Federal Register announcement, July 21, 1995, from the Office of Technology Transfer, NIH

National Institutes of Health

Prospective Grant of Exclusive License: Delta-Like Gene
Expressed in Neuroendocrine Tumors

Agency: National Institutes of Health, Public Health Service,

Action: Notice

Summary: This is 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 Application 07/989,537 and
corresponding foreign patent applications entitled, "Delta-Like
Gene Expressed in Neuroendocrine Tumors" to ImClone Systems
Incorporated of New York, NY. The patent rights 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 present patent application covers a novel gene, delta-like,
dlk and its corresponding protein. The protein contains EGF-like
repeats and a transmembrane domain and appears to be a novel
member of the family of EGF-like neurogenic genes. Such genes
were initially found in Drosophila and are involved in embryonic
developmental decisions to differentiate into epidermal or
neuronal cells. One of these genes in Drosophila is termed,
"Delta", hence the name of the current gene. dlk can be employed
in genetic assays for detection of a primary or secondary
pheochromocytoma, neuroblastoma, and small cell lung cancer or
identification of a stage of these tumors.

Although dlk may have utility as a cancer marker, recent research
indicates another important application of this technology, as a
hematopoietic stem cell growth factor. The adult bone marrow is
the site of hematopoiesis with an estimated 0.01% of the cells
being stromal cells. It is thought that the stem cells are found
in micro-environments associated with stromal cells which produce
factor(s) which allows the maintenance and self-renewal of the
stem cells. One or more stromal cell produced factor(s) may be
required to keep the stem cells in an uncommitted state. When
stem cells leave this micro-environment they would no longer be
in contact with this factor(s) and, consequently, they would
differentiate toward one of the hematopoietic cell lineages.

Delta is a 43 kDa protein which belongs to the epidermal growth
factor-like superfamily. Delta was cloned by another group from
a mouse stromal cell line PA-6, a cell line which has been
reported to support the growth of hematopoietic stem cells.
Delta may function as a ligand by binding to the extracellular
domain of a Drosophila protein called Notch. Notch encodes a
transmembrane protein with a large extracellular domain, is
widely expressed including by hematopoietic cells, and its
activation may keep cells in an uncommitted state.

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 September 19, 1995 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.
Published in the Federal Register on Friday, July 21, 1995 [60 FR