NIH Invention Disclosures, Feb. 1996 Federal Register Announcement

National Institutes of Health

Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health

ACTION: Notice

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.

ADDRESS: Licensing information and copies of the U.S. patent
applications listed below may be obtained by writing to the
indicated licensing specialist at the Office of Technology
Transfer, National Institutes of Health, 6011 Executive
Boulevard, Suite 325, Rockville, Maryland 20852-3804 (telephone
301/496-7057; fax 301/402-0220). A signed Confidential
Disclosure Agreement will be required to receive copies of the
patent applications.

Alzheimer's Disease Index (ADI)
Alkon, D.L. (NINDS)
Filed 26 Sep 95
DHHS Reference No. E-092-93/2
Licensing Contact: Stephen Finley, 301/496-7735 ext 215
Under currently available technology, Alzheimer's disease
can only be presumptively diagnosed by pathological examination
of brain tissue during autopsy in conjunction with a clinical
history of dementia. The present invention provides a highly
reliable laboratory method of identifying Alzheimer's disease in
a patient. The method consists of: measuring the presence or
absence of a specific potassium channel, measuring the effect of
potassium channel blockers specific for the 113 pS potassium
channel on intracellular calcium levels, measuring the increase
of intracellular calcium in response to an activator of
intracellular calcium release in the cells of a patient, and
measuring the amount of the G-protein, cp20. An index calculated
on the basis of any two of these four tests identifies
Alzheimers's disease with very high sensitivity and specificity
(n=100, initial sample) in comparisons between Alzheimer's
disease patients and other non-Alzheimer's dementias as well as
age-matched controls. (portfolio: Central Nervous System -
Diagnostics, in vitro, other)

Antipsychotic Composition And Method For Treatment
Pickar, D., Litman, R.E., Potter, W.Z. (NIMH)
Filed 7 Jun 95
Serial No. 08/479,039 (CIP of 07/987,728)
Licensing Contact: Stephen Finley, 301/496-7735 ext 215
This invention comprises a novel treatment method for
patients suffering from serious psychotic mental illness that
offers to significantly improve the treatment of such illnesses.
Conventional antipsychotic drugs are effective in improving
symptoms of schizophrenia, but a significant number of patients
have proven resistant to such treatments. Recently, the drug
clozapine has been found effective in treating such
drug-resistant patients; however, clozapine has severe toxic side
effects. This newly developed treatment method, which combines
the use of an Ó2-adrenergic receptor antagonist with a standard
antipsychotic drug, is effective in treating psychosis without
serious side effects. It is especially effective in patients who
previously had been resistant to treatment with standard
antipsychotic drugs alone. (portfolio: Central Nervous System -
Therapeutics, psychotherapeutics, antipsychotics)

4'- And 4',4"-Substituted-3Ó(diphenylmethoxy)tropane Analogs As
Cocaine Therapeutics
Newman, A.H., Allen, A.C., Kline, R.H., Izenwasser, S.,
Katz, J.L. (NIDA)
Filed 21 Jun 95
Serial No. 60/000,378
Licensing Contact: Leopold J. Luberecki, Jr., 301/496-7735 ext
The invention provides a series of 4'- and 4',4"-substituted
benztropine analogs that demonstrate high affinity binding (K1<30
nM) to the dopamine transporter and bind selectively (>100-fold)
over the other monoamine transporters. These compounds block
dopamine reuptake in vitro and yet do not demonstrate a cocaine-
like behavioral profile in animal models of psychomotor stimulant
abuse. Structure-Activity Relationships suggest that these
compounds interact at a binding domain that differs from that of
cocaine at the dopamine transporter. These compounds represent
an unprecedented class of dopamine uptake inhibitors that may
have potential as cocaine-abuse therapeutics, since they have
neurochemical similarities to cocaine and yet do not appear to
have abuse liability. Further, radiolabeled analogs will be
suitable for imaging the dopamine transporter in mammalian brain
using SPECT and PET and thus would be useful in the diagnoses and
monitoring of neurodegenerative disorders involving the
dopaminergic system (e.g., Parkinson's disease). In addition,
the invention provides pharmaceutical compositions comprising an
analog of the invention and a pharmaceutically acceptable carrier
excipient. (portfolio: Central Nervous System - Therapeutics,
psychotherapeutics, drug dependence; Central Nervous System -
Therapeutics, neurological, antiparkinsonian)

