US 11,814,421 B2
Truncated von Willebrand Factor polypeptides for treating hemophilia
Stefan Schulte, Marburg (DE); Thomas Weimer, Gladenbach (DE); Sabine Pestel, Marburg (DE); Hubert Metzner, Marburg (DE); and Steve Dower, Fitzroy North (AU)
Assigned to CSL BEHRING LENGNAU AG, Lengnau (CH)
Appl. No. 16/348,934
Filed by CSL BEHRING LENGNAU AG, Lengnau (CH)
PCT Filed Nov. 10, 2017, PCT No. PCT/EP2017/078834
§ 371(c)(1), (2) Date May 10, 2019,
PCT Pub. No. WO2018/087267, PCT Pub. Date May 17, 2018.
Claims priority of application No. 16198501 (EP), filed on Nov. 11, 2016.
Prior Publication US 2019/0263890 A1, Aug. 29, 2019
Int. Cl. C07K 14/755 (2006.01); A61P 7/04 (2006.01); A61K 9/00 (2006.01); A61K 38/37 (2006.01); C07K 14/765 (2006.01); A61K 38/36 (2006.01)
CPC C07K 14/755 (2013.01) [A61K 9/0019 (2013.01); A61K 38/36 (2013.01); A61K 38/37 (2013.01); A61P 7/04 (2018.01); C07K 14/765 (2013.01); A61K 2300/00 (2013.01); C07K 2319/30 (2013.01); C07K 2319/31 (2013.01)] 24 Claims
 
1. A method of treating a blood coagulation disorder, comprising
administering an effective amount of a polypeptide comprising a truncated von Willebrand Factor (VWF) and a half-life extending moiety to a human subject having a blood coagulation disorder and having endogenous Factor VIII (FVIII), wherein the blood coagulation disorder is von-Willebrand disease,
wherein the truncated VWF comprises an amino acid sequence having a sequence identity of at least 90% to 764 to 1242 of SEQ ID NO:4,
wherein the activity level of endogenous FVIII in said human subject before treatment with said polypeptide is reduced relative to the activity level of FVIII in normal human plasma (NHP) provided that the activity level of endogenous FVIII in said human subject is from 0.5% to 40% of the activity level of endogenous FVIII in normal human plasma (NHP),
wherein the polypeptide is capable of binding to endogenous FVIII, and wherein the endogenous FVIII level is increased following administration of said polypeptide, wherein said polypeptide is administered for prophylactic treatment of said human subject,
wherein said treatment does not comprise co-administration of exogenous FVIII, and wherein the polypeptide is administered to the human subject in a molar ratio of the polypeptide to endogenous VWF in the human subject of at least 50.