Immunotoxins License to Sandoz

Released on September 6, 1996 for publication in the Federal Register
National Institutes of Health

Prospective Grant of Exclusive License: Immunotoxins With In-Vivo T Cell Suppressant Activity And Methods Of Use and Immunotoxins

AGENCY: National Institutes of Health, Public Health Service, DHHS

ACTION: Notice

SUMMARY: This notice in accordance with 35 U.S.C. 209(c)(1) and 37 CFR 404.7(a) (1) (I) that the National Institutes of Health (NIH), Department of Health and Human Services, is contemplating the grant of an exclusive world-wide license to practice the inventions embodied in U.S. Patent Number 5,167,956, and entitled; "Immunotoxins With In-Vivo T Cell Suppressant Activity And Methods of Use," Patent Applications USSN 08/308,730, 60/008,104 and 60/015,459, and corresponding U.S. and foreign patent applications, all entitled; "Immunotoxins With In-Vivo T Cell Suppressant Activity And Methods Of Use" and U.S. Patent Number 5,208,021, and entitled; "Immunotoxins" and corresponding foreign patent applications to Sandoz Pharma Ltd., Basel, Switzerland. The patent rights for NIH inventors in these inventions have been assigned to the United States of America.

The prospective exclusive license will be royalty-bearing and will comply with the terms and conditions of 35 U.S.C. 209 and 37 CFR 404.7. The prospective exclusive license may be granted unless within sixty (60) days from the date of this published notice, NIH receives written evidence and argument that establishes that the grant of the license would not be consistent with the requirements of 35 U.S.C. 209 and 37 CFR 404.7.

The field of use for this prospective exclusive license may be limited to "Induction of Tolerance to Transplanted Organs." The field of use for this prospective exclusive license for U.S. Patent Number 5,208,021 will exclude, at a minimum, fields of use of, "for therapeutic treatment of all cancers" and "for therapeutic treatment of all muscle diseases and disorders."

A major goal in transplant immunobiology is the development of specific immunologic tolerance to organ transplants. This therapy holds the potential of freeing patients from the side effects of continuous pharmacologic immunosuppression and its attendant complications and costs. Dr. David Neville's laboratory at the National Institute for Mental Health, NIH has developed immunotoxins (IT) targeted to the pan-T cell marker CD3 (anti-CD3-IT) and demonstrated that it has a profound immunosuppressive effect on human and rhesus T cells in vivo. A collaboration with Dr. Stewart Knechtle's laboratory (University of Wisconsin, Madison) has shown that a 3-day administration of anti-CD3-IT in rhesus monkeys can transiently deplete T cells to <1% of initial values in both the blood and lymph node compartments. Donor lymphocytes were injected intrathymically in some animals. All monkeys with T cell depletion had prolonged allograft survival. Tolerance was confirmed by skin grafting in 5 of 6 long-surviving recipients (>150 days). No other drug or treatment regimen has come close to achieving these results. In a collaboration with Dr. Judith Thomas' laboratory (University of Alabama, Birmingham), a lower dose of anti-CD3-IT given 15 hours before transplant with other conditioning agents (donor bone marrow or total lymphoid irradiation), markedly prolongs the lifetime of mismatched renal allografts and has lead to stable tolerance in some recipients. These studies suggest that the anti-CD3 immunotoxin can induce allospecific CTL hyporesponsiveness in rhesus kidney allograft recipients and this treatment has potential for inducing tolerance to allografts in humans.

Another application of this technology is in the treatment of autoimmune diseases. Dr. Neville's laboratory has demonstrated that anti-CD3-IT treatment moderates the course of an experimental T cell driven autoimmune disease (myelin basic protein induced experimental allergic encephalomyelitis or EAE) in rhesus monkeys. EAE in non-treated control monkeys progressed rapidly and paralysis occurred 4-6 days after induction. In monkeys treated with anti-CD3-IT at induction, paralysis was either delayed or never occurred. These results have been achieved with a chemically-coupled reagent. Development of a molecularly engineered anti-CD3-IT is ongoing. Anti-CD3 immunotoxin may be useful in treating T cell driven autoimmune diseases such as rheumatoid arthritis and multiple sclerosis.

ADDRESS: Requests for copies of the patent applications, inquiries, comments and other materials relating to the contemplated licenses should be directed to: Raphe Kantor, Ph.D., Technology Licensing Specialist, Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; Telephone: (301) 496-7735 ext. 247; Facsimile: (301) 402-0220. A signed Confidentiality Agreement will be required to receive copies of the patent applications. Applications for a license in the field of use filed in response to this notice will be treated as objections to the grant of the contemplated licenses. Only written comments and/or applications for a license which are received by NIH on or before [Federal Register - insert date 60 days from date of notice] will be considered. Comments and objections submitted to this notice will not be made available for public inspection and, to the extent permitted by law, will not be released under the Freedom of Information Act, 5 U.S.C. 552.