Notice: Government-Owned Inventions; Availability for Licensing

Federal Register: April 22, 2008 (Volume 73, Number 78)    
                  Page 21633-21636

AGENCY: National Institutes of Health, Public Health Service, HHS.

ACTION: Notice.

SUMMARY: The inventions listed below are owned by an agency 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.

Platform for the High Throughput Screening of Single Nucleotide 
Polymorphisms and Small Insertions and Deletions

    Description of Technology: Available for licensing and commercial 
development is an oligoarray-based process for gene-specific single 
nucleotide polymorphism (SNP) genotyping based on comparative 
hybridization. This process can detect, even in heterozygous 
conditions, known and potentially flag unknown variants (point 
mutations, base insertion or deletion) along the complete sequence of a 
given gene while drastically cutting the time and costs compared to 
high-throughput direct sequencing without affecting sensitivity and 
specificity. The accuracy and efficiency of the invention was validated 
based on the BRCA-1 breast and ovarian cancer predisposing gene. This 
process can easily be custom designed to include within the same 
platform a relatively large number of genes relevant to a specific 
clinical condition and it is particularly useful for the screening of 
long genomic region with relatively infrequent but clinically relevant 
variants.
    More specifically, the invention is made reliable by the 
development of two tailored algorithms: the first automatically designs 
the complete data set of gene-specific probes starting from the genomic 
sequence according to the user specification (size of the probes, 
relative position, etc.); and the other is based on an algorithm that 
flags gene variants in the test sample. This allows detecting unknown 
variants in the region in which only the reference hybridizes to the 
probes. These features drastically reduce the amount of sequencing (the 
gold standard for SNP detection) to small regions in which a 
discrepancy between test signal and reference signal is found. 
Moreover, there is no limit, other than the physical area of the slide, 
to the number of probes that can be added to the array and the number 
of genes that can be queried simultaneously. Thus, a repertoire of 
considerable size can be scanned in a single test for each sample with 
sensitivity and specificity comparable to direct sequencing.
    Applications: The immediate clinical applications of this platform 
is a remarkable improvement of genetic testing by increasing the number 
of target genes that can be screened in a short time, at a minimal cost 
using an automated simplified analysis, such as the sequencing-grade 
screening for BRCA-1 variants and the detection of mutations in 
cancerous tissues. The method can be also applied to other human genes 
(coding and non-coding sequences), and other sequences from animals, 
bacterial and viruses.
    Development Status: Method fully developed and validated.
    Inventors: Ena Wang (CC), Alessandro Monaco (CC), Francesco M 
Marincola (CC), et al.
    Patent Status: U.S. Provisional Application No. 61/068,182 filed 05 
Mar 2008 (HHS Reference No. E-082-2008/0-US-01).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Cristina Thalhammer-Reyero, Ph.D., M.B.A.; 301-
435-4507; thalhamc@mail.nih.gov.

Generation of Wild-Type Dengue Viruses for Use in Rhesus Monkey 
Infection Studies

    Description of Technology: Dengue virus is a positive-sense RNA 
virus belonging to the Flavivirus genus of the family Flaviviridae. 
Dengue virus is widely distributed throughout the tropical and 
semitropical regions of the world and is transmitted to humans by 
mosquito vectors. Dengue virus is a leading cause of hospitalization 
and death in children in at least eight tropical Asian countries. There 
are four serotypes of dengue virus (DEN-1, DEN-2, DEN-3, and DEN-4) 
that annually cause an estimated 50-100 million cases of dengue fever 
and 500,000 cases of the more severe form of dengue virus infection 
known as dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). This 
latter disease is seen predominately in children and adults 
experiencing a second dengue virus infection with a serotype different 
than that of their first dengue virus infection and in primary 
infection of infants who still have circulating dengue-specific 
maternal antibody. A vaccine is needed to lessen the disease burden 
caused by dengue virus, but none is licensed.
    Because of the association of more severe disease with secondary 
dengue

