THERAPEUTIC COMPOSITIONS FOR THE TREATMENT OF DRY EYE DISEASE

• US 20130045927A1
• Filed: 02/25/2011
• Published: 02/21/2013
• Est. Priority Date: 02/25/2010
• Status: Active Grant

• Current Assignee: Schepens Eye Research Institute
• Original Assignee: Schepens Eye Research Institute
• Inventors: Dana, Reza, Chauhan, Sunil
• Granted Patent: US 9,328,162 B2
• Time in Patent Office: Days
• US Class Current: 514/20.8
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61K 31/502 ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 38/179 for growth factors; for growth regulators
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

Described herein are materials and methods of treating dry eye disease in a subject.

Claims

1. A method of treating dry eye disease (DED) in a human subject comprising:

administering a composition comprising a polypeptide comprising a soluble VEGFR-3 fragment that binds VEGF-C or VEGF D and a pharmaceutically acceptable carrier to the human subject, in an amount effective to treat dry eye disease.

2. The method of claim 1, wherein the composition is administered to the eye of the human.

6. The method of claim 1, wherein the DED is an autoimmune DED or a DED associated with Sjogren'"'"'s syndrome.

7. The method of claim 1, wherein the DED is DED due to excessively fast tear evaporation (evaporative dry eyes) or inadequate tear production.

8. The method of claim 1, wherein the dry eye disease is attributable to one or more causes selected from:

aging, contact lens usage and medication usage.

9. The method of claim 1, wherein the dry eye disease is a complication of LASIK refractive surgery.

25. The method of claim 1, further comprising administering an anti-inflammatory agent to the subject.

26. The method of claim 25, further comprising administering cyclosporine to the subject.

27. The method of claim 1, wherein said composition further comprises a molecule that inhibits an activity of an inflammatory cytokine selected from the group consisting of IL-1, IL-7, IL23, IL-6 and TNF-α

.

28. The method of claim 1, wherein the method further comprises administering an antibiotic to the subject.

30. The method of claim 28, wherein the antibiotic is selected from the group consisting of amikacin, gentamicin, kanamycin, neomycin, netilmicin, streptomycin, tobramycin, teicoplanin, vancomycin, azithromycin, clarithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, troleandomycin, amoxicillin, ampicillin, azlocillin, carbenicillin, clozacillin, dicloxacillin, flucozacillin, meziocillin, nafcillin, penicillin, piperacillin, ticarcillin, bacitracin, colistin, polymyxin B, ciprofloxacin, enoxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, oflazacin, trovafloxacin, mafenide, sulfacetamide, sulfamethizole, sulfasalazine, sulfisoxazole, trimethoprim, cotrimoxazole, demeclocycline, soxycycline, minocycline, oxytetracycline, or tetracycline.

31. The method of claim 1, wherein the eye comprises a tissue or gland in or around the eye selected from the group consisting of ocular tissue, eyelids of the subject, ocular surface, meibomian gland and or lacrimal gland of the human.

32. The method of claim 1, wherein said composition is administered topically to the eye.

33. The methods of claim 1, wherein the composition is formulated for topical administration.

34. The method of claim 1, wherein said composition is in the form of a solid, a paste, an ointment, a gel, a liquid, an aerosol, a mist, a polymer, a film, an emulsion, or a suspension.

35. The method of claim 1, wherein said composition further comprises a compound selected from the group consisting of physiological acceptable salt, poloxamer analogs with carbopol, carbopol/hydroxypropyl methyl cellulose (RP MC), carbopol-methyl cellulose, carboxymethylcellulose (CMC), hyaluronic acid, cyclodextrin, and petroleum.

36. The method of claim 1, wherein the soluble VEGFR-3 fragment comprises at least the one Ig-like domains of VEGFR-3 extracellular domain.

37. The method of claim 1, wherein the soluble VEGFR-3 fragment comprises at least three Ig-like domains of VEGFR-3 extracellular domain.

38. The method of claim 1, wherein the soluble VEGFR-3 fragment consists essentially of the first, second and third Ig-like domains of the VEGFR-3 extracellular domain.

39. The method of claim 1, wherein the soluble VEGFR-3 fragment consists essentially of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, or 95% identical the first, second and third Ig-like domains of the VEGFR-3 extracellular domain.

3-5. -5. (canceled)

10-24. -24. (canceled)

29. (canceled)