[Federal Register Volume 61, Number 145 (Friday, July 26, 1996)]
[Notices]
[Pages 39142-39144]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-18970]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Government-Owned Inventions; Availability for Licensing
AGENCY: National Institutes of Health, HHS.
ACTION: Notice.
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The inventions listed below are owned by agencies of the U.S.
Government and are available for licensing in the U.S. in accordance
with 35 U.S.C. 207 to achieve expeditious commercialization of results
of federally funded research and development. Foreign patent
applications are filed on selected inventions to extend market coverage
for U.S. companies and may also be available for licensing.
ADDRESSES: Licensing information and copies of the U.S. patent
applications listed below may be obtained by contacting Jaconda Wagner,
J.D., at the Office of Technology Transfer, National Institutes of
Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-
3804; telephone: 301/496-7735 ext 284; fax: 301/402-0220). A signed
Confidential Disclosure Agreement will be required to receive copies of
the patent applications.
Methods of Treating Established Colitis Using Antibodies Against
IL-12
W Strober, M Neurath, I Fuss (NIAID)
Filed 25 Oct 95
Serial No. 08/547,979
Interleukin-12 (IL-12) is a recently characterized cytokine with
unique structure and pleiotropic effects. IL-12 is produced mainly by
macrophages/monocytes and can be efficiently induced by intracellular
parasites, bacteria and bacterial products. A method for treating the
established colitis of an inflammatory bowel disease, including Cohn's
disease and ulcerative colitis, by inhibiting the colitis-inducing
effects of the cytokine IL-12 has been invented. Additionally, a method
for treating their effectiveness in reducing the inflammatory response
is also presented. (portfolio: Internal Medicine--Diagnostics, anti-
inflammatory; Internal Medicine--Therapeutics, anti-inflammatory;
Internal Medicine--Miscellaneous)
Truncated Hepatocyte Growth Factor Variants
AML Chan, JS Rubin, DP Bottaro, SA Aaronson, SJ Stahl,
PT Wingfield, V Cioce (NCI)
Filed 07 Jun 95
Serial No. 08/484,841 (CIP of 08/130,134, which is CIP of 07/655,502)
[HGF/NK2], a truncated form of a hepatocyte growth factor (HGF),
may offer an improved method of diagnosing and treating proliferative
disorders such as cancers. Elevated levels of HGF are associated with
both cancerous and noncancerous conditions. This truncated form of HGF
is an antagonist of HGF and can be used to effectively counteract its
effects on cells. Its cDNA can also be used as a probe to detect
increased levels of HGF mRNA in cells.
HGF/NK1, another truncated form of HGF, has partial agonist/
antagonist properties. Thus, it may be useful either as an antagonist
of an HGF or as an agonist to reinforce the action of endogenous growth
factor, depending on the circumstances. A technique has been developed
to produce large quantities of biologically active HGF/NK1 and HGF/NK2
using a prokaryotic expression system. (portfolio: Cancer--
Therapeutics, biological response modifiers, growth factors; Cancer--
Diagnostics)
IL-13 Receptor Specific Chimeric Proteins and Uses Thereof
R Puri (FDA), W Debinski (Penn State), I Pastan (NCI), N Obiri (FDA)
Filed 15 Mar 95
Serial No. 08/404,685
A chimeric molecule that binds specifically to IL-13 receptors has
been identified. The molecule, IL13-PE38QQR, targets tumor cells with
less binding to healthy cells in comparison
[[Page 39143]]
to other chimeric molecules. The improved specific targeting of this
molecule is premised upon the discovery that tumor cells overexpress
IL-13 receptors at extremely high levels. This phenomena permits the
use of lower dosages of chimeric molecules to deliver effecter
molecules to targeted tumor cells.
