IP Library › Granted Patent US 12,595,482
Granted Patent B2
US 12,595,482 · App. 18/159,465 · Granted Apr 7, 2026

Linkage modified oligomeric compounds and uses thereof

Inventors: Brooke A. Anderson (San Diego, CA); Xue-Hai Liang (Del Mar, CA); William John Drury, III (Oceanside, CA); Michael Oestergaard (Carlsbad, CA); Michael T. Migawa (Carlsbad, CA); Punit P. Seth (Carlsbad, CA)
Assignee: Ionis Pharmaceuticals, Inc.
C12N15/113C12N2310/11C12N2310/314C12N2310/315C12N2310/321C12N2310/341C12N2310/351
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Quick Facts
Patent No.
US 12,595,482
App. No.
18/159,465
Granted
Apr 7, 2026
Kind
B2
Abstract

The present disclosure provides oligomeric compounds (including oligomeric compounds that are antisense agents or portions thereof) comprising a modified oligonucleotide having at least one modified internucleoside linking group.

Claims (33)

1 . An oligomeric compound comprising a modified oligonucleotide consisting of 12-30 linked nucleosides linked through internucleoside linking groups, wherein:

at least one nucleoside comprises a modified sugar moiety;

the modified oligonucleotide comprises a deoxy region consisting of 6-11 linked nucleosides wherein each nucleoside of the deoxy region is a stereo-standard DNA nucleoside; and

at least one of the internucleoside linking groups of the modified oligonucleotide has Formula XVII:

wherein independently for each internucleoside linking group having Formula XVII:

X is selected from O or S;

R 1 is selected from H, C 1 -C 6 alkyl, and substituted C 1 -C 6 alkyl; and

T is SO 2 R 2 , wherein R 2 is selected from a heterocycle, a substituted heterocycle, an aromatic heterocycle, a substituted aromatic heterocycle, a diazole, a substituted diazole, a C 1 -C 6 alkoxy, C 1 -C 6 alkyl, C 1 -C 6 alkenyl, C 1 -C 6 alkynyl, substituted C 1 -C 6 alkyl, substituted C 1 -C 6 alkenyl substituted C 1 -C 6 alkynyl, and a conjugate group.

2 . The oligomeric compound of claim 1 , wherein X is O, R 1 is H, and T is SO 2 Me.

3 . The oligomeric compound of claim 1 , wherein the deoxy region is flanked on the 5′-side by a 5′-region consisting of 1-6 linked 5′-region nucleosides, wherein each of the 5′-region nucleosides comprises a modified sugar moiety.

4 . The oligomeric compound of claim 3 , wherein each of the 5′-region nucleosides comprises a sugar moiety selected from 2′-MOE and cEt.

5 . The oligomeric compound of claim 3 , wherein the deoxy region is flanked on the on the 3′ side by a 3′-region consisting of 1-6 linked 3′-region nucleosides; wherein each of the 3′-region nucleosides comprises a modified sugar moiety.

6 . The oligomeric compound of claim 5 , wherein each of the 3′-region nucleosides comprises a sugar moiety selected from 2′-MOE and cEt.

7 . The oligomeric compound of claim 1 , wherein each internucleoside linkage that is not an internucleoside linkage of Formula XVII is selected from a phosphorothioate internucleoside linkage and a phosphodiester internucleoside linkage.

8 . The oligomeric compound of claim 1 , wherein the deoxy region comprises at least one region having the formula (N g1 ) L1 (N g2 ) L2 (N g3 ) L3 , wherein each Ng is a nucleoside and each L is an internucleoside linking group; wherein each of L 1 , L 2 , and L 3 is a phosphodiester internucleoside linking group, a phosphorothioate internucleoside linking group, or an internucleoside linking group of Formula XVII:

wherein at least one of L 1 , L 2 , and L 3 is an internucleoside linking group of Formula XVII; and at least one of L 1 , L 2 , and L 3 is a phosphorothioate or a phosphodiester internucleoside linking group,

wherein independently for each internucleoside linking group having Formula XVII:

X is selected from O or S;

R 1 is selected from H, C 1 -C 6 alkyl, and substituted C 1 -C 6 alkyl; and

T is SO 2 R 2 , wherein R 2 is selected from a heterocycle, a substituted heterocycle, an aromatic heterocycle, a substituted aromatic heterocycle, a diazole, a substituted diazole, a C 1 -C 6 alkoxy, C 1 -C 6 alkyl, C 1 -C 6 alkenyl, C 1 -C 6 alkynyl, substituted C 1 -C 6 alkyl, substituted C 1 -C 6 alkenyl substituted C 1 -C 6 alkynyl, and a conjugate group.

9 . The oligomeric compound of claim 8 , wherein X is O, Riis H, and T is SO 2 Me.

10 . The oligomeric compound of claim 8 , wherein the at least one region having the formula (N g1 )L 1 (N g2 )L 2 (N g3 )L 3 is at the 3′ end of the deoxy region.

11 . The oligomeric compound of claim 8 , wherein the at least one region having the formula (N g1 )L 1 (N g2 )L 2 (N g3 )L 3 is at the 5′ end of the deoxy region.

12 . The oligomeric compound of claim 8 , wherein a second region having the formula (N g1 )L 1 (N g2 )L 2 (N g3 )L 3 is at the 5′ end of the deoxy region.

13 . The oligomeric compound of claim 8 , wherein L 1 and L 3 are phosphorothioate internucleoside linking groups, and L 2 is an internucleoside linking group of formula XVII.

14 . The oligomeric compound of claim 8 , wherein L 1 is a phosphorothioate internucleoside linking group, and L 2 and L 3 are internucleoside linking groups of formula XVII.

15 . The oligomeric compound of claim 8 , wherein the deoxy region is flanked on the 5′-side by a 5′-region consisting of 1-6 linked 5′-region nucleosides, wherein each of the 5′-region nucleosides comprises a modified sugar moiety.

16 . The oligomeric compound of claim 15 , wherein each of the 5′-region nucleosides comprises a sugar moiety selected from 2′-MOE and cEt.

17 . The oligomeric compound of claim 8 , wherein the deoxy region is flanked on the on the 3′ side by a 3′-region consisting of 1-6 linked 3′-region nucleosides; wherein each of the 3′-region nucleosides comprises a modified sugar moiety.

18 . The oligomeric compound of claim 17 , wherein each of the 3′-region nucleosides comprises a sugar moiety selected from 2′-MOE and cEt.

19 . The oligomeric compound of claim 8 , wherein each internucleoside linkage that is not an internucleoside linkage of Formula XVII is selected from a phosphorothioate internucleoside linkage and a phosphodiester internucleoside linkage.

20 . The oligomeric compound of claim 1 , wherein each nucleobase of the modified oligonucleotide is independently selected from thymine, uracil, guanine, cytosine, 5-methylcytosine, and adenine.

21 . The oligomeric compound of claim 8 , wherein each nucleobase of the modified oligonucleotide is independently selected from thymine, uracil, guanine, cytosine, 5-methylcytosine, and adenine.

Continuity (7)
Continuation 17671924 · Feb 15, 2022
Continuation PCTUS2020046561 · Aug 14, 2020
Provisional Application 63050042 · Jul 9, 2020
Provisional Application 62989442 · Mar 13, 2020
Provisional Application 62953121 · Dec 23, 2019
Provisional Application 62887525 · Aug 15, 2019
Related Publication 20240002851A1 · Jan 4, 2024
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