Text of NIH Invention Disclosures, released July 19, 1996 for publication in the Federal Register


Novel Epidermal Growth Factor Receptor (ErbB-3) And Antibodies


Description of Invention:
ErbB-3 is a member of the type I family of growth factor receptors. ErbB-3 is
a 148 kd transmembrane polypeptide which has between 64-67% homology to
contiguous regions within the tyrosine kinase domains of the EGFR and erbB-2
proteins, respectively. ErbB-3 has been mapped to human chromosome 12 ql
11-13 and has been shown to be expressed as a 6.2 kb transcript in a variety
of normal tissues of epithelial origin. Markedly elevated erbB-3 MRNA levels
have been demonstrated in certain human mammary tumor cell lines. These
findings suggest that increased erbB-3 expression may play a role in
oncogenesis.

U.S. Patent 5,183,884 includes claims to the cDNA encoding erbB-3, vectors
containing the cDNA and cells transformed with the vector containing the cDNA
encoding erbB-3. The DNA can be used in diagnostic applications or for
production of the protein.

U.S. Patent 5,480,968 includes claims to the erbB-3 protein and antibodies to
erbB-3. Such antibodies include both monoclonal and polyclonal antibodies.
The antibodies may be labeled allowing for detection of erbB-3, or conjugated
with a cytotoxic agent for use as a therapeutic.

The divisional applications, 08/473,119 and 08/475,352, include claims to DNA
and antibody based diagnostic methods, drug screening assays, therapeutic
applications utilizing antibody conjugates or ligands which block the binding
of an activating ligand to erbB-3; activating or blocking ligands which bind
to erbB-3.

Inventors:
M Kraus, SA Aaronson (NCI)

Patent Status:
Serial No. 07/444,406 filed 04 Dec 89, which issued as U.S. Patent No.
5,183,884 on 02 Feb 93; and
Serial No. 07/978,895 filed 10 Nov 92, which issued as U.S. Patent No.
5,480,968 on 02 Jan 96; and
Serial No. 08/473,119 filed 07 Jun 95; and
Serial No. 08/475,352 filed 07 Jun 95

Portfolios:
Cancer - Diagnostics, in vitro, MAb based
Cancer - Diagnostics, in vivo, MAb
Cancer - Therapeutics, immunoconjugates, MAb
Cancer - Research Reagents

For additional information, please contact:
Susan Rucker, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7056 ext 245
Fax: 301/402-0220
Peptide Antagonist Of Keratinocyte Growth Factor Activity


Description of Invention:
A novel peptide antagonist of the keratinocyte growth factor (KGF) activity
has been isolated that may prove to be an effective treatment for diseases in
which activation of the KGF receptor plays a role. Growth factors are
important mediators of intercellular communication. These molecules are
generally released by one cell type and influence proliferation of other cell
types. Interest in growth factors has been heightened by evidence of their
involvement in neoplasia. In addition, a number of oncogenes are homologs of
genes encoding growth factor receptors, and their receptor-mediated signal
transduction pathways provide insights into mechanisms of both normal and
malignant cell growth. The fibroblast growth factor family affects the growth
of a wide variety of cells including connective tissue cells. KGF is a member
of this family, but is unique in that its activity is restricted to cells of
epithelial origin. Since a vast majority of human malignancies are derived
from epithelial tissues, identification of compounds that modulate the effect
of KGF may be important in the treatment of carcinomas as well as other
conditions in which ligand-dependent proliferation, mediated by the KGF
receptor, contributes to the pathologic disorder. These novel peptides
effectively inhibit binding between KGF and its epithelial cell receptor and,
thus, are useful in treating carcinomas and other conditions involving
epithelial cell proliferation.

