Lead Inventor: Jahar Bhattacharya, M.D., Ph.D.


Tech Ventures Reference: IR 2235 / 2710


Problem or Unmet Need:

Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS) are life-threatening lung conditions where fluid fills the air sacs, preventing oxygen from reaching the blood and vital organs. ALI may be caused by aspiration, sepsis, or pneumonia, among other conditions. ALI is fatal for a third of the patients and may result in significant cognitive deficits. Currently, ARDS is managed by treating the underlying cause and providing breathing and fluid support. This technology represents the first protein therapy for directly treating ARDS.



Details of the Invention:

ARDS is characterized by the hyperpermeability of air sacs to fluid. This technology consists of a protein, focal adhesion kinase (FAKp), which prevents the endothelial cells of the lungs from becoming hyperpermeable. When delivered intravenously by a protein carrier, such as Chariot, FAKp is taken up by endothelial cells and has been shown to prevent induced hyperpermeability in mice. FAKp may be fused to a histidine tag which, in turn, may be chelated to a metal. The metal can then be attached to a transport protein.



Applications:

• Treatment of:

o Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS)

o Tumor metastasis in cancer

o Inflammatory diseases such as sepsis, arthritis, hepatitis, arthritis, hyaline membrane disease, and cerebral inflammation

o Pulmonary and cerebral edema

o Neonatal bronchopulmonary dysplasia



Advantages:

• Direct treatment of ARDS

• Can utilize a number of commercially-available transport proteins such as Chariot, perpetratin, and thrombin-antithrombin (TAT) fragment

• FAKp may be fused to a histidine tag which can be linked to a variety of metals including copper, nickel, and zinc

• May be administered through an intravenous, buccal, parenteral, or oral route, or via inhalation



Patent Status: Patent Issued (WO2009046129) ~ see link below.



Licensing Status: Available for Licensing



Publications:
Quadri, S., and Bhattacharya, J. 2007. Resealing of Endothelial Junctions by Focal Adhesion Kinase. Am. J. Physiol. Lung Cell. Mol. Physiol. 292:L334-42.



Safdar, Z., Yiming, M., Grunig, G., and Bhattacharya, J. 2005. Inhibition of Acid-induced Lung Injury by Hyperosmolar Sucrose in Rats. Am. J. Resp. and Crit. Care Med. 172: 1002-1007.



Quadri, S., Bhattacharjee, M., Parthasarathi, K., Tanita, T., and Bhattacharya, J. 2003. Endothelial Barrier Strengthening by Activation of Focal Adhesion Kinase. J. Bio. Chem. 278: 13342-13349.



Safdar, Z., Wang, P., Ichimura, H., Issekutz, A.C., Quadri, S., and Bhattacharya J. 2003. Hyperosmolarity enhances the lung capillary barrier. J. of Clin. Invest.
112(10): 1541-1549.






Other Links:

• WIPO - WO/2009/046129

Further Information
Peter Golikov
Email: TechTransfer@columbia.edu

File Number: 2235