Single domain antibodies directed against tumor necrosis factor-alpha and uses therefor
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. An anti-TNF-alpha polypeptide comprising at least one anti-TNF-alpha single domain antibody comprising:
(a) an amino acid sequence comprising SEQ ID NO: 1, or
(b) an amino acid sequence with more than 85% identity to the amino acid sequence of SEQ ID NO: 1, and which comprises an arginine residue at position 103 (numbering according to Kabat).
2. The anti-TNF-alpha polypeptide according to claim 1 , comprising an arginine at position 45 and a tryptophan at position 47 (numbering according to Kabat).
3. The anti-TNF-alpha polypeptide according to claim 1 , wherein at least one anti-TNF-alpha single domain antibody is humanized.
4. The anti-TNF-alpha polypeptide according to claim 3 , wherein at least one anti-TNF-alpha single domain antibody is a humanized Camelidae VHH.
5. The anti-TNF-alpha polypeptide according to claim 1 , wherein the number of anti-TNF-alpha single domain antibodies is at least two.
6. The anti-TNF-alpha polypeptide according to claim 1 further comprising at least one single domain antibody that binds a serum protein.
7. The anti-TNF-alpha polypeptide according to claim 6 wherein said serum protein is any of serum albumin, serum immunoglobulins, thyroxine-binding protein, transferrin, or fibrinogen.
8. The anti-TNF-alpha polypeptide according to claim 6 , wherein the number of single domain antibodies directed against TNF-alpha is at least two.
9. A composition comprising the anti-TNF-alpha polypeptide according to claim 1 .
10. A composition comprising the anti-TNF-alpha polypeptide according to claim 2 .
11. A composition comprising the anti-TNF-alpha polypeptide according to claim 3 .
12. A composition comprising the anti-TNF-alpha polypeptide according to claim 4 .
13. A composition comprising the anti-TNF-alpha polypeptide according to claim 5 .
14. A composition comprising the anti-TNF-alpha polypeptide according to claim 6 .
15. A composition comprising the anti-TNF-alpha polypeptide according to claim 7 .
16. A composition comprising the anti-TNF-alpha polypeptide according to claim 8 .