RNAi agents for inhibiting expression of complement component C3 (C3), pharmaceutical compositions thereof, and methods of use

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:
• 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.