[Federal Register Volume 73, Number 188 (Friday, September 26, 2008)]
[Notices]
[Pages 55855-55858]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-22610]
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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, HHS.
ACTION: Notice.
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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.
Inhibitors of the Plasmodial Surface Anion Channel as Antimalarials
Description of Technology: The inventions described herein are
antimalarial small molecule inhibitors of the plasmodial surface anion
channel (PSAC), an essential nutrient acquisition ion channel expressed
on human
[[Page 55856]]
erythrocytes infected with malaria parasites. These inhibitors were
discovered by high-throughput screening of chemical libraries and
analysis of their ability to kill malaria parasites in culture. Two
separate classes of inhibitors were found to work synergistically in
combination against PSAC and killed malaria cultures at markedly lower
concentrations than separately. These inhibitors have high affinity and
specificity for PSAC and have acceptable cytotoxicity profiles.
Preliminary in vivo testing of these compounds in a mouse malaria model
is currently ongoing.
Applications: Treatment of malarial infections.
Advantages: Novel drug treatment for malarial infections;
Synergistic effect of these compounds on PSAC.
Development Status: In vitro and in vivo data can be provided upon
request.
Market: Treatment of malarial infection.
Inventor: Sanjay A. Desai (NIAID).
Publications:
1. Kang M, Lisk G, Hollingworth S, Baylor SM, Desai SA. Malaria
parasites are rapidly killed by dantrolene derivatives specific for the
plasmodial surface anion channel. Mol. Pharmacol. 2005 Jul;68(1):34-40.
2. Desai SA, Bezrukov SM, Zimmerberg J. A voltage-dependent channel
involved in nutrient uptake by red blood cells infected with the
malaria parasite. Nature. 2000 Aug 31;406(6799):1001-1005.
Patent Status: U.S. Provisional Application No. 61/083,000 filed 23
Jul 2008 (HHS Reference No. E-202-2008/0-US-01).
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: Kevin W. Chang, PhD; 301-435-5018;
[email protected].
Collaborative Research Opportunity: The NIAID Office of Technology
Development is seeking statements of capability or interest from
parties interested in collaborative research to further develop,
evaluate, or commercialize antimalarial drugs that target PSAC or other
parasite-specific transporters. Please contact either Charles Rainwater
or Dana Hsu at 301-496-2644 for more information.
Aerosolized Vaccines
Description of Technology: Vaccine delivery to humans by mucosal
routes may offer some operational and immunological advantages over
intramuscular administration by needle-and-syringe. Potential targets
include the oral, nasal, rectal conjunctival, and vaginal surfaces with
the oral and nasal routes being the most practical to consider for
infants, children and adults of both sexes. Needle-free delivery
methods may improve compliance, reduce discomfort, and improve safety
of vaccines; particularly in the developing world, needle-free delivery
could mitigate the risk of blood-borne pathogen transmission by unsafe
injection practices or inadequately sterilized equipment, and be easier
and safer to deploy by non-medical personnel.
Mucosal vaccination may offer a potential immunological advantage
of recruiting mucosal lymphoid tissues that are important in mediation
of immune responses, particularly at the entry site for infectious
pathogens. Optimally formulated and delivered antigens may elicit a
variety of responses in these tissues including secretory IgA, serum
IgG capable of neutralizing toxins or viruses, and cell-mediated
immunity as measured by cytotoxic T-cell responses and cytokine
production.
In the case of respiratory delivery, specific particle sizes can
target particular microenvironments within the lung. Efficient
penetration of the lung parenchyma depends upon optimizing the size of
the droplet in relation to the diameter of the respiratory airways. It
has been recommended that school age children and adults be immunized
with respiratory particles that are between 3 and 5 [mu]m in diameter,
since a larger particle cannot effectively penetrate deep into the
lung.
