National Institutes of Health, Public Health Service, DHHS.
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 Start Printed Page 54288development. Foreign patent applications are filed on selected inventions to extend market coverage for companies and may also be available for licensing.
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: firstname.lastname@example.org. 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 Start Printed Page 54289mycobacteria 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.Start Signature
Dated: August 29, 2000.
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