Text of a Federal Register released by the Office of Technology Transfer, NIH, on July 10, 1995.

DEPARTMENT OF HEALTH AND HUMAN SERVICES
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 Mr. Arthur J. Cohn, J.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 284; fax 301/402-0220). A signed
Confidential Disclosure Agreement will be required to receive copies of the
patent applications.

Ultraselective Opioidmimetic Peptides and Pharmacological and Therapeutic Uses
Thereof
Lazarus, L.H., Salvadori, S., Temussi, P.A. (NIEHS)
Filed 30 Nov 94
Serial No. 08/347,531
Opioids and opioid receptors mediate a variety of effects in mammalian
physiology including the production of analgesia, modification of the
secretion of circulating peptide hormones, alteration of body temperature,
depression of respiration, gastrointestinal function, and immune system
activities. Opioids also have a wide range of therapeutic utilities, such as
treatment of opiate and alcohol abuse, neurological diseases, neuropeptide or
neurotransmitter imbalances, neurological and immune system dysfunctions,
graft refections, pain control, shock and brain injuries. Various subclasses
of opioid receptors are implicated in any particular physiological function or
disease process. Accordingly, it would be desirable to have opioid drugs that
exhibit specificity for one subclass of the receptor so as to avoid
undesirable side effects during a therapeutic regimen. This invention
provides novel opioidmimetic dipeptides, tripeptides and cyclic peptides which
exhibit ultraselective specificity and potency for the opiate receptor.
Additionally, methods of inducing analgesia and treating drug and alcohol
addiction are provided. [portfolio: Central Nervous System - Therapeutics]

A Method Of Identifying CFTR-Binding Compounds Useful For Activating Chloride
Conductance In Animal Cells
Pollard, H.B., Jacobson, K.B. (NIDDK)
Filed 22 Nov 94
Serial No. 08/343,714 (CIP of 07/952,965 issued as U.S. Patent 5,366,977)
Cystic fibrosis is the most common fatal genetic disease of Caucasians
in the world today. The life expectancy of those affected with the disease is
approximately 28 years. Cystic fibrosis affects some 30,000 children and
young adults in the United States and approximately 24,000 children and young
adults in Europe. Cystic fibrosis is caused by mutations in the cystic
fibrosis transmembrane regulator (CFTR) gene. Chloride (Cl-) and sodium
transport across epithelial membranes of an individual afflicted with cystic
fibrosis is abnormal. Many of the present efforts to combat the disease have
focused on drugs that are capable of either activating the mutant CFTR gene
product or otherwise causing additional secretion of Cl- from affected cells.
Antagonism of the A1 adenosine receptor has been shown to result in
stimulating Cl- efflux from cystic fibrosis cells. Many of the drugs
currently in use or under development function by antagonizing the A1
adenosine receptor but lack specificity for the receptor and, thus, produce
undesirable side effects. Likewise, antagonism of A1 adenosine receptors
probably will have an additional impact on an animal that is unrelated to the
cystic fibrosis affliction. The present invention provides compositions and
methods of identifying compositions that overcome these disadvantages, as well
as methods of treating cystic fibrosis. The compounds provided activate
impaired Cl- conductance channels and exhibit high potency, low toxicity, and
little or no specificity for adenosine receptors. [portfolio: Internal
Medicine - Therapeutics, pulmonary]