Inventors:
D Bottaro, JS Rubin, SA Aaronson (NCI)

Patent Status:
Serial No. 08/059,030 filed 04 May 93

Portfolio:
Cancer - Therapeutics, biological response modifiers, growth factors

For additional information, please contact:
Susan Rucker, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7056 ext 245
Fax: 301/402-0220


Expression Cloning Of A Human Phosphatase


Description of Invention:
The identification of genes has traditionally been accomplished through the
use of nucleic acid hybridization. In general, highly conserved sequences or
DNA structures which are associated with a particular function or gene family
are used in hybridization techniques in order to discover other related genes
and associated polypeptide products. This is accomplished by construction of
nucleic acid probes corresponding to those conserved DNA sequences of
interest. The present invention involves "expression cloning," and provides
an alternative method of isolating genes of interest by using the expression
of the polypeptide corresponding to that gene as a means of screening clones
containing the gene. The invention describes methods of detecting clones
containing the functional polypeptide either directly, or through
immunological methods. The invention further describes a new dual specificity
protein tyrosine phosphatase, called VHR, discovered using this method. This
phosphatase is structurally unrelated to other commonly known enzymes with
similar function and provides support for the invention's utility. The
invention also describes methods for treatment of VHR related disease. This
invention is ideally suited for use in the isolation of previously unknown
genes with similar functions of interest. The invention allows isolation of
fewer false positive clones because DNA sequences with areas of high
structural homology but dissimilar function, will not be identified. The
invention, in contrast, favors the isolation of clones which are structurally
disparate, yet functionally equivalent.

Inventors:
SA Aaronson, DP Bottaro, T Ishibashi, T Miki (NCI)

Patent Status:
Serial No. 07/988,273 filed 14 Dec 92; U.S. Patent No. 5,512,434 issued
30 Apr 96
WO 94/13796, PCT/US93/12019

Portfolios:
Gene Based Therapies - Diagnostics
Gene-Based Therapies - Research Tools and Reagents
Devices/Instrumentation - Diagnostics, physical medicine
Devices/Instrumentation - Research Tools, methods
Devices/Instrumentation - Biologicals and Chemicals

For additional information, please contact:
Susan Rucker, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7056 ext 245
Fax: 301/402-0220


The Many Roles Of Adrenomedulin In Human Pathology And Physiology


Description of Invention:
Adrenomedullin (AM) is an Ó-amidated 52-amino acid peptide that shows slight
similarity to calcitonin gene-related peptide (CGRP). The effects of AM and
its fragments in the cardiovascular system have been widely studied.
Endothelial cells secrete the peptide that acts on specific receptors present
in the vascular smooth muscle cells and other contractile cells. Some diuretic
functions have been also described. In the respiratory system, two major
roles have been described to date: relaxation of the vascular bed and
bronchodilation.

The present invention provides methods for the prevention and treatment of
cancers, in particular, lung, colon, ovarian, and breast cancers by inhibiting
the growth of the cancerous cells with an effective amount of anti-AM
monoclonal antibody. This invention provides methods for diagnosing or
monitoring diseases by measuring the levels of AM in a sample. Examples of
diseases include, diabetes, renal diseases, such as severe uremia; bone
diseases, such as neoplastic disease; and skin diseases. The present
invention also provides a method of preventing or treating type II diabetes
using the anti-AM monoclonal antibody. AM peptides and antibodies can also be
utilized for diagnosis and treatment of preeclampsia and to promote fetal
growth.

The present invention provides a method of regulating activity in areas of the
central nervous system by administering to a subject an effective amount of AM
peptides or antibodies for the regulation of neurotransmission or neuron
growth. i.e. Alzheimer's disease. Administering antibodies to AM can inhibit
the degranulation of mast cells and provide a method of lessening or
inhibiting the allergic response due to the degranulation of mast cells. AM
peptides have also been found to inhibit bacterial or fungal growth and
facilitate the healing of chaffed skin, skin lesions, wound repair, and
surgical incisions. AM peptides promote organ and bone development.

