	US 12,404,318 B2
	Combination HBV therapy
Anna Bakardjiev, San Francisco, CA (US); Phillip S. Pang, Menlo Park, CA (US); and Davide Corti, Bellinzona (CH)
Assigned to Vir Biotechnology, Inc., San Francisco, CA (US); and Humabs BioMed SA, Bellinzona (CH)
Appl. No. 17/415,529
Filed by Vir Biotechnology, Inc., San Francisco, CA (US); and Humabs Biomed SA, Bellinzona (CH)
PCT Filed Dec. 19, 2019, PCT No. PCT/US2019/067643 § 371(c)(1), (2) Date Jun. 17, 2021, PCT Pub. No. WO2020/132346, PCT Pub. Date Jun. 25, 2020.
Claims priority of provisional application 62/782,896, filed on Dec. 20, 2018.
Prior Publication US 2022/0056110 A1, Feb. 24, 2022
Int. Cl. C07K 16/08 (2006.01); A61K 31/7105 (2006.01); A61K 39/00 (2006.01); A61K 39/42 (2006.01); A61K 47/54 (2017.01); A61P 31/20 (2006.01)

CPC C07K 16/082 (2013.01) [A61K 31/7105 (2013.01); A61K 39/42 (2013.01); A61K 47/549 (2017.08); A61P 31/20 (2018.01); A61K 2039/505 (2013.01); A61K 2039/545 (2013.01); C07K 2317/24 (2013.01); C07K 2317/76 (2013.01)]

16 Claims

1. A method of treating chronic hepatitis B virus (HBV) infection or a HBV-associated disease in a subject in need thereof, comprising:

administering to the subject an agent that reduces HBV antigenic load or inhibits HBV gene expression, wherein the agent that reduces HBV antigenic load or inhibits HBV gene expression is an siRNA that inhibits expression of an HBV transcript, the siRNA having a sense strand comprising 5′-gsusguGfcAfCfUfucgcuucacaL96-3′ (SEQ ID NO:7) and an antisense strand comprising 5′-usGfsuga(Agn)gCfGfaaguGfcAfcacsusu-3′ (SEQ ID NO:8), wherein:

(i) a, c, g, and u are 2′-O-methyladenosine-3′-phosphate, 2′-O-methylcytidine-3′-phosphate, 2′-O-methylguanosine-3′-phosphate, and 2′-O-methyluridine-3′-phosphate, respectively;

(ii) Af, Cf, Gf, and Uf are 2′-fluoroadenosine-3′-phosphate, 2′-fluorocytidine-3′-phosphate, 2′-fluoroguanosine-3′-phosphate, and 2′-fluorouridine-3′-phosphate, respectively;

(iii) (Agn) is adenosine-glycol nucleic acid (GNA);

(iv) s is a phosphorothioate linkage; and

(v) L96 is

and administering to the subject an anti-HBV antibody, wherein the anti-HBV antibody comprises (i) CDRH1, CDRH2, and CDRH3 amino acid sequences according to SEQ ID NOs:44, 45, and 47, respectively; and (ii) CDRL1, CDRL2, and CDRL3 amino acid sequences according to SEQ ID NOs:48, 49, and 52, respectively.