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virus infection, a successful vaccine must induce immunity to all four 
serotypes. Immunity is primarily mediated by neutralizing antibody 
directed against the envelope (E) glycoprotein, a virion structural 
protein. Infection with one serotype induces long-lived homotypic 
immunity and a short-lived heterotypic immunity. Therefore, the goal of 
immunization is to induce a long-lived neutralizing antibody response 
against DEN-1, DEN-2, DEN-3, and DEN-4, which can best be achieved 
economically using live attenuated virus vaccines. This is a reasonable 
goal since a live attenuated vaccine has already been developed for the 
related yellow fever virus, another mosquito-borne flavivirus present 
in tropical and semitropical regions of the world.
    The evaluation of live attenuated dengue vaccine candidates in 
rhesus monkeys requires wild type control viruses for each of the four 
dengue serotypes. These control viruses are used for comparison to the 
attenuated strains and post-vaccination challenge to assess vaccine 
efficacy. As such, these viruses need to be well characterized and 
sufficiently pure to ensure that they will replicate to consistent 
levels in rhesus monkeys. Characterization generally includes sequence 
analysis, titration, and evaluation in monkeys. The following viruses 
have been characterized: (1) DEN1 WP (2) DEN1 Puerto Rico/94 (3) DEN2 
NGC prototype (4) DEN2 Tonga/74 (5) DEN3 Sleman/78 and (6) DEN4 
Dominica/81.
    Application: Dengue/flavivirus vaccine studies, dengue/flavivirus 
diagnostics, dengue/flavivirus research tools.
    Development Status: Materials are available for transfer.
    Inventors: Stephen S. Whitehead and Joseph E. Blaney, Jr. (NIAID).
    Publications:
    1. AP Durbin, RA Karron, W Sun, DW Vaughn, MJ Reynolds, JR 
Perreault, B Thumar, R Men, C-J Lai, WR Elkins, RM Chanock, BR Murphy, 
SS Whitehead. A live attenuated dengue virus type 4 vaccine candidate 
with a 30 nucleotide deletion in the 3' untranslated region is highly 
attenuated and immunogenic in humans. Am J Trop Med Hyg. 2001 
Nov;65(5):405-413.
    2. SS Whitehead, B Falgout, KA Hanley, JE Blaney Jr., L Markoff, BR 
Murphy. A live, attenuated dengue virus type 1 vaccine candidate with a 
30-nucleotide deletion in the 3' untranslated region is highly 
attenuated and immunogenic in monkeys. J Virol. 2003 Jan;77(2):1653-
1657.
    3. SS Whitehead, KA Hanley, JE Blaney Jr., LE Gilmore, WR Elkins, 
BR Murphy. Substitution of the structural genes of dengue virus type 4 
with those of type 2 results in chimeric vaccine candidates which are 
attenuated for mosquitoes, mice, and rhesus monkeys. Vaccine 2003 Oct 
1;21(27-30):4307-4316.
    4. JE Blaney Jr., CT Hanson, KA Hanley, BR Murphy, SS Whitehead. 
Vaccine candidates derived from a novel infectious cDNA clone of an 
American genotype dengue virus type 2. BMC Infect Dis. 2004 Oct 4;4:39.
    5. JE Blaney Jr., CT Hanson, CY Firestone, KA Hanley, BR Murphy, SS 
Whitehead. Genetically modified, live attenuated dengue virus type 3 
vaccine candidates. Am J Trop Med Hyg. 2004 Dec;71(6):811-821.
    6. JE Blaney Jr., JM Matro, BR Murphy, SS Whitehead. Recombinant, 
live-attenuated tetravalent dengue virus vaccine formulations induce a 
balanced, broad, and protective neutralizing antibody response against 
each of the four serotypes in rhesus monkeys. J Virol. 2005 
May;79(9):5516-5528.
    7. JE Blaney Jr., NS Sathe, CT Hanson, CY Firestone, BR Murphy, SS 
Whitehead. Vaccine candidates for dengue virus type 1 (DEN1) generated 
by replacement of the structural genes of rDEN4 and rDEN4Delta30 with 
those of DEN1. Virol J. 2007 Feb 28;4:23.
    Patent Status: HHS Reference No. E-042-2008/0--Research Tool. 
Patent protection is not being sought for this technology.
    Licensing Status: Available for nonexclusive biological materials 
licensing only.
    Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; 
soukasp@mail.nih.gov.

