11594 Federal Register / Vol. 66, No. 38 / Monday, February 26, 2001 / Notices

specific mutations in HIV–1 Env on

humoral and cellular immune responses

after DNA vaccination has been

investigated. The modifications of Env

enhance antibody production to this

viral protein that may facilitate the

generation of broadly neutralizing

antibodies to HIV. In addition, the

immune response to HIV–1 Gag and Pol

after plasmid DNA immunization with

Rev-independent expression vectors

encoding various forms of these proteins

has been examined. The Gag-Pol fusion

protein induced the most broad and

potent CTL responses to Gag and Pol in

DNA-vaccinated mice. These DNA

sequences and proteins may be

important immunogens for the

treatment and prevention of HIV

infection.

Mucosal Cytotoxic T Lymphocyte

Responses

Jay A. Berzofsky (NCI), Igor M. Belyakov

(NCI), Michael A. Derby (NCI), Brian L.

Kelsall (NIAID), Warren Strober (NIAID)

Serial Number 09/508,552 filed June 12,

2000; DHHS Reference No. E–268–97/4

filed January 10, 2001

Licensing Contact: Peter Soukas; 301/496–

7056, ext. 268; e-mail: soukasp@od.nih.gov

This invention claims methods and

compositions for inducing a protective

mucosal cytotoxic T lymphocyte (CTL)

response in a mammal involving

administering a soluble antigen or a

soluble antigen with one or more active

agents such as a cytokine or costimulatory molecule to a mucosal

surface or tissue. As a preferred

embodiment, the invention

contemplates intrarectal administration

of the peptide vaccine because the

inventors have shown that there is a

greater CTL response through intrarectal

administration rather than intranasal

administration. The synthetic peptide

vaccines utilized in the invention to

elicit protective immune responses after

mucosal infection comprise a

multideterminant helper peptide

containing a cluster of overlapping

helper epitopes (a PCLUS or cluster

peptide) colinearly synthesized with a

peptide epitope target for neutralizing

antibodies and CTL. The inventors have

generated data showing that an

intrarectally administered synthetic

multiepitope HIV/SIV peptide vaccine

administered to macaques in

conjunction with mutant E. coli heat

labile enterotoxin as an adjuvant

induces mucosal CTL responses that

provide better protection against

intrarectal SHIV infection when

compared to a subcutaneously

administered vaccine comprising the

same peptides inducing as high or

higher systemic CTL responses. The

invention is further described in

Belyakov et al., Proc. Natl. Acad. Sci.

USA 1998 Feb 17;95(4):1709–14 and

Belyakov et al., J. Clin. Invest. 102:

2072–2081, 1998.

A Novel Chimeric Protein for

Prevention and Treatment of HIV

Infection

Edward A. Berger (NIAID), Christie M. Del

Castillo

Serial No. 60/124,681 filed 16 Mar 1999 and

PCT/US00/06946 filed 16 Mar 2000

Licensing Specialist: Peter Soukas; 301/496–

7056 ext. 268; e-mail: soukasp@od.nih.gov

This invention relates to bispecific

fusion proteins effective in viral

neutralization. Specifically, the

invention is a genetically engineered

chimeric protein containing a soluble

extracellular region of human CD4

attached via a flexible polypeptide

linker to a single chain human

monoclonal antibody directed against a

CD4-induced, highly conserved HIV

gp120 determinant involved in

coreceptor interaction. Binding of the

sCD4 moiety to gp120 induces a

conformational change that enables the

antibody moiety to bind, thereby

blocking Env function and virus entry.

This novel bispecific protein displays

neutralizing activity against genetically

diverse primary HIV–1 isolates, with

potency at least 10-fold greater than the

best described HIV–1 neutralizing

monoclonal antibodies. The agent has

considerable potential for prevention of

HIV–1 infection, both as a topical

microbicide and as a systemic agent to

protect during and after acute exposure

(e.g. vertical transmission; postexposure prophylaxis). It also has

potential utility for treatment of chronic

infection. Such proteins, nucleic acid

molecules encoding them, and their

production and use in preventing or

treating viral infections are claimed.

Antimicrobial Magainin Peptides

Michael A. Zasloff, Hao-Chia Chen, Judith H.

