Using Antibodies to Inhibit Glycoprotein Ib-IX Mediated Platelet Signaling and Clearance for the Treatment of Thrombocytopenia



A therapeutic agent to treat thrombocytopenia, the lack of sufficient platelets which can lead to excessive bleeding.

Key Benefits

  • This molecule modulates platelet signaling without blocking its ligand binding domain. Its mechanism of action targets a different part of the platelet life cycle from currently available therapeutics.
  • RAM.1 is the only molecule in the world that inhibits GPIb-IX-mediated signaling in platelets. Many inhibitors have been developed to target the ligand-binding domain (LBD) of GPIbα. Unlike RAM.1, they inhibit GPIb-IX function by directly blocking VWF binding to the LBD, and they have the potential of causing bleeding and/or thrombocytopenia. In contrast, RAM.1 does not interfere with the hemostatic process in vivo.
  • RAM.1 derivatives do not function by blocking LBD binding, hence do not interfere with primary hemostasis.

Market Summary

Blood platelets play an important role in hemostasis by mediating blood coagulation. Thrombocytopenia is a blood condition resultant from a low platelet count, typically when lower than 2.5ths of the normal platelet count distribution. The condition can be caused by several factors, including but not limited to alcoholism, autoimmune disease, bone marrow disease (aplastic anemia & leukemia), chemotherapy or radiotherapy, along with viruses such as hepatitis C and HIV. Medical attention is typically required when platelet counts drop below 30 × 109/L. Without medical intervention, patients can experience spontaneous bruising, purpura, or continuous bleeding from injuries and wounds. The condition can be managed by treating the underlying cause, but more aggressive options such as blood transfusion, splenectomy, steroids, or immunoglobulin therapy may be considered for severe cases.

Technical Summary

The inhibition of GPIb-IX mediated signaling maybe used in conjunction with other drugs as a treatment for thrombocytopenia. The researchers developed a chimeric protein capable of indirect inhibition of GBIb-IX mediated signaling without interfering with the von Willebrand factor (VWF)-GPIbα interaction. The researchers investigated inhibitory properties of RAM.1-GCN4 in both platelets and CHO cells expressing the GPIb-IX complex and the result was that RAM.1-GCN4 reduced filopodia formation and RAM.1-GCN4 vastly improved the life span of the platelet in IL4R-IbαTg rodent models.

Patent Information

App Type Country Serial No. Patent No. File Date Issued Date Patent Status
PCT PCT PCT/US2022/081232   12/9/2022   Pending
Tech ID: 21153
Published: 5/13/2022