Federal Register / Vol. 62, No. 5 / Wednesday, January 8, 1997 / Notices 1123

all data to the Collaborator as soon as

they become available.

3. Conduct controlled clinical trials of

antiflammin formulations that have

been determined to have therapeutic

potential in ocular and skin

inflammatory diseases.

The role of the Collaborator(s) will be

to:

1. Perform an exhaustive evaluation of

these compounds with respect to their

biological activities and to develop

appropriate vehicles for drug delivery

for disease processes covered under the

CRADA. The Collaborator(s) will supply

data to the NEI and/or NIAMS in a

timely fashion.

2. Synthesize and formulate structural

variants of these subject compounds to

optimize desired effects.

3. Expand the basic toxicological data

as needed in preparation for additional

clinical studies.

4. Conduct basic studies designed to

better understand the potential for

antiflammins in the treatment of

inflammatory diseases, bioavailability

and how to best administer these agents.

5. Support the execution of clinical

trials designed to evaluate efficacy and

toxicity. This may include providing

pharmaceutical grade compound,

equipment and supplies, and support

personnel.

6. Provide new and improved

formulations in appropriate vehicles.

Selection criteria for choosing the

CRADA partner(s) will include but not

be limited to:

1. Ability to complete the quality

pharmacological evaluations required

according to an appropriate timetable to

be outlined in the Collaborator’s

proposal. The target commercial

application as well as the strategy for

evaluating the test agents’ potential in

that capacity must be clearly delineated

therein.

2. The level of financial support the

Collaborator will supply for CRADArelated Government activities.

3. A willingness to cooperate with the

NEI and NIAMS in publication of

research results.

4. An agreement to be bound by the

DHHS rules involving human subjects,

patent rights, ethical treatment of

animals, and randomized clinical trials.

5. Agreement with provisions for

equitable distribution of patent rights to

any inventions developed under the

CRADA(s). Generally, the rights of

ownership are retained by the

organization which is the employer of

the inventor, with (1) an irrevocable,

non-exclusive, royalty-free license to the

Government (when a company

employee is the sole inventor) or (2) an

option to negotiate an exclusive or nonexclusive license to the company on

terms that are appropriate (when the

Government employee is the sole

inventor).

Dated: December 23, 1996.

Barbara M. McGarey,

Deputy Director, Office of Technology

Transfer.

[FR Doc. 97–333 Filed 1–7–97; 8:45 am]

BILLING CODE 4140–01–M

National Institutes of Health

National Center for Research

Resources: Licensing Opportunity

and/or Opportunity for a Cooperative

Research and Development Agreement

(CRADA) for the Development of

Technologies and Applications for

Spatial and Temporal Control of Gene

Expression Using a Heat Shock

Protein Promoter in Combination With

Local Heat

AGENCY: National Institutes of Health,

PHS, HHS.

ACTION: Notice.

SUMMARY: The National Center for

Research Resources (NCRR) and

collaborating institutes of the NIH are

seeking CRADA partners and/or

licensees for the development of

different technologies and applications

to provide a safe and efficient

introduction of exogenous genes under

the control of a heat-sensitive promoter

and to assess the efficacy of spatial and

temporal control of gene expression

using MRI guided FUS. This project is

with the In Vivo NMR Research Center,

NCRR, in a collaborative study with the

National Institute on Aging, the

National Heart Lung and Blood

Institute, and the National Institute of

Dental Research of the National

Institutes of Health, Bethesda, Maryland

The NCRR has applied for patents

claiming this core technology. Nonexclusive and/or exclusive licenses for

these patents covering core aspects of

this project are available (in accordance

with 35 U.S.C. 207 and 37 CFR Part 404)

to interested parties.

DATES: There is no deadline by which

license applications or CRADA

proposals must be received.

ADDRESSES: CRADA capability

statements/proposals and questions

about this opportunity should be

addressed to Mr. Tom Ingalls,

Technology Transfer Specialist, NCRR,

Bldg. 12A/Room 4057, Bethesda,

Maryland 20892–2490; Phone: 301/496–

6235.

Licensing applications and licensing

inquiries regarding this technology

should be addressed to Mr. Larry

Tiffany, Office of Technology Transfer,

6011 Executive Boulevard, Suite 325,

Rockville, Maryland 20852–3804;

Phone: 301/496–7735, ext. 206; Fax:

301/402–0220.

