	US 11,890,327 B2
	Truncated von Willebrand factor polypeptides for extravascular administration in the treatment or prophylaxis of a blood coagulation disorder
Sabine Pestel, Marburg (DE); Elmar Raquet, Frankenberg (DE); and Thomas Weimer, Gladenbach (DE)
Assigned to CSL Behring Lengnau AG, Lengnau (CH)
Appl. No. 16/349,002
Filed by CSL BEHRING LENGNAU AG, Lengnau (CH)
PCT Filed Nov. 10, 2017, PCT No. PCT/EP2017/078840 § 371(c)(1), (2) Date May 10, 2019, PCT Pub. No. WO2018/087271, PCT Pub. Date May 17, 2018.
Claims priority of application No. 16198497 (EP), filed on Nov. 11, 2016.
Prior Publication US 2021/0268071 A1, Sep. 2, 2021
Int. Cl. A61K 38/37 (2006.01); A61P 7/04 (2006.01)

CPC A61K 38/37 (2013.01) [A61P 7/04 (2018.01)]

23 Claims

1. 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 K_Dof less than 1 nM, and

wherein the molar ratio of the recombinant polypeptide to the FVIII is higher than 50.