This application claims aerosolized immunogenic compositions
comprising aerosolized immunogenic particles between 0.01 [mu]m and 15
[mu]m. The application also claims methods for delivering immunogenic
compositions, methods for generating immune responses, and methods for
treating infections by producing and administering aerosolized
immunogenic compositions. More specifically, the invention claims
replication-defective recombinant adenoviruses encoding human
immunodeficiency virus (HIV), simian immunodeficiency virus (SIV) and
tuberculosis (TB) genes delivered by aerosolization into the lung. The
inventors have shown that this regimen induces very high, stable
cellular immune responses localized to the lung, as well as humoral
responses in the lung, systemically, and, importantly, at distal
mucosal sites. This regimen may prove highly useful for vaccination
against respiratory infections such as TB, influenza, and respiratory
syncytial virus, and provide a platform for generating mucosal antibody
responses against other pathogens.
Applications: Improved immunogenic compositions and vaccine
formulations, delivery of viral vectors, plasmid DNA, proteins, and
adjuvants.
Development Status: Vaccines have been formulated and preclinical
studies have been performed.
Inventors: Mario Roederer and Srinivas Rao (NIAID).
Patent Status: U.S. Provisional Application No. 61/038,534 filed 21
Mar 2008 (HHS Reference No. E-053-2008/0-US-01).
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646;
[email protected].
Use of Saccharides Cross-Reactive With Bacillus anthracis Spore
Glycoprotein as a Vaccine Against Anthrax
Description of Technology: Bacillus anthracis is a spore-forming
bacterium that causes anthrax in humans and in other mammals. The
glycoprotein BclA (Bacillus collagen-like protein of anthracis) is a
major constituent of the exosporium, the outermost surface of B.
anthracis spores. The glycosyl part of BclA is an oligosaccharide
composed of 2-O-methyl-4-(3-hydroxy-3-methylbutanamido)-4,6-dideoxy-d-
glucose, referred to as anthrose, and three rhamnose residues. A
structure similar to anthrose, 4-(3-hydroxy-3-methylbutanamido)-4,6-
dideoxy-d-glucose is found in the side chain of the capsular
polysaccharide (CPS) of Shewanella spp. MR-4. Under certain growth
conditions the bacteria produce a variant CPS lacking one methyl group
on the hydroxybutyrate, 4-(3-hydroxybutanamido)-4,6-dideoxy-d-glucose.
Contrary to anthrose, neither of the Shewanella CPSs is 2-O methylated.
The inventors have found that both Shewanella CPS variants react
with anti-B. anthracis spore sera. The inventors have also found that
these antisera reacted with flagellae of Pseudomonas syringae, reported
to be glycosylated with a similar terminal saccharide, 4-(3-
hydroxybutanamido)-4,6-dideoxy-2-O-methyl-d-glucose. Sera produced by
immunization with Shewanella or P. syringae cells bound to B. anthracis
spores but not to Bacillus cereus spores in a fluorescent microscopy
assay. The inventors' experiments show that methylation of the anthrose
at the O-2 of the sugar ring and at the C-3 of 3-hydroxybutyrate are
not essential for induction of cross-reactive antibodies.
[[Page 55857]]
The application claims the use of Shewanella CPS conjugates as a
component of an anthrax vaccine. The application also claims the use of
capsular polysaccharides from Shewanella and compounds from the
flagella of Pseudomonas syringae for the development of anthrax
vaccines.
Application: Development of anthrax vaccines, diagnostics and
therapeutics.
Development Status: Conjugates have been synthesized and
preclinical studies have been performed.
Inventors: Joanna Kubler-Kielb (NICHD), Rachel Schneerson (NICHD),
Haijing Hu (NIAID), Stephen H. Leppla (NIAID), John B. Robbins (NICHD),
et al.
Publication: Kubler-Kielb J. et al. Saccharides cross-reactive with
Bacillus anthracis spore glycoprotein as an anthrax vaccine component.
Proc Natl Acad Sci USA. 2008 Jun 24;105(25):8709-8712. This publication
reports the preparation, characterization, and antibody responses to
protein conjugates of the two variants of Shewanella CPS.
Significantly, both conjugates induced antibodies that bound to both
Shewanella CPS variants by ELISA and to B. anthracis spores, as
detected by fluorescent microscopy.
Patent Status: U.S. Provisional Application No. 61/066,509 filed 19
Feb 2008 (HHS Reference No. E-032-2008/0-US-01).
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646;
[email protected].
