BRAKE v. SINGH - Page 45




                Interference 102,728                                                                                                          
                position, Singh appeared to urge that Dr. Singh’s conception occurred sometime before                                         
                Brake’s January 12, 1983, filing date.  Id., p. 88                                                                            
                         As to the events which were said to have occurred between December 1, 1982,                                          
                and January 12, 1983, Singh argued (Paper No. 151, pp. 85-87):                                                                
                                 By December 1, 1982, Dr. Singh had devised a plan to delete from the                                         
                         DNA construct contained in p60, the DNA encoding “Gh [sic, Glu] -Ala-Glu-Ala-                                        
                         Leu-Glu-Phe-Met.”  The resulting construct would conform to the Count.  Dr.                                          
                         Singh's solution was to use a new methodology developed by his Genentech co-                                         
                         workers called “loop-deletion mutagenesis.”                                                                          
                                 The loop-deletion mutagenesis process utilized methodology that was                                          
                         developed at Genentech late in 1982 and was first published late in 1983 by                                          
                         several Genentech scientists which included Mr. Vasser. (Vasser, SR 1059-                                            
                         1060; SX 53).  As shown and described in the article, the DNA to be deleted was                                      
                         looped-out by the annealing of a synthetic oligodeoxyribonucleotide to the coding                                    
                         strand of the gene contained on the single stranded form of the recombinant                                          
                         phage M13mp8 DNA.  The resulting heteroduplex structure was then stabilized                                          
                         using primer-directed in vitro DNA synthesis in the presence of T4 DNA ligase.                                       
                         On transformation of E. coli, the heteroduplex DNAs yield phage whose                                                
                         genomes contained either the original or the partially deleted gene, and                                             
                         genotypes were distinguished by in situ plaque hybridization with synthetic                                          
                         oligonucleotide probes.                    %%%                                                                       
                                 On December 1, 1982, Dr. Singh requested the synthesis of an                                                 
                         oligonucleotide 24 nucleotides in length to be used in his loop-deletion                                             
                         mutagenesis process.  This is corroborated by Mr. Ng (Ng, SR 478, 516-517).                                          
                         This request was verified by the signatures of Mr. Vasser dated December 1,                                          
                         1982 and Mr. Ng dated December 20, 1982.  The request was also corroborated                                          
                         by other records kept by the DNA Synthesis department. (Ng, SR 478; SX 6,                                            
                         Bates No. 186; SX 7, Bates No. 192).  Mr. Ng also verified that the synthesis was                                    
                         completed December 20, 1982 (Ng, SR 478).  Dr. Singh and his co-workers                                              
                         subsequently used that methodology, and those materials, to successfully                                             
                         complete the reduction to practice.                                                                                  
                         Thus, on this record, the merits panel concluded that Singh had not met its                                          
                burden of proving, by a preponderance of the evidence, that it had conceived of the                                           
                invention of Count 1 on either October 1, or prior to January 12, 1983.                                                       

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