This invention will be useful in the treatment of cancer. The
targeting method could be used in conjunction with current methods,
e.g., chemotherapy to help maintain the healthy cells. To date, the
molecule has been shown to be effective against a variety of solid
tumor cancers, including adenocarcinoma, colon cancer, breast cancer,
ovarian cancer, kidney cancer, brain cancer and AIDS associated
Kaposi's sarcoma. (portfolio: Cancer--Diagnostics, in vivo, conjugate
chemistry; Cancer--Therapeutics, immunoconjugates, toxins; Cancer--
Therapeutics, immunomodulators and immunostimulants)
Janus Family Kinases (JAK) and Identification of Immune Modulators
JJ O'Shea, WJ Leonard, JA Johnston, SM Russell, D McVicar, M Kawamura
(NCI)
Filed 13 Jan 95
Serial No. 08/373,934
This invention relates to an isolated polynucleotide encoding the
JAK-3 protein. JAK-3 is a protein tyrosine kinase having a molecular
weight of approximately 125 kDa and tandem non-identical catalytic
domians, lacks SH2 or SH3 domains, and is expressed in NK cells and
stimulated or transformed T cells, but not in resting T cells. The JAK-
3 protein itself, antibodies to this protein, and methods of
identifying therapeutic agents for modulating the immune system which
make use of the foregoing. (portfolio: Cancer--Research Reagents;
Cancer--Diagnostics)
Pigment Epithelium Derived Factor: Characterization of its Novel
Biological Activity and Sequences Encoding and Expressing the Protein
GJ Chader, SP Becerra, JP Schwartz, T Taniwaki (NEI)
Filed 07 Jun 94
Serial No. 08/257,963 (CIP of 07/952,796)
Pigment epithelium-derived factor (PEDF), which is also known as
pigment epithelium differentiation factor and is a neurotrophic,
neuron-survival and gliastatic protein, has been produced using
recombinant DNA techniques. The invention concerns nucleic acids
encoding PEDF and functional fragments thereof, vectors comprising the
nucleic acids, host cells containing the vectors, a recombinant method
for producing PEDF and equivalent proteins, antibodies (monoclonal and
polyclonal) to PEDF, and an immunoassay for PEDF. This technology has
potential therapeutic use in the treatment of inflammatory, vascular,
degenerative, and dystrophic diseases of the retina and central nervous
system (CNS). (portfolio: Ophthalmology--Diagnostics; Ophthalmology--
Therapeutics, biological; Ophthalmology--Miscellaneous)
T Cell Receptor Ligands, And Methods For Use
RN Germain, L Racioppi (NIAID)
Filed 15 Jan 93
Serial No. 08/004,936
T lymphocytes are key cellular elements of the immune system. The
growth, effector functions (cytokine secretion, cytotoxicity), and
survival of these cells are regulated by signals arising from the
interaction of ligands consisting of polypeptide-MHC molecule complexes
with specific receptors (TCR) on the cell membrane. All antigen-
specific attempts at modulation of T-cell dependent immunity involve
this key TCR-ligand interaction. This application describes a novel
class of TCR ligands (called variant TCR ligands, a sometimes referred
to in the scientific literature as altered peptide ligands) with
selective antagonist or mixed agonist-antagonist properties that can
modulate the function of T cells in unique ways. For example, these
compounds can induce T lymphocyte unresponsiveness while preventing T
cell effector activity or can permit secretion of some cytokines while
inhibiting the secretion of others typically produced upon exposure to
the normal stimulatory ligand of the TCR in question. These effects can
thus modulate in vivo immune responses by inactivating T cells or by
changing the effector response of such cells from a damaging to a
benign pattern. These properties should be extremely useful in the
development of antigen-specific immunotherapies for various autoimmune
diseases, including but not limited to diabetes, rheumatoid arthritis,
and multiple sclerosis. These compounds could also be useful in
modifying responses to tumor antigens, to vaccine components, or tissue
transplants. Because these novel immunomodulatory compounds are
produced by slight alteration of the normal peptide-MHC molecule ligand
for the TCR, it is believed that all current attempts to modify such
diseases using as antigen either species variants or synthetic variants
rather than native, unmodified human self-antigens involve materials
whose properties and mode of action fall within the scope of this
patent application. (portfolio: Cancer--Therapeutics, immunomodulators
and immunostimulants)
Macrophage Stimulating Protein
EJ Leonard, AH Skeel, T Yoshimura, E Appella, S Showalter, S Tanaka
(NCI)
Serial No. 07/586,085 filed 21 Sep 90
U.S. Patent No. 5,219,991 issued 15 Jun 93 and
Serial No. 08/076,880 filed 6/15/93 (DIV of 07/586,085)
U.S. Patent No. 5,527,685 issued 18 Jun 96
Macrophage stimulating protein (MSP), a relative of the hepatocyte
growth factor (HGF), is a component of human and animal (mammalian)
blood plasma which accelerates the movement and increases the activity
of macrophages. Macrophages, when activated, can kill foreign
microorganisms and tumor cells.
