Compounds and methods for modulating angiotensinogen expression
AssigneeIonis Pharmaceuticals, Inc.
InventorsAdam Mullick, Mark J. Graham, Punit P. Seth, Susan M. Freier
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Abstract
Disclosed herein are compositions and compounds comprising modified oligonucleotides for modulating AGT and modulating a RAAS pathway related disease, disorder and/or condition in an individual in need thereof. A RAAS pathway related disease, disorder and/or condition in an individual such as hypertension can be treated, ameliorated, delayed or prevented with the administration of antisense compounds targeted to AGT.
Claims28
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A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides wherein the modified oligonucleotide has a nucleobase sequence comprising a portion of at least 8 contiguous nucleobases fully complementary to an equal length portion of nucleobases 2281 to 2300 of SEQ ID NO:
- 1, wherein the nucleobase sequence of the modified oligonucleotide is at least 80% complementary to SEQ ID NO:
- 1.
3-9. (canceled)
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A compound comprising a single-stranded modified oligonucleotide consisting of 20 linked nucleosides having the nucleobase sequence consisting of SEQ ID NO:
- 1914, wherein the modified oligonucleotide comprises:
- a. a gap segment consisting often linked 2′-deoxynucleosides;
- b. a 5′ wing segment consisting of five linked nucleosides;
- and
- c. a 3′ wing segment consisting of five linked nucleosides;
- wherein the gap segment is positioned immediately adjacent to and between the 5′ wing segment and the 3′ wing segment, wherein each nucleoside of each wing segment comprises a 2′-O-methoxyethyl sugar, wherein each internucleoside linkage is a phosphorothioate linkage and wherein each cytosine residue is a 5-methylcytosine.
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The compound of 26, wherein the conjugate group comprises a GalNAc moiety.
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A modified oligonucleotide according to the following formula:
31-35. (canceled)
Dependencies are inferred from the claim text.