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###### Department of Health and Human Services

###### National Institutes of Health 

# 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                           ( print 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 μm 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 μm and 15 μm. 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.                           ( print 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                           ( print 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] 

BILLING CODE 4140-01-P