This invention describes the preparation of highly purified MSP and
the production of antibodies to the purified MSP. These methods
overcome the primary problem with natural MSP, i.e., that its
concentration in the plasma is too low for purification by conventional
techniques and for use as an effective therapeutic agent. The highly
purified MSP and/or its antibodies can be used as a diagnostic and
therapeutic agent and a basic research tool for diseases characterized
by macrophage-mediated inflammation. The invention also describes a
bioassay for the detection of antibodies to that bind MSP. (portfolio:
Internal Medicine--Diagnostics; Internal Medicine--Therapeutics;
Internal Medicine--Miscellaneous)
75 Kilodalton Interleukin-2 Receptor Proteins and Their Use
KA Smith
Serial No. 06/944,337 filed 19 Dec 86
U.S. Patent 5,352,772 issued 04 Oct 94
A cellular protein produced by activated T cells and involved in
high affinity binding of interleukin-2 has been discovered. The protein
is substantially unreactive with anti-Tac antibodies and is believed to
interact with the previous 55,000 dilaton receptor protein to form high
affinity interleukin-2 receptor which triggers the growth and mitosis
of T cells during an immune response. Methods for isolating and
purifying the protein and raising monoclonal antibodies to the proteins
[[Page 39144]]
are included as well as techniques for cloning and expressing the
protein in related materials.
T cells play a central role in the induction and regulation of the
immune response. Thus, the structure of IL-2 receptors and their
relationship to T cell growth and proliferation is on considerable
scientific and clinical importance. The present technology could be
used in the development of T cell antagonists compounds which could be
to treat a wide range of autoimmune diseases, such as rheumatoid
arthritis and other T cell-driven inflammatory diseases. The technology
could also be used to develop immunosuppressants, which could be useful
in combating tissue and organ graft rejection in kidney, liver, heart
and other transplants and so-called ``graft versus host'' disease in
bone marrow transplants without the side effect associate with
conventional immunosuppressants. (portfolio: Internal Medicine--
Miscellaneous; Internal Medicine--Diagnostics, anti-inflammatory;
Internal Medicine--Therapeutics, anti-inflammatory)
Soluble Interleukin-2 Receptor as a Disease Indicator and a Method of
Assaying the Same
D Nelson, W Biddison, L Rubin, W Greene, W Leonard, R Yarchoan (NCI)
Serial No. 06/724,897 filed 19 Apr 85
U.S. Patent No. 4,707,443 issued 17 Nov 87
Soluble IL-2 receptor is produced in response to immune activation
and by some malignant cells. For instance, elevated levels of IL-2 have
been detected in patients with adult T-cell leukemia, Sezary syndrome,
Hodgkin's disease, chronic lymphocytic leukemia, multiple myeloma, and
solid tumors. The systemic level of IL-2 receptor is also relevant in
the diagnosis and treatment of such diseases as rheumatoid arthritis
and systemic lupus erythematosis and may be used to titrate
immunosuppressive therapy in such applications as graft rejection.
The invention disclosed in the patent is a sandwich immunoassay
useful for determining the amount of IL-2 receptor in a sample. The
invention also discloses a method of detecting such disturbed or
abnormal conditions in humans which release soluble IL-2 receptor in
bodily fluids. (portfolio: Internal Medicine--Diagnostics, anti-
inflammatory; Internal Medicine--Therapeutics, anti-inflammatory;
Cancer--Diagnostics; Cancer--Therapeutics, biological response
modifiers)
Enhanced Stem Cell Engraftment Using Cytokines
M. Mardiney III, HL Malech (NIAID)
Filed 21 Jul 95
Serial No. 60/001,386
The invention relates to be a method for establishing high levels
of chimerism of transplanted hematopoietic stem cells in humans to
treat disease, more particularly, to accomplish this with a significant
reduction in the level of recipient conditioning prior to
transplantation. This technology can be used to achieve successful
engraftment in individuals who must undergo bone marrow
transplantation.
