Oligonucleotide compositions and methods thereof

• US 10,479,995 B2
• Filed: 07/22/2016
• Issued: 11/19/2019
• Est. Priority Date: 07/22/2015
• Status: Active Grant

• Current Assignee: WAVE Life Sciences Ltd.
• Original Assignee: WAVE Life Sciences Ltd.
• Inventors: Vargeese, Chandra, Meena, Svrzikapa, Nenad, Mohapatra, Susovan, Francis, Christopher J., Verdine, Gregory L., Sokolovska, Anna
• Primary Examiner(s): Zara, Jane J
• Application Number:
  US15/746,220
• Publication Number:
  US 20180216108A1
• Time in Patent Office: 1,215 Days
• Field of Search: 435 61, 435 911, 435 9131, 536 231, 536 243, 536 2431, 536 2433, 536 245
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 15/115 Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/322 2'-R Modification
• CPC Class Codes: C12N 2310/341 Gapmers, i.e. of the type ===---===
• CPC Class Codes: C12N 2310/346 having a combination of backbone and sugar modifications
• CPC Class Codes: C12N 2310/3525 MOE, methoxyethoxy

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.

Claims

1. An oligonucleotide having the structure of:

mG*SmGmCmAmC*SA*SA*SG*SG*SG*SC*SA*SC*RA*SG*SmAmCmUmU*SmC (SEQ ID NO;

     360), 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. An oligonucleotide, wherein the oligonucleotide is a sodium salt of:

mG*SmGmCmAmC*SA*SA*SG*SG*SG*SC*SA*SC*RA*SG*SmAmCmUmU*SmC (SEQ ID NO;

     360), wherein;

*S represents a Sp phosphorothioate;

*R represents a Rp phosphorothioate; and

m represents a 2′

-OMe modification to a nucleoside.

4. A chirally controlled composition of an oligonucleotide having the structure of:

mG*SmGmCmAmC*SA*SA*SG*SG*SG*SC*SA*SC*RA*SG*SmAmCmUmU*SmC (SEQ ID NO;

     360), 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.

5. The composition of claim 4, wherein the oligonucleotide is in a salt form.

6. The composition of claim 4, wherein the oligonucleotide is a sodium salt.

7. A pharmaceutical composition, comprising a therapeutically efficient amount of an oligonucleotide and at least on pharmaceutical acceptable inactive ingredient selected from pharmaceutically acceptable diluents, pharmaceutically acceptable excipients, and pharmaceutically acceptable carriers, wherein the oligonucleotide has the structure of:

mG*SmGmCmAmC*SA*SA*SG*SG*SG*SC*SA*SC*RA*SG*SmAmCmUmU*SmC (SEQ ID NO;

     360), 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.

8. The composition of claim 7, wherein the oligonucleotide is in a salt form.

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