[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