Federal Register / Vol. 62, No. 207 / Monday, October 27, 1997 / Notices 55649

received by NIH on or before December

26, 1997 will be considered.

ADDRESSES: Requests for a copy of these

patents, inquiries, comments and other

materials relating to the contemplated

license should be directed to: Elaine F.

Gese, Technology Licensing Specialist,

Office of Technology Transfer, National

Institutes of Health, 6011 Executive

Blvd., Suite 325, Rockville, MD 20852;

Telephone: (301) 496–7056, ext. 282;

Facsimile: (301) 402–0220.

SUPPLEMENTARY INFORMATION: U.S.

Patent No. 5,157,110 describes a

synthetic protein which is capable of

inhibiting the complement cascade by

binding to the C4b component of

complement, and thereby provides a

method for controlling the complement

cascade. U.S. Patent No. 5,187,268

describes the cloned gene encoding this

protein. Complement inhibitors may be

used in compositions to prevent

complement mediated attack and injury

to cells prior to or during

transplantation, or to prevent transplant

rejection. In addition, complement

inhibitors may be used in developing

products for allogeneic and xenogeneic

transplantation.

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 60 days from the date of this

published notice, NIH receives written

evidence and argument that establishes

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

contemplated 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: October 15, 1997.

Barbara M. McGarey,

Deputy Director, Office of Technology

Transfer.

[FR Doc. 97–28381 Filed 10–24–97; 8:45 am]

BILLING CODE 4140–01–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

Prospective Grant of Exclusive

License: IL–4 Pseudomonas Exotoxin

Fusion Protein Therapeutics

AGENCY: National Institutes of Health,

Public Health Service, DHHS.

ACTION: Notice.

SUMMARY: This 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 limited

field of use exclusive world-wide

license to practice the invention

embodied in USPA SN 06/911,227 (U.S.

Patent 4,892,827) entitled,

‘‘Recombinant Pseudomonas Exotoxins:

Construction of an Active Immunotoxin

with Low Side Effects’’; USPA SN 08/

225,224 (U.S. Patent 5,635,599) entitled,

‘‘Circularly Permuted Ligands and

Circularly Permuted Chimeric

Molecules’’; USPA SN 08/722,258

entitled, ‘‘Proteins Comprising

Circularly Permuted Ligands’’; and

USPA SN 08/616,785 entitled,

‘‘Convection-Enhanced Drug Delivery’’,

to Neurocrine Biosciences of San Diego,

California. The patent rights in these

inventions have been assigned to the

United States of America.

The field of use would be limited to

IL–4 pseudomonas exotoxin fusion

protein therapeutics.

DATES: Only written comments and/or

applications for a license which are

received by NIH on or before January 26,

1998 will be considered.

ADDRESSES: Requests for copies of the

subject issued patents and pending

patent applications, inquiries,

comments and other materials relating

to the contemplated license should be

directed to: Mr. Steven Ferguson, Senior

Licensing Specialist, Office of

Technology Transfer, National Institutes

of Health, 6011 Executive Boulevard,

Suite 325, Rockville, MD 20852.

Telephone: (301) 496–7056, ext. 266;

Facsimile: (301) 402–0220. A signed

Confidentiality Agreement will be

required to receive copies of the

pending patent applications.

SUPPLEMENTARY INFORMATION: The

present inventions relate to a fusion

protein construct which is able to target

malignant glial cells in the brain and

potentially other malignant cells

throughout the body which overexpress

the IL–4 receptor protein. The construct

has two parts; a targeting moiety and a

toxin. The targeting moiety is the IL–4

cytokine while the toxin is a modified

pseudomonas-exotoxin. The construct

can be delivered to the brain using a

convention-enhanced methodology to

target and destroy cancerous cells.

