[Federal Register Volume 82, Number 112 (Tuesday, June 13, 2017)]
[Notices]
[Pages 27068-27069]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-12147]


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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 invention listed below is owned by an agency of the U.S. 
Government and is available for licensing 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: Dr. Natalie Greco, 301-761-7898; 
[email protected]. Licensing information and copies of the patent 
applications listed below may be obtained by communicating with the 
indicated licensing contact at the Technology Transfer and Intellectual 
Property Office, National Institute of Allergy and Infectious Diseases, 
5601 Fishers Lane, Rockville, MD 20852; tel. 301-496-2644. A signed 
Confidential Disclosure Agreement will be required to receive copies of 
unpublished patent applications.

SUPPLEMENTARY INFORMATION: Technology description follows.

Human and Veterinary Cancer Therapeutic Agent Utilizing Anthrax Toxin-
Based Technology

Description of Technology

    Due to the disorganized nature of blood vessels that run through 
tumors, chemotherapeutic agents often fail to penetrate tumors and kill 
cancer cells at the tumor's center. This can lead to ineffective 
chemotherapeutic treatments, because tumors can quickly grow back if 
the entire tumor is not destroyed. NIH researchers have developed a 
therapeutic agent that solves this problem facing current chemotherapy 
treatments. By elegantly

[[Page 27069]]

exploiting cell surface proteases present at high levels in tumors, 
they have developed a tumor-targeted anthrax based toxin that 
inactivates the blood vessels within tumors. While in some cases cancer 
cells are also killed by the tumor-targeted toxin, the primary 
mechanism of action is thought to be a decrease in blood flow to the 
center of tumors, causing cancer cell death and tumor necrosis. 
Preliminary and on-going studies have demonstrated that the targeted 
toxins have antitumor effects on melanomas, lung cancers and colon 
cancer in mouse models, and on feline and canine oral tumors. 
Interestingly, this therapy does not target a specific type of cancer 
cell, rather it targets the vasculature in and around tumors. 
Therefore, it has great potential to treat a wide range of solid 
tumors. Additionally, because few non-surgical treatments are available 
to treat many human and veterinary solid tumors, this technology would 
fill an unmet need in cancer therapy.
    This technology is available for licensing for commercial 
development in accordance with 35 U.S.C. 209 and 37 CFR part 404, as 
well as for further development and evaluation under a research 
collaboration.

Potential Commercial Applications

    Therapeutic agent for a wide range of human and veterinary solid 
tumors, including:
 Melanomas
 Lung and colon cancers
 Oral squamous carcinomas

Competitive Advantages

     Proven effective in a variety of models, including models 
of important veterinary cancers.
     Agent is only active in tumor micro-environments, 
resulting in low toxicity to healthy tissue.
     Cancer cells are not directly targeted, so this agent can 
be used to treat a broad spectrum of solid tumors and resistance is 
unlikely to arise.
     Fills an unmet need in cancer therapy, because few non-
surgical treatments exist.

Development Stage

 in vitro data available
 in vivo data available (animal)
 prototype
    Inventors: S. Leppla (NIAID); S.-H. Liu (NIAID); T. Bugge (NIDCR); 
A.Wein (NIAID); D. Peters (NIDCR); J. Liu (NHLBI); K.-H.Chen (NIAID); 
H. Birkedal-Hansen (NIDCR); S. Netzel-Arnett (NIDCR); D. Phillips 
(NIAID); C. Leysath (NIAID); C. Bachran (NIAID)

Publications

Chen KH, et al., Selection of anthrax toxin protective antigen variants 
that discriminate between the cellular receptors tem8 and cmg2 and 
achieve targeting of tumor cells. J Biol Chem. 2007 Mar 30; 282(13): 
9834-9845 [PMID: 17251181 PMCID: PMC2530824]
Liu S, et al., Solid tumor therapy by selectively targeting stromal 
endothelial cells. Proc Natl Acad Sci U S A. 2016 Jul 12; 113(28): 
E4079-E4087 [PMID: 27357689 PMCID: PMC4948345]
Wein AN, et al., An anthrax toxin variant with an improved activity in 
tumor targeting. Sci Rep. 2015; 5: 16267 [PMID: 26584669 PMCID: 
PMC4653645]
Peters DE, et al., Comparative toxicity and efficacy of engineered 
anthrax lethal toxin variants with broad anti-tumor activities. Toxicol 
Appl Pharmacol. 2014 Sep 1; 279(2): 220-229 [PMID: 24971906 PMCID: 
PMC4137396]
Bachran C, et al., Cytolethal distending toxin B as a cell-killing 
component of tumor-targeted anthrax toxin fusion proteins. Cell Death 
Dis. 2014 Jan; 5(1): e1003 [PMID: 24434511 PMCID: PMC4040664]
Wein AN, et al., Tumor therapy with a urokinase plasminogen activator-
activated anthrax lethal toxin alone and in combination with 
paclitaxel. Invest New Drugs. 2013 Feb; 31(1): 206-212 [PMID: 22843210 
PMCID: PMC3757568]
Phillips DD, et al., Engineering Anthrax Toxin Variants That 
Exclusively Form Octamers and Their Application to Targeting Tumors. J 
Biol Chem. 2013 Mar 29; 288(13): 9058-9065 [PMID: 23393143 PMCID: 
PMC3610978]
Liu S, et al., Intermolecular complementation achieves high specificity 
tumor targeting by anthrax toxin. Nat Biotechnol. 2005 Jun; 23(6): 725-
730 [PMID: 15895075 PMCID: PMC2405912]

Intellectual Property

HHS E-256-2015--US Application Nos. 62/210,771, filed 27 Aug 2015; 62/
323,218, filed 15 Apr 2016; PCT App. No. PCT/US16/48706, filed 25 Aug 
2016.
HHS E-120-2013--US App. No. 14/898,248, filed 14 Dec 2015; PCT App. No. 
PCT/US2014/043131, filed 19 Jun 2014.
HHS E-246-2012--US App. No. 14/423,408, filed 23 Feb 2015; PCT App. No. 
PCT/US13/56205
HHS E-059-2004--US Patent No. 7,947,289, filed 09 Feb 2005.
HHS E-293-1999--US Patent Nos. 7,468,352, filed 22 Mar 2002; 8,791,074, 
filed 20 Oct 2008, and 9,403,872 filed 24 Jun 2014.
    Licensing Contact: Dr. Natalie Greco, 301-761-7898; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Allergy and Infectious Diseases is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate or commercialize anthrax toxin-based cancer 
therapeutics. For collaboration opportunities, please contact Dr. 
Natalie Greco, 301-761-7898; [email protected].

    Dated: June 1, 2017.
Suzanne Frisbie,
Deputy Director, Technology Transfer and Intellectual Property Office, 
National Institute of Allergy and Infectious Diseases.
[FR Doc. 2017-12147 Filed 6-12-17; 8:45 am]
 BILLING CODE 4140-01-P