[Federal Register Volume 61, Number 180 (Monday, September 16, 1996)]
[Notices]
[Pages 48714-48715]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-23633]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

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.

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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 
val-es 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,

[[Page 48715]]

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 enginerred 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.

ADDRESSES: 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 recieve 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 licneses. Only written comments and/or 
applications for a license which are received by NIH on or before 
November 15, 1996 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.

    Dated: September 6, 1996.
Barbara M. McGarey,
Deputy Director, Office of Technology Transfer.
[FR Doc. 96-23633 Filed 9-13-96; 8:45 am]
BILLING CODE 4140-01-M