A Rapid Ultrasensitive Assay for Detecting Prions in Samples Based on 
the Seeded Polymerization of Recombinant Normal Prion Protein (rPrP-
sen)

    Description of Technology: Prion diseases are infectious 
neurodegenerative diseases of great public concern. Humans may be 
infected by eating infected animals (primarily hoofed animals or 
ungulates). Blood transfusions have also been documented as a cause of 
human cases of prion infection. Prion diseases include: Creutzfeldt-
Jakob disease (CJD) (humans); variant Creutzfeldt-Jakob disease (vCJD) 
(humans); Scrapie (sheep); Bovine Spongiform Encephalopathy (BSE) 
(cattle); and Chronic Wasting Disease (deer, elk and moose). Currently 
available rapid tests for infectious prions, which are routinely used 
to monitor slaughtered animals, are not sensitive enough to detect 
prion infections in samples from live animals or humans and must be 
performed post-mortem. Additionally, these tests cannot be used to 
detect subinfectious concentrations of infectious prions in humans or 
animals. An ultrasensitive assay for infectious prions, the protein-
misfolding cyclic amplification assay (PMCA), is available for testing 
live animals or humans; however, this test is expensive because it is 
difficult to perform, relies on the use of brain homogenates, and can 
take 2-3 weeks to perform.
    This technology enables the rapid detection of extremely low, sub-
lethal, concentrations of prions. This assay, like PMCA, is based on 
the prion-induced polymerization of normal prion protein (PrP-sen). 
However, this assay, unlike PMCA uses recombinant normal prion protein 
(rPrP-sen) rather than normal prion protein derived from brain 
homogenate. The use of rPrP-sen provides major advantages over PMCA. 
rPrP-sen provides a relatively inexpensive, abundant, and concentrated 
source of pure PrP-sen as a substrate for the PMCA prion amplification 
reaction. This permits the detection of PrP-res in 2-3 hours and the 
ultrasensitive detection of PrP-res in 2 to 3 days. Moreover, relative 
to PrP-sen in brain tissue, rPrP-sen is much easier to mutate and 
chemically modify to facilitate detection of prion-induced PMCA 
amplification products in potentially high-throughput formats. In its 
current embodiment, the ultrasensitive assay has been used to 
consistently detect (by western blot) around 50 ag of hamster PrP-Sc 
(0.003 lethal dose) in cerebral spinal fluid and brain tissue within 2 
to 3 days.
    Applications:
    A diagnostic assay for detecting prion diseases early.
    An assay for monitoring the progression of prion disease and the 
effectiveness of treatments.
    A veterinary assay for detecting PrP-res in live animals and 
assessing the extent of prion disease in live herds.
    An assay for the detection of prion in commercial products (e.g., 
biotechnological or agricultural), blood and blood products, 
transplantation tissues, medical devices, and environmental samples.
    Market:
    Currently, there is a need for a rapid, ultrasensitive, veterinary 
test for prion diseases in live animals used for human consumption and 
a need for assessing the extent of prion infection in live herds.

