Methods of treating neurodegenerative inflammation 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 neurodegenerative inflammation in a human in need thereof, comprising administering to the cerebrospinal fluid (CSF) of said human an effective TNF-inhibiting amount of an anti-TNF antibody or TNF binding fragment thereof sufficient to treat the neurodegenerative inflammation.  
     
     
         2 . A method of treating neurodegenerative inflammation in a human in need thereof, comprising administering to the cerebrospinal fluid (CSF) of said human an effective TNF-inhibiting amount of an anti-TNF antibody or TNF binding fragment thereof sufficient to treat the neurodegenerative inflammation, wherein said anti-TNF antibody or fragment is a chimeric TNF antibody.  
     
     
         3 . A method of treating neurodegenerative inflammation in a human in need thereof, comprising administering to the cerebrospinal fluid (CSF) of said human an effective TNF-inhibiting amount of an anti-TNF antibody or TNF binding fragment thereof sufficient to treat the neurodegenerative inflammation, wherein said anti-TNF antibody or fragment competitively inhibits the binding of TNF to the TNF antibody cA2.  
     
     
         4 . The method of  claim 3 , wherein the chimeric TNF antibody comprises non-human variable region.  
     
     
         5 . The method of  claim 1 , wherein said administration comprises a single or divided 0.1-100 mg/kg dose of said anti-TNF antibody or fragment thereof.  
     
     
         6 . The method of  claim 2 , wherein said administration comprises a single or divided 0.1-100 mg/kg dose of said anti-TNF antibody or fragment thereof.  
     
     
         7 . The method of  claim 3 , wherein said administration comprises a single or divided 0.1-100 mg/kg dose of said anti-TNF antibody or fragment thereof.  
     
     
         8 . 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, hemopoietic growth factors and immunoglobulins.  
 
     
     
         9 . The method of  claim 2  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, hemopoietic growth factors and immunoglobulins.  
 
     
     
         10 . The method of  claim 3  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, hemopoietic growth factors and immunoglobulins.  
 
     
     
         11 . The method of  claim 8 , wherein the therapeutic agent is a disease-modifying anti-rheumatic drug.  
     
     
         12 . The method of  claim 1  1, 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.  
     
     
         13 . The method of  claim 8 , wherein the therapeutic agent is an anti-inflammatory agent.  
     
     
         14 . The method of  claim 13 , 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.  
     
     
         15 . The method of  claim 8 , wherein the therapeutic agent is a pain control agent.  
     
     
         16 . The method of  claim 15 , wherein the pain control agent is selected from the group consisting of: paracetamol and dextropropoxyphene.  
     
     
         17 . 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.  
     
     
         18 . The method of  claim 1 , wherein the anti-TNF chimeric antibody is of 5 immunoglobulin class IgG1, IgG2, IgG3, IgG4 or IgM.  
     
     
         19 . 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.