Brown, John L. Morell, Charng-Ming

Huang (NICHD)

Serial No. 07/280,363 filed 12/06/1988, now

U.S. Patent 5,221,732; Serial No. 07/

021,493 filed 03/04/1987, now U.S. Patent

4,810,777; Serial No. 07/834,992 filed 02/

14/1992, now U.S. Patent 5,567,681; Serial

No. 07/963,007 filed 10/19/1992, now U.S.

Patent 5,643,876

Licensing Contact: Peter Soukas; 301/496–

7056 ext. 268; e-mail: soukasp@od.nih.gov

First isolated from the skin of the

African clawed frog Xenopus laevis,

magainin peptides have been shown by

the inventors to have broad-spectrum

antimicrobial properties. Both synthetic

and natural magainin peptides are

active against many species of bacteria

and fungi and induce osmotic lysis of

protozoa. Magainin peptides are water

soluble, nonhemolytic at effective

antimicrobial concentrations, have

molecular weights of 2500 or less and

are amphiphilic. Compositions and

methods for their use are claimed in the

patents. These inventions are available

for nonexclusive or exclusive licensing.

The inventions are further described in

Zasloff et al., P.N.A.S. USA 1987

Aug.;84(15):5449–53; Marion et al.,

FEBS Lett. 1988 Jan.18;227(1):21–6;

Soravia et al., FEBS Lett. 1988 Feb.

15;228(2):337–40; Westerhoff et al.,

P.N.A.S. USA 1989 Sep.;86(17):6597–

601; and Gwadz et al., Infect. Immun.

1989 Sep.; 57(9):2628–33.

Dated: February 15, 2001.

Jack Spiegel,

Director, Division of Technology Development

and Transfer, Office of Technology Transfer,

National Institutes of Health.

[FR Doc. 01–4616 Filed 2–23–01; 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.

Plasmids Expressing START Domains

of StAR and MLN64

Dr. Yosuke Tsujishita and Dr. James Hurley

(NIDDK)

DHHS Reference No. E–020–01/0

Licensing Contact: Marlene Shinn; 301/496–

7056 ext. 285; e-mail: shinnm@od.nih.gov

Federal Register / Vol. 66, No. 38 / Monday, February 26, 2001 / Notices 11595

Steroidogenic acute regulatory protein

(StAR) manages acute steroidogenesis in

the adrenal cortex and gonads by

promoting the translocation of

cholesterol to the mitochondrial inner

membrane where initial steroid

biosynthesis is catalyzed. Within StAR

are StAR related lipid transfer (START)

domains which are 200–210 amino acid

motifs that occur in a remarkably wide

range of proteins involved in diverse

cell functions such as lipid transport

and metabolism, signal transduction

and transcription regulation. The closest

homolog to StAR is MLN64, with 35%

sequence identity between their START

domains.

The technology embodied in this

invention encompasses plasmids

expressing START domains of StAR and

MLN64. These fragments enable

expression of proteins for many

biochemical studies and specifically

towards cholesterol transfer in acute

steroidegenesis. Possible commercial

applications include targets for cancer

treatment to known over expressed

MLN64 in breast carcinoma.

Macromolecular Enzyme Substrates

Glen L. Hortin (CC)

DHHS Reference No. E–233–99/0 filed 31 Jul

2000

Licensing Contact: Dennis Penn; 301/496–

7056 ext. 211; e-mail: pennd@od.nih.gov

This invention discloses a new class

of reagents used to measure the activity

of enzymes. The inventor discovered

that connecting a small reagent

molecule onto a polymer that serves as

a large carrier molecule confers

advantages in the measurement of

enzyme activity. Advantages of the new

class of reagents are: (1) Better modeling

of the size of natural targets (substrates)

of many biologically important

enzymes, (2) improved specificity of

measurements, (3) ability to measure the

influence of substrates size on enzyme

activity (carrier group size can be varied

over a wide range), (4) improved

substrate solubility, and (5) the potential

for easier methods of synthesis and

purification of some enzyme substrates.

Reagents of this class can be used to

measure the activity of components

forming and breaking down blood clots,

of digestive components, of components

of the complement system, and of many

other components with essential

biological functions.

