[Federal Register Volume 60, Number 139 (Thursday, July 20, 1995)]
[Notices]
[Pages 37456-37458]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-17780]



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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 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 

[[Page 37457]]
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] 

[[Page 37458]]


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]

    Dated: July 6, 1995.
Barbara M. McGarey,
Deputy Director, Office of Technology Transfer.
[FR Doc. 95-17780 Filed 7-19-95; 8:45 am]
BILLING CODE 4140-01-P