Pegylated Factor VIII
AssigneesBaxter International Inc., Baxter Healthcare S.A.
InventorsJuergen Siekmann, Katalin Varadi, Herbert Gritsch, Peter Turecek
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Abstract
The invention is a proteinaceous construct comprising a Factor VIII molecule having at least a portion of the B domain intact, which is conjugated to a water-soluble polymer such as polyethylene glycol having a molecular weight of greater than 10,000 Daltons. The construct has a biological activity of at least 80% of the biological activity of native Factor VIII, and the in vivo half-life of the construct is increased by at least 1.5 fold as compared to the in vivo half-life of native factor FVIII.
Claims22
-10. (canceled)
A proteinaceous molecule having Factor VIII activity comprising, (a) a Factor VIII molecule;
- and (b) at least four polyethylene glycol molecules bound to said Factor VIII molecule, wherein three polyethylene glycol molecules are bound to said Factor VIII molecule in the A3 domain and at least one polyethylene glycol molecule is bound to said Factor VIII molecule in the B domain;
- said polyethylene glycol molecules having a molecular weight of greater than 10,000 Daltons;
- said proteinaceous molecule having increased resistance to thrombin inactivation compared to native Factor VIII, wherein resistance to thrombin inactivation of the proteinaceous molecule and of native Factor VIII are determined by chromogenic activity.
A proteinaceous molecule having Factor VIII activity comprising, (a) a Factor VIII molecule;
- and (b) at least four soluble polymer or carbohydrate molecules bound to said Factor VIII molecule in the A1, A2 or A3 domain;
- said soluble polymer or carbohydrate molecules having a molecular weight of greater than 10,000 Daltons;
- said proteinaceous molecule having increased resistance to thrombin inactivation compared to native Factor VIII, wherein resistance to thrombin inactivation of the proteinaceous molecule and of native Factor VIII are determined by chromogenic activity.
A proteinaceous molecule having Factor VIII activity comprising, (a) a Factor VIII molecule;
- and (b) at least four soluble polymer or carbohydrate molecules bound to said Factor VIII molecule, wherein three soluble polymer or carbohydrate molecules are bound to said Factor VIII molecule in the A1, A2 or A3 domain and at least one soluble polymer or carbohydrate molecule is bound to said Factor VIII molecule in the B domain;
- said soluble polymer or carbohydrate molecules having a molecular weight of greater than 10,000 Daltons;
- said proteinaceous molecule having increased resistance to thrombin inactivation compared to native Factor VIII, wherein resistance to thrombin inactivation of the proteinaceous molecule and of native Factor VIII are determined by chromogenic activity.
A proteinaceous molecule having Factor VIII activity comprising, (a) a Factor VIII molecule;
- and (b) at least four soluble polymer or carbohydrate molecules bound to said Factor VIII molecule, wherein at least one soluble polymer or carbohydrate molecule is bound to said Factor VIII molecule in the B domain;
- said soluble polymer or carbohydrate molecules having a molecular weight of greater than 10,000 Daltons;
- said proteinaceous molecule having increased resistance to thrombin inactivation compared to native Factor VIII, wherein resistance to thrombin inactivation of the proteinaceous molecule and of native Factor VIII are determined by chromogenic activity.
Dependencies are inferred from the claim text.