STICE et al. V. STICE et al. V. STRELCHENKO et al. V. HENSEN et al. - Page 23





                                  cloned embryos can also be combined with fertilized embryos to produce                                                  
                                  chimeric embryos, fetuses and/or offspring.                                                                             
                 Strelchenko Ex. 2001, col. 1, 11. 5-14. The use of differentiated cells is also said to significantly                                    
                 simplify the cloning process involving transgenic mammals:                                                                               
                                           The present invention also allows simplification of transgenic                                                 
                                  procedures by working with a differentiated cell source that can be clonally                                            
                                  propagated. This eliminates the need to maintain the cells in an                                                        
                                  undifferentiated state, thus, genetic modifications, both random integration                                            
                                  and gene targeting, are more easily accomplished. Also by combining nuclear                                             
                                  transfer with the ability to modify and select for these cells in vitro, this                                           
                                  procedure is more efficient than previous transgenic embryo techniques.                                                 
                                  According to the present invention, these cells can be clonally propagated                                              
                                  without cytokines, conditioned media and/or feeder layers, further                                                      
                                  simplifying and facilitating the transgenic procedure. When transfected cells                                           
                                  are used in cloning procedures according to the invention, transgenic                                                   
                                  embryos are produced which can develop into fetuses and offspring. Also,                                                
                                  these transgenic cloned embryos can be used to produce CICM cell lines or                                               
                                  other embryonic cell lines. Therefore, the present invention eliminates the                                             
                                  need to derive and maintain in vitro an undifferentiated cell line that is                                              
                                  conducive to genetic engineering techniques.                                                                            
                 Strelchenko Ex. 2001, col, 6,11. 40-59.                                                                                                  
                          The prosecution history of Stice application 08/781,752 which matured into the Stice 577                                        
                 patent, similarly demonstrates that the use of differentiated rather than totipotent (undifferentiated)                                  
                 cells was contemplated. Thus, the original title of the application was "Cloning Using Donor Nuclei                                      
                 from Differentiated Fetal and Adult Cells." Stice Application 08/781,752, Paper 1, title page. In                                        
                 response to a rejection and in summarizing a discussion with an examiner during an interview,                                            
                 applicant characterized the invention as using somatic cells and that those cells were differentiated:                                   
                                  It was explained that the subject invention comprises a pioneering discovery,                                           
                                  i.e., that somatic cells or cells committed to a somatic cell lineage may be                                            
                                  used as nuclear transfer donors for cloning desired non-human mammals by                                                
                                  nuclear transfer techniques. It was indicated that this was a surprising                                                
                                  discovery as it was contravened by previous accepted dogma in the art.                                                  
                                  Essentially, prior to the present invention, it was thought that once a cell                                            
                                  becomes differentiated that it loses its ability to be a suitable donor cell                                            
                                  during nuclear transfer.                                                                                                



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