Inhibiting Cell Proliferation By Inhibiting Mitogenic Activity Of Macrophage
Migration Inhibitor Factor
Wistow, G.J., Paralkar, V. (NEI)
Filed 16 Nov 94
Serial No. 08/340,826
The control of cell growth is of interest in the understanding of normal
physiological activity and pathological conditions such as cancer. Certain
mechanisms of cell proliferation in cancer appear to mimic the growth-factor-
induced mitogenic pathway. Peptide growth factors act by binding to receptors
on the cell surface and inducing gene expression. This invention demonstrates
that one of the genes induced by growth factors, macrophage migration
inhibitory factor (MIF), is involved in cell proliferation and that inhibiting
MIF expression in turn inhibits both peptide-growth-factor-induced and
transformed cell proliferation. The invention provides methods for inhibiting
cell growth by inhibiting the mitogenic activity of MIF in the cell. Such
inhibition can be performed through providing the cell with a nucleic acid
that inhibits MIF expression or through inhibiting MIF activity by hindering
the binding of MIF to retinoblastoma protein. The invention also provides
pharmaceutical compositions having an agent that inhibits the mitogenic
activity of MIF in a cell and a pharmaceutically acceptable carrier. This
invention would provide a means to inhibit growth factors in cancer cells in
vivo and thereby prevent their proliferation. The inhibition of MIF activity
in vitro is useful to investigate the sequence of events comprising the cell
cycle. Issuance of a patent on this invention is currently pending.
[portfolio: Gene-Based Therapies - Therapeutics, oligonucleotide-based
therapies, antisense, sequences]

Cell Tests For Alzheimer's Disease
Alkon, D., Etcheberrigaray, R., Kim, C., Han, Y., Nelson, T. (NINDS)
Filed 26 Sep 94
Serial No. 08/312,202 (CIP of 08/056,456)
Alzheimer's disease represents the fourth leading cause of death in the
United States, killing over 100,000 annually, and afflicting some 4 million
Americans. Various reports indicate that the incidence of Alzheimer's disease
increases with age and estimate that the prevalence of Alzheimer's disease in
people over 80 years of age is between 20 and 50%. 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 utilizes newly discovered
differences between cells from healthy donors and those with Alzheimer's
disease. In particular, differences in the levels of a memory associated GTP-
binding protein between cells from health donors and Alzheimer's patients are
assessed by immunoassay. Thus, the invention provides a quick and reliable
test for assessing whether a patient is suffering from Alzheimer's disease.
[portfolio: Central Nervous System - Diagnostics, in vitro, other]

Allelic Variation Of The Serotonin 5HT2C Receptor
Lappalainen, J., Linnoila, M., Goldman, D. (NIAAA)
Filed 21 Sep 94
Serial No. 08/310,271
An allelic variation of the serotonin 5HT2C receptor that is
functionally different from the predominant wild-type receptor. One
embodiment of this discovery relates to isolated DNA encoding that serotonin
5HT2C receptor wherein the DNA encodes a serine at amino acid position 23 of
the receptor. The isolated DNA may, for example, be provided in a recombinant
vector. Preferably the isolated DNA has the nucleic acid sequence of SEQ ID
NO:1.
This invention may make it possible to find biochemical and genetic
variables that predict vulnerability to psychiatric disorders, including
antisocial personality, and therefore predict these behaviors and also
facilitate implementation of preventative and therapeutic measures. The
patent application is pending, and the technology is available through a non-
exclusive license. [portfolio: Central Nervous System - Research Tools and
Reagents, receptors and cell lines]

Sulfo Derivatives Of Adenosine
Jacobson, K., Maillard, M.C. (NIDDK)
Filed 21 Jul 94
Serial No. 08/278,704 (FWC of 07/914,428)
A newly-developed, novel class of adenosine compounds are valuable for
the prevention or treatment of injuries related to oxygen deprivation, or
ischemia. Adenosine has numerous physiologic roles in the body including
increasing tissue oxygen supply. Certain compounds that bind to adenosine
receptors in the body have been found to protect against ischemia-induced
tissue injury. Previously, however, adenosine agonists that have been tested
for treating or preventing such injuries have caused serious behavioral
effects, making them too risky for use in humans. This new class of adenosine
agonist are sulfo derivatives of adenosine and do not effectively cross the
blood-brain barrier. Thus, they can be used effectively as adenosine agonists
-- especially in preventing ischemia-induced tissue damage -- without the
toxic side effects.