Information on the patent and patent

applications and pertinent information

not yet publicly described can be

obtained under a Confidential

Disclosure Agreement. Respondees

interested in licensing the invention(s)

will be required to submit an

Application for License to Public Health

Service Inventions. Respondees

interested in submitting a CRADA

proposal should be aware that it may be

necessary to secure a license to the

above patent rights in order to

commercialize products arising from a

CRADA agreement.

SUPPLEMENTARY INFORMATION: In many

instances, it is desirable to express

exogenous genes only in certain tissues,

and/or at will at certain times, and/or

only to a certain degree. However,

current gene transfer and exogenous

gene expression protocols do not

provide adequate means of

simultaneously controlling which cells

in a heterogeneous population are

transformed and when, where, and to

what degree the transferred genes are

expressed. Here, we seek to accomplish

the spatial and local control of

expression of exogenous genes using a

heat-inducible promoter (such as the

inducible hsp70 promoter) in

combination with local heat, preferably

provided by Magnetic Resonance

Imaging (MRI) guided Focused

Ultrasound (FUS).

The goals of this project are to use the

respective strengths of both parties to

achieve one or more of the following:

1. Evaluate the feasibility and safety

of gene therapy utilizing a range of

suitable vectors as a treatment approach

to carry out a systemic gene transfer in

which the therapeutic gene is under the

control of a heat-sensitive promoter

showing negligible constitutive

expression at normal body temperature.

2. Evaluate the feasibility of

controlling the local and temporal

induction of gene expression

(pharmacokinetics) using local heat

provided by Magnetic Resonance

Imaging guided Focused Ultrasound.

3. Develop and evaluate gene therapy

products for use in experimental animal

models and for human use based on the

above control of expression.

It is anticipated that the commercial

collaborator(s) will participate in

ongoing studies on one or more of the

research projects involving:

1. The transfer of genes for various

lymphokines into experimental animal
1124 Federal Register / Vol. 62, No. 5 / Wednesday, January 8, 1997 / Notices

models based on an adenovirus vector

or other vectors. It is highly desirable

that the collaborator have the resources

to provide new effective vectors for gene

transfer.

2. The modulation of the inducibility

of the heat-sensitive promoter using

appropriate modifications of the

promoter and by using antiinflammatory or other drugs.

3. Dosage and toxicity of local

production of lymphokines applied to

cancer and other diseases.

4. Initial applications in the field of

anticancer therapy, immunomodulatory

gene products and angiogenesis.

The collaborator may also be expected

to contribute financial support under

this CRADA for supplies and personnel

to support these projects.

Dated: December 19, 1996.

Barbara M. McGarey,

Deputy Director, Office of Technology

Transfer.

[FR Doc. 97–335 Filed 1–7–97; 8:45 am]

BILLING CODE 4140–01–M

Government-Owned Inventions;

Availability for Licensing

AGENCY: National Institutes of Health,

HHS.

ACTION: Notice.

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 U.S. companies and may

also be available for licensing.

ADDRESSES: Licensing information and

copies of the U.S. patent applications

and issued patents listed below may be

obtained by contacting the indicated

licensing specialist 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.

Chimeric GAG Pseudovirions

GJ Tobin, MA Gonda (NCI)

OTT Reference No. E–105–96/0 filed 16 May

96

Licensing Contact: Cindy K. Fuchs, J.D., 301/

496–7735 ext 232

This technology is based upon a novel

method for generating pseudovirions

containing HIV Gag and chimeric GagEnv fusion proteins that may be used in

a prophylactic vaccine or to boost the

immune response of HIV-infected

individuals. In addition to the foregoing

method, the invention provides

recombinant chimeric nucleic acids

encoding a Gag-frameshift (fs)-fusion

partner fusion protein; a pseudovirion

comprising a retroviral Gag protein and

a fusion partner; an immunogenic

composition comprising a pseudovirion;

and a Gag-fs-fusion partner fusion

protein. Mice inoculated with the

pseudovirions developed cytotoxic T

lymphocyte responses specific to both

HIV Gag and Env epitopes as well as a

strong humoral response to Gag. The

method allows the packaging of other

non-viral proteins such as interleukins,

interferons, and other cytokines.

