Selective antisense compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-10260069-B2
Application number	US-201414765633-A
Country	US
Kind code	B2
Filing date	Feb 4, 2014
Priority date	Feb 4, 2013
Publication date	Apr 16, 2019
Grant date	Apr 16, 2019

Abstract

The present disclosure provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell. In certain embodiments, certain oligomeric compounds selectively reduce the expression of a target nucleic acid transcript relative to a non-target nucleic acid transcript.

First claim

We claim:

1. A oligomeric compound comprising a modified oligonucleotide consisting of a modification motif selected from:
eeek-d7-eeeeeeee,
eek-d7-eeeeeeeee,
ek-d7-eeeeeeeeee,
ek-d8-eeekk,
k-d8-eeekeke,
k-d8-eeekekee,
k-d9-eekek,
ek-d7-eeeekeke,
ek-d8-eeekek,
eek-d9-keeke,
ek-d9-eekek,
ek-d9-keek,
eek-d8-eeekek,
ek-d8-keeekee,
ek-d9-eekeke,
ek-d8-eeekeke, and
ek-d7-eeeekek;
wherein the modified oligonucleotide has a nucleobase sequence complementary to the nucleobase sequence of a target region of a huntingtin transcript, wherein the target region comprises single nucleotide polymorphism (SNP) rs7685686;
wherein the nucleobase sequence of the target region of the huntingtin transcript differs from the nucleobase sequence of at least one non-target nucleic acid by 1-3 differentiating nucleobases; and wherein at least one non-target nucleic acid is bone morphogenetic protein receptor, type IA;
wherein each “e” is a 2′MOE modified nucleoside, each “k” is a cEt modified nucleoside, and each d is an unmodified deoxynucleoside.

2. The oligomeric compound of claim 1 , wherein the nucleobase sequence of the target region of the huntingtin transcript differs from the nucleobase sequence of bone morphogenetic protein receptor, type IA by a single differentiating nucleobase.

3. The oligomeric compound of claim 1 , wherein the modification motif is selected from:
eeek-d7-eeeeeeee,
eek-d7-eeeeeeeee,
ek-d7-eeeeeeeeee,
ek-d8-eeekk,
k-d8-eeekeke,
k-d8-eeekekee,
k-d9-eekek,
ek-d7-eeeekeke,
ek-d8-eeekek,
eek-d9-keeke,
ek-d9-eekek, and
ek-d9-keek;
wherein each “e” is a 2′MOE modified nucleoside, each “k” is a cEt modified nucleoside, and each “d” is an unmodified deoxynucleoside.

4. The oligomeric compound of claim 2 , comprising at least one modified internucleoside linkage.

5. The oligomeric compound of claim 4 , wherein each internucleoside linkage is a modified internucleoside linkage.

6. The oligomeric compound of claim 4 , comprising at least one phosphorothioate internucleoside linkage.

7. The oligomeric compound of claim 5 , wherein each internucleoside linkage is a phosphorothioate internucleoside linkage.

8. The oligomeric compound of claim 6 , wherein the 5′-most internucleoside linkage of the 5′-region is a phosphorothioate internucleoside linkage, wherein the 3′-most internucleoside linkage of the 3′-region is a phosphorothioate internucleoside linkage, and wherein each internucleoside linkage of the central region is a phosphorothioate internucleoside linkage.

9. The oligomeric compound of claim 6 , wherein the 5′-most internucleoside linkage of the 5′-region is a phosphorothioate internucleoside linkage, wherein the 3′-most internucleoside linkage of the 3′-region is a phosphorothioate internucleoside linkage, wherein each internucleoside linkage of the central region is a phosphorothioate internucleoside linkage, and wherein each remaining internucleoside linkage is a phosphodiester internucleoside linkage.

10. The oligomeric compound of claim 6 , wherein the oligomeric compound contains 2 phosphodiester internucleoside linkages.

11. The oligomeric compound of claim 6 , wherein the oligomeric compound contains 3 phosphodiester internucleoside linkages.

12. The oligomeric compound of claim 1 , wherein the nucleobase sequence of the target region of the huntingtin transcript differs from the nucleobase sequence of bone morphogenetic protein receptor, type IA by two differentiating nucleobases.

Assignees

• Ionis Pharmaceuticals Inc

Inventors

• Oestergaard Michael
• Seth Punit P
• Swayze Eric E

Classifications

• C12N2310/341

  Gapmers, i.e. of the type ===---=== · CPC title

• C12N2320/53

  reducing unwanted side-effects · CPC title

• C12N2310/315

  Phosphorothioates · CPC title

• C12N2310/335

  Modified T or U · CPC title

• C07H21/02 Primary

  with ribosyl as saccharide radical · CPC title