Truncated von Willebrand factor polypeptides for extravascular administration in the treatment or prophylaxis of a blood coagulation disorder
AssigneeCsl Behring Lengnau AG
InventorsSabine Pestel, Elmar Raquet, Thomas Weimer
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Abstract
The invention pertains to a recombinant polypeptide comprising a truncated von Willebrand Factor (VWF) for use in the treatment or prophylaxis of a blood coagulation disorder, said treatment or prophylaxis comprising administering the recombinant polypeptide and a Factor VIII protein (FVIII) extravascular to a subject having a blood coagulation disorder, wherein said recombinant polypeptide is capable of binding to said FVIII, and wherein the molar ratio of the recombinant polypeptide to be administered to the FVIII to be administered is higher than 50.
Claims23
A method for the treatment of a blood coagulation disorder, comprising administering an effective amount of (i) a recombinant polypeptide consisting of (a) a truncated von Willebrand Factor (VWF) and (b) at least one non-VWF sequence, and (ii) a Factor VIII protein (FVIII) to a subject having a blood coagulation disorder,
- wherein at least one of the non-VWF sequences is a half-life extending moiety (HLEM),
- wherein the truncated VWF has a sequence identity of at least 90% to amino acids 764 to 1242 of SEQ ID NO:4,
- wherein at least one of the recombinant polypeptide and the FVIII is administered extravascularly,
- wherein the recombinant polypeptide is present as a dimer and wherein the ratio of dimer:monomer of the recombinant polypeptide is at least 1.5,
- wherein said dimeric recombinant polypeptide is capable of binding to said FVIII and has a FVIII binding affinity characterized by a dissociation constant KD of less than 1 nM, and
- wherein the molar ratio of the recombinant polypeptide to the FVIII is higher than 50.
Dependencies are inferred from the claim text.