Ex Parte LIGLER et al - Page 7


                 Appeal No.  1999-1384                                                                                 
                 Application No.  08/583,912                                                                           
                 flow rates to provide optimal reactions times can also be found in Ligler et al.                      
                 (‘740)(columns 5-10).”  Ligler discloses (column 6, lines 48-54) that:                                
                               The flow rate of the liquid stream in the method of this                                
                        invention should be between 0.1 and 2.0 milliliters per minute,                                
                        preferably between 0.3 and 0.8 milliliters per minute.  The optimum                            
                        flow rate is such that the residence time of the target on the                                 
                        exchanger is sufficient to generate displacement of measurable                                 
                        quantities of labelled antigen in the shortest possible time.                                  
                 Ligler discloses (column 9, lines 53-54) that “[t]ypical flow rates used with the                     
                 system are 0.3-0.8 ml/min, and that “picomoles of antigen can be detected under                       
                 continuous flow rates as fast as 0.8 ml/min” (column 10, lines 28-29).  However,                      
                 the examiner recognizes (Answer, bridging paragraph, pages 4-5) that Ligler’s                         
                 exemplified support medium is a sepharose bead.  While Ligler discloses other                         
                 alternative support media (column 9, lines 6-16), Ligler does not teach a porous                      
                 membrane as claimed.                                                                                  
                        To make up for this deficiency the examiner applies Kidwell.  According to                     
                 the examiner (Answer, page 5) “Kidwell teaches a displacement assay device                            
                 and method wherein the binding elements having labelled analogs of a target                           
                 analyte are immobilized on a porous [supporting] membrane.”  According to                             
                 Kidwell (column 6, lines 22-38):                                                                      
                        The semipermeable membrane can be any membrane that,                                           
                        together with the supporting membrane, regulates the fluid flow                                
                        rate so that the proper reactions take place.  Preferably, this                                
                        interaction time is between about one to about five minutes, with                              
                        two minutes being most preferred.  Hence, one can vary the pore                                
                        size and the area of the supporting and semipermeable                                          
                        membranes to achieve the proper interaction time.  The smaller the                             
                        pore size and the smaller the surface area of the membranes, the                               
                        longer the interaction time and the greater the sensitivity.  Also,                            
                        depending upon the pore size of the supporting membrane, an                                    
                        additional semipermeable membrane may not be required.  In the                                 
                        displacement mode using a nitrocellose [sic] membrane, optimum                                 
                        performance in both time and sensitivity results from 0.45 µm pore                             
                        size, with a three-sixteenth inch diameter membrane and                                        

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