Methods of treatment using anti-erbb antibody maytansinoid conjugates

Abstract

The application concerns methods of treatment using anti-ErbB receptor antibody-maytansinoid conjugates, and articles of manufacture suitable for use in such methods. In particular, the invention concerns ErbB receptor-directed cancer therapies, using anti-ErbB receptor antibody-maytansinoid conjugates.

1 - 36 . (canceled) 
     
     
         37 . A method of treating a breast cancer characterized by overexpression of ErbB2 in a mammal comprising administering to the mammal a therapeutically effective amount of huMAb4D5-8 conjugated to DM1 via a disulfide or thioether group. 
     
     
         38 . The method of  claim 37 , wherein huMab4D5-8 and DM1 are conjugated via a disulfide group. 
     
     
         39 . The method of  claim 38 , wherein the disulfide group is N-succinimidyl-4-(2-pyridylthio)pentanoate. 
     
     
         40 . The method of  claim 38 , wherein the disulfide group is N-succinimidyl-3-(2-pyridyldithio)propionate. 
     
     
         41 . The method of  claim 37 , wherein huMab4D5-8 and DM1 are conjugated via a thioether group. 
     
     
         42 . The method of  claim 41 , wherein the thioether group is succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate. 
     
     
         43 . The method of  claim 37 , wherein the mammal is a human. 
     
     
         44 . The method of  claim 37 , wherein the breast cancer does not respond or responds poorly to treatment with huMAb4D5-8. 
     
     
         45 . The method of  claim 41 , wherein the breast cancer does not respond or responds poorly to treatment with huMAb4D5-8. 
     
     
         46 . The method of  claim 42 , wherein the breast cancer does not respond or responds poorly to treatment with huMAb4D5-8. 
     
     
         47 . The method of  claim 43 , wherein the breast cancer does not respond or responds poorly to treatment with huMAb4D5-8. 
     
     
         48 . The method of  claim 37 , wherein the breast cancer overexpresses ErbB2 at a 2+ level or more. 
     
     
         49 . The method of  claim 37 , wherein the breast cancer overexpresses ErbB2 at a 3+ level or more. 
     
     
         50 . The method of  claim 43 , wherein the breast cancer overexpresses ErbB2 at a 3+ level or more. 
     
     
         51 . The method of  claim 37 , wherein administration is intravenous. 
     
     
         52 . The method of  claim 37 , wherein the conjugate comprises from 3 to 5 maytansinoid molecules per huMAb4D5-8 molecule. 
     
     
         53 . The method of  claim 37 , wherein the method further comprises treatment with a second anti-ErbB2 antibody. 
     
     
         54 . The method of  claim 53 , wherein the second anti-ErbB2 antibody is 2C4 or a humanized variant thereof.