Ex parte KAMBOJ et al.; Ex parte NUTT; Ex parte FOLDES et al. - Page 57


                  Appeal No.  1999-1393                                                                                       
                  Application No.  08/242,344                                                                                 
                  homologous to rat GluR1, the second clone was found to be homologous to GluR2.                              
                  Sun, page 1444, bridging paragraph, columns 1-2.  Sun localizes the HBGR2-                                  
                  encoding gene on chromosome 4q25-34.3.  Sun does not disclose any specific                                  
                  sequence for GluR2.                                                                                         
                         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 6) 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.”                                                                               



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