[Federal Register Volume 79, Number 236 (Tuesday, December 9, 2014)]
[Notices]
[Pages 73087-73090]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-28748]


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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, 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. 209 and 37 CFR part 404 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.

FOR FURTHER INFORMATION CONTACT: 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.

SUPPLEMENTARY INFORMATION: Technology descriptions follow.

Vaccine for Protection Against Shigella sonnei Disease

    Description of Technology: Shigellosis is a global human health 
problem. Transmission usually occurs by contaminated food and water or 
through person-to-person contact. The bacterium is highly infectious by 
the oral route, and ingestion of as few as 10 organisms can cause an 
infection in volunteers. An estimated 200 million people worldwide 
suffer from shigellosis, with more than 650,000 associated deaths 
annually. A recent CDC estimate indicates the occurrence of over 
440,000 annual shigellosis cases in the United States alone, 
approximately eighty percent (80%) of which are caused by Shigella 
sonnei. Shigella sonnei is more active in developed countries. Shigella 
infections are typically treated with a course of antibiotics. However, 
due to the emergence of multidrug resistant Shigella strains, a safe 
and effective vaccine is highly desirable. No vaccines against Shigella 
infection currently exist. Immunity to Shigellae is mediated largely by 
immune responses directed against the serotype specific O-
polysaccharide. Claimed in the invention are compositions and methods 
for inducing an immunoprotective response against S. sonnei. 
Specifically, an attenuated bacteria capable of expressing an S. sonnei 
antigen comprised of the S. sonnei form I O-polysaccharide expressed 
from the S. sonnei rfb/rfc gene cluster is claimed. The inventors have 
shown that the claimed vaccine compositions showed one hundred percent 
(100%) protection against parenteral challenge with virulent S. sonnei 
in mice.
    Potential Commercial Applications:
     Shigella/Typhoid vaccine for travelers, military
     Shigella/Typhoid vaccine for developing countries
     Shigella/Typhoid diagnostics
    Competitive Advantages:
     Low cost of production
     Temperature stable formulation
     Safety/efficacy of Ty21a established in humans
    Development Stage: In vivo data available (animal)
    Inventors: Dennis J. Kopecko (FDA), De Qi Xu (NIDCR), John O. Cisar 
(NICHD)
    Publication: Kopecko DJ, et al. Molecular cloning and 
characterization of genes for Shigella sonnei form I O polysaccharide: 
proposed biosynthetic pathway and stable expression in a live 
salmonella vaccine vector. Infect Immun. 2002 Aug;70(8):4414-23. [PMID: 
12117952]

[[Page 73088]]

    Intellectual Property: HHS Reference No. E-210-2001/0 -
     US Patent No. 7,541,043 issued 02 Jun 2009
     US Patent No. 8,071,084 issued 06 Dec 2011
     US Patent No. 8,337,832 issued 25 Dec 2012
     US Patent Application No. 13/686,299 filed 27 Nov 2012
    Licensing Contact: Peter A. Soukas; 301-435-4646; soukasp@mail/
nih.gov

Live Oral Shigella dysenteriae Vaccine

    Description of Technology: This application claims a Salmonella 
typhi Ty21a construct comprising a Shigella dysenteriae O-specific 
polysaccharide (O-Ps) inserted into the Salmonella typhi Ty21a 
chromosome, where heterologous Shigella dysenteriae serotype 1 O-
antigen is stably expressed together with homologous Salmonella typhi 
O-antigen. The constructs of this invention elicit immune protection 
against virulent Shigella dysenteriae challenge, as well as Salmonella 
typhi challenge. Also claimed in this application are methods of making 
the constructs of this invention and methods for inducing an immune 
response.
    Shigella cause millions of cases of dysentery every year, which 
result in about seven hundred thousand deaths worldwide. Shigella 
dysenteriae serotype 1, one of about forty serotypes of Shigella, 
causes a more severe disease with a much higher mortality rate than 
other serotypes. There are no licensed vaccines available for 
protection against Shigella. The fact that many isolates exhibit 
multiple antibiotic resistance complicates the management of dysentery 
infections.
    Potential Commercial Applications:
     One component of a multivalent anti-shigellosis vaccine 
under development.
     Shigella vaccines, therapeutics and diagnostics.
    Competitive Advantages:
     Vector is well-characterized.
     Simple manufacturing process.
     Potential low-cost vaccine.
     Oral vaccine--avoids need for needles.
     Temperature-stable formulation allows for vaccine 
distribution without refrigeration.
    Development Stage:
     In vitro data available
     In vivo data available (animal)
    Inventors: Dennis J. Kopecko and De Qi Xu (FDA/CBER)
    Publication: Xu DQ, et al. Core-linked LPS expression of Shigella 
dysenteriae serotype 1 O-antigen in live Salmonella typhi vaccine 
vector Ty21a: Preclinical evidence of immunogenicity and protection. 
Vaccine. 2007 Aug 14;25(33):6167-75. [PMID 17629369]
    Intellectual Property: HHS Reference No. E-214-2004/0 -
     US Patent No. 8,071,113 issued 06 Dec 2011
     US Patent No. 8,337,831 issued 25 Dec 2012
     US Patent No. 8,790,635 issued 29 Jul 2014
     US Patent Application No. 14/145,104 filed 31 Dec 2013 
(allowed)
     Various international patent applications pending
    Licensing Contact: Peter A. Soukas; 301-435-4646; 
nih.gov">soukasp@mail.nih.gov

