US2023227571A1PendingUtilityA1

Anti-c5 antibodies and uses thereof

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Assignee: UNIV PENNSYLVANIAPriority: Mar 6, 2017Filed: Jan 12, 2023Published: Jul 20, 2023
Est. expiryMar 6, 2037(~10.6 yrs left)· nominal 20-yr term from priority
Inventors:Wenchao SongSayaka SatoTakashi MiwaDamodar Gullipalli
C07K 16/2896C07K 2317/55C07K 2317/24A61K 2039/505C07K 2317/622C07K 2317/565A61P 37/00C07K 16/18C12N 15/09C07K 2317/528C07K 2317/76C07K 2317/92
68
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Claims

Abstract

This invention relates to inhibition of the complement signaling using an anti-C5 antibody. Specifically, the invention relates to methods of treating a complement-mediated disease or complement-mediated disorder in an individual by contacting the individual with an anti-C5 antibody.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . An antibody that specifically binds to human C5. 
     
     
         2 . The antibody of  claim 1 , wherein the antibody is a chimeric antibody. 
     
     
         3 . 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. 
     
     
         4 . 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. 
     
     
         5 . 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. 
     
     
         6 . 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. 
     
     
         7 . 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. 
     
     
         8 . 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. 
     
     
         9 . 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. 
     
     
         10 . 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. 
     
     
         11 . 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. 
     
     
         12 . 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. 
     
     
         13 . 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:23; VH-CDR2: SEQ ID NO:24; VH-CDR3: SEQ ID NO:25; VL-CDR1: SEQ ID NO:28; and VL-CDR2: SEQ ID NO:29, or a variant or variants thereof. 
     
     
         14 . The antibody of  claim 1 , wherein the antibody comprises the CDRs: VH-CDR1: SEQ ID NO:23; VH-CDR2: SEQ ID NO:24; VH-CDR3: SEQ ID NO:25; VL-CDR1: SEQ ID NO:28; and VL-CDR2: SEQ ID NO:29, or a variant or variants thereof. 
     
     
         15 . The antibody of  claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:22, or a variant thereof. 
     
     
         16 . The antibody of  claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO:27, or a variant thereof. 
     
     
         17 . The antibody of  claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:22 and a light chain comprising the amino acid sequence of SEQ ID NO:27, or a variant or variants thereof. 
     
     
         18 . 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:32; VH-CDR2: SEQ ID NO:33; VH-CDR3: SEQ ID NO:34; VL-CDR1: SEQ ID NO:37; VL-CDR2: SEQ ID NO:38, VL-CDR3: SEQ ID NO:39, or a variant or variants thereof. 
     
     
         19 . The antibody of  claim 1 , wherein the antibody comprises the CDRs: VH-CDR1: SEQ ID NO:32; VH-CDR2: SEQ ID NO:33; VH-CDR3: SEQ ID NO:34; VL-CDR1: SEQ ID NO:37; VL-CDR2: SEQ ID NO:38, VL-CDR3: SEQ ID NO:39, or a variant or variants thereof. 
     
     
         20 . The antibody of  claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:31, or a variant thereof. 
     
     
         21 . The antibody of  claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO:36, or a variant thereof. 
     
     
         22 . The antibody of  claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:31 and a light chain comprising the amino acid sequence of SEQ ID NO:36, or a variant or variants thereof. 
     
     
         23 . 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:42; VH-CDR2: SEQ ID NO:43; VH-CDR3: SEQ ID NO:44; VL-CDR1: SEQ ID NO:47; VL-CDR2: SEQ ID NO:48, VL-CDR3: SEQ ID NO:49, or a variant or variants thereof. 
     
     
         24 . The antibody of  claim 1 , wherein the antibody comprises the CDRs: VH-CDR1: SEQ ID NO:42; VH-CDR2: SEQ ID NO:43; VH-CDR3: SEQ ID NO:44; VL-CDR1: SEQ ID NO:47; VL-CDR2: SEQ ID NO:48, VL-CDR3: SEQ ID NO:49, or a variant or variants thereof. 
     
     
         25 . The antibody of  claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 41, or a variant thereof. 
     
     
         26 . The antibody of  claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO:46, or a variant thereof. 
     
     
         27 . The antibody of  claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:41 and a light chain comprising the amino acid sequence of SEQ ID NO:46, or a variant or variants thereof. 
     
     
         28 . 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:52; VH-CDR2: SEQ ID NO:53; VH-CDR3: SEQ ID NO:54; VL-CDR1: SEQ ID NO:57; VL-CDR2: SEQ ID NO:58, VL-CDR3: SEQ ID NO:59, or a variant or variants thereof. 
     
     
         29 . The antibody of  claim 1 , wherein the antibody comprises the CDRs: VH-CDR1: SEQ ID NO:52; VH-CDR2: SEQ ID NO:53; VH-CDR3: SEQ ID NO:54; VL-CDR1: SEQ ID NO:57; VL-CDR2: SEQ ID NO:58, VL-CDR3: SEQ ID NO:59, or a variant or variants thereof. 
     
     
         30 . The antibody of  claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:51, or a variant thereof. 
     
     
         31 . The antibody of  claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO:56, or a variant thereof. 
     
     
         32 . The antibody of  claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:51 and a light chain comprising the amino acid sequence of SEQ ID NO:56, or a variant or variants thereof. 
     
     
         33 . A method of treating a complement pathway-mediated disease or disorder in an individual, comprising the step of administering to said individual the anti-C5 antibody of any one of  claims 1 - 32 . 
     
     
         34 . The method of  claim 33 , 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, lupus, ulcerative colitis, stroke, post-surgery systemic inflammatory syndrome, asthma, allergic asthma, chronic obstructive pulmonary disease (COPD), paroxysmal nocturnal hemoglobinuria (PNH) syndrome, myasthenia gravis, neuromyelitis optica, (NMO), multiple sclerosis, delayed graft function, antibody-mediated rejection, atypical hemolytic uremic (aHUS) syndrome, central retinal vein occlusion (CRVO), central retinal artery occlusion (CRAO), epidermolysis bullosa, sepsis, organ transplantation, inflammation (including, but not limited to, inflammation associated with cardiopulmonary bypass surgery and kidney dialysis), C3 glomerulopathy, membranous nephropathy, IgA nephropathy, glomerulonephritis (including, but not limited to, anti-neutrophil cytoplasmic antibody (ANCA)-mediated glomerulonephritis, lupus nephritis, and combinations thereof), ANCA-mediated vasculitis, Shiga toxin induced HUS, and antiphospholipid antibody-induced pregnancy loss, or any combinations thereof. 
     
     
         35 . A method of reducing the activity 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 is the antibody of any one of  claims 1 - 32 . 
     
     
         36 . The method of  claim 35 , wherein the antibody is an antibody fragment selected from the group consisting of a Fab, Fab′, F(ab)2, F(ab′)2, scFv, and combinations thereof. 
     
     
         37 . A cell comprising the antibody of at least one of  claims 1 - 32 . 
     
     
         38 . The cell of  claim 37 , wherein the cell produces the antibody of at least one of  claims 1 - 32 . 
     
     
         39 . The cell of  claim 37 , wherein the cell is a hybridoma.

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