Federal Register / Vol. 65, No. 79 / Monday, April 24, 2000 / Notices 21771

specific for prostate adenocarcinomas

and other prostate cancer cells.

Accordingly, methods of therapy can be

employed with this monoclonal

antibody to destroy prostate cancer

cells, and hence, this monoclonal

antibody may be useful in therapy and/

or the diagnosis of prostate cancer. This

monoclonal antibody can be produced

by recombinant DNA techniques, the

host cell being a eucaryotic or

procaryotic cell, preferably a eucaryotic

cell and more preferably mammalian.

Hence, a monoclonal antibody, a

recombinant monoclonal antibody,

single polypeptide binding molecules,

and binding fragments thereof coupled

to molecules which are cytotoxic to

prostate cancer cells (e.g.,

chemotherapeutic agents, prodrugs,

cytotoxic or inhibitory peptides,

cytokines, enzymes, diphtheria toxin,

Pseudomonas Exotoxin, etc.) could be

used to develop a prostate cancer

therapeutic or diagnostic test system.

The above mentioned Invention and

technology are available for licensing.

Dated: April 18, 2000.

Jack Spiegel,

Director, Division of Technology Development

& Transfer, Office of Technology Transfer.

[FR Doc. 00–10177 Filed 4–21–00; 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

contacting Girish C. Barua, 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. 263; fax: 301/402–0220;

e-mail: BaruaG@od.nih.gov. A signed

Confidential Disclosure Agreement will

be required to receive copies of the

patent applications.

Compositions and Methods for

Treatment of Breast Cancer—the

Synergistic Effect of Farnesyl

Transferase Inhibitors and Tamoxifen

Combination Therapy

Geoffrey J. Clark, Joanne Zujewski (NCI)

Serial No. 60/171,928 filed 22 Dec 1999

This invention discloses compositions

that act in a synergistic manner to

inhibit and or prevent breast cancer cell

growth. Specifically, this invention

discloses methods for treating and

preventing breast cancer using a

combination of selective estrogen

receptor modulators (SERMs) and

farnesyl transferase inhibitors (FTIs).

The combination therapy comprising of

at least one SERM and at least one FTI

has shown enhanced therapeutic

efficacy in killing cancer cells. Thus the

combination therapy may lead to

enhance efficacy of Tamoxifen or other

SERM treatment regimes. For example,

it is contemplated that the present

invention will find use in a treatment

therapy using lower doses of SERMs for

a shorter duration. In some

embodiments of the invention,

therapeutic agents are administered to

subjects suspected of having cancer or

being susceptible to cancer, subjects

with cancer, subjects experiencing a

recurrence of cancer, or subjects who

are post-operative for cancer.

Additionally, the treatment agents could

be administered prophylactically to

patients at risk for development of

cancer.

Tyrosyl-DNA Phosphodiesterases (TDP)

and Related Polypeptides, Nucleic

Acids, Vectors, TDP-Producing Host

Cell, Antibodies and Methods of Use

Jeffrey J Pouliot, Howard A Nash

(NIMH)

Serial No. 60/157,690, filed 05 Oct 1999

Topisomerases are cellular enzymes

that are vital for replication of the

genome. However, if topisomerase and

DNA form covalent complexes that

prevent the resealing of DNA, this may

lead to cell death. Essentially, this

invention consists of a new isolated and

cloned enzyme, tyrosyl-DNA

phosphodiesterase (TDP1), that is

capable of hydrolyzing the covalent

complexes between topisomerase and

DNA, allowing the DNA to reseal. The

mechanism that defines topisomerases

is their capacity to break DNA and, after

an interval in which topological changes

may occur, to reseal the break without

the intervention of a high energy

cofactor. The breakage of the DNA is

accompanied by the formation of a

covalent bond between topisomerase

and DNA to create an intermediate that

is resolved during the resealing step.

However, if the resealing step fails, the

covalent intermediates between

topisomerase I and DNA can become

complexes that lead to cell death. The

failure of the resealing is increased by

some chemotherapies such as

camptothecin. Thus, this technology has

many potential commercial uses

including: a method for screening

camptothecin analogues or other

compounds for their resistance to repair

by this enzyme or to prescreen patients

for their sensitivity to topisomerase

inhibitors which could identify patients

most likely to respond to camptothecin

therapy. Further, this invention

provides for a vector comprising of the

nucleic acid molecule for TDP1 as well

as the method of altering the level of

TDP1 in a cell, a tissue, an organ or an

organism. Finally, this invention

consists of a method for identifying a

compound that stabilizes a covalent

bond complex that forms between DNA

and topisomerase I, wherein the

covalent bond cannot be cleaved.

Novel Vacuolar-Type (H+)-V-ATPaseInhibitory Compounds, Compositions

and Methods of Use

Michael R. Boyd (NCI)

Serial No. 60/122,953 filed 05 Mar 1999

and Serial No. 60/169,564 filed 08

Dec 1999

The present invention relates to a new

class of vacuolar-type (H+)-ATPaseinhibitory compounds. Vacuolar-type

(H+)-ATPases (V-ATPases) have been

described as a universal proton pump

which are present in many tissues and

cells of the human body. Vacuolar-type

(H+)-ATPases are present intracellularly

within certain organelles and are

responsible for maintaining internal

acidity thereof; V-ATPases are also

located within specialized plasma

membranes of certain cells, e.g. kidney

intercated cells, osteoclasts and sperm

cells. V-ATPases are important for a

myriad of physiological functions such

as: sorting of membrane and organellar

proteins; proinsulin conversion;

neurotransmitter uptake; receptor

recycling; and cellular degradative

processes. V-ATPase isoform-specific

inhibitors may preferentially modulate

V-ATPase activities in different cells

and tissues, and may thereby provide

diverse and distinctive pharmacological

utilities. Accordingly, the disclosed

compounds and compositions may be

used to inhibit such biological processes

as: intra-organellar acidification, urinary

acidification; bone resorption; fertility;

21772 Federal Register / Vol. 65, No. 79 / Monday, April 24, 2000 / Notices

tumor cell proliferation; and, drug

resistance of tumor cells.

