Federal Register / Vol. 63, No. 94 / Friday, May 15, 1998 / Notices 27095

and Drug Administration, 5600 Fishers

Lane, Rockville, MD 20857, or Office of

Communication, Training and

Manufacturers Assistance (HFM–40),

1401 Rockville Pike, Rockville, MD

20852–1448, or by calling 1–800–835–

4709 or 301–827–1800. Submit written

comments on the guidance to the

Dockets Management Branch (HFA–

305), Food and Drug Administration,

12420 Parklawn Dr., rm. 1–23,

Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT:

Shiew-Mei Huang, Center for Drug

Evaluation and Research (HFD–

850), Food and Drug

Administration, 5600 Fishers Lane,

Rockville, MD 20857, 301–594–

5671; or

Martin D. Green, Center for Biologics

Evaluation and Research (HFM–

579), 1401 Rockville Pike,

Rockville, MD 20852–1448, 301–

827–5344.

SUPPLEMENTARY INFORMATION: FDA is

announcing the availability of a

guidance entitled ‘‘Pharmacokinetics in

Patients with Impaired Renal

Function—Study Design, Data Analysis,

and Impact on Dosing and Labeling.’’

The pharmacokinetics (PK) and

pharmacodynamics (PD) of drugs

primarily eliminated through the

kidneys may be altered by impaired

renal function to the extent that the

dosage regimen needs to be changed

from that used in patients with normal

renal function. Although the most

obvious type of change arising from

renal impairment is a decrease in renal

excretion (or possibly renal metabolism)

of a drug or its metabolites, renal

impairment also has been associated

with other changes, such as changes in

hepatic metabolism, plasma protein

binding, and drug distribution. These

changes may be particularly prominent

in patients with severely impaired renal

function and have been observed even

when the renal route is not the primary

route of elimination of a drug. Thus, for

most drugs that are likely to be

administered to patients with renal

impairment, PK characterization may

need to be assessed in subjects with

such impairment to provide appropriate

dosing recommendations.

The guidance provides specific

information on when studies of PK in

patients with impaired renal function

should be performed and when they

may be unnecessary. It also addresses

the design and conduct of PK studies in

patients with impaired renal function,

the design and conduct of PK studies in

end stage renal disease patients treated

with dialysis, the analysis and reporting

of the results of such studies, and

representation of these results in

approved product labeling.

In the Federal Register of June 16,

1997 (62 FR 32617), FDA announced the

availability of a draft version of this

guidance, entitled ‘‘Pharmacokinetics

and Pharmacodynamics in Patients with

Impaired Rental Function: Study

Design, Data Analysis, and Impact on

Dosing and Labeling.’’ The June 16,

1997, document gave interested persons

an opportunity to submit comments

through August 15, 1997. All comments

received through the end of September

have been carefully reviewed and

incorporated, where appropriate, in this

revised guidance.

This guidance is being issued as a

Level 1 guidance consistent with FDA’s

good guidance practices (62 FR 8961,

February 27, 1997). It represents the

agency’s current thinking on conducting

PK studies on patients with impaired

renal function. 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

requirement of the applicable statute,

regulations, or both.

Interested persons may, at any time,

submit written comments on the

guidance to the Dockets Management

Branch (address above). Comments

should be identified with the docket

number found in brackets in the

heading of this document. A copy of the

guidance is available for public

examination in the Dockets

Management Branch between 9 a.m. and

4 p.m., Monday through Friday.

Dated: May 8, 1998.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

[FR Doc. 98–12898 Filed 5–14–98; 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,

Public Health Service, DHHS.

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.

Molecular Computing Elements: Gates

and Flip-Flops

TD Schneider, PN Hengen (NCI)

DHHS Reference No. E–170–97/0 filed

Feb. 20, 1998

Licensing Contact: John Fahner-Vihtelic,

301/496–7735 ext. 270

The present invention is a method

and apparatus for molecular computing

which provides for molecular logic

devices analogous to those of electronic

computers, such as flip-flops, AND

gates, etc. Coupling of the gates allows

for molecular computing. The method

allows data storage, the transformation

of binary information and signal

readout. Possible applications include

encoding ‘‘read only’’ memory for

microscopic identifiers, digital control

of gene expression, and quantification of

analytes. The computing elements also

provide means for complex regulation of

gene expression.

