63872 Federal Register / Vol. 65, No. 207 / Wednesday, October 25, 2000 / Notices

you envision the Subcommittee

providing, and what type of outreach

would you intend to do in order to

formulate your recommendations to the

Board of Scientific Counselors?

lllllllllllllllllllll

[FR Doc. 00–27372 Filed 10–24–00; 8:45 am]

BILLING CODE 4163–70–P

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Agency for Toxic Substances and

Disease Registry

Community/Tribal Subcommittee and

the Board of Scientific Counselors,

Agency for Toxic Substances and

Disease Registry: Meetings.

In accordance with section 10(a)(2) of

the Federal Advisory Committee Act

(Pub. L. 92–463), the Agency for Toxic

Substances and Disease Registry

(ATSDR) announces the following

subcommittee and committee meetings.

Name: Community/Tribal Subcommittee

(CTS).

Times and Dates:

8:30 a.m.–4 p.m., November 28, 2000

8:30 a.m.–4 p.m., November 29, 2000

Place: The Westin Peachtree Plaza Hotel,

210 Peachtree Street, NW., Atlanta, Georgia

30303.

Status: Open to the public, limited by the

available space. The meeting room

accommodates approximately 60 people.

Purpose: This subcommittee brings to the

Board advice, citizen input, and

recommendations on community and tribal

programs, practices, and policies of the

Agency.

Matters To Be Discussed: Agenda items

include an update on Action Items and

Recommendations from previous meeting;

CTS update on Cultural Sensitivity Training;

discussion on implementation of task forces;

discussion of Freedom of Information Act

(FOIA) process at Department of Defense and

Department of Energy sites; update on the

Office of Urban Affairs health intervention

and health care activities at sites; and, an

update on Research Agenda Building

activities.

Name: Board of Scientific Counselors,

ATSDR.

Times and Dates:

8:30 a.m.–5:05 p.m., November 30, 2000.

8:30 a.m.–12:10 p.m., December 1, 2000.

Place: The Westin Peachtree Plaza Hotel,

210 Peachtree Street, NW., Atlanta, Georgia

30303.

Status: Open to the public, limited by the

available space. The meeting room

accommodates approximately 60 people.

Purpose: The Board of Scientific

Counselors, ATSDR, advises the Secretary;

the Assistant Secretary for Health; and the

Administrator, ATSDR, on ATSDR programs

to ensure scientific quality, timeliness,

utility, and dissemination of results.

Specifically, the Board advises on the

adequacy of science in ATSDR-supported

research, emerging problems that require

scientific investigations, accuracy and

currency of the science in ATSDR reports,

and program areas to emphasize or deemphasize. In addition, the Board

recommends research programs and

conference support for which the Agency

awards grants to universities, colleges,

research institutions, hospitals, and other

public and private organizations.

Matters To Be Discussed: Agenda items

will include ATSDR updates; review of the

ATSDR Research Agenda, and a review of the

public comments and implementation plans;

discussion on exposure investigations and

biomarkers; discussion on current events

impacting ATSDR; an overview of

Community and Tribal Subcommittee

meeting issues and recommendations;

discussion of activities related to Libby,

Montana, growth of environmental pediatric

units, and Minority Health Program; and, an

overview on ATSDR new directions. Written

comments are welcomed and should be

received by the contact person listed below

prior to the opening of the meeting.

Agenda items are subject to change as

priorities dictate.

Contact Person for More Information:

Robert Spengler, Sc.D., Executive Secretary,

BSC, ATSDR, M/S E–28, 1600 Clifton Road,

NE, Atlanta, Georgia 30333, telephone 404/

639–0708.

The Director, Management Analysis and

Services Office, has been delegated the

authority to sign Federal Register notices

pertaining to announcements of meetings and

other committee management activities for

both CDC and the Agency for Toxic

Substances and Disease Registry.

Dated: October 17, 2000.

Carolyn J. Russell,

Director, Management Analysis and Services

Office, Centers for Disease Control and

Prevention.

[FR Doc. 00–27374 Filed 10–24–00; 8:45 am]

BILLING CODE 4163–70–P

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Centers for Disease Control and

Prevention

ICD–9–CM Coordination and

Maintenance Committee; Meeting

National Center for Health Statistics

(NCHS), Data Policy and Standards

Staff, announces the following meeting.

Name: ICD–9–CM Coordination and

Maintenance Committee meeting.