Dated: April 17, 2000.

Jack Spiegel,

Director, Division of Technology Development

and Transfer, Office of Technology Transfer,

National Institutes of Health.

[FR Doc. 00–10178 Filed 4–21–00; 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

contacting Carol A. Salata, Ph.D., at the

Office of Technology Transfer, National

Institutes of Health, 6011 Executive

Boulevard, Suite 325, Rockville,

Maryland 20852–3804; telephone: 301/

496–7735 ext. 232; fax: 301/402–0220;

e-mail: cs253n@nih.gov. A signed

Confidential Disclosure Agreement will

be required to receive copies of the

patent applications.

Molecular Clones With Mutated HIV

GAG/POL and SIV Genes

George N Pavlakis (NCI)

Serial No. 60/173,036 filed 23 Dec 1999

The invention is a DNA construct

which can be used as part of an HIV

DNA vaccine or as a lentiviral vector to

deliver heterologous DNA to cells. The

advantage of lentiviral vectors, over

retroviral vectors, is that they can

transduce quiescent cells, such as

terminally differentiated neurons. The

advantage of the lentiviral vectors of the

invention over the lentiviral vectors of

the prior art are that they can be highly

expressed in human or mammalian cells

in the absence of any other regulatory or

structural protein of HIV, including

REV. The advantage of vectors based on

SIV is that they are divergent from HIV–

1.

The construct encodes the gag/pol

region of the HIV–1 genome in which

the instability regions (INS) have been

removed by multiple point mutations,

without changing the protein sequence.

The INS are regions in the unspliced

RNA which decrease the amount of

expression from the RNA, a decrease

which is overcome by the interaction of

the HIV protein REV with the RRE (Rev

Response Element) found on the RNA

constructs encoding gag, pol and env of

HIV–1. Under certain situations the

construct can result in the formation of

infectious viral particles which contain

only gag and pol from HIV. These viral

particles can be used as vaccines or for

gene therapy.

Time-Gated Imaging With a Split-Beam

Source

Ronald W. Waynant (FDA)

Serial No. 60/153,100 filed 09 Sep 1999

The present invention provides a new

apparatus and methods for generating a

split-beam electromagnetic source for

imaging devices and methodologies.

With this invention, one part of a split

beam is used for generating an image of

an object and another part of the split

beam is used for timely capturing the

generated image. The present invention

offers many advantages over earlier

technologies. For example: (1) switching

with a short duration pulse allows for a

fast time gate; (2) utilization of an

electromagnetic pulse source to both

image and time gate allows for easier

and more precise synchronization of the

time gate with the imaging source; and

(3) optically switching the time gate

solves the problem of jitter and

inhomogeneous gating.

Identification of the Domain of

Plasmodium falciparum Erythrocyte

Membrane Protein (PfEMP1) that

Mediates Adhesion to Chondroitin

Sulfate A

Arthur Scherf et al. (NIAID)

Serial No. 60/152,023 filed 01 Sep 1999

Plasmodium falciparum malaria is

more severe in pregnant women and

causes disease in the mother and fetal

death, even in those women who were

previously immune. Severe malaria

during pregnancy is more common

during the first pregnancy

(primigravida) and much less after

multiple pregnancies (multigravid).

Pregnant women are infected by

parasites that sequester in the placenta

and such sequestration contributes to

growth retardation, infant mortality and

severe anemia. Multigravid women

develop antibodies that block the

adhesion of infected erythrocytes to

their placental receptor, chondroitin

sulfate A (CSA). This interaction is

mediated by specific var (PfEMP1) genes

that bind to the host receptor CSA. The

domain of the CSA-binding var gene

that mediates adherence to CSA has

been identified. This domain and

potentially other parts of the molecule

can give rise to development of anti

malaria vaccines and therapeutics that

will protect women from placental

malaria, particularly during their first

pregnancy.

Method for Generating NMR Relaxation

Data and Identifying Ligands to Target

Molecules From Multiple Field NMR

Spectra

David Fushman, Nico Tjandra (NHLBI),

David Cowburn

Serial No. 09/385,227 filed 27 Aug 1999

The present invention provides a

nuclear magnetic resonance relaxation

method of screening compounds for

their ability to bind to target molecules

and elicit site specific changes in the

target molecule’s structure. Specifically,

this application pertains to a method of

generating site specific nuclear

relaxation data for target molecules and

their ligands. These data can be used for

exploration into the thermodynamic

requirements of ligand binding, the

calculation of structural constraints

helpful in predicting the solution

structure of a target molecule and its

ligand complexes, and to design new

ligands for target molecules.

Fast Displacement Encoding with

Stimulated Magnetic Resonance Echoes

by Sampling Both Components of a

Stimulated Echo

Anthony H. Aletras, Han Wen (NHLBI)

Serial No. 60/147,314 filed 05 Aug 1999

The present invention provides a

nuclear magnetic resonance method of

phase contrast motion encoding. This

methodology samples both the

simulated-echo and the simulated-antiecho by means of multiple 180 degree

refocusing radiofrequency pulses. The

pulses produced by the disclosed

methods are compatible for

reconstructing images without the need

for elaborate data processing steps. By

combining this method with pulses with

unequal first order moments, dynamic

range of motion measurements, in the

heart, can be extended within the time

period of a breath-hold in humans.

Utilizing this powerful new

methodology, a variety of diagnostic

information can be learned about

cardiac function in normal and diseased

states.