RAGE fusion proteins and methods of use
OwnerAdnan Mjalli, David Stern +3inventors
InventorsAdnan Mjalli, David Stern, Ye Tian, Jeffrey Webster, Robert Rothlein
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Abstract
Disclosed are RAGE fusion proteins comprising RAGE polypeptide sequences linked to a second, non-RAGE polypeptide. The RAGE fusion protein may utilize a RAGE polypeptide domain comprising a RAGE ligand binding site and an interdomain linker directly linked to an immunoglobulin CH2 domain. Such fusion proteins may provide specific, high affinity binding to RAGE ligands. Also disclosed is the use of the RAGE fusion proteins as therapeutics for RAGE-mediated pathologies.
Claims58
A fusion protein comprising a RAGE polypeptide linked to a second, non-RAGE polypeptide wherein the RAGE polypeptide comprises a RAGE ligand binding site.
An isolated nucleic acid sequence encoding a RAGE polypeptide linked to a second, non-RAGE polypeptide wherein the RAGE polypeptide comprises a RAGE ligand binding site.
A composition comprising a therapeutically effective amount of a RAGE fusion protein in a pharmaceutically acceptable carrier, wherein the RAGE fusion protein comprises a RAGE polypeptide linked to a second, non-RAGE polypeptide wherein the RAGE polypeptide comprises a RAGE ligand binding site.
A method of making a RAGE fusion protein comprising the step of covalently linking a RAGE polypeptide linked to a second, non-RAGE polypeptide wherein the RAGE polypeptide comprises a RAGE ligand binding site.
A method for the detection of RAGE modulators comprising:
- (a) providing a fusion protein comprising a RAGE polypeptide comprising a RAGE ligand binding site linked to a second, non-RAGE polypeptide;
- (b) mixing a compound of interest and a ligand having a known binding affinity for RAGE with the fusion protein;
- and (c) measuring binding of the known RAGE ligand to the RAGE fusion protein in the presence of the compound of interest.
A kit for the detection of RAGE modulators comprising:
- (a) compound having known binding affinity to RAGE as a positive control;
- (b) a RAGE fusion protein comprising a RAGE polypeptide comprising a RAGE ligand binding site linked to a second, non-RAGE polypeptide;
- and (c) instructions for use.
A method of treating a RAGE-mediated disorder in a subject comprising administering to a subject a polypeptide comprising a RAGE polypeptide comprising a RAGE ligand binding site linked to a second, non-RAGE polypeptide.
Dependencies are inferred from the claim text.