The practice of bone marrow transplantation or peripheral blood
stem cell transplantation involves placing a suspension of allogeneic
or autologous hematopoietic pluripotent cells into the blood stream of
the recipient. Successful engraftment of these cells requires
conditioning of the recipient prior to transplantation. This is
accomplished by subjecting the recipient to systemic radiation, or
chemotherapy, or a combination of radiation and chemotherapy. This
treatment kills bone marrow cells, including stem cells, and open
spaces for transplanted stem cells to engraft. However, current
conditioning regimens used to ensure successful engraftment are
associated with immune deficiency, multi-organ toxicity, secondary
malignancies, and increased risk of death.
The current invention provides a method for successful
transplantation by enhancing radiation or chemotherapy potentiated
engraftment at doses which are much smaller than those used in current
practice. The mechanism of this process relates, in part, to the
ability of cytokines to upregulate receptors necessary for homing of
transplanted hematopoietic stem cells. Thus, successful transplantation
can be performed with minimal conditioning-related morbidity.
(portfolio: Cancer--Therapeutics, biological response modifiers, growth
factors; Infectious Diseases--Miscellaneous; Internal Medicine--
Miscellaneous)
Depigmenting Activity of Agouti Signal Protein and Peptides Thereof
VJ Hearing (NCIA)
Filed 23 Jun 95
DHHS Reference No. E-165-95/0
Pigmentation is controlled at many levels in mammals. One important
regulatory protein known to be physiologically active is the Agouti
signal protein (ASP), which has depigmenting activity. This invention
provides biologically active peptides of ASP and a method of using ASP
and its peptides to inhibit melanin synthesis by down regulating the
melanogenic enzymes involved in melanin synthesis. Using a method also
provided in this invention, ASP and its peptides can be used to treat
hyperpigmentary conditions, such as melasma photoaging spots, solar
keratosis, and hyperpigmentation at wound healing sites. ASP and its
peptides are also useful for cosmetic purposes. These compounds may
potentially be used for other therapeutics in the prevention or
treatment of damaged skin. The invention also gives a pharmaceutical
composition of ASP or its peptides and a screening method for ASP
peptides. Issuance of a patent for this invention is currently pending.
(portfolio: Internal Medicine--Therapeutics, skin disorders, other)
Selective Elimination of T-Cells That Recognize Specific
Preselected Targets
A Rosenberg (FDA)
Filed 30 Aug 95
DHHS Reference No. E-116-95/0
The invention relates to methods and compositions for the
elimination of T cells that recognize specific preselected targets
which can be used to treat autoimmune diseases and graft rejection.
The invention provides a method for selectively inhibiting or
killing T cells that recognize a specific preselected target molecule
and also for modified killer cells that bear a signal transduction
molecule to which is attached the preselected target molecule.
Recognition of the preselected molecule by a T-cell activates the
killer cell which then kills or inhibits the T cell. Where the
preselected molecule is an extracellular domain of an MHC from a
xenograft or an allograft, treatment of the graft recipient with the
modified killer T-cells delays or inhibits graft rejection. Similarly,
where the preselected molecule is an MHC that binds the antigenic
determinant of the autoimmune disease, treatment of the organism with
the modified T-cells mitigates the autoimmune response directed against
that antigenic determinant. (portfolio: Internal Medicine--
Miscellaneous; Internal Medicine--Therapeutics, anti-inflammatory)
Dated: July 16, 1996.
Barbara M. McGarey,
Deputy Director, Office of Technology Transfer.
[FR Doc. 96-18970 Filed 7-25-96; 8:45 am]
BILLING CODE 4140-01-M
