Methods of treating lung pathologies with chimeric anti-TNF antibodies

Abstract

Anti-TNF antibodies, fragments and regions thereof which are specific for human tumor necrosis factor-α (TNFα) and are useful in vivo diagnosis and therapy of a number of TNFα-mediated pathologies and conditions, as well as polynucleotides coding for murine and chimeric antibodies, methods of producing the antibody, methods of use of the anti-TNF antibody, or fragment, region or derivative thereof, in immunoassays and immunotherapeutic approaches are provided.

What is claimed is:  
     
         1 . A method of treating a TNF-mediated lung pathology in a human comprising administering to the human an effective TNF-inhibiting amount of an anti-TNF chimeric antibody, wherein said anti-TNF antibody competitively inhibits binding of TNF to monoclonal antibody cA2.  
     
     
         2 . A method of treating a TNF-mediated lung pathology in a human comprising administering to the human an effective TNF-inhibiting amount of an anti-TNF chimeric antibody cA2, or a TNF binding fragment thereof.  
     
     
         3 . A method of treating a TNF-mediated lung pathology in a human comprising administering to the human an effective TNF-inhibiting amount of an anti-TNF chimeric antibody, wherein said anti-TNF chimeric antibody binds to at least one epitope included in amino acids between 87-108 or both 59-80 and 87-108 of SEQ ID NO: 1 of hTNF, as determined by Gysen epitope mapping comprising use of TNF decapeptide pins which overlap at every second amino acid.  
     
     
         4 . A method of treating a TNF-mediated lung pathology in a human comprising administering to the human an effective TNF-inhibiting amount of an anti-TNF chimeric antibody, wherein said anti-TNF chimeric antibody binds to at least one epitope included in amino acids between 87-108 or both 59-80 and 87-108 of SEQ ID NO: 1 of hTNF, as determined by Gysen epitope mapping comprising use of TNF dodecapeptide pins which overlap at every second amino acid.  
     
     
         5 . A method of treating a TNF-mediated lung pathology in a human comprising administering to the human an effective TNF-inhibiting amount of an anti-TNF chimeric antibody, wherein said anti-TNF chimeric antibody comprises a non-human variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 3 and SEQ ID NO: 5.  
     
     
         6 . The method of  claim 5 , wherein the non-human variable region is murine.  
     
     
         7 . The method of  claim 5 , wherein the non-human variable region comprises a polypeptide encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 4.  
     
     
         8 . A method of treating a TNF-mediated lung pathology in a human comprising administering to the human a single or divided 0.1-100 mg/kg dose of an anti-TNF chimeric antibody, wherein said anti-TNF antibody competitively inhibits binding of TNF to monoclonal antibody cA2.  
     
     
         9 . The method of  claim 8 , wherein the single or divided dose of anti-TNF chimeric antibody is selected from the group consisting of: a 0.1-1 mg/kg dose, a 1.0-5 mg/kg dose, a 5-10 mg/kg dose and a 10-20 mg/kg dose.  
     
     
         10 . The method of  claim 1 , wherein the anti-TNF chimeric antibody is administered to the human by means of parenteral administration.  
     
     
         11 . The method of  claim 1 , wherein the anti-TNF chimeric antibody is administered to the human by means of intravenous administration, subcutaneous administration, or intramuscular administration.  
     
     
         12 . The method of  claim 1 , wherein the anti-TNF chimeric antibody is administered orally.  
     
     
         13 . The method of  claim 1  further comprising administering to the human an effective amount of a therapeutic agent selected from the group consisting of: 
 disease-modifying anti-rheumatic drugs, anti-inflammatory agents, anti-neoplastic agents, radionuclides, radiotherapeutics, immunosuppressives, cytotoxic drugs, monoclonal antibodies, murine antibodies, chimeric antibodies, antibody fragments, antibody regions, lymphokines, cytokines, hemopoictic growth factors and immunoglobulins.  
 
     
     
         14 . The method of  claim 13 , wherein the therapeutic agent is a disease-modifying anti-rheumatic drug.  
     