Lipooligosaccharide-Based Vaccine for

the Prevention of Moraxella

(Branhamella) Catarrhalis Infections In

Humans

X–X Gu, JB Robbins (NIDCD)

Serial No. 60/071,483 filed Jan 13, 1998

Licensing Contact: Robert Benson, 301/

496–7056 ext. 267

This invention is a vaccine for the

prevention of disease caused by M.

catarrhalis, which is the third most

common causative agent of otitis media

(middle ear infection) and sinusitis in

children. The emergence of antibiotic

resistant bacteria has caused concern

that treatment of otitis media will

become more problematic. This

invention offers a new approach to

managing otitis media. The vaccine is

composed of lipooligosaccharide (LOS),

isolated from the surface of strains of M.

catarrhalis and detoxified by removing

esterified fatty acids to produce

detoxified LOS (dLOS), which is then

conjugated to an immunogenic protein

carrier such as tetanus toxiod. The

conjugates have been shown to be

nontoxic by the limulus amebocyte
27096 Federal Register / Vol. 63, No. 94 / Friday, May 15, 1998 / Notices

assay. Antisera raised in rabbits

immunized with the conjugate is

bacteriocidal in vitro against

homologous and many heterologous

strains of M. catarrhalis.

Conjugate Vaccine for Nontypeable

Haemophilus Influenzae

X–X Gu, C–M Tsao, DJ Lim, JB Robbins

(NIDCD)

Serial No. 08/842,409 filed April 23,

1997

Licensing Contact: Robert Benson, 301/

496–7056 ext. 267

This invention is a vaccine for the

prevention of disease caused by

nontypeable H. influenzae (NTHi),

which causes 25%–40% of otitis media

cases (middle ear infections) in

children. The emergence of antibiotic

resistant bacteria has caused concern

that treatment of otitis media will

become more problematic. This

invention offers a new approach to

managing otitis media. The vaccine is

composed of lipooligosaccharide,

isolated from the surface of strains of

NTHi and treated with hydrazine to

remove esterified fatty acids, covalently

conjugated to an immunogenic carrier,

such as tetanus toxoid. The conjugates

have been shown to be nontoxic by the

limulus amebocyte assay, rabbit pyrogen

test and in an mouse lethal toxicity test.

Antisera raised in rabbits immunized

with the conjugate is bacteriocidal in

vitro against homologous and many

heterologous strains of NTHi. A blind

controlled trial in chinchillas, an animal

model for otitis media, showed that the

vaccines are protective against challenge

by NTHi.

Calorimeter and Method for

Simultaneous Measurement of Thermal

Conductivity and Specific Heat of

Fluids

NL Gershfeld, CP Mudd, AJ Jin, K

Fukada (NIAMS)

Serial No. 08/994,230 filed December

19, 1997

Licensing Contact: John Fahner-Vihtelic,

301/496–7735 ext. 270

The present invention is a novel

calorimeter and calorimetry apparatus

and method for the ultrasensitive

simultaneous measurement of heat

capacity and thermal conductivity of

fluids. The unique simultaneous

measurement of the two parameters

avoids sources of error in other

methods. The calorimeter shows

excellent accuracy of 1 part in 10,000

and run-to-run variability of 1 part in

100,000, as well as excellent long-term

reproducibility. The invention is well

suited for the study of biomaterials,

such as lipids and proteins and other

colloidal systems, which are not easily

analyzed using conventional

commercial instruments.

A Multi-Slice PET Scanner Constructed

From Side-Looking Phoswich

Scintillators Coupled to Miniature

Position-Sensitive Photomultiplier

Tubes: Application in Small Animal

Imaging

MV Green (CC)

DHHS Reference No. E–288–97/0 filed

Nov 12, 1997

Licensing Contact: John Fahner-Vihtelic,

301/496–7735 ext. 270

The present application describes a

new positron emission tomography

(PET) scanner. The design of this

scanner allows reduction of the detector

ring size relative to conventional

scanners (thereby reducing cost) while

increasing resolution, resolution

uniformity and sensitivity. This

combination of features makes the

invention particularly well-suited for

small animal imaging in biomedical

research, e.g. evaluating changes in

organ function due to genetic

manipulations.

Chimeric Vaccine Against Tick-Borne

Encephalitis Virus

A Pletenev, R Men, RM Chanock, C–J

Lai (NIAID)

Serial No. 60/061, 441 filed Oct 08, 1997

Licensing Contact: Carol Salata, 301/

496–7735 ext. 232

The present invention relates to a

chimeric virus vaccine against tickborne encephalitis virus (TBEV). The

preM and E structural genes of the tickborne encephalitis Langat virus and the

non-structural genes of the mosquitoborne dengue virus form a live,

attenuated chimeric virus vaccine

against tick-borne encephalitis virus.

The live chimeric vaccine was

administered intraperitoneally and

exhibited complete attenuation in mice

while at the same time providing

protection against subsequent challenge

with the virulent parental Langat virus

which is virulent for mice.

