Amino acid sequences directed against il-17a, il-17f and/or il-17a/f and polypeptides comprising the same

Abstract

The present disclosure relates to amino acid sequences that are directed against (as defined herein) any of IL-17A, IL-17F and/or IL-17A/F including combinations thereof, as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences.

What is claimed is: 
     
         1 . A polypeptide comprising a llama-derived, VHH-based domain, which domain binds to IL-17A. 
     
     
         2 . The polypeptide of  claim 1 , which is linked to one or more constant domains and a light chain. 
     
     
         3 . The polypeptide of  claim 2 , which in combination with the one or more constant domains and light chain forms an IgG antibody. 
     
     
         4 . The polypeptide of  claim 1 , which binds to human IL-17A with a dissociation constant (K D ) of 10 −5 -10 −12  moles/liter or less. 
     
     
         5 . The polypeptide of  claim 1 , wherein the llama-derived, VHH-based domain comprises an amino acid sequence selected from SEQ ID NOs: 623 to 693 or an amino acid sequence having at least 70% amino acid identity with a CDR sequence of at least one of the amino acid sequences of SEQ ID NOs: 623 to 693. 
     
     
         6 . The polypeptide of  claim 1 , wherein the llama-derived, VHH-based domain comprises an amino acid sequence selected from SEQ ID NO: 623 to 693 or an amino acid sequence having at least 70% amino acid identity with at least one of SEQ ID NOs: 623 to 693. 
     
     
         7 . The polypeptide of  claim 6 , wherein the llama-derived, VHH-based domain comprises an amino acid sequence having at least 70% amino acid identity with SEQ ID NO: 660, SEQ ID NO: 664, or SEQ ID NO: 690. 
     
     
         8 . The polypeptide of  claim 1 , wherein the llama-derived, VHH-based domain comprises:
 a first CDR comprising (i) the amino acid sequence AMG or (ii) an amino acid sequence that has 1 amino acid difference with the amino acid sequence AMG; and   a second CDR comprising (i) the amino acid sequence AISGSGDDTYYADSVKG or (ii) an amino acid sequence that has only 1-7 amino acid differences with the amino acid sequence   
       
         
           
                 
                 
               
                     
                   AISGSGDDTYYADSVKG. 
                 
             
                
               
            
           
         
       
     
     
         9 . The polypeptide of  claim 8 , which comprises an FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4 structure, and wherein FR4 comprises SEQ ID NO: 619. 
     
     
         10 . A pharmaceutical composition comprising a polypeptide comprising a humanized variant of a llama-derived VHH domain linked to a human variable light chain, and which is configured to specifically bind to human IL-17A. 
     
     
         11 . The pharmaceutical composition of  claim 10 , which further comprises a pharmaceutically acceptable excipient. 
     
     
         12 . A method of treating systemic lupus erythematosis, rheumatoid arthritis, osteoarthritis, juvenile chronic arthritis, spondyloarthropathies, systemic sclerosis, idiopathic inflammatory myopathies, Sjogren's syndrome, systemic vasculitis, sarcoidosis, autoimmune hemolytic anemia, autoimmune thrombocytopenia, thyroiditis, diabetes mellitus, immune-mediated renal disease, demyelinating diseases of the central and peripheral nervous systems, multiple sclerosis, idiopathic demyelinating polyneuropathy, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, hepatobiliary diseases, infectious, autoimmune chronic active hepatitis, primary biliary cirrhosis, granulomatous hepatitis, sclerosing cholangitis, inflammatory bowel disease, gluten-sensitive enteropathy, Whipple's disease, autoimmune or immune-mediated skin diseases, bullous skin diseases, erythema multiforme, contact dermatitis, psoriasis, allergic diseases, asthma, allergic rhinitis, atopic dermatitis, food hypersensitivity, urticaria, eosinophilic pneumonia, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, transplantation associated diseases, graft rejection, or graft-versus-host-disease, the method comprising administering to a patient in need thereof an effective amount of the polypeptide according to  claim 1 . 
     
     
         13 . The method of  claim 12 , which is a method of treating psoriasis.