MicroRNA compounds and methods for modulating MIR-21 activity

Patent metadata

Field	Value
Publication number	US-9181547-B2
Application number	US-201214111976-A
Country	US
Kind code	B2
Filing date	Apr 25, 2012
Priority date	Apr 25, 2011
Publication date	Nov 10, 2015
Grant date	Nov 10, 2015

Abstract

Described herein are compositions and methods for the inhibition of miR-21 activity. The compositions have certain nucleoside modification patterns that yield potent inhibitors of miR-21 activity. The compositions may be used to inhibit miR-21, and also to treat diseases associated with abnormal expression of miR-21, such as fibrosis and cancer.

First claim

What is claimed is:

1. A modified oligonucleotide consisting of 19 linked nucleosides and having the structure:
5′-A E C S ATC S AGTC S TGAU S AAGC S TA E -3′ (SEQ ID NO: 3), wherein nucleosides not followed by a subscript are β-D-deoxyribonucleosides; nucleosides followed by a subscript “E” are 2′-methoxyethyl (2′-MOE) nucleosides; and nucleosides followed by a subscript “S” are S-constrained ethyl (S-cEt) nucleosides; and wherein each internucleoside linkage is a phosphorothioate linkage.

2. A pharmaceutical composition comprising the modified oligonucleotide of claim 1 and a pharmaceutically acceptable diluent.

3. The pharmaceutical composition of claim 2 , which is a sterile aqueous solution.

4. A pharmaceutical composition consisting essentially of a modified oligonucleotide in a sterile aqueous solution, wherein the modified oligonucleotide consists of 19 linked nucleosides and has the structure:
5′-A E C S ATC S AGTC S TGAU S AAGC S TA E -3′ (SEQ ID NO: 3), wherein nucleosides not followed by a subscript are β-D-deoxyribonucleosides; nucleosides followed by a subscript “E” are 2′-methoxyethyl (2′-MOE) nucleosides; and nucleosides followed by a subscript “S” are S-constrained ethyl (S-cEt) nucleosides; and wherein each internucleoside linkage is a phosphorothioate linkage.

5. A lyophilized composition comprising a modified oligonucleotide consisting of 19 linked nucleosides and having the structure:
5′-A E C S ATC S AGTC S TGAU S AAGC S TA E -3′ (SEQ ID NO: 3), wherein nucleosides not followed by a subscript are β-D-deoxyribonucleosides; nucleosides followed by a subscript “E” are 2′-methoxyethyl (2′-MOE) nucleosides; and nucleosides followed by a subscript “S” are S-constrained ethyl (S-cEt) nucleosides; and wherein each internucleoside linkage is a phosphorothioate linkage.

6. A lyophilized composition consisting essentially of a modified oligonucleotide consisting of 19 linked nucleosides and having the structure:
5′-A E C S ATC S AGTC S TGAU S AAGC S TA E -3′ (SEQ ID NO: 3), wherein nucleosides not followed by a subscript are β-D-deoxyribonucleosides; nucleosides followed by a subscript “E” are 2′-methoxyethyl (2′-MOE) nucleosides; and nucleosides followed by a subscript “S” are S-constrained ethyl (S-cEt) nucleosides; and wherein each internucleoside linkage is a phosphorothioate linkage.

Assignees

• Bhat Balkrishen
• Regulus Therapeutics Inc

Inventors

• Bhat Balkrishen

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title