Ex Parte KOREN et al - Page 3


               Appeal No. 2004-2138                                                                        Page 3                  
               Application No. 08/765,324                                                                                          

                       Each of the classes of lipoproteins (LDL, HDL, etc.) in turn includes different                             
               apolipoproteins in different proportions.  LDL includes only Apo B-100 as its protein                               
               component, although Apo B-100 is also present in VLDL and intermediate density                                      
               lipoproteins (IDL).  By contrast, approximately 90% of the apolipoprotein in HDL is Apo                             
               A-I or Apo A-II, while apolipoproteins in the Apo C and Apo E groups are present in all                             
               types of lipoprotein except LDL.  Specification, page 2.                                                            
                       “Many epidemiological and clinical studies have shown that increased LDL levels                             
               in the blood are associated with increased risk of CHD [coronary heart disease].”  Page                             
               4.  “In contrast . . ., individuals with high concentrations of HDL . . .  seldom express                           
               symptoms of CHD.”  Page 5.  The specification discloses “antibodies immunoreactive                                  
               with specific epitopes on lipoproteins, such as those on LDL, VLDL and HDL, that                                    
               enable rapid and reliable determinations of levels of lipoproteins and/or apolipoproteins                           
               in whole blood, serum or plasma.”  Page 14.                                                                         
                       In particular, the specification discloses that “[c]onventional ways of producing                           
               MAbs [monoclonal antibodies] to Apo B-100 include immunization of mice with LDL. . . .                              
               However, MAbs produced using LDL as an immunogen tend to be sensitive to                                            
               conformational changes of Apo B-100 caused by variations in the lipid composition of                                
               LDL particles.”  Page 26.  “To obtain an anti-LDL MAb whose binding to LDL particles is                             
               not dependent on variations in LDL composition and/or conformation, mice were                                       
               immunized with soluble Apo B-100 which had been delipidized, reduced,                                               
               carboxymethylated and, purified by electrophoration in polyacrylamide gels containing 8                             
               M urea (Lee, D.M. et al., Biochim. Biophys. Acta, 666:133-146 (1981)).”  Id., page 27.                              







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