Federal Register / Vol. 63, No. 119 / Monday, June 22, 1998 / Notices 33939

applications of the technology outlined

in the agreement.

5. Providing immunotoxin for

laboratory and animal studies.

6. Publishing research results.

Selection criteria for choosing the

CRADA Collaborator may include, but

not be limited to:

1. The ability to collaborate with NCI

on further research and development of

this technology. This ability can be

demonstrated through experience and

expertise in this or related areas of

technology indicating the ability to

contribute intellectually to ongoing

research and development.

2. The demonstration of adequate

resources to perform the research and

development of this technology (e.g.,

facilities, personnel and expertise) and

accomplish objectives according to an

appropriate timetable to be outlined in

the CRADA Collaborator’s proposal.

3. 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.

4. The demonstration of expertise in

the commercial development and

production of products related to this

area of technology.

5. The level of financial support the

CRADA Collaborator will provide for

CRADA-related Government activities.

6. The demonstration of expertise

pertinent to the development of models

to evaluate and improve the efficacy of

immunotoxin in the prevention or

treatment of graft-versus-host disease

and/or allograft rejection.

7. The willingness to cooperate with

the National Cancer Institute in the

timely publication of research results.

8. 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.

9. The willingness to accept the legal

provisions and language of the CRADA

with only minor modifications, if any.

These provisions govern the distribution

of patent rights to CRADA inventions.

Generally, the right 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 for an option

to elect an exclusive or nonexclusive

license to the CRADA Collaborator

when the Government employee is the

sole inventor.

Dated: June 11, 1998.

Kathleeen Sybert,

Acting Director, Technology Development

and Commercialization Branch, National

Cancer Institute, National Institutes of Health.

Dated: April 30, 1998.

Jack Spiegel,

Director, Division of Technology Development

and Transfer, Office of Technology Transfer,

National Institutes of Health.

[FR Doc. 98–16427 Filed 6–19–98; 8:45 am]

BILLING CODE 4140–01–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

Licensing Opportunity and/or

Cooperative Research and

Development Agreement (‘‘CRADA’’)

Opportunity: Drug and Method for the

Therapeutic Treatment of Ovarian

Cancer and Mesotheliomas

AGENCY: National Institutes of Health,

PHS, DHHS.

ACTION: Notice.

SUMMARY: The NIH is a seeking

Licensee(s) and/or Cooperative Research

and Development Agreement

(‘‘CRADA’’) Collaborators to further

develop, evaluate, and commercialize a

recombinant immunotoxin, termed

SS(dsFv)–PE38. SS(dsFv)–PE38 is a

disulfide-linked recombinant

immunotoxin fused to PE38, a mutant

form of Pseudomonas Exotoxin, that

binds to mesothelin. Mesothelin is a

differentiation antigen present on the

surface of most ovarian cancers,

mesoltheliomas, and several other types

of human cancers including cervical

cancer. In normal tissue, mesothelin is

limited in its expression to mesothelial

cells and basal cells of the trachea (low

expression). Therefore, it represents an

excellent target for antibody-mediated

delivery of cytotoxic agents. The antigen

is a 40 kD glycoprotein that is attached

to the cell surface by

phosphatidylinositol. SS (dsFv)–PE38

immunotoxin is very cytotoxic to cancer

cells expressing mesothelin and binds

with an affinity of approximately 11

nanomolar. The SS (dsFv)–PE38

immunotoxin also produces complete

regressions of mesothelin containing

solid tumors growing in nude mice. The

goal is to move this drug and

methodology into clinical trials. The

invention is claimed in USPA SN 08/

776,271 and PCT patent application

PCT/US97/00224, entitled: ‘‘Mesothelin,

A Differentiation Antigen Present on

Mesothelium, Mesotheliomas and

Ovarian Cancers and Methods and Kits

for targeting the Antigen’’ and is

available for either exclusive or nonexclusive licensing (in accordance with

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

DATES: Respondees interested in

licensing the invention(s) will be

required to submit an ‘‘Application for

License to Public Health Service

Inventions’’ on or before September 21,

1998 for priority consideration.

