Federal Register / Vol. 62, No. 222 / Tuesday, November 18, 1997 / Notices 61519

4.8 Carcinogenicity Studies

Standard carcinogenicity bioassays are

generally inappropriate for biotechnologyderived pharmaceuticals. However, productspecific assessment of carcinogenic potential

may still be needed depending upon duration

of clinical dosing, patient population, and/or

biological activity of the product (e.g., growth

factors, immunosuppressive agents, etc.).

When there is a concern about carcinogenic

potential, a variety of approaches may be

considered to evaluate risk.

Products that may have the potential to

support or induce proliferation of

transformed cells and clonal expansion

possibly leading to neoplasia should be

evaluated with respect to receptor expression

in various malignant and normal human cells

that are potentially relevant to the patient

population under study. The ability of the

product to stimulate growth of normal or

malignant cells expressing the receptor

should be determined. When in vitro data

give cause for concern about carcinogenic

potential, further studies in relevant animal

models may be needed. Incorporation of

sensitive indices of cellular proliferation in

long-term repeated dose toxicity studies may

provide useful information.

In those cases where the product is

biologically active and nonimmunogenic in

rodents and other studies have not provided

sufficient information to allow an assessment

of carcinogenic potential, then the utility of

a single rodent species should be considered.

Careful consideration should be given to the

selection of doses. The use of a combination

of pharmacokinetic and pharmacodynamic

endpoints with consideration of comparative

receptor characteristics and intended human

exposures represents the most scientifically

based approach for defining the appropriate

doses. The rationale for the selection of doses

should be provided.

4.9 Local Tolerance Studies

Local tolerance should be evaluated. The

formulation intended for marketing should

be tested; however, in certain justified cases,

the testing of representative formulations

may be acceptable. In some cases, the

potential adverse effects of the product can

be evaluated in single or repeated dose

toxicity studies, thus obviating the need for

separate local tolerance studies.

Notes

Note 1

Animal models of disease may be useful in

defining toxicity endpoints, selection of

clinical indications, and determination of

appropriate formulations, route of

administration, and treatment regimen. It

should be noted that with these models of

disease there is often a paucity of historical

data for use as a reference when evaluating

study results. Therefore, the collection of

concurrent control and baseline data is

critical to optimize study design.

Note 2

There may be extensive public information

available regarding potential reproductive

and/or developmental effects of a particular

class of compounds (e.g., interferons) where

the only relevant species is the nonhuman

primate. In such cases, mechanistic studies

indicating that similar effects are likely to be

caused by a new but related molecule may

obviate the need for formal reproductive/

developmental toxicity studies. In each case,

the scientific basis for assessing the potential

for possible effects on reproduction/

development should be provided.

Note 3

With some biopharmaceuticals, there is a

potential concern about accumulation of

spontaneously mutated cells (e.g., via

facilitating a selective advantage of

proliferation) leading to carcinogenicity. The

standard battery of genotoxicity tests is not

designed to detect these conditions.

Alternative in vitro or in vivo models to

address such concerns may have to be

developed and evaluated.

Dated: November 12, 1997.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

[FR Doc. 97–30274 Filed 11–17–97; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

National Institute of Arthritis and

Musculoskeletal and Skin Diseases;

Notice of Closed Meeting

Pursuant to Section 10(d) of the

Federal Advisory Committee Act, as

amended (5 U.S.C. Appendix 2), notice

is hereby given of the following

National Institute of Arthritis and

Musculoskeletal and Skin Diseases

Special Emphasis Panel (SEP) meeting:

Name of SEP: Mechano Transduction in

Bone.

Date: December 18, 1997.

Time: 8:00 a.m.–5:00 p.m.

Place: Holiday Inn Bethesda, 8120

Wisconsin Avenue, Bethesda, Maryland

20814.

Contact Person: Tommy L. Broadwater,

Ph.D., Scientific Review Administrator,

Natcher Building, 45 Center Drive, Rm

5AS25U, Bethesda, Maryland 20892–6500,

Telephone: 301–594–4952.

