39916 Federal Register / Vol. 65, No. 125 / Wednesday, June 28, 2000 / Notices

Dated: June 15, 2000.

Jack Spiegel,

Director, Division of Technology Development

and Transfer, Office of Technology Transfer,

National Institutes of Health.

[FR Doc. 00–16325 Filed 6–27–00; 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.

Gene Profiling Arrays

Ena Wang, Lance Miller, Francesco

Marincola (NCI)

DHHS Reference No. E–086–00/0 filed

28 Mar 2000

Licensing Contact: Richard Rodriguez;

301/496–7056 ext. 287; e-mail:

rr154z@nih.gov

The invention(s) embodied in this

application, provides for ordered arrays

of mixtures of nucleic acid molecules,

which reflect the gene expression

profile of one or more specimens, such

as different cell types or tissues. In

particular embodiments, complete

mRNA mixtures (i.e. gene transcripts) or

cDNA representatives from specimens

are individually arrayed on a substrate.

Such mixtures of nucleic acids can be

derived from any specimen source,

including animal, plant and/or

microbial cells and can be assembled in

any collection desired. The collections

can, for instance, include nucleic acid

mixtures from different cell types,

different phenotypes, cells grown under

different conditions, cells of different

ages or developmental stages, and so

forth. The nucleic acid arrays are

provided in both macro- and microformats and are suitable for measuring

the relative abundance of particular

gene transcripts across a collection of

complex nucleic acid mixtures.

Techniques are also disclosed for

producing high-fidelity, amplified

mixtures of nucleic acid molecules

using a combination of RNA (sense or

anti-sense) amplification and templateswitching synthesis. Amplified mixtures

produced using this method can, for

instance, be applied to the disclosed

arrays. The disclosed arrays allow high

throughput analysis of differential gene

expression in a specimen, such as a

tumor, or a variety of specimens, such

as a variety of tumors, and is suitable for

automated preparation and analysis.

The Isolation of a New Gene, TRAG,

Associated with TGF–Beta

Snorri S. Thorgeirsson, Sean R. Sanders

(NCI)

DHHS Ref. No. E–047–00/0 filed 07 Mar

2000 and 60/187,848 filed 08 Mar

2000

Licensing Contact: Susan S. Rucker;

301/406–7056 ext. 245; e-mail:

sr156v@nih.gov

A new gene has been isolated from a

cell line resistant to a protein, TGF-beta,

which can block the proliferation of

cancer cells. This resistance endows the

cell with cancer forming abilities. The

protein encoded by the newlydiscovered TRAG gene has been found

at much higher levels in these cancerforming cells than their non-cancerous

ancestors. In addition, the TRAG protein

is greatly elevated in many other rodent

and human cancer cell lines and in

primary mouse liver tumors, but not in

surrounding non-tumorous tissue. This

indicates a strong association between

TRAG and cancer-forming potential.

TRAG may be involved in the

mechanism by which normal cells

become cancerous. The TRAG gene

could provide an excellent target for

cancer or gene therapy. Abrogation of

TRAG protein production using antisense oligonucleotides or antibodies

could conceivably prevent, reduce, or

destroy certain types of tumors.

Identification of a Novel Domain in the

Tumor Necrosis Factor Receptor Ligand

Family that Mediates Pre-Ligand

Receptor Assembly and Function

MJ Lenardo, FK Chan, R Siegel (all of

NIAID)

Serial No. 60/181,909 filed 11 Feb 2000

Licensing Contact: Susan S. Rucker;

301/496–7056 ext. 245; e-mail:

sr156v@nih.gov

This application discloses the

identification of a functional domain,

which is essential for signaling

involving receptors of the Tumor

Necrosis Factor Superfamily (TFNR’s)

including TNFR–1 (p60), TNFR–2 (p80),

Fas, TRAIL–R, LTβR, CD40, CD30,

CD27, HVEM, OX40 and DR4. The

functional domain, denoted the PreLigand Assembly Domain (PLAD), can

be isolated as functional polypeptides

which can be useful in inhibiting the

first step in TNFR mediated signaling,

ligand-independent assembly of

members of the TNFR Superfamily. The

ability to inhibit TNFR signaling

suggests that these PLAD polypeptides

may be useful in developing new

therapeutic molecules or as therapeutic

molecules themselves for modulation of

immune responses, apoptosis, and

inflammation.

In addition to being available for

license, the investigators who have

developed this technology are also

willing to consider entering into a

CRADA relationship with companies

interested in commercial development

of this technology.

Transition Metal Complexes of N,N′,N′′-

trialkyl-cis,cis-1,3,5-

triaminocyclohexane and Related

Compositions and Methods

Martin W Brechbiel, Roy P. Planalp,

Kim A. Deal (NCI)

DHHS Reference No. E–072–99/0 filed

10 Aug 1999

Licensing Specialist: Girish C. Barua;

301/496–7735 ext. 263; gb18t@nih.gov

The invention is directed to copper

complexes of N,N′,N′′-trimethyl-cis,cis1,3,5-triaminocyclohexane and N,N′,N′′-

triethyl-cis,cis-1,3,5-

triaminocyclohexane as well as methods

of producing and using said complexes.

These complexes are capable of cleaving

DNA and RNA in vitro and could be

used for the treatment of cancer or other

disease states that are characterized by

abnormal cellular proliferation. The

complexes could also be used as

delivery agents or as imaging-tracers.

These complexes offer advantages over

previously described cleaving

methodologies, e.g., oxidative or

transesterification protocols. The

disclosed copper-complexes act via

hydrolytic reactions. These advantages

could offer significant benefits over

related therapeutic approaches to the

aforementioned abnormal conditions.

