ANGIOPOIETIN-LIKE 3 (ANGPTL3) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
AssigneeAlnylam Pharmaceuticals, Inc.
InventorsBrian Bettencourt, William Querbes, Kevin Fitzgerald, Maria Frank-Kamenetsky, Stuart Milstein, Svetlana Shulga Morskaya
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Abstract
The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ANGPTL3 gene, as well as methods of inhibiting expression of ANGPTL3 and methods of treating subjects having a disorder of lipid metabolism, such as hyperlipidemia or hypertriglyceridemia, using such dsRNA compositions.
Claims20
A double-stranded ribonucleic acid (dsRNA) agent for inhibiting expression of Angiopoietin-like 3 (ANGPTL3), comprising a sense strand and an antisense strand,
- wherein the antisense strand comprises at least 17 contiguous nucleotides which differ by no more than three nucleotides from the nucleotide sequence of 5′-AAAGACUGAUCAAAUAUGUUGAG-3′ (nucleotides 274-296 of SEQ ID NO:1),
- wherein each strand is independently 17-25 nucleotides in length,
- wherein all of the nucleotides of the sense strand and all of the nucleotides of the antisense strand are modified nucleotides,
- 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, a nucleotide comprising a 5′-phosphorothioate group, and a 2′-amino modified nucleotide, and
- wherein a ligand comprising an N-acetylgalactosamine (GalNAc) derivative is conjugated to at least one strand of the dsRNA agent.
A double-stranded ribonucleic acid (dsRNA) agent for inhibiting expression of Angiopoietin-like 3 (ANGPTL3), comprising a sense strand and an antisense strand,
- wherein the antisense strand comprises at least 17 contiguous nucleotides which differ by no more than three nucleotides from the nucleotide sequence of 5′-AAGACUGAUCAAAUAUGUUGAGU-3′ (nucleotides 273-295 of SEQ ID NO:1),
- wherein each strand is independently 17-25 nucleotides in length,
- wherein all of the nucleotides of the sense strand and all of the nucleotides of the antisense strand are modified nucleotides,
- 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, a nucleotide comprising a 5′-phosphorothioate group, and a 2′-amino modified nucleotide, and
- wherein a ligand comprising an N-acetylgalactosamine (GalNAc) derivative is conjugated to at least one strand of the dsRNA agent.
A double-stranded ribonucleic acid (dsRNA) agent for inhibiting expression of Angiopoietin-like 3 (ANGPTL3), comprising a sense strand and an antisense strand,
- wherein the antisense strand comprises at least 17 contiguous nucleotides which differ by no more than three nucleotides from the nucleotide sequence of 5′-AGACUGAUCAAAUAUGUUG-3′ (nucleotides 276-294 of SEQ ID NO:1),
- wherein each strand is independently 17-25 nucleotides in length,
- wherein all of the nucleotides of the sense strand and all of the nucleotides of the antisense strand are modified nucleotides,
- 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, a nucleotide comprising a 5′-phosphorothioate group, and a 2′-amino modified nucleotide, and
- wherein a ligand comprising an N-acetylgalactosamine (GalNAc) derivative is conjugated to at least one strand of the dsRNA agent.
Dependencies are inferred from the claim text.