Federal Register / Vol. 65, No. 225 / Tuesday, November 21, 2000 / Notices 69949

1. A demonstrated record of success

in some or all of the following areas:

molecular biology, the development of

small molecule therapeutics, and high

throughput screening of compounds.

2. A demonstrated background and

expertise in growth factor and cytokine

research.

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:November 12, 2000.

Kathleen Sybert,

Chief, Technology Development and

Commercialization Branch, National Cancer

Institute, National Institutes of Health.

[FR Doc. 00–29718 Filed 11–20–00; 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.

Enhanced Homologous Recombination

Mediated by Lambda Recombination

Proteins

Donald L. Court, Daiguan Yu, EChaing Lee, Hilary Ellis, Nancy A.

Jenkins, Neal G. Copeland (NCI), DHHS

Reference No. E–177–00/0 filed 14 Aug

2000, Licensing Contact: Dennis Penn;

301/496–7056 ext. 211; e-mail:

pennd@od.nih.gov.

The present invention concerns

methods to enhance homologous

recombination in bacteria and

eukaryotic cells using recombination

proteins derived from bacteriophage

lambda. It also concerns methods for

promoting homologous recombination

using other recombination proteins.

Concerted use of restriction

endonucleases and DNA ligases allows

in vitro recombination of DNA

sequences. The recombinant DNA

generated by restriction and ligation

may be amplified in an appropriate

microorganism such as E. coli, and used

for diverse purposes including gene

therapy. However, the restrictionligation approach has two practical

limitations: first, DNA molecules can be

precisely combined only if convenient

restriction sites are available; second,

because useful restriction sites often

repeat in a long stretch of DNA, the size

of DNA fragments that can be

manipulated are limited, usually to less

than about 20 kilobases.

Homologous recombination, generally

defined as an exchange of homologous

segments anywhere along a length of

two DNA molecules, provides an

alternative method for engineering

DNA. In generating recombinant DNA

with homologous recombination, a

microorganism such as E. coli, or a

eukaryotic cell such as a yeast or

vertebrate cell, is transformed with an

exogenous strand of DNA. The center of

the exogenous DNA contains the desired

transgene, whereas each flank contains

a segment of homology with the cell’s

DNA. The exogenous DNA is introduced

into the cell with standard techniques

such as electroporation or calcium

phosphate-mediated transfection, and

recombines into the cell’s DNA, for

example with the assistance of

recombination-promoting proteins in

the cell.

In generating recombinant DNA by

homologous recombination, it is often

advantageous to work with short linear

segments of DNA. For example, a

mutation may be introduced into a

linear segment of DNA using

polymerase chain reaction (PCR)

techniques. Under proper

circumstances, the mutation may then

be introduced into cellular DNA by

homologous recombination. Such short

linear DNA segments can transform

yeast, but subsequent manipulation of

recombinant DNA in yeast is laborious.

It is generally easier to work in bacteria,

but linear DNA fragments do not readily

transform bacteria (due in part to

degradation by bacterial exonucleases).

Accordingly, recombinants are rare,

require special poorly-growing strains

(such as RecBCD-strains) and generally

require thousands of base pairs of

homology. This invention teaches an

improved method of promoting

homologous recombination in bacteria.

In eukaryotic cells, targeted

homologous recombination provides a

basis for targeting and altering

essentially any desired sequence in a

duplex DNA molecule, such as targeting

a DNA sequence in a chromosome for

replacement by another sequence. This

invention teaches methods useful for

treating human genetic diseases, the

creation of transgenic animals, or

modifying the germline of other

organisms.

Amelogenin Knockout Mice and Use as

Models for Tooth Disease

Dr. Ashok Kulkarni et al. (NIDCR),

DHHS Reference No. E–167–00/0,

Licensing Contact: John Rambosek; 301/

69950 Federal Register / Vol. 65, No. 225 / Tuesday, November 21, 2000 / Notices

496–7056 ext. 270; e-mail:

rambosej@od.nih.gov.

This technology relates to transgenic

knockout mice that may serve as an

animal model for dental disease. Using

gene-targeting techniques, mice have

been created which are disrupted for the

amelogenin gene. These mice lack the

amelogenin protein, which is normally

expressed only in the teeth. Since these

mice lack this protein, they are expected

to mimic an inherited tooth disorder

called ‘‘amelogenesis imperfecta (AI)’’.

AI is an inherited condition that is

transmitted as a dominant trait and

causes the enamel of the tooth to be soft

and thin resulting in discoloration,

disintegration and disfigurement of the

teeth. The damaged teeth are also

susceptible to decay. The amelogenin

knockout mice display an interesting

tooth phenotype. Their maxillary

incisors are chalky white in color and

opaque in appearance.