Oral Shigellosis Vaccine

    Description of Technology: This application claims a Salmonella 
typhi Ty21a construct comprising a Shigella sonnei O-antigen 
biosynthetic gene region inserted into the Salmonella typhi Ty21a 
chromosome, where heterologous Shigella sonnei form 1 O-antigen is 
stably expressed together with homologous Salmonella typhi O-antigen. 
The constructs of this invention elicit immune protection against 
virulent Shigella sonnei challenge, as well as Salmonella Typhi 
challenge. Also claimed in this application are methods of 
recombineering a large antigenic gene region into a bacterial 
chromosome.
    Bacillary dysentery and enteric fevers continue to be important 
causes of morbidity in both developed and developing nations. Shigella 
cause greater than one hundred and fifty million cases of dysentery and 
enteric fever occurs in greater than twenty-seven million people 
annually. Currently, there is no licensed vaccine to prevent the 
occurrence of shigellosis. Increasing multiple resistance in Shigella 
commonly thwarts local therapies.
    Potential Commercial Applications:
     One component of a multivalent Shigellosis vaccine under 
development
     Research tool
    Competitive Advantages:
     Low cost production
     Lower cost vaccine
     Oral vaccine--no needles required
     Temperature-stable manufacturing process--avoids need for 
refrigeration during vaccine distribution
    Development Stage:
     In vitro data available
     In vivo data available (animal)
    Inventors: Dennis J. Kopecko and Madushini N. Dharmasena (FDA/CBER)
    Publication: Dharmasena MN, et al. Stable expression of Shigella 
sonnei form I O-polysaccharide genes recombineered into the chromosome 
of live Salmonella oral vaccine vector Ty21a. Int J Med Microbiol. 2013 
Apr;303(3):105-13. [PMID 23474241]
    Intellectual Property: HHS Reference No. E-168-2012/0 -
     US Provisional Application No. 61/701,939 filed 17 Sep 
2012
     PCT Application No. PCT/US2013/059980 filed 16 Sep 2013, 
which published as WO 2014/043637 on 20 Mar 2014
    Licensing Contact: Peter A. Soukas; 301-435-4646; 
nih.gov">soukasp@mail.nih.gov

Acid-Resistant, Attenuated Microbial Vector for Improved Oral Delivery 
of Multiple Targeted Antigens

    Description of Technology: Ty21a, the licensed oral live, 
attenuated bacterial vaccine for Salmonella typhi (the causative agent 
of typhoid fever), has been engineered to stably express a variety of 
target LPS (lipopolysaccharides) and protein antigens to protect 
against shigellosis, anthrax, and plague. Ty21a induces mucosal, 
humoral, and cellular immunity and can be utilized as a multivalent 
vaccine vector that is inexpensive to produce. Salmonella species 
encode inducible acid tolerance, but this genus does not survive well 
below pH 4. Shigella and enterohemorrhagic E. coli isolates have more 
effective acid resistance systems than Salmonella and can survive an 
extreme acid challenge of pH 1-2 (the acidity of the human stomach when 
full).
    This application claims an engineered Ty21a vector that can survive 
a very low pH for two to three hours (i.e., normal transit time through 
a full stomach), allowing for a final delivery format for Ty21a as a 
rapidly dissolvable wafer, instead of the large bullet-size enteric-
coated capsule, which small children cannot swallow. This formulation 
enhances the ability of the immunogenic composition and/or vaccine to 
stimulate immune responses sublingually and throughout the intestinal 
tract.
    Potential Commercial Applications:
     Shigella vaccines
     Biodefense vaccines
     Diagnostics
    Competitive Advantages:
     Ease of manufacture
     Inexpensive to manufacture
     Ease of administration
     Known live attenuated bacterial vector
    Development Stage:
     In vitro data available
     In vivo data available (animal)
    Inventors: Madushini N. Dharmasena and Dennis J. Kopecko (FDA/CBER)

