Single domain antibodies directed against tumor necrosis factor-alpha and uses therefor

Abstract

The present invention relates to polypeptides derived from single domain heavy chain antibodies directed to Tumor Necrosis Factor-alpha. It further relates to single domain antibodies that are Camelidae VHHs. It further relates to methods of administering said polypeptides. It further relates to protocols for screening for agents that modulate the TNF-alpha receptor, and the agents resulting from said screening.

1 . A ligand comprising a single variable domain, wherein the single variable domain specifically binds to an antigen, and the variable domain comprises a Kd for the antigen of better than 10 −6  M. 
     
     
         2 . The ligand of  claim 1 , wherein the antigen is selected from the group consisting of human protein, animal protein, cytokine, cytokine receptor, TNF-alpha, IFN-gamma, a serum protein, serum albumin, serum immunoglobulins, thyroxine-binding protein, transferrin, and fibrinogen. 
     
     
         3 . A dual specific ligand comprising a first single variable domain and a second a single variable domain where at least one of the first single variable domain and the second single variable domain comprises a Kd for the antigen of better than 10 −6  M. 
     
     
         4 . The dual specific ligand of  claim 3 , wherein said first single variable domain specifically binds to an antigen selected from the group consisting of, human, protein, animal protein, cytokine, cytokine receptor, TNF-alpha, IFN-gamma, a serum protein, serum albumin, serum immunoglobulins, thyroxine-binding protein, transferrin, and fibrinogen; and wherein said second single variable domain specifically binds to an antigen selected from the group consisting of, human, protein, animal protein, cytokine, cytokine receptor, TNF-alpha, IFN-gamma, a serum protein, serum albumin, serum immunoglobulins, thyroxine-binding protein, transferrin, and fibrinogen. 
     
     
         5 . A dual specific ligand comprising a first single variable domain and a second single variable domain, wherein the first single variable domain specifically binds to an antigen and the second single variable domain specifically binds to an antigen, wherein at least one of the first single variable domain and the second single variable domain comprises a Kd for the antigen of better than 10 −6  M. 
     
     
         6 . The dual specific ligand of  claim 5 , wherein said first single variable domain specifically binds to an antigen selected from the group consisting of human protein, animal protein, cytokine, cytokine receptor, TNF-alpha, IFN-gamma, a serum protein, serum albumin, serum immunoglobulins, thyroxine-binding protein, transferrin, and fibrinogen; and wherein said second single variable domain specifically binds to an antigen selected from the group consisting of human protein, animal protein, cytokine, cytokine receptor, TNF-alpha, IFN-gamma, a serum protein, serum albumin, serum immunoglobulins, thyroxine-binding protein, transferrin, and fibrinogen.