63874 Federal Register / Vol. 65, No. 207 / Wednesday, October 25, 2000 / Notices

invention discloses a device and

method for improving the accuracy of

fluorescence spot counting. This has

been accomplished mainly through the

following improvements: (1) A method

to analyze ratios of test and reference

spot signals in a field of view, (2) an

imaging system to acquire confocal

images to cells to provide a set of

different layers of the same cells, at

different positions along the Z-axis, and

(3) a software program to make use of

the three-dimensional nature of the

images, which makes the identification

of FISH signals more accurate. Licensing

of an algorithm for automated FISH spot

counting is recommended for

manufacturers of scientific and medical

instrumentation and in particular for

manufacturers of commercial imaging

devices as well as companies that

specialize in providing fluorescent

probes for molecular biology research.

Licensing of Applications of Tissue

Microarrays

(4) NIH Reference No. E–007–99/0

(USSN 60/106,038, PCT/US99/04000),

entitled ‘‘Tissue Microarrays for Rapid

Molecular Profiling’’, originally filed 10/

28/98, PCT filed 02/24/99. Inventors: O.

Kallioniemi, G. Sauter and J. Kononen.

(5) NIH Reference No. E–274–99/0

(USSN 60/171,262), entitled ‘‘Methods

of Making and Using Microarrays’’, filed

12/15/99. Inventors: O. Kallionemi and

G. Sauter.

These two inventions disclose

methods of using tissue microarrays for

a wide variety of clinical applications.

E–007–99/0 describes in great detail

high-throughput screening studies of

thousands of tissue samples. These

studies, ordinarily requiring many days

to perform, can be completed in only a

few hours when tissue microarrays are

used. Licensees of this invention will be

able to manufacture tissue microarrays

using clinical samples and distribute the

panels and companion reagents to the

medical and research community.

Commercially produced microarrays

could be developed for use as reference

standards for certain diseases or custom

made for specific needs.

E–274–99/0 describes the use of tissue

microarrays for educational,

standardization and OC (histological

test kits) purposes. With respect to the

first proposed use, licensees will be

able, for example, to distribute

microarray panels and companion

reagents in medical teaching

institutions. With respect to the latter

two uses, standard microrray panels

could be included in clinical test kits

that are histological (IHC or ISH)

procedures.

Tissue Microarray technology and its

applications have been described in

several publications, such as Nature

Medicine 4:844 (1998), Cancer Research

59:803 (1999), J Natl Cancer Inst.

91:1758 (1999), Clin Cancer Res 5:1966

(1999), J Natl Cancer Inst, 92:1252

(2000).

Dated: October 6, 2000.

Jack Spiegel,

Director, Division of Technology Development

and Transfer, Office of Technology Transfer.

[FR Doc. 00–27355 Filed 10–24–00; 8:45 am]

BILLING CODE 4140–01–M

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.

A Cultured Cell Line which Expresses

the GLU4 Glucose Transporter Isoform

Labeled with a Short Hemaglutinin

Peptide and a Modified Green

Fluorescence Protein

Samuel W. Cushman (NIDDK), DHHS

Reference No. E–264–00/0 filed 26

Jul 2000; Licensing Contact:

Marlene Shinn; 301/496–7056 ext.

285; email: shinnm@od.nih.gov.

The aforementioned invention is

currently available through a Biological

Materials License as a research tool.

Insulin regulates glucose uptake by

inducing the translocation of GLUT4, a

glucose transporter isoform expressed in

fat and muscle, from intracellular

components to the plasma membrane.

The NIH announces the discovery of a

cell line that expresses the GLUT4

glucose transporter isoform with a short

hemaglutin peptide (HA) and a

modified green fluorescent protein

(GFP). The HA peptide is recognized by

a specific antibody when GLUT4 is in

the plasma membrane but not when

GLUT4 is sequestered inside the cell.

