# US 11,028,389 B2 · Methods for enhancing utrophin production via inhibition of microRNA

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- Number: US 11,028,389 B2
- Document ID: US11028389B2
- Status: Granted
- Kind: B2
- Application number: 16/319,355
- Filed: 2017-07-19
- Published: 2019-10-03
- Granted: 2021-06-08
- Earliest claimed: 2016-07-19
- Assignees: The Trustees of the University of Pennsylvania
- Applicants: The Trustees of the University of Pennsylvania; Murdoch University
- Inventors: Tejvir S. Khurana; Steve Wilton
- Web page: https://patentgrep.com/patent/US11028389B2

## CPC

- 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)}
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- C12N 2310/113: targeting other non-coding nucleic acids, e.g. antagomirs
- C12N 2310/314: Phosphoramidates
- C12N 2310/315: Phosphorothioates
- C12N 2310/321: 2'-O-R Modification
- C12N 2310/3233: Morpholino-type ring
- C12N 2320/32: Special delivery means, e.g. tissue-specific
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This invention provides a method for enhancing utrophin protein production in a cell by inhibiting an utrophin microRNA molecule. Moreover, the invention provides that methods for enhancing utrophin protein production in a muscle cell are used for treating a muscular dystrophy and/or other myopathies.

## Claims

### Claim 1

A pharmaceutical composition comprising an antisense oligonucleotide that specifically hybridizes to a Let-7c microRNA binding sequence in a 3′-UTR of a utrophin mRNA 3′ untranslated region (UTR) and inhibits the binding of the Let-7c microRNA to the utrophin mRNA 3′-UTR and at least one pharmaceutically acceptable excipient, wherein the antisense oligonucleotide is present in an amount effective in a human subject to inhibit the binding of Let-7 micro RNA with its utrophin mRNA 3′-UTR binding sequence, and wherein the antisense oligonucleotide comprises the sequence of SEQ ID NO: 25 (5′-CUG AGG UAG AAA GGU GGU CAU GGC UU-3′).

### Claim 2 (depends on 1)

The composition of claim 1, wherein the antisense oligonucleotide is a 2′-0-methyl phosphorothioate oligonucleotide.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the composition is formulated for injection to the subject.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the composition is formulated for intramuscular administration to the subject.

### Claim 5 (depends on 1)

The composition of claim 1, further comprising at least one additional antisense oligonucleotide that specifically hybridizes to at least one additional microRNA binding sequence in the utrophin mRNA 3′-UTR and inhibits the binding of the at least one additional micro RNA to the utrophin mRNA 3′-UTR, wherein the additional micro RNA is selected from the group consisting of miR-133b, miR-150, miR-196b, miR-206, and miR-296-5p, and wherein the additional antisense oligonucleotide is present in an amount effective in a human subject to inhibit its binding with its corresponding utrophin mRNA 3′-UTR binding sequence.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the antisense oligonucleotide is present in an amount effective in the human subject to increase basal levels of translation of utrophin in a muscle cell in the subject by about 1.1 fold or more.