Ex parte TERSTAPPEN et al. - Page 5




              Appeal No. 1997-2391                                                                                       
              Application 08/239,265                                                                                     


                     myeloid cells and non-hematopoietic cells (i.e., stromal and epithelial cells).                     
                     (Specification, page 2).                                                                            
                     Kansas describes the pattern of expression of three classes of leukocyte adhesion                   
              molecules during normal differentiation of monocytes, granulocytes, and erythrocytes in                    
              humans: the CD11/CD18 heterodimers (including CD11a/CD18, the leukocyte function-                          
              associated antigen 1 (LFA-1)), the CD44 family, and the LAM-1 (leukocyte adhesion                          
              molecule 1) molecule(s).  Differential expression of transferrin receptor/CD71 and CD45                    
              was noted in the course of investigating the down regulation of CD44 during erythroid                      
              development:                                                                                               
                     Although the absence of any markers specific for glycoG erythroid cells make                        
                     analysis of the phenotype of these cells difficult, the data described below                        
                                                                                              hi                         
                     indirectly suggest that these early committed erythroid cells are CD44 LFA-                         
                     1GLAM-1G.  No cells coexpressing glyco and either LFA-1 or LAM-1 were                               
                     detectable . . . , consistent with the loss of these markers being an early                         
                     event in erythropoiesis.  In contrast, CD44 was expressed at high levels on a                       
                                     +                                              +     hi                          
                     subset of glyco  cells; further analysis showed that these glyco CD44  cells                        
                     coexpressed CD45, a marker found on all leukocytes and early erythroid                              
                                  +                                                                                      
                     cells.   Glyco  cells that expressed intermediate levels of CD44 were                               
                                                +        +                                                               
                     transferrin receptor/CD71 .  Glyco  cells expressing neither CD45 nor CD71                          
                     expressed low levels of CD44, similar to that found on normal, circulating                          
                     RBC.  Thus, CD44 expression declines gradually in a stepwise fashion                                
                     during normal erythropoiesis.  (Kansas, page 2486, citations and references                         
                     to figures omitted).                                                                                
                                                                                                                        
                                                                        +      +               int                      
              In addition, Figure 4b of Kansas shows that “most glyco CD71  cells are CD44 , but a                       
                                        +      +           hi                                                            
              minor subset of the glyco CD71  are CD44 .”                                                                




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