     
         15 . The method of  claim 14 , wherein the disease-modifying anti-rheumatic drug is selected from the group consisting of: auranofin, azathioprine, chloroquine, D-penicillamine, gold sodium thiomalate hydroxychloroquine, Myocrisin and sulfasalzine methotrexate.  
     
     
         16 . The method of  claim 13 , wherein the therapeutic agent is an anti-inflammatory agent.  
     
     
         17 . The method of  claim 16 , wherein the anti-inflammatory agent is selected from the group consisting of: pentasa, mesalazine, asacol, codeine phosphate, benorylate, fenbufen, naprosyn, diclofenac, etodolac and indomethacin, aspirin and ibuprofen.  
     
     
         18 . The method of  claim 13 , wherein the therapeutic agent is an anti-neoplastic agent.  
     
     
         19 . The method of  claim 18 , wherein the anti-neoplastic agent is selected from the group consisting of: daunorubicin, doxorubicin, Mitomycin C and cyclophosphamide.  
     
     
         20 . The method of  claim 13 , wherein the therapeutic agent is a pain control agent.  
     
     
         21 . The method of  claim 20 , wherein the pain control agent is selected from the group consisting of: paracetamol and dextropropoxyphene.  
     
     
         22 . The method of  claim 1  further comprising administering to the human an effective amount of at least one therapeutic agent selected from the group consisting of: at least one antibiotic and at least one steroid.  
     
     
         23 . The method of  claim 1 , wherein the anti-TNF chimeric antibody is of immunoglobulin class IgG1, IgG2, IgG3, IgG4, or IgM.  
     
     
         24 . The method of  claim 1 , wherein the anti-TNF chimeric antibody is a fragment selected from the group consisting of Fab, Fab′, F(ab′) 2  and Fv.  
     
     
         25 . A method of treating a TNF-mediated lung pathology in a human comprising administering to the human an effective TNF-inhibiting amount of an anti-TNF chimeric antibody, wherein said anti-TNF chimeric antibody comprises an IgG1 constant region and competitively inhibits binding of TNF to monoclonal antibody cA2.  
     
     
         26 . A method of treating a TNF-mediated lung pathology in a human comprising administering to the human an effective TNF-inhibiting amount of an anti-TNF chimeric antibody, wherein said anti-TNF chimeric antibody comprises an IgG1 constant region and binds to at least one epitope included in amino acids between 87-108 or both 59-80 and 87-108 of SEQ ID NO: 1 of hTNF, as determined by Gysen epitope mapping comprising use of TNF decapeptide pins which overlap at every second amino acid.  
     
     
         27 . A method of treating a TNF-mediated lung pathology in a human comprising administering to the human an effective TNF-inhibiting amount of an anti-TNF chimeric antibody, wherein said anti-TNF chimeric antibody comprises an IgG1 constant region and binds to at least one epitope included in amino acids between 87-108 or both 59-80 and 87-108 of SEQ ID NO: 1 of hTNF, as determined by Gysen epitope mapping comprising use of TNF dodecapeptide pins which overlap at every second amino acid.  
     
     
         28 . A method of treating a TNF-mediated lung pathology in a human comprising administering to the human an effective TNF-inhibiting amount of an anti-TNF chimeric antibody, wherein said anti-TNF chimeric antibody comprises a non-human variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 3 and SEQ ID NO: 5 and an IgG1 human constant region.  
     
     
         29 . The method of  claim 28 , wherein the non-human variable region is murine.  
     
     
         30 . The method of  claim 28 , wherein the non-human variable region comprises a polypeptide encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 4.  
     
     
         31 . The method of  claim 1  wherein the TNF-mediated lung pathology is a chronic inflammatory disease.  
     
     
         32 . The method of  claim 1  wherein the TNF-mediated lung pathology is associated with a heart pathology.  
     
     
         33 . The method of  claim 1  wherein the TNF-mediated lung pathology is associated with a vascular inflammatory pathology.