BRAKE v. SINGH - Page 74




            Interference 102,728                                                                              
            declarants mention that the 24-mer is of the precise length and complementarity                   
            needed to perform loop deletion mutagenesis.                                                      
                   Singh argues that the “oligonucleotide is one of 2.8 x 1014 possible 24-mers that          
            Dr. Singh could have ordered.”43  Paper No. 180, p. 18.  According to Singh, the:                 


                   43 Singh’s argument is not clear.  That is, it is not clear whether Singh intends to       
            argue that if Dr. Singh were to make (i) any 24-mer oligonucleotide that there are 2.8 x          
            1014 possible nucleotide combinations, or (ii) a 24-mer which is complementary to the             
            eight (8) amino acids at the junction (SX 3, Bates No. 108) that there are 2.8 x 1014             
            possible nucleotide combinations.  We address the former argument on p. 76, wherein               
            we state that there is only one oligonucleotide sequence which is an exact complement             
            of the junction region.                                                                           
                   However, if Singh intends to argue the latter, we point out that the mathematical          
            calculation wherein there are said to be four (4) possible nucleotides for all 24                 
            nucleotides (8 codons) comprising an oligonucleotide (a 24-mer) which complements                 
            the eight (8) amino acids at the junction (i.e., leu-asp-lys-arg-cys-asp-leu-pro), is             
            incorrect.  Degeneracy of the genetic code does not involve each nucleotide in the                
            codon.  The degeneracy usually occurs with the third nucleotide codon, and with the               
            eight (8) amino acids under consideration here, never in all three positions.  For                
            example, if we consider the amino acid “lys” which occurs once in the series of amino             
            acids at the junction, and use a genetic dictionary (BX 25), we find that it is encoded by        
            “AAA” or “AAG.”  Thus, there are only two (2) possible codons for this amino acid or,             
            conversely, only two codons which will complement the nucleotide sequence.  However,              
            according to Singh’s method of calculating there would be 4 to the 3rd power (43) or 64           
            possibilities.  We point out that of the eight (8) amino acids at the junction, “leu” and         
            “arg” are encoded by the greatest number of codons; i.e., “leu” and “arg” are each                
            encoded by six (6) different codons.  For example “leu” is encoded by “TTA,” “TTG,”               
            “CTT,” “CTC,” “CTA” and “CTG.”  However, according to Singh’s method of calculating,              
            “leu” (and “arg”) would be encoded by 4 to the 3rd power (43) or 64 possible codons.              
            Continue this faulty method of calculating for the remaining codons, and the problem              
            becomes greatly exaggerated, as it has been here.  Thus, we find that only attorney               
            argument could turn a sequence of eight (8) amino acids into a sequence which is                  
            encoded (or complemented) by 2.8 x 1014 possible oligonucleotides.  Accordingly, it is            
            with good reason the Court has held on numerous occasions that arguments of counsel               
            cannot take the place of objective evidence.  In re Payne, 606 F.2d at 315, 203 USPQ              
            at 256; Meitzner v. Mindick, 549 F.2d at 782, 193 USPQ at 22; In re Lindner, 457 F.2d             
            at 508, 173 USPQ at 358.   While we have taken the time to point out the error in this            
            argument, we nevertheless adhere to our original position, i.e., if Dr. Singh wanted an           
            oligonucleotide which was complementary to the eight (8) amino acids at the junction,             
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