Ex Parte 5854038 et al - Page 3




                       Appeal No. 2006-0735                                                                                         
                       Reexamination Control No. 90/006,036                                                                         

                               tethering a localization signal to said therapeutic agent, wherein said                              
                       localization signal causes said therapeutic agent to be localized with said viral                            
                       target in a cellular or viral compartment of said cell.                                                      

               7.  According to the ‘038 specification:                                                                             
                               Prior localization of inhibitory RNAs which may be left in or transported                            
                       to the nucleus attempt to flood a large organelle, approximately 10 µM in                                    
                       diameter...with either antisense or decoy RNA inhibitors.  These strategies do not                           
                       specifically localize such inhibitors with any specific mRNA and pre-mRNA                                    
                       target even though approximately 105-106 different targets exist inside the                                  
                       nucleus.                                                                                                     
                               The present invention however, localizes an inhibitory RNA to a much                                 
                       smaller compartment, e.g., the core of a retroviral particle approximately 50 nM                             
                       in diameter and 10-6 to 10-7 the volume of the nucleus, in which a single large                              
                       RNA or DNA species, the viral genomic RNA or DNA exists...This million fold                                  
                       difference in localization specificity is achieved by targeting the therapeutic to a                         
                       sorting pathway which distinguishes viral genomic RNAs and DNAs from the rest                                
                       of the RNAs and DNAs in the cell.                                                                            
               (‘038 at 1:40-62).                                                                                                   
                                                                                                                                   
               8.  Regarding the “targeting” of the therapeutic agent, the ‘038 specification states the                            
                   following:                                                                                                       
                               Those in the art will recognize that many methods can be used for                                    
                       modification of existing therapeutic agents such that they are caused to be                                  
                       localized in an appropriate compartment with a viral target.  Thus for example,                              
                       RNA molecules (all of which are well known in the art) such as decoy RNAs,                                   
                       ribozymes, antisense RNA or DNA molecules can be synthesized in vivo from                                    
                       DNA molecules (or formed in vitro) such that they are covalently bonded with a                               
                       viral targeting agent, examples of which are provided below.  These agents are                               
                       termed “localization signals”.                                                                               






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