Targeting microRNAs for the treatment of fibrosis
Inventors
Assignees
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Publication Number
US-9970007-B2
Publication Date
2018-05-15
Expiration Date
Abstract
Provided herein are compositions and methods for the modulation of miR-214 for the treatment and/or prevention of fibrosis and fibroproliferative conditions.
Core Innovation
The invention relates to targeting miR-214 to treat, prevent, or delay fibrosis. A compound is administered to a subject having fibrosis or at risk of developing fibrosis, where the compound comprises a modified oligonucleotide with a nucleobase sequence fully complementary to the nucleobase sequence of miR-214. The modified oligonucleotide is characterized as having phosphorothioate internucleoside linkages.
The document provides that the fibrosis treated is kidney fibrosis, and the subject may have fibrosis or may be at risk of developing fibrosis. The modified oligonucleotide consists of 8 to 12 linked nucleosides in the kidney fibrosis method, and embodiments further define specific sequence complementarity to a reference miR-214 nucleobase sequence (SEQ ID NO: 1).
The disclosed modified oligonucleotides further include phosphorothioate internucleoside linkages and may include nucleosides bearing modified sugars. Example embodiments described include modified sugars selected from 2′-O-methoxyethyl and 2′-fluoro, and other embodiments define allowable modified sugars including 2′-O-methoxyethyl sugar, 2′-fluoro sugar, 2′-O-methyl sugar, and a bicyclic sugar moiety.
Claims Coverage
The independent claim identified is clm-00001. It contains 3 main inventive features: a modified oligonucleotide fully complementary to miR-214, phosphorothioate internucleoside linkages, and application to kidney fibrosis treatment, prevention, or delay.
miR-214 fully complementary modified oligonucleotide (8 to 12 linked nucleosides)
A method comprising administering to a subject having fibrosis or at risk of developing fibrosis a compound comprising a modified oligonucleotide consisting of 8 to 12 linked nucleosides and having a nucleobase sequence fully complementary to the nucleobase sequence of miR-214.
Phosphorothioate internucleoside linkage in the anti-miR oligonucleotide
The modified oligonucleotide has each internucleoside linkage as a phosphorothioate internucleoside linkage.
Kidney fibrosis treatment, prevention, or delay
The fibrosis is kidney fibrosis in a method of treating, preventing, or delaying the onset of fibrosis by administering the modified oligonucleotide compound.
Overall claim coverage centers on a method for kidney fibrosis that administers a modified oligonucleotide consisting of 8 to 12 linked nucleosides, fully complementary to miR-214, with phosphorothioate internucleoside linkages.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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