Polypeptides

Abstract

There is provided inter alia a polypeptide comprising an immunoglobulin chain variable domain which binds to IL-6R, wherein the immunoglobulin chain variable domain comprises three complementarity determining regions (CDR1-CDR3) and four framework regions (FR1-FR4), wherein CDR1-CDR3 and FR1-FR4 are as defined in the specification.

1 . A polypeptide comprising an immunoglobulin chain variable domain which binds to IL-6R, wherein the immunoglobulin chain variable domain comprises three complementarity determining regions (CDR1-CDR3) and four framework regions (FR1-FR4), wherein CDR3 comprises a sequence having no more than 3 additions, substitutions and deletions compared to SEQ ID NO: 3. 
     
     
         2 . A polypeptide comprising an immunoglobulin chain variable domain which binds to IL-6R, wherein the immunoglobulin chain variable domain comprises three complementarity determining regions (CDR1-CDR3) and four framework regions (FR1-FR4), wherein CDR3 comprises a sequence having no more than 6 additions, substitutions and deletions compared to SEQ ID NO: 3 and wherein the immunoglobulin chain variable domain comprises one or more amino acids selected from V33, G52, G56 and Y93, and optionally one or more amino acids selected from T18, T21 and F62, according to Kabat numbering. 
     
     
         3 . The polypeptide according to  claim 1 , wherein CDR3 comprises a sequence having no more than 2 additions, substitutions and deletions compared to SEQ ID NO: 3. 
     
     
         4 . The polypeptide according to  claim 1 , wherein the sequence of CDR3 comprises any one of SEQ ID NO: 3, SEQ ID NO: 14, SEQ ID NO: 48 to 53 or SEQ ID NO: 55 to 58. 
     
     
         5 . The polypeptide according to  claim 1 , wherein CDR1 comprises a sequence having no more than 2 additions, substitutions and deletions compared to SEQ ID NO: 1. 
     
     
         6 . The polypeptide according to  claim 5 , wherein CDR1 comprises SEQ ID NO 1 or SEQ ID NO: 8. 
     
     
         7 . The polypeptide according to  claim 1 , wherein CDR2 comprises a sequence having no more than 8 additions, substitutions and deletions compared to SEQ ID NO: 2. 
     
     
         8 . The polypeptide according to  claim 7 , wherein CDR2 comprises any one of SEQ ID NOs: 2, SEQ ID NO: 9, SEQ ID NO: 46 or SEQ ID NO: 47. 
     
     
         9 . The polypeptide according to  claim 1  which comprises any one of SEQ ID NOs: 15-39, 43 or 44. 
     
     
         10 . The polypeptide according to  claim 1 , wherein the polypeptide is an antibody. 
     
     
         11 . The polypeptide according to  claim 1 , wherein the polypeptide is an immunoglobulin chain variable domain. 
     
     
         12 . The polypeptide according to  claim 11 , wherein the polypeptide is selected from the list consisting of: a VHH, a VH, a VL, a V-NAR, a Fab fragment and a F(ab′)2 fragment. 
     
     
         13 . The polypeptide according to  claim 12 , wherein the polypeptide is a VHH. 
     
     
         14 . The polypeptide according to  claim 1 , wherein the polypeptide binds to TNF-alpha with a Kd of less than 10 −6  M. 
     
     
         15 . The polypeptide according to  claim 1 , which is substantially resistant to one or more proteases present in the stomach or the small or large intestine. 
     
     
         16 . The polypeptide according to  claim 1 , wherein the polypeptide or construct retains 10% or more of the original potency of the polypeptide after at least 16 hours' exposure to human faecal extract in the standard human faecal extract assay. 
     
     
         17 . A pharmaceutical composition comprising the polypeptide according to  claim 1  and one or more pharmaceutically acceptable diluents or carriers. 
     
     
         18 . The pharmaceutical composition according to  claim 17  wherein the composition is presented in enterically coated form. 
     
     
         19 . A method of treating autoimmune and/or inflammatory disease comprising administering to a person in need thereof a therapeutically effective amount of the polypeptide according to  claim 1 . 
     
     
         20 . The method of treating autoimmune disease according to  claim 19  wherein the polypeptide is administered orally.