High-affinity RAGE fusion proteins for treating RAGE-mediated pathologies

This technology is a RAGE (Receptor for Advanced Glycated Endproducts) fusion protein that can be used as an effective therapy for RAGE-mediated diseases by antagonistically binding RAGE ligands with high affinity and specificity.

Unmet Need: Stable and specific downregulation of RAGE-ligand interactions

Increased levels of RAGE and its ligand, Advanced Glycosylation Endproducts (AGE), are associated with a wide breadth of pathologies including cardiovascular disease, coronary artery disease, diabetes, chronic inflammation, nephropathy, arteriosclerosis, retinopathy, and Alzheimer’s Disease. RAGE-AGE ligand binding induces both oxidative stress and inflammation, therefore, antagonists of this interaction are desirable for therapeutically treating RAGE-mediated diseases. Current treatments attempt to reduce binding using soluble RAGE; however, the limited half-life of this drug treatment reduces its practicality as a viable therapeutic option. Furthermore, other pharmacological treatments aim at preventing AGE formation, but there are limited drug therapies that effectively, stably, and safely prevent RAGE activation by blocking RAGE-ligand binding.

The Technology: RAGE fusion protein that effectively reduces RAGE-ligand binding

This technology is a framework for producing RAGE fusion proteins by combining a RAGE polypeptide sequence with a non-RAGE immunoglobulin domain. The ability of these proteins to bind RAGE with high affinity enables effective antagonism of RAGE-ligand interactions, preventing downstream pathologies associated with RAGE activation. These fusion proteins offer an appealing pharmaceutical treatment for reducing RAGE-ligand binding and reducing symptoms of RAGE-mediated diseases.

Applications:

• RAGE-ligand antagonist
• Therapeutic treatment for RAGE-mediated diseases
• Reduces RAGE-ligand interactions
• Potential to reduce oxidative stress and inflammation
• In vivo RAGE binding and reduction of RAGE activation

Advantages:

• Binds RAGE with high affinity and specificity
• Effective reduction of RAGE activation
• Stable drug half-life

Lead Inventor:

Ann Marie Schmidt, M.D.

Patent Information:

Patent Status

Related Publications:

• Zhou B, Rothlein R, Shen J, Valcarce C, Selmer J, Hanhan M, Kindy MS, Mjalli AMM, Kostura. “TTP4000, a soluble fusion protein inhibitor of Receptor for Advanced Glycation End Products (RAGE) is an effective therapy in animal models of Alzheimer’s disease” FASEB. 2013 Apr 1; 27.

• Kislinger T, Fu C, Huber B, Qu W, Taguchi A, Yan SD, Hofmann M, Yan SF, Pischetsrieder M, Stern D, Schmidt AM. “Ne-*(Carboxymethyl)Lysine Adducts of Proteins are ligands for receptor for advanced glycation end products that activate cell signaling pathways and modulate gene expression” The Journal of Biological Chemistry. 1999 Oct 29; 274:31740-31749.

Tech Ventures Reference:

• IR Proxy35

• Licensing Contact: Jerry Kokoshka