Targeting Alternative N-terminal Kinases

Background:

Bruton’s tyrosine kinase (BTK) plays an active role in the development, maturation, and signaling of B cells. BTK regulates cell proliferation, survival, and migration in various B-cell malignancies, such as Burkitt lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and others. Several therapeutics that target BTK have been approved by the Food and Drug Administration for the treatment of several hematological malignancies. Development of BTK-based therapies has transformed the treatment of several B-cell malignancies. One isoform of BTK, BTK-C, is uniquely expressed in a wide variety of epithelial tumor types where it impacts apoptosis resistance, therapeutic escape, and glucose uptake.

Technology Overview:

This technology is based on the fact that BTK-C differs from other BTK isoforms in that it is expressed in solid tumors, has a unique mRNA, and is palmitoylated (undergoes covalent attachment of fatty acids) on two cysteine residues. Palmitoylation affects localization and regulation of BTK-C in epithelial tumor cells where it functions as an important survival factor. Nine other soluble kinases possess similar alternative N-termini (ANT) encoding palmitoylated isoforms. Tumors that do not express BTK-C have higher levels of ERBB2, the estrogen receptor, and the androgen receptor among others. This may mean that targeting BTK-C with inhibitors could be used in tumors that do not respond to inhibitors of other proteins.

Advantages:

•    Can treat tumors that do not respond to inhibitors of other proteins.
•    May be applicable to a number of different tumor types.

Intellectual Property Summary:

Issued patents:
•    US 8,513,212 B2, “Bruton's tyrosine kinase as anti-cancer drug target,” issued August 20, 2013
•    US 9,095,592 B2, “Bruton's tyrosine kinase as anti-cancer drug target,” issued August 4, 2015 
•    US 9,637,554 B2, “Bruton's tyrosine kinase as anti-cancer drug target,” issued May 2, 2017
•    U.S. Provisional Filing 63/345,605, Filed 5/22/22.

Stage of Development:

TRL 3 - Experimental proof of concept

Licensing Status:

This technology is available for licensing.

Licensing Potential:

This technology would be of interest to anyone involved in the development of cancer therapeutics, including:
•    Pharmaceutical companies.
•    Hospitals.
•    Medical research laboratories.
•    Universities and other educational facilities.