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  claim 1 . 
     
     
         7 . A proteinaceous construct comprising:
 (a) a Factor VIII molecule; and   (b) at least one water soluble polymer bound to said Factor VIII 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.