Factor viii: remodeling and glycoconjugation of factor viii

Abstract

The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.

What is claimed is: 
     
         1 . A covalent conjugate comprising Factor VIII and a linear or a branched poly(ethylene glycol), wherein the a linear or a branched poly(ethylene glycol) is conjugated directly onto the peptide backbone of Factor VIII or conjugated onto the peptide backbone of Factor VIII via a linker, wherein the in vivo half-life of the conjugate is increased by at least about 40% compared to the in vivo half-life of a wild-type Factor VIII, wherein the linear or branched poly(ethylene glycol) has a degree of polymerization of from about 1 to about 5,000. 
     
     
         2 . The covalent conjugate of  claim 1 , wherein the linear or branched poly(ethylene glycol) has a degree of polymerization of from about 1 to about 1,000. 
     
     
         3 . The covalent conjugate of  claim 2 , wherein the poly(ethylene glycol) is conjugated directly onto the peptide backbone of Factor VIII. 
     
     
         4 . The covalent conjugate of  claim 2 , wherein the poly(ethylene glycol) is conjugated onto the peptide backbone of Factor VIII via a linker. 
     
     
         5 . The covalent conjugate of  claim 3 , wherein the conjugate comprises at least two poly(ethylene glycol) moieties. 
     
     
         6 . The covalent conjugate of  claim 4 , wherein the conjugate comprises at least two poly(ethylene glycol) moieties. 
     
     
         7 . The covalent conjugate of  claim 1 , wherein the in vivo half-life of the conjugate is increased by at least about 60% compared to the in vivo half-life of a wild-type Factor VIII. 
     
     
         8 . The covalent conjugate of  claim 1 , wherein the in vivo half-life of the conjugate is increased by at least about 80% compared to the in vivo half-life of a wild-type Factor VIII. 
     
     
         9 . The covalent conjugate of  claim 1 , wherein the in vivo half-life of the conjugate is increased by at least about 100% compared to the in vivo half-life of a wild-type Factor VIII. 
     
     
         10 . The covalent conjugate of  claim 5 , wherein the in vivo half-life of the conjugate is increased by at least about 60% compared to the in vivo half-life of a wild-type Factor VIII. 
     
     
         11 . The covalent conjugate of  claim 5 , wherein the in vivo half-life of the conjugate is increased by at least about 80% compared to the in vivo half-life of a wild-type Factor VIII. 
     
     
         12 . The covalent conjugate of  claim 5 , wherein the in vivo half-life of the conjugate is increased by at least about 100% compared to the in vivo half-life of a wild-type Factor VIII. 
     
     
         13 . The covalent conjugate of  claim 6 , wherein the in vivo half-life of the conjugate is increased by at least about 60% compared to the in vivo half-life of a wild-type Factor VIII. 
     
     
         14 . The covalent conjugate of  claim 6 , wherein the in vivo half-life of the conjugate is increased by at least about 80% compared to the in vivo half-life of a wild-type Factor VIII. 
     
     
         15 . The covalent conjugate of  claim 6 , wherein the in vivo half-life of the conjugate is increased by at least about 100% compared to the in vivo half-life of a wild-type Factor VIII.