Oligonucleotide compositions and methods thereof

Patent metadata

Field	Value
Publication number	US-10724035-B2
Application number	US-201716098836-A
Country	US
Kind code	B2
Filing date	May 3, 2017
Priority date	May 4, 2016
Publication date	Jul 28, 2020
Grant date	Jul 28, 2020

Abstract

Among other things, the present disclosure relates to chirally controlled oligonucleotides of select designs, chirally controlled oligonucleotide compositions, and methods of making and using the same. In some embodiments, a provided chirally controlled oligonucleotide composition provides different cleavage patterns of a nucleic acid polymer than a reference oligonucleotide composition. In some embodiments, a provided chirally controlled oligonucleotide composition provides single site cleavage within a complementary sequence of a nucleic acid polymer. In some embodiments, a chirally controlled oligonucleotide composition has any sequence of bases, and/or pattern or base modifications, sugar modifications, backbone modifications and/or stereochemistry, or combination of these elements, described herein.

First claim

The invention claimed is:

1. An oligonucleotide having the structure of:
mG * SmUmGmCmA * SC * SA * SC * SA * SG * ST * SA * SG * RA * ST * SmGmAmGmG * SmG (SEQ ID NO: 1467), or a pharmaceutically acceptable salt thereof, wherein:
*S represents a Sp phosphorothioate;
*R represents a Rp phosphorothioate; and
m represents a 2′-OMe modification to a nucleoside.

2. The oligonucleotide of claim 1 , wherein the oligonucleotide is in a salt form.

3. The oligonucleotide of claim 1 , wherein the salt is a sodium salt.

4. An oligonucleotide, wherein the oligonucleotide is a sodium salt of:
mG * SmUmGmCmA * SC * SA * SC * SA * SG * ST * SA * SG * RA * ST * SmGmAmGmG * SmG (SEQ ID NO: 1467), wherein:
*S represents a Sp phosphorothioate;
*R represents a Rp phosphorothioate;
m represents a 2′-OMe modification to a nucleoside; and

the number of sodium ions in the sodium salt equals the total number of phosphorothioate and phosphate linkages in the oligonucleotide.

5. A chirally controlled composition of an oligonucleotide having the structure of:
mG * SmUmGmCmA * SC * SA * SC * SA * SG * ST * SA * SG * RA * ST * SmGmAmGmG * SmG (SEQ ID NO: 1467), or a pharmaceutically acceptable salt thereof, wherein:
*S represents a Sp phosphorothioate;
*R represents a Rp phosphorothioate; and
m represents a 2′-OMe modification to a nucleoside,
wherein the composition is enriched, relative to a substantially racemic preparation of the oligonucleotide for the oligonucleotide.

6. The composition of claim 5 , wherein the oligonucleotide is in a salt form.

7. The composition of claim 5 , wherein the oligonucleotide is a sodium salt.

8. The composition of claim 7 , wherein the number of sodium ions in the sodium salt equals the total number of phosphorothioate and phosphate linkages in the oligonucleotide.

9. A pharmaceutical composition, comprising a therapeutically effective amount of an oligonucleotide and at least one pharmaceutically acceptable inactive ingredient selected from pharmaceutically acceptable diluents, pharmaceutically acceptable excipients, and pharmaceutically acceptable carriers, wherein the oligonucleotide has the structure of:
mG * SmUmGmCmA * SC * SA * SC * SA * SG * ST * SA * SG * RA * ST * SmGmAmGmG * SmG (SEQ ID NO: 1467), or a pharmaceutically acceptable salt thereof, wherein:
*S represents a Sp phosphorothioate;
*R represents a Rp phosphorothioate; and
m represents a 2′-OMe modification to a nucleoside.

10. The composition of claim 9 , wherein the oligonucleotide is in a salt form.

11. The composition of claim 9 , wherein the oligonucleotide is a sodium salt.

12. The composition of claim 9 , wherein the number of sodium ions in the sodium salt equals the total number of phosphorothioate and phosphate linkages in the oligonucleotide.

Assignees

• Wave Life Sciences Ltd

Inventors

• Vargeese Chandra
• Meena
• Svrzikapa Nenad
• Mohapatra Susovan
• Francis Christopher J
• Verdine Gregory L
• Sokolovska Anna

Classifications

• C12N2310/315

  Phosphorothioates · CPC title

• C12N2310/11

  Antisense · CPC title

• A61P25/14

  for treating abnormal movements, e.g. chorea, dyskinesia · CPC title

• C12N2310/346

  having a combination of backbone and sugar modifications · CPC title

• C12N2310/14

  interfering nucleic acids [NA] · CPC title