[[Page 21635]]

    Currently, there is a need for a human diagnostic assay to detect 
prion disease early when treatment is most effective and a need for 
monitoring the effectiveness of treatments for prion diseases.
    Currently, there is a need for a rapid, ultrasensitive test for 
prions in commercial products (e.g., biotechnological or agricultural), 
blood and blood products, transplantation tissues, medical devices, and 
environmental samples in which prion contamination might be a concern.
    Inventors: Ryuichiro Atarashi, Roger A. Moore, Suzette A. Priola, 
and Byron W. Caughey (NIAID).
    Related Publication: R Atarashi et al. Ultrasensitive detection of 
scrapie prion protein using seeded conversion of recombinant prion 
protein. Nat Methods 2007 Aug;4(8):645-650.
    Patent Status: U.S. Provisional Application No.60/961,364 filed 20 
Jul 2007 (HHS Reference No. E-109-2007/0-US-01).
    Licensing Status: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: RC Tang, J.D., LL.M.; 301-435-5031; 
tangrc@mail.nih.gov.
    Collaborative Research Opportunity: The NIAID Laboratory of 
Persistent Viral Diseases, TSE/Prion Biochemistry Section, is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
this technology. Please contact Byron Caughey, Ph.D. at (406) 363-9264 
or bcaughey@niaid.nih.gov for more information.

Identification of a Cell-Surface Co-Receptor That Mediates the Uptake 
and Immunostimulatory Activity of ``D'' Type CpG Oligonucleotides

    Description of Technology: Unmethylated CpG motifs are present at 
high frequency in bacterial DNA. They provide a danger signal to the 
mammalian immune system that triggers a protective immune response 
characterized by the production of Th1 and proinflammatory cytokines 
and chemokines. Although the recognition of CpG DNA by B cells and 
plasmacytoid dendritic cells is mediated by TLR 9, these cell types 
differ in their ability to bind and respond to structurally distinct 
classes of CpG oligonucleotides. The inventors' work established that 
CXCL16, a membrane-bound scavenger receptor, influences the uptake, 
subcellular localization, and cytokine profile induced by D 
oligonucleotides.
    Knowing that CXCL16 can be used to selectively internalize ODN 
could be useful for (1) Improving the activity of D type ODN, (2) 
improving recognition (and side effects) of other types of ODNs by 
deleting regions that interact with CXCL16 (3) potentially improving 
the targeting of any drug or biologic to CXCL16 expressing cells, (4) 
targeting antisense ODNs to immune cells or preventing side effects 
from antisense therapy, and also applications to (5) DNA vaccines and 
other agents that require targeting to CXCL16 expressing cells such as 
dendritic cells and monocytes.
    This application claims methods of inducing an immune response that 
include administering agents that increase the activity and/or 
expression of CXCL16 and a D ODN. The application also claims methods 
of decreasing an immune response to a CpG ODN, including administering 
agents that decrease the activity and/or expression of CXCL16. 
Compositions including one or more D type ODNs and an agent that 
modulates the activity and/or expression of CXCL16 are also claimed.
    Application: Vaccine adjuvants, production of vaccines, 
immunotherapeutics.
    Developmental Status: Preclinical studies have been performed; 
oligonucleotides have been synthesized.
    Inventors: Dennis Klinman (FDA/CBER; NCI), Ihsan Gursel (FDA/CBER), 
Mayda Gursel (FDA/CBER).
    Publication: M Gursel et al. CXCL16 influences the nature and 
specificity of CpG-induced immune activation. J Immunol. 2006 Aug 
1;177(3):1575-1580.
    Patent Status: U.S. Provisional Application No. 60/713,547 filed 31 
Aug 2005 (HHS Reference No. E-036-2005/0-US-01); PCT Application No. 
PCT/US2006/033774 filed 28 Aug 2006 (HHS Reference Number E-036-2005/0-
PCT-02); U.S. Patent Application No. 12/065,085 filed 27 Feb 2008 (HHS 
Reference Number E-036-2005/0-US-03).
    Licensing Status: Available for exclusive or nonexclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; 
soukasp@mail.nih.gov.
    Collaborative Research Opportunity: The National Cancer Institute, 
Laboratory of Experimental Immunology, Immune Modulation Group, is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or 
hewesj@mail.nih.gov for more information.

Use of Suppressive Oligonucleotides To Treat Uveitis

    Description of Technology: Uveitis is a major cause of visual loss 
in industrialized nations. Uveitis refers to an intraocular 
inflammation of the uveal tract, namely, the iris, choroids, and 
ciliary body. Uveitis is responsible for about ten percent (10%) of the 
legal blindness in the United States. Complications associated with 
uveitis include posterior synechia, cataracts, glaucoma and retinal 
edema.
    Suppressive CpG oligodeoxynucleotides (ODNs) are ODNs capable of 
reducing an immune response, such as inflammation. Suppressive ODNs are 
DNA molecules of at least eight nucleotides in length, where the ODN 
forms a G-tetrad, and has a circular dichroism value greater than 2.9. 
In a suppressive ODN, the number of guanosines is at least two.
    This application claims compositions and methods for the treatment 
of uveitis. Specifically, the application claims use of suppressive CpG 
ODNs to treat uveitis. The compositions and methods of the application 
can be used for the treatment of anterior, posterior and diffuse 
uveitis.
    Application: Vaccine adjuvants, production of vaccines, 
immunotherapeutics.
    Developmental Status: Preclinical studies have been performed; 
oligonucleotides have been synthesized.
    Inventors: Dennis Klinman (FDA/CBER; NCI), Igal Gery (NEI), Chiaki 
Fujimoto (NEI).
    Patent Status: U.S. Provisional Application No. 60/569,276 filed 06 
May 2004 (HHS Reference No. E-152-2004/0-US-01); PCT Application No. 
PCT/US2005/015761 filed 05 May 2005, which published as WO 2005/11539 
on 09 Dec 2006 (HHS Reference No. E-152-2004/0-PCT-02); U.S. Patent 
Application No. 11/579,518 filed 03 Nov 2006 (HHS Reference Number E-
152-2004/0-US-03); International filings in Australia, Canada, China, 
Europe, India, Japan, Mexico.
    Licensing Status: Available for exclusive or nonexclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; 
soukasp@mail.nih.gov.
    Collaborative Research Opportunity: The National Cancer Institute, 
Laboratory of Experimental Immunology, Immune Modulation Group, is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
this technology. Please contact John D. Hewes, Ph.D. at 301-

[[Page 21636]]

435-3121 or hewesj@mail.nih.gov for more information.

Mapping Internal and Bulk Motion of an Object With Phase Labeling in 
Magnetic Resonance Imaging

    Description of Technology: Current MRI methods for tracking the 
motion of an object over a relatively long period of time requires the 
use of precisely defined grid points that may be inexact because of 
limited image resolution or the size of the element being tracked. 
Phase contrast velocity mapping generally provides high spatial 
resolution and simple data processing. However, it is generally 
unsuitable for motion tracking and prone to error. This invention is a 
cutting edge Magnetic Resonance Imaging (MRI) technique that provides a 
method for mapping the internal and bulk motion of a specimen by 
labeling the phase of the specimen magnetization with a selected 
spatial function and measuring changes in the phase of the 
magnetization. The special function is selectable to provide 
magnetization phase modulation corresponding to displacements in a 
selected direction such as Cartesian or radial or azimuthal direction. 
This method and associated apparatus is capable of producing images 
based on magnetization phase modulation using data from stimulated 
echoes and anti-echoes. This invention has important applications in, 
among other areas, cardiac functional imaging and can be used to 
compute accurate strain maps of the heart.
    Inventors: Anthony H. Aletras and Han Wen (NHLBI).
    Patent Status: U.S. Patent No. 7,233,818 issued 19 Jun 2007 (HHS 
Reference No. E-234-1999/3-US-06); U.S. Patent Application No. 11/
800,398 filed 03 May 2007 (HHS Reference No. E-234-1999/3-US-08).
    Licensing Status: Available for non-exclusive licensing.
    Licensing Contact: Susan Ano, Ph.D.; 301-435-5515; 
anos@mail.nih.gov.

    Dated: April 14, 2008.
David Sadowski,
Deputy Director, Division of Technology Development and Transfer, 
Office of Technology Transfer, National Institutes of Health.
 [FR Doc. E8-8620 Filed 4-21-08; 8:45 am]

BILLING CODE 4140-01-P