Ex Parte BENNETT et al - Page 2



              Appeal No. 2003-1678                                                                Page 2                
              Application No. 08/722,659                                                                                

              Zimmermann et al. (Zimmermann)            5,997,863            Dec. 7, 1999                               
                     Claims 1 through 7, 18, and 19 stand rejected under 35 U.S.C. § 102(e) or                          
              § 102(f) as anticipated by Zimmermann.  We affirm the rejection premised upon                             
              35 U.S.C. § 102(e).  Since that constitutes a disposition of the appeal, we need not                      
              reach the merits of the alternative rejection under 35 U.S.C. § 102(f).                                   
                                                     Background                                                         
                     The invention set forth in the written description of this application is directed to              
              the use of heparinase enzyme to reduce localized inflammatory responses.                                  
              Specification, page 1.  Heparinase acts to degrade heparin and heparan sulfate                            
              moieties on the surface of endothelial cells and from  basement membranes.  Id., page                     
              8.  The release of heparin and heparan sulfate moieties in this manner also serves to                     
              release chemokines which are bound to the heparin and heparan sulfate.  As                                
              explained:                                                                                                
                            The removal of heparin and heparan sulfate from endothelial cells                           
                     interferes with L-selectin interactions with endothelium, preventing                               
                     increased leukocyte rolling.  The removal of glycosaminoglycans from                               
                     endothelial cells and basement membranes also removes                                              
                     glycosaminoglycan bound chemokines, which are critical for leukocyte                               
                     recruitment.  Loss of endothelial cells bound chemokines decreases                                 
                     activation of leukocyte integrins and inhibits firm adhesion by the                                
                     leukocytes.  It also inhibits extravasation of leukocytes, because the                             
                     leukocytes require the presence of a bound gradient of chemokine for                               
                     transmigration.  It is believed, without being limited, that unbound                               
                     chemoattractants are depleted from the endothelium layer by blood flow,                            
                     preventing formation of a significant soluble chemoattractant gradient.                            

                            Generally, after a one hour heparinase treatment, 50% of the                                
                     digested cell surface and basement membrane heparin and heparan                                    
                     sulfate are replaced within 2 to 4 hours, and it is completely replaced                            
                     within 12 to 16 hours.  Longer treatment times (3 and 5 hours) greatly                             





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