The modified GFP can be detected by its

fluorescence whether it is inside the cell

or on the cell surface. This allows the

HA label to quantitate the GLUT4

subcellular distribution and the GFP

label, the total GLUT4 expression.

Therefore, this invention can be used in

high through-put screening, as an assay

reagent, and it may aid specifically in

ascertaining compounds that have the

insulin-like effect of stimulating GLU4

translocation from an intracellular

compartment to the cell surface.

Dmt-tic Di- and Tri-Peptidic Derivatives

and Related Compositions and Methods

of Use

Lawrence H. Lazarus (NIEHS), DHHS

Reference No. E–103–00/0 filed 24

Mar 2000; Licensing Contact:

Marlene Shinn; 301/496–7056 ext.

285; e-mail: shinnm@od.nih.gov.

A major obstacle in the treatment of

many cancers involves the clinical

manifestation of drug resistance.

Currently, toxic substances are used in

clinical and therapeutic settings to

inhibit glycoproteins in the cell

membrane of some cancer cells that

have the ability to pump out of the cell

drugs that would be potentially lethal.

The most common of these

glycoproteins is the 170-kd ATPdependent transmembrane efflux pump.

The multidrug resistance (MDR1)

phenotype, however, is not the sole

source of drug resistance since MDR1 is

a member of a superfamily of proteins

structurally related to the

transmembrane P-glycoproteins.

NIH scientists have prepared a series

of δ-opiod analogs of Dmt-tic (2′,6′-

dimethyl-L-tyrosine-1,2,3,4-

tetrahydroisoquinoline-3-carboxylic

acid). At least one of the analogs, which

is biologically stable and exerts no

known side effects, has been observed to

inhibit the ability of MDR1 to pump out

a fluorescent probe from the cell

membrane. Thus, these analogs might

represent novel chemosensitizing agents

to treat both hematologic malignancies

(lymphomas) and solid tumors (e.g.

breast and colon) without toxic effects

in patients.

In addition, this invention provides

more potent δ-opioid antagonists and δopiod antagonists with duel binding

Federal Register / Vol. 65, No. 207 / Wednesday, October 25, 2000 / Notices 63875

affinity and biological activity toward δopiod and μ-opiod receptors. These

compounds therefore, have the potential

to treat opiate and alcohol abuse,

neurological diseases, neuropeptide or

neurotransmitter imbalances,

neurological and immune dysfunction,

graft rejections through

immunosuppression with antagonists,

pain control through short half-life

agonists, and shock and brain injuries.

Scratch Wound Assay Device

Katherine Malinda et al. (NINR), Serial

No. 09/496,134 filed 01 Feb 2000;

Licensing Contact: Dale Berkley;

301/496–7735 ext. 223; e-mail:

berkleyd@od.nih.gov.

Tissue wounds undergo a complex

and ordered series of events to repair

tissue. These events may include

infiltration of inflammatory immune

cells as part of the process to remove

and destroy necrotic tissue, increased

vascularization by angiogenic factors,

and increased cell proliferation and

extracellular matrix deposition.

Although the basic process of tissue

repair has been characterized, the

individual steps and factors necessary to

carry out this complex series of events

are not yet well understood or fully

identified. Accordingly, there is a need

to develop a way of reproducibly

injuring a layer of cells to study the

effects of different compounds of

treatments on the ability of the

remaining cells to repair the damaged

area.

The present invention provides a

device that reproducibly makes a

wound of a desired size in a cell layer

grown on a cell culture material. The

device allows researchers to use small

volumes of cells and test materials

suggesting its use as a tool in high

throughput screening of compounds.

This provides researchers with a faster,

more accurate way of screening large

numbers of factors and determining the

effects of cell growth and migration

agents in model wounds produced in

the cell, organ, or tissue layer.

Method of in vitro T cell Differentiation

of CD34+ Progenitor Cells

Ruiz et al. (NIAID), DHHS Reference No.