Stannylated 3-Quinuclidinyl Benzilates And Methods For Preparing *AQNB
Lee, K.S., He, X-S, Weinberger, D.R. (NIMH)
Filed 19 Apr 94
Serial No. 08/229,837
A unique method for synthesizing tomographic imaging agents has been
developed that offers to significantly improve the use of tomographic imaging
in studying the brain and other parts of the nervous system. Muscarinic
cholinergic receptors (mAChrs) play a vital role in a number of psychological
and behavioral responses including sleep, avoidance behavior, learning, and
memory. Single-photon emission-computed tomography (SPECT) has emerged as a
leading diagnostic tool for diagnosing and researching mAChr activity. At
present, the potential of SPECT imaging of muscarinic receptors as a
diagnostic and analytical tool has not been fully attained, primarily due to
the high cost and difficulty of preparing the tomographic imaging agent *IQNB.
This invention overcomes such limitations by halogenating, particularly
iodinating, stannylated 3-quinuclidinyl benzilate compounds, which converts
them to *AQNB (wherein *A is a halogen). The halogenation of stannylated 3-
quinuclidinyl benzilates proceeds in as little as five minutes compared to up
to an hour with previous methods. In addition, radiolabeling with this method
produces yields of *AQNB as high as 80 percent. [portfolio: Central Nervous
System - Research Tools and Reagents; Central Nervous System - Diagnostics]

Method Of Adenovirus-Mediated Cell Transfection
Seth, P., Crystal, R.G., Rosenfeld, M., Yoshimura, K., Jessee, J.A. (NHLBI)
Filed 4 Feb 94
Serial No. 08/191,669
Development of an efficient and less toxic method for adenovirus-
mediated cell transfection offers to significantly improve efforts at
correcting genetic disorders and other diseases through gene augmentation
therapy. Adenoviruses are useful as a vector for gene therapy, since they do
not require the host cell proliferation that is necessary to employ retroviral
vectors. In addition, adenoviral vectors have low recombination event
frequencies. Adenovirus exhibits tropism for the respiratory epithelium, and
can infect almost every human tissue including lung, gastrointestinal, liver,
brain, salivary glands, kidney, and other tissues. Therefore, adenoviruses
are a useful tool in somatic gene therapy of many inheritable and metabolic
diseases, particularly those of the lung and gastrointestinal tract. Present
approaches for using adenovirus for transfer of nucleic acids are limited in
that the specific receptor to the ligand employed (e.g., transferrin) must be
present on the cell surface for transfection to be accomplished.
Additionally, it was recently discovered that better transfection results are
obtained when the DNA is not physically attached to any molecule upon
introduction into the cell. This invention overcomes such limitations by
incubating the DNA to be transfected with a cationic agent or polycationic
liposome and contacting the target cell with the nucleic acids in the presence
of adenovirus. Because the nucleic acid(s) is not bound to any molecule
capable of effecting its entry into the cell, the transfection is more
efficient. Furthermore, no specific ligand need be present for transfection
to occur. Issuance of a patent on this invention is currently pending.
[portfolio: Gene-Based Therapies - Therapeutics; Gene-Based Therapies -
Research Tools and Reagents]

Diagnosing Alzheimer's Disease And Schizophrenia
Merril, C., Johnson, G., Ghanbari, H. (NIMH)
Filed 17 Jun 92
Serial No. 07/904,045
Alzheimer's disease represents the fourth leading cause of death in the
United States, killing over 100,000 annually, and afflicting some 4 million
Americans. Various reports indicate that the incidence of Alzheimer's disease
increases with age and estimate that the prevalence of Alzheimer's disease in
people over 80 years of age is between 20 and 50%. Schizophrenia occurs in
approximately 1.5% of adults. Over 2.5 million people in the U.S. and nearly
47 million people worldwide suffer from schizophrenia. 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. In the diagnosis of schizophrenia, the
clinician is limited to aberrations of behavior. Although there has
previously been no generally accepted laboratory markers for either of these
two diseases of the central nervous system it has been discovered that
production of certain proteins is increased in acute phase reactions
associated with these disorders. The present invention provides methods of
diagnosing Alzheimer's disease and schizophrenia by detecting elevated levels
of such proteins in a biological sample from a patient either by immunoassay
or 2D-gel electrophoresis. [portfolio: Central Nervous System -
Diagnostics]