Use of complement pathway inhibitors to treat ocular diseases

Abstract

The present invention relates to the treatment of ocular diseases and conditions by administering a complement pathway inhibitor, particularly an alternative pathway inhibitor. Ocular diseases include age-related macular degeneration, diabetic M retinopathy, and ocular angiogenesis. One embodiment comprises the administration of an anti-Factor D antibody in the form of a whole antibody, a Fab fragment or a single domain antibody. Other complement component inhibitors that may be useful in the present method include Factor H or inhibitors that block the action of properdin, factor B, factor Ba, factor Bb, C2, C2a, C3a, C5, C5a, C5b, C6, C7, C8, C9, or C5b-9.

1 .- 27 . (canceled) 
     
     
         28 . A method for preventing or ameliorating an ocular disease that involves complement activation, comprising administering an effective amount of a complement inhibitor to a subject in need thereof. 
     
     
         29 . The method of  claim 28 , wherein the ocular disease is selected from the group consisting of macular degeneration, diabetic retinopathy, and ocular angiogenesis. 
     
     
         30 . The method of  claim 28 , wherein the subject requires inhibition of ocular neovascularization that affects the choroid, retinal pigmented epithelium, or retinal tissue. 
     
     
         31 . The method of  claim 28 , wherein the complement inhibitor inhibits the alternative complement pathway. 
     
     
         32 . The method of  claim 28 , wherein the complement inhibitor is Factor H, or a functional peptide thereof or a peptidomimetic thereof. 
     
     
         33 . The method according to  claim 28 , wherein the complement inhibitor is an antibody or an antigen-binding fragment thereof. 
     
     
         34 . The method according to  claim 33  wherein the antibody or the antigen-binding fragment thereof specifically binds to Factor D, properdin, Factor B, Factor Ba, Factor Bb, C2, C2a, C3a, C5, C5a, C5b, C6, C7, C8, C9 or C5b-9. 
     
     
         35 . The method according to  claim 33 , wherein the antibody is monoclonal antibody 166-32 produced from the hybridoma deposited with the ATCC and designated HB 12476. 
     
     
         36 . The method according to  claim 33 , wherein the antibody or the antigen-binding fragment thereof specifically binds to the same epitope as monoclonal antibody 166-32 produced from the hybridoma deposited with the ATCC and designated HB 12476. 
     
     
         37 . The method according to  claim 33 , wherein the antibody is a humanized monoclonal antibody derived from monoclonal antibody 166-32 produced from the hybridoma deposited with the ATCC and designated HB 12476. 
     
     
         38 . The method according to  claim 33 , wherein the antibody or the antigen-binding fragment thereof specifically binds to complement component C5a. 
     
     
         39 . The method according to  claim 38 , wherein the antibody is 137-26 produced from the hybridoma deposited with the ATCC and designated PTA-3650. 
     
     
         40 . The method according to  claim 38 , wherein the antibody or the antigen-binding fragment thereof binds to the same epitope as monoclonal antibody 137-26 produced from the hybridoma deposited with the ATCC and designated PTA-3650. 
     
     
         41 . The method of  claim 28 , wherein the complement inhibitor is administered by intraocular administration, intravitreal administration, or subconjunctival administration, parenteral administration, intradermal administration, intramuscular administration, intraperitoneal administration, intravenous administration, subantaneous administration, intranasal administration, oral administration, enteral administration, topical administration, intrathecal administration, intraventricular administration, epidural, inhalation, a biocompatible or bioerodable sustained release implant, or implantation of an infusion pump. 
     
     
         42 . The method according to  claim 28 , wherein the complement inhibitor is administered in an eye wash solution, an eye ointment, an eye shield or an eye drop solution. 
     
     
         43 . The method according to  claim 28 , further comprising the step of administering an immunomodulatory compound, an immunosuppressive compound, an anti-inflammatory compound, or an anti-angiogenic compound, to said subject. 
     
     
         44 . The method of  claim 28 , further comprising administering to the subject an anti-angiogenesis therapy targeting vascular endothelial growth factor (VEGF). 
     
     
         45 . The method of  claim 28 , further comprising administering to the subject a steroid. 
     
     
         46 . A method of preventing or ameliorating an ocular disease that involves complement activation, comprising administering an siRNA specific for a complement pathway protein to a subject in need thereof. 
     
     
         47 . A method of preventing or ameliorating an ocular disease that involves complement activation, comprising administering a nucleic acid encoding a complement inhibitor to a subject in need thereof. 
     
     
         48 . The method of  claim 29 , wherein the macular degeneration is age-related macular degeneration. 
     
     
         49 . The method  claim 48 , wherein the age-related macular degeneration is the dry form of age-related macular degeneration.