Modified Sugar Substrates and Methods of Use
Description of Technology: Glycans can be classified as linear or
branched sugars. The linear sugars are the glycosaminoglycans
comprising polymers of sulfated disaccharide repeat units that are O-
linked to a core protein, forming a proteoglycan aggregate. The
branched glycans are found as N-linked and O-linked sugars on
glycoproteins or on glycolipids. These carbohydrate moieties of the
linear and branched glycans are synthesized by a super family of
enzymes, the glycosyltransferases (GTs), which transfer a sugar moiety
from a sugar donor to an acceptor molecule. Although GTs catalyze
chemically similar reactions in which a monosaccharide is transferred
from an activated derivative, such as a UDP-sugar, to an acceptor, very
few GTs bear similarity in primary structure.
Eukaryotic cells express several classes of oligosaccharides
attached to proteins or lipids. Animal glycans can be N-linked via
beta-GlcNAc to Asparagine (N-glycans), O-linked via UDP-GalNAc to
Serine/Threonine (O-glycans), or can connect the carboxyl end of a
protein to a phosphatidylinositol unit (GPI-anchors) via a common core
glycan structure. Thus, there is potential to develop carbohydrate
substrates comprising bioactive agents that can be used to produce
glycoconjugates carrying sugar moieties with bioactive agents. Such
glycoconjugates have many therapeutic and diagnostic uses, e.g. in
labeling or targeted delivery. Further, such glycoconjugates can be
used in the assembly of bio-nanoparticles to develop targeted-drug
delivery systems or contrast agents for medical uses.
This application claims methods and compositions for making and
using functionalized sugars. Also claimed in the application are
methods for forming a wide variety of products at a cell or in an in
vitro environment. More specifically, the claimed compositions of the
invention comprise a sugar nucleotide and one or more functional
groups.
Applications: Production of therapeutic or diagnostic
glycoconjugates, assembly of bio-nanoparticles, development of contrast
agents.
Development Status: Enzymes have been synthesized and initial
studies have been performed.
Inventors: Pradman K. Qasba and Maria R. Manzoni (NCI).
Publications:
1. B Ramakrishnan et al. Applications of glycosyltransferases in
the site-specific conjugation of biomolecules and the development of a
targeted drug delivery system and contrast agents for MRI. Expert Opin
Drug Deliv. 2008 Feb;5(2):149-153. Review.
2. PK Qasba et al. Site-specific linking of biomolecules via glycan
residues using glycosyltransferases. Biotechnol Prog. 2008 May-
Jun;24(3):520-526.
Patent Status: U.S. Patent Application No. 61/027,782 filed 11 Feb
2008 (HHS Reference No. E-016-2008/0-US-01).
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646;
[email protected].
Collaborative Research Opportunity: The National Cancer Institute's
Nanobiology Program is seeking statements of capability or interest
from parties interested in collaborative research to further develop,
evaluate, or commercialize the synthesis of UDP derivatives of C2
modified galactose for use as donor substrates for
glycosyltransferases. Please contact John D. Hewes, Ph.D. at 301-435-
3121 or [email protected] for more information.
Immunogenic Peptides Against Influenza Virus
Description of Technology: The invention described herein are
peptides and polypeptides derived from the HA, NA, PB2, PB1, PA, M1,
M2, NP, NS1, and NS2 proteins of influenza virus that elicit
immunogenic responses; particularly neutralizing antibodies, against
human and avian influenza strains H1N1, H3N2, H5N1 and H7N7. Materials
in the form of immunogenic compositions including these peptides and
polypeptides can also be in-licensed along with the patent rights.
Pharmaceutical compositions including these peptides and polypeptides
with or without adjuvants are within the scope of the invention. The
inventors are currently investigating the vaccine potential of specific
peptides and polypeptides.
Applications:
Vaccines against influenza virus infection;
Diagnostics for the detection of influenza virus
infection; and
Generation of influenza virus specific antibodies.
Advantages:
Peptides can be expressed in a number of different
expression systems; and
Peptides were identified based on the specificity of
antibodies derived from human and avian influenza virus infected
individuals.
Development Status: In vitro data can be provided upon request.
Market:
Preventative or treatment for influenza virus infection;
and
Diagnostic for influenza virus infection.
