Anti-angiogenic compounds

Abstract

The present invention provides AA targeting compounds which comprise AA targeting agent-linker conjugates which are linked to a combining site of an antibody. Various uses of the compounds are provided, including methods to treat disorders connected to abnormal angiogenesis.

1 - 175 . (canceled) 
     
     
         176 . A compound of the formula: 
       
         
           
           
               
               
           
         
       
       wherein Z is of the formula: 
       
         
           
           
               
               
           
         
       
       wherein Antibody is an aldolase catalytic antibody, and v is 1, 2, 3, 4, or 5; w is 1, 2, 3, 4, or 5; and R b  is hydrogen, substituted or unsubstituted C 1-10  alkyl, substituted or unsubstituted C 3-7  cycloalkyl-C 0-6  alkyl, or substituted or unsubstituted aryl-C 0-6  alkyl, and q is 0, 1, 2 or 3. 
     
     
         177 . A compound as claimed in  claim 176 , wherein v is 1, w is 1, R b  is hydrogen. 
     
     
         178 . A compound of the formula: 
       
         
           
           
               
               
           
         
       
       wherein Antibody is an aldolase catalytic antibody, and v is 1, 2, 3, 4, or 5; w is 1, 2, 3, 4, or 5; and R b  is hydrogen, substituted or unsubstituted C 1-10  alkyl, substituted or unsubstituted C 3-7  cycloalkyl-C 0-6  alkyl, or substituted or unsubstituted aryl-C 0-6  alkyl, q is 0, 1, 2 or 3, and AAn-AA2-AA1-N is an Anti-Angiogenic peptide. 
     
     
         179 . A compound as claimed in  claim 178 , wherein v is 1, w is 1, R b  is hydrogen and q is 2. 
     
     
         180 . A compound as claimed in  claim 176 , wherein said Antibody is selected from full length antibody, Fab, Fab′, F(ab′) 2 , F v , dsF v , scF v , V H , diabody, or minibody comprising V H  and V L  domains from h38c2. 
     
     
         181 . A compound according to  claim 176 , wherein said Antibody comprises a variable light chain comprising SEQ ID NO:32 and a variable heavy chain comprising SEQ ID NO:33. 
     
     
         182 . A compound according to  claim 176 , wherein said Antibody comprises a light chain comprising SEQ ID NO:40 and a heavy chain comprising SEQ ID NO:41. 
     
     
         183 . A compound as claimed in  claim 178 , wherein said Antibody is selected from full length antibody, Fab, Fab′, F(ab′) 2 , F v , dsF v , scF v , V H , diabody, or minibody comprising V H  and V L  domains from h38c2. 
     
     
         184 . A compound according to  claim 178 , wherein said Antibody comprises a variable light chain comprising SEQ ID NO:32 and a variable heavy chain comprising SEQ ID NO:33. 
     
     
         185 . A compound according to  claim 178 , wherein said Antibody comprises a light chain comprising SEQ ID NO:40 and a heavy chain comprising SEQ ID NO:41. 
     
     
         186 . A compound of the formula: 
       
         
           
           
               
               
           
         
       
     
     
         187 . A method of synthesizing a compound according to  claim 186 , comprising the following route: 
       
         
           
           
               
               
           
         
       
     
     
         188 . A compound of the formula: 
       
         
           
           
               
               
           
         
       
     
     
         189 . A use of a compound according to  claim 188  in the manufacture of a compound of the formula: 
       
         
           
           
               
               
           
         
       
     
     
         190 . A compound of the formula: 
       
         
           
           
               
               
           
         
       
     
     
         191 . Use of a compound according to  claim 190  in the manufacture of a compound of the formula: