Federal Register / Vol. 66, No. 107 / Monday, June 4, 2001 / Notices 29979

Virus-Like Particles as Unlinked

Adjuvants

John Schiller, Bryce Chackerian, Joseph

Lee, Douglas Lowy (NCI)

Serial No. 60/219,763, filed 20 Jul 2000

This invention claims

immunostimulating or vaccine

compositions in which non-infectious

virus-like particles (VLPs) serve as

unlinked adjuvants. Co-administration

of VLPs with an antigen enhances

induction of high titer IgG antibodies to

self or foreign antigens and promotes T

cell responses to foreign antigens. The

VLP-target antigen combination can be

administered alone or with a traditional

adjuvant. The VLPs of the current

invention are contemplated to comprise

capsid protein(s) of a virus assembled

into a shell resembling a virion, but not

containing pathogenic viral DNA or

RNA. The VLPs are unlinked, rather

than physically linked to the antigen

because this may reduce the

manufacturing complexity of the

vaccine. Unlinked VLP adjuvants, for

example papillomavirus VLPs, of the

invention have a number of advantages:

(1) They are non-inflammatory in

humans, (2) are potent at amplifying IgG

antibody responses to self antigens, (3)

induce a pronounced Th1 type of T cell

response, and (4) may provide two-fold

protection, against the virus

corresponding to the VLP type, as well

as against the disease associated with

the other component in the VLP-target

antigen combination.

Peptides That Stabilize Protein

Antigens and Enhance Presentation to

CD8+ T Cells

Roger Kurlander, Elizabeth Chao, Janet

Fields (CC)

Serial No. 60/169,227, filed 06 Dec 1999

and PCT/US00/33027, filed 12 Dec

2000

This invention relates to compositions

and methods for stabilizing an antigen

against proteolytic degradation and

enhancing its presentation to CD8+

cells. The invention claims ‘‘fusion

agents,’’ isolated molecules comprising

a hydrophobic peptide joined to an

epitope to which a CD8+ T cell response

is desired. Also claimed in the

invention are the nucleic acid sequences

that encode the fusion agents. Recently,

there has been great interest in

developing vaccines to induce

protective CD8+ T cell responses,

however, there are practical obstacles to

this goal. Although purified antigenic

peptides are effectively presented in

vitro, introduced in a purified form they

often do not stimulate effective T cell

responses in vivo because the antigens

are insufficiently immunogenic and too

easily degraded. Adjuvants or infectious

‘‘carriers’’ often can enhance these

immune responses, however, these

added agents can cause unacceptable

local or systemic side effects. The

present invention increases antigen

stability and promotes in vivo responses

in the absence of an adjuvant or active

infection.

The invention describes three variants

of lemA, an antigen recognized by CD8+

cells in mice infected with Listeria

monocytogenes. The antigenic and

stabilizing properties of lemA can be

accounted for by the covalent

association of the immunogenic

aminoterminal hexapeptide with the

protease resistant scaffolding provided

by amino acids 7 to 33 of the lemA

sequence (lemA(7–33)). Variants t-lemA,

and s-lemA bearing an antigenic

sequence immediately preceding

lemA(7–33), and lemS containing an

immunogenic sequence immediately

after lemA(7–33), each induce a CD8+ T

cell response and protect the crucial

immunogenic oligopeptide from

protease degradation. The site of antigen

insertion relative to lemA(7–33) can

influence antigen processing by

preferentially promoting processing

either in the cytoplasm or endosomal

compartment. Therefore, several

embodiments of the invention involve

the construction of antigen processing

protein molecules and their methods of

use. Alternatively, a DNA sequence

coding lemA(7–33) may be inserted at

an appropriate site to enhance the

immunogenicity of the antigenic

element coded by a DNA vaccine. In

sum, this invention is an attractive,

nontoxic alternative to protein/adjuvant

combinations in eliciting CD8 responses

in vivo and a useful element for

enhancing the efficiency with which

products coded by DNA vaccines are

processed and presented in vivo.

Because lemA(7–33) is particularly

effective in protecting oligopeptides

from proteases, this invention may have

particular usefulness in enhancing local

T cell at sites such as mucosal surfaces

where there may be high proteolytic

activity.

