Disulfide Bridging Conjugates

Abstract

Provided are bispecific conjugates having the general formula: pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and their use in the treatment of cancer.

What is claimed is: 
     
         1 . An injectable formulation comprising:
 (i) an effective amount of antibody Fab conjugate having a Formula I or a Formula II:   
       
         
           
           
               
               
           
         
         
           or a pharmaceutically acceptable salt thereof, wherein each n is independently an integer from 2 to 20; each m is independently an integer from 2 to 15, wherein each FAB fragment is connected to a pyrrolidine-dione moiety or a CH 2 -quinoxalinyl moiety through native cysteine residues in the Fab fragment; and 
         
         (ii) water, Ringer's solution U.S.P., isotonic sodium chloride solution, synthetic mono- or diglycerides, or oleic acid. 
       
     
     
         2 . The injectable formulation of  claim 1 , wherein n is an integer from 2 to 12. 
     
     
         3 . The injectable formulation of  claim 2 , wherein n is an integer from 4 to 10. 
     
     
         4 . The injectable formulation of  claim 3 , wherein n is 8. 
     
     
         5 . The injectable formulation of  claim 1 , wherein m is an integer from 2 to 10. 
     
     
         6 . The injectable formulation of  claim 5 , wherein m is an integer from 4 to 8. 
     
     
         7 . The injectable formulation of  claim 6 , wherein m is 6. 
     
     
         8 . The injectable formulation of  claim 1 , wherein the FAB fragment comprises a CD3 binding region. 
     
     
         9 . The injectable formulation of  claim 1 , wherein the solvent is water. 
     
     
         10 . The injectable formulation of  claim 1 , wherein the solvent is Ringer's solution U.S.P. 
     
     
         11 . The injectable formulation of  claim 1 , wherein the solvent is an isotonic sodium chloride solution. 
     
     
         12 . The injectable formulation of  claim 1 , wherein the solvent is a synthetic monoglyceride. 
     
     
         13 . The injectable formulation of  claim 1 , wherein the solvent is a synthetic diglyceride. 
     
     
         14 . The injectable formulation of  claim 1 , wherein the solvent is an oleic acid. 
     
     
         15 . A method of treating prostate cancer or adenocarcinoma, comprising administering to a subject in need thereof an injectable formulation of  claim 1 , or a pharmaceutically acceptable salt thereof. 
     
     
         16 . The method of  claim 15 , wherein the subject has prostate cancer. 
     
     
         17 . The method of  claim 15 , wherein the subject has adenocarcinoma.