Time and Date: 9 a.m.–5 p.m., November

17, 2000.

Place: The Health Care Financing

Administration (HCFA), Multi-purpose

Room, 7500 Security Boulevard, Baltimore,

Maryland.

Status: Open to the public, limited only by

the space available.

Purpose: The ICD–9–CM Coordination and

Maintenance (C&M) Committee will hold its

final meeting of the calendar year 2000 cycle

on Friday November 17, 2000. The C&M

meeting is a public forum for the

presentation of proposed modifications to the

International Classification of Diseases,

Ninth-Revision, Clinical Modification.

Matters to be Discussed: Agenda items

include:

Hemophilia carrier status

Developmental hip dislocation

Heart failure

Constipation

Urologic conditions

Clinical trial participant

Dental caries

Implementation of the ICD–10–PCS coding

system

Removal of Intra-aortic balloon pump

Transcervical fetal oxygen saturation

Abdominal cerclage (FspOs) monitoring

Addenda

Contact Person for Additional Information:

Amy Blum, Medical Classification Specialist,

Data Policy and Standards Staff, NCHS, 6526

Belcrest Road, Room 1100, Hyattsville,

Maryland 20782, telephone 301/458–4106

(diagnosis), Amy Gruber, Health Insurance

Specialist, Division of Acute Care, HCFA,

7500 Security Blvd., Room C4–07–07,

Baltimore, Maryland, 21244 telephone 410–

786–1542 (procedures).

Notice: In the interest of security, HCFA

has instituted stringent procedures for

entrance into the building by nongovernment employees. Persons without a

government I.D. must show a photo I.D. and

sign-in at the security desk upon entering the

building.

The Director, Management Analysis and

Services Office, has been delegated the

authority to sign Federal Register notices

pertaining to announcements of meetings and

other committee management activities, for

both CDC and the Agency for Toxic

Substances and Disease Registry.

Dated: October 17, 2000.

Carolyn J. Russell,

Director, Management Analysis and Services

Office, Centers for Disease Control and

Prevention.

[FR Doc. 00–27373 Filed 10–24–00; 8:45 am]

BILLING CODE 4160–18–P

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

Government-Owned Invention;

Availability for Licensing: Tissue

Microarrays for Rapid Molecular

Profiling

AGENCY: National Institutes of Health,

Public Health Service, DHHS.

ACTION: Notice.

SUMMARY: The inventions listed below

are owned by agencies of the U.S.

Federal Register / Vol. 65, No. 207 / Wednesday, October 25, 2000 / Notices 63873

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 may

be obtained by contacting Uri

Reichman, Ph.D., M.B.A., at the Office

of Technology Transfer, National

Institutes of Health, 6011 Executive

Boulevard, Suite 325, Rockville,

Maryland 20852–3804; Telephone: 301/

496–7736 ext. 240; Fax: 301/402–0220;

E-mail: reichmau@od.nih.gov. A signed

Confidential Disclosure Agreement will

be required to receive copies of the

patent applications.

SUPPLEMENTARY INFORMATION: Advances

in medical research and the successful

development of new, improved

diagnostic tools and therapeutic agents

are often dependent on the ability to

screen thousands of clinical samples for

molecular markers in a high-throughput

fashion. This is particularly critical in

the ‘‘post-genomics’’ era, where the

number of genes to be analyzed is often

much high than the number of samples

evaluated. DNA microarray (‘‘DNA

chip’’) and related genome-screening

tools have made it possible to screen the

genome to discover genes with medical

utility. However, before they can be

utilized in developing improved

diagnostics and therapeutic applications

these early discoveries in genomics and

proteomics need to be tested and

validated.

The technology presented here, called

Tissue Microarrays or ‘‘Tissue Chips’’ is

specifically designed to fill the need of

the medical community for high

throughput screening of hundreds of

molecular markers in thousands of cell

or tissue samples on a single microscope

slide.

Tissue Microarrays include hundreds

or even thousands of tiny discs (approx.

1 mm in diameter) of tissue specimens,

fixed and arranged on a single

microscope slide. The technology

provides an automated means to

generate thousands of copies of this

kind of slide, slides that then can be

used for specific molecular analyses,

such as DNA and mRNA in situ

hybridization and protein

immunostaining.