For more specific information about

the invention or to request a copy of the

patent application, please contact Peter

Soukas at the telephone number or email listed above. Additionally, please

see a related article published in the

Journal of Immunology at:

1999;163:6741–6747.

Dated: May 25, 2001.

Jack Spiegel,

Director, Division of Technology,

Development and Transfer, Office of

Technology Transfer, National Institutes of

Health.

[FR Doc. 01–13888 Filed 6–1–01; 8:45 am]

BILLING CODE 4140–01–P

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

Prospective Grant of Exclusive

License: Development of Live,

Attenuated Vaccines for Human Use

Against Respiratory Syncytial Viruses

Types A and B, and Parainfluenza

Viruses Types 1, 2 and 3

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, is

contemplating the grant of an exclusive

license worldwide to practice the

inventions embodied in the patent

applications referenced below to

American Home Products Corporation

through its Wyeth-Ayerst Laboratories

Division, Wyeth-Lederle Vaccines

business unit, having a place of business

in Madison, N.J. The United States of

America is an assignee to the patent

rights of these inventions.

USPA 09/291,894, filed 4/13/99,

entitled ‘‘Production of attenuated

Chimeric RSV vaccines from cloned

nucleotide sequences’’ (now PCT/

US00/08802, filed 3/31/00)

USPA 09/350,821, filed 7/9/99, entitled

‘‘Recombinant PIV vaccines

attenuated by deletion or ablation of

non-essential gene’’ (now PCT/

US00/18523, filed 7/6/00)

USPA 60/143,132, filed 7/9/99, entitled

‘‘Production of attenuated, humanbovine chimeric RSV vaccines’’

(now USPA 09/602,212 and PCT/

US00/17755, both filed 6/23/00)

USPA 60/143,425, filed 7/13/99,

entitled ‘‘Production of

recombinant RSV expressing

immune modulatory molecules’’

(now USPA 09/614,285 and PCT/

US00/19042, both filed 7/12/00)

USPA 60/143,097, filed 7/7/99, entitled

‘‘Production of attenuated RSV

vaccines involving modification of

M2 open reading frame (ORF) 2’’

(now USPA 09/611,829 and PCT/

US00/18534, both filed 7/7/00)

29980 Federal Register / Vol. 66, No. 107 / Monday, June 4, 2001 / Notices

USPA 60/143,134, filed 7/9/99, entitled

‘‘Attenuated human-bovine

chimeric PIV vaccines’’ (now USPA

09/586,479 and PCT/US00/17066,

both filed 6/15/00)

USPA 60/129,006, filed 4/13/99,

entitled ‘‘Production of attenuated

negative stranded RNA virus

vaccines from cloned nucleotides’’

(now PCT/US00/09695, filed 4/12/

00)

USPA 60/170,195, filed 12/10/99,

entitled ‘‘Use of recombinant PIVs

as vectors to protect against

infectious Diseases caused by PIV

and other human Pathogens’’ (now

USPA 09/733,692 and PCT/US00/

33293, both filed 12/8/00)

USPA 60/213,708, filed 6/23/00,

entitled ‘‘RSV vaccines expressing

protective antigens from promoterproximal genes’’

USPA 60/215,809, filed 7/5/00, entitled

‘‘Attenuated human-bovine

chimeric PIV vaccines’’

USPA 60/007,083, filed 9/27/95,

entitled ‘‘Production of infectious

Respiratory Syncytial Virus from

cloned nucleotide sequences’’ (now

USPA 08/720,132 and PCT/US96/

15524, both filed 9/27/96)

The contemplated exclusive license

may be limited to the development of

live, attenuated vaccines for human use

against Respiratory Syncytial Viruses

Types A and B, and Parainfluenza

Viruses Types 1, 2 and 3.

DATES: Only written comments and/or

applications for a license which are

received by the NIH Office of

Technology Transfer on or before

August 3, 2001 will be considered.