Pteridine Nucleotide Analogs As Fluorescent DNA Probes
Hawkins, M.E., Pfleiderer, W., Davis, M.D., Balis, F.M. (NCI)
Filed 26 May 95
Serial No. 08/451,641 (DIV of 08/245,923)
Licensing Contact: Robert Benson, 301/496-7056 ext 267
The invention concerns a series of pteridine
deoxyribonucleotide analogs which are highly fluorescent and
resemble purine nucleotides in chemical structure and properties.
The phosphoramidite form of these fluorophores can be site-
specifically incorporated into oligonucleotides using
conventional DNA synthesis techniques. The fluorescence
intensity of the pteridine nucleotide analogs is highly dependent
on their physicochemical environment, thus making them ideal for
the study of DNA-protein interactions. A real-time assay for HIV
integrase has been developed using one of the pteridine
nucleotide analogs that resembles guanosine. Other uses foreseen
are as fluorescent labels for DNA probes and PCR primers and for
investigating protein-DNA interactions. The claims include the
phosphoramidite derivatives of the pteridine nucleotide analogs
useful as starting materials for oligonucleotide synthesis and
oligonucleotides incorporating the pteridine nucleotide analogs.
(portfolio: Gene-Based Therapies - Research Tools and Reagents;
Gene-Based Therapies - Diagnostics)

Amino Acid Sequencing Peptides And Methods For Their Use
Parmelee, D.C., Sechi, S. (NCI)
Filed 6 Feb 95
Serial No. 08/384,212 (DIV of 07/920,130)
Licensing Contact: J. Peter Kim, 301/496-7056 ext 264
The present invention provides a novel internal standard for
amino acid sequencing which consist of a peptide containing at
least two different unnatural amino acid residues, such as
ornithine, norvaline, norleucine and Ó-aminobutyric acid. The
PTH-derivatives of these have retention times distinct from those
of natural amino acids. This peptide can be sequenced
simultaneously with an unknown peptide or protein without
interfering with the analysis. Simultaneous sequencing of this
standard provides information which allows for the determination
of repetitive yields, lags, N-terminal blockage and
discrimination between blank cycles caused by missed injection
and blank cycles caused by faulty delivery of chemicals during
the sequencing reactions. (portfolio: Gene-Based Therapies -
Research Tools and Reagents)

Attenuated Human Rotavirus Vaccine
Hoshino, Y., Kapikian, A.Z., and Chanock, R.M. (NIAID)
Filed 11 July 95 (priority to 11 Jul 94)
Serial No. 08/500,564 (CIP of 08/481,644)
Licensing Contact: Robert Benson, 301/496-7056 ext 267
Rotaviruses are recognized as the single most important
etiologic agent of severe diarrhea in both developed and non-
developed countries. This invention embodies an attenuated
rotavirus as a vaccine. The claims of the invention relate to
the generation of a cold-adapted virus that is not efficient in
replication at normal human body temperatures and therefore may
be capable of stimulating an immune response without causing
illness. In a limited clinical trial, administration of a cold-
adapted rotavirus vaccine to 26 adults demonstrated that the
vaccine was safe, attenuated, and was capable of inducing a
virus-specific serologic response. This invention has been PCT
filed on July 11, 1995. (portfolio: Infectious Diseases -
Vaccines, viral, non-AIDS)