These changes are associated with

mild attrition of incisor tips and molar

cusps. Detailed analysis of this

phenotype is in progress. The

amelogenin knockout mice may be used

as an animal model to develop

therapeutic approaches to AI.

Transgenic Mouse Model for Tooth

Disorders Such as Dentin Dysplasia and

Dentinogenesis Imperfecta

Drs. Thyagarajan, Sreenath, and

Kulkarni (NIDCR), DHHS Reference No.

E–150–00/0, Licensing Contact: John

Rambosek, Ph.D.; 301/496–7056; e-mail:

rambosej@od.nih.gov.

This technology describes transgenic

mice that selectively overexpress

transforming growth factor beta-1 (TGFbeta1) in odontoblast and ameloblast

cells of teeth. Ameloblasts mainly make

enamel, whereas odontoblasts make

dentin. These transgenic mice mimic

dental symptoms similar to those seen

in common tooth disorders such as

dentin dysplasia and dentinogenesis

imperfecta. Both of these human dentin

defects are inherited in an autosomal

dominant manner and appear to be

caused by abnormal dentin production

by odontoblasts and associated poor

mineralization of the dentin matrix. In

both diseases, teeth are discolored and

fractured, causing difficulties in eating

food. Experimentally, these mice

display discolored and fractured teeth

with defective dentin. This transgenic

mice model will be valuable to advance

our understanding of the molecular

pathogenesis underlying dentin

dysplasia and dentinogenesis imperfecta

and also for developing therapeutic

strategies.

This material is available for licensing

through a PHS Biological Materials

License.

Dated: November 13, 2000.

Jack Spiegel,

Director, Division of Technology Development

and Transfer, Office of Technology Transfer,

National Institutes of Health.

[FR Doc. 00–29716 Filed 11–20–00; 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 Dale Berkley, Ph.D., J.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. 223; fax:

301/402–0220; e-mail:

berkleyd@od.nih.gov. A signed

Confidential Disclosure Agreement will

be required to receive copies of the

patent applications.

Automated Core Biopsy Instrument

Erik Kass, Carter Vanwaes (NIDCD),

DHHS Reference No. E–269–00/0 filed

20 Sep 2000.

The invention is an automated core

biopsy instrument that may be operated

with one hand. The instrument has a

single activation element that causes a

stylet to advance into the tissue of

interest as a cutting cannula disposed

around the stylet is fired to shear off the

tissue into specimen notches disposed

in the stylet. The invention is

constructed so that the stylet and

cutting cannula may be separately

driven and biased. The cocking

mechanism of the automated core

biopsy instrument is used to cock both

the stylet assembly and cutting cannula

assemblies against separate biasing

springs. Manipulation of the cocking

mechanism permits the exposure of

tissue in the specimen notches when

desired. The instrument has a locking

mechanism that is used to prevent

inadvertent firing of the automated core

biopsy instrument.

EZ Navigator and EZ Forms Software

Andrew Schwartz, William K. Jones,

Michelle R. Ugas, Ta-Jen Hu (CIT),

DHHS Reference No. E–236–00/0.

The EZStart invention is a method of

accessing a database management

system that can be used to convert nonrelational data to relational data and

create and manage relational data over

a network such as the Internet. The

invention provides user-friendly access

to data stored in a database management

system, allowing users with little or no

knowledge of database management

systems to access, store and manage

data using only a web browser. EZStart

provides a generic platform from which

any user can select, insert, update and

delete data without creating a custom

software application for each user. The

invention automatically generates

navigation and data forms, allowing

access to a Relational Database

Management System (RDBMS) while

masking the complexity of the RDBMS.

Using a function of EZStart coined

EZNavigator, users can easily maneuver

through the RDBMS, view lists of

objects, drill-down into column, view

and index definitions, and manage

object privileges. A separate function of

EZStart, known as EZForms, allows a

user to select, insert, update and delete

rows in tables. No Structured Query

Language (SQL) knowledge is required

to perform these functions, but

advanced users can use EZForms to

generate SQL into a text area for

modification and execution of the SQL.

The SQL can be saved into and retrieved

from a repository.

Integrated Low Field MRI/RF EPRI for

Co-Registering Imaging of In Vivo

Physiology and Anatomy in Living

Objects

Murali K. Cherukuri et al. (NCI),

DHHS Reference No. E–120–99/0 filed

01 Nov 1999.

Obtaining physiological information

in a non-invasive manner from living

tissue will provide valuable

information, rather than invasive

methods that are sometimes not

available and also may damage living

tissue. EPRI (Electron Paramagnetic

Resonance Imaging) is the technique to

investigate physiological information

such as oxygen imaging and