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 conjugate comprising a Factor IX moiety covalently and cleavably attached, either directly or through a spacer moiety comprised of one or more atoms, to a water-soluble polymer, wherein the molecular weight of the water-soluble polymer is greater than 5,000 Daltons and less than about 150,000 Daltons. 
     
     
         2 . The conjugate of  claim 1 , wherein the Factor IX moiety is covalently and cleavably attached via a bond selected from the consisting of carbonate, carboxylate ester, phosphate ester, thiolester, anhydride, acetal, ketal, acyloxyalkyl ether, imine, and orthoester. 
     
     
         3 . The conjugate of  claim 2 , wherein the bond is a carbonate. 
     
     
         4 . The conjugate of  claim 1 , wherein the water-soluble polymer is selected from the group consisting of a poly(alkylene oxide), poly(vinyl pyrrolidone), poly(vinyl alcohol), polyoxazoline, and poly(acryloylmorpholine). 
     
     
         5 . The conjugate of  claim 4 , wherein the water-soluble polymer is a poly(alkylene oxide). 
     
     
         6 . The conjugate of  claim 5 , wherein the poly(alkylene oxide) is a poly(ethylene glycol). 
     
     
         7 . The conjugate of  claim 6 , wherein the poly(ethylene glycol) is terminally capped with an end-capping moiety selected from the group consisting hydroxy, alkoxy, substituted alkoxy, alkenoxy, substituted alkenoxy, alkynoxy, substituted alkynoxy, aryloxy and substituted aryloxy. 
     
     
         8 . The conjugate of  claim 6 , wherein the poly(ethylene glycol) is terminally capped with methoxy. 
     
     
         9 . The conjugate of  claim 6 , wherein the poly(ethylene glycol) has a total weight-average molecular weight in the range of from about 6,000 Daltons to about 100,000 Daltons. 
     
     
         10 . The conjugate of  claim 9 , wherein the poly(ethylene glycol) has a total weight-average molecular weight in the range of from about 10,000 Daltons to about 85,000 Daltons. 
     
     
         11 . The conjugate of  claim 10 , wherein the poly(ethylene glycol) has a total weight-average molecular weight in the range of from about 20,000 Daltons to about 85,000 Daltons. 
     
     
         12 . The conjugate of  claim 1 , wherein each water-soluble polymer is linear. 
     
     
         13 . The conjugate of  claim 1 , wherein each water-soluble polymer is branched. 
     
     
         14 . The conjugate of  claim 1 , wherein the Factor IX moiety is selected from the group consisting of Factor IX and Factor IXa. 
     
     
         15 . The conjugate of  claim 14 , wherein the Factor IX moiety is Factor IX. 
     
     
         16 . The conjugate of  claim 14 , wherein the Factor IX moiety is Factor IXa. 
     
     
         17 . The conjugate of  claim 1 , wherein the Factor IX moiety is recombinantly derived.