Polymer factor ix moiety conjugates

Abstract

Conjugates of a Factor IX moiety and one or more water-soluble polymers are provided. Typically, the water-soluble polymer is poly(ethylene glycol) or a derivative thereof. Also provided (among other things) are compositions comprising the conjugates, methods of making the conjugates, and methods of administering to a patient compositions comprising the conjugates.

1 . A method for administration, the method comprising administering to a subject in need thereof a composition comprising a plurality of polyethylene glycol (PEG)-Factor IX moiety conjugates, the conjugates comprising a branched polyethylene glycol covalently attached via a spacer moiety comprised of one or more atoms to a Factor IX moiety that is either Factor IX or Factor IXa, where at least about 85% of the polyethylene glycol-Factor IX moiety conjugates in the composition are monoPEGylated. 
     
     
         2 . The method of  claim 1 , wherein the branched polyethylene glycol comprises two polyethylene glycol chains attached to a polyol core. 
     
     
         3 . The method of  claim 2 , wherein the polyol core is a glycerol core. 
     
     
         4 . The method of  claim 3 , wherein the branched polyethylene glycol has a weight average molecular weight of about 40,000 daltons. 
     
     
         5 . The method of  claim 4 , wherein the branched polyethylene glycol comprises two polyethylene glycol chains each having a weight average molecular weight of about 20,000 Daltons. 
     
     
         6 . The method of  claim 1 , wherein the spacer intervening between the Factor IX moiety and the polyethylene glycol chains comprises a carbamate group. 
     
     
         7 . The method of  claim 3 , where the polyol core is a glycerol core. 
     
     
         8 . The method of  claim 1 , where at least about 95% of the polyethylene glycol-Factor IX moiety conjugates in the composition are monoPEGylated. 
     
     
         9 . The method of  claim 1 , wherein at least about 99% of the conjugates in the composition have from one to two of the branched polyethylene glycols covalently attached to the Factor IX moiety. 
     
     
         10 . The method of  claim 1 , where the branched polyethylene glycol is covalently attached to the Factor IX moiety via an amide linkage. 
     
     
         11 . The method of  claim 1 , wherein the Factor IX moiety is Factor IX. 
     
     
         12 . The method of  claim 1 , wherein the Factor IX moiety is Factor IXa. 
     
     
         13 . The method of  claim 1 , wherein the Factor IX moiety is recombinantly derived. 
     
     
         14 . The method of  claim 1 , wherein the Factor IX moiety is blood-derived. 
     
     
         15 . The method of  claim 1 , wherein the composition comprises a pharmaceutically acceptable excipient. 
     
     
         16 . The method of  claim 1 , wherein the composition is in a liquid form suitable for injection. 
     
     
         17 . The method of  claim 16 , wherein the administering is via injection. 
     
     
         18 . The method of  claim 17 , wherein the administering is via intravenous injection. 
     
     
         19 . The method of  claim 1 , wherein the subject has hemophilia B and the composition is used for replacement therapy.