Ex parte KAMBOJ et al.; Ex parte FOLDES et al. - Page 65


                  Appeal No.  1997-3221                                                                                         
                  Application No.  08/249,241                                                                                   
                  4q25-34.3.                                                                                                    
                          At this point we find that under high stringency hybridization conditions, a                          
                  probe for GluR1 cross-reacts with GluR2.  Little more is provided in Sun, other than                          
                  the “note” at page 1447 which states “[a]fter submission of this manuscript a paper                           
                  [referring to Puckett] appeared reporting …GluH1.  This cDNA shows differences                                
                  with HBGR1 … in a region corresponding to the alternatively spliced exon identified                           
                  in the rodent clones by Sommer [‘92]… and designated as flip and flop forms of                                
                  GluR1.”  So not only is there cross-reactivity between the receptors, there is also the                       
                  possibility of alternative splicing events.                                                                   
                          Puckett, relied upon by the examiner (Answer, page 5) to teach isolation of                           
                  human GluR1, teaches the use of a reduced stringency hybridization (bridging                                  
                  paragraph pages 7557-558).  Furthermore, Puckett also teaches the existence of                                
                  alternative splicing events (page 7560, column 1), later confirmed by Sun’s “note,”                           
                  supra.                                                                                                        
                          The examiner relies upon Heinemann to teach GluR2 (Answer, page 4).  We                               
                  note Heinemann’s Example 8 (page 27) which teaches “cDNA clones encoding the                                  
                  GluR2 and GluR3 genes were isolated from an adult rat forebrain library using a                               
                  low-stringency hybridization screening protocol … and a radiolabeled fragment of                              
                  the GluR1 cDNA as a probe.”                                                                                   
                          Thus a GluR1 probe cross-reacts with GluR2 and GluR3.  Heinemann further                              
                  teaches that a GluR2 probe cross-reacts with GluR4 and GluR5 (Heinemann,                                      
                  Example 14, page 33).                                                                                         



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