Chimeric proteins with cell-targeting specificity and apoptosis-inducing activities

Abstract

The present invention relates to chimeric proteins with cell-targeting specificity and apoptosis-inducing activities. In particular, the invention is illustrated by examples of chimeric proteins of a cell-targeting moiety and an apoptosis-inducing moiety, such as cytochrome C, a caspase, e.g., Caspase3, DNA fragmentation factor (DFF40), a fragment of an apoptotic protein of the Bcl-2 family, such as Bik, Bax and Bak, etc,. The chimeric proteins specifically target cells expressing a binding site for the target protein, and induce cell-specific apoptosis.

1 - 36 . (canceled)  
     
     
         37 . A chimeric protein comprising a cell-specific targeting moiety and an apoptosis-inducing moiety, wherein the apoptosis-inducing moiety is a capsase, cytochrome C, a DNA fragmentation factor (DFF), a fragment of an apoptotic protein of the Bcl-2 family which fragment has apoptosis-inducing activity, or a domain of a capsase, cytochrome C or DFF which domain has apoptosis-inducing activity.  
     
     
         38 . The chimeric protein of  claim 37  in which the apoptosis-inducing moiety is a protein of human origin.  
     
     
         39 . The chimeric protein of  claim 37  in which the apoptosis-inducing moiety is DFF 40.  
     
     
         40 . The chimeric protein of  claim 37  in which the apoptosis-inducing moiety is a caspase.  
     
     
         41 . The chimeric protein of  claim 37  in which the apoptosis-inducing moiety is caspase 3.  
     
     
         42 . The chimeric protein of  claim 37  in which the apoptosis-inducing moiety is cytochrome C.  
     
     
         43 . The chimeric protein of  claim 37  in which the apoptosis-inducing moiety is a fragment of an apoptotic protein of the Bcl-2 family.  
     
     
         44 . The chimeric protein of  claim 37  in which the cell-specific targeting moiety binds interleukin 2 receptor-expressing cells.  
     
     
         45 . The chimeric protein of  claim 37  in which the cell-specific targeting moiety is an interleukin.  
     
     
         46 . The chimeric protein of  claim 45  in which the cell-specific targeting moiety is an interleukin 2.  
     
     
         47 . The chimeric protein of  claim 37  in which the cell-specific targeting moiety is myelin basic protein.  
     
     
         48 . The chimeric protein of  claim 37  in which the cell-specific targeting moiety binds tumor cells.  
     
     
         49 . The chimeric protein of  claim 37  in which the cell-specific targeting moiety is an antibody or a fragment thereof.  
     
     
         50 . The chimeric protein of  claim 49  in which the cell-specific targeting moiety is a single chain antibody.  
     
     
         51 . The chimeric protein of  claim 49  in which the cell-specific targeting moiety is a Fc fragment of an IgE antibody.  
     
     
         52 . The chimeric protein of  claim 37  in which the cell-specific targeting moiety is a cytokine.  
     
     
         53 . The chimeric protein of  claim 37  in which the cell-specific targeting moiety is epidermal growth factor.  
     
     
         54 . The chimeric protein of  claim 37  in which the cell-specific targeting moiety is insulin-like growth factor.  
     
     
         55 . The chimeric protein of  claim 37  which is produced by a recombinant DNA method.  
     
     
         56 . The chimeric protein of  claim 37  which is produced by a chemical conjugation method.  
     
     
         57 . The chimeric protein of  claim 37  in which the two moieties are connected by a polylinker.  
     
     
         58 . A pharmaceutical composition comprising a chimeric protein according to  claim 37  and a pharmaceutically acceptable carrier.  
     
     
         59 . A pharmaceutical composition comprising a chimeric protein according to claim  38 - 40  and a pharmaceutically acceptable carrier.  
     
     
         60 . A pharmaceutical composition comprising a chimeric protein according to claim  41 - 42  and a pharmaceutically acceptable carrier.  
     
     
         61 . A pharmaceutical composition comprising a chimeric protein according to  claim 43  and a pharmaceutically acceptable carrier.  
     
     
         62 . A pharmaceutical composition comprising a chimeric protein according to claim  44 - 46  and a pharmaceutically acceptable carrier.  
     
     
         63 . A pharmaceutical composition comprising a chimeric protein according to  claim 47  and a pharmaceutically acceptable carrier.  
     
     
         64 . A pharmaceutical composition comprising a chimeric protein according to  claim 48  and a pharmaceutically acceptable carrier.  
     
     
         65 . A pharmaceutical composition comprising a chimeric protein according to claim  49 - 51  and a pharmaceutically acceptable carrier.  
     
     
         66 . A pharmaceutical composition comprising a chimeric protein according to claim  52 - 54  and a pharmaceutically acceptable carrier.  
     
     
         67 . A pharmaceutical composition comprising a chimeric protein according to claim  55 - 57  and a pharmaceutically acceptable carrier.  
     
     
         68 . A method of treating a pathological disorder associated with undesirable target cells, comprising administering to a patient in need thereof a chimeric protein comprising a targeting moiety specific for the undesirable cells and an apoptosis-inducing