Compositions and Methods for Treating Inflammatory Conditions of the Ocular Surface

Abstract

This application discloses ophthalmic formulations and methods for treating inflammatory disease and conditions of the ocular surface with one or more C-C chemokine receptor type 7 (CCR7) antagonists. The compositions may be formulated for subconjunctival or topical administration to the eye and are effective in the treatment of inflammatory disease and conditions of the ocular surface.

What is claimed is: 
     
         1 . A method for treating an inflammatory condition of the ocular surface, said method comprising administering to the eye of a subject in need thereof an ophthalmic formulation comprising an effective amount of one or more C-C chemokine receptor type 7 (CCR7) antagonists. 
     
     
         2 . The method of  claim 1 , wherein one or more CCR7 antagonists comprises a small organic molecule, a protein, a peptide, a peptidomimetic, a nucleic acid, or a carbohydrate. 
     
     
         3 . The method of  claim 1 , wherein one or more CCR7 antagonists is an N-terminal truncation mutant of CCL19. 
     
     
         4 . The method of  claim 1 , wherein one or more CCR7 antagonists is an N-terminal truncation mutant of CCL21. 
     
     
         5 . The method of  claim 1 , wherein the concentration of CCR7 antagonists are from 0.10% to 2.0% (w/v). 
     
     
         6 . The method of  claim 1 , wherein the condition is an allergic condition of the ocular surface. 
     
     
         7 . The method of  claim 1 , wherein the condition is selected from the group consisting of conjunctivitis, hay fever conjunctivitis, allergic conjunctivitis, perennial allergic conjunctivitis, seasonal allergic conjunctivitis, atopic conjunctivitis, vernal conjunctivitis, keratoconjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, allergic rhinoconjunctivitis, and giant papillary conjunctivitis. 
     
     
         8 . The method of  claim 1 , wherein the condition is selected from the group consisting of ocular inflammation, uveitis, scleritis, keratitis, retinitis, iritis, uveoretinitis, uveoscleritis, conjunctivitis, episcleritis, optic neuritis, retrobulbar neuritis, blepharitis, Mooren's ulcer and inflammatory ocular manifestations in allergies. 
     
     
         9 . The method of  claim 1 , wherein the formulation further comprises one or more tear substitutes. 
     
     
         10 . The method of  claim 1 , wherein the formulation further comprises an ophthalmic lubricant. 
     
     
         11 . The method of  claim 1 , wherein the subject is human. 
     
     
         12 . An ophthalmic formulation comprising one or more CCR7 antagonists, wherein the formulation is suitable for administration to the eye of a subject. 
     
     
         13 . The ophthalmic formulation of  claim 12 , formulated for subconjunctival administration. 
     
     
         14 . The ophthalmic formulation of  claim 12 , formulated for topical administration. 
     
     
         15 . The ophthalmic formulation of  claim 12 , wherein the pH of the formulation is between 5.5 and 7. 
     
     
         16 . The ophthalmic formulation of  claim 12 , wherein the formulation is an aqueous formulation. 
     
     
         17 . The ophthalmic formulation of  claim 12 , wherein the formulation is in the form of a single dose unit. 
     
     
         18 . The ophthalmic formulation of  claim 12 , wherein the formulation further comprises one or more tear substitutes. 
     
     
         19 . The ophthalmic formulation of  claim 12 , wherein the formulation further comprises an ophthalmic lubricant. 
     
     
         20 . A method for treating ocular surface inflammation, said method comprising administering to the eye of a subject in need thereof an ophthalmic formulation comprising an effective amount of one or more C-C chemokine receptor type 7 (CCR7) antagonists. 
     
     
         21 . A method for treating perennial allergic conjunctivitis, said method comprising administering to the eye of a subject in need thereof an ophthalmic formulation comprising an effective amount of one or more C-C chemokine receptor type 7 (CCR7) antagonists. 
     
     
         22 . A method for treating seasonal allergic conjunctivitis, said method comprising administering to the eye of a subject in need thereof an ophthalmic formulation comprising an effective amount of one or more C-C chemokine receptor type 7 (CCR7) antagonists. 
     
     
         23 . A method for treating atopic keratoconjunctivitis, said method comprising administering to the eye of a subject in need thereof an ophthalmic formulation comprising an effective amount of one or more C-C chemokine receptor type 7 (CCR7) antagonists. 
     
     
         24 . A method for treating atopic conjunctivitis, said method comprising administering to the eye of a subject in need thereof an ophthalmic formulation comprising an effective amount of one or more C-C chemokine receptor type 7 (CCR7) antagonists. 
     
     
         25 . A method for treating vernal keratoconjunctivitis, said method comprising administering to the eye of a subject in need thereof an ophthalmic formulation comprising an effective amount of one or more C-C chemokine receptor type 7 (CCR7) antagonists. 
     
     
         26 . A method for treating vernal conjunctivitis, said method comprising administering to the eye of a subject in need thereof an ophthalmic formulation comprising an effective amount of one or more C-C chemokine receptor type 7 (CCR7) antagonists. 
     
     
         27 . The method of  claim 1 , wherein CCR7 antagonist comprises a soluble chemokine receptor or a blocking fusion protein against CCR7. 
     
     
         28 . The method of  claim 2 , wherein said nucleic acid comprises an isolated cDNA polynucleotide or an isolated RNA polynucleotide. 
     
     
         29 . The method of  claim 27 , wherein said soluble chemokine receptor comprises a soluble CCR7. 
     
     
         30 . The method of  claim 29 , wherein said soluble CCR7 comprises a fragment of a wild type CCR7. 
     
     
         31 . The method of  claim 30 , wherein said soluble CCR7 comprises an extracellular fragment of said wild type CCR7. 
     
     
         32 . The method of  claim 2 , wherein said organic molecule comprises a molecular weight of more than 50 and less than about 2,500 daltons. 
     
     
         33 . The method of  claim 1 , wherein said CCR7 antagonist comprises a thiadiazoledioxide or a thiadiazoleoxide. 
     
     
         34 . The method of  claim 1 , wherein said CCR7 antagonist comprises a tertiary amine containing a multiplicity of heteroaromatic substituents. 
     
     
         35 . The method of  claim 1 , wherein said CCR7 antagonist comprises a piperazinylpiperidine derivative. 
     
     
         36 . An ophthalmic formulation comprising one or more CCR7 antagonists, wherein the formulation is suitable for administration to the eye of a subject and wherein said CCR7 antagonist comprises an antibody, a small organic molecule, a protein, a peptide, a peptidomimetic, a nucleic acid, or a carbohydrate.