BRAKE v. SINGH - Page 67




            Interference 102,728                                                                              
                         3.     Other corroborating evidence relied upon by Singh                             
                                a.  “Hitzeman SR158:8” and SX 25, Bates No. 483                               
                   Singh argues that Dr. Singh discussed his objective with his supervisor and at a           
            meeting with his coworkers.  Paper No. 180, p. 12.  Singh relies on “Hitzeman SR158:8”            
            and SX 25, Bates No. 483 for support.  Id. at pp. 12, 17, 19.                                     
                   Singh’s reliance throughout its brief (Paper No. 180) on “SR158:8,”40 i.e.,                


                   40 We note that in its original brief, Singh relied on the declaration of Dr.              
            Hitzeman (SR 168, para. 8).  Dr. Hitzeman states:                                                 
                         8.     On December 14, 1982, I gave a presentation on yeast secretion to             
                   the RRG.  In addition to myself, Arjun Singh presented his work on "-factor                
                   yeast secretion.  As evidenced by the Research Summary of this meeting                     
                   (Document GP530002489-2521) (Singh Exhibit 25, Bates Nos. 000455-000487,                   
                   in which all but the pertinent information has been blocked out), Arjun Singh              
                   describes the "-factor gene organization and the structure of the spacer                   
                   including the lys arg glu ala glu ala construct at this meeting.  Arjun also               
                   indicated at this meeting that his future work would include the removal of these          
                   sequences from the interferon D expression plasmid using site directed                     
                   mutagenesis and the construction of expression plasmids with a restriction                 
                   following the "-factor preprosequence.                                                     
                   However, even if we assume, arguendo, that Singh intended to rely on Dr.                   
            Hitzeman’s declaration, we find that it fails to corroborate the claim that Dr. Singh had         
            formulated a definite and permanent idea to employ the new loop deletion mutagenesis              
            method to remove the nucleotide sequence encoding the glu-ala residues of the "                   
            factor spacer sequence present in the interferon D expression plasmid on December 1,              
            1982.  Dr. Hitzeman not only fails to specify which amino acids would be removed, but             
            he also fails to mention the technique of loop deletion mutagenesis.  To the contrary,            
            Dr. Hitzeman only mentions site-directed mutagenesis which is further described in                
            paragraph 9 of his declaration.  According to Dr. Hitzeman:                                       
                         9.     During the period 1982 to 1983, site-directed deletion mutagenesis            
                   was a known technique.  As set forth in Sambrook, et al. “Molecular Cloning, “             
                   2nd Edition (1989) at pages 15.51 and 15.52 (Singh Exhibit 26, Bates Nos.                  
                   000564-566), this technique was known in the early 1970’s and had developed                
                   into an established methodology by 1982.                                                   
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