replacing the proteolytic cleavage site of an existing propeptide                          
                  with a non-native site.”  In addition, appellants argue (Brief, page 5) that:                            
                         [o]ne would have to turn Carter on its head to fuse a collagen                                    
                         propeptide to a collagen protein and then call it an “affinity handle”.                           
                         The whole point of Carter and affinity handles is to take a protein                               
                         that doesn’t provide a good binding target and stick a convenient                                 
                         tag on it.  If collagen propeptides provided affinity tags, there would                           
                         be no point in making a fusion protein – a suitable handle is already                             
                         there.                                                                                            
                         In response, the examiner argues (Answer, page 4) that:                                           
                                [a]pplicants do not argue that putting two (or three) well                                 
                                known sequences together with a “non-natural site-specific                                 
                                proteolytic agent recognition site” between them would not                                 
                                have been obvious over the prior art but rather [they] argue                               
                                that there would be no motivation to do so.  As stated in the                              
                                final rejection this construct could be made to purify the                                 
                                collagen with an afifnity handle.  This is taught in Carter, first                         
                                paragraph.  For instance, an antibody could be made to                                     
                                particular procollagen, the construct of the instant claims                                
                                could be put on an affinity column containing this antibody                                
                                bound to a solid matrix, the contaminating proteins washed                                 
                                out and then the site-specific cleavage means could be                                     
                                employed to cleave the collagen molecule, thereby                                          
                                facilitating purification.  This same procedure could also                                 
                                have been done batch-wise, not using a column.                                             
                  The examiner further argues (Answer, bridging paragraph, pages 5-6) that:                                
                         [o]ne could make a cleavage site that could be readily and easily                                 
                         cleaved using a site-specific cleavage means instead of using the                                 
                         cleavage means used in the processing of natural collagen, [sic].                                 
                         This process[ing of natural collagen] uses enzymes thought to be                                  
                         expressed only in cells that naturally produce collagen.  In addition,                            
                         the use of the construct in a purification scheme involving solubility                            
                         discussed supra has not been addressed by applicants.                                             
                         As set forth in In re Soderquist, 326 F.2d 1016, 1018, 140 USPQ                                   
                  387, 389 (CCPA 1964)                                                                                     
                         It is not necessary in a combination rejection that the structure of                              
                         one reference be substituted bodily in that of the reference with                                 


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