[Federal Register Volume 65, Number 154 (Wednesday, August 9, 2000)]
[Notices]
[Pages 48722-48724]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-20037]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, DHHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: 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 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 the indicated 
licensing contact 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.

Mouse Strain Deficient for the Protein MT1-MMP (MMP14)

Kenn Holmbeck et al. (NIDCR)
DHHS Reference No. E-191-00/0
Licensing Contact: Marlene Shinn; 301/496-7056 ext. 285; e-
mail:[email protected]

    Matrix metalloproteinases (MMPs) constitute a family of zinc 
endopeptidases that are capable of degrading most of the structural 
components of the extracellular matrix. The NIH announces a new mouse 
model deficient in MT1-MMP activity. This mouse model demonstrates the 
necessity of MT1-MMP for normal development of cranial bones, long 
bones and general housekeeping of connective tissues throughout the 
body. Since studies in the pharmaceutical industry are currently aiming 
at inhibiting the MMP family at large for purposes of cancer and 
arthritis treatment, this mouse model provides a valuable demonstration 
of the possible side effects that such treatment may lead to. As such 
this mouse model may also provide a test bed for the substances that 
can alleviate the unwanted side effects of MMP inhibitor treatments.

HIV Protease Inhibitors, Ritonavir and Saquinavir Are Potent 
Inhibitors of Calcium Activated Neutral Peptidases, Calpains

Paolo DePetrillo, Wenshuai Wan (NIAAA)
DHHS Reference Number E-041-00/0 filed 04 May 2000
Licensing Contact: John Rambosek, Ph.D.; 301/496-7056 ext. 270; e-mail: 
[email protected]

    This invention discloses a novel use for compounds that are 
inhibitors of the HIV Protease: specifically, the invention shows that 
HIV protease inhibitors are also potent inhibitors of Calcium Activated 
Neutral Proteases (Calpain). Activation of calpain plays a central role 
in tissue destructive processes following tissue trauma caused by, for 
example, stroke, heart attack, brain trauma, and spinal cord injury. 
Thus specific inhibition of calpain is an important therapeutic target 
in these disease processes. The estimated total market for these 
classes of therapeutic agents is on the order $500 million to 1 billion 
annually. The inventor has specifically demonstrated that in vitro the 
HIV protease inhibitors ritonavir and saquinavir are also potent 
inhibitors of calpain. This technology has a variety of practical 
applications: (1) Existing HIV

[[Page 48723]]

proteases may be used as calpain inhibitors; (2) Existing HIV protease 
inhibitors which are FDA approved drugs will require less studies to 
develop as therapeutics; (3) HIV proteases inhibitors are small 
molecules with oral availability; (4) Other lead compounds developed as 
HIV protease inhibitors, but not commercialized, may be reevaluated as 
calpain inhibitors; (5) HIV protease inhibitors used as calpain 
inhibitors will not require chronic administration; and (6) calpain 
inhibitors may address therapeutic areas where there are not current 
effective therapies.
    A Provisional Patent Application Serial Number 60/202,378 has been 
filed for this technology. It is available for licensing through a DHHS 
Patent license.

Synthesis of Soluble Magnetodendrimer

Jeff W. Bulte (CC), Trevor Douglas
Serial No. 60/193,360 filed 31 Mar 2000
Licensing Contact: Norbert Pontzer; 301/496-7735, ext. 284; e-mail: 
[email protected]

    The invention provides a soluble composite material comprising an 
organic polymer and nanoparticles of a magnetic iron oxide. 
Poly(amidoamine) (PAMAM)dendrimers aggregate with magnetic particles in 
an oligocrystalline structure which makes them extremely magnetic and 
soluble in solution. These superparamagnetic nanoparticles are readily 
taken up by cells. Because the preparation is superparamagnetic rather 
than ferromagnetic there is a very large relaxation effect and 
hysteresis is not shown. The combination of solubility, cellular uptake 
and strong paramagnetic properties give these novel magnetodendrimers a 
number of potential uses.
    Magnetodendrimers have a high non-specific affinity for cellular 
membranes and will label cells by simple in vitro incubation regardless 
of the cells origin or surface proteins. After uptake of 
magnetodendrimer, cells can be readily separated by simple permanent 
magnets within seconds. When used as a magnetic resonance imaging (MRI) 
contrast agent, the magnetically labeled cells allow non-invasive 
monitoring of the temporal spatial dynamics of a wide variety of cell 
transplants. After incubation with magnetodendrimer, cellular 
relaxation enhancement is 3-5 times higher than earlier approaches. For 
example, the magnetically labeled cells can be injected into a patient 
undergoing stem cell therapy to follow the migration, distribution and 
integration of new tissue. Magnetic dendrimers could also be injected 
into tumors and other areas to directly label cells and tissues in 
vivo. Such uses include cancer hyperthermia therapy, ultrasound 
imaging-microwave radiation, and nuclear isotope imaging using \59\Fe 
preparations. The magnetodendrimer could be attached to therapeutic 
compounds or other clinically relevant molecules for research, 
diagnostic or therapeutic purposes.

