Il-11 antibodies

Abstract

Provided are antigen-binding molecules capable of binding to IL-11, and methods of medical treatment and prophylaxis using the same.

1 .- 25 . (canceled) 
     
     
         26 . An antigen-binding molecule which binds specifically to IL-11, wherein the antigen-binding molecule comprises:
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO: 95; 
 HC-CDR2 having the amino acid sequence of SEQ ID NO: 96, or a variant of SEQ ID NO: 96 comprising one amino acid substitution; and 
 HC-CDR3 having the amino acid sequence of SEQ ID NO: 97; and 
   (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO: 101; 
 LC-CDR2 having the amino acid sequence of SEQ ID NO: 102, or a variant of SEQ ID NO: 102 comprising one amino acid substitution; and 
 LC-CDR3 having the amino acid sequence of SEQ ID NO: 103. 
   
     
     
         27 . The antigen-binding molecule according to  claim 26 , wherein the antigen-binding molecule comprises:
 a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 117; and   a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 122.   
     
     
         28 . The antigen-binding molecule according to  claim 26 , wherein the antigen-binding molecule comprises:
 a VH region comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 117; and   a VL region comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 122.   
     
     
         29 . The antigen-binding molecule according to  claim 26 , wherein the antigen-binding molecule comprises:
 a VH region incorporating the following framework regions (FRs):
 HC-FR1 having the amino acid sequence of SEQ ID NO: 130; 
 HC-FR2 having the amino acid sequence of SEQ ID NO: 133; 
 HC-FR3 having the amino acid sequence of SEQ ID NO: 137; and 
 HC-FR4 having the amino acid sequence of SEQ ID NO: 140. 
   
     
     
         30 . The antigen-binding molecule according to  claim 26 , wherein the antigen-binding molecule comprises:
 a VL region incorporating the following framework regions (FRs):
 LC-FR1 having the amino acid sequence of SEQ ID NO: 141; 
 LC-FR2 having the amino acid sequence of SEQ ID NO: 145; 
 LC-FR3 having the amino acid sequence of SEQ ID NO: 147; and 
 LC-FR4 having the amino acid sequence of SEQ ID NO: 149. 
   
     
     
         31 . The antigen-binding molecule according to  claim 26 , wherein the antigen-binding molecule comprises a heavy chain constant sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 85. 
     
     
         32 . The antigen-binding molecule according to  claim 26 , wherein the antigen-binding molecule comprises a light chain constant sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 90. 
     
     
         33 . A nucleic acid, or a plurality of nucleic acids, encoding an antigen-binding molecule which binds specifically to IL-11, wherein the antigen-binding molecule comprises:
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO: 95; 
 HC-CDR2 having the amino acid sequence of SEQ ID NO: 96, or a variant of SEQ ID NO: 96 comprising one amino acid substitution; and 
 HC-CDR3 having the amino acid sequence of SEQ ID NO: 97; and 
   (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO: 101; 
 LC-CDR2 having the amino acid sequence of SEQ ID NO: 102, or a variant of SEQ ID NO: 102 comprising one amino acid substitution; and 
 LC-CDR3 having the amino acid sequence of SEQ ID NO: 103. 
   
     
     
         34 . The nucleic acid or plurality of nucleic acids according to  claim 33 , wherein the antigen-binding molecule comprises:
 a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 117; and   a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 122;   optionally wherein the antigen-binding molecule comprises:   a VH region comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 117; and   a VL region comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 122.   
     
     
         35 . The nucleic acid or plurality of nucleic acids according to  claim 33 , wherein the antigen-binding molecule comprises:
 a VH region incorporating the following framework regions (FRs):
 HC-FR1 having the amino acid sequence of SEQ ID NO: 130; 
 HC-FR2 having the amino acid sequence of SEQ ID NO: 133; 
 HC-FR3 having the amino acid sequence of SEQ ID NO: 137; and 
 HC-FR4 having the amino acid sequence of SEQ ID NO: 140. 
   
     
     
         36 . The nucleic acid or plurality of nucleic acids according to  claim 33 , wherein the antigen-binding molecule comprises:
 a VL region incorporating the following framework regions (FRs):
 LC-FR1 having the amino acid sequence of SEQ ID NO: 141; 
 LC-FR2 having the amino acid sequence of SEQ ID NO: 145; 
 LC-FR3 having the amino acid sequence of SEQ ID NO: 147; and 
 LC-FR4 having the amino acid sequence of SEQ ID NO: 149. 
   
     
     
         37 . The nucleic acid or plurality of nucleic acids according to  claim 33 , wherein the antigen-binding molecule comprises a heavy chain constant sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 85. 
     
     
         38 . The nucleic acid or plurality of nucleic acids according to  claim 33 , wherein the antigen-binding molecule comprises a light chain constant sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 90. 
     