The prospective exclusive license will

be royalty-bearing and will comply with

the terms and conditions of 35 U.S. 209

and 37 CFR § 404.7. The prospective

exclusive license may be granted unless,

within 90 days from the date of this

published Notice, NIH receives written

evidence and argument that establishes

that the grant of the license would not

be consistent with the requirements of

the 35 U.S.C. 209 and 37 CFR § 404.7.

Applications for a license to the field

of use described in this Notice will be

treated as objections to the

contemplated license. Comments and

objections will not be made available for

public inspection and, to the extent

permitted by law, will not be subject to

disclosure under the Freedom of

Information Act, 5 U.S.C. 552.

Dated: October 17, 1997.

Barbara M. McGarey,

Deputy Director, Office of Technology

Transfer.

[FR Doc. 97–28380 Filed 10–24–97; 8:45 am]

BILLING CODE 4140–01–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Public Health Service

National Institute of Environmental

Health Sciences (NIEHS); Notice of

Meeting To Discuss the Procedures

and Activities of the National

Toxicology Program (NTP) Center for

the Evaluation of Alternative

Toxicological Methods and the

Interagency Coordinating Committee

on the Validation of Alternative

Methods (ICCVAM)

SUMMARY: Pursuant to Public Law 103–

43, notice is hereby given of a public

meeting sponsored by the NIEHS and

the NTP, U.S. Public Health Service, to

discuss the planned procedures and

activities of a new NTP Center for the

Evaluation of Alternative Toxicological

Methods and the ICCVAM, and to

receive comments from invited

participants and the public to assist

with future activities and priorities.

The meeting will be held in the

Conference Center, Building 101, South

Campus, NIEHS, 111 Alexander Drive,

Research Triangle Park, North Carolina

27709, on November 7, 1997, from 8:45

a.m. to 4:00 p.m.

Background Information: Public Law

103–43 directed the NIEHS to develop

and validate alternative methods that
55650 Federal Register / Vol. 62, No. 207 / Monday, October 27, 1997 / Notices

1This proposal was originally discussed at an

NIEHS/NTP Workshop on ‘‘Developing

Partnerships for the Validation of New Approaches

for Toxicological Evaluation,’’ held July 22, 1996 at

the NIEHS, Research Triangle Park, NC.

2Final Report: National Toxicology Program

Workshop on Validation and Regulatory

Acceptance of Alternative Toxicological Test

Methods,’’ March, 1996, National Institute of

Environmental Health Sciences, Research Triangle

Park, NC, USA.

3 Validation and Regulatory Acceptance of

Toxicological Test Methods: A Report of the ad hoc

Interagency Coordinating Committee on the

Validation of Alternative Methods,’’ NIH

Publication 97–3981, March 1997. National

Institute of Environmental Health Sciences,

Research Triangle Park, NC. USA.

can reduce or eliminate the use of

animals in acute or chronic toxicity

testing, establish criteria for the

validation and regulatory acceptance of

alternative testing methods, and

recommend a process through which

scientifically validated alternative

methods can be accepted for regulatory

use. Criteria and processes for

validation and regulatory acceptance

were developed in conjunction with 14

other Federal agencies and programs

with broad input and participation from

the public. These are described in the

document ‘‘Validation and Regulatory

Acceptance of Toxicological Test

Methods: A Report of the Ad—Hoc

Interagency Coordinating Committee on

the Validation of Alternative Methods,’’

NIH Publication 97–3981, March 1997.

The Report’s recommendations include

the establishment of an interagency

coordinating committee whose

functions would include the

coordination of interagency reviews of

toxicological test methods and

communication with stakeholders

throughout the process of test method

development and validation. In

response to these recommendations, the

NIEHS, in collaboration with 13 other

Federal agencies and programs, recently

established the Interagency

Coordinating Committee on the

Validation of Alternative Methods

(ICCVAM). The ICCVAM is composed of

representatives from NTP Executive

Committee agencies and several other

federal regulatory and research agencies.