Purpose/Agenda: To evaluate and review a

research grant application.

This meeting will be closed in accordance

with the provisions set forth in sections

552b(c)(4) and 552b(c)(6), Title 5 U.S.C. The

discussion of this application could reveal

confidential trade secrets or commercial

property such as patentable material and

personal information concerning individual

associated with the application, the

disclosure of which would constitute a

clearly unwarranted invasion of personal

privacy.

(Catalog of Federal Domestic Assistance

Program Nos. [93.846, Project Grants in

Arthritis, Musculoskeletal and Skin Disease

Research], National Institutes of Health,

HHS)

Dated: November 10, 1997.

LaVerne Y. Stringfield,

Committee Management Officer, NIH.

[FR Doc. 97–30204 Filed 11–17–97; 8:45 am]

BILLING CODE 4140–01–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

Prospective Grant of Exclusive

License: Immunodampening

Technology

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, ins contemplating

the grant of an exclusive world-wide

license to practice the invention

embodied in U.S. Patent Number

5,585,250 and pending U.S. Patent

Application Serial No. 08/764.575 both

entitled ‘‘Dampening of an

Immunodominant Epitope of an Antigen

for Use in Plant, Animal and Human

Compositions and Immunotherapies’’

and related foreign patent applications

to Biological Memetics, Inc., of

Frederick, Maryland. The patent rights

in this invention have been assigned to

the United States of America.

It is anticipated that this license will

be limited to the field of vaccines for the

treatment and prevention of infectious

diseases in animals and humans.

DATES: Only written comments and/or

applications for a license which are

received by NIH on or before February

17, 1998 will be considered.

ADDRESSES: Requests for a copy of the

patent and/or patent application,

inquires, comments and other materials

relating to the contemplated license

should be directed to: Robert Benson,

Patent Advisor, Office of Technology

Transfer, National Institutes of Health,

6011 Executive Blvd., Suite 325,

Rockville, MD 20852–3804; Telephone:

(301) 496–7056, x267; Facsimile: (301)

402–0220.

SUPPLEMENTARY INFORMATION: The patent

and pending patent application describe

a broadly applicable method of

redirecting the immune response to an

antigen from an immunodominant

epitope to another epitope by altering

the immunogenicity of the

immunodominant epitope. The method

is most useful for those pathogens with

a highly variable immunodominant

epitope, such as HIV, HCV or gonorrhea.
61520 Federal Register / Vol. 62, No. 222 / Tuesday, November 18, 1997 / Notices

By immunodampening the dominant

epitope the immune system then reacts

to other more conserved epitopes.

The prospective exclusive license will

be royalty-bearing and will comply with

the terms and conditions of 35 U.S.C.

209 and 37 CFR 404.7. This prospective

exclusive license may be granted unless

within 90 days from the date of this

published notice, NIH receives written

evidence and argument that established

that the grant of the license would not

be consistent with the requirements of

35 U.S.C. 209 and 37 CFR 404.7.

Applications for a license filed in

response to this notice will be treated as

objections to the grant of the

contempleted license. Comments and

objections submitted to this notice will

not be made available for public

inspection and, to the extent permitted

by law, will not be released under the

Freedom of Information Act, 5 U.S.C.

§ 552.

Dated: November 5, 1997.

Barbara M. McGarey,

Deputy Director, Office of Technology

Transfer.

[FR Doc. 97–30202 Filed 11–17–97; 8:45 am]

BILLING CODE 4140–01–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Public Health Service

National Toxicology Program; National

Toxicology Program (NTP), Board of

Scientific Counselors’ Meeting; Review

of Draft NTP Technical Reports

Pursuant to Public Law 92–463,

notice is hereby given of the next

meeting of the NTP Board of Scientific

Counselors’ Technical Reports Review

Subcommittee on December 9 and 10,

1997, in the Conference Center,

Building 101, South Campus, National

Institute of Environmental Health

Sciences (NIEHS), 111 Alexander Drive,

Research Triangle Park, North Carolina.

