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 . A composition comprising a first and a second anti-TNF-alpha antibody single variable domain and an anti-serum albumin antibody single variable domain, wherein said first and second anti-TNF-alpha antibody single variable domains have the same TNF-alpha epitope binding specificity.
2 . The composition of claim 1 , wherein said first and second anti-TNF-alpha antibody single variable domains are identical.
3 . The composition of claim 1 , wherein the anti-TNF-alpha antibody single variable domains have a monomer surface plasmon resonance K D of about 300 nM to about 5 pM.
4 . The composition of claim 3 , wherein said monomer surface plasmon resonance K D is about 50 nM to about 20 pM.
5 . The composition of claim 4 , wherein said monomer surface plasmon resonance K D is about 1 nM to about 100 pM.
6 . The composition of claim 1 , wherein said composition has at beta half-life of at least 24 hours.
7 . The composition of claim 1 , wherein said composition has at beta half-life of 12 hours to 48 hours.
8 . The composition of claim 1 , wherein said composition has at beta half-life of 12 hours to 26 hours.
9 . A composition comprising a first and a second anti-TNF-alpha antibody single variable domain and an anti-serum albumin antibody single variable domain, wherein said composition has at beta half-life of at least 12 hours.
10 . The composition of claim 9 , wherein said composition has at beta half-life of at least 24 hours.
11 . The composition of claim 9 , wherein said composition has at beta half-life of 12 hours to 48 hours.
12 . The composition of claim 9 , wherein said composition has at beta half-life of 12 hours to 26 hours.
13 . The composition of claim 9 , comprising one anti-serum albumin antibody single variable domain.
14 . The composition of claim 9 , wherein said first and second anti-TNF-alpha antibody single variable domains and said anti-serum albumin antibody single variable domains form a fusion polypeptide.
15 . The composition of claim 9 , wherein said first and second anti-TNF-alpha antibody single variable domains compete with TAR1-5-19 to bind TNF-alpha in an ELISA assay.
16 . The composition of claim 9 , wherein the anti-TNF-alpha antibody single variable domains have the same TNF-alpha epitope binding specificity.
17 . The composition of claim 9 , wherein said first and second anti-TNF-alpha antibody single variable domains are identical.
18 . The composition of claim 9 , wherein the anti-TNF-alpha antibody single variable domains have a monomer surface plasmon resonance K D of about 300 nM to about 5 pM.
19 . The composition of claim 18 , wherein said monomer surface plasmon resonance K D is about 50 nM to about 20 pM.
20 . The composition of claim 19 , wherein said monomer surface plasmon resonance K D is about 1 nM to about 100 pM.
21 . The composition of claim 9 , wherein each antibody single variable domain is linked to a polypeptide linker.
22 . The composition of claim 9 , wherein said first and second anti-TNF-alpha antibody single variable domain and said anti-serum albumin antibody single variable domain are linked.
23 . A kit comprising the composition of claim 9 , and instructions for its use.
24 . A pharmaceutical composition comprising the composition of claim 9 and a pharmaceutically acceptable carrier.