VISSER et al v. HOFVANDER et al - Page 119




          Interference 103,579                                                        
          achieved using any particular fragment thereof in the antisense             
          direction.  Compare the successful results using Kuipers’ pKGBA10           
          constructs comprising SUB10 in the antisense direction to the               
          unsuccessful results using Kuipers’ pKGBA20 and pKGBA25                     
          constructs respectively comprising SUB20 and SUB25 genomic DNA              
          fragments of SUB10 full length genomic DNA coding for PGBSS in              
          the antisense direction.                                                    
               Long after the effective filing dates of Hofvander’s and               
          Visser’s involved applications, Kuipers’ 1995 publication                   
          reported that, while the knowledge of persons skilled in the art            
          of antisense technology had greatly increased since 1988, still             
          (VDX 4, pp. 752-754 [sic 753], bridging para.):                             
                   . . . variation[s] in the inhibitory effects of the               
               partial genomic antisense constructs [can no more than]                
               point . . . towards a function for certain regions of                  
               the gene in antisense inhibition.                                      
          According to Kuipers’ 1995 publication, most recently reported              
          studies in the art “might indicate that certain sequence                    
          characteristics are involved in the process of antisense                    
          inhibition” (VDX 4, p. 752, col. 2, final incomplete para.;                 
          emphasis added).  On the other hand, they might not (VDX 4,                 
          pp. 752-754 [sic 753], bridging para.).  Alas, Kuipers’ 1995                
          publication points to evidence that “might indicate, that in                
          contrast to what has often been hypothesized” (VDX 4, p. 754                
          [sic 753], col. 1, last sentence of the first incomplete para.),            

                                        -119-                                         





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