Notice (B): Government-Owned Inventions; Availability for Licensing

Federal Register: September 26, 2008 (Volume 73, Number 188)           
                  Page 55855-55858

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.

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; 
changke@mail.nih.gov.
    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; 
soukasp@mail.nih.gov.

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; 
soukasp@mail.nih.gov.

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; 
soukasp@mail.nih.gov.
    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 hewesj@mail.nih.gov 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; 
changke@mail.nih.gov.
    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 alice.welch@fda.hhs.gov 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; 
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 Rosemary Walsh at 301-451-3528 or 
rcwalsh@niaid.nih.gov.

    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]

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