[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