# US 10,119,135 B2 · Therapeutic micro RNA targets in chronic pulmonary diseases

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,119,135 B2
- Document ID: US10119135B2
- Status: Granted
- Kind: B2
- Application number: 14/402,586
- Filed: 2013-05-15
- Published: 2015-05-21
- Granted: 2018-11-06
- Earliest claimed: 2012-05-22
- Assignees: Ruprecht-Karls-UniversitäT Heidelberg
- Applicants: Ruprecht-Karls-Universitaet Heidelberg
- Inventors: Marcus Mall; Raman Agrawal; Martina Muckenthaler
- Web page: https://patentgrep.com/patent/US10119135B2

## 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 31/713: Double-stranded nucleic acids or oligonucleotides
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/543: {Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine}
- A61P 11/00: Drugs for disorders of the respiratory system
- 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 2310/315: Phosphorothioates
- C12N 2310/321: 2'-O-R Modification
- C12N 2310/3515: Lipophilic moiety, e.g. cholesterol
- 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

The present invention relates to the identification of microRNAs of the miR-148 family that are involved in the pathogenesis of chronic pulmonary diseases. The present invention relates to micro RNA of the miR-148 family selected from miR-148a, miR-148b and miR-152 for use in the diagnosis, prognosis, prevention and/or therapy of a chronic pulmonary disease. The present invention further relates to miR-148 inhibitors, pharmaceutical compositions comprising such inhibitors, their use in preventing and/or treating chronic pulmonary diseases, and methods for preventing and/or treating chronic pulmonary diseases. The present invention further relates to transgenic, non-human mammals and methods for identifying modulators of miR-148 and methods for diagnosis and/or prognosis of chronic pulmonary diseases.

## Claims

### Claim 1

A method of treating a chronic pulmonary disease selected from chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) lung disease, in a subject in need thereof, the method comprising:
inhibiting a micro RNA 148b (miR-148b) expression and/or activity by administering to the subject an effective amount of at least one inhibitor of miR-148b, wherein the at least one inhibitor of miR-148b comprises a sequence complementary to at least 13 contiguous nucleotides of a nucleotide sequence of SEQ ID NO:1 or a sequence having at least 95% sequence identity to a nucleotide sequence of SEQ ID NO:1.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the at least one miR-148b inhibitor is 13 to 22 nucleotides in length; and wherein the at least one miR-148b inhibitor comprises at least one 2′-O-modified nucleotide.

### Claim 3 (depends on 2)

The method according to claim 2, wherein the at least one miR-148b inhibitor comprises RNA, LNA, or combinations thereof.

### Claim 4 (depends on 2)

The method according to claim 2, wherein the at least one miR-148b inhibitor sequence is 20 to 22 nucleotides in length.

### Claim 5 (depends on 2)

The method according to claim 2, wherein the at least one miR-148b inhibitor comprises one or more phosphorothioate linkages.

### Claim 6 (depends on 2)

The method according to claim 2, wherein the at least one miR-148b inhibitor is conjugated at an end.

### Claim 7 (depends on 6)

The method according to claim 6, wherein the at least one miR-148b inhibitor is conjugated with a hydrophobic moiety.

### Claim 8 (depends on 7)

The method according to claim 7, wherein the hydrophobic moiety is cholesterol.

### Claim 9 (depends on 2)

The method according to claim 2, wherein the at least one miR-148b inhibitor comprises a cellular delivery construct or carrier for the oligonucleotide.

### Claim 10 (depends on 9)

The method according to claim 9, wherein the at least one miR-148b inhibitor comprises an expression vector, a virus or parts thereof, or a liposome.

### Claim 11 (depends on 2)

The method according to claim 2, wherein the at least one miR-148b inhibitor is an antagomir of miR-148b.

### Claim 12 (depends on 2)

The method according to claim 2, wherein the at least one miR-148b inhibitor is administered to a subject in need thereof by inhalation, intravenous, oral, suppository, or sublingual administration.

### Claim 13 (depends on 12)

The method according to claim 12, wherein inhalation administration is as aerosol, dry powder, solution, or sustained release aerosol, powder or solution.

### Claim 14 (depends on 2)

The method according to claim 2, wherein the at least one miR-148b inhibitor is administered to a subject in need thereof in combination with a second pulmonary therapy.

### Claim 15 (depends on 14)

The method according to claim 14, wherein said second therapy is selected from a therapy or treatment with bronchodilators, inhaled corticosteroids (ICS) or inhaled mucolytics.