ADDRESSES: Requests for a copy of the

patent application, inquiries, comments

and other materials relating to the

contemplated license should be directed

to Uri Reichman, Ph.D., Technology

Licensing Specialist, Office of

Technology Transfer, National Institutes

of Health, 6011 Executive Boulevard,

Suite 325, Rockville, MD 20852–3804;

Telephone: (301) 496–7056, ext. 240;

Facsimile: (301) 402–0220; E-mail:

reichmau@od.nih.gov. A signed

Confidential Disclosure Agreement will

be required to receive copies of the

patent application.

SUPPLEMENTARY INFORMATION: The Patent

Applications cover a wide range of

methods to produce live attenuated

vaccines for PIV and RSV. This

includes, for example, deletion or

ablation of non-essential genes (PIV,

USPA 09/350,821), insertion of genes

expressing immune modulatory

molecules (RSV, USPA 60/143,425),

modification of the second translational

open reading frame of the M2 gene

(RSV, USPA 60/143,097), and shifts in

gene positions that modulate expression

of selected genes (RSV, USPA 60/

213,708). It also includes human-bovine

chimeric constructs (PIV, USPA 60/

215,809, USPA 60/143,134; RSV, USPA

60/143,132) or RSV–PIV chimeric

constructs (USPA 60/170,195 for

PIV1,2,3 and USPA 09/291,894 for

RSVA/B). US Provisional Application

60/129,006 relates to a new attenuation

strategy applicable for the development

of RSV and PIV vaccine candidates. It

generally describes the finding that

attenuating mutations identified in

certain negative stranded RNA viruses

are transferable to other viruses of the

Mononegavirale order. US Provisional

Application 60/007,083 describes an

expression system for recovery of RSV

viruses from the corresponding cDNA

sequences.

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. The 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.

Properly filed competing applications

for a license filed in response to this

notice will be treated as objections to

the contemplated license. Comments

and objections submitted in response 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: May 25, 2001.

Jack Spiegel,

Director, Division of Technology Development

and Transfer, Office of Technology Transfer.

[FR Doc. 01–13887 Filed 6–1–01; 8:45 am]

BILLING CODE 4140–01–P

DEPARTMENT OF THE INTERIOR

Fish and Wildlife Service

Meeting of the Alaska Migratory Bird

Co-management Council

AGENCY: Fish and Wildlife Service,

Interior.

ACTION: Notice of meeting.

SUMMARY: The Alaska Migratory Bird

Co-management Council has scheduled

a public meeting to discuss financial

needs and sources for funding the

operation of the Council and the

regional management bodies.

DATES: The Co-management Council

will meet June 26, 2001.

ADDRESSES: The meeting will be

conducted at the Hawthorn Suites Hotel

at 1110 W. 8th Avenue in Anchorage,

Alaska.

FOR FURTHER INFORMATION CONTACT: For

additional information call Bob Stevens

at 907/786–3499. Individuals with a

disability who may need special

accommodations in order to participate

in the public comment portion of the

meeting should call the above number.

SUPPLEMENTARY INFORMATION: The U.S.

Fish and Wildlife Service formed the

Alaska Migratory Bird Co-Management

Council, which includes Native, State,

and Federal representatives as equals,

by means of a Notice of Decision

published in the Federal Register, 65 FR

16405–16409, March 28, 2000. The

amended Migratory Bird Treaty with

Canada required the formation of such

a management body. The Comanagement Council will make

recommendations for regulations for

spring/summer subsistence harvesting

of migratory birds in Alaska. In addition

the Co-management Council will make

recommendations regarding population

and harvest monitoring, law

enforcement policies, habitat protection,

research and use of traditional

knowledge, and education programs.

The meeting of the Co-management

Council will begin at 8:30 a.m. on

Tuesday, June 26, 2001. The session

will end no later than 5 p.m. that day.

The primary agenda item will be a

discussion of funding alternatives for

the operation of the Co-management

Council and the regional management

bodies that provide recommendations to

the Co-management Council. The public

is invited to attend. The Co-management

Council will provide opportunities for

public comment on agenda items at the

end of the morning session and at the

end of the afternoon session. Additional

opportunities may be provided at the

discretion of the Co-management

Council. Agendas will be available at

the door.

Dated: May 23, 2001.

David B. Allen,

Regional Director, Anchorage, Alaska.

[FR Doc. 01–13936 Filed 6–1–01; 8:45 am]

BILLING CODE 4310–55–P