[Federal Register Volume 81, Number 177 (Tuesday, September 13, 2016)]
[Notices]
[Pages 62916-62917]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-21906]


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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 and/or co-development 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 and/or co-development.

ADDRESSES: Invention Development and Marketing Unit, Technology 
Transfer Center, National Cancer Institute, 9609 Medical Center Drive, 
Mail Stop 9702, Rockville, MD, 20850-9702.

FOR FURTHER INFORMATION CONTACT: Information on licensing and co-
development research collaborations, and copies of the U.S. patent 
applications listed below may be obtained by contacting: Attn. 
Invention Development and Marketing Unit, Technology Transfer Center, 
National Cancer Institute, 9609 Medical Center Drive, Mail Stop 9702, 
Rockville, MD, 20850-9702, Tel. 240-276-5515 or Email 
[email protected]. A signed Confidential Disclosure 
Agreement may be required to receive copies of the patent applications.

SUPPLEMENTARY INFORMATION: Technology description follows.
    Title of invention: Immunotoxins with Increased Stability for 
Cancer Therapy.
    Keywords: Recombinant Immunotoxin, RIT, Antibody, Mesothelin, 
Mesothelioma.

Description of Technology

    Recombinant immunotoxins (RITs) are fusions of an antibody-based 
targeting moiety and a toxin. Pseudomonas exotoxin A (PE) is a 
bacterial toxin that has been used in several RITs evaluated in 
clinical trials.1 2 Once the Fv portion of the immunotoxin 
binds to its target receptor, the immunotoxin is internalized by 
endocytosis. Following internalization, Furin cleavage is critically 
important for proper cytosolic shuttling of the immunotoxin. Early PE-
containing RITs were effective, but also had issues of off-target 
toxicity.
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    \1\ Fitzgerald DJ, Kreitman R, et al. Int J Med Microbiol. 
2004;293:577-582.
    \2\ Sampson JH, Akabani G, Archer GE, et al. J Neurooncol. 
2003;65(1):27-35.
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    To mitigate off-target toxicity of PE, the inventors removed 
specific sequences of domain II, and connected the Fv domain to domain 
III (PE24) by a furin linker peptide. These PE24-RITs are very active 
and better tolerated by mice. However, the PE24-containing RITs could 
potentially be cleaved and inactivated before internalization by cell 
surface furin or other proteases in the bloodstream or the tumor 
microenvironment, due to the absence of a key disulfide bond (lost 
after removal of domain II sequences).
    Researchers at the National Cancer Institute's Laboratory of 
Molecular Biology (NCI LMB) developed and isolated several de-
immunized, low toxicity, PE24-based RITs with a longer serum half-life. 
This was enabled by using a disulfide bond to protect the furin 
cleavage sequence (FCS). Collectively, the new RITs are designated 
``DS-PE24'' immunotoxins. The goal of the disulfide bond is to protect 
the RIT from cleavage-based deactivation before internalization. The 
most active of these new RITs has longer serum half-life than an RIT 
without the disulfide bond, has the same anti-tumor activity, while 
remaining less cytotoxic in vitro. Currently, the inventors are working 
with mouse models to further develop the DS-PE24 RITs towards 
developing an anti-mesothelin RIT for treatment of mesothelin-
expressing cancers, such as mesothelioma.

Potential Commercial Applications

     A more stable cancer therapeutic for currently used PE-
coupled RITs, for example, anti-mesothelin PE-based immunotoxins.

Value Proposition

     Protection of the FCS by a disulfide bond results in more 
stable RIT, which can lead to fewer off-target effects.
    Development Stage: In-vivo.
    Inventor(s): Ira Pastan M.D. (NCI), et al.
    Intellectual Property: United States Provisional Patent Application 
62/323,668 (NIH Reference E-157-2016/0-US-01), entitled ``New, More 
Stable

[[Page 62917]]

Immunotoxin Variants with a Disulfide Bond Protecting the Furin 
Cleavage Site.''

Related Technologies

 NIH Reference E-262-2005, entitled ``Mutated Pseudomonas 
Exotoxins with Reduced Antigenicity''
 NIH Reference E-292-2007, entitled ``Deletions in Domain II of 
Pseudomonas Exotoxin A that Reduce Non-Specific Toxicity''
 NIH Reference E-174-2011, entitled ``Pseudomonas Exotoxin A 
with Less Immunogenic T-Cell and/or B-Cell Epitopes''
 NIH Reference E-263-2011, entitled ``Pseudomonas Exotoxin A 
with Less Immunogenic B-Cell Epitopes''
    Collaboration Opportunity: Researchers at the NCI seek parties 
interested in licensing DS-PE24 RITs.
    Contact Information: Requests for copies of the patent application 
or inquiries about licensing, research collaborations, and co-
development opportunities should be sent to John D. Hewes, Ph.D., 
email: [email protected].

    Dated: September 5, 2016.
John D. Hewes,
Technology Transfer Specialist, Technology Transfer Center, National 
Cancer Institute.
[FR Doc. 2016-21906 Filed 9-12-16; 8:45 am]
 BILLING CODE 4140-01-P