Inventor:
FF Cuttitta (NCI)

Patent Status:
DHHS Reference No. E-206-95/0 filed 18 Aug 95 and
DHHS Reference No. E-206-95/1 filed 30 Aug 95

Portfolios:
Cancer - Therapeutics
Central Nervous System - Therapeutics
Infectious Diseases - Therapeutics
Internal Medicine - Therapeutics

For additional information, please contact:
Susan Rucker, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7056 ext 245
Fax: 301/402-0220


Inhibition Of Retroviral LTR Promoters
By Calcium Response Modifiers


Description of Invention:
The pathogenesis of HIV infection can be divided into two phases based upon
the activity of the HIV virus. The latent phase is characterized by low
transcriptional activity and/or low replication frequency of the virus whereas
the lytic phase is characterized by high transcriptional activity and/or high
replication frequency. Although the mechanism(s) involved in the switch from
the latent to lytic phase is not completely understood, inhibition of the
viral LTR promoter is an important strategy in AIDS treatment. The invention
concerns the use of the compound carboxyamidotriazole (CAI), a calcium
response modifier, and structurally related compounds that are capable of
preventing the activation of the LTR promoter in the treatment of HIV
infection and AIDS. In addition, CAI has antimetastatic properties and
currently is being tested in clinical trials for the treatment of cancer. A
further advantage is that CAI has shown no severe side effects during these
trials. Therefore treatment of AIDS patients with CAI would also allow for
the treatment of related cancers such as Kaposi's sarcoma.

Inventors:
EC Kohn, LA Liotta, KL Gardner (NCI)

Patent Status:
Serial No. 08/353,765 filed 12 Dec 94

Portfolio:
Infectious Diseases - Therapeutics, anti-virals, AIDS

For additional information, please contact:
Cindy K. Fuchs, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 232
Fax: 301/402-0220


Diastereoselective Process Leading To A Key Intermediate For The Preparation
Of Fluorinated Reverse Transcriptase Inhibitors


Description of Invention:
A novel process has been developed for synthesizing a key intermediate in the
preparation of fluorinated reverse transcriptase inhibitors. Recently,
several fluorinated dideoxynucleotides have been found to be effective
inhibitors of reverse transcriptase and, thus, offer promise for replacing or
augmenting current drugs for the treatment of HIV-1 infection; however,
chemically synthesizing these fluorinated dideoxynucleotides is quite
expensive, making it economically difficult to produce large-scale amounts for
testing. This new process allows the synthesis of a key intermediate in the
production of fluorinated dideoxynucleotides at much lower costs because the
reaction is diastereoselective, meaning that there are fewer side reactions
and more primary product is produced.

Inventors:
VE Marquez, JS Driscoll, MA Siddiqui (NCI)

Patent Status:
Serial No. 08/189,095 filed 31 Jan 94, which issued as U.S. Patent No.
5,498,719 on 12 Mar 96

Portfolio:
Infectious Diseases - Therapeutics, anti-virals, AIDS

For additional information, please contact:
Cindy K. Fuchs, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 232
Fax: 301/402-0220


C-C Chemokines That Inhibit Retrovirus Infection


Description of Invention:
This invention concerns three members of the human C-C chemokine family,
RANTES, macrophage inflammatory protein 1Ó (MIP-1Ó) and macrophage
inflammatory protein 1■ (MIP-1■), which are produced and secreted by several
cell types, including CD8-positive T lymphocytes, and which act in vitro as
HIV suppressive factors. These factors and their respective genes may be used
in the diagnosis, prognosis, treatment and prevention of AIDS and other
retrovirus-induced diseases. The invention provides a therapeutic
preparation, methods for therapeutic and prophylactic treatment of retroviral
infection, and a method of prognosis for retroviral infection. The technology
was reported in BioWorld Today 6(234):1 (December 7, 1995) and Science
270(8):1560-1561 (December 8, 1995).