(portfolio: Infectious Diseases—

Vaccines, viral, AIDS)

MHC Class II–Restricted Melanoma

Antigens and Their Use in Therapeutic

Methods

SL Topalian, SA Rosenberg, P Robbins (NCI)

Serial No. 08/533,895 filed 26 Sep 95

Licensing Contact: Joseph Contrera, M.S.,

J.D., 301/496–7056 ext 244

The present invention relates to MHC

class II-restricted melanoma antigens

and their use in the treatment of human

cancers. Cytotoxic CD8∂ T cells have

been shown to recognize autologous and

MHC class I compatible allogenic

melanomas expressing shared tumorassociated antigens. Several class Irestricted melanoma-associated antigens

have been identified on a molecular

level. These antigens and derivative

class I-restricted peptides 8 to 10 amino

acids in length are being developed as

clinical vaccines to stimulate CD8∂ T

cell responses against melanoma. While

CD8∂ T cells are important in the

effector phase of the immune response,

the CD4∂ helper arm has been shown to

mediate critical priming and effector

functions as well. T cell receptors on

CD4∂ T cells recognize a complex of

antigenic peptide in conjunction with

MHC class II molecules. Most of these

antigenic peptides are 10–34 amino

acids in length. Strong and lasting

immunity depends, in part, on CD4∂ T

cell function. Therefore, class IIrestricted melanoma antigens may be

useful in immunotherapeutic

approaches to melanoma.

The present invention relates to MHC

class II-restricted melanoma antigens

recognized by CD4∂ T cells and the

nucleic acid sequences that encode

them. The invention contains claims to

MHC class II immunogenic peptides of

tyrosinase and methods of producing an

immune response to these peptides.

This invention also provides a method

for identifying additional class IIrestricted melanoma antigens. (portfolio:

Cancer—Therapeutics, vaccines;

Cancer—Therapeutics,

immunomodulators and

immunostimulants; Cancer—

Therapeutics, biological response

modifiers)

eps15, Substrate for the Epidermal

Growth Factor Receptor Kinase

PP DiFiore, F Fazioli (NCI)

Filed 07 Jun 95

Serial Nos. 08/480,145 and 08/477,389 (both

DIV of 08/095,737, now U.S. Patent

5,487,979)

Licensing Contact: Susan Rucker, J.D., 301/

496–7056 ext 245

These applications describe eps15, a

substrate for the Epidermal Growth

Factor Receptor (EGFR). This substrate

is distinct from a previously identified

substrate for the EGFR known as eps8

(U.S. Patent 5,378,809). EGFR is a cell

surface receptor, with tyrosine kinase

activity, which as been implicated in

mitogenesis via a process known as

mitogenic signal transduction.

Substrates for the EGFR, such as eps15,

may be useful in research on signal

transduction involving EGFR, and as

diagnostic or prognostic indicators due

to their ability to be used in determining

the tyrosine kinase activity of tissue

sample. In particular, recent work with

eps15 fusion proteins has shown that

eps15 may be linked to myeloid

leukemia due to its translocation. Thus,

eps15 may also serve as a tumor marker.

In addition to the cDNA, constructs

expressing eps15, antibodies to eps15,

and methods for assaying eps15

(immunological and DNA based) are

described. (portfolio: Research Tools

and Reagents, receptors and cell lines;

Cancer—Research Reagents)

T-Cell Receptors and Their Use In

Therapeutic and Diagnostic Methods

P Hwu, M Nishimura, SA Rosenberg (NCI)

Serial No. 08/411,098 filed 27 Mar 95

Licensing Contact: Joseph Contrera, M.S.,

J.D., 301/496–7056 ext 244

Tumor infiltrating lymphocytes (TIL)

play an important role in tumor

regression. TIL cells that recognize a

variety of specific tumor antigens have

been identified. This invention

embodies nucleic acid and amino acid

sequences of T-cell receptors which

recognize or bind tumor antigens. The

claims of this invention relate to the use

of these T-cell receptors or

hematopoietic stem cells engineered to

carry these receptors or chimeric

receptors comprised of an antibody

variable region joined to the

cytoplasmic region of CD28 from a Tcell for therapeutic uses. This