Method For Generating Influenza A Viruses Bearing Attenuating
Mutations In Internal Protein Genes
Murphy, B., Subbarao, K.E., Kawaoka, Y. (NIAID)
Filed 7 Jun 95
Serial No. 08/481,631 (CIP of 08/309,521, CIP of 08/123,933)
Licensing Contact: Robert Benson, 301/496-7056 ext 267
This invention describes a method of producing attenuated
Influenza A strains for use as live Influenza A virus vaccine
candidates. This method involves the introduction of three
temperature-sensitive attenuating mutations into the polymerase
basic protein 2 (PB2) gene of the Influenza A virus. These
mutations are introduced by site-directed mutagenesis at specific
sites into a cDNA copy of the PB2 gene. An RNA transcript of
this mutant PB2 gene is recovered into an infectious Influenza A
virus using a host range restricted helper virus. This
attenuating mutant PB2 gene can be transferred to each new
variant of Influenza A virus as it appears in nature. The patent
application covering this invention is available for licensing
and contains claims to: the methods of producing the attenuated
strains; the attenuated strains produced by the methods; and
methods of vaccination using the attenuated strains. Viruses
containing mutant PB2 genes are also available for licensing.
(portfolio: Infectious Diseases - Vaccines, viral, non-AIDS)

Attenuated Influenza A Virus
Palese, P., Muster, T., Murphy, B.R., Enami, M., Bergmann, M.,
Subbaro, E.K., Chanock, R.M. (NIAID)
Filed 7 Jun 95 (priority to 3 Feb 92)
Serial No. 08/480,939 (FWC of 07/938,716)
Licensing Contact: Robert Benson, 301/496-7056 ext 267
This invention describes the development of a novel live
attenuated influenza A virus for use in intranasal vaccines.
This virus is unique in that it is a chimera of two influenza
strains. This results in an attenuated virus capable of invoking
an immune response and therefore protection against influenza.
The claims of this invention cover a method for generating the
attenuated influenza virus, introducing the viral construct into
cell lines, and vaccinating a vertebrate with the attenuated
virus. Animal studies have demonstrated that infection with the
chimeric virus leads to resistance to a challenge with wild-type
virus. (portfolio: Infectious Diseases - Vaccines, viral, non-

Methods For Treating Autoimmune Diseases And Transplantation
Singer, D.S., Kohn, L.D., Mozes, E., Saji, M. (NCI)
Serial No. 08/503,525 filed 21 Aug 95 (CIP of 08/480,525) and
Serial No. 08/464,130 filed 7 Jun 95 (DIV of 08/073,830)
Licensing Contact: Carol Lavrich, 301/496-7735 ext 287
Methods for treating autoimmune diseases in mammals and for
preventing or treating transplantation rejection in a transplant
recipient are described in this invention. The invention relates
to methods for treating and preventing these diseases, using
drugs capable of suppressing expression of the major
histocompatability complex (MHC) Class I molecules. The
invention further includes method for in vivo and in vitro
assays, for the development and assessment of drugs capable of
suppressing expression of MHC Class I molecules. Furthermore,
the invention provides a method for preventing rejection of cells
containing a recombinant gene transplanted into a mammal in need
of a gene therapy. (portfolio: Internal Medicine - Therapeutics,

Methods For Treating Autoimmune Diseases And Transplantation
Singer, D.S., Kohn, L.D., Mozes, E., Saji, M. (NCI)
Filed 7 Jun 95
Serial No. 08/480,525 (FWC of 08/073,830)
Licensing Contact: Carol Lavrich, 301/496-7735 ext 287
Methods for treating autoimmune diseases by suppressing the
expression of the major histocompatibility complex (MHC) class I
molecules by administering either methimazole, methimazole
derivatives, carbimazole, propylthiouracil, thionamides,
thiourelylenes, thioureas, and thiourea derivatives. These
compounds can be used to treat diseases such as rheumatoid
arthritis, psoriasis, juvenile diabetes, primary idiopathic
myxedema, myasthenia gravis, scleroderma, De Quervains
thyroiditis, systemic lupus erythematosus dermatomyositis,
polyarteritis nodosa, and polymyositis. This invention also
provides the means for inhibiting transplantation rejection in
humans. Also provided are in vivo and in vitro means for
assessing and developing drugs capable of suppressing the MHC
class I molecules. (portfolio: Internal Medicine - Therapeutics,

