Method of administering therapeutic polypeptides, and polypeptides therefor

Abstract

The invention relates to a method suitable for administering protein therapeutic molecules orally, sublingually, topically, intravenously, subcutaneously, nasally, vaginally, rectally or by inhalation so as to avoid inactivation, by using VHH polypeptides derived from Camelidae antibodies. The invention further relates to the said therapeutic molecules. The invention further a method for delivering therapeutic molecules to the interior of cells. The invention further relates to anti-IgE therapeutic molecules.

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 1×10 −6  M or better. 
     
     
         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, IgE, IFN-gamma, CEA,  H. pylori , TB ( M. tuberculosis ), influenza, Hepatitis E, MMP-12, epidermal growth factor receptor (EGFR), ErBb2 receptor on tumor cells, LDL receptor, FGF2 receptor, ErbB2 receptor, transferrin receptor, PDGF receptor, VEGF receptor, PsmAr, PDK1, GSK1, Bad, caspase-9, Forkhead, an antigen of  Helicobacter pylori , an antigen of  Mycobacterium tuberculosis , an antigen of influenza virus, 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 1×10 −6  M or better. 
     
     
         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, IgE, IFN-gamma, CEA,  H. pylori , TB ( M. tuberculosis ), influenza, Hepatitis E, MMP-12, epidermal growth factor receptor (EGFR), ErBb2 receptor on tumor cells, LDL receptor, FGF2 receptor, ErbB2 receptor, transferrin receptor, PDGF receptor, VEGF receptor, PsmAr, PDK1, GSK1, Bad, caspase-9, Forkhead, an antigen of  Helicobacter pylori , an antigen of  Mycobacterium tuberculosis , an antigen of influenza virus, 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, IgE, IFN-gamma, CEA,  H. pylori , TB ( M. tuberculosis ), influenza, Hepatitis E, MMP-12, epidermal growth factor receptor (EGFR), ErBb2 receptor on tumor cells, LDL receptor, FGF2 receptor, ErbB2 receptor, transferrin receptor, PDGF receptor, VEGF receptor, PsmAr, PDK1, GSK1, Bad, caspase-9, Forkhead, an antigen of  Helicobacter pylori , an antigen of  Mycobacterium tuberculosis , an antigen of influenza virus, 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 1×10 −6  M or better. 
     
     
         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, IgE, IFN-gamma, CEA,  H. pylori , TB ( M. tuberculosis ), influenza, Hepatitis E, MMP-12, epidermal growth factor receptor (EGFR), ErBb2 receptor on tumor cells, LDL receptor, FGF2 receptor, ErbB2 receptor, transferrin receptor, PDGF receptor, VEGF receptor, PsmAr, PDK1, GSK1, Bad, caspase-9, Forkhead, an antigen of  Helicobacter pylori , an antigen of  Mycobacterium tuberculosis , an antigen of influenza virus, 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, IgE, IFN-gamma, CEA,  H. pylori , TB ( M. tuberculosis ), influenza, Hepatitis E, MMP-12, epidermal growth factor receptor (EGFR), ErBb2 receptor on tumor cells, LDL receptor, FGF2 receptor, ErbB2 receptor, transferrin receptor, PDGF receptor, VEGF receptor, PsmAr, PDK1, GSK1, Bad, caspase-9, Forkhead, an antigen of  Helicobacter pylori , an antigen of  Mycobacterium tuberculosis , an antigen of influenza virus, a serum protein, serum albumin, serum immunoglobulins, thyroxine-binding protein, transferrin, and fibrinogen.