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
Life of this patent
Estimating the term…
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 of the nucleotide sequence 5′-AAGACUGAUCAAAUAUGUUGAGU-3′ (SEQ ID NO:
- 543);
- wherein the sense strand comprises at least 17 contiguous nucleotides of the nucleotide sequence 5′-UCAACAUAUUUGAUCAGUCUU-3′ (SEQ ID NO:
- 358);
- wherein all of the nucleotides of the sense strand and all of the nucleotides of the antisense strand are modified nucleotides,
- wherein the sense strand and the antisense strand form a double stranded region of at least 17 nucleotides in length;
- 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, an abasic nucleotide, 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 of the nucleotide sequence 5′-AAAGACUGAUCAAAUAUGUUGAG-3′ (SEQ ID NO:1199);
- wherein the sense strand comprises at least 17 contiguous nucleotides of the nucleotide sequence of 5′-CAACAUAUUUGAUCAGUCUUU-3′ (SEQ ID NO:1018);
- wherein all of the nucleotides of the sense strand and all of the nucleotides of the antisense strand are modified nucleotides,
- wherein the sense strand and the antisense strand form a double stranded region of at least 17 nucleotides in length,
- 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, an abasic nucleotide, 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.