Inventors:
P Lusso, R Gallo, F Cocchi, A De Vico, A Garzino-Demo (NCI)

Patent Status:
DHHS Reference No. E-008-96/0 filed 30 Nov 95

Portfolios:
Infectious Diseases - Therapeutics, anti-virals, AIDS
Infectious Diseases - Diagnostics, viral, AIDS

For additional information, please contact:
Cindy K. Fuchs, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 232
Fax: 301/402-0220


Methods Of Treating Established Colitis
Using Antibodies Against IL-12


Description of Invention:
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 Crohn'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.

Potential Areas of Application:
Gastrointestinal disorders -- treatment of inflammatory bowel diseases
including Crohn's disease and ulcerative colitis

Main Advantages of Invention:
Anti IL-12 inhibits the primary underlying mechanism of granulomatous
inflammation rather than the secondary (downstream) mediators of inflammation.
Thus, it is a more effective, more permanent therapy for such inflammation.

Stage of Development:
Positive preliminary studies in mice with induced colitis
Positive preliminary studies in mice with spontaneous colitis

Further Development Required:
Production of humanized anti IL-12 antibodies
Toxicity/pharmacology studies

Recent Relevant Publication:
MS Neurath, I Fuss, BL Kelsall, E Stuber, W Strober: Antibodies to interleukin
12 abrogate established experimental colitis in mice. J Exp Med 182:1281-90,
1995

Inventors:
W Strober, M Neurath, I Fuss (NIAID)

Patent Status:
Serial No. 08/547,979 filed 25 Oct 95
PCT filed 29 Mar 96

Licensing Status:
Available for exclusive or non-exclusive licensing

Portfolios:
Internal Medicine - Diagnostics, anti-inflammatory
Internal Medicine - Therapeutics, anti-inflammatory
Internal Medicine - Miscellaneous

For additional information, please contact:
Jaconda Wagner, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 284
Fax: 301/402-0220


Truncated Hepatocyte Growth Factor Variants


Description of Invention:
[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.

Inventors:
AML Chan, JS Rubin, DP Bottaro, SA Aaronson, SJ Stahl, PT Wingfield, V Cioce
(NCI)

Patent Status:
Serial No. 08/484,841 filed 07 Jun 95 (CIP of 08/130,134, which is CIP of
07/655,502)

Portfolios:
Cancer - Therapeutics, biological response modifiers, growth factors
Cancer - Diagnostics

For additional information, please contact:
Jaconda Wagner, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 284
Fax: 301/402-0220


IL-13 Receptor Specific Chimeric Proteins And Uses Thereof


Description of Invention:
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 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 effector
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.

Inventors:
R Puri (FDA), W Debinski (Penn State), I Pastan (NCI), N Obiri (FDA)

Patent Status:
Serial No. 08/404,685 filed 15 Mar 95

Portfolios:
Cancer - Diagnostics, in vivo, conjugate chemistry
Cancer - Therapeutics, immunoconjugates, toxins
Cancer - Therapeutics, immunomodulators and immunostimulants

For additional information, please contact:
Jaconda Wagner, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 284
Fax: 301/402-0220


Janus Family Kinases (JAK) And Identification
Of Immune Modulators


Description of Invention:
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 domains, 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.

Inventors:
JJ O'Shea, WJ Leonard, JA Johnston, SM Russell, D McVicar, M Kawamura (NCI)

Patent Status:
Serial No. 08/373,934 filed 13 Jan 95

Portfolios:
Cancer - Research Reagents
Cancer - Diagnostics

For additional information, please contact:
Jaconda Wagner, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 284
Fax: 301/402-0220


Pigment Epithelium Derived Factor:
Characterization Of Its Novel Biological Activity
And Sequences Encoding And Expressing The Protein


Description of Invention:
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).

