Ex parte LA DUCA - Page 4




              Appeal No. 1996-1811                                                                                       
              Application No. 08/169,968                                                                                 


              be rapidly obtained from the blood sample added with heparin without affecting the results                 
              of blood biochemistry tests” (page 4, lines 7-9).  The blood sample clotted within 30                      
              minutes (page 7, line 10).                                                                                 
                     Table 4 (page 132) in Lewis compares the effect of various clotting reagents on                     
              citrated normal and citrated heparinized plasma.  The clotting reagents are (1) bovine                     

              thrombin, (2) human thrombin, (3) Crotalus h. horridus snake venom, (4) Arvin                              

              (Ancestrodon rhodostoma) snake venom, (5) bovine thrombin combined with BaCl  and                          
                                                                                                    2                    
              (6) bovine thrombin combined with protamine.  According to Lewis,                                          
                            Heparin inhibits the thrombin clotting of fibrinogen but not the clotting                    
                     caused by some snake venoms.  Heparin is adsorbed from citrated plasma                              
                     onto insoluble barium citrate, which is formed when barium chloride is added                        
                     to citrated plasma.  Heparin is neutralized by protamine sulfate. [Page 132,                        
                     second full paragraph.]                                                                             
                                                                                                                        
                     JP 61-53567 describes preparing a thrombin-like enzyme from Trimeresurus                            

              okinavensis snake venom for use as a blood coagulation enhancing agent (page 4).                           

              Approximately 1.5 µg thrombin-like enzyme (i.e., 50 µg/ml x 0.30 µl used) can coagulate 5                  
              ml of normal human blood or heparinized blood within 20 to 25 minutes (page 6).                            
                     According to the examiner, “[t]he references disclose only the use of venom alone                   
              or protamine alone or thrombin in combination with protamine to clot heparinized blood or                  
              plasma” (answer, page 4, last sentence).  Thus,                                                            
                     ... it is prima facie obvious to combine two or more ingredients each of which                      
                     is taught by the prior art to be useful for the same purpose in order to form a                     

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