Federal Register / Vol. 65, No. 79 / Monday, April 24, 2000 / Notices 21773

MRI Contrast Agents Depending on

Proton Chemical Exchange

Robert S. Balaban, Kathleen Ward,

Anthony H. Aletras (NHLBI)

DHHS Reference No. E–240–98/0 filed

21 Apr 1999

Recently, methods have been

developed to Magnetic Resonance

Imaging (MRI) contrast using exogenous

agents with exchangeable protons.

These methods incorporate the use of

selective reagents, such as sugars, amino

acids, and nucleosides with appropriate

proton exchange sites. Image contrast is

generated by using saturation transfer

techniques to selectively affect the water

protons used in forming the MR image.

The contrast agents developed do not

contain metals or metal chelates. The

agents have appropriate exchangeable

proton sites which can be irradiated at

known frequencies to obtain MRI

images with specific contrast. This

permits the image contrast to be turned

off and on based on the irradiation

scheme. This method also uses a

controlled irradiation scheme to

overcome the obstacle of broad proton

resonance that limits contrast

enhancement. In-Vivo data has shown

the utility of this invention.

Oligomeric HIV–1 Envelope

Glycoproteins

Patricia L. Earl, Chris C. Broder, Robert

W. Doms, Bernard Moss (NIAID)

Serial Nos. 08/165,314 filed December

10, 1993; 08/805,889 filed March 3,

1997; 09/070,291 filed April 30, 1998;

and 09/415,326 filed October 8, 1999

This invention embodies a method for

generating antibodies to HIV–1 envelope

glycoproteins, which could hold

powerful implications toward both the

diagnosis and the treatment of AIDS.

Specifically, the method involves the

expression of a soluble protein, gp140,

and the generation of antibodies to this

protein. gp140 is a recombinant version

of gp160, a protein which normally is

cleaved in vivo to generate two

glycoprotein subunits which are

expressed on the surface of the HIV–1

envelope. Unlike previously isolated

versions of gp160, gp140 is purified in

a manner which preserves the

quaternary structural elements of the

protein. Due to the conserved nature of

these structural elements, antibodies

generated against gp140 may be more

broadly reactive against various forms of

AIDS than other antibodies generated to

date.

Dated: April 17, 2000.

Jack Spiegel,

Director, Division of Technology Development

and Transfer, Office of Technology Transfer,

National Institutes of Health.

[FR Doc. 00–10179 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 Susan S. Rucker, J.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. 245; fax: 301/402–0220;

e-mail: sr156v@nih.gov. A signed

Confidential Disclosure Agreement will

be required to receive copies of the

patent applications.

Hybrid Adeno-Retroviral Vector for the

Transformation of Cells

C Zheng, B O’Connell, BJ Baum (NIDCR)

Serial No. E–258–98/0 filed 31 Jan 2000

The invention described and claimed

in this patent application provides for

novel hybrid vectors which may be used

for cell transformation, either in vivo or

in vitro. The hybrid vectors have an

adenoviral backbone with retroviral

long terminal repeats (LTRs). Such

vectors are capable of transforming

dividing or non-dividing cells and

integrate stably into the chromosome

providing a means of efficient, reliable,

long-term gene expression. The vector

was packaged as a recombinant

adenovirus and delivered to the target

cell. Unlike other chimeric or hybrid

vector systems, only a single vector is

required to deliver a transgene of

interest, and retroviral structural

proteins are not required.

This work has been published in part

in Nature Biotechnology Zheng, et al.

18(2): 176–180 (Feb 2000).

Calcium Channel Compositions and

Methods of Use Thereof

MI Lerman (NCI) et al.