Fluorescent Magnesium Indicators

Robert London, Pieter Otten, Louis A. Levy (NIEHS)
DHHS Reference Number E-067-00/0 filed 24 March 2000
Licensing Contact: John Rambosek; 301/496-7056 ext. 270; e-mail: 
[email protected]

    Links between magnesium status and diseases such as ischaemic heart 
disease, hypertension, atherosclerosis, osteoporosis, migraine 
headaches, and other chronic diseases have been reported. These 
correlations have been difficult to confirm, however, mainly because of 
poor methods for determining free magnesium levels. This invention 
discloses new compounds that are fluorescent indicators for free 
(ionized) magnesium--the physiologically important form of magnesium. 
These compounds are analogs of fluoroquinolone antibiotics. Unlike 
other methods and indicators, they show a particularly high degree of 
specificity for Mg2+ versus Ca2+. They represent 
an exciting improvement over other methods and indicators used to 
measure Mg2+ because they significantly increase the ability 
to accurately measure intra and extracellular Mg2+ levels in 
a wide variety of cells, tissues, and fluids under conditions where 
calcium is elevated. These compounds will be important research 
reagents, and have the potential to be very useful as diagnostic 
reagents in a variety of therapeutic areas.

Methods for Wound Treatment

Sharon M. Wahl et al. (NIDCR)
DHHS Reference No. E-131-99/0 filed 01 Mar 2000
Licensing Contact: Marlene Shinn; 301/496-7056 ext. 285; e-mail: 
[email protected]

    Impaired wound healing states in the elderly have lead to major 
problems in terms of morbidity and mortality, affecting over four 
million U.S. citizens per annum and costing over 9 billion dollars. NIH 
investigators have recently found that Secretory Leukocyte Protease 
Inhibitor (SLPI) plays an important and specific role in cutaneous 
wound healing. SLPI is an inhibitor of serine proteases, and evidence 
demonstrates a requirement for SLPI as an anti-proteolytic defense 
against elastase and possibly additional tissue degradative enzymes and 
is consistent with excess elastolytic activity in pathologic, 
nonhealing wounds and venous ulcers. Our researchers have found that 
the absence of SLPI causes delayed or aberrant wound healing, an 
increased and prolonged inflammatory response, enhanced elastase 
activity, and delayed matrix accumulation in mice.
    This new technology provides an improved method for treating 
diseases or disorders involving tissue destruction. The use of SLPI in 
such treatment provides a combination of advantages, including improved 
anti-bacterial, anti-viral, anti-fungal, and anti-inflammatory 
functions. SLPI also provides a number of relevant functions that 
accelerate the wound healing process of a variety of tissues, including 
skin, mucosal surfaces, and joints. Additionally, our investigators 
have developed a SLPI gene knock out mouse which is a useful animal 
model to study the functions of SLPI in the host innate immune 
response.

Inhibition of Cell-Mediated Immunity by Inhibition of fMLP Receptor 
Function by Bile Acids

Joost J. Oppenheim et al. (NCI)
DHHS Reference No. E-044-00/0 filed 03 Dec 1999
Licensing Contact: Marlene Shinn; 301/496-7056 ext. 285; e-mail: 
[email protected]

    It is well known that patients with bilary cholestatic diseases are 
susceptible to complications of systemic infection and endotoxemia, 
which may be attributable to impaired host immunity. Extensive studies 
in the past have shown that some bile acids, particularly 
chenodeoxycholic acid (CDCA), one of two major human primary bile 
acids, possessed immunosuppressive properties including inhibiting the 
production of Interleukin 1 (IL-1), IL-6 and tumor necrosis factor-
 (TNF-) by monocytes. The precise mechanistic basis 
for the immune suppression was unclear.
    The NIH announces the discovery that deoxycholic acid and many of 
its naturally occurring variants block the function of formyl peptide 
receptors by reversibly blocking the ligand-binding site on the 
receptors. The formyl peptide receptors are responsible for inducing 
many cell types to migrate to sites of inflammation and infection and 
have been shown to participate in host defense against microbial 
agents, the formation of atherosclerosis plaques,

[[Page 48724]]

granulomas, autoimmune disease and possibly Alzheimer's disease. In 
particular, our researchers have shown that co-incubation of the 
bacterially derived N-formyl peptide (fMLP) with major components of 
human bile, namely dexocholic acid or chenodeoxycholic acid, inhibited 
chemotaxis and binding by monocytes that act as phagocytic leukocytes 
in cell-mediated immunity. Deoxycholic acid and its variants therefore 
have potential usefulness as anti-inflammatory agents with a broad 
range of potential applications.

    Dated: July 31, 2000.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 00-20037 Filed 8-8-00; 8:45 am]
BILLING CODE 4140-01-P