Inventors: Hana Golding and Surender Khurana (FDA).
Publications:
1. Pandemic Influenza preparedness: New molecular tools for
evaluation of influenza vaccines and identification of serological
epitopes for avian influenza diagnostic assays at ``Options for the
Control of Influenza VI'' June 17-23, 2007, Toronto, Canada. (oral
presentation)
2. Pandemic Influenza preparedness: Identification of serological
epitopes for use in development of broadly cross-reactive influenza
vaccines at ``National Foundation for Infectious Diseases--11th Annual
Conference on Vaccine Research'', Baltimore: May 5-7, 2008. (oral
presentation).
3. Analysis of antibody repertoires in H5N1 infected and vaccinated
[[Page 55858]]
individuals using influenza whole genome phage display at
``Immunobiology and Pathogenesis of Influenza Infection'', Atlanta:
June 1-3, 2008. (poster presentation).
Patent Status: International Patent Application PCT/US2008/067001
filed 13 Jun 2008 (HHS Reference No. E-236-2007/3-PCT-01).
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: Kevin W. Chang, Ph.D.; 301-435-5018;
[email protected].
Collaborative Research Opportunity: The FDA, Center for Biologics
Evaluation and Research (CBER), Division of Viral Products, is seeking
statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or commercialize
these peptides as vaccine candidates or diagnostics. Please contact
Alice Welch at [email protected] or 301-827-0359 for more
information.
A Rapid Ultrasensitive Assay for Detecting Prions Based on the Seeded
Polymerization of Recombinant Normal Prion Protein (rPrP-sen)
Description of Technology: Prion diseases are neurodegenerative
diseases of great public concern because humans may be infected from
hoofed animals used as food, food products such as milk, or blood
products. Currently available tests for disease-causing prions are
either incapable of detecting low concentrations of prions and must be
used post-mortem or are incapable of detecting low concentrations of
prions economically or accurately. This technology enables rapid and
economical detection of sub-lethal concentrations of prions by using
recombinant, normal, prion protein (rPrP-sen) as a marker or indicator
of infectious prions in a sample. Specifically, prions (contained in a
sample) seed the polymerization of rPrP-sen, and polymerized rPrP-sen
is detected as an amplified indicator of prions in the sample. This
assay differs from the protein-misfolding cyclic amplification assay
(PMCA) because it enables the effective use of rPrP-sen and does not
require multiple amplification cycles unless a higher degree of
sensitivity is required. It is anticipated that this technology can be
combined with additional prion-detection technologies to further
improve the sensitivity of the assay. In its current embodiment, this
assay has been used to detect prions in brain tissue or cerebral spinal
fluid (CSF) from humans (variant CJD), sheep (scrapie), and hamsters
(scrapie).
Advantages:
Uses a consistent, concentrated source of normal prion
protein (rPrP-sen)
Prions are detectable to low levels after a single
amplification round
May be combined with complimentary detection technologies
to improve sensitivity
Demonstrated to be effective at detecting prions from
different species
May be applicable to blood products
Economical
Applications:
A test for live animals or food products
A human diagnostic for early detection of prion diseases
Monitor for effectiveness of treatments or disease
progression
Inventors: Byron W. Caughey, Ryuichiro Atarashi, Roger A. Moore,
and Suzette A. Priola (NIAID).
Related Publications:
1. R Atarashi et al. Simplified ultrasensitive prion detection by
recombinant PrP conversion with shaking. Nat Methods 2008 Mar;5(3):211-
212.
2. 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:
PCT Application No. PCT/US2008/070656 filed 21 Jul 2008
(HHS Reference No. E-109-2007/1-PCT-01).
U.S. Application No. 12/177,012 filed 21 Jul 2008 (HHS
Reference No. E-109-2007/1-US-02).
Licensing Status: Available for exclusive and non-exclusive
licensing.
Licensing Contact: RC Tang, JD, LLM; 301-435-5031;
[email protected].
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 Rosemary Walsh at 301-451-3528 or
[email protected].
Dated: September 18, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E8-22610 Filed 9-25-08; 8:45 am]
BILLING CODE 4140-01-P