mAbs Inhibit Human RAGE by Blocking Its Binding to Heparan Sulfate

Monoclonal antibodies that block heparan sulfate binding to human RAGE, preventing its activation in disease states to serve as a therapeutic treatment.

Background:

Receptor for Advanced Glycation End products (RAGE), a widely expressed inflammatory receptor for disease states such as atherosclerosis, cancer, Alzheimer disease, drug-induced liver injury and sepsis.  The blocking of RAGE activation is highly effective in reducing the severity of these diseases in murine models.  Heparan sulfate (HS), a universal cell surface glycosaminoglycan expressed in all mammalian cells, has been established as the origin of the RAGE signaling cascade.  Blocking the interaction of HS and RAGE inhibits RAGE signaling and provides a therapeutic mechanism for diseases.

Technology Overview:

This University at Buffalo invention describes three new murine mAbs that display high affinity to human RAGE (0.1 to 0.3 nM) and bind to different sections of the HS-binding site of RAGE.  These antibodies block RAGE signaling in an innovative fashion that lends itself to more efficient therapeutic use than traditional RAGE blockers.
Source: Juan Gärtner

Advantages:

  • Noncompetitive binding of RAGE by HS
  • High affinity to human RAGE from a murine model
  • Blocking of HS and RAGE interaction differently than other commercial blockers

Applications:

  • Therapeutic treatment for disease states such as atherosclerosis, cancer, Alzheimer disease, drug-induced liver injury and sepsis
  • Research tool for cell signaling studies

Intellectual Property Summary

US Provisional Patent Application 63/610,259 filed on December 14, 2023.

Stage of Development:

Laboratory demonstration through in vitro studies and analytical chemical analysis.

Licensing Status:

Available for licensing or collaboration.

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