[Federal Register Volume 65, Number 174 (Thursday, September 7, 2000)]
[Notices]
[Pages 54287-54289]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-22883]


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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.

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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

[[Page 54288]]

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 Uri Reichman, Ph.D., at 
the Office of Technology Transfer, National Institutes of Health, 6011 
Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; 
telephone: 301/496-7736 ext. 240; fax: 301/402-0220; e-mail: 
[email protected]. A signed Confidential Disclosure Agreement will be 
required to receive copies of the patent applications.

Use of Recombinant Parainfluenza Viruses (PIVs) as Vectors To 
Protect Against Infection and Disease Caused by PIV and Other Human 
Pathogens

B. Murphy, P. Collins, A. Durbin, M. Skiadopoulos and T. Tao (NIAID)
DHHS Reference No. E-099-99/0 filed 10 Dec 1999

    The invention relates to the design and creation of recombinant 
chimeric parainfluenza viruses, novel vaccine candidates against PIV 
and non-PIV pathogens. The chimeric viruses utilize the PIV genome as a 
carrier/vector for heterologous PIV or non-PIV genes that code for the 
protective antigens of the pathogens. For example, the glycoproteins 
genes of PIV1 and PIV2 can be incorporated into PIV3 genome, either 
substituting for or in addition to the vector's glycoprotein genes. The 
latter design can serve as a single vaccine against the three types of 
PIV pathogens. Furthermore, PIV can serve as a carrier for the 
``protective'' genes of non-PIV pathogens such as measles, RSV, mumps, 
herpes, influenza and more. In this design, again, the ``donor'' genes 
can substitute for or be added to the vector's protecting genes. The 
latter design can serve as a single vaccine against plurality of 
pathogens. In particular, the invention describes the potential benefit 
of developing new vaccine candidates against the measles virus.
    The live attenuated measles virus currently in commercial use must 
be administered by intramuscular injection, and cannot be given until 
12 months of age due to neutralization by maternal antibodies present 
in young infants. There is a strong need to develop a vaccine which 
will be effective in the first year of life. A chimeric PIV3-measles 
vaccine described in this invention has shown to confer protection 
against the two pathogens. Initial studies indicate that this vaccine 
candidate will be able to circumvent the difficulties encountered by 
the currently licensed vaccine, i.e., it will be possible to administer 
the vaccine by intranasal route so that it will be effective in the 
presence of maternal antibodies. This vaccine will make it possible, 
for the first time, to immunize young infants against the deadly 
measles virus.

Attenuated Human-Bovine Chimeric Parainfluenza Virus (PIV) Vaccines

M. Skiadopoulos, P. Collins, B. Murphy and A. Schmidt (NIAID)
DHHS Reference No. E-201-00/0 filed 05 Jul 2000

    The invention relates to the engineering and creation of 
recombinant chimeric human-bovine parainfluenza viruses (PIVs) and 
novel vaccine candidates against PIV. The chimera of the invention 
include a partial or complete ``background'' PIV genome or antigenome 
derived from or patterned after a bovine PIV virus, combined with one 
or more heterologous gene(s) or genome segment(s) of a human PIV virus 
to form a human-bovine chimeric PIV genome or antigenome. The inverted 
design is also possible, where the chimeric PIV incorporates a partial 
or complete human PIV ``background'' genome or antigenome, combined 
with one or more heterologous gene(s) or genome segment(s) from bovine 
PIV, whereby the resultant chimeric virus is attenuated by virtue of 
the host-range restriction specified by the bovine genes. In 
particular, the invention describes the creation of chimera where the 
human PIV HN and F ``protective'' genes are incorporated into a bovine 
``background'' genome, and another one where bovine PIV3 P and M open 
reading frames replace that of human in a human PIV3 ``background'' 
genome. The vaccine candidates created by this recombinant technique 
can be further attenuated by incorporating specific point mutations and 
nucleotide modifications into the genome to yield desired phenotypic 
and structural effects.

