# US 11,078,535 B2 · Presymptomatic micro RNA targets for treatment of neurodegeneration pathology

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- Number: US 11,078,535 B2
- Document ID: US11078535B2
- Status: Granted
- Kind: B2
- Application number: 16/631,866
- Filed: 2018-07-07
- Published: 2020-05-21
- Granted: 2021-08-03
- Earliest claimed: 2017-07-18
- Assignees: The Trustees of Indiana University
- Applicants: The Trustees of Indiana University
- Inventors: Salil Sharma; Hui-Chen Lu
- Web page: https://patentgrep.com/patent/US11078535B2

## CPC

- C12Q 1/6883: for diseases caused by alterations of genetic material
- A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- 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)}
- C12Q 1/686: Polymerase chain reaction [PCR]
- C12N 2310/113: targeting other non-coding nucleic acids, e.g. antagomirs
- C12N 2310/14: interfering nucleic acids [NA]
- C12Q 2600/178: miRNA, siRNA or ncRNA
- 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
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Compositions and methods are provided for the early detection of neuroinflammation in a patient in a presymptomatic stage of a neurodegenerative disease. The method comprises identifying patients with elevated expression levels of a micro RNA selected from the group consisting of miR142-3p, miR142-5p, miR181a, miR181b, miR219-3p and miR219-5p. The identified patients can then be treated with a therapeutic pharmaceutical composition comprising antimiR oligonucleotides.

## Claims

### Claim 1

A method of treating neuroinflammation in a patient having a neurodegenerative condition and exhibiting elevated levels of two or more micro RNAs selected from the group consisting of miR142-3p, miR142-5p, and miR219-3p, said method comprising:
identifying in patients having a neurodegenerative condition, those patients having elevated levels of two or more micro RNAs selected from the group consisting of miR219-3p, miR142-3p and miR142-5, by
i) obtaining a reference expression level of two or more micro RNAs selected from the group consisting of miR219-3p, miR142-3p and miR142-5p;
ii) determining an expression level of two or more micro RNAs selected from the group consisting of miR219-3p, miR142-3p and miR142-5p, and corresponding to those of step i), in a sample obtained from said patient having a neurodegenerative condition, wherein an increase in the expression level of said two or more micro RNAs selected from the group consisting of miR142-3p and miR142-5p in said patient's sample as compared to the reference expression level identifies the patient as having neuroinflammation; and
administering to said patient having a neurodegenerative condition and identified as having elevated levels of said two or more micro RNAs selected from the group consisting of miR142-3p, miR142-5p, and miR219-3p a therapeutic composition comprising an antisense or interference oligonucleotide that is complementary to a micro RNA selected from the group consisting of miR142-3p, miR142-5p, and miR219-3p, wherein said antisense or interference oligonucleotide reduces the expression of a micro RNA selected from the group consisting of miR219-3p, miR142-3p and miR142-5p and provides treatment of said neuroinflammation.

### Claim 2

A method of treating neuroinflammation in a patient with a neurodegenerative condition, said method comprising
i) obtaining a reference expression level of miR142-3p and miR219-3p;
ii) determining an expression level of miR142-3p and miR219-3p, in a sample obtained from said patient, wherein an increase in the expression level of miR142-3p and miR219-3p in said patient's sample as compared to the reference expression level identifies the patient as having neuroinflammation; and
administering a therapeutic composition comprising antisense or interference oligonucleotides that are complementary to the sequence of miR142-3p and miR219-3p to reduce the expression of miR142-3p and miR219-3p and treat said neuroinflammation.

### Claim 3 (depends on 2)

The method of claim 2 further comprising the steps of
iii) obtaining a reference expression level of a micro RNA selected from the group consisting of miR142-5p, miR181a, miR181b, and miR219-5p;
iv) determining an expression level of a micro RNA selected from the group consisting of miR142-5p, miR181a, miR181b, and miR219-5p, in said test patient's sample, wherein an increase in the expression level of one or more of miR142-5p, miR181a, miR181b, and miR219-5p in said test patient's sample as compared to the reference expression level, in addition to the detected increase in expression levels of miR142-3p and miR219-3p, identifies the patient as having neuroinflammation.