EP4092120A1 — Angiopoietin-like 3 (anglptl3) irna compositions and methods of use thereof

USPTO Abstract

The invention relates to a double-stranded ribonucleic acid (dsRNA) agent for inhibiting expression of Angiopoietin-like 3 (ANGPTL3), comprising a sense strand and an antisense strand forming a duplex region, wherein the sense strand comprises at least 15, preferably at least 16 and most preferably at least 17 contiguous nucleotides of the nucleotide sequence 5'-GUCUCAAAAUGGAAGGUUAUA-3' (SEQ ID NO: 1160), wherein the antisense strand comprises at least 15 contiguous nucleotides of the nucleotide sequence 5'-UAUAACCUUCCAUUUUGAGACUU-3' (SEQ ID NO: 1341), wherein at least one of the modified nucleotides is selected from the group consisting of a 2'-O-methyl modified nucleotide, a 2'-fluoro modified nucleotide, and a nucleotide comprising a 5'-phosphorothioate group, and wherein a ligand comprising an N-acetylgalactosamine (GaINAc) is conjugated to at least one strand of the dsRNA agent.