Federal Register / Vol. 63, No. 18 /Wednesday, January 28, 1998 / Notices 4273

of the limitations of sterility testing,

FDA has determined that alternative

methods are available that may more

reliably confirm the integrity of the

container and closure system in the

final form throughout the entire dating

period.

The draft guidance was prepared

jointly by the following Centers: Center

for Biologics Evaluation and Research

(CBER), Center for Drug Evaluation and

Research (CDER), Center for Veterinary

Medicine (CVM), and Center for Devices

and Radiological Health (CDRH). At the

request of CBER’s Stability and

Formulation Committee, representatives

from the Centers met on May 19, 1994,

to discuss sterility testing as a

component of the stability protocol. The

ability of containers/packaging to

maintain sterility should be proven for

all sterile products.

As with other guidance documents,

FDA does not intend this document to

be all-inclusive and cautions that not all

information may be applicable to all

situations. The document is intended to

provide information and does not set

forth requirements. Alternative

approaches may be warranted in

specific situations, and certain aspects

may not be applicable to all situations.

If a manufacturer believes that the

procedure described in the draft

guidance is inapplicable to a particular

method and other procedures are

appropriate for FDA’s consideration, the

manufacturer may wish to discuss the

matter further with the agency to

prevent expenditure of money and effort

on activities that later may be

determined to be unacceptable by FDA.

FDA will continue to review alternative

methods on a case-by-case basis.

The draft guidance represents the

agency’s current thinking on container

and closure integrity testing during

stability monitoring for sterile products.

It does not create or confer any rights for

or on any person and does not operate

to bind FDA or the public. An

alternative approach may be used if

such approach satisfies the

requirements of the applicable statute,

regulations, or both. The draft guidance

document is being distributed for

comment purposes only and is not

intended for implementation at this

time.

II. Request for Comments

Interested persons may, at any time,

submit written comments to the Dockets

Management Branch (address above)

regarding this draft guidance document.

Two copies of any comments are to be

submitted, except that individuals may

submit one copy. Comments and

requests for copies are to be identified

with the docket number found in the

brackets in the heading of this

document. A copy of the draft guidance

and received comments are available for

public examination in the Dockets

Management Branch between 9 a.m. and

4 p.m., Monday through Friday.

III. Electronic Access

In order to receive the ‘‘Guidance for

Industry: Container and Closure

Integrity Testing in Lieu of Sterility

Testing as a Component of the Stability

Protocol for Sterile Products’’ via your

fax machine, call the FAX Information

System at 1–888–CBER–FAX or 301–

827–3844.

Persons with access to the Internet

may obtain the draft guidance document

by using the World Wide Web (WWW).

For WWW access, connect to CBER at

‘‘http://www.fda.gov/cber/

guidelines.htm’’. Received comments

will be considered in determining

whether further revision of the draft

guidance document is warranted.

Dated: January 21, 1998.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

[FR Doc. 98–2021 Filed 1–27–98; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

Government-Owned Inventions;

Availability for Licensing

AGENCY: National Institutes of Health,

HHS.

ACTION: Notice.

SUMMARY: 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 companies and may also be available

for licensing.

ADDRESSES: Licensing information and

copies of the U.S. patent applications

listed below may be obtained by writing

to the indicated licensing contact 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.

Novel Attenuated Strains

Mycobacterium Tuberculosis

CE Barry, Y. Yuan (NIAID).

Serial No.: 60/025,199 filed 10 July

97.

Licensing Contact: Carol Salata, 301/

496–7735 ext 232.

This invention provides for novel

attenuated strains of Mycobacterium

tuberculosis and M. bovis. Attenuation

is achieved by down-regulating the

expression of the α-crystallin heat shock

protein gene (‘‘acr gene’’). This gene is

essential for virulence of the organism.

Since this strain is isogenic with

virulent M. tuberculosis but for this

deletion, the full complement of

antigens remains present and the

organism is viable in vitro. The

invention provides for vaccines and

methods of vaccinating mammals for

protection against Mycobacterium sp.

that cause tuberculosis.

Method of Promoting Tumor Necrosis

Using MIG

G Tosato (FDA), J Farber (NIAID), C

Sgardari (FDA).

