Ex parte DE LA BROUSSE et al. - Page 2


                Appeal No. 2001-1148                                                  Page 2                  
                Application No. 09/114,552                                                                    

                      Claims 11 and 14 are illustrative of the claims on appeal and read as follows:          
                11.  An isolated genetic knock-in primary mammalian adipocyte isolated from a                 
                transgenic mouse, wherein the adipocyte is a progeny of a genetic knock-in cell               
                made by homologous recombination of a native ob allele with a transgene                       
                comprising a sequence encoding a reporter flanked by flanking sequences which                 
                effect, in conjunction with the cell, the homologous recombination of the transgene           
                with the native ob allele, whereby the transgene resides on a chromosome in the               
                transgenic mouse, wherein the expression of the reporter is under the control of              
                native gene expression regulatory sequences of the native ob allele.                          
                14. A cell-based method for screening for modulators of ob gene expression, the               
                method comprising steps:                                                                      
                      (a) determining a first reporter expression level in a first isolated mammalian         
                adipocyte according to claim 11;                                                              
                      (b) contacting a second isolated mammalian adipocyte according to claim                 
                11 with a candidate agent under conditions whereby but for the presence of the                
                agent, the reporter is expressed at the first reporter expression level;                      
                      (c) determining a second reporter expression level in the second isolated               
                mammalian adipocyte; and                                                                      
                      (d) comparing the first expression level with the second expression level ,             
                wherein a difference between the first and second expression levels indicates that            
                the candidate agent modulates ob gene expression.                                             
                      The references relied upon by the examiner are:                                         
                Tartaglia                U.S. 5,741,666           April 21, 1998                             
                Kitamoto et al. (Kitamoto), "Humanized Prion Protein Knock-in Cre-Induced Site-               
                Specific Recombination in the Mouse," Biochemical and Biophysical Research                    
                Communications, 222, 742-747 (1996).                                                          
                Kress et al. (Kress), "Hox-2.3 upstream sequences mediate lacZ expression in                  
                intermediate mesoderm derivatives of transgenic mice," Development ,109,                      
                775-786 (1990).                                                                               
                Halaas et al. (Halaas), "Weight-Reducing Effects of the Plasma Protein Encoded by             
                the obese Gene," Science, Vol. 269, pp. 543-546, 28 July 1995.                                
                Cusin et al. (Cusin), "The ob Gene and Insulin  A Relationship Leading to Clues to            
                the  Understanding of Obesity," Diabetes, Vol. 44, pp. 1467-1470 (December                    
                1995).                                                                                        







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