Respiratory Syncytial Virus Vaccines Expressing Protective Antigens 
From Promoter-Proximal Genes

C. Krempl, P. Collins, B. Murphy, U. Buchholz and S. Whitehead (NIAID)
DHHS Reference No. E-225-00/0 filed 23 Jun 2000

    The invention relates to the engineering and creation of novel 
live-attenuated RSV vaccine candidates. The viruses of this invention 
have been modified by shifting the position of one or more of various 
viral genes relative to the viral promoter. The gene-shifted RSVs are 
constructed by insertion, deletion and rearrangement of genes or genome 
segments within the recombinant genome or antigenome. Shifting the 
position of the gene(s) in this manner provides for a selective 
increase or decrease in expression of the gene(s), depending on the 
nature and degree of the positional shift. Genes of interest for 
manipulation to create gene position-shifted RSV include any of the 
NS1, NS2, N, P, M, SH, M2(ORF1), M2(ORF2), L, F or G genes or genome 
segment.
    One modification of particular interest is to place the G and F 
protective antigen genes in a promoter-proximal position for increased 
expression. The gene position-shifted RSV can be further manipulated by 
the addition of specific nucleotide and amino acid point mutations or 
host range restriction determinants to yield desired phenotypic and 
structural effects. This technique offers the possibility of producing 
a vaccine that is ``better than nature'' by increasing the relative 
expression of particular genes.

Multiple Hybridization System for the Identification of Pathogenic 
Mycobacterium Species and Method of Use

Steven Fischer, Gary Fahle, Patti Conville and Jang Rampall (CC)
DHHS Reference No. E-278-99/0 filed 03 March 2000

    The invention relates to a multiplex system that allows 
simultaneous detection and identification of any one of six different 
species of mycobacteria, M. gordonae, M. intracellulare, M. avium, M. 
tuberculosis, M. marinum, or M. kansasii. The Mycobacterium species 
included in this detection system, collectively, constitute about 90% 
of the patient isolates detected in many clinical mycobacteriology lab 
sections. The system includes primers and amplification reagents that, 
when applied to the clinical specimen can generate detection 
oligonucleotide for the Mycobacterium species, in one step and in a 
single tube. The system also includes a plastic device comprising an 
array of the corresponding capture oligonucleotides of known sequences. 
Upon generating the amplified detection probes, the detection mixture 
is applied to the plastic device for hybridization to take place. 
Following a wash step, the hybridized locations on the array are 
detected by fluorescence or chemiluminescence to determine which of the 
six possible Mycobacterium species are present in the sample. The 
system is simple to operate and permits the identification of these six

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mycobacteria in patient samples in a single day.

Method of Diagnosing Multidrug Resistant Tuberculosis

Clifton E. Barry, III, Andrea E. DeBarber, Khisimuzi Mdluli and Linda-
Gail Bekker (NIAID)
DHHS Reference No. E-093-00/0 filed 26 Jun 2000

    The invention relates to the discovery that a putative gene of 
Mycobacterium tuberculosis (MTb) with no previously identified function 
is responsible for the ability of the bacteria to activate a class of 
second line thioamide drugs used for MTb infections. The gene, termed 
``etaA'', codes for the synthesis of a monooxigenase, the enzyme 
responsible for the oxidative activation of the drugs. Mutation in the 
etaA gene leads to the expression of mutated, inactivated enzyme, thus 
resulting in thioamide drug-resistant bacteria. The significance of 
this discovery is that now, resistance to the class of thioamide drugs 
in clinical isolates can be identified in a relatively short time, 
eliminating the need to perform lengthy culturing procedures. The 
invention claims test methods for determining resistance to thioamide 
drugs by detecting gene mutation. These include (a) amplifying the etaA 
gene or a portion of it containing the mutation, with a set of primers 
which provide amplified product, and sequencing the amplified product 
to compare the sequence with a known sequence of the wild-type etaA. A 
difference in sequence patterns indicate mutation, (b) subjecting the 
amplified gene product to digestion by restriction enzymes and 
comparing the cleaved DNA gel pattern to the one obtained from 
digestion of the wild type etaA gene. A difference indicates mutation 
in etaA, and (c) detecting the mutations by probe hybridization 
techniques, where the amplified product hybridizes to a nucleic acid of 
known sequence under stringent conditions, and the hybridized product 
is detected. In addition to the above, the invention proposes other 
detection methods such as commonly used for SNPs. Other methods claimed 
in the invention are immunoassay (i.e. ELISA) for the etaA gene product 
or mutated versions of it, or immunoassay and chemical analysis of the 
drug metabolites, whereby the absence of the metabolites indicates gene 
mutation and impaired activating ability.

    Dated: August 29, 2000.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 00-22883 Filed 9-6-00; 8:45 am]
BILLING CODE 4140-01-P