IP Library › Granted Patent US 12,606,826
Granted Patent B2
US 12,606,826 · App. 18/060,965 · Granted Apr 21, 2026

Modulation of transthyretin expression

Inventor: Susan M. Freier (San Diego, CA)
Assignee: Ionis Pharmaceuticals, Inc.
C12N15/113A61K31/712C12N2310/11C12N2310/14C12N2310/315C12N2310/321C12N2310/3341C12N2310/341C12N2310/52C12N2320/30
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Quick Facts
Patent No.
US 12,606,826
App. No.
18/060,965
Granted
Apr 21, 2026
Kind
B2
Abstract

Provided herein are methods, compounds, and compositions for reducing expression of transthyretin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate transthyretin amyloidosis, or a symptom thereof.

Claims (14)

1 . A compound comprising a modified oligonucleotide consisting of 19 to 30 linked nucleosides wherein the linked nucleosides comprise at least a 19 contiguous nucleobase portion of SEQ ID NO: 38;

wherein the modified oligonucleotide comprises:

a gap segment consisting of linked deoxynucleosides;

a 5′ wing segment consisting of linked nucleosides; and a 3′ wing segment consisting of linked nucleosides;

wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment, and wherein at least one nucleoside comprises a modified sugar.

2 . The compound of claim 1 , wherein the modified oligonucleotide comprises the nucleobase sequence of SEQ ID NO: 38.

3 . The compound of claim 1 , wherein the modified oligonucleotide has at least one modified internucleoside linkage.

4 . The compound of claim 3 , wherein the modified internucleoside linkage is a phosphorothioate internucleoside linkage.

5 . The compound of claim 1 , wherein the modified oligonucleotide each nucleoside of each wing segment comprises a modified sugar.

6 . The compound of claim 5 , wherein the modified sugar is a bicyclic sugar comprising a 4′-CH(CH 3 )—O-2′ bridge or the modified sugar comprises a 2′-O-methoxyethyl moiety.

7 . The compound of claim 1 , wherein the modified oligonucleotide of the compound comprises:

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 of the modified oligonucleotide is a 5-methylcytosine.

8 . A composition comprising the compound of claim 1 , or a salt thereof, and a pharmaceutically acceptable carrier or diluent.

9 . A method of treating transthyretin amyloidosis in an animal comprising administering to the animal a compound comprising a modified oligonucleotide consisting of 19 to 30 linked nucleosides wherein the linked nucleosides comprise at least a 19 contiguous nucleobase portion of SEQ ID NO: 38.

Continuity (11)
Continuation 16889470 · Jun 1, 2020
Continuation 16229643 · Dec 21, 2018
Continuation 15729860 · Oct 11, 2017
Continuation 15190533 · Jun 23, 2016
Continuation 14717746 · May 20, 2015
Division 14184984 · Feb 20, 2014
Division 13944786 · Jul 17, 2013
Continuation 13098303 · Apr 29, 2011
Provisional Application 61405163 · Oct 20, 2010
Provisional Application 61329538 · Apr 29, 2010
Related Publication 20240132885A1 · Apr 25, 2024
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