Serial No.: 08/850,914 filed 2 May 97.

Licensing Contact: Jaconda Wagner,

301/496–7735 ext 284.

Monokine induced by IFN–γ (Mig),

which is structurally related to

interferon-inducible protein 10 (IP–10),

has been shown to exhibit antitumor

activity. Mig is a member of the α

chemokine family. Members of this

chemokine family, PF4, PBP, CTAP–III

βTG, NAP–2, IL–8 GROα, GROβ, GROγ,

and IP–10, have been shown to act as an

angiogenic or angiostatic factor. This

invention relates to the use of Mig to

promote the death of tumor tissue. It

also relates to a method of inhibiting

angiogenesis at a tumor site using Mig.

This research has been published in

Blood 1997 Apr 15;89(8):2635–43 and J

Leukoc Biol 1997 Mar;61(3):246–57.

A related case is also available for

licensing: Serial No. 08/455,079 filed 31

May 95 entitled ‘‘Interferon-Inducible

10 (IP–10) is a Potent Inhibitor of

Angiogenesis’’; inventors are G Tosato,

AL Angiolillo, and C Sgardari.

Formation of Human Bone In Vivo

PG Robey (NIDR), P Bianco

(Universita dell Aquilla), Sa Kuznetsov

(NIDR), PH Krebsback (NIDR), DW Rowe

(University of Connecticut.

Serial No.: 08/798, 715 filed 12 Feb.

97.

Licensing Contact: Jaconda Wagner,

301/496–7735 ext 284.

This invention provides a model for

studying human bone metabolism in
4274 Federal Register / Vol. 63, No. 18 /Wednesday, January 28, 1998 / Notices

vivo. The model system can be used to

screen compounds which inhibit or

stimulate bone formation. A protocol

using marrow stromal fibroblasts is also

presented. Use of the protocol results in

the formation of self-maintained human

bone which supports hematopoiesis.

The marrow stromal fibroblasts

combined with the described delivery

vehicles can be implanted into humans

to augment bone implants or to repair

bone defects.

This research has been published in J

Bone Miner Res 1997 Sep;12(9):1335–47

and Transplantation 1997 Apr

27;63(8):1059–69.

Synthesis and Purification of Hepatitis

C Virus Like Particles In Vitro

TJ Liang and TF Baumert (NIDDK).

Serial No.: 60/030,238 filed 8 Nov 96;

PCT/US97/05096 filed 25 Mar. 97.

Licensing Contact: Carol Salata, 301/

496–7735 ext 232.

Hepatitis C virus (HCV) is a major

causative agent of posttransfusion and

community-acquired hepatitis worldwide. Analysis of the structural features

of HCV has been hampered by the

inability to propagate the virus

efficiently in cultural cells and the lack

of a convenient animal model. This

invention discloses the production and

purification of HCV-like particles in

eukaryotic cells. Infection of insect cells

with a recombinant baculovirus

containing the cDNA for the HCV

structural proteins resulted in the

formation of HCV-like particles in

cytoplasmic cisternae of the insect cells.

Sucrose gradient purification HCV-like

particles exhibited similar biophysical

properties as putative HCV virions.

HCV-like particles, purified in large

quantities, may be useful in HCV

vaccine development or in diagnostic

kits.

An Enzyme-Linked Immunosorbent

Assay (ELISA) to Detect Antibodies to a

Nonstructural Protein of Hepatitis A

Virus (HAV)

RH Purcell, T Schultheiss, D Stewart,

S Emerson (NIAID).

Serial No.: 60/013, 333 filed 13 Mar.

96; PCT/US97/03428 filed 13 Mar.

97.

Licensing Contact: George Keller, 301/

496–7735 ext 246.

The current invention embodies an

assay which can differentiate between

an individual who has been vaccinated

against Hepatitis A Virus (HAV), and

one who has actually been infected with

the virus. HAV infection results in the

production of antibodies against both

structural and nonstructural proteins of

the virus. Inactivated HAV vaccines,

which are commonly used for

immunization against HAV, cause the

production of antibodies against the

structural proteins. Assays currently in

use for determining exposure to HAV

measure only antibodies to structural

proteins, and therefore are incapable of

differentiating between individuals who

have been infected with HAV and those

who have merely been immunized with

the inactivated virus.

