Ex Parte GLUSENKAMP et al - Page 2


                Appeal No.  2001-0756                                                   Page 2                
                Application No.  08/666,400                                                                   
                                compound in methanol in the presence of triethylamine to form                 
                                active matrices with active groups;                                           
                             b) dissolving a protein containing at least one primary or                       
                                secondary amino group and adding the protein to the activated                 
                                matrices;                                                                     
                             c) incubating the activated matrices and the protein of step b) at a             
                                pH of 7-10 and a temperature of +4ºC to +60ºC in an aqueous                   
                                buffer system, free of primary and secondary amines, to thereby               
                                immobilize the protein of step b) on the matrices.                            
                      The references relied upon by the examiner are:                                         
                Arnold                         4,560,504                Dec. 24, 1985                       
                Lau                           4,952,519                Aug. 28, 1990                       
                Cuatrecasas et al. (Cuatrecasas), Affinity Chromatography, in Methods in                      
                Enzymology, Vol. XXII, pp. 345-378 (William B. Jakoby ed., Academic Press)                    
                (1971)                                                                                        
                (Harlow), ANTIBODIES, A Laboratory Manual, pp. 522-32, and 528 (Ed Harlow                     
                et al., eds., Cold Spring Harbor Laboratory) (1988)                                           
                Glüsenkamp et al., “Squaric Acid Diethylester: A Simple and Convenient                        
                Coupling Reagent,” J. Biosciences, Vol. 46, pp. 498-501 (1991)                                
                Tietze et al. (Tietze), “Squaric Acid Diethyl Ester: A New Coupling Reagent for               
                the Formation of Drug Polymer Conjugates.  Synthesis of Squaric Acid Ester                    
                Amides and Diamides,” Chem. Ber., Vol. 124, No. 5, pp 1215-21 (1991)                          
                                         GROUND OF REJECTION                                                  
                      Claims 58-67 stand rejected under 35 U.S.C. § 103 as being unpatentable                 
                over Tietze or Glüsenkamp in view of Harlow, Arnold, Cuatrecasas and Lau.                     
                      We reverse.                                                                             
                                                DISCUSSION                                                    
                      The examiner relies (Answer, page 5) on Tietze and Glüsenkamp in the                    
                alternative to “teach the use of a cyclobutane carboxylic acid derivative to                  
                conjugate amine bearing molecules conducting the reaction in either inert                     
                solvents (viz, ethanol) or non-amine containing aqueous buffers at pH7.”                      






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