Federal Register / Vol. 65, No. 213 / Thursday, November 2, 2000 / Notices 65863

41. Kyle Youngberg Ames, Iowa, Court

of Federal Claims Number 00–

0345V

42. Wanda E. Dennis on behalf of Brian

Keith Wingate, Manning, South

Carolina, Court of Federal Claims

Number 00–0346V

43. Tracy and Scott Weeks on behalf of

Jenica Weeks, Deceased, Boston,

Massachusetts, Court of Federal

Claims Number 00–0348V

44. Chue Xiong, Sacramento, California,

Court of Federal Claims Number

00–350V

45. Marion Underwood on behalf of

Cesar Zachary Moreno, Deceased,

Boston, Massachusetts, Court of

Federal Claims Number 00–0357V

46. Ann Haynes on behalf of Elizabeth

Haynes, Boston, Massachusetts,

Court of Federal Claims Number

00–0358V

47. Cynthia Wells on behalf of Ezra

James McCorkle, Boone, North

Carolina, Court of Federal Claims

Number 00–0359V

48. Sandra and William Spoon on behalf

of William Spoon, Phoenix,

Arizona, Court of Federal Claims

Number 00–0360V

49. Kimberly Willingham on behalf of

Courtney Willingham, Rockford,

Illinois, Court of Federal Claims

Number 00–0363V

50. Kristin and Mark Rogers on behalf

of Colin Rogers, Chapel Hill, North

Carolina, Court of Federal Claims

Number 00–0368V

51. Stephanie and Cory Geho on behalf

of Griffin Cole Geho, Portsmouth,

Ohio, Court of Federal Claims

Number 00–0370V

52. Sherri Lynn Boothby, Vienna,

Virginia, Court of Federal Claims

Number 00–0371V

53. Kristin Rogers on behalf of Colin

Rogers, Chapel Hill, North Carolina,

Court of Federal Claims Number

00–0372V

54. Anthony Joseph Tedesco, Clinton

Township, Michigan, Court of

Federal Claims Number 00–0373V

Dated: October 26, 2000.

Claude Earl Fox,

Administrator.

[FR Doc. 00–28136 Filed 11–1–00; 8:45 am]

BILLING CODE 4160–15–U

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

National Cancer Institute: Opportunity

for a Cooperative Research and

Development Agreement (CRADA) for

the Identification and Development of

Chemical Compounds That Interact

With the Polo-Box of Polo Kinases, as

Potential Therapeutic Targets for the

Inhibition of Cellular Proliferation

AGENCY: National Institutes of Health,

PHS, DHHS

ACTION: Notice.

SUMMARY: Members of the polo

subfamily of protein kinases play

important roles in cell proliferation, and

regulation of polo kinases may be

crucial in the control of cell division.

The polo kinases contain a distinct

region of homology in the C-terminal

non-catalytic domain, termed the polobox. Scientists from the National Cancer

Institute (NCI) have demonstrated that

over-expression of this non-catalytic Cterminal domain in budding yeast

results in a dominant-negative

inhibition of cell division. NCI seeks a

Cooperative Research and Development

Agreement (CRADA) Collaborator to aid

in the identification and development of

chemical compounds that interact with

the polo-box of polo kinases, as

potential therapeutic targets for the

inhibition of cellular proliferation.

DATES: Interested parties should notify

this office in writing of their interest in

filing a formal proposal no later than

January 2, 2000. Potential CRADA

Collaborators will then have an

additional thirty (30) days to submit a

formal proposal. CRADA proposals

submitted thereafter may be considered

if a suitable CRADA Collaborator has

not been selected.

ADDRESSES: Inquires and proposals

regarding this opportunity should be

addressed to Laurie W. Whitney, Ph.D.,

Technology Development Specialist

(Tel: 301–496–0477, FAX: 301–402–

2117), Technology Development and

Commercialization Branch, National

Cancer Institute, 6120 Executive Blvd.,

Suite 450, Rockville, MD 20852.

Inquiries directed to obtaining patent

license(s) needed for participation in the

CRADA opportunity should be

addressed to Vasant Gandhi, J.D., Ph.D.,

Technology Licensing Specialist, Office

of Technology Transfer, National

Institutes of Health, 6011 Executive

Blvd., Suite 325, Rockville, MD 20852,

(Tel: 301–496–7056, ext. 224, FAX: 301–

402–0220).