Serial No. 09/470,443 filed 22 Dec 1999

and 60/114,359 filed 30 Dec 1998

(now abandoned)

This invention described in this

patent application relates to the

identification, isolation and cloning of a

three cDNAs identified during a search

of the short arm of chromosome 3 for a

tumor suppressor gene (TSG) associated

with lung cancer. The cDNA’s are

alternative isoforms which encode a

protein which functions as a subunit of

L-type voltage-dependent calcium

channel. Type L voltage-dependent

calcium channels represent one of five

families of calcium channels, L, R, P, N,

Q, which have been identified. Type L

voltage-dependent calcium channels are

found in a wide variety of tissues

including the brain, muscle and the

endocrine system.

The gene has been mapped to the

short arm of chromosome 3 at 3p21.3.

The gene, which corresponds to this

cDNA is an alpha2delta-2 (α2δ-2)

subunit, and has been shown to be

deleted in lung and breast cancer. The

scientists have demonstrated that the

expression of this calcium channel has

been shut off in lung cancer cells and

hypothesize that this may lead to a

malignant phenotype. Other cancers

which may be associated with this α2δ2 subunit include cervical cancer and

head and neck carcinoma. Other nonmalignant diseases which may also be

associated with this α2δ-2 subunit

include CNS diseases and

cardiovascular diseases.

Possible applications of this

technology include its use in drug

screening assays; its use as an early

diagnostic marker and/or as a prognostic

or treatment indicator; its use in gene

therapy where defective cells would be

reconstituted with the gene and as a

therapeutic agent for clearing

autoantibodies which develop toward

the alpha2delta-2 subunit in the disease

Lambert-Eton myasthenia syndrome.

Monoclonal Antibody Against Met

Protein

G Vande Woude, M Oskarsson, J Resau,

S Rulong, Y Chui (NCI–FCRDC)

Serial No. 60/168,835 filed 03 Dec 1999

The invention described in this

application relates to the Hepatocyte

Growth Factor/Scatter Factor/Tumor

Cytotoxic Factor (HGF/SF/F–TCF)-met/

Hepatocyte Growth Factor Receptor

21774 Federal Register / Vol. 65, No. 79 / Monday, April 24, 2000 / Notices

(HGFr) pathway. In particular, the

invention described in this application

is a murine monoclonal antibody,

designated D1, which specifically binds

to an epitope in the extracellular

domain of human HGFr/met. The

monoclonal antibody can be used, for

example, to visualize HGFr/met

expression in paraffin-embedded tumor

samples and in drug screening assays

(competitive binding assays) for

antagonists/agonists of HGFr/met.

Determination of AM Binding Proteins

and the Association of Adrenomedullin

(AM) Therewith

F Cuttitta (NCI), A Martinez (NCI), R Pio

(NCI), TH Elasser (USDA–ARS),

Serial No. 60/153,397 filed 10 Sep 99

This application relates to isolation

and identification of a polypeptide

which binds to the hormone

adrenomedullin designated

adrenomedullin binding protein 1

(AMBP1). Adrenomedullin (AM), a

peptide hormone, has been implicated

in a variety of physiological functions

including the regulation of insulin

production, anti-microbial activity,

mitogenesis and angiogenesis. The

activities of AM are believed to be

mediated by a variety of binding

proteins in a manner similar to the way

in which Insulin-like Growth Factor

(IGF) is regulated. AMBP1 has been

purified to homogeneity and its amino

acid sequence determined.

The application is directed to

methods of measuring AM levels in

plasma based on the finding that

AMBP1 binds in a specific and

reversible competitive fashion with AM

and methods of treating AM related

disease by administering AMBP1. Other

aspects of the invention are complexes

of AM with AMBP1 and antibodies

which specifically bind to an epitope by

the complex of AM with AMBP1 as well

as assays for detecting the complex of

AM with AMBP1.

This work has been published in part

in Elsasser TH, et al. Endocrinology

140(10):4908–11 (Oct. 1999).

In addition to being available for

licensing the NIH is willing to consider

interest from companies who are

interested in pursuing

commercialization opportunities

through a Cooperative Research and

Development Agreement (CRADA).