[[Page 73089]]

    Intellectual Property: HHS Reference No. E-535-2013/0 -
     US Provisional Application No. 61/862,815 filed 06 Aug 
2013
     PCT Application No. PCT/US2014/049933 filed 06 Aug 2014
    Licensing Contact: Peter A. Soukas; 301-435-4646; 
nih.gov">soukasp@mail.nih.gov

Attenuated Salmonella as a Delivery System for siRNA-Based Tumor 
Therapy

    Description of Technology: This technology comprises live, 
attenuated Salmonella strains as a delivery system for small 
interfering double-stranded RNA (siRNA)-based tumor therapy. The 
inventors' data provide the first convincing evidence that Salmonella 
can be used for delivering plasmid-based siRNAs into tumors growing in 
vivo. Claimed in the related patent application are methods of 
inhibiting the growth or reducing the volume of solid cancer tumors 
using the si-RNA constructs directed against genes that promote tumor 
survival and cancer cell growth. The Stat3-siRNAs carried by an 
attenuated S. typhimurium described in the application exhibit tumor 
suppressive effects not only on the growth of the primary tumor but 
also on the development of metastases, suggesting that an appropriate 
attenuated S. typhimurium combined with the RNA interference (RNAi) 
approach may offer a clinically feasible method for cancer therapy.
    Potential Commercial Applications:
     Development of live attenuated bacterial cancer vaccines, 
cancer therapeutics and diagnostics.
     Developing/developed world vaccine.
    Competitive Advantages:
     Low cost of production
     Vaccine vector safety/efficacy in humans established
    Development Status: In vivo data available (animal)
    Inventors: Dennis J. Kopecko (FDA), De Qi Xu (FDA), Ling Zhang 
(Jilin University), Xuejian Zhao (Jilin University), Jiadi Hu 
(University of Maryland)
    Publications:
    1. Zhang L, et al. Intratumoral delivery and suppression of 
prostate tumor growth by attenuated Salmonella enterica serovar 
typhimurium carrying plasmid-based small interfering RNAs. Cancer Res. 
2007 Jun 15;67(12):5859-64. [PMID 17575154]
    2. Zhang L, et al. Effects of plasmid-based Stat3-specific short 
hairpin RNA and GRIM-19 on PC-3M tumor cell growth. Clin Cancer Res. 
2008 Jan 15;14(2):559-68. [PMID 18223232]
    Intellectual Property: HHS Reference No. E-278-2007/0 -
     PCT Application No. PCT/US2007/074272 filed 27 Jul 2007, 
which published as WO 2008/091375 on 31 Jul 2008
     U.S. Patent Application No. 12/374,916 filed 23 Jan 2009
     International Application No. 200610017045.5 filed in 
China 27 Jul 2006
    Licensing Contact: Peter A. Soukas; 301-435-4616; 
nih.gov">soukasp@mail.nih.gov

