VISSER et al v. HOFVANDER et al - Page 118




          Interference 103,579                                                        
          antisense technology, because the art remains unpredictable.                
          Kuipers’ 1995 publication shows that constructs comprising SUB30            
          in the antisense direction include the same SstI-SpeI sequence in           
          the antisense direction as do effective constructs comprising               
          SUB31 in the antisense direction or effective constructs                    
          comprising Visser’s full length genomic DNA coding for PGBSS in             
          the antisense direction.  Nevertheless constructs comprising                
          SUB30 in the antisense direction do not inhibit PGBSS gene                  
          expression while constructs comprising SUB31 and full length                
          genomic DNA coding for PGBSS in the antisense direction fo                  
          inhibit PGBSS gene expression.  All three DNA sequences include             
          the same homologous SstI-SpeI sequence.  Kuipers suspects                   
          “premature transcription termination” with antisense SUB30                  
          inserts because “[t]he genomic fragment used for the SUB30                  
          constructs contains a 3' non-GBSS sequence” (VDX 4, p. 752,                 
          col. 2, second para.).  However, Kuipers also points to prior               
          art which indicates that “[a] premature transcription stop does             
          not necessarily result in the absence of antisense inhibition”              
          (VDX 4, p. 752, col. 2, second para.).                                      
               The results in Kuipers’ 1995 publication also show that                
          prior knowledge in the art that full length genomic DNA coding              
          for PGBSS in the antisense direction will inhibit PGBSS gene                
          expression reasonably would not have led persons having ordinary            
          skill in the art to expect that similar success would or could be           
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