Interested CRADA Collaborators must

submit a confidential proposal summary

to the NCI on or before September 21,

1998 for consideration. Guidelines for

preparing full CRADA proposals will be

communicated shortly thereafter to all

respondents with whom initial

confidential discussions will have

established sufficient mutual interest.

CRADA proposals submitted thereafter

may be considered if a suitable CRADA

Collaborator has not been selected.

ADDRESSES: Questions about licensing

opportunities may be addressed to J.R.

Dixon, Ph.D., Technology Licensing

Specialist, Office of Technology

Transfer, National Institutes of Health,

6011 Executive Boulevard, Suite 325,

Rockville, Maryland 20852–3804;

Telephone: (301) 496–7056 ext. 206;

Facsimile: (301) 402–0220; E-Mail:

‘‘DixonJOD.NIH.GOV’’. Information

about Patent Applications and pertinent

information not yet publicly described

can be obtained under the terms of 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’’.

Depending upon the mutual interests

of the Licensee(s) and the National

Cancer Institute (‘‘NCI’’), a Cooperative

Research and Development Agreement

(CRADA) to collaborate to improve the

properties of the SS(dsFv)–PE38

immunotoxin may also be negotiated.

Proposals and questions about this

CRADA opportunity may be addressed

to Ms. Karen Maurey, Acting Deputy

Director, National Cancer Institute,

Technology Development &

Commercialization Branch, 6120

Executive Plaza South-Room 450,

Rockville, Maryland 20852; Telephone:

(301) 496–0477; Facsimile: (301) 402–

2117. Respondees interested in

submitting a CRADA proposal should be

aware that it may be necessary to secure

a license to the above mentioned patent

rights in order to commercialize

products arising from a CRADA.

SUPPLEMENTARY INFORMATION: NIH/NCI

scientists have done toxicity studies

with the SS(dsFv)-PE38 immunotoxin in

mice and with an earlier single chain

variant (SSFv-PE38) in Cynomolgus

monkeys. Treatment of mice with 5μg
33940 Federal Register / Vol. 63, No. 119 / Monday, June 22, 1998 / Notices

QOD × 3 (0.25 mg/kilo) produced

complete tumor regressions without

death or toxicity. Since the antibody

does not react with mouse mesothelin,

possible toxicities in mice are due to

non-specific (liver) toxicity. NIH/NCI

scientists have also administered this

aforementioned single chain form to

monkeys. SS(Fv)-PE38 reacts just as

strongly with monkey mesothelin as it

does with human mesothelin, and

therefore, one would expect the monkey

to be a good predictor of toxicity in

humans. At a 0.05 mg/kilo dose level,

no toxicity was experienced. A second

monkey received 0.5 mg/kilo and

showed a transient elevation in liver

enzymes and non-specific physical

signs (inactivity), but fully recovered.

In the United States, an estimated

15,000 patients die of ovarian cancer

each year despite therapy. Although less

common, mesotheliomas are known to

be resistant to all chemotherapeutic

agents. Development of new therapeutic

modalities to treat these malignancies is

needed.

A Cooperative Research and

Development Agreement or CRADA

means the anticipated joint agreement to

be entered into by NCI pursuant to the

Federal Technology Transfer Act of

1986 and Executive Order 12591 of

April 10, 1987 as amended by the

National Technology Transfer

Advancement Act of 1995 to collaborate

to improve the properties of the

SS(dsFv)-PE38 immunotoxin.

The rule of the NCI in the CRADA

may include, but are not be limited to:

1. Providing intellectual, scientific,

and technical expertise and experience

to the research project.

2. Providing the Collaborator with

samples of the subject compounds to

create, optimize, test and develop

targeted drugs for clinical studies.

