Oligomeric compounds comprising bicyclic nucleosides and uses thereof

Patent metadata

Field	Value
Publication number	US-9695418-B2
Application number	US-201314435109-A
Country	US
Kind code	B2
Filing date	Oct 11, 2013
Priority date	Oct 11, 2012
Publication date	Jul 4, 2017
Grant date	Jul 4, 2017

Abstract

The present invention 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, the present invention provides compounds comprising oligonucleotides. In certain embodiments, such oligonucleotides comprise a region having a gapmer sugar motif. In certain embodiments, oligonucleotides comprise one or more type of modified sugar moieties and/or naturally occurring sugar moieties arranged along an oligonucleotide or region thereof in a defined pattern or sugar modification motif.

First claim

We claim:

1. A compound comprising:
a modified oligonucleotide consisting of 10 to 20 linked nucleosides, wherein the modified oligonucleotide has a motif selected from: BBB-(D) 8 -BBBAA; BBB-(D) 7 -BBBAA; BBB-(D) 8 -BBBAAA; BBB-(D) 7 -BBBAAA; BABA-(D) 8 -ABAB; BABA-(D) 7 -ABAB; ABAB-(D) 8 -ABAB; ABAB-(D) 7 -ABAB; AABB-(D) 8 -BBAA; AABB-(D) 7 -BBAA; BBB-(D) 9 -BBA; BBB-(D) 8 -BBA; BBB-(D) 7 -BBA; ABBB-(D) 8 -BBBA; ABBB-(D) 7 -BBBA; ABBB-(D) 8 -BBBAA; ABBB-(D) 7 -BBBAA; AABBB-(D) 8 -BBB; AABBB-(D) 7 -BBB; AABBB-(D) 8 -BBBA; AABBB-(D) 7 -BBBA; ABBAABB-(D) 8 -BB; ABBAABB-(D) 7 -BB; ABBABB-(D) 8 -BBB; and ABBABB-(D) 7 -BBB;
wherein each B is a bicyclic nucleoside, each A is a non-bicyclic modified nucleoside, and each D is a 2′-deoxynucleoside.

2. The compound of claim 1 , wherein at least one B is a cEt nucleoside.

3. The compound of claim 2 , wherein each B is a cEt nucleoside.

4. The compound of claim 1 , wherein at least one B is a LNA nucleoside.

5. The compound of claim 4 , wherein each B is a LNA nucleoside.

6. The compound of claim 1 , wherein each B is either a cEt nucleoside or a LNA nucleoside.

7. The compound of claim 1 , wherein each B comprises the same bicyclic sugar moiety.

8. The compound of claim 1 , wherein at least one A is a 2′-MOE nucleoside.

9. The compound of claim 1 , wherein at least one A is a 2′-OMe nucleoside.

10. The compound of claim 1 , wherein each A comprises the same non-bicyclic modified sugar moiety.

11. The compound of claim 1 comprising at least one modified internucleoside linkage.

12. The compound of claim 11 comprising at least one phosphorothioate internucleoside linkage.

13. A method of modulating expression of a target nucleic acid in a cell comprising contacting the cell with a compound according to claim 1 .

14. The method of claim 13 , wherein the cell is in an animal.

15. The method of claim 14 , wherein the animal is a human.

16. A pharmaceutical composition comprising the compound according to claim 1 and a pharmaceutically acceptable diluent.

17. A method of modulating expression of a target nucleic acid in an animal comprising administering to the animal a pharmaceutical composition according to claim 16 .

Assignees

• Ionis Pharmaceuticals Inc

Inventors

• Seth Punit P
• Freier Susan M
• Monia Brett P
• Swayze Eric E

Classifications

• C12N2310/3521

  Methyl · CPC title

• C12N2310/346

  having a combination of backbone and sugar modifications · CPC title

• C12N2320/51

  modulating the chemical stability, e.g. nuclease-resistance · CPC title

• C12N2310/34

  Spatial arrangement of the modifications · CPC title

• C12N15/111 Primary

  General methods applicable to biologically active non-coding nucleic acids · CPC title