Ex Parte MALFROY-CAMINE - Page 8


                 Appeal No. 2001-2379                                                         Page 8                    
                 Application No. 08/931,666                                                                             

                 barrier, and then diffuse across the cytoplasm before being exocytosed on the                          
                 other side.  See the Examiner’s Answer, page 6.  The examiner argues that this                         
                 would have led those of skill in the art to expect that “this cytoplasmic stage of                     
                 the transport process would then make the antibody available for binding to                            
                 intracellular antigens.”  Id.                                                                          
                        The evidence of record does not support the examiner’s position.                                
                 Appellant have provided evidence that those of skill in the art would not have                         
                 expected cationized antibodies to be available for antigen binding during the                          
                 cytoplasmic stage of traversing the blood-brain barrier.  The instant specification                    
                 cites Pardridge1 as disclosing that transcytosis across the blood-brain barrier                        
                 involves diffusion “presumably in nonclathrin-containing smooth vesicles.”  Thus,                      
                 the evidence suggests that those of skill in the art would have understood                             
                 Triguero’s reference to cationized antibodies diffusing through the cytoplasm to                       
                 mean diffusion of the antibodies in vesicles.  The examiner has pointed to no                          
                 evidence supporting an alternative reading of the reference, which would show                          
                 that those skilled in the art would have expected the antibodies to diffuse freely                     
                 through the cytoplasm and be available to bind to intracellular targets.                               
                        In addition, the evidence shows that many cells, including lymphoid cells,                      
                 commonly degrade endocytosed material in lysosomes.  See Renau-Piqueras,                               
                 page 745 (“As is well known, lysosomal degradation of endocytosed material is                          
                 common in many cell types, including resting and stimulated lymphoid cells.”).                         

                                                                                                                        
                 1 Pardridge, “Receptor-mediated peptide transport through the blood-brain barrier,” Endocrine          
                 Reviews, Vol. 7, No. 3, pp. 314-330 (1986), of record.                                                 





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