Humanized Anti-Factor D Antibodies And Uses Thereof

Abstract

The invention relates to anti-Factor D antibodies, their nucleic acid and amino acid sequences, the cells and vectors that harbor these antibodies and their production and their use in the preparation of compositions and medicaments for treatment of diseases and disorders associated with excessive or uncontrolled complement activation. These antibodies are useful for diagnostics, prophylaxis and treatment of disease.

1 - 76 . (canceled) 
     
     
         77 . An anti-Factor D antibody or an antigen-binding fragment thereof, wherein the anti-Factor D antibody or antigen-binding fragment thereof comprises:
 (a) a heavy chain variable domain comprising: i. an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 39; ii. an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 40; and iii. an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 41; and   (b) a light chain variable domain comprising: i. an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 30; ii. an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 35; and iii. an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 38;   wherein the amino acid residue at position 1 of the heavy chain variable domain is an E.   
     
     
         78 . An anti-Factor D antibody or an antigen-binding fragment thereof, wherein the anti-Factor D antibody or antigen-binding fragment thereof comprises the heavy chain variable domain sequence of SEQ ID NO: 19 and the light chain variable domain sequence of SEQ ID NO: 7. 
     
     
         79 . The anti-Factor D antibody or antigen-binding fragment of claim  1  or  2 , wherein the anti-Factor D antibody is a humanized antibody. 
     
     
         80 . The anti-Factor D antibody or antigen-binding fragment of claim  1  or  2 , wherein the Factor D is mammalian Factor D. 
     
     
         81 . The anti-Factor D antibody or antigen-binding fragment of claim  1  or  2 , wherein the Factor D is human Factor D. 
     
     
         82 . The anti-Factor D antibody or antigen-binding fragment of claim  1  or  2 , wherein the anti-Factor D antibody is a monoclonal antibody. 
     
     
         83 . The anti-Factor D antibody or antigen-binding fragment of claim  1  or  2 , wherein the antigen-binding fragment is a Fab, Fab′-SH, Fv, scFv, or (Fab′) 2  fragment. 
     
     
         84 . The anti-Factor D antibody or antigen-binding fragment of claim  1  or  2 , which is produced in bacteria. 
     
     
         85 . The anti-Factor D antibody or antigen-binding fragment of claim  1  or  2 , which is produced in CHO cells. 
     
     
         86 . A pharmaceutical formulation comprising the anti-Factor D antibody or antigen-binding fragment of claim  1  or  2 , and a pharmaceutically acceptable diluent, carrier or excipient. 
     
     
         87 . An article of manufacture comprising:
 a. the pharmaceutical formulation of  claim 86 ;   b. a container; and   c. a package insert or label indicating that the pharmaceutical formulation-can be used to treat a complement-associated disorder.   
     
     
         88 . A kit comprising the anti-Factor D antibody or antigen-binding fragment of claim  1  or  2 , and instructions for administering said antibody to treat a complement-associated disorder. 
     
     
         89 . The kit of  claim 88 , wherein the complement-associated disorder is an ocular disease. 
     
     
         90 . The kit of  claim 89 , wherein the ocular disease is selected from the group consisting of age-related macular degeneration (AMD), diabetic retinopathy, choroidal neovascularization (CNV), uveitis, diabetic macular edema, pathological myopia, von Hippel-Lindau disease, histoplasmosis of the eye, Central Retinal Vein Occlusion (CRVO), corneal neovascularization, and retinal neovascularization. 
     
     
         91 . The kit of  claim 89 , wherein the ocular disease is age-related macular degeneration (AMD). 
     
     
         92 . The kit of  claim 91 , wherein the age-related macular degeneration is intermediate dry AMD. 
     
     
         93 . The kit of  claim 91 , wherein the age-related macular degeneration is geographic atrophy.