The ICCVAM addresses toxicological

test method issues that are common to

multiple agencies without impinging on

considerations unique to individual

programs and agencies. Coordinated test

method peer reviews are expected to

facilitate the acceptance decision

process, with final regulatory

acceptance recognized as the purview of

each Federal agency according to its

regulatory mandates.

A NTP Center for the Evaluation of

Alternative Toxicological Methods is

being established to work with ICCVAM

to carry out related activities and to

implement the Report’s

recommendations. The Center proposal

includes the opportunity for publicprivate partnerships to enhance the

level and scope of the Center’s

activities. The planned procedures and

activities of the Center and ICCVAM

will be discussed at this meeting. NIEHS

has invited knowledgeable individuals

to participate in this meeting from a

cross section of stakeholder

organizations and institutions

concerned with the development,

validation, and use of alternative

toxicological methods.

Tenetative Agenda: The NIEHS and

Interagency Staff will present the

proposed procedures and activities of

the Center and the ICCVAM;

opportunities for public-private

partnerships in the development,

validation, and review of alternative

methods; and the role of the Advisory

Committee on Alternative Toxicological

Methods.

8:45 a.m. Welcome and Introduction

9:05 a.m. Procedures and Activities of

the Center and ICCVAM

11:45 a.m. Public comment

12:00 p.m. Lunch Break

1:00 p.m. Partnership Opportunities

2:45 p.m. Discussion on the Role of the

Advisory Committee

3:30 p.m. Public Comment

4:00 p.m. Adjourn

A description of the Center follows

this announcement.

Public Participation: The entire

meeting will be open to the public with

attendance limited only by space

available. Members of the public who

wish to present oral statements should

contact Dr. Larry Hart below by

telephone, fax, or mail as soon as

possible, but no later than October 31,

Speakers will be assigned on a first

come, first serve basis, and will be

limited to five minutes in length to

allow for a maximum number of

presentations. Written comments

accompanying the oral statements are

encouraged and should be submitted in

advance if possible by mail or fax to Dr.

Hart, NIEHS, P.O. Box 12233, MD: A3–

07, Research Triangle Park, North

Carolina 27709, telephone (919) 541–

3971 or FAX (919) 541–0295. Persons

needing special assistance, such as sign

language interpretation or other special

accommodations should contact Dr.

Hart as soon as possible.

FOR FURTHER INFORMATION CONTACT: Dr.

William S. Stokes, Co-Chair, ICCVAM,

Environmental Toxicology Program,

P.O. Box 12233, NIEHS, Research

Triangle Part, North Carolina 27709,

telephone (919) 541–7997, FAX (919)

541–0947. The NIH Publication 97–

3981, Validation and Regulatory

Acceptance of Toxicological Test

Methods, a Report of the ad hoc

Interagency Coordinating Committee on

the Validation of Alternative Methods,

can be located on the internet at httpp:/

/ntp-server.niehs.nih.gov/htdocs/

ICCVAM/ICCVAM.html, or a copy may

be requested from the NTP Liaison

Office, P.O. Box 12233, MD A3–01,

Research Triangle Park, NC, 27709, Fax

919–541–0295, tel 919–541–0530, or

email: britton@niehs.nih.gov.

Attachment

Dated: October 20, 1997.

Kenneth Olden,

Director, National Toxicology Program.

[Revised 10–15–97 1]

NTP Center for the Evaluation of Alternative

Toxicological Methods

Background/Need: Government, industry,

and public interest groups have the

responsibility to protect public health and

the environment, and to prevent unnecessary

exposure to hazards. In carrying out these

responsibilities, scientists develop and adopt

health and ecotoxicological testing methods

to evaluate the potential adverse effects of

chemicals or to demonstrate their safety.

These methods are used to generate hazard

identification and dose-response data to

support health and environmental risk

assessments for chemicals and products

during their development, manufacture,

distribution, use, and disposal.

