Ex Parte CASTRO - Page 6



              Appeal No. 2003-0892                                                                  Page 6                
              Application No. 09/454,385                                                                                  
              nucleosides commonly found in DNA and RNA, methods of their derivatization and                              
              subsequent use in the synthesis of fluorescent oligonucleotides . . . having prescribed                     
              sequences” (column 1, lines 13-19).  According to the examiner (Answer, pages 5-6),                         
                     Conrad teaches a method for identifying target DNA or RNA sequences                                  
                     (column 27, lines 50-55) comprising: a) selecting a primer of more than 15                           
                     nucleotides . . . having a 3' hydroxyl group at one end and having a                                 
                     sequence of nucleotides to specifically hybridize with an identifying                                
                     sequence of nucleotides in the target DNA (column 27, lines 55-60), b)                               
                     hybridizing the primer to the identifying nucleotide sequences of the target                         
                     RNA sequence (column 27, lines 60-65), c) extending the primer along                                 
                     the target sequence by progressively binding a plurality of nucleotides to                           
                     the primer that are complementary to the corresponding nucleotides on                                
                     the target sequence to form a reporter molecule, where the                                           
                     complementary nucleotides include rUTP nucleotides labeled with a                                    
                     fluorophore and unlabelled rATP, rCTP, and rGTP nucleotides . . . [and]                              
                     d) detecting fluorescence emitted by fluorophores on individual reporter                             
                     molecules to identify the target DNA sequence (column 28, lines 2-10).                               
                                                                                                                         
                     Castro describes “single-molecule electrophoresis,” which “promises to combine                       
              the advantages of free-solution capillary electrophoresis (system automation, speed,                        
              reproducibility) with the unsurpassed sensitivity of single-molecule detection” (page                       
              3186).  According to the examiner, “[i]t would have been prima facie obvious to one                         
              having ordinary skill in the art at the time the invention was made to combine the                          
              method of Conrad with the use of single molecule electrophoresis as taught by                               
              Castro[,]” “for the express advantages of improved speed, reproducibility and                               
              unsurpassed sensitivity” (Answer, page 6).                                                                  
                     Appellant argues that one skilled in the art would not have had reason to detect                     
              Conrad’s fluorescent polynucleotides using Castro’s method because “[t]he advantages                        
              of single molecule electrophoresis taught by Castro [ ] are for sorting and detecting                       
              single molecules by size . . . but [sic, not?] for detecting the presence or absence of a                   
              fluorescent probe” (Brief, pages 6-7).  We disagree.  Castro specifically teaches that the                  
              “technique is sensitive enough to detect and analyze a small, single-fluorophore                            



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