Single domain antibodies directed against tumour 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 - 25 . (canceled)  
     
     
         26 . A method for treating rheumatoid arthritis comprising administering to a subject in need of such treatment an effective amount of of an anti-TNF-alpha polypeptide comprising at least one anti-TNF-alpha single domain antibody.  
     
     
         27 - 49 . (canceled)  
     
     
         50 . A method of treating rheumatoid arthritis, the method comprising administering to an individual in need thereof a therapeutically effective amount of an anti-TNF-alpha polypeptide comprising at least one anti-TNF-alpha single domain antibody, and whereby said rheumatoid arthritis is treated.  
     
     
         51 . The method of  claim 50 , wherein said anti-TNF-alpha polypeptide comprising at least one anti-TNF-alpha single domain antibody prevents an increase in arthritic score when administered to a mouse which is a mouse model of arthritis.  
     
     
         52 . The method of  claim 51 , wherein said anti-TNF-alpha polypeptide comprising at least one anti-TNF-alpha single domain antibody has an efficacy in an assay that is greater than or equal to that of an agent selected from the group consisting of Etanercept and Infliximab.  
     
     
         53 . The method of  claim 51 , wherein said anti-TNF-alpha polypeptide comprising at least one anti-TNF-alpha single domain antibody has an efficacy in a mouse arthritis assay that is greater than or equal to that of an agent selected from the group consisting of Etanercept and Infliximab.  
     
     
         54 . The method of  claim 50 , wherein said treating comprises preventing rheumatoid arthritis.  
     
     
         55 . The method of  claim 50 , wherein said administering results in alleviating the symptoms of rheumatoid arthritis.  
     
     
         56 . The method of  claim 50 , wherein said anti-TNF-alpha polypeptide comprises at least one human anti-TNF-alpha single domain antibody.  
     
     
         57 . The method of  claim 50 , wherein said anti-TNF-alpha polypeptide comprising at least one anti-TNF-alpha single domain antibody antagonizes human TNF-alpha as measured in an assay.  
     
     
         58 . The method of  claim 50 , wherein said anti-TNF-alpha polypeptide comprising at least one anti-TNF-alpha single domain antibody antagonizes human TNF-alpha as measured in a standard L929 cell assay.  
     
     
         59 . A method of treating rheumatoid arthritis, the method comprising administering to an individual in need thereof a therapeutically effective amount of an anti-TNF-alpha polypeptide comprising at least one anti-TNF-alpha single domain antibody, wherein said single domain antibody polypeptide construct inhibits the binding of human TNF-alpha to a TNF-alpha receptor, and whereby said rheumatoid arthritis is treated.  
     
     
         60 . A composition comprising an anti-TNF-alpha polypeptide comprising at least one anti-TNF-alpha single domain antibody, wherein the anti-TNF-alpha polypeptide prevents an increase in arthritic score when administered to a mouse which is a mouse model of arthritis, wherein said single domain antibody polypeptide construct neutralizes human TNF-alpha as measured in a standard L929 cell assay.  
     
     
         61 . A method of treating rheumatoid arthritis, the method comprising administering to an individual in need thereof a therapeutically effective amount of a composition comprising a single domain antibody polypeptide construct that antagonizes human TNF-alpha's binding to a receptor, whereby said rheumatoid arthritis is treated.  
     
     
         62 . The method of  claim 61 , wherein said treating comprises preventing or delaying the onset of rheumatoid arthritis.  
     
     
         63 . The method of  claim 61 , wherein said administering results in a statistically significant change in one or more indicia of RA.  
     
     
         64 . The method of  claim 61 , wherein said single domain antibody polypeptide construct comprises a human single domain antibody polypeptide.  
     
     
         65 . The method of  claim 64 , wherein said human single domain antibody polypeptide binds TNF-alpha.  
     
     
         66 . The method of  claim 61 , wherein said single domain antibody polypeptide construct antagonizes human TNF-alpha as measured in a standard L929 cell assay.  
     
     
         67 . A method of treating rheumatoid arthritis, the method comprising administering to an individual in need thereof a therapeutically effective amount of a composition comprising a single domain antibody polypeptide construct that antagonizes human TNF-alpha's binding to a receptor, wherein said single domain antibody polypeptide construct inhibits the binding of human TNF-alpha to a TNF-alpha receptor, and whereby said rheumatoid arthritis is treated.