Federal Register / Vol. 65, No. 125 / Wednesday, June 28, 2000 / Notices 39917

Dated: June 15, 2000.

Jack Spiegel,

Director, Division of Technology Development

and Transfer, Office of Technology Transfer,

National Institutes of Health.

[FR Doc. 00–16326 Filed 6–27–00; 8:45 am]

BILLING CODE 4140–01–P

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

Government-Owned Inventions;

Availability for Licensing: Novel

Multiple Peptide Conjugate System

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.

This novel multiple peptide conjugate

system is described in DHHS Reference

Nos. E–208–99/0, E–280–99/0, and E–

114–00/0—all now incorporated under a

PCT application, DHHS Reference No.

E–208–99/1.

ADDRESSES: Licensing information and

copies of the U.S. patent applications

listed below may be obtained by Carol

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:

SalataC@od.nih.gov. A signed

Confidential Disclosure Agreement will

be required to receive copies of the

patent applications.

Novel Multiple Peptide Conjugate

System

I. Pathogenic TAT Peptides

Subhash Dhawan, Robert A. Boykins,

Kenneth M. Yamada (FDA)

Infection with HIV, the causative

agent of Acquired Immune Deficiency

Syndrome (AIDS), is responsible for a

large number of deaths annually and

represents a significant threat to human

health. Accordingly, an extensive effort

has been mounted to characterize the

HIV virus and to identify potential

targets for therapeutics. The present

invention relates to the identification of

functional domains within the HIV Tat

protein which are capable of mediating

many of the effects of the full length Tat

protein. In particular, this invention

describes the use of peptides comprising

functional domains to induce an

immune response against the HIV Tat

protein and the identification of

dominant-negative mutants and

chimeras of these functional domains

which may be used as therapeutics.

Another aspect of the present invention

relates to the use of these functional

domains as reagents for elucidating the

biochemical mechanisms of HIV gene

expression. This invention is described

further in Boykins et al. July 1999, J.

Immunol. 163:15–20.

II. Multiple Peptide Conjugates

Robert A. Boykins, Manju B. Joshi,

Chiang Syin, Subhash Dhawan, Hira

Nakhasi (FDA)

This invention describes the design

and synthesis of a multi-peptide

conjugate (MPC) system containing

antigens from the human malaria

parasite (Plasmodium falciparium) and

the Tat protein of HIV type-1 (HIV–1–

Tat) for use as a subunit vaccine. Prior

multiple antigen peptides (MAPs)

prepared by the classical solid phase

synthesis led to heterogeneity, due in

part to the aggregation and steric

hindrance of the growing peptide chains

during synthesis. Aggregation of the

peptide chain may be a factor in the

formation of intra-chain hydrogen

bonding by the peptide backbone,

causing the formation of beta sheets or

other secondary structures. The current

multiple peptide conjugates (MPCs)

have distinct advantages over prior

MAPs because only two adjacent

peptide branches are elongated on the

solid phase at either the alpha or

epsilon amino groups thereby allowing

maximum spacing between the resin

bound peptide chains. Cysteine is

inserted at the respective position in the

sequence thus permitting the thiol

groups to be used in the formation of

stable thioether bonds with haloacetyl

peptides coupled through solution

chemistry. A modification to the

coupling solvent and key amino acid

derivatives are used in the sequence to

minimize peptide chain aggregation.

Furthermore, the elongation of only two

peptide chains at the alpha or epilson

groups of opposite lysine residues

yields a dimeric or base peptide. These

modifications of the solid phase

methodology for the traditional MAP

plus a coupling solvent modification,

and the addition of key amino acid

derivatives for amide bond protection

allow the synthesis of base peptides on

the solid phase greater than 7500kDa.

These peptides are then reacted with

high performance liquid

chromatography purified haloacetyl

peptides to generate multiple peptide

conjugates with molecular masses of 10

to 13 kDa. This invention is described

further in Boykins et al., Peptides Jan

2000;21(1):9–17.

III. HIV–1–Tat-Multiple Peptide

Conjugate: A Potential Synthetic AIDS

Vaccine Candidate

Subhash Dhawan and Robert A. Boykins

(FDA)

The present invention is directed to a

novel highly immunogenic synthetic

multiple peptide conjugate constituting

three Tat functional domains.

Vaccination of mice with this HIV–1–

Tat multiple peptide conjugate induces

an effective immune response to three

Tat functional domains. Anti-HIV–1–Tat

multiple peptide conjugate antibodies

efficiently inhibit Tat-induced viral

activation in monocytes infected with

HIVBa–L as well as with various clinical

HIV–1 isolates, and reduce Tatmediated cytopathicity in infected cells

by greater than 75%. The results

indicate that anti-HIV–1–Tat multiple

peptide conjugate antibodies inhibit

viral pathogenesis, possibly by blocking

functional determinants of Tat and

disrupting autocrine and paracrine

actions of secreted Tat protein. This

epitope-specific synthetic Tat construct

provides a subunit AIDS vaccine for

inducing and effective

immunoprophylaxis response to reduce

progression of HIV infection.

Dated: June 15, 2000.

Jack Spiegel,

Director, Division of Technology Development

and Transfer, Office of Technology Transfer,

National Institutes of Health.

[FR Doc. 00–16327 Filed 6–27–00; 8:45 am]

BILLING CODE 4140–01–P

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Substance Abuse and Mental Health

Services Administration (SAMHSA)

Notice of Meetings

Pursuant to Public Law 92–463,

notice is hereby given of the following

meetings of SAMHSA Special Emphasis

Panels I in July, August and September

2000.

A summary of the meetings and a

roster of the members may be obtained

from: Ms. Coral Sweeney, Review

Specialist, SAMHSA, Office of Policy

and Program Coordination, Division of

Extramural Activities, Policy, and