Ligands that bind tgf-beta receptor ii

Abstract

The disclosure provides an anti-TGFbetaRII immunoglobulin single variable domain. Suitably, an anti-TGFbetaRII immunoglobulin single variable domain in accordance with the disclosure is one having an amino acid sequence as set forth in any one of SEQ ID NO:1-28 having up to 5 amino acid substitutions, deletions or additions. The disclosure further provides a polypeptide and pharmaceutical composition for treating a disease associated with TGFbeta signalling and suitably a disease selected from the group of: tissue fibrosis, such as pulmonary fibrosis, including idiopathic pulmonary fibrosis; liver fibrosis, including cirrhosis and chronic hepatitis; rheumatoid arthritis; ocular disorders; fibrosis of the skin, including keloid of skin; Dupuytren's Contracture; kidney fibrosis such as nephritis and nephrosclerosis; wound healing; scarring reduction; and a vascular condition, such as restenosis.

1 . A method of treating and/or preventing a Transforming Growth Factor-beta receptor II (TGFbetaRII)-mediated condition in a human patient, the method comprising the step of: administering a composition comprising an anti-TGFbetaRII immunoglobulin single variable domain comprising an amino acid sequence as set forth in SEQ ID NO: 267, having up to 5 amino acid substitutions, deletions or additions, in any combination, or an isolated nucleic acid sequence encoding said anti-TGFbetaRII immunoglobulin single variable domain. 
     
     
         2 . A method of treating or preventing a disease or condition associated with TGFbeta signalling in a human, the method comprising administering to the patient an anti-TGFbetaRII immunoglobulin single variable domain comprising an amino acid sequence as set forth in SEQ ID NO: 267, having up to 5 amino acid substitutions, deletions or additions, in any combination, or an isolated nucleic acid sequence encoding said anti-TGFbetaRII immunoglobulin single variable domain. 
     
     
         3 . A method as claimed in  claim 1 , wherein the immunoglobulin single variable domain comprises the amino acid sequence as set forth in SEQ ID NO: 267. 
     
     
         4 . A method as claimed in  claim 1 , wherein the isolated nucleic acid comprises the nucleic acid molecule set out in SEQ ID NO: 266. 
     
     
         5 . A method as claimed in  claim 1 , wherein the disease is selected from the group of: cancer, including colon, gastric, pancreatic cancer, glioma and NSCLC, scarring reduction, tissue fibrosis, such as pulmonary fibrosis, including idiopathic pulmonary fibrosis; liver fibrosis, including cirrhosis and chronic hepatitis; rheumatoid arthritis; ocular disorders; fibrosis of the skin, including keloid of skin, and Dupuytren's Contracture; kidney fibrosis such as nephritis and nephrosclerosis, wound healing; and a vascular condition, such as restenosis. 
     
     
         6 . A method as claimed in  claim 1 , wherein the anti-TGFbetaRII immunoglobulin single variable domain is linked to an antibody Fc region comprising one or both of CH2 and CH3 domains and optionally a hinge region. 
     
     
         7 . An anti-TGFbetaRII immunoglobulin single variable domain or polypeptide as claimed in  claim 1  for use in targeting cancer by modulating TGFbeta signalling in tumour angiogenesis.