# US 10,119,139 B2 · Treatment for conditions associated with fibrosis and collagen deposition

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

- Number: US 10,119,139 B2
- Document ID: US10119139B2
- Status: Granted
- Kind: B2
- Application number: 15/265,813
- Filed: 2016-09-14
- Published: 2017-03-16
- Granted: 2018-11-06
- Earliest claimed: 2015-09-14
- Assignees: Vanderbilt University; Yale University
- Applicants: Vanderbilt University; Yale University
- Inventors: David G. Harrison; Kim Ramil Montaniel; Kasey C. Vickers; Jing Wu; Jay D. Humphrey; Matthew R. Bersi
- Web page: https://patentgrep.com/patent/US10119139B2

## 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
- A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C12Q 1/6883: for diseases caused by alterations of genetic material
- A61B 17/22: Implements for squeezing-off ulcers or the like on inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; for invasive removal or destruction of calculus using mechanical vibrations; for removing obstructions in blood vessels, not otherwise provided for
- A61B 2017/22001: {Angioplasty, e.g. PCTA}
- A61B 2017/22051: {with an inflatable part, e.g. balloon, for positioning, blocking, or immobilisation (A61B2017/22048, A61B2017/3486 take precedence)}
- C12N 2310/113: targeting other non-coding nucleic acids, e.g. antagomirs
- C12N 2310/3231: having an additional ring, e.g. LNA, ENA
- 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)
- 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
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)

## Abstract

Methods, compositions, devices, and kits for treating and/or reducing the risk of developing a condition associated with fibrosis and/or collagen deposition are provided. The method of treating and/or reducing the risk of developing a condition associated with fibrosis and/or collagen deposition in a subject includes administering an effective amount a miRNA-762 inhibitor to the subject, wherein the subject is identified as having a risk of developing and/or a need for treatment of the condition associated with fibrosis and/or collagen deposition. The kit includes a vial containing an miRNA-762 inhibitor and a device for use in a surgery creating a risk of fibrosis and/or collagen deposition. The composition includes a pharmaceutical composition comprising a miRNA-762 inhibitor and a second agent selected from the group consisting of: an angiotensin-converting enzyme (ACE) inhibitors, an angiotensin receptor blocker (ARB), another antihypertensive agent, a steroid, and combinations thereof.

## Claims

### Claim 1

A treatment method for HTN-induced kidney damage, Ang II induced aortic fibrosis, or upregulation of matrix degrading matrix metalloproteinases (MMPs), comprising:
administering an effective amount of a miRNA-762 inhibitor to a subject;
wherein the subject is in need of treatment for HTN-induced kidney damage, Ang II induced aortic fibrosis, or upregulation of matrix degrading MMPs.

### Claim 2 (depends on 1)

The method of claim 1, and further comprising determining the levels of miR-762 in a sample from the subject.

### Claim 3 (depends on 2)

The method of claim 2, wherein the sample includes excess levels of miR-762 as compared to a control.

### Claim 4 (depends on 1)

The method of claim 1, wherein the miRNA-762 inhibitor is an oligonucleotide of 8-49 nucleotides in length having a sequence targeted to miRNA-762, or a precursor thereof.

### Claim 5 (depends on 4)

The method of claim 4, wherein the oligonucleotide is an antisense oligonucleotide that is at least partially complementary to the sequence of the target miRNA, or a precursor thereof.

### Claim 6 (depends on 5)

The method of claim 5, wherein the antisense oligonucleotide is selected from the group consisting of a ribonucleotide, a deoxyribonucleotide, an anti-sense molecule, a siRNA molecule, a shRNA molecule, a miRNA sponge, a cDNA, an antagomir, a locked nucleic acid (LNA) oligonucleotide, a decoy oligonucleotide, a peptide nucleic acid (PNA), a morpholino oligonucleotide, or a combination thereof.

### Claim 7 (depends on 5)

The method of claim 5, wherein the oligonucleotide consists of a locked nucleic acid (LNA) oligonucleotide.

### Claim 8 (depends on 7)

The method of claim 7, wherein the oligonucleotide is selected from the group consisting of:
(a) a nucleotide sequence comprising at least 16 contiguous nucleotides complementary to the sequence of SEQ ID NO: 1 and modifications excluding base substitutions thereof;
(b) a nucleotide sequence comprising at least 16 contiguous nucleotides complementary to the sequence of SEQ ID NO. 2 and modifications excluding base substitutions thereof; and
(c) a nucleotide sequence comprising at least 8 contiguous nucelotides complementary to the sequence of a fragment consisting of a subsequence of SEQ ID NO: 2 of at least 8 contiguous nucleotides thereof.

### Claim 9 (depends on 4)

The method of claim 4, wherein the oligonucleotide is modified to include a 2′-deoxy-2′-fluoro-beta-D-arabinose backbone.

### Claim 10 (depends on 1)

The method of claim 1, wherein the miRNA-762 inhibitor is associated with a carrier molecule selected from the group consisting of a nanoparticle, a liposome, and a lipoprotein.

### Claim 11 (depends on 1)

The method of claim 1, wherein the subject does not have vascular calcification.

### Claim 12 (depends on 1)

The method of claim 1, wherein the inhibitor is administered at a site of fibrosis, scarring, or keloid.

### Claim 13 (depends on 12)

The method of claim 12, wherein the inhibitor is administered topically or by local injection.

### Claim 14 (depends on 1)

The method of claim 1, wherein the inhibitor is associated with a device selected from the group consisting of a stent coated with the inhibitor and a bandage comprising the inhibitor.

### Claim 15

A method of upregulating matrix degrading matrix metalloproteinases (MMPs) in a subject having fibrosis, scarring, or keloid, comprising:
administering an effective amount a miRNA-762 inhibitor to the subject.

### Claim 16 (depends on 15)

The method of claim 15, wherein the miRNA-762 inhibitor is administered at a site of fibrosis, scarring, or keloid.

### Claim 17

A method of upregulating matrix degrading matrix metalloproteinases (MMPs) in a subject, comprising:
administering an effective amount a miRNA-762 inhibitor to the subject;
wherein the subject is identified as having or being at risk for developing perivascular fibrosis, fibrosis of a blood vessel, aortic stiffening/hypertension, vascular fibrosis, vascular disease, and vascular inflammation.
