# US 11,299,735 B2 · Compositions and methods for detecting and treating insulin resistance

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- Number: US 11,299,735 B2
- Document ID: US11299735B2
- Status: Granted
- Kind: B2
- Application number: 16/475,549
- Filed: 2018-08-24
- Published: 2020-06-04
- Granted: 2022-04-12
- Earliest claimed: 2017-08-25
- Assignees: The Governing Council of the University of Toronto
- Applicants: The Governing Council of the University of Toronto
- Inventors: Denise Belsham; Jennifer Chalmers
- Web page: https://patentgrep.com/patent/US11299735B2

## 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 9/0043: {Nose}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61P 3/08: for glucose homeostasis (pancreatic hormones A61P5/48)
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/50: for increasing or potentiating the activity of insulin
- C12Q 1/6883: for diseases caused by alterations of genetic material
- C12N 2310/113: targeting other non-coding nucleic acids, e.g. antagomirs
- C12N 2310/141: MicroRNAs, miRNAs
- C12N 2310/313: Phosphorodithioates
- C12N 2310/315: Phosphorothioates
- C12N 2310/3231: having an additional ring, e.g. LNA, ENA
- C12N 2310/346: having a combination of backbone and sugar modifications
- C12N 2320/30: Special therapeutic applications
- C12N 2320/51: modulating the chemical stability, e.g. nuclease-resistance
- C12Q 2600/118: Prognosis of disease development
- C12Q 2600/158: Expression markers
- C12Q 2600/178: miRNA, siRNA or ncRNA
- 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
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

A miR-1983 inhibitor comprising an anti-miR-1983 oligonucleotide that is complementary to at least part of CTCACCTGGAGCATGTTTTCT (SEQ ID NO: 1), the part comprising at least nucleotides 2 to 8 of CTCACCTGGAGCATGTTTTCT (SEQ ID NO: 1).

## Claims

### Claim 1

A miR-1983 inhibitor that comprises an anti-miR-1983 oligonucleotide consisting of a nucleotide sequence selected from nucleotides 9 to 15, 8 to 15, 7 to 15, 6 to 15, 5 to 15, 4 to 15, 3 to 15, 2 to 15 or 1 to 15 of 5′-3′, A*C*A*T/U*G*C*T/U*C*C*A*G*G*T/U*G*A (SEQ ID NO: 2).

### Claim 2 (depends on 1)

The miR-1983 inhibitor of claim 1, wherein the anti-miR-1983 oligonucleotide comprises RNA.

### Claim 3 (depends on 1)

The miR-1983 inhibitor of claim 1, wherein the anti-miR-1983 oligonucleotide is chemically modified.

### Claim 4 (depends on 3)

The miR-1983 inhibitor of claim 3, wherein the chemically modified anti-miR-1983 oligonucleotide comprises a chemical modification at a 2′ position.

### Claim 5 (depends on 4)

The miR-1983 inhibitor of claim 4, wherein the chemical modification is selected from the group consisting of 2′-O-methyl (2′: 0-Me), 2′-O-methoxyethyl (2′O-MOE), 2′-fluoro (2′zF), and locked nucleic acid monomer (LNAM).

### Claim 6 (depends on 5)

The miR-1983 inhibitor of claim 5, wherein the anti-miR-1983 oligonucleotide comprises a plurality of chemically modified nucleotide monomers.

### Claim 7 (depends on 6)

The miR-1983 inhibitor of claim 6, wherein the anti-miR-1983 oligonucleotide comprises a plurality of LNAMs.

### Claim 8 (depends on 7)

The miR-1983 inhibitor of claim 7, wherein the anti-miR-1983 oligonucleotide is a locked nucleic acid (LNA) or a LNA/DNA mixmer.

### Claim 9 (depends on 8)

The miR-1983 inhibitor of claim 8, wherein the LNA comprises sequence 5′-3′, A*C*A*T/U*G*C*T/U*C*C*A*G*G*T/U*G*A (SEQ ID NO: 2).

### Claim 10 (depends on 9)

The miR-1983 inhibitor of claim 9, wherein the LNA comprises sequence 5′-3′, A*C*A*T*G*C*T*C*C*A*G*G*T*G*A (SEQ ID NO: 2).

### Claim 11 (depends on 9)

The miR-1983 inhibitor of claim 9, wherein the LNA comprises sequence 5′-3′, A*C*A*U*G*C*U*C*C*A*G*G*U*G*A (SEQ ID NO: 2).

### Claim 12 (depends on 1)

The miR-1983 inhibitor of claim 1, wherein the anti-miR-1983 oligonucleotide comprises at least one mismatch and up to 4 mismatches.

### Claim 13 (depends on 1)

The miR-1983 inhibitor of claim 1, wherein the anti-miR-1983 oligonucleotide is double stranded.

### Claim 14 (depends on 1)

The miR-1983 inhibitor of claim 1, wherein the anti-miR-1983 oligonucleotide is single stranded.

### Claim 15 (depends on 1)

The miR-1983 inhibitor of claim 1, wherein the miR-1983 inhibitor consists of the anti-miR-1983 oligonucleotide.

### Claim 16 (depends on 1)

A composition comprising the miR-1983 inhibitor of claim 1 and a diluent.

### Claim 17 (depends on 16)

The composition of claim 16 formulated as an intranasal formulation.

### Claim 18 (depends on 16)

The composition of claim 16, wherein the diluent comprises saline.

### Claim 19

A method of improving insulin sensitivity in a subject, the method comprising administering a miR-1983 inhibitor to a subject in need thereof.

### Claim 20 (depends on 19)

The method of claim 19 wherein the miR-1983 inhibitor comprises an anti-miR-1983 oligonucleotide that is complementary to at least part of CTCACCTGGAGCATGTTTTCT (SEQ ID NO: 1), the part comprising at least nucleotides 2 to 8 of CTCACCTGGAGCATGTTTTCT (SEQ ID NO: 1) or a composition comprising said inhibitor.

### Claim 21 (depends on 19)

The method of claim 19 wherein the miR-1983 inhibitor is administered intranasally.