Anti-factor d antibodies and uses thereof

Abstract

This invention relates to selective inhibition of the alternative pathway (AP) of the complement system using an anti-factor D antibody. Specifically, the invention relates to methods of treating an AP-mediated disease or AP-mediated disorder in an individual by contacting the individual with an anti-factor D antibody.

1 . An antibody that specifically binds to human factor D. 
     
     
         2 . The antibody of  claim 1 , wherein the antibody comprises at least one of the CDRs selected from the group consisting of: VH-CDR1: SEQ ID NO:3; VH-CDR2: SEQ ID NO:4; VH-CDR3: SEQ ID NO:5; VL-CDR1: SEQ ID NO:8; VL-CDR2: SEQ ID NO:9; and VL-CDR3: SEQ ID NO:10, or a variant or variants thereof. 
     
     
         3 . The antibody of  claim 1 , wherein the antibody comprises the CDRs: VH-CDR1: SEQ ID NO:3; VH-CDR2: SEQ ID NO:4; VH-CDR3: SEQ ID NO:5; VL-CDR1: SEQ ID NO:8; VL-CDR2: SEQ ID NO:9; and VL-CDR3: SEQ ID NO:10, or a variant or variants thereof. 
     
     
         4 . The antibody of  claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:2, or a variant thereof. 
     
     
         5 . The antibody of  claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO:7, or a variant thereof. 
     
     
         6 . The antibody of  claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:2 and a light chain comprising the amino acid sequence of SEQ ID NO:7, or a variant or variants thereof. 
     
     
         7 . The antibody of  claim 1 , wherein the antibody comprises at least one of the CDRs selected from the group consisting of: VH-CDR1: SEQ ID NO:13; VH-CDR2: SEQ ID NO:14; VH-CDR3: SEQ ID NO:15; VL-CDR1: SEQ ID NO:18; VL-CDR2: SEQ ID NO:19; and VL-CDR3: SEQ ID NO:20, or a variant or variants thereof. 
     
     
         8 . The antibody of  claim 1 , wherein the antibody comprises the CDRs: VH-CDR1: SEQ ID NO:13; VH-CDR2: SEQ ID NO:14; VH-CDR3: SEQ ID NO:15; VL-CDR1: SEQ ID NO:18; VL-CDR2: SEQ ID NO:19; and VL-CDR3: SEQ ID NO:20, or a variant or variants thereof. 
     
     
         9 . The antibody of  claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:12, or a variant thereof. 
     
     
         10 . The antibody of  claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO:17, or a variant thereof. 
     
     
         11 . The antibody of  claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:12 and a light chain comprising the amino acid sequence of SEQ ID NO:17, or a variant or variants thereof. 
     
     
         12 . The antibody of  claim 1 , wherein the antibody binds to an epitope comprising at least one amino acid within at least one amino acid sequence of factor D selected from the group consisting of SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23 and SEQ ID NO:24, or a variant or variants thereof. 
     
     
         13 . A method of treating an alternative pathway (AP)-mediated disease or disorder in an individual, comprising the step of administering to said individual the anti-factor D antibody of  claim 1 . 
     
     
         14 . The method of  claim 13 , wherein the disease or disorder is at least selected from the group consisting of: macular degeneration (MD), age-related macular degeneration (AMD), ischemia reperfusion injury, arthritis, rheumatoid arthritis, asthma, allergic asthma, paroxysmal nocturnal hemoglobinuria (PNH) syndrome, atypical hemolytic uremic (aHUS) syndrome, epidermolysis bullosa, sepsis, organ transplantation, inflammation (including, but not limited to, inflammation associated with cardiopulmonary bypass surgery and kidney dialysis), C3 glomerulopathy, membranous nephropathy, glomerulonephritis (including, but not limited to, anti-neutrophil cytoplasmic antibody (ANCA)-mediated glomerulonephritis, lupus, and combinations thereof), ANCA-mediated vasculitis, Shiga toxin induced HUS, and antiphospholipid antibody-induced pregnancy loss, and combinations thereof. 
     
     
         15 . A genetically modified non-human animal, wherein the genetically modified non-human animal expresses human factor D, and wherein the genetically modified non-human animal does not express murine factor D. 
     
     
         16 . A method of reducing the activity of an alternative pathway of a complement system of an individual, wherein the method comprises administering an antibody to the individual via a route of administration selected from the group consisting of enteral administration, parenteral administration, and a combination thereof, and wherein the antibody comprises six complementarity determining regions having the following amino acid sequences:
 a. SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10, or a variant or variants thereof, or   b. SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 18, SEQ ID NO: 19, and SEQ ID NO: 20, or a variant or variants thereof.   
     
     
         17 . The antibody of  claim 1 , wherein the antibody is an isolated antibody that binds to an epitope of human factor D having an amino acid sequence comprising at least one selected from the group consisting of SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, and SEQ ID NO: 24. 
     
     
         18 . A cell comprising the antibody of  claim 1 . 
     
     
         19 . A cell comprising a nucleic acid encoding the antibody of  claim 1 .