     
         39 . A method of treating or preventing a disease or condition in a subject, the method comprising administering to a subject in need thereof a therapeutically or prophylactically effective amount of an antigen-binding molecule that specifically binds to IL-11, wherein the antigen-binding molecule comprises:
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO: 95; 
 HC-CDR2 having the amino acid sequence of SEQ ID NO: 96, or a variant of SEQ ID NO: 96 comprising one amino acid substitution; and 
 HC-CDR3 having the amino acid sequence of SEQ ID NO: 97; and 
   (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO: 101; 
 LC-CDR2 having the amino acid sequence of SEQ ID NO: 102, or a variant of SEQ ID NO: 102 comprising one amino acid substitution; and 
 LC-CDR3 having the amino acid sequence of SEQ ID NO: 103; 
   wherein the disease or condition is selected from the group consisting of: fibrosis, a disease characterised by fibrosis, a cancer, inflammation, a disease characterised by inflammation, hepatotoxicity, a disease characterised by hepatotoxicity, a metabolic disease, a wasting disorder, kidney injury, nephrotoxicity, and a disease characterised by hepatotoxicity.   
     
     
         40 . The method according to  claim 39 , wherein the antigen-binding molecule comprises:
 a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 117; and   a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 122;   optionally wherein the antigen-binding molecule comprises:   a VH region comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 117; and   a VL region comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 122.   
     
     
         41 . The method according to  claim 39 , wherein the antigen-binding molecule comprises:
 a VH region incorporating the following framework regions (FRs):
 HC-FR1 having the amino acid sequence of SEQ ID NO: 130; 
 HC-FR2 having the amino acid sequence of SEQ ID NO: 133; 
 HC-FR3 having the amino acid sequence of SEQ ID NO: 137; and 
 HC-FR4 having the amino acid sequence of SEQ ID NO: 140. 
   
     
     
         42 . The method according to  claim 39 , wherein the antigen-binding molecule comprises:
 a VL region incorporating the following framework regions (FRs):
 LC-FR1 having the amino acid sequence of SEQ ID NO: 141; 
 LC-FR2 having the amino acid sequence of SEQ ID NO: 145; 
 LC-FR3 having the amino acid sequence of SEQ ID NO: 147; and 
 LC-FR4 having the amino acid sequence of SEQ ID NO: 149. 
   
     
     
         43 . The method according to  claim 39 , wherein the antigen-binding molecule comprises a heavy chain constant sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 85. 
     
     
         44 . The method according to  claim 39 , wherein the antigen-binding molecule comprises a light chain constant sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 90. 
     
     
         45 . The method according to  claim 39 , wherein the disease or condition is selected from the group consisting of: pulmonary fibrosis, cystic fibrosis, idiopathic pulmonary fibrosis, progressive massive fibrosis, scleroderma, obliterative bronchiolitis, Hermansky-Pudlak syndrome, asbestosis, silicosis, chronic pulmonary hypertension, AIDS associated pulmonary hypertension, sarcoidosis, tumor stroma in lung disease, asthma, chronic liver disease, primary biliary cirrhosis, schistosomal liver disease, liver cirrhosis, steatohepatitis, non-alcoholic steatohepatitis, early-stage NASH, late-stage NASH, alcoholic steatohepatitis, steatosis, chronic pancreatitis, pancreatic fibrosis, hypertrophic cardiomyopathy, dilated cardiomyopathy, fibrosis of the atrium, atrial fibrillation, fibrosis of the ventricle, ventricular fibrillation, myocardial fibrosis, Brugada syndrome, myocarditis, endomyocardial fibrosis, myocardial infarction, fibrotic vascular disease, hypertensive heart disease, arrhythmogenic right ventricular cardiomyopathy, tubulointerstitial fibrosis, glomerular fibrosis, atherosclerosis, varicose veins, cerebral infarcts, gliosis, Alzheimer's disease, muscular dystrophy, Duchenne muscular dystrophy, Becker's muscular dystrophy, Crohn's disease, microscopic colitis, primary sclerosing cholangitis, scleroderma, nephrogenic systemic fibrosis, cutis keloid, arthrofibrosis, Dupuytren's contracture, mediastinal fibrosis, retroperitoneal fibrosis, myelofibrosis, Peyronie's disease, adhesive capsulitis, chronic kidney disease, renal fibrosis, nephritic syndrome, Alport's syndrome, HIV associated nephropathy, polycystic kidney disease, Fabry's disease, diabetic nephropathy, chronic glomerulonephritis, nephritis associated with systemic lupus, kidney interstitial fibrosis, kidney injury, acute kidney injury, renal failure, nephrotoxicity, progressive systemic sclerosis, chronic graft versus host disease, Grave's opthalmopathy, epiretinal fibrosis, diabetic retinopathy, glaucoma, subretinal fibrosis, macular degeneration, wet age-related macular degeneration, macular edema, drusen formation, choroidal neovascularization, diabetic retinopathy, glaucoma, corneal fibrosis, post-surgical fibrosis of the posterior capsule following cataract surgery, post-surgical fibrosis of the bleb following trabeculectomy, conjunctival fibrosis, subconjunctival fibrosis, arthritis, fibrotic pre-neoplastic disease, fibrotic neoplastic disease, and fibrosis induced by chemical or environmental insult. 
     
     
         46 . An antigen-binding molecule which binds specifically to IL-11, wherein the antigen-binding molecule comprises:
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO: 95; 
 HC-CDR2 having the amino acid sequence of SEQ ID NO: 96; and 
 HC-CDR3 having the amino acid sequence of SEQ ID NO: 97; and 
   (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO: 101; 
 LC-CDR2 having the amino acid sequence of SEQ ID NO: 102; and 
 LC-CDR3 having the amino acid sequence of SEQ ID NO: 103.