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Technology Transfer Program
Please Note: The technology listed below is not available to the public at this time. This technology is in the early stage of research and requires further development before it is ready for the marketplace. The VA is currently in the process of identifying potential companies who may be interested in licensing and/or further developing the technology through Cooperative Research and Development Agreements (CRADA). Through cooperative research initiatives such as these, it is our hope and goal that commercial products will be fully developed and made available to benefit veterans and others.
VA TECHNOLOGY OPPORTUNITY BRIEF
Chronic Lymphocytic Leukemia Treatment
OPPORTUNITY:
The Department of Veterans Affairs (VA) has developed a method of use for NOS1 inhibitors for promotion of chronic lymphocytic leukemia (CLL) cell apoptosis and treatment of CLL. The VA is seeking a commercial partner to further develop this technology through a Cooperative Research & Development Agreement (CRADA).
BACKGROUND:
CLL is a malignancy characterized by the buildup of white blood cells (lymphocytes) in the bone marrow, blood, lymph tissue and other organs. Because they have longer than normal life spans, these cells eventually crowd out and limit the generation of healthy blood cells, and this condition can become fatal. While the cause of CLL is unknown, the accumulation of lymphocytes in the blood is due more to a decreased rate of normal cell death (apoptosis) than to an increased rate of cell production by the bone marrow. CLL is the most common form of leukemia in men, and the second most common form in women. Although various drugs are available for the treatment of CLL and its complications, there is no specific curative treatment.
TECHNOLOGY OVERVIEW:
Nitric oxide (NO), a highly reactive gas that serves as a control mechanism for many processes in living organisms, is made in cells by the enzyme nitric oxide synthase (NOS). Both NO and NOS have been implicated in certain cancers and leukemias in the control of cell proliferation, sensitivity to chemotherapeutic agents, and apoptosis. Research shows that in CLL cells, NO appears to protect leukemic cells from apoptosis in response to a variety of stimuli.
There are three different known NOS isoforms that catalyze the formation of NO. NOS1 and NOS3 are expressed constitutively, but NOS2 is increased by factors such as cytokines that induce NOS2 gene transcription. NOS1 and NOS3 usually produce relatively low levels of NO important for regulation of cellular function, while NOS2 produces higher levels of NO that may mediate inflammation and tissue injury.
TECHNICAL MERIT:
The inventors have discovered a very important feature of CLL with therapeutic implications. NOS1 (rather than NOS2) may be the most important NOS isoenzyme involved in the suppression of apoptosis in CLL cells. The inventors discovered that CLL cells have an excess of NOS1 that prevents the cells from dying in the usual way. The inventors found that NOS1 inhibitors appeared to be more potent inducers of apoptosis in the CLL cells than were either the non-specific NOS inhibitors or the NOS2-specific inhibitors. Treatment with NOS1 inhibitors also appears to cause the malignant cells to die more rapidly and at lower treatment doses than does treatment with inhibitors of NOS2 and NOS3 or with inhibitors that affect all three types of NOS. Strategies designed to inhibit CLL cell nitric oxide synthases and NO production may be effective for the treatment of CLL.
POTENTIAL APPLICATION:
The commercial application for this technology is CLL chemotherapy, most likely in combination with other agents.
PATENT STATUS:
A U.S. provisional patent application was filed on November 10, 2003 (60/518,304).
Federal register: April 19, 2004 (Vol. 69, Number 75) p. 20965.
US application was filed on November 9, 2004 (10/983,978).
CIP application (of 10/983,978) was filed on Dec 29, 2008 (12/318,349)
FOR MORE INFORMATION CONTACT:
Saleem Sheredos
Program Manager
Technology Transfer Program
Veterans Affairs
Office of Research & Development (12TT)
5th Floor
103 South Gay Street
Baltimore, MD 21202
202-380-5080
Fax 410.962.2141
e-mail: saleem.sheredos@va.gov
Last Updated - June 22, 2009