DNA Promoters and Anthrax Vaccines

    Description of Technology: Currently, the only licensed vaccine 
against anthrax in the United States is AVA BioThrax[supreg], which, 
although efficacious, suffers from several limitations. This vaccine 
requires six injectable doses over 18 months to stimulate protective 
immunity, requires a cold chain for storage, and in many cases has been 
associated with adverse effects.
    This application claims a modified B. anthracis protective antigen 
(PA) gene for optimal expression and stability, linked it to an 
inducible promoter for maximal expression in the host, and fused to the 
secretion signal of the Escherichia coli alpha-hemolysin protein (HlyA) 
on a low-copy-number plasmid. This plasmid was introduced into the 
licensed typhoid vaccine strain, Salmonella enterica serovar Typhi 
strain Ty21a, and was found to be genetically stable. Immunization of 
mice with three vaccine doses elicited a strong PA-specific serum 
immunoglobulin G response with a geometric mean titer of 30,000 (range, 
5,800 to 157,000) and lethal-toxin-neutralizing titers greater than 
16,000. Vaccinated mice demonstrated 100% protection against a lethal 
intranasal challenge with aerosolized spores of B. anthracis 7702.
    Potential Commercial Applications: Anthrax vaccines, therapeutics 
and diagnostics.
    Competitive Advantages:
     Vector is well-characterized.
     Simple manufacturing process.
     Potential low-cost vaccine.
     Oral vaccine--avoids needles and can be administered 
rapidly during emergencies.
     Temperature-stable manufacturing allows for vaccine 
distribution without refrigeration.
    Development Stage:
     In vitro data available
     In vivo data available (animal)
    Inventors: Dennis J. Kopecko, Siba Bhattacharyya, Milan Blake (all 
of FDA/CBER)
    Publication: Osorio M, et al. Anthrax protective antigen delivered 
by Salmonella enterica serovar Typhi Ty21a protects mice from a lethal 
anthrax spore challenge. Infect Immun. 2009 Apr;77(4):1475-82. [PMID 
19179420]
    Intellectual Property: HHS Reference No. E-344-2003/1 -
     U.S. Patent No. 7,758,855 issued 20 Jul 2010
     U.S. Patent No. 8,247,225 issued 21 Aug 2012
     U.S. Patent No. 8,709,813 issued 29 Apr 2014
     U.S. Patent Application No. 14/185,353 filed 20 Feb 2014
     Various international patents issued
    Licensing Contact: Peter A. Soukas; 301-435-4646; 
nih.gov">soukasp@mail.nih.gov

Typhoid-Plague Bivalent Vaccine

    Description of Technology: Yersinia pestis (Y. pestis) bacteria is 
the causative agent of plague, typically transmitted from animals to 
humans by the bite of an infected flea. Y. pestis infection of the 
lungs leads to pneumonic plague, which is highly contagious and 
generally fatal. Y. pestis is a potential bioterrorist threat agent for 
which no vaccine yet exists.
    This invention claims the generation and development of a candidate 
oral vaccine against plague. The vaccine consists of a synthetic gene 
construct that expresses a Y. pestis F1-V fusion antigen linked to a 
secretion signal, resulting in the production of large amounts of the 
F1-V antigen. The F1-V synthetic gene fusion is housed within Ty21a, an 
attenuated typhoid fever strain that is licensed for human use as a 
live oral bacterial vaccine. Ty21a serves as a carrier to deliver the 
F1-V fusion antigens of the plague bacteria; the combined F1-V fusion 
in the Ty21a carrier has been shown to stimulate a robust immune 
response in mice. The possibility of combining the oral plague vaccine 
of this invention with FDA's candidate oral anthrax vaccine exists and 
would result in an easy-to-administer oral delivery system to 
streamline administration of the vaccine to large numbers of recipients 
in emergency situations.
    Potential Commercial Applications: Plague vaccines, therapeutics 
and diagnostics.
    Competitive Advantages:
     Vector is well-characterized.
     Simple manufacturing process.
     Potential low-cost vaccine.
    Development Stage:
     In vitro data available
     In vivo data available (animal)
    Inventors: Dennis J. Kopecko, Manuel A. Osorio, Monica R. Foote 
(all of FDA/CBER)
    Intellectual Property: HHS Reference No. E-105-2011/0 -
     U.S. Provisional Application No. 61/650,676 filed 23 May 
2012

[[Page 73090]]

     PCT Application No. PCT/US2013/042240 filed 22 May 2013, 
which published as WO 2013/177291 on 28 Nov 2013
    Related Technologies: HHS Reference No. E-344-2003/1-
     U.S. Patent No. 7,758,855 issued 20 Jul 2010
     U.S. Patent No. 8,247,225 issued 21 Aug 2012
     U.S. Patent No. 8,709,813 issued 29 Apr 2014
     U.S. Patent Application No. 14/185,353 filed 20 Feb 2014
     Various international patents issued
    Licensing Contact: Peter A. Soukas; 301-435-4616; 
nih.gov">soukasp@mail.nih.gov

    Dated: December 3, 2014.
Richard U. Rodriguez,
Acting Director, Office of Technology Transfer, National Institutes of 
Health.
[FR Doc. 2014-28748 Filed 12-8-14; 8:45 am]
BILLING CODE 4140-01-P