Toxicological testing methods are being

developed and revised by the public and

private sector with increasing frequency to

provide for improved assessment of toxicity,

to evaluate toxicity endpoints not previously

assessed, to incorporate advances in

biotechnology and out understanding of toxic

mechanisms at the molecular and cellular

level, to provide for improved efficiency (less

time and expense), and to replace, reduce,

and refine animal use. Requirements for the

use of new test methods to generate

information for regulatory purposes are

twofold. First, the method must meet the

criteria for validation, i.e., there must be

scientific evidence that the method is reliable

and relevant for its proposed use. Second, the

method must meet the criteria for acceptance,

e.g., there must be a determination that the

use of the method will fulfill a specific need

for one or more federal agencies. Until now,

there has been no established process for

federal agencies to coordinate the review of

proposed methods with other federal

agencies that may find the method useful.

Participants at a recent National

Toxicology Program (NTP) sponsored

workshop 2 and an ad hoc interagency

committee 3 recommended that an

interagency coordinating committee be

established whose functions would include

the coordination of interagency reviews of

toxicological test methods and

communication with stakeholders

throughout the process of test method
Federal Register / Vol. 62, No. 207 / Monday, October 27, 1997 / Notices 55651

4The project concept was peer reviewed and

approved by the NTP Board of Scientific Counselors

at their December 13, 1996 meeting.

development and validation. The NIEHS, in

collaboration with 13 other federal agencies

and programs, has recently established a

standing committee that will carry out these

functions. Designated as the Interagency

Coordinating Committee on the Validation of

Alternative Methods (ICCVAM), it is

composed of representatives form the NTP

Executive Committee agencies and several

other federal regulatory and research

agencies. The ICCVAM focuses on

toxicological test method issues that are

common to multiple agencies without

impinging on considerations unique to

individual programs and agencies. Final

regulatory acceptance will be the purview of

each Federal agency according to its

regulatory mandates; however, the ICCVAM

coordinated peer review should facilitate the

acceptance decision process.

In order to implement the NTP workshop

and ad hoc interagency committee

recommendations, an NTP Center for the

Evaluation of Alternative Toxicological

Methods is being established to work with

ICCVAM to carry out related activities. The

Center includes the opportunity for publicprivate partnerships to enhance the level and

scope of its activities. The Interagency

Committee and Center initiatives implement

Public Law 103–43 that directs NIEHS to

develop a process to achieve regulatory

acceptance of alternative test methods.

Goal: The goal of the Center and ICCVAM

is to promote the scieitnifc validation and

regulatory acceptance of new test methods

that are more predictive of human and

ecological effects than currently available

methods.

Objective: To achieve this goal, the Center

will collaborate with the ICCVAM to

facilitate scientific peer review and

interagency consideration of new test

methods of multi-agency interest. Emphasis

will be on methods with an appropriate

biological basis for the species of concern

that provide: improved toxicity

characterization; savings in time and costs;

and where possible, the refinement,

reduction, and replacement of animal use.

Regulatory Impact/Benefits: The expected

benefits of this initiative include:

• Increased efficiency and effectiveness of

test method review;

• Elimination of duplicative efforts across

regulatory agencies;

• Utilization of shared expertise across the

Federal system;

• Optimal utilization of scientific expertise

outside the Federal government;

• Decreased total transaction costs and

time to evaluate new and revised test

methods;

• Elimination of redundant testing;

• Increased likelihood that new test

methods will meet the needs of agencies; and

• Increased harmonization of testing

requirements across the federal government

and internationally.

This program will benefit all parties by

creating a forum to solicit expert input and

provide communication during development,

validation and review of proposed new test

methods. Such methods, after acceptance by

regulatory agencies, will provide for

improved human health and ecological risk

assessment and potential savings in time and

costs. The program will also benefit animal

welfare by the adoption of methods that

refine, reduce, or replace the use of animals

where scientifically feasible.

Structure/Function: The overall structure

encompasses the ICCVAM, a Center Office,

Peer Review and Expert Panels, and a Federal

Advisory Committee.

