	US 12,433,960 B2
	Vivo gene therapy using intraosseous delivery of a lentiviralgene construct
Carol Hsing Miao, Seattle, WA (US); David J. Rawlings, Seattle, WA (US); and Chong Li, Seattle, WA (US)
Assigned to Seattle Children's Hospital, Seattle, WA (US)
Filed by Seattle Children's Hospital, Seattle, WA (US)
Filed on Jul. 15, 2024, as Appl. No. 18/773,400.
Application 18/773,400 is a continuation of application No. 17/051,137, abandoned, previously published as PCT/US2019/029490, filed on Apr. 26, 2019.
Claims priority of provisional application 62/663,930, filed on Apr. 27, 2018.
Prior Publication US 2024/0366797 A1, Nov. 7, 2024
Int. Cl. A61K 48/00 (2006.01); A61K 31/573 (2006.01); A61K 39/395 (2006.01); A61P 7/04 (2006.01); C07K 16/28 (2006.01)

CPC A61K 48/0058 (2013.01) [A61K 31/573 (2013.01); A61K 39/3955 (2013.01); A61K 48/0075 (2013.01); A61P 7/04 (2018.01); C07K 16/2815 (2013.01)]

13 Claims

1. A method of treating a subject having hemophilia A (hemA) or von Willebrand disease in need of plasma Factor VIII without inducing formation of detectable anti-Factor VIII antibodies in the subject, the method comprising:

administering to the subject a therapeutically effective amount of an inflammation suppressor;

administering to the subject a therapeutically effective amount of a CD8+ T cell depleting agent; and

administering to the subject a therapeutically effective amount of a composition comprising a lentiviral vector (LV) comprising a FVIII expression cassette expressibly linked to a megakaryocyte-specific promoter, wherein the FVIII expression cassette comprises:

a sequence that encodes hF8/N6K12RH;

wherein administration is via:

intraosseous (IO) infusion;

and wherein the administering does not induce formation of detectable anti-Factor VIII antibodies against the encoded hF8/N6K12RH in the subject having hemA or von Willebrand disease.