E–206–98/0 filed 29 Oct 1999;

Licensing Contact: J. P. Kim; 301/

496–7056 ext. 264; e-mail:

kimj@od.nih.gov.

The present invention relates to a

human in vitro system for inducing the

growth and de novo differentiation of T

cells from CD34+ progenitor cells in the

presence of various cytokine cocktails

and lymph node stroma. The mature T

cells which are generated may be used

to treat individuals with primary or

acquired T cell immunodeficiencies,

including HIV infection.

Dated: October 13, 2000.

Jack Spiegel,

Director, Division of Technology,

Development and Transfer, Office of

Technology Transfer, National Institutes of

Health.

[FR Doc. 00–27356 Filed 10–24–00; 8:45 am]

BILLING CODE 4140–01–P

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.

A Plasmid for Expression of a Soluble

Form of HIV–1 Integrase Protein

Robert Craigie et al. (NIDDK), NIH

Reference No. E–108–00/0;

Licensing Contact: J.P. Kim; 301/

496–7056 ext. 264; e-mail:

kimj@od.nih.gov.

Integrase is an essential HIV enzyme

and a promising target for antiviral

therapy. Integrase protein is required to

assay for inhibitors of this enzyme and

for mechanistic studies on HIV DNA

integration. Further, drugs targeted to

integrase would provide a new

therapeutic approach to the treatment of

AIDS and could be used in combination

therapy with drugs that target RT and

protease. The subject plasmid can be

used to produce large quantities of a

soluble form of HIV–1 integrase protein

for such work.

TTP as a Regulator of GM–CSF mRNA

Deadenylation and Stability

Ester Carballo-Jane, Wi S. Lai, Perry J.

Blackshear (NIEHS), NIH Reference

No. E–204–99/0 filed 13 Aug 1999;

Licensing Contact: Vasant Gandhi;

301/496–7056 ext. 244; e-mail:

gandhiv@od.nih.gov.

The disclosed invention provides

materials and methods to treat

granulocytopenia (low white cell count

in the blood) which is characterized by

a reduced number of granulocytes

(relative) or an absence of granulocytes

(absolute). This condition is commonly

associated with cancer chemotherapy,

but is seen less frequently in a number

of conditions including the use of

propylthiouracil, radiotherapy for

marrow ablation for bone marrow

transplantation, aplastic anemia,

systemic lupus erythematosus, AIDS

and a variety of other situations. The

invention proposes a method to increase

GM–CSF levels in a treated subject, and

this increase is achieved by inhibiting

the degradation of GM–CSF messenger

RNA (mRNA). Tristetraprolin (TTP) is

one member of a family of cys-cys-cyshis (CCCH) zinc finger proteins, and it

is a factor that binds to and causes the

instability of GM–CSF mRNA. Methods

are provided for the development of

screening assays for molecules that

inhibit the binding of TTP and its

related proteins to GM–CSF mRNA, or

otherwise inhibit the effect of TTP to

promote breakdown of the mRNA,

leading in turn to increased mRNA

stability and enhanced production of

GM–CSF. Compounds identified by

such screens, and their derivatives,

could be useful in treating

granulocytopenia from whatever cause.

Novel Post-Transcriptional Regulatory

Elements and Uses Thereof

George N. Pavlakis and Filomena Nappi

(NCI), NIH Reference Nos. E–143–

98/0 filed 22 May 1998 and E–143–

98/1 filed 22 May 1999; Licensing

Contact: Carol Salata; 301/496–7735

ext. 232; e-mail: salatac@od.nih.gov.

This invention concerns a novel posttranscriptional regulatory element that

can function as an RNA nucleocytoplasmic transport element (NCTE)

and its use to make recombinant

attenuated HIV strains useful as

vaccines. HIV regulates its expression

by controlling the nuclear transport of

unspliced mRNA encoding structural

proteins. HIV utilizes the Rev/RRE

system. RRE (Rev responsible element)

is an HIV encoded NCTE, which is part

of every HIV RNA encoding the