AAV5 Vector and Uses Thereof

JA Chiorini, RM Kotin (NHLBI)

Serial No. PCT/US99/11958 filed 28

May 1999 based on USSN 60/087,029

filed 28 May 1998

The invention described and claimed

in this patent application provides for

novel vectors and viral particles which

comprise adeno-associated virus

serotype 5 (AAV5). AAV5 is genetically

distinct from others AAVs with respect

to its capsid proteins, VP1, VP2, and

VP3, which contributes to different

tissue tropisms for AAV5. The ITR and

Rep proteins of AAV5 are also distinct

which results in a biochemically unique

mechanism of replication compared to

the other AAVs. This difference in

replication activity contributes to the

fact that AAV5 is only able to replicate

and package AAV5 ITR containing DNA

in contrast to AAV2 which is able to

replicate and package other AAV

serotypes. Vectors produced using

AAV5 proteins may be useful in gene

therapy.

AAV5 offers several advantages which

make it attractive for use in gene

therapy: (1) increased production (10–

50 fold greater than AAV2); (2) its

distinct replication mechanism when

compared to AAV2; (3) its Rep protein

and ITR regions which do not

complement other serotypes; (4) it

appears to utilize different cell surface

attachment molecules than those of

AAV type 2; and (5) improved efficiency

of transduction of certain cell types

including airway epithelial, striated

muscle, endothelial, and neuronal cells

when compared to AAV type 2.

This work has been published, in

part, in J. Virol. 73(5): 4293–98 (May

1999) and J. Virol. 73(2): 1309–19 (Feb.

1999).

Prevention of Fetal Alcohol Syndrome

and Neuronal Cell Death with ADNF

Polypeptides

DE Brenneman (NICHD), CY Spong

(NICHD), I Gozes (TAU), M Bassan

(TAU), R Zamostiano (TAU)

Serial No. 09/267,511 filed 12 Mar 1999

This patent application describes an

extension of prior work related to

peptides derived from proteins known

as ADNF and ADNF III/ADNP. These

peptides are known as SAL (ADNFderived) and NAP (ADNP-derived). SAL

and NAP (L-isomers) have previously

been demonstrated, in in vitro work, to

be able to prevent neuronal cell death

and to protect against the toxic activities

of a cholinotoxin suggesting that they

are useful as therapeutics for

neurodegenerative diseases. The new

work presented in this EIR demonstrates

that NAP and SAL (L-isomers), alone or

in combination, prevent damage to

neurons due to oxidative stress. In

particular, the new work shows that

NAP and SAL (L-isomers) alone or

together are effective in preventing

damage due to oxidative stress in a

model for fetal alcohol syndrome. Thus,

NAP and SAL (L-isomers), alone or

together may be useful therapeutically

to treat fetal alcohol syndrome.

In addition, a number of other patent

applications and patents related to this

technology have been filed by PHS and

are available for licensing. These

include: USP 5,767,240 (PCT/US92/

03109); 08/324,297 (PCT/US95/12929);

60/037,404 (PCT/US98/07485); 09/

187,330 (PCT/US99/26213) 60/149,956;

and 09/364,609.

Dated: April 18, 2000.

Jack Spiegel,

Director, Division of Technology Development

and Transfer, Office of Technology Transfer,

National Institutes of Health.

[FR Doc. 00–10180 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 Richard U. Rodriguez,

M.B.A., at the Office of Technology

Transfer, National Institutes of Health,

6011 Executive Boulevard, Suite 325,

Rockville, Maryland 20852–3804;

telephone: 301/496–7056 ext. 287; fax:

301/402–0220; e-mail: rr154z@nih.gov.

A signed Confidential Disclosure

Agreement will be required to receive

copies of the patent applications.

Identification of a Novel Amplified

Gene, MB1, at 17q23

Anne H Kallioniemi, Maarit T Barlund,

Outi M Monni, Juha T Kononen, Olli

P Kallioniemi (NHGRI)

DHHS Reference No. E–038–00/0 filed

13 Dec 1999

DNA amplification at 17q23 is one of

the most common genetic alterations in

breast cancer. Genes affected by this

amplification may have a critical role in