A typical application of tissue

microarrays in cancer research and

product development is the analysis of

several hundred breast tumors from

patients at different stages of disease

development (normal breast, atypia, in

situ cancer, invasive cancer, metastases)

to identify the specific step at which

gene alterations take place, as well as

the frequency of these alterations. In

another example, tissue microarrays can

be constructed from tissue materials in

a retrospective study design, where one

can immediately correlate the

expression of a molecular marker with

poor prognosis. Furthermore, tissue

microarrays can be used to screen many

different diseases at once, such as

multiple different tumor types, nonmalignant tissues, and normal tissues

and cells.

The data accumulated from these type

of studies can serve as the basis for the

development of diagnostic and

prognostic tools for disease,

classification of diseases into

molecularly defined subgroups, as well

as for identifying targets for therapeutic

regimens for treating the disease.

Tissue microarrays are useful in the

early-stage discovery of gene targets in

genomic research, in validation of such

targets, in the testing and optimization

of diagnostic tests, as well as in the

quality control of molecular detection

schemes. In the quality control field, it

would be possible to provide a copy of

a tissue microarray with commercial

histological (IHC or ISH) test kits for QC

procedure. Tissue microarrays could

also be used to standardize pathology

interpretations by sending copies of the

same slides to different pathologists.

Electronic database archives of

previously analyzed tissue arrays could

also be utilized as a teaching tool of

anatomy and pathology for students,

clinical lab technicians and physicians.

The manufacturing of tissue

microarrays is a critical step in the

success of the technology. The NIH

group has developed a manual tissue

microarray device, which facilitates

development of tissue microarrays. In

addition, a prototype of an automated

tissue microarrayer has been developed.

This instrument consists of a donor

specimen station and a recipient block

station. An XY robotic arm retrieves

cylindrical tissue specimens from the

donor block and inserts them into

assigned locations at cylindrical

receptacles in the donor paraffin block.

When the recipient tissue microarray

block has been constructed, it is

sectioned into 200 to 300 thin sections

with a microtome. The resulting

sections are then laid down and fixed

on a microscope slide. The apparatus is

controlled by a computer, which also

stores the addressable sample locations.

The commercial potential of the

present technology is enormous. It is

estimated that the total market for

microarray high-throughput screening

in 1999 was $176 million. With an

estimated annual rate growth of 33%,

the market size is expected to approach

$1 billion by 2005 (Source: Biosearch

Online). Tissue microarray market is

tied in with the other biochip markets,

but it also presents an opportunity to

expand microarray research and

development into an entirely new

direction. For example, most of the

current microscopic tissue based

analyses could in the future take place

in a tissue microarray format, which

provides several hundred-fold higher

throughput than conventional analyses.

The technology is available for

licensing in its entirety or in parts. A list

of the inventions available for licensing,

along with a brief summary of each

invention, is shown below.

Licensing of Tissue Microarrays

Instrumentation and Related

Fluorescence Systems

(1) NIH Reference No. E–002–98/0

(USSN 60/075,979, PCT/US99/04001),

entitled ‘‘Tumor Tissue Microarrays for

Rapid Molecular Profiling’’, originally

filed 02/25/98, PCT filed 02/24/99.

Inventors: S. Leighton, O. Kallionemi

and J. Kononen.

(2) NIH Reference No. E–273–99/0

(USSN 60/170,461), entitled ‘‘Methods

and Apparatus for Constructing Tissue

Microarrays’’, filed 12/13/99. Inventors:

O. Kallionemi, G. Sauter, S. Leighton

and J. Kononen.

These two patent applications

disclose the specifics of the microarraymaker instrument. With the advances in

the field of genomics it is predicted that

the demand for tissue microarrays and

thus the demand for tissue microarray

instruments will increase rapidly in the

next several years. Also offered for

licensing (E–273–90/0) is an integrated

tissue microarray system. The system

includes three stations, i.e. array-making

station, array processing station and a

detection system (fluorescent imager).

Licensing of either and/or both of the

instrument inventions is particularly

recommended for manufacturers of

scientific and medical instrumentation.

(3) NIH Reference No. E–272–99/0

(USSN 60/154,601), entitled ‘‘Signal

Counting for In Situ Hybridization’’,

filed 9/17/99. Inventors: O. Kallionemi,

J. Kononen, L. Buendorf, E. Dougherty

and A. Grigoryan.

The accurate detection and

quantitation of fluorescence signal

associated with FISH is critical for the

molecular analysis of arrayed tissue

specimens. In spite of recent

improvements in fluorescence optics

and related techniques, quantitation of

FISH has not been perfected yet. This

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