TNF receptor death domain ligand proteins and inhibitors of ligand binding
View Patent ↗Novel TNF receptor death domain (“TNF-R1-DD”) ligand proteins are disclosed. Polynucleotides encoding the TNF-R1-DD ligand protein are also disclosed, along with vectors, host cells, and methods of making the TNF-R1-DD ligand protein. Pharmaceutical compositions containing the TNF-R1-DD ligand protein, methods of treating inflammatory conditions, and methods of inhibiting TNF-R death domain binding are also disclosed. Methods of identifying inhibitors of TNF-R death domain binding and inhibitors identified by such methods are also disclosed.
1. An isolated antibody which specifically binds to a protein
comprising the amino acid sequence of SEQ ID NO:2 or a fragment thereof,
wherein said antibody binds specifically to an epitope in the amino acid sequence of SEQ ID NO:2 or a fragment thereof.
2. The antibody of claim 1 , wherein said antibody is a neutralizing antibody.
3. The antibody of claim 1 , wherein said antibody blocks binding of TNF-R1-DD to a polypeptide TNF-R1-DD ligand protein comprising the amino acid sequence of SEQ ID NO:2.
4. The antibody of claim 1 , wherein said antibody is a polyclonal antibody.
5. The antibody of claim 1 , wherein said antibody is a monoclonal antibody.
6. The antibody of claim 1 , wherein said antibody specifically reacts with a protein comprising the amino acid sequence of SEQ ID NO:2.
7. The antibody of claim 1 , wherein said antibody specifically reacts with a protein comprising the amino acid sequence of SEQ ID NO:12.
8. The antibody of claim 1 , wherein said antibody specifically reacts with a protein comprising the amino acid sequence of SEQ ID NO:16.
9. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
10. A neutralizing antibody that binds specifically to an epitope in the amino acid sequence of SEQ ID NO:2;
wherein said neutralizing antibody blocks binding of TNF-R1-DD to a TNF-R1-DD ligand protein comprising the amino acid sequence of SEQ ID NO:2.
11. The antibody of claim 10 , wherein said antibody is an isolated antibody.
12. A pharmaceutical composition comprising the antibody of claim 10 and a pharmaceutically acceptable carrier.
13. An antibody that specifically binds to an enitope in a protein with the amino acid seciuence of SEQ ID NO:2, wherein said antibody is obtained using as an immunogen TNF-R1-DD ligand protein, wherein said TNF-R1-DD ligand protein comprises the amino acid sequence of SEQ ID NO:2.
14. The antibody of claim 13 , wherein said antibody is obtained using as an immunogen a protein with tyrosine residues replaced with sulfated tyrosine residues.
15. The antibody of claim 13 , wherein said immunogen is conjugated to a hapten.
16. The antibody of claim 15 , wherein said hapten is keyhole limpet hemocyanin (KLH).