Heparin- And Sulfatide-Binding Peptides From The Type I Repeats
Of Human Thrombospondin
Roberts, D.D., Browning, P.J., Bryant, J., Inman, J.K.,
Krutzsch, H.C., Guo, N. (NCI)
Filed 21 Mar 94
Serial No. 08/215,085 (CIP of 07/801,812, U.S. Patent 5,357,041
issued 18 Oct 94)
Licensing Contact: Carol Lavrich, 301/496-7735 ext 287
This invention describes a new family of related peptides
that bind with high affinity to heparin or to heparin sulfate
proteoglycans and inhibit specific functions of these molecules.
The peptides thus are antagonists of basic fibroblast growth
factor. Some of the peptides contain a second sequence that
mediates activation of transforming growth factor-■. Stable
analogs of these peptides have been prepared that resist
proteolysis and retain activity in vivo. The ability of these
peptides to modulate tumor growth and angiogenesis has been
demonstrated, and suggest that they might be useful as cancer
therapeutic agents. Furthermore, the peptides may be useful for
promoting adhesion to substrates coated with the peptides. The
novel compounds, which are derived from the adhesive protein
thrombospondin, have binding constants 10 to 100 times greater
than those of currently available inhibitors; in addition, the
heparin-binding sequence does not require an ionic charge, thus
making them suitable for pharmaceutical preparations. It is
expected that the high potency of these agents will lower the
effective dose needed, and, subsequently, will reduce the
immunological response against the peptides and the risks of
toxicity. (portfolio: Internal Medicine - Therapeutics, anti-

Peptide Derivatives Of Cytochrome b558 And Their Use As
Medicaments [As Anti-Inflammatory Agents]
Malech, H., Rotrosen, D. (NIAID)
Filed 24 May 90
Serial No. 07/527,767 (CIP of 07/331,652)
Licensing Contact: Carol Lavrich, 301/496-7735 ext 287
A new anti-inflammatory agent based on two c-terminal amino
acid sequences of cytochrome b558 has been shown to inhibit the
production of toxic oxygen products (superoxide, peroxide) by
human phagocytic cells. Because of its specificity for
phagocytic cells, it is expected that these peptide derivatives
would not have the side effects of other anti-inflammatory agents
in general use. (portfolio: Internal Medicine - Therapeutics,

Mutants Having a Deficit of Functional Steroid Hormone Receptors
Korach, K.S. (NIEHS)
Filed 7 Jun 95
Serial Number 08/480,854
Licensing Contact: Carol Lavrich, 301/496-7735 ext 287
This invention concerns ■knockout■ animals, including mice,
which have a deficit of functional steroid hormone receptors, DNA
constructs containing the mutations, and methods for producing
the animals. The mutation is introduced into the animal or its
ancestors at an embryonic stage. These knockout animals provide
a model system for studying the biological role of hormones,
including steroid hormones and sex steroids, in growth,
development, morphological differentiation, and sexual and
reproductive behavior and cycles, etc. More specifically, the
animals may serve as models for testing sex hormones and
synthetics that mimic or antagonize sex hormones for use in birth
control methods or as hormone replacement therapies. In
addition, they provide a system for the characterization of
materials suspected of precipitating or conferring protection
against osteoporosis, cardiovascular disease, breast cancer,
endometrial cancer, and other cancers. (portfolio: Internal
Medicine - Miscellaneous)

Nitroxides As Protectors Against Oxidative Stress
Mitchell, J.B., Samui, A., DeGraff, W., Hahn, S. (NCI)
Filed 7 Jun 95
Serial No. 08/473,960 (CIP of 07/859,622, U.S. Patent 5,462,946
issued 31 Oct 95; CON of 07/494,532)
Licensing Contact: Carol Lavrich, 301/496-7735 ext 287
New metal-independent nitroxide compounds are antioxidants
capable of protecting cells, tissues, and organs against the
harmful effects of toxic oxygen-related species (hydroxyl
radical, hydrogen peroxide, superoxide). These toxic oxygen-
related species have been implicated in tissue damage from
ionizing radiation, reperfusion injury, adult respiratory
distress syndrome, inflammation, and agents involved in such
processes as carcinogenesis and aging. These mimetic agents have
several advantages over natural antioxidants such as superoxide
dismutase in that they can exert protection inside the cell since
they are small and uncharged. Additionally, long-term
administration of these agents to animals induces weight
reduction without untoward effects. (portfolio: Internal
Medicine - Miscellaneous)