Novel TNF receptor death domain ligand proteins and inhibitors of ligand binding
AssigneeGenetics Institute, Inc.
InventorsLih-Ling Lin, Jennifer Chen, Andrea R. Schievella, James Graham
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Abstract
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.
Claims46
A composition comprising an isolated polynucleotide encoding a protein having TNF-R1-DD ligand protein activity.
A composition comprising a protein having TNF-R1-DD ligand protein activity.
A method of preventing or ameliorating an inflammatory condition which comprises administering to a mammalian subject a therapeutically effective amount of a composition comprising a pharmaceutically acceptable carrier and a protein selected from the group consisting of IGFBP-5 and fragments thereof having TNF-R1-DD ligand protein activity.
A method of inhibiting TNF-R death domain binding comprising administering to a mammalian subject a therapeutically effective amount of a composition comprising a pharmaceutically acceptable carrier and a protein selected from the group consisting of IGFBP-5 and fragments thereof having TNF-R1-DD ligand protein activity.
A composition comprising a pharmaceutically acceptable carrier and a protein selected from the group consisting of IGFBP-5 and fragments thereof having TNF-R1-DD ligand protein activity.
A method of identifying an inhibitor of TNF-R death domain binding which comprises:
- (a) transforming a cell with a first polynucleotide encoding an TNF-R death domain protein, a second polynucleotide encoding an TNF-R1-DD ligand protein, and at least one reporter gene, wherein the expression of the reporter gene is regulated by the binding of the TNF-R1-DD ligand protein encoded by the second polynucleotide to the TNF-R death domain protein encoded by the first polynucleotide;
- (b) growing the cell in the presence of and in the absence of a compound;
- and
- (c) comparing the degree of expression of the reporter gene in the presence of and in the absence of the compound;
- wherein the compound is capable of inhibiting TNF-R death domain binding when a decrease in the degree of expression of the reporter gene occurs.
Dependencies are inferred from the claim text.