Granted Patent B2

US 12,624,358 · App. 19/268,623 · Granted May 12, 2026

Inventors: Dieter A. Kubli (Santee, CA); Brooke A. Anderson (San Diego, CA); Adam Mullick (Carlsbad, CA); Eric E. Swayze (Encinitas, CA)

Assignee: Ionis Pharmaceuticals, Inc.

C12N15/1138A61P9/04C12N2310/14C12N2310/313C12N2310/321C12N2310/3341C12N2310/3513

Abstract

Claims (44)

1 . An oligomeric duplex comprising:

i) a modified oligonucleotide according to the following chemical notation:

(SEQ ID NO: 1255)

vPT es A fs U yo A yo A yo A yo U yo A yo G yo A yo U yo U yo C yo U fo G yo U fo

A yo G yo C yo U yo U ys A e sA e ;

 wherein:

A=an adenine nucleobase,

C=a cytosine nucleobase,

G=a guanine nucleobase,

T=a thymine nucleobase,

U=a uracil nucleobase,

e=a 2′-MOE sugar moiety,

f=a 2′-fluoro sugar moiety,

y=a 2′-OMe sugar moiety,

o=a phosphodiester internucleoside linkage,

s=a phosphorothioate internucleoside linkage, and

vP=a 5′ vinyl phosphonate group; and

ii) a conjugated modified oligonucleotide according to the following chemical notation:

(SEQ ID NO: 1041)

[X] 1 -

A es A es G yo C yo U yo A yo C yo A yo G yo A fo A fo U yo C yo U yo A yo U yo U yo U yo A ys T es A e,

 wherein:

C=a cytosine nucleobase,

A=an adenine nucleobase,

G=a guanine nucleobase,

U=a uracil nucleobase,

T=a thymine nucleobase,

e=a 2′-MOE sugar moiety,

f=a 2′-fluoro sugar moiety,

y=a 2′-OMe sugar moiety,

o=a phosphodiester internucleoside linkage,

s=a phosphorothioate internucleoside linkage,

[X] 1 =a conjugate group having the following structure (SEQ ID NO: 1301):

or a pharmaceutically acceptable salt thereof.

2 . The oligomeric duplex of claim 1 , wherein the pharmaceutically acceptable salt is a sodium salt.

3 . The oligomeric duplex of claim 1 , wherein the pharmaceutically acceptable salt is a potassium salt.

4 . A pharmaceutical composition comprising the oligomeric duplex of claim 1 and a pharmaceutically acceptable diluent or carrier.

5 . An oligomeric duplex according to the following chemical structure:

or a pharmaceutically acceptable salt thereof.

6 . The oligomeric duplex of claim 5 , wherein the pharmaceutically acceptable salt is a sodium salt.

7 . The oligomeric duplex of claim 5 , wherein the pharmaceutically acceptable salt is a potassium salt.

8 . A pharmaceutical composition comprising the oligomeric duplex of claim 5 and a pharmaceutically acceptable diluent or carrier.

9 . An oligomeric duplex according to the following chemical structure:

10 . A pharmaceutical composition comprising the oligomeric duplex of claim 9 and a pharmaceutically acceptable diluent or carrier.

Assignments (1)

Continuity (5)

References Cited (360)