Therapeutic compositions for the treatment of dry eye disease

Abstract

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

1 . A method of treating dry eye disease (DED) in a human comprising:
 administering a composition comprising at least one anti-lymphangiogenic agent and a pharmaceutically acceptable carrier to the human, in an amount effective to treat dry eye disease.   
     
     
         2 . The method of  claim 1 , wherein the anti-lymphangiogenic agent is administered to the eye of the human. 
     
     
         3 . The method of  claim 1 , wherein the anti-lymphangiogenic agent is an inhibitor of VEGF-C or VEGF-D mediated signal transduction by VEGFR-2 or VEGFR-3. 
     
     
         4 - 9 . (canceled) 
     
     
         10 . The method of  claim 1 , wherein the at least one anti-lymphangiogenic agent is purified or isolated. 
     
     
         11 . The method of  claim 1 , wherein said at least one anti-lymphangiogenic agent comprises a member selected from the group consisting of: a nucleic acid molecule, an aptamer, an antisense molecule, an RNAi molecule, a protein, a peptide, a cyclic peptide, an antibody or antibody fragment, a polysaccharide, or a small molecule. 
     
     
         12 . The method of  claim 1 , wherein said at least one anti-lymphangiogenic agent comprises a member selected from the group consisting of a VEGFR-3 inhibitor, a VEGF-D inhibitor and a VEGF-C inhibitor. 
     
     
         13 . The method of  claim 1 , wherein the at least one anti-lymphangiogenic agent comprises a member selected from the group consisting of a VEGF-C antibody, a VEGF-D antibody, a VEGF-R3 antibody, and a polypeptide comprising a soluble VEGFR-3 fragment that binds VEGF-C or VEGF-D. 
     
     
         14 - 20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein the at least one anti-lymphangiogenic agent comprises a soluble VEGFR-3 fragment that binds VEGF-C or VEGF-D. 
     
     
         22 . The method of  claim 1 , wherein the at least one anti-lymphangiogenic agent comprises a human or humanized antibody. 
     
     
         23 . The method of  claim 1 , wherein the at least one anti-lymphangiogenic agent comprises a VEGFR-2 inhibitor. 
     
     
         24 . The method of  claim 1 , wherein the at least one anti-lympnahgiogenic agent comprises a tyorine kinase inhibitor that inhibits the activity of VEGFR-3. 
     
     
         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 human. 
     
     
         29 - 30 . (canceled) 
     
     
         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 . (canceled) 
     
     
         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 the 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.