The ICCVAM consists of representatives

from federal regulatory and research agencies

that generate or use information from

toxicological test methods to support human

health or environmental risk assessments.

Members serve as points of contact and as

sources to identify technical experts from

their agencies to serve on specific topical

workgroups. Committee activities may

include the following, as appropriate:

• Evaluate the status of validation and

make recommendations to agencies regarding

the scientific usefulness of test methods and

their potential applicability;

• Coordinate technical reviews of

proposed new and revised test methods of

interagency interest;

• Facilitate interagency communication

and information sharing;

• Serve as an interagency resource and

communication link with parties outside of

the Federal government, including academic,

other government, industry, and public

interest groups;

• Assist agencies in assessing test method

needs;

• Provide guidance to agencies and other

stakeholders on criteria and processes for the

development, validation and acceptance of

tests;

• Promote awareness of accepted U.S. test

methods; and

• Advocate harmonization of test methods

nationally and internationally.

The Center Office is located at NIEHS and

consists of 3–5 government professional and

administrative staff augmented with

appropriate contract support.4 The Center

will collaborate with the ICCVAM to carry

out activities to accomplish the following;

• Communicate with interested

stakeholders, and facilitate communication

during the development and validation

process with appropriate agencies; and

• Assess the completeness of submissions

and determine if there are sufficient data for

test methods to undergo independent public

scientific peer review;

• Arrange for scientific peer reviews;

• Organize expert panels and/or

workshops to assess the validation status of

a method or group of methods;

• Provide recommendations and results to

research and regulatory agencies;

• Prepare, publish, and distribute reports

and information about new test methods.

Peer Review Panels will be asked to

develop scientific consensus on the

usefulness of test methods to generate

information for specific human health and/or

ecological risk assessment purposes. They

will discuss the biological relevance of the

new test to the toxicity of interest. They will

address how and when the new test method

can partially or fully replace existing

methods or approaches. When appropriate,

panels will be asked to identify whether

additional validation studies are necessary to

adequately evaluate a method, and to identify

additional research to support the

development of mechanism-based test

methods.

It is anticipated that expert review panels

will also be convened to evaluate the

adequacy of current methods for assessing

specific toxicities, to identify areas in need

of improved or new methods, and to evaluate

proposed validation studies. Agencies would

use this information to establish priorities for

appropriate research, development, and

validation efforts in collaboration with

interested parties.

Products of the review process will be

published reports that present a

comprehensive peer review of the data

substantiating the validity of a new method.

The ICCVAM will forward recommendations

regarding the scientific validity and potential

acceptability of test methods to agencies for

consideration. Each Federal agency will then,

according to its regulatory mandates,

determine the regulatory acceptability of a

method.

A Federal Advisory Committee on

Alternative Toxicological Methods,

composed of knowledgeable representatives

from academia, industry, public interest/

animal welfare organizations, federal and

state government agencies, and the

international community will review and

provide advice on the activities and priorities

of the Center, and advice on ways to foster

partnership activities and interactions among

all the stakeholders.

Funding: Activities of the Center will be

funded by a pooling of financial resources

from interested partners, which may include

federal agencies, industry, and other parties.

NIEHS will provide core funding and

professional and administrative staff for the

Center. Other agencies will provide

appropriate representatives and expert staff

for the ICCVAM and its associated activities,

including appropriate agency liaisons for

peer review activities.

Conflict of Interest Issues: Scientific peer

review must be conducted by persons that

are financially unencumbered with the

outcome of the evaluation. All peer reviews

will be required to comply with Federal

government conflict of interest standards.

Similarly, financial support of peer review

activities must be free of any direct or

apparent conflict of interest. To this end,

funds to support Center activities will

normally be deposited to the federal

government and designated for the Center.

NIEHS will disburse funds in accordance

with federal regulations and guidelines.

[FR Doc. 97–28373 Filed 10–24–97; 8:45 am]

BILLING CODE 4140–01–M