	US 12,257,288 B2
	Methods of inducing immune tolerance to clotting factors
Jennifer Dumont, Waltham, MA (US); Nisha Jain, Waltham, MA (US); and Stefan Lethagen, Stockholm (SE)
Assigned to BIOVERATIV THERAPEUTICS INC., Waltham, MA (US); and SWEDISH ORPHAN BIOVITRUM AB, Stockholm (SE)
Appl. No. 16/464,105
Filed by BIOVERATIV THERAPEUTICS INC., Waltham, MA (US); and SWEDISH ORPHAN BIOVITRUM AB, Stockholm (SE)
PCT Filed Dec. 1, 2017, PCT No. PCT/US2017/064323 § 371(c)(1), (2) Date May 24, 2019, PCT Pub. No. WO2018/102760, PCT Pub. Date Jun. 7, 2018.
Claims priority of provisional application 62/582,829, filed on Nov. 7, 2017.
Claims priority of provisional application 62/558,790, filed on Sep. 14, 2017.
Claims priority of provisional application 62/529,866, filed on Jul. 7, 2017.
Claims priority of provisional application 62/466,937, filed on Mar. 3, 2017.
Claims priority of provisional application 62/429,516, filed on Dec. 2, 2016.
Prior Publication US 2020/0085915 A1, Mar. 19, 2020
Int. Cl. A61K 38/37 (2006.01); A61K 38/48 (2006.01); A61P 7/04 (2006.01)

CPC A61K 38/37 (2013.01) [A61K 38/4846 (2013.01); A61P 7/04 (2018.01); C12Y 304/21022 (2013.01); C07K 2319/21 (2013.01); C07K 2319/30 (2013.01); C07K 2319/31 (2013.01)]

19 Claims

1. A method of treating a human with hemophilia A who has developed an inhibitory response to factor VIII (FVIII), the method comprising the following steps:

(a) identifying a human subject who has hemophilia A and who has failed to respond to one or more previous immune tolerance therapies against FVIII,

(b) administering between 85 IU/kg and 300 IU/kg of a chimeric protein comprising a FVIII and an Fc region (FVIII-Fc) daily to the human subject for a period sufficient to induce immune tolerance; and

(d) following the tapering regimen, administering a prophylactic dose of the chimeric protein to the human;

thereby reducing or eliminating an inhibitory immune response to FVIII.