3466 Federal Register / Vol. 65, No. 14 / Friday, January 21, 2000 / Notices

FOR FURTHER INFORMATION CONTACT: To

request more information on this project

or to obtain a copy of the data collection

plans and instrument, write to Dr.

Margaret Tucker, Chief, Genetic

Epidemiology Branch, National Cancer

Institute, NIH, Executive Plaza South,

Room 7122, 6120 Executive Blvd.,

Bethesda, MD 20892, or call non-tollfree number (301) 496–4375, or E-mail

your request, including your address to:

tuckerp@mail.nih.gov.

Comments Due Date

Comments regarding this information

collection are best assured of having

their full effect if received on or before

60 days from the date of this

publication.

Dated: January 12, 2000.

Reesa Nichols,

OMB Project Clearance Liaison.

[FR Doc. 00–1422 Filed 1–20–00; 8:45 am]

BILLING CODE 4140–01–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICE

National Institutes of Health

Government-Owned Invention;

Availability for Licensing: ‘‘Therapeutic

Methods to Treat Tumor Cells—

Mutated Anthrax Toxin Protective

Antigen Proteins That Specifically

Target Cells Containing High Amounts

of Cell-Surface Metalloproteinases or

Plasminogen Activators’’

AGENCY: National Institutes of Health,

Public Health Service, DHHS.

ACTION: Notice.

SUMMARY: The invention listed below is

owned by an agency of the U.S.

Government and is 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.

ADDRESSES: Licensing information and

a copy of the U.S. patent application

referenced below may be obtained by

contacing J.R. Dixon, Ph.D., at the Office

of Technology Transfer, National

Institutes of Health, 6011 Executive

Boulevard, Suite 325, Rockville,

Maryland 20852–3804 (telephone 301/

496–7056 ext 206; fax 301/402–0220; EMail: jd212g@NIH.GOV). A signed

Confidential Disclosure Agreement is

required to receive a copy of any patent

application.

SUPPLEMENTARY INFORMATION:

Invention Title: ‘‘Mutated Anthrax

Toxin Protective Antigen Proteins that

Specifically Target Cells Containing

High Amounts of Cell-Surface

Metalloproteinases or Plasminogen

Activators.’’

Inventors: Drs. Stephen H. Leppla

(NIDCR), Shi-Hui Liu (NIDCR), Sarah

Netzel-Arnett (NIDCR), Henning

Birkedal-Hansen (NIDCR), and Thomas

H. Bugge (NIDCR).

USPA SN: 60/155,061 [=DHHS Ref.

No. E–293–99/0]—Filed with the

U.S.P.T.O. on Friday, September 24,

1999.

Abstract

Anthrax toxin is a three-part toxin

secreted by Bacillus anthracis consisting

of Protective Antigen (‘‘PA’’, 83kDa),

Lethal Factor (‘‘LF’’, 90 kDa) and Edema

Factor (‘‘EF’’, 89kDa), which are

individually non-toxic. PA, recognized

as central, receptor-binding component,

binds to an unidentified receptor and is

cleaved at the sequence RKKR167 by

cell-surface furin or furin-like proteases

into two fragments: PA63, a 63 kDa Cterminal fragment, which remains

receptor-bound and PA20, a 20 kDa Nterminal fragment, which is released

into the medium. The resulting heterooligomeric complex is internalized by

endocytosis and acidification of the

vesicle causes insertion of the PA63

heptamer into the endosomal membrane

to produce a channel through which LF

or EF translocate to the cytosol, where

LF or EF induce cytotoxic events. Thus,

the combination of PA+LF, named

anthrax lethal toxin, kills animals and

certain cultured cells, due to

intracellular delivery and action of LF,

recently proven to be a zinc-dependent

metalloprotease that is known to cleave

at least two targets, mitogen-activated

protein kinase kinase 1 and 2. The

combination of PA+EF, named edema

toxin, disables phagocyte and probably

other cells, due to the intracellular

adenylate cyclase activity of EF.

Technology

The technology disclosed in the 60/

155,961 patent application relates to

anthrax toxin protective antigen (PA)

mutants in which the furin site is

replaced by sequences specifically

cleaved by matrix metalloproteinases

(MMPs) or plasminogen activators.

These MMP or plasminogen activator

targeted PA mutants are only activated

by plasminogen activator or MMPexpressing tumor cells so as to

specifically deliver a toxin or a

therapeutic agent. This is important

because a wide variety of tumor cell

lines and tissues overexpress MMPs or

plasminogen activators, and this

overexpression is highly correlated to

tumor invasion and metastasis.

Activation of these mutants occurs

mainly on the cell surface and the

targeted agent is then translocated to the

interior of the cell. Current treatment

models include the use of MMP

inhibitors. The disclosed technology

provides a viable alternative to this

model and has the advantage of being

highly targetable and specific to tumor

cells expressing MMPs or plasminogen

activators.

The above mentioned Invention is

available, including any available

foreign intellectual property rights, for

licensing.

Dated: January 12, 2000.

Jack Spiegel,

Division of Technology Development &

Transfer, Office of Technology Transfer.

[FR Doc. 00–1423 Filed 1–20–00; 8:45 am]

BILLING CODE 4140–01–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

Government-Owned Invention;

Availability for Licensing:

‘‘Compositions and Methods for

Specifically Targeting Tumors—Using

a Blocker Reagent’’

AGENCY: National Institutes of Health,

Public Health Service, DHHS.

ACTION: Notice.

SUMMARY: The invention listed below is

owned by an agency of the U.S.

Government and is 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.

ADDRESSES: Licensing information and a

copy of the U.S. patent application

referenced below may be obtained by

contacting J.R. Dixon, Ph.D., at the

Office of Technology Transfer, National

Institutes of Health, 6011 Executive

Boulevard, Suite 325, Rockville,

Maryland 20852–3804 (telephone 301/

496–7056 ext 206; fax 301/402–0220; EMail: jd212g@NIH.GOV). A signed

Confidential Disclosure Agreement is

required to receive a copy of any patent

application.

SUPPLEMENTARY INFORMATION: Invention

Title: ‘‘Compositions and Methods for

Specifically Targeting Tumors’’

Inventors: Drs. Waldemar Debinski

(EM) and Raj K. Puri (U.S.F.D.A.).

USPA SN: 08/706,207 [=DHHS Ref.

No. E–042–00/0]—Filed with the

U.S.P.T.O. on August 30, 1996.

Abstract

In a chimeric molecule, two or more

molecules that exist separately in their

native state are joined together to form