BRAKE v. SINGH - Page 25




                Interference 102,728                                                                                                          
                1983.  Declaration, p. 3, para. 5.  Dr. Tekamp-Olson credibly describes how this                                              
                technique would have been employed by such persons, at the time the application was                                           
                filed, to make the “n=0” DNA construct described in Brake 1.  Dr. Tekamp-Olson                                                
                testified that one skilled in the art would have mutagenized (modified) the DNA                                               
                construct pYEGF-8 (Brake 1, p. 14, line 13),17 using an oligonucleotide primer which                                          
                lacks the sequence encoding the DPAP A (the glu-ala residues in the "-factor spacer                                           
                sequence) site to make the construct of the count.18  Id., p. 3, para. 5a.                                                    
                         We find credible Dr. Tekamp-Olson’s testimony that given the Brake 1 disclosure                                      
                and general knowledge in the art, one skilled in the art would have been able “to make”                                       
                a DNA construct within the scope of Count 1 at the time the Brake 1 application was                                           
                filed.  That is, we find that the technique of in vitro mutagenesis described by Dr.                                          
                Tekamp-Olson involves digesting the DNA construct described in Brake 1 with a well-                                           
                known restriction enzyme (BamHI), subcloning the digested DNA into a well-known                                               


                         17 pYEGF-8 is the same as pY"EGF-21 of Brake 2.                                                                      
                         18 We note that in its Opposition, Singh does not challenge this method of                                           
                making the invention of the count.  We further note that two of Singh’s declarants, Dr.                                       
                Singh and Dr. Hitzeman, testify that site-directed mutagenesis was well known in the art                                      
                by 1982.  To that end Dr. Singh testified:                                                                                    
                         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 36, Bates Nos. 000564-000566),                                        
                         this technique was known in the early 1970's and had developed into an                                               
                         established methodology by 1982.  SR 0568, para. 58.                                                                 
                         Dr. Hitzeman’s statement is identical to that of Dr. Singh.  SR 0168-0169,                                           
                para. 9.  Thus, we find Dr. Singh’s declarants agree with Dr. Tekamp-Olson’s                                                  
                statements.                                                                                                                   
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