Methods and Apparatuses for

Processing Synthesized Models of

Complex Medical Structures

RM Summers (CC)

Serial No. 60/056, 452 filed Aug 19,

1997

Licensing Contact: John Fahner-Vihtelic,

301/496–7735 ext. 270

The present invention provides a new

algorithm for generating computer

models of complex anatomical

structures from data such as CT. This

algorithm minimizes the problem of

‘‘leakage’’ found in existing algorithms,

which leads to incorrect assignment of

voxels as belonging to the feature of

interest. This improvement greatly

speeds computation time, and

anatomical features modeled with this

algorithm may be displayed in real time,

allowing ‘‘virtual endoscopy.’’ The

method has been demonstrated in

clinical ‘‘virtual bronchoscopy.’’ A

method for computer-assisted detection

of lesions within body cavities is also

disclosed.

Simultaneous Multicolor Visualization

of Chromogenic Dyes Using Brightfield

Microscopy and Spectral Imaging

T Ried, M MacVille (NHGRI)

Serial No. 60/055,439 filed Aug 8, 1997

Licensing Contact: John Fahner-Vihtelic,

301/496–7735 ext. 270

The present application describes a

method and apparatus for spectral

imaging. This invention enables one to

distinguish permanent chromogenic

dyes attached to DNA probes and

hybridized to interphase cells from

cytological preparations. This

technology has application in areas such

as analysis of Pap smears or cells from

fine needle aspirations. Color

identification is based on the

measurement of the entire absorption

spectrum of chromogenic dyes by means

of spectral imaging, which allows for

the unambiguous identification of

otherwise not discernable dyes. This

approach also allows for multiparameter analysis of

immunocytochemical markers and RNA

in situ hybridization. The diagnosis,

staging, and prognosis of human cancers

could be greatly improved by

complementing morphology with

genetic markers for tumor progression

using this method.

Methods For Treating Parasitic

Infection Using Thiopeptides

MJ Rogers, TF McCutchan, GA

McConkey, A Fairfield (NIAID) DHHS

Reference No. E–202–97/0; PCT/

US97/11939 filed July 7, 1997.

Licensing Contact: Carol Salata, 301/

496–7735 ext. 232

This invention provides a method for

treating a parasitic infection (when the

parasite has a plastid-like organelle)

with a thiopeptide. The parasitic

infection may be caused by parasites of

the Apicomplexa phylum, the

Microspora phylum or the Ascetospora

phylum. The thiopeptide used to treat

the parasitic infection can be any

member of the class of compounds

characterized as sulfur-rich peptide

antibiotics with multiple thiazole rings

which inhibit protein synthesis in the

plastid-like organelle of the parasites.
Federal Register / Vol. 63, No. 94 / Friday, May 15, 1998 / Notices 27097

The disclosed thiopeptides can be, but

are not limited to, thiostrepin,

micrococcin P. nosiheptide, siomycin,

sporangiomycin, althiomycin, the

thiocillins and/or thiopeptin, as well as

sulfur-rich peptide antibiotic containing

multiple thiazole rings, produced by

streptomycetes or other peptide

antibiotic-producing organisms.

Image Registration Using Closest

Corresponding Voxels With an Iterative

Registration Process

J Ostuni (LDRR)

Serial No. 08/847,733 filed Apr 28, 1997

(claiming priority date of Apr 29,

1996)

Licensing Contract: John FahnerVihtelic, 301/496-7735 ext. 270

The present invention provides a

novel method of 3D medical image

registration, that is, the alignment of two

or more related 3D images. This method

overcomes problems seen in

conventional registration techniques

arising from mismatching of voxel

intensities. This is of particular

importance when registering images

derived from different techniques, such

as MRI and CT. The invention allows

the registration of images despite the

lack of direct relationship between

intensity levels in the different

techniques, varying patient placement,

and occlusion and noise in the image.

System for Synergistic Combination of

Multiple Automatic Induction Methods

and Automatic Re-Representation of

Data

L Hunter (NLM)

DH Reference No. E–118–96/0; PCT/

US97/08951 filed May 23 1996

Licensing Contact: John Fahner-Vihtelic,

301/496-–7735 ext. 270

The present application describes a

unique prototype of an advanced

framework which relates to the field of

multidimensional data mining, machine

learning, and analysis that has been

named COEV (for COEVolutional).

COEV synergistically combines different

methods of statistical analysis, neural

networks, decision trees and genetic

algorithms for the resolution of data

queries. COEV automatically determines

the optimal methods and data

representations to apply at each step of

inquiry and, as a result, can provide

outcomes that are significantly more

accurate than can be achieved by use of

any one methodology alone. The

invention uses an evolutionary learning

technology to improve predictive

outcomes with continued use. COEV is

designed to advance the accuracy,

flexibility, speed and ease of use of

advanced data analysis technologies.

Characteristics of problems that are

appropriate for the application of the

COEV method are: (1) Appropriate for

machine learning, in that there is a welldefined set of input variables and a clear

prediction target; (2) difficult for

traditional methods, and where a

modest improvement in accuracy over

existing machine learning methods (e.g.,

neural networks) would be significant;

(3) there is a large amount of training

data, ideally thousands of cases.