Efficient Generation of Midbrain

Neurons From Mouse Embryonic Stem

Cells

Sang-Hun Lee, Nadya Lumelsky, Lorenz

Studer and Ronald McKay (NINDS)

DHHS Reference No. E–291–99/0 filed May

1, 2000

Licensing Contact: Norbert Pontzer; 301/496–

7735, ext. 284; e-mail:

pontzern@od.nih.gov

Parkinson’s disease is a progressive

neurological disorder affecting an

estimated one million patients in the

United States. Parkinson’s disease

occurs when dopamine producing cells

in the central nervous system

degenerate. Currently patients receive

medications to treat the symptoms, but

not cure or stop the progression of the

disease. As the disease progresses the

medications usually become less

effective. One encouraging new form of

therapy replaces the lost dopamine

producing neurons with transplanted

cells. A major obstacle to cell

replacement therapy has been obtaining

sufficient dopamine producing cells.

Therapeutic or ethical problems exit for

all presently available sources of cells

for transplantation.

This invention provides a method for

efficiently generating dopaminergic

neurons from embryonic stem cells.

Embryonic cells are totipotent cells

which can proliferate indefinitely in the

undifferentiated state. A method of

generating specific differentiated cells

from embryonic stem cells thus

provides a potentially unlimited source

of those cells. A sequence of culturing

steps involving exposure to specific

neurotrophic factors and other agents

produces a high percentage of cultured

dopaminergic neurons. An unlimited

supply of dopaminergic neurons which

may be suitable for transplantation is

thus provided. Details of some aspects

of this invention can be found in Nature

Biotechnology Vol. 18, pages 675–679,

June 2000.

Methods for Delivering Biologically

Active Molecules Into Cells

Jeffrey L. Miller, Urszula Wojda, Paul K.

Goldsmith (NIDDK)

DHHS Reference Nos. E–174–98/0 filed 15

Jan 1999 and E–174–98/1 filed 14 Jan 2000

Licensing Contact: Dennis Penn; 301/496–

7056 ext. 211; e-mail: pennd@od.nih.gov

The appropriate gene therapy delivery

system depends greatly on the cells

being targeted and the means by which

delivery is anticipated. Numerous

clinical trials are currently ongoing for

gene therapy, each typically usually a

different mode of delivery. It is still too

early to determine which mode will be

approved and which will be the most

effective. The polyethylenimineDNA

(PEI–DNA) complex is known to be an

effective system for delivery of DNA. In

vitro models of a new delivery system

based on the cationic properties of PEI

have found that the cellular

incorporation is significantly enhanced

using an Avidin-PEI–DNA complex.

Experiments have shown that there is, at

a minimum, a 3x to 10x increase in the

cellular uptake of the DNA. It is

believed that this gene delivery system

can be targeted to any cell of interest. It

was demonstrated that the transfection

can be targeted to native and

biotinylated cells. For cells, with a

known surface phenotype, biotinylated

monoclonal antibodies can be attached

to specific sites and the Avidin-PEI–

DNA complex then binds and enters the

cell via endocytosis.

Alternatively, cells without a known

surface phenotype, biotin can be

covalently attached to the cell surface

and the Avidin-PEI–DNA complex is

then able to bind and carry the DNA

into the cells. This system appears to be

not only applicable to gene therapy, but

to the diagnostic market and to the

delivery of other anionic materials into

cells. This Avidin-PEI–DNA system may

find a niche market or it may become

utilitarian, such that it can be effectively

utilized in more than one gene therapy

treatment. This technology is available

for immediate licensing and

independent commercialization and/or

a Cooperative and Development

Research Agreement can be considered.

Dated: February 15, 2001.

Jack Spiegel,

Director, Division of Technology Development

and Transfer, Office of Technology Transfer,

National Institutes of Health.

[FR Doc. 01–4617 Filed 2–23–01; 8:45 am]

BILLING CODE 4140–01–P

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

Prospective Grant of Co-Exclusive

License: Homogeneous Tests for

Sequentially Determining Lipoprotein

Fractions

AGENCY: National Institutes of Health,

Public Health Service, DHHS.

ACTION: Notice.

SUMMARY: This is notice, in accordance

with 35 U.S.C. 209(c)(1) and 37 CFR

404.7(a)(1)(i), that the National

Institutes of Health (NIH), Department

of Health and Human Services, is

contemplating the grant of a coexclusive worldwide to practice the

inventions embodied in US Patent

Application Serial Number (60/136,709

(PCT/US00/14827) entitled

‘‘Homogeneous Tests for Sequentially

Determining Lipoprotein Fractions’’,

provisionally filed May 28, 1999 and

PCT filed May 26, 2000, to Genzyme

Diagnostics, having a place of business