3. Planning research studies and

interpreting research results.

4. Carrying out research to improve

the properties of the SS(dsFv)-PE38

which include, but are not restricted to,

increased production yield, decreased

side effects, increased cytotoxic activity

and better tissue penetration.

5. Publishing research results.

The role of the CRADA Collaborator

may include, but not be limited to:

1. Providing significant intellectual,

scientific, and technical expertise or

experience to the research project.

2. Planning research studies and

interpreting research results.

3. Providing samples of the subject

compounds to create, optimize, test and

develop targeted drugs for clinical

studies.

4. Providing technical and/or

financial support to facilitate scientific

goals and for further design of

applications of the technology outlined

in the agreement.

5. Incorporating the immunotoxin

into liposomes or producing other

formulations in order to increase the

therapeutic efficacy.

6. Providing immunotoxin for

laboratory and animal studies.

7. Publishing research results.

Selection criteria for choosing the

CRADA Collaborator may include, but

not be limited to:

1. The ability to collaborate with NCI

on further research and development of

this technology. This ability can be

demonstrated through experience and

expertise in this or related areas of

technology indicating the ability to

contribute intellectually to ongoing

research and development.

2. The demonstration of adequate

resources to perform the research and

development of this technology (e.g.

facilities, personnel and expertise) and

accomplish objectives according to an

appropriate timetable to be outlined in

the CRADA Collaborator’s proposal.

3. 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.

4. The demonstration of expertise in

the commercial development and

production of products related to this

area of technology.

5. The level of financial support the

CRADA Collaborator will provide for

CRADA-related Government activities.

6. The demonstration of expertise

pertinent to the development of models

to evaluate and improve the efficacy of

the SS (dsFv)-PE38 immunotoxin for the

treatment of ovarian cancer and

mesotheliomas.

7. The demonstration of expertise in

the formulation of drugs into liposomes

or other delivery vehicles.

8. The willingness to cooperate with

the NCI 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 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: May 18, 1998.

Jack Spiegel,

Director, Division of Technology Development

and Transfer, Office of Technology Transfer,

National Institutes of Health.

Dated: May 26, 1998.

Kathleen Sybert,

Acting Director, Technology Development

and Commercialization Branch, National

Cancer Institute, National Institutes of Health.

[FR Doc. 98–16426 Filed 6–19–98; 8:45 am]

BILLING CODE 4140–01–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

Government-Owned Inventions;

Availability for Licensing: Novel

Antitumor Macrocyclic Lactones,

Compositions and Methods of Use

AGENCY: National Institutes of Health,

Public Health Service, DHHS.

ACTION: Notice.

SUMMARY: The National Institutes of

Health is seeking licensees for the

further development, evaluation and

commercialization of materials and

methods for novel cancer treatment

agents. The invention claimed in DHHS

Reference No. E–244–97/0, ‘‘Novel

Antitumor Macrocyclic Lactones,

Compositions and Methods of Use,’’

(Boyd, M. et al.) filed on 29 June 1997

as USSN 60/053,784, is available for

licensing (in accordance with 35 USC

207 and 37 CFR Part 404).

ADDRESSES: Questions about the

licensing opportunity should be

addressed to Girish C. Barua, Ph.D.,

Office of Technology Transfer, National

Institutes of Health, 6011 Executive

Boulevard, Suite 325, Rockville,

Maryland 20852–3804; Telephone: 301/

496–7056 ext. 263; Fax: 301/402–0220.

SUPPLEMENTARY INFORMATION: The

invention relates to a series of

macrocyclic lactones based on

compounds isolated from certain marine

sponges and tunicates. These

compounds have in vitro activity against

certain human solid tumors, including

non-small cell lung cancer, renal cancer

and melanoma, all important killers

which are resistant to currently used

drugs.

Of particular interest is the cell-line

activity profile of these lactones, which

indicates a novel mechanism of action.

Such compounds hold the promise of in