SUPPLEMENTARY INFORMATION: A

Cooperative Research and Development

Agreement (CRADA) is the anticipated

joint agreement to be entered into with

NCI pursuant to the Federal Technology

Transfer Act of 1986 and Executive

Order 12591 of April 10, 1987 as

amended by the National Technology

Transfer Advancement Act of 1995. NCI

is looking for a CRADA partner to aide

NCI in the identification and

development of chemical compounds

which act as polo-box inhibitors. The

expected duration of the CRADA would

be from one (1) to five (5) years.

Members of the polo subfamily of

protein kinases appear to play pivotal

roles in cell division and proliferation.

These include mammalian Plk, Snk, and

Fnk/Prk, Xenopus laevis Plx1,

Drosophila melanogaster polo,

Schizosaccharomyces pombe Plo1, and

Saccharomyces cerevisiae Cdc5. The

polo subfamily members are

characterized by the presence of a

distinct region of homology in the Cterminal non-catalytic domain, termed

the polo-box, which is essential for

subcellular localization and mitotic

functions of the polo kinases.

Regulation of polo kinases may be

crucial in the control of cell division. In

mammalian cells, Plk is expressed at

high levels in mitotically active cells

and in tumors of various origins.

Constitute expression of Plk in NIH3T3

cells induces oncogenic focus

formation, and these Plk-transformed

cells can form tumors in nude mice.

These data suggest that Plk expression

is closely related to cellular

proliferation, and that uncontrolled Plk

expression may lead to the development

of cancers in humans. Genetic and

biochemical analyses indicate that polo

kinases regulate diverse cellular events

at various stages of the M phase. In

addition to their roles in spindle

formation and centrosome maturation,

polo kinases appear to regulate

important biochemical steps at the G2/

M transition, such as activation of Cdc2

through Cdc25C phosphatase, DNA

damage checkpoint adaptation, and

activation of the anaphase-promoting

complex (APC) in various eukaryotic

systems. In addition, recent data suggest

that polo kinases play important roles in

cytokinesissea.

In budding yeast, overexpression of

the non-catalytic C-terminal domain of

either Plk or Cdc5 (plk∆N or cdc5∆N),

but not the corresponding polo-box

mutant, results in severe connected cell

morphology. Provision of functional

Cdc5 remedies this phenotype,

indicating that over-expression of

cdc5∆N or plk∆N results in a dominantnegative inhibition of cell division and

65864 Federal Register / Vol. 65, No. 213 / Thursday, November 2, 2000 / Notices

that an intact polo-box is required for

this event. These data raise an intriguing

possibility that conditional expression

of the polo-box domain may selectively

inhibit the mitotic functions of polo

kinases. Furthermore, our observation

suggests that the polo-box peptide may

act as a potential anti-cancer therapeutic

agent. Alternatively, isolation of small

chemical compounds that bind to the

polo-box and interfere with its function

may yield a strategy to regulate highly

proliferative malignant cells. We have

developed two yeast strains that

conditionally express the polo-box

domains of Plk (KLY1212) or Cdc5

(KLY1083). Isolation of chemical

compounds alleviating the dominantnegative cell division defect of these

strains may lead to identification of

polo-box inhibitors. Since the polo-box

is an essential and unique domain for

polo kinases, these inhibitors may likely

provide selective tools to control the

cell proliferation without interfering

with other protein kinases.

The described methods are the subject

of a U.S. provisional patent application

filed May 23, 2000 by the Public Health

Service on behalf of the Federal

Government. Furthermore, the initial

report and characterization of the

invention is described in: Song S, and

Lee KS. A novel function of

Saccharomyces cerevisiae CDC5 in

cytokinesis (submitted for publication).

Further reference to the invention can

be found in: (1) Song S, Grenfell TX,

Garfield S, Erikson RL, and Lee KS.

(2000). Essential function of the polobox of Cdc5 in subcellular localization

and induction of cytokinetic structures.

Mol. Cell. Biol. 20, 286–298, and (2) Lee

KS, Grenfell TZ Yarm, FR, and Erikson

RL (1998). Mutation of the polo-box

disrupts localization and mitotic

functions of the mammalian polo kinase

Plk. Proc. Natl. Acad. Sci. USA

95:9301–9306.

Under the present proposal, the goal

of the CRADA will involve the

following:

(1) Identification and isolation of

chemical compounds that alleviate the

dominant-negative cell division defect

of yeast strains that conditionally

express the polo-box domains of Plk or

Cdc5.

