Controlled release auris sensory cell modulator compositions and methods for the treatment of otic disorders

• US 8,575,122 B2
• Filed: 04/26/2010
• Issued: 11/05/2013
• Est. Priority Date: 07/21/2008
• Status: Active Grant

• Current Assignee: Otonomy, Inc.
• Original Assignee: Otonomy, Inc.
• Inventors: Lichter, Jay, Lebel, Carl, Piu, Fabrice, Trammel, Andrew M.
• Primary Examiner(s): EPPS -SMITH, JANET L
• Application Number:
  US12/767,461
• Publication Number:
  US 20100273864A1
• Time in Patent Office: 1,289 Days
• Field of Search: None
• US Class Current: 514/44.R
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/4535 containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0046 Ear
• CPC Class Codes: A61P 27/16 Otologicals

Abstract

Disclosed herein are compositions and methods for the treatment of otic diseases or conditions with auris sensory cell modulating agent compositions and formulations administered locally to an individual afflicted with an otic disease or condition, through direct application of these compositions and formulations onto or via perfusion into the targeted auris structure(s).

Claims

1. A pharmaceutical otic formulation comprising:

between about 0.2% to about 20% by weight of an agent that modulates the Atoh1 gene or pharmaceutically acceptable prodrug or salt thereof; and

a thermoreversible gel having a gelation temperature between about room temperature and about body temperature;

a non-gelation viscosity that allows injection at or about room temperature with a needle having a gauge in the range of 18-31 through the tympanic membrane to an area on or near the round window membrane, and with a gelation viscosity between about 15,000 cP and about 1,000,000 cP;

wherein the otic formulation provides a sustained release of an effective amount of the agent to the inner ear for a period of from 5 days to 6 months, and wherein the agent is essentially in the form of micronized particles.

2. The formulation of claim 1, wherein the agent comprises a vector engineered to carry the human Atoh1 gene.

3. The formulation of claim 1, wherein the agent that modulates the Atoh1 gene induces auris sensory hair cell regeneration.

4. The formulation of claim 1, wherein the thermoreversible gel comprises a polymer composed of polyoxypropylene and polyoxyethylene.

5. The formulation of claim 1, wherein the thermoreversible gel comprises between about 16% to about 21% by weight of polymers composed of polyoxypropylene and polyoxyethylene.

6. A method for treating an otic disease or condition comprising administering to a patient in need thereof a composition, the composition comprising:

between about 0.2% to about 20% by weight of an agent that modulates the Atoh1 gene or pharmaceutically acceptable prodrug or salt thereof; and

a thermoreversible gel having a gelation temperature between about room temperature and about body temperature;

a non-gelation viscosity that allows injection at or about room temperature with a needle having a gauge in the range of 18-31 through the tympanic membrane to an area on or near the round window membrane, and with a gelation viscosity between about 15,000 cP and about 1,000,000 cP;

wherein the composition provides a sustained release of an effective amount of the agent to the inner ear of the patient for a period of from 5 days to 6 months, and wherein the agent is essentially in the form of micronized particles.

7. The method of claim 6, wherein the agent comprises a vector engineered to carry the human Atoh1 gene.

8. The method of claim 6, wherein the agent that modulates the Atoh1 gene induces auris sensory hair cell regeneration.

9. The method of claim 6, wherein the thermoreversible gel comprises a polymer composed of polyoxypropylene and polyoxyethylene.

10. The method of claim 6, wherein the thermoreversible gel comprises between about 16% to about 21% by weight of polymers composed of polyoxypropylene and polyoxyethylene.

11. The method of claim 6, wherein the otic disease or condition is hearing loss.

12. The method of claim 11, wherein the hearing loss is from Meniere'"'"'s disease, sudden sensorineural hearing loss, noise induced hearing loss, age related hearing loss, auto immune ear disease or tinnitus.

13. The method of claim 6, wherein the pharmaceutical composition is administered at or near the round window membrane of the patient in need.