# US 11,298,328 B2 · Sensorineural hair cell differentiation

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- Number: US 11,298,328 B2
- Document ID: US11298328B2
- Status: Granted
- Kind: B2
- Application number: 16/813,668
- Filed: 2020-03-09
- Published: 2020-10-29
- Granted: 2022-04-12
- Earliest claimed: 2014-04-28
- Assignees: Massachusetts Eye and Ear Infirmary
- Applicants: Massachusetts Eye and Ear Infirmary
- Inventors: Albert Edge; Judith Kempfle; Dunia Abdul-Aziz
- Web page: https://patentgrep.com/patent/US11298328B2

## CPC

- A61K 31/19: Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60)
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/0046: {Ear}
- A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone}
- A61K 31/165: having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 38/12: Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)}
- A61K 38/1709: {from mammals}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 27/16: Otologicals
- 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

The present disclosure provides compositions and methods for treating subjects at risk for or with sensorineural hearing loss. Such compositions and methods include modulating the epigenetic status of the cell, or rate of protein degradation, to increase expression and/or levels of Atoh1 protein.

## Claims

### Claim 1

A method for treating sensorineural hearing loss associated with loss of auditory hair cells in a subject, the method comprising administering a therapeutically effective amount of a pharmaceutical composition comprising a histone methyltransferase (HMT) inhibitor to the subject having sensorineural hearing loss, wherein the therapeutically effective amount is an amount sufficient to improve hearing at one or more frequencies.

### Claim 2 (depends on 1)

The method of claim 1, wherein the HMT inhibitor is selected from the group consisting of Deazaneplanocin A (DZNep), PR-SET7, GSK126, GSK J1, EPZ005687; E7438; EI1; EPZ-6438; GSK343; BIX-01294, UNC0638, BRD4770, EPZ004777, AZ505 and PDB 4e47.

### Claim 3 (depends on 1)

The method of claim 1, comprising administering the pharmaceutical composition to the inner ear of the subject.

### Claim 4 (depends on 1)

The method of claim 1, comprising application of the pharmaceutical composition to the round window membrane.

### Claim 5 (depends on 4)

The method of claim 4, wherein the pharmaceutical composition is applied via intra-tympanic injection or direct delivery into the inner ear fluids.

### Claim 6 (depends on 5)

The method of claim 5, wherein the direct delivery into the inner ear fluids is applied using a microfluidic device.

### Claim 7 (depends on 1)

The method of claim 1, wherein the pharmaceutical composition is formulated for administration to the inner ear of the subject.