US 12,110,492 B2
RNAi agents for inhibiting expression of complement component C3 (C3), pharmaceutical compositions thereof, and methods of use
Jeffrey Carlson, Madison, WI (US); Yichen Wang, San Diego, CA (US); Tao Pei, Middleton, WI (US); James C. Hamilton, Arcadia, CA (US); and Hamid Moradi, Laguna Hills, CA (US)
Assigned to Arrowhead Pharmaceuticals, Inc., Pasadena, CA (US)
Filed by Arrowhead Pharmaceuticals, Inc., Pasadena, CA (US)
Filed on Oct. 26, 2023, as Appl. No. 18/495,278.
Claims priority of provisional application 63/493,564, filed on Mar. 31, 2023.
Claims priority of provisional application 63/486,944, filed on Feb. 24, 2023.
Claims priority of provisional application 63/381,200, filed on Oct. 27, 2022.
Prior Publication US 2024/0167035 A1, May 23, 2024
Int. Cl. C07H 21/04 (2006.01); C12N 15/113 (2010.01)
CPC C12N 15/113 (2013.01) [C12N 2310/14 (2013.01); C12N 2310/321 (2013.01); C12N 2310/351 (2013.01)] 14 Claims
 
1. A method of treating IgA nephropathy (IgAN) or C3 glomerulopathy (C3G) in a human subject in need thereof, the method comprising administering to the human subject a pharmaceutical composition comprising a therapeutically effective amount of a RNAi agent for inhibiting expression of a C3 gene, wherein the RNAi agent comprises an antisense strand and a sense strand, wherein the antisense strand comprises the nucleotide sequence (5′→3′) usUfsusCfgAfacaacAfgAfgUfaGfGfgsu (SEQ ID NO:13), and the sense strand comprises the nucleotide sequence (5′→3′) (NAG37)s(invAb)sacccuacuCfUfGfuuguucgaaas(invAb) (SEQ ID NO:14), wherein a is 2′-O-methyl adenosine; c is 2′-O-methyl cytidine; g is 2′-O-methyl guanosine; u is 2′-O-methyl uridine, Af is 2′-fluoro adenosine, Cf is 2′-fluoro cytidine; Gf is 2′-fluoro guanosine; Uf is 2′-fluoro adenosine; s is a phosphorothioate linkage; (invAb) is an inverted abasic deoxyribose residue; and (NAG37)s comprises the following chemical structure:

OG Complex Work Unit Chemistry
and wherein the RNAi agent is administered by subcutaneous injection at a dose of between about 25 mg and about 400 mg of RNAi agent.