Inventors:
GJ Chader, SP Becerra, JP Schwartz, T Taniwaki (NEI)

Patent Status:
Serial No. 08/257,963 filed 07 Jun 94 (CIP of 07/952,796)

Portfolios:
Ophthalmology - Diagnostics
Ophthalmology - Therapeutics, biological
Ophthalmology - Miscellaneous

For additional information, please contact:
Jaconda Wagner, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 284
Fax: 301/402-0220


T Cell Receptor Ligands, And Methods For Use


Description of Invention:
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, 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.

Inventors:
RN Germain, L Racioppi (NIAID)

Patent Status:
Serial No. 08/004,936 filed 15 Jan 93

Portfolio:
Cancer - Therapeutics, immunomodulators and immunostimulants

For additional information, please contact:
Jaconda Wagner, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 284
Fax: 301/402-0220


Macrophage Stimulating Protein

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.

Inventors:
EJ Leonard, AH Skeel, T Yoshimura, E Appella, S Showalter, S Tanaka (NCI)

Patent Status:
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; U.S. Patent No. 5,527,685 issued 18
Jun 96 (DIV of 07/586,085)

Portfolios:
Internal Medicine - Diagnostics
Internal Medicine - Therapeutics
Internal Medicine - Miscellaneous

For additional information, please contact:
Jaconda Wagner, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 284
Fax: 301/402-0220


75 Kilodalton Interleukin-2 Receptor Proteins And Their Use


Description of Invention:
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 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 associated with
conventional immunosuppressants.

Inventor:
KA Smith

Patent Status:
Serial No. 06/944,337 filed 19 Dec 86; U.S. Patent 5,352,772 issued 04 Oct 94

Portfolios:
Internal Medicine - Miscellaneous
Internal Medicine - Diagnostics, anti-inflammatory
Internal Medicine - Therapeutics, anti-inflammatory

For additional information, please contact:
Jaconda Wagner, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 284
Fax: 301/402-0220


Soluble Interleukin-2 Receptor As A Disease Indicator
And A Method Of Assaying The Same



Description of Invention:
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.

Inventors:
D Nelson, W Biddison, L Rubin, W Greene, W Leonard, R Yarchoan (NCI)

Patent Status:
Serial No. 06/724,897 filed 19 Apr 85; U.S. Patent No. 4,707,443 issued 17 Nov
87

Portfolios:
Internal Medicine - Diagnostics, anti-inflammatory
Internal Medicine - Therapeutics, anti-inflammatory
Cancer - Diagnostics
Cancer - Therapeutics, biological response modifiers

For additional information, please contact:
Jaconda Wagner, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 284
Fax: 301/402-0220


Enhanced Stem Cell Engraftment Using Cytokines


Description of Invention:
The invention relates to 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 opens 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.

Inventors:
M Mardiney III, HL Malech (NIAID)

Patent Status:
Serial No. 60/001,386 filed 21 Jul 95

Portfolio:
Cancer - Therapeutics, biological response modifiers, growth factors
Infectious Diseases - Miscellaneous
Internal Medicine - Miscellaneous

For additional information, please contact:
Jaconda Wagner, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 284
Fax: 301/402-0220


Depigmenting Activity Of Agouti Signal Protein
And Peptides Thereof


Description of Invention:
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.

Inventor:
VJ Hearing (NCI)

Patent Status:
DHHS Reference No. E-165-95/0 filed 23 Jun 95

Portfolio:
Internal Medicine - Therapeutics, skin disorders, other

For additional information, please contact:
Jaconda Wagner, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 284
Fax: 301/402-0220


Selective Elimination Of T-Cells That Recognize
Specific Preselected Targets


Description of Invention:
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.

Inventor:
A Rosenberg (FDA)

Patent Status:
DHHS Reference No. E-116-95/0 filed 30 Aug 95

Portfolios:
Internal Medicine - Miscellaneous
Internal Medicine - Therapeutics, anti-inflammatory

For additional information, please contact:
Jaconda Wagner, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 284
Fax: 301/402-0220