The assay embodied in the current

invention is capable of detecting

antibodies to the 3C proteinase, which

is a nonstructural protein of HAV. This

assay, which utilizes an ELISA for the

detection of such antibodies, should

represent a significant improvement

over assays which are currently

available.

Restriction Display (RD–PCR) of

Differentially Expressed mRNAs

JN Weinstein, J. Buolamwini (NCI).

Serial No.: 60/011, 379 filed 09 Feb

96; PCT/US97/02009 filed 7 Feb.

97.

Licensing Contact: J. Peter Kim, 301/

496–7056 ext 264.

This invention provides a kit and

methods for detecting gene expression

in cells by reverse transcribing mRNA

molecules into cDNA, and selectively

amplifying a subset of the cDNA by a

polymerase chain reaction (PCR) to

present a two-dimensional display of

the fragments or for cloning into a

vector using restriction enzyme

recognition sites added during the PCR.

In one aspect of this invention, only

cDNA corresponding to the 3′ end of the

mRNA is amplified and displayed or

cloned. In another aspect of the

invention, cDNA corresponding to the

entire mRNA molecule is amplified for

display or cloning. The method and kit

may be useful in characterizing cells

based on their mRNA content,

representing expressed genes, and

discovering therapeutics that alter

cellular gene expression by

characterizing cells of different types

under a variety of physiological

conditions. In addition to drug

discovery, this approach may be used

whenever expression of mRNA is to be

assessed, for example, in studies of

malignant transformation,

carcinogenesis, immune activation, and

developmental biology.

Selective Elimination of T-Cells that

Recognize Specific Preselected Targets

A Rosenberg (FDA).

Serial No.: 60/002, 964 filed 30 Aug.

95; PCT filed 30 /Aug. 96.

Licensing Contact: Jaconda Wagner,

301/496–7735 ext 284

The invention relates to methods and

compositions for the elimination of T

cells that recognize specific preselected

targets which can be used to threat

autoimmune diseases and graft

rejection.

The invention provides a method for

selectively inhibiting or killing T cells

that recognize a specific preselected

target molecule and also for modified

killer cells that bear a signal

transduction molecule to which is

attached the preselected target

molecule. Recognition of the preselected

molecule by a T cell activates the killer

cell which then kills or inhibits the T

cell. Where the preselected molecule is

an extracellular domain of an MHC from

a xenograft or an allograft, treatment of

the graft recipient with the modified

killer T cells delays or inhibits graft

rejection. Similarly, where the

preselected molecule is an MHC that

binds the antigenic determinant of the

autoimimune disease, treatment of the

organism with the modified T cells

mitigates the autoimmune response

directed against the antigenic

determinant.

This research was published in

Transpl Immunol 1993; 1(2):93–9.

Dated: January 16, 1998.

Barbara M. McGarey,

Deputy Director, Office of Technology

Transfer.

[FR Doc. 98–1967 Filed 1–27–98; 8:45 am]

BILLING CODE 4140–01–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

National Institute of General Medical

Sciences; Closed Meeting

Pursuant to section 10(d) of the

Federal Advisory Committee Act, as

amended (5 United States Code

Appendix 2), notice is hereby given of

the following National Institute of

General Medical Sciences Initial Review

Group (IRG) meeting:

Name of IRG: Minority Biomedical

Research Support.

Date: March 10–12, 1998.

Time: March 10—8 p.m.–11 p.m.; March

11—8:30 a.m–6 p.m.; March 12—8:30 a.m.–

adjournment.

Place: Holiday Inn—Bethesda, 8120

Wisconsin Avenue, Bethesda, Maryland

20814.

Contact Person: Dr. Michael A. Sesma,

Scientific Review Administrators, NIGMS,

Natcher Building—Room 1AS–19, Bethesda,

Maryland 20892, Telephone: 301–594–2048.

Purpose/Agenda: To evaluate and review

research training grant applications.

The meeting will be closed in accordance

with the provisions set forth in secs.

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