Ex Parte Short - Page 13



          Interference No. 105,188                                                    
          Short v. Punnonnen                                                          
          response to the unaltered antigen comprises: a) creating a                  
          library of DNA encoding a natural B7-2 antigen and DNA altered to           
          encode a B7-2 variant having reduced activity or enhanced                   
          inactivity; b) inducing homologous recombination between the                
   5      natural DNA and the altered DNA comprising a DNA library; and               
          c) screening all new DNA resulting from homologous recombination            
          of natural DNA and altered DNA comprising the DNA library for               
          expression of B7-2 variants which reduce the animal’s immune                
          response to a vaccine as compared to its natural immune response.           
  10      See the following excerpts from the Freeman PCT (Exh. 2040,                 
          p. 22, l. 17, to p. 23, l. 17; emphasis added):                             
               A transgene is a DNA which is integrated into the genome of            
               a cell from which a transgenic animal develops.  In one                
               embodiment, murine B7-2 cDNA or an appropriate sequence                
  15           thereof can be used to generate transgenic animals that                
               contain cells which express B7-2 protein.  Methods for                 
               generating transgenic animals, particularly animals such as            
               mice, have become conventional in the art and are described,           
               for example, in U.S. Patent Nos. 4,736,866 and 4,870,009.              
  20           Typically, particular cells would be targeted for B7-2                 
               transgene incorporation with tissue specific enhancers,                
               which could result in T cell costimulation and enhanced T              
               cell proliferation and autoimmunity.  Transgenic animals               
               that include a copy of a B7-2 transgene introduced into the            
  25           germ line of the animal at an embryonic stage can be used              
               to examine the effect of increased B7 expression.  Such                
               animals can be used to examine the effect of increased B7              
               expression.  Such animals can be used as tester animals for            
               reagents thought to confer protection from, for example,               
  30           autoimmune disease.  In accordance with this facet of the              
               invention, an animal is treated with the reagent and a                 
               reduced incidence of the disease, compared to untreated                
               animals bearing the transgene, would indicate a potential              
               therapeutic intervention for the disease.                              
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