JANUS KINASE INHIBITORS FOR TREATMENT OF DRY EYE AND OTHER EYE RELATED DISEASES

• US 20120301464A1
• Filed: 08/01/2012
• Published: 11/29/2012
• Est. Priority Date: 10/02/2008
• Status: Abandoned Application

• Current Assignee: Incyte Holdings Corporation And Incyte Corporation
• Original Assignee: Incyte Corporation
• Inventors: Friedman, Paul A., Fridman, Jordan S., Luchi, Monica E., Williams, William V.
• Application Number:
  US13/564,271
• Publication Number:
  US 20120301464A1
• Time in Patent Office: Days
• US Class Current: 424/133.1
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/04 Artificial tears; Irrigation solutions
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Methods, kits, and compositions for treating dry eye disorders and other related eye diseases are provided, wherein the methods, kits, and compositions utilize a JAK inhibitor.

Claims

1. A method of treating a dry eye disorder in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of an agent selected from:

(a) compounds of Formula I;

2. A method according to claim 1, wherein said dry eye disorder is aqueous tear-deficient dry eye.

3. A method according to claim 1, wherein said dry eye disorder is evaporative dry eye.

4. A method according to claim 1, wherein said dry eye disorder is Sjogren syndrome dry eye.

5. A method according to claim 1, wherein said dry eye disorder is non-Sjogren syndrome dry eye.

6. A method according to claim 1, wherein said treating comprises ameliorating a symptom selected from eye discomfort, visual disturbance, tear film instability, tear hyperosmolarity, and inflammation of the ocular surface.

7. A method according to claim 1, wherein said treating comprises administering a pharmaceutical composition to said patient, said composition comprising said agent and a pharmaceutically acceptable carrier.

8. A method according to claim 7, wherein said pharmaceutical composition is an oral dosage form.

9. A method according to claim 1, wherein said treating comprises administering an ophthalmic composition to said patient, said composition comprising said agent and an ophthalmically acceptable carrier.

10. A method according to claim 9, wherein said ophthalmic composition is a topical composition.

11. A method according to claim 9, wherein said topical composition is an aqueous formulation, an aqueous suspension, an ointment or a gel.

12. A method according to claim 9, wherein said ophthalmic composition is an ophthalmic insert.

17. A method according to claim 1, further comprising administering at least one additional therapeutic agent.

18. A method according to claim 17, wherein said additional therapeutic agent is fluocinolone acetonide, rimexolone, cyclosporine, riaminolone, dexamethasone, fluocinolone, cortisone, prednisolone, flumetholone, civamide, testosterone, ecabet sodium, 15-(s)-hydroxyeicosatetracnoic acid, 2S,3S,4R,5R)-3,4-dihydroxy-5-[6-[(3-iodophenyl)methylamino]purin-9-yl]-N-methyl-oxolane-2-carboxamide, gefarnate, cevilemine, doxycline, minocycline, oxytetracycline, voclosporin, rivoglitazone, lacritin rebamipide, pilocarpine, tacrolimus, pimecrolimus, loteprednol etabonate, rituximab, diquafosol tetrasodium, dehydroepiandrosterone, anakinra, efalizumab, mycophenolate sodium, etanercept, hydroxychloroquine, or thalidomide.

20. A method according to claim 1, wherein said agent is selected from compounds of Formula I:

36. A method according to claim 20, wherein said agent is selected from 3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile and pharmaceutically acceptable salts thereof.

37. A method according to claim 20, wherein said agent is selected from (3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile and pharmaceutically acceptable salts thereof.

13-16. -16. (canceled)

19. (canceled)

21-35. -35. (canceled)

38-49. -49. (canceled)

50. An ophthalmic insert comprising a therapeutically effective amount of an agent selected from:

(a) compounds of Formula I;

51-56. -56. (canceled)