Eribulin-based antibody-drug conjugates and methods of use

Abstract

Linker toxins and antibody-drug conjugates that bind to human oncology antigen targets such as folate receptor alpha and/or provide anti-tubulin drug activity are disclosed. The linker toxins and antibody-drug conjugates comprise an eribulin drug moiety and can be internalized into target antigen-expressing cells. The disclosure further relates to methods and compositions for use in the treatment of cancer by administering the antibody-drug conjugates provided herein.

1 - 183 . (canceled) 
     
     
         184 . A composition comprising -L-D, wherein D is eribulin; and L is a cleavable linker covalently attached to D, wherein the cleavable linker comprises Mal-(PEG) m -Val-Cit-pAB and m is an integer from 1 to 6,
 wherein the nitrogen atom in the Mal is attached to PEG, and   wherein the pAB (p-aminobenzyloxycarbonyl) is attached to eribulin via a C-35 amine and the amino group in the pAB is attached to Cit.   
     
     
         185 . The composition of claim  1 , wherein m is an integer from 2 to 5. 
     
     
         186 . The composition of claim  1 , wherein m is 2, 3, or 4. 
     
     
         187 . The composition of claim  1 , wherein the cleavable linker comprises Mal-(PEG) 2 -Val-Cit-pAB. 
     
     
         188 . The composition of claim  1 , wherein the Mal is attached to a sulfhydryl group.