Methods of inhibition of protein fucosylation in vivo using fucose analogs

Abstract

The invention provides methods and compositions for the inhibition of fucosylation of proteins, including antibodies, in vivo by administration of a fucose analog.

1 - 59 . (canceled) 
     
     
         60 . A pharmaceutical composition comprising a therapeutically effective amount of a fucose analog selected from the group consisting of one of the following formulae (V) or (VI): 
       
         
           
           
               
               
           
         
         or a biologically acceptable salt or solvate thereof, wherein each fucose analog of formula (V) or (VI) can be the alpha or beta anomer or the corresponding aldose form; 
         wherein each of R 1 , R 3 , and R 4  is independently selected from the group consisting of —OH and —OC(O)C 1 -C 10  alkyl; and R 2  is F, R 2a  and R 3a  are each H, and R 5  is —CH 3 . 
       
     
     
         61 . The pharmaceutical composition of  claim 60 , wherein each of R 1 , R 3 , and R 4  is independently selected from the group consisting of —OH and —OAc, R 2  is F, R 2a  and R 3a  are each H, and R 5  is —CH 3 . 
     
     
         62 . The pharmaceutical composition of  claim 60 , wherein the fucose analog is 2-deoxy-2-fluorofucose. 
     
     
         63 . The pharmaceutical composition of  claim 60 , wherein the fucose analog is 2-deoxy-2-fluorofucose peracetate. 
     
     
         64 . The pharmaceutical composition of  claim 60 , wherein the composition is suitable for oral administration.