(2) Development of these chemical

compounds as tools to control cellular

proliferation without interfering with

other protein kinases.

Party Contributions

The role of the NCI in the CRADA

may include, but not be limited to:

1. Providing intellectual, scientific,

and technical expertise and experience

to the research project.

2. Providing the CRADA Collaborator

with information and data relating to

polo kinases.

3. Planning research studies and

interpreting research results.

4. Carrying out research with

validates and expands on the role of the

dominant-negative inhibition of cell

proliferation found using the intact

polo-box.

5. Publishing research results.

6. Developing additional potential

applications related to inhibition of cell

proliferation using polo-box inhibitors.

The role of the CRADA Collaborator

may include, but not be limited to:

1. Providing significant intellectual,

scientific, and technical expertise or

experience to the research project.

2. Planning research studies and

interpreting research results.

3. Providing technical and/or

financial support to facilitate scientific

goals and for further design of

applications of the technology outlined

in the agreement.

4. Publishing research results.

Selection criteria for choosing the

CRADA Collaborator may include, but

not be limited to:

1. A demonstrated record of success

in the areas of isolation, purification,

characterization, and therapeutic

development of chemical compounds.

2. A demonstrated background and

expertise in cancer-related sciences.

3. The ability to collaborate with NCI

on further research and development of

this technology. This ability will be

demonstrated through experience and

expertise in this or related areas of

technology indicating the ability to

contribute intellectually to ongoing

research and development.

4. The demonstration of adequate

resources to perform the research and

development of this technology (e.g.

facilities, personnel and expertise) and

to accomplish objectives according to an

appropriate timetable to be outlined in

the CRADA Collaborator’s proposal.

5. The willingness to commit best

effort and demonstrated resources to the

research and development of this

technology, as outlined in the CRADA

Collaborator’s proposal.

6. The demonstration of expertise in

the commercial development and

production of products related to this

area of technology.

7. The level of financial support the

CRADA Collaborator will provide for

CRADA-related Government activities.

8. The willingness to cooperate with

the national Cancer Institute in the

timely publication of research results.

9. The agreement to be bound by the

appropriate DHHS regulations relating

to human subjects, and all PHS policies

relating to the use and care of laboratory

animals.

10. The willingness to accept the legal

provisions and language of the CRADA

with only minor modifications, if any.

These provisions govern the distribution

of future patent rights to CRADA

inventions. Generally, the rights of

ownership are retained by the

organization that is the employer of the

inventor, with (1) the grant of a license

for research and other Government

purposes to the Government when the

CRADA Collaborator’s employee is the

sole inventor, or (2) the grant of an

option to elect an exclusive or

nonexclusive license to the CRADA

Collaborator when the Government

employee is the sole inventor.

Dated: October 17, 2000.

Kathleen Sybert,

Chief, Technology Development and

Commercialization Branch, National Cancer

Institute, National Institutes of Health.

[FR Doc. 00–28120 Filed 11–1–00; 8:45 am]

BILLING CODE 4140–01–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

National Cancer Institute, Notice of

Closed Meeting.

Pursuant to section 10(d) of the

Federal Advisory Committee Act, as

amended (5 U.S.C. Appendix 2), notice

is hereby given of a meeting of the

President’s Cancer Panel.

The meeting will be closed to the

public in accordance with the

provisions set forth in section

552b(c)(9)(B), Title 5 U.S.C., as amended

because the premature disclosure of

other and the discussions would likely

to significantly frustrate implementation

of recommendations.

Name of Committee: President’s Cancer

Panel.

Date: October 26, 2000.

Time: 4 pm to 6 pm.

Agenda: To review and evaluate other.

Place: National Institutes of Health, 31

Center Drive, Building 31, Room 4A48,

Bethesda, MD 20892–2473 (Telephone

Conference Call).

Contact Person: Maureen O. Wilson, Phd,

Executive Secretary, National Cancer

Institute, National Institutes of Health, 31

Center Drive, Building 31, Room 4A48,

Bethesda, MD 20892, 301/496–1148.

This notice is being published less than 15

days to the meeting due to scheduling

conflicts.

(Catalogue of Federal Domestic Assistance

Program Nos. 93.392, Cancer Construction;

93.393, Cancer Cause and Prevention

Research; 93.394, Cancer Detection and

Diagnosis Research; 93.395, Cancer