# US 9,750,749 B2 · Methods of treating thyroid eye disease

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- Number: US 9,750,749 B2
- Document ID: US9750749B2
- Status: Granted
- Kind: B2
- Application number: 15/061,727
- Filed: 2016-03-04
- Published: 2016-07-14
- Granted: 2017-09-05
- Earliest claimed: 2010-05-03
- Assignees: University of Rochester
- Applicants: Richard P. Phipps; Naxin Guo; Steven Feldon
- Inventors: Richard P. Phipps; Naxin Guo; Steven Feldon
- Web page: https://patentgrep.com/patent/US9750749B2

## CPC

- A61K 31/557: Eicosanoids, e.g. leukotrienes {or prostaglandins}
- A61K 31/166: having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
- A61K 31/201: having one or two double bonds, e.g. oleic, linoleic acids
- A61K 31/403: condensed with carbocyclic rings, e.g. carbazole
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/5575: having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
- 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 31/713: Double-stranded nucleic acids or oligonucleotides
- A61P 27/02: Ophthalmic agents
- C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- A61K 9/0048: {Eye, e.g. artificial tears}
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2320/31: Combination therapy
- 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

The present invention relates to a methods and compositions for the treatment of and management of symptoms for thyroid eye disease. The methods include administering to a patient having thyroid eye disease an agent that interferes with hyaluronan synthesis in an amount that is effective to inhibit hyaluronan synthesis in a retro-ocular space. The pharmaceutical compositions that includes a carrier suitable for ophthalmic delivery and an agent that interferes with hyaluronan synthesis. Combination therapies are also disclosed.

## Claims

### Claim 1

A method of treating thyroid eye disease comprising:
selecting a patient having thyroid eye disease and
administering to the selected patient a composition comprising an agent that interferes with hyaluronan synthesis in an amount that is effective to inhibit hyaluronan synthesis in a retro-ocular space, wherein the agent is 4-benzhydryloxy-1-[3-(1H-tetrazol-5-yl)-propyl]-piperidine (HQL-79), ethyl 3-(2-(3-fluorophenyl)pyrimidine-5-carboxamido)pyrrolidine-1-carboxylate, N-(1-(7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)pyrrolidin-3-yl)-2-(3-fluorophenyl)pyrimidine-5-carboxamide, 2-(3-fluorophenyl)-N-{1-[(methylamino)carbonyl]piperidin-4-yl}pyrimidine-5-carboxamide, 2-(3-fluorophenyl)-N-[1-(6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)pyrrolidin-3-yl]pyrimidine-5-carboxamide, or 2-(3-fluorophenyl)-N-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]pyrimidine-5-carboxamide.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the composition comprises a PPARγ ligand, wherein the PPARγ ligand is 15-deoxy-Δ12,14-Prostaglandin J2 or a thiazolidinedione.

### Claim 3 (depends on 1)

The method according to claim 1, wherein said administering is carried out by injecting the agent into the retro-ocular space or application of a composition comprising the agent onto a surface of the patient's eye.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the composition is a pharmaceutical composition further comprising a carrier selected from the group consisting of a liquid, suspension, polymeric delivery vehicle, mucoadhesive substance, and nanosphere.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the agent that interferes with hyaluronan synthesis is 4-benzhydryloxy-1-[3-(1H-tetrazol-5-yl)-propyl]-piperidine (HQL-79).