Ex Parte LUPTON - Page 4


                   Appeal No. 2001-0766                                                                Page 4                      
                   Application No. 08/483,941                                                                                      

                   rejection@ of claims 1, 2, 6, 11, 16, 26 and 36 is set forth at pages 5-7 of the                                
                   Examiner’s Answer as follows:                                                                                   
                                  Germann et al. disclose the use of a[n] in-frame chimeric                                        
                                  fusion gene between the genes encoding a dominant selectable                                     
                                  marker and a protein of interest as a simple means of selecting                                  
                                  for eukaryotic cells expressing the protein of interest and the                                  
                                  use of retroviral vectors as the means of introduction of the                                    
                                  chimeric genes into the cells.  Germann et al. teach on page                                     
                                  7418, paragraph 1 the advantages of fusing the dominant                                          
                                  selectable gene to the gene of interest in contrast to vectors in                                
                                  which the dominant selectable gene and unselectable gene of                                      
                                  interest are under the control of different promoters i.e.[,] the                                
                                  use of a fusion gene encoding a chimeric protein ensures that                                    
                                  the expression of both the selected and unselected constituents                                  
                                  occurs in the selected cells.                                                                    
                                  Borrelli et al. and Moolten et al. each disclose that the                                        
                                  expression of negative selectable markers, particularly the                                      
                                  HSV1 thymidine kinase gene (HSV1-TK) within eukaryotic cells                                     
                                  (which are naturally TK+), is useful for the selective elimination                               
                                  of particular cell types within a living organism.  Moolten et al.                               
                                  further disclose the use of the neomycin phosphotransferase                                      
                                  gene (NeoR) as a dominant selectable marker to select for cells                                  
                                  expressing the HSV1-TK gene as well[] as vectors for the                                         
                                  introduction of the HSV1-TK gene into cells which comprise both                                  
                                  a dominant selectable marker (NeoR) and the negatively                                           
                                  selectable gene (HSV1-TK) each under the control of a different                                  
                                  promoter.  Cells expressing the HSV1-TK gene are selected for                                    
                                  by growing the transformed cells in the presence of neomycin.                                    
                                  Therefore, as positive selection for cells which express the                                     
                                  HSV1-TK gene is possible only in mutant TK- cells (whereas                                       
                                  both Borrelli et al. and Moolten et al. teach that one would                                     
                                  desire to produce cells which are naturally TK+ expressing this                                  
                                  gene), it would have been obvious to one of ordinary skill in the                                
                                  art to construct a vector comprising a chimeric gene fusion                                      
                                  between the HSV1-TK gene and a dominant selectable marker                                        
                                  (such as NeoR) in order to be able to select for cells expressing                                
                                  this useful gene within any cell type.  One of ordinary skill in the                             
                                  art would have been motivated to fuse the HSV1-TK gene to the                                    
                                  dominant selectable marker instead of using a vector similar to                                  
                                  that of Moolten et al. by the advantages of such a strategy                                      
                                  taught by Germann et al.  It would have been further obvious to                                  
                                  transduce this vector into eukaryotic cells and to grow these                                    
                                  cells under the selection pressure of the dominant selectable                                    






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