Possible application areas of interest

include the analysis of high-throughput

screening data for pharmaceutical

discovery, detecting patterns of fraud in

insurance claims, or automating

screening of medical images.

This invention requires further R&D

and testing to make it a practical system

for widespread use.

Dated: May 7, 1998.

Jack Spiegel,

Director, Division of Technology Development

and Transfer, Office of Technology Transfer.

[FR Doc. 98–13011 Filed 5–14–98; 8:45 am]

BILLING CODE 4140–01–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

National Institute on Aging; Closed

Meetings

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

meetings:

Name of SEP: National Institute on Aging

Special Emphasis Panel Stress, Aging and

Wound Healing.

Date of Meeting: May 27, 1998.

Time of Meeting: 12:00 p.m. to

adjournment.

Place of Meeting: Holiday Inn on the Lane,

Columbus, Ohio.

Purpose/Agenda: To review a program

project application.

Contact Person: Dr. Mary Nekola, Scientific

Review Administrator, Gateway Building,

Room 2C212, National Institutes of Health,

Bethesda, Maryland 20892–9205, (301) 496–

9666.

Name of SEP: National Institute on Aging

Special Emphasis Panel QTL, Analysis of

Age-Related Phenotypes.

Date of Meeting: May 29, 1998.

Time of Meeting: 11:00 a.m. to

adjournment.

Place of Meeting: Chicago O’Hare Marriott,

Chicago, Illinois.

Purpose/Agenda: To review a program

project application.

Contact Person: Dr. James Harwood,

Scientific Review Administrator, Gateway

Building, Room 2C212, National Institutes of

Health, Bethesda, Maryland 20892–9205,

(301) 496–9666.

Name of Committee: National Institute on

Aging, Initial Review Group Biology, Aging

Review Committee.

Dates of Meeting: June 1–2, 1998.

Times of Meeting: June 1–7:30 p.m. to

recess, June 2–8:00 a.m. to adjournment.

Place of Meeting: Chevy Chase Holiday

Inn, 5520 Wisconsin Avenue, Chevy chase,

Maryland 20815.

Purpose/Agenda: To review a program

project application.

Contact Person: Dr. James Harwood,

Scientific Review Administrator, Gateway

Building, Room 2C212, National Institutes of

Health, Bethesda, Maryland 20892–9205,

(301) 496–9666.

Name of Committee: National Institute on

Aging Initial Review Group, Clinical Aging

Review Committee.

Date of Meeting: June 2, 1998.

Time of Meeting: 8:00 a.m. to adjournment.

Place of Meeting: Holiday Inn Bethesda,

8120 Wisconsin Avenue, Bethesda, Maryland

20815.

Purpose/Agenda: to perform the various

grant applications.

Contact Person: Dr. William Kachadorian,

Scientific Review Administrator, Gateway

Building, Room 2C212, National Institutes of

Health Bethesda, Maryland 20892–9205,

(301) 496–9666.

Name of Committee: National Institute on

Aging Initial Review Group, Neurosciences of

Aging Review Committee.

Date of Meeting: June 8–10, 1998.

Times of Meeting: June 8–7:00 p.m. to

recess, June 9–8:00 a.m. to recess, June 10–

8:00 a.m. to adjournment.

Place of Meeting: Chevy Chase Holiday

Inn, 5520 Wisconsin Avenue, Chevy Chase,

Maryland 20815.

Purpose/Agenda: To review grant

applications.

Contact Person: Dr. Louise Hsu, Scientific

Review Administrator, Gateway Building,

Room 2C212, National Institutes of Health,

Bethesda, Maryland 20892–9205, (301) 496–

9666.

Name of SEP: National Institute on Aging

Special Emphasis Panel Alzheimers Disease

Patient Registry.

Date of Meeting: June 10, 1998.

Time of Meeting: 4:00 p.m. to adjournment.

Place of Meeting: Chevy Chase Holiday

Inn, 5520 Wisconsin Avenue, Chevy Chase,

Maryland 20815.

Purpose/Agenda: To review research

project.

Contact Person: Dr. Louise Hsu, Scientific

Review Administrator, Gateway Building,

Room 2C212, National Institutes of Health,

Bethesda, Maryland 20892–9205, (301) 496–

9666.

Name of SEP: National Institute on Aging

Special emphasis Panel Group A.

Date of Meeting: June 10, 1998.

Time of Meeting: 8:00 a.m. to 12:00 noon.

Place of Meeting: Chevy Chase Holiday

Inn, 5520 Wisconsin Avenue, Chevy Chase,

Maryland 20815.

Purpose/Agenda: To pilot study review a

grant application mostly concerning

molecular biology, Alzheimer’s disease,

biochemistry and neurology of aging.

Contact Person: Dr. Arthur Schaerdel,

Scientific Review Administrator, Gateway