JabI Inhibitor: Bone Forming Small Molecule for Use in Spinal Fusion Devices


Bone forming therapeutic for use in spinal fusion devices and treatment of systemic bone diseases and disorders.

Key Benefits

  • Current devices for bone grafting procedures require high concentrations of bone morphogenetic protein (BMP) which results in a high cost and create a barrier for routine clinical use.
  • Small molecule therapeutics that modulate Jab1 (part of the signaling pathway for BMP) have been identified and could be used locally or systemically to promote bone formation.

Market Summary

Millions of bone grafting procedures are performed worldwide each year. For spinal fusions the bone healing failure rate may be as high as 40%. The iliac crest is often used as a donor site for autologous grafts but there are many complications that can develop from this type of bone graft harvesting including pain, nerve damage, and hematoma. There is also limited supply of iliac bone as well as substantial cost associated with this surgery. Bone morphogenetic proteins (BMP) are being used increasingly in orthopedic surgeries. These small molecules are capable of inducing new bone formation when delivered in the appropriate concentration and on the appropriate scaffold and do not require harvesting bone from remote sites of the patient. The FDA has approved several devices including INFUSETM which is used in spinal surgeries. The high cost and need for high concentrations of BMP create barriers for routine clinical use so there is a need for other compounds that can substitute or complement the use of BMPs.

Technical Summary

Jab1 is a protein that regulates the level of many proteins in the cell by tagging them for ubiquination and proteasomal degradation. In the BMP signaling pathway, Jab1 facilitates the degradation of Smad4. Interruption of Jab1 function should thus result in increased levels of Smad4 and increased responsiveness to BMPs. This inhibition of Jab1 should promote bone and cartilage formation. Through an in silico design and screening process, Emory researchers have identified several lead compounds to perform this function. At present, two lead compounds have shown activity to enhance BMP function in a reporter assay system.

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Patent Information

App Type Country Serial No. Patent No. File Date Issued Date Patent Status
Nationalized PCT - United States United States 13/980,593 11,179,500 7/19/2013 11/23/2021 Issued
Nationalized PCT - Foreign EP 12748998.7 2678052 9/19/2013 9/26/2018 Issued
Divisional United States 17/501,463   10/14/2021   Pending
Tech ID: 11071
Published: 3/27/2012