Ex parte ADAMS - Page 4




              Appeal No. 1997-1668                                                                                        
              Application No. 08/361,024                                                                                  


                     Landegren describes an assay for determining the nucleic acid sequence in a                          
              region of a nucleic acid test substance having a known normal sequence and a known                          
              possible mutation at a target nucleotide position involving use of two probes (i.e.,                        
              primers), i.e., a target probe and an adjacent probe, capable of hybridizing to immediately                 
              adjacent parts of a complementary test substance.  The target probe has an end region                       
              nucleotide which is complementary to the normal or mutation nucleotide at the                               
              corresponding target nucleotide position.  When the target probe and the adjacent probe                     
              hybridize to one strand of the nucleic acid test substance in the presence of a linking                     
              agent, e.g., a ligase, the target probe and the adjacent probe will link (i.e., ligate) only if the         
              target nucleotide is correctly base paired with the target probe.  Determining the presence                 
              or absence of ligation indicates whether the target nucleotide is normal or a mutation.  See                
              col. 2, line 34 - col. 3, line 20.  Landegren discloses a kit comprising a target probe, an                 
              adjacent probe and a ligase (col. 3, lines 39-52).                                                          
                     Mullis describes a process known as the polymerase chain reaction (PCR)                              
              comprising treating separated complementary strands of a nucleic acid with a molar                          
              excess of two oligonucleotide primers, selected such that each primer hybridizes to the 3'                  
              terminus of a different strand of the double-stranded molecule, and extending the                           
              hybridized primers by a polymerase.  The duplexes formed by the extension are then                          
              separated and each newly formed nucleic acid sequence becomes the template of the                           


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