# US 11,123,285 B2 · Auris formulations for treating OTIC diseases and conditions

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- Number: US 11,123,285 B2
- Document ID: US11123285B2
- Status: Granted
- Kind: B2
- Application number: 16/389,213
- Filed: 2019-04-19
- Published: 2019-10-10
- Granted: 2021-09-21
- Earliest claimed: 2008-04-21
- Assignees: Otonomy, Inc.; The Regents of the University of California
- Applicants: Otonomy, Inc.; The Regents of the University of California
- Inventors: Jay Lichter; Andrew M. Trammel; Fabrice Piu; Qiang Ye; Luis A. Dellamary; Carl Lebel; Jeffrey P. Harris
- Web page: https://patentgrep.com/patent/US11123285B2

## CPC

- A61K 9/0046: {Ear}
- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K 9/14: Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)}
- A61K 9/16: Agglomerates; Granulates; Microbeadlets {; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction (A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51)}
- A61K 31/05: Phenols {(cannabinoids A61K31/658)}
- A61K 31/13: Amines {(A61K31/04 takes precedence)}
- A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone}
- A61K 31/325: Carbamic acids; Thiocarbamic acids; Anhydrides or salts thereof (thiurams A61K31/145)
- A61K 31/43: Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula [IMAGE cpc-sch-A61K-0952.gif], e.g. penicillins, penems
- A61K 31/436: the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/5513: 1,4-Benzodiazepines, e.g. diazepam {or clozapine}
- A61K 31/5517: condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
- A61K 38/18: Growth factors; Growth regulators
- A61K 38/1808: {Epidermal growth factor [EGF] urogastrone}
- A61K 38/1825: {Fibroblast growth factor [FGF]}
- A61K 38/185: {Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3}
- A61K 38/1858: {Platelet-derived growth factor [PDGF]}
- A61K 38/1883: {Neuregulins, e.g.. p185erbB2 ligands, glial growth factor, heregulin, ARIA, neu differentiation factor}
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- A61K 47/18: Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone}
- A61K 47/38: Cellulose; Derivatives thereof
- A61P 25/02: for peripheral neuropathies
- A61P 25/22: Anxiolytics
- A61P 27/16: Otologicals
- A61P 31/04: Antibacterial agents
- A61P 37/02: Immunomodulators
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/241: {Tumor Necrosis Factors}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- 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
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

Disclosed herein are compositions and methods for the treatment of otic disorders with immunomodulating agents and auris pressure modulators. In these methods, the auris compositions and formulations are administered locally to an individual afflicted with an otic disorder, through direct application of the immunomodulating and/or auris pressure modulating compositions and formulations onto the auris media and/or auris interna target areas, or via perfusion into the auris media and/or auris interna structures.

## Claims

### Claim 1

A pharmaceutical composition comprising: between about 0.1 mg/ml to about 20 mg/ml of one and no more than one growth factor selected from brain-derived neurotrophic factor (BDNF) or neurotrophin-3, or pharmaceutically acceptable salt thereof, wherein the pharmaceutical composition is a thermoreversible gel formulated for intratympanic administration, wherein the pharmaceutical composition comprises from 14% to 17% by weight of Poloxamer 407, and wherein the growth factor is not a glial cell-line derived neurotrophic factor (GDNF).

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein the pharmaceutical composition has a gelation temperature of from 20° C. to 25° C.

### Claim 3 (depends on 1)

The pharmaceutical composition of claim 1, wherein the pharmaceutical composition has a pH of from 7.0 to 8.0.

### Claim 4 (depends on 1)

The pharmaceutical composition of claim 1, wherein the pharmaceutical composition has an osmolarity of from 250 mOsm/L to 320 mOsm/L.

### Claim 5 (depends on 1)

The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises from 15% to 16% by weight of Poloxamer 407.

### Claim 6 (depends on 1)

The pharmaceutical composition of claim 1, wherein the growth factor is in the form of non-coated micronized particles.

### Claim 7 (depends on 1)

The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is formulated to provide sustained release of the growth factor into an inner ear for a period of at least 5 days following a single administration.

### Claim 8 (depends on 7)

The pharmaceutical composition of claim 7, wherein the pharmaceutical composition is formulated to provide sustained release of the growth factor into an inner ear for a period of at least 7 days following a single administration.

### Claim 9 (depends on 1)

The pharmaceutical composition of claim 1, wherein the growth factor is an otic hair cell growth factor.

### Claim 10 (depends on 9)

The pharmaceutical composition of claim 9, wherein the growth factor is a neurotroph.

### Claim 11 (depends on 1)

The pharmaceutical composition of claim 1, wherein the growth factor is neurotrophin-3.

### Claim 12 (depends on 1)

The pharmaceutical composition of claim 1, wherein the growth factor is BDNF.

### Claim 13 (depends on 1)

The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises between about 0.1 mg/ml to about 5 mg/ml of the growth factor.

### Claim 14 (depends on 13)

The pharmaceutical composition of claim 13, wherein the pharmaceutical composition comprises between about 0.5 mg/ml to about 5 mg/ml of the growth factor.

### Claim 15 (depends on 13)

The pharmaceutical composition of claim 13, wherein the pharmaceutical composition comprises between about 0.1 mg/ml to about 0.5 mg/ml of the growth factor.

### Claim 16 (depends on 1)

The pharmaceutical composition of claim 1, wherein the growth factor is dissolved in the pharmaceutical composition.

### Claim 17 (depends on 1)

The pharmaceutical composition of claim 1, wherein the composition comprises: between about 0.1 mg/ml to about 10 mg/ml of the growth factor.