Factor viii polymer conjugates

Abstract

The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

1 . A method of conjugating a water soluble polymer to an oxidized carbohydrate moiety of Factor VIII comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. 
     
     
         2 . The method according to  claim 1  wherein the water soluble polymer is selected from the group consisting of PEG. PSA and dextran. 
     
     
         3 . The method according to  claim 1  wherein the activated water soluble polymer is selected from the group consisting of PEG-hydrazide, PSA-hydrazine and aldehyde-activated dextran. 
     
     
         4 . The method according to  claim 1  wherein the carbohydrate moiety is oxidized by incubation in a buffer comprising NaIO 4 . 
     
     
         5 . The method according to  claim 1  wherein the oxidized carbohydrate moiety of FVIII is located in the B domain of Factor VIII. 
     
     
         6 . A modified Factor VIII produced by the method according to any one of  claims 1 - 5 . 
     
     
         7 . A proteinaceous construct comprising:
 (a) a Factor VIII molecule; and   (b) at least one water soluble polymer bound to said Factor VI I molecule,   
       wherein said water soluble polymer is attached to the Factor VIII via one or more carbohydrate moieties located in the B domain Factor VIII. 
     
     
         8 . The proteinaceous construct of  claim 7  wherein the water soluble polymer is selected from the group consisting of PEG, PSA and dextran.