The meeting will begin at 1:30 p.m. on

December 9, and at 8:30 a.m. on

December 10, and is open to the public.

The agenda topic is the peer review of

draft Technical Reports of long-term

toxicology and carcinogenesis studies

from the National Toxicology Program.

Additionally, there will be a

presentation made concerning data

obtained from transgenic mouse models

on several of the chemicals being

reviewed.

Tentatively scheduled to be peer

reviewed on December 9–10 are draft

Technical Reports of 10 two-year

studies, listed alphabetically, along with

supporting information in the attached

table. All studies were done using

Fischer 344 rats and B6C3F1 mice. The

order of review is given in the far right

column of the table. Copies of the draft

Reports may be obtained, as available,

from: Central Data Management, MD

E1–02, P.O. Box 12233, Research

Triangle Park, NC 27709 (919/541–

3419), FAX (919/541–3687), email:

CDM@niehs.nih.gov.

Public comment on any of the

Technical Reports is welcome. Persons

wanting to make a formal presentation

regarding a particular Technical Report

must notify the Executive Secretary by

telephone, by FAX, by mail, or by email

no later than December 4, 1997, and

provide a written copy in advance of the

meeting so copies can be made and

distributed to all Subcommittee

members, ad hoc expert consultants,

and staff, and made available at the

meeting for attendees. Written

statements should supplement and may

expand on the oral presentation. Oral

presentations should be limited to no

more than five minutes.

The program would welcome

receiving toxicology and carcinogenesis

information from completed, ongoing,

or planned studies by others, as well as

current production data, human

exposure information, and use patterns

for any of the chemicals listed in this

announcement. Please contact Central

Data Management at the address given

above, and they will relay the

information to the appropriate staff

scientist.

The Executive Secretary, Dr. Larry G.

Hart, P.O. Box 12233, Research Triangle

Park, North Carolina 27709 (telephone

919/541–3971; FAX 919/541–0295;

email hart@niehs.nih.gov) will furnish

agenda and a roster of Subcommittee

members and expert consultants prior to

the meeting. Summary minutes

subsequent to the meeting will be

available upon request to Central Data

Management.

Attachment.

Charles E. Leasure, Jr.,

Acting Director, National Toxicology

Program.

SUMMARY DATA FOR TECHNICAL REPORTS TENTATIVELY SCHEDULED FOR REVIEW AT THE MEETING OF THE NTP BOARD

OF SCIENTIFIC COUNSELOR’S TECHNICAL REPORTS REVIEW SUBCOMMITTEE

[December 9–10, 1997]

Chemical CAS No.

Technical

route/

report

number

Primary uses Exposure levels Review

order

1-Chloro-2-Propanol, Technical, 127–

00–4.

TR–477 Chemical intermediate for propylene

oxide & other organic compounds.

Dosed-Water (deionized water): Rats:

0, 150, 325, or 650 ppm; Mice: 0,

250, 500, or 1000 ppm (50/sex/

group).

10

Coconut Oil Acid, Diethanolamine Condensate, 68603–42–9.TR–479 Foam stabilizer in shampoos and dishwashing liquids; dyeing assistant in

textile processing.

Topical (95% ethanol): Rats: 0, 50, or

100 mg/kg; Mice: 0, 100, or 200 mg/

kg (50 sex/species/group).

2

Diethanolamine, 111–42–2 ..................... TR–478 Production of textile lubricants. Rubber

chemicals intermediate; emulsifier in

agricultural chemicals, cosmetics,

and pharmaceuticals; gas conditioning agent.

Topical (ethanol): Male Rats: 0, 16, 32,

or 64 mg/kg; Female Rats: 0, 8, 16,

or 32 mg/kg; Mice: 0, 40, 80, or 160

mg/kg (50/sex/species/group).

1