81 FR 62916 - Government-Owned Inventions; Availability for Licensing

DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health

Federal Register Volume 81, Issue 177 (September 13, 2016)

Page Range		62916-62917
FR Document		2016-21906

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.

Federal Register, Volume 81 Issue 177 (Tuesday, September 13, 2016)

[Federal Register Volume 81, Number 177 (Tuesday, September 13, 2016)]
[Notices]
[Pages 62916-62917]
From the Federal Register Online  [www.thefederalregister.org]
[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

62916 Federal Register / Vol. 81, No. 177 / Tuesday, September 13, 2016 / Notices

breast cancer patient’s survival. In this Dated: September 5, 2016. trials.1 2 Once the Fv portion of the
array, SNPs are analyzed from a John D. Hewes, immunotoxin binds to its target
patient’s genomic DNA (gDNA); the Technology Transfer Specialist, Technology receptor, the immunotoxin is
result can be used to predict whether a Transfer Center, National Cancer Institute. internalized by endocytosis. Following
patient is likely to respond to current [FR Doc. 2016–21905 Filed 9–12–16; 8:45 am] internalization, Furin cleavage is
breast cancer treatment strategies. This BILLING CODE 4140–01–P critically important for proper cytosolic
invention can reassure newly diagnosed shuttling of the immunotoxin. Early PE-
patients that they have a high containing RITs were effective, but also
probability of responding to treatment DEPARTMENT OF HEALTH AND had issues of off-target toxicity.
and can also identify those patients that HUMAN SERVICES To mitigate off-target toxicity of PE,
require alternative, more aggressive the inventors removed specific
therapeutic strategies. Importantly, this National Institutes of Health sequences of domain II, and connected
invention has several advantages over the Fv domain to domain III (PE24) by
the currently-offered gene expression- Government-Owned Inventions; a furin linker peptide. These PE24–RITs
based breast cancer prognostic tests. Availability for Licensing are very active and better tolerated by
Since this array can be completed AGENCY: National Institutes of Health, mice. However, the PE24-containing
following routine blood draw, rather HHS. RITs could potentially be cleaved and
than through a tumor biopsy, the inactivated before internalization by cell
ACTION: Notice.
samples are more stable, the process is surface furin or other proteases in the
quicker, simpler, less-invasive, and SUMMARY: The invention listed below is bloodstream or the tumor
more cost-effective than current owned by an agency of the U.S. microenvironment, due to the absence
methods. Government and is available for of a key disulfide bond (lost after
licensing and/or co-development in the removal of domain II sequences).
Potential Commercial Applications
U.S. in accordance with 35 U.S.C. 209 Researchers at the National Cancer
• Identification of patients with and 37 CFR part 404 to achieve Institute’s Laboratory of Molecular
higher susceptibility to tumor expeditious commercialization of Biology (NCI LMB) developed and
progression (i.e., metastasis). results of federally-funded research and isolated several de-immunized, low
• Prediction of breast cancer survival development. Foreign patent toxicity, PE24-based RITs with a longer
(less than 10 years, for example) using applications are filed on selected serum half-life. This was enabled by
array and methods. inventions to extend market coverage using a disulfide bond to protect the
• Personalization of patient for companies and may also be available furin cleavage sequence (FCS).
treatment. for licensing and/or co-development. Collectively, the new RITs are
Value Proposition: Since the array designated ‘‘DS–PE24’’ immunotoxins.
ADDRESSES: Invention Development and
processes DNA from blood rather than The goal of the disulfide bond is to
Marketing Unit, Technology Transfer
tissue from a standard biopsy or protect the RIT from cleavage-based
Center, National Cancer Institute, 9609
resection of a primary tumor, it is faster, deactivation before internalization. The
Medical Center Drive, Mail Stop 9702,
simpler, more stable, more cost- most active of these new RITs has longer
Rockville, MD, 20850–9702.
efficient, and less-invasive because serum half-life than an RIT without the
gDNA is more stable than tumor mRNA. FOR FURTHER INFORMATION CONTACT: disulfide bond, has the same anti-tumor
Development Stage: Pre-clinical (in Information on licensing and co- activity, while remaining less cytotoxic
vivo validation). development research collaborations, in vitro. Currently, the inventors are
Inventor(s): Kent W. Hunter, Ph.D. and copies of the U.S. patent working with mouse models to further
(NCI), Howard H. Yang, Ph.D. (NCI), applications listed below may be develop the DS–PE24 RITs towards
Maxwell P. Lee, Ph.D. (NCI). obtained by contacting: Attn. Invention developing an anti-mesothelin RIT for
Intellectual Property: HHS Reference Development and Marketing Unit, treatment of mesothelin-expressing
No. E–082–2015/0–US–01 Technology Transfer Center, National cancers, such as mesothelioma.
US Provisional Application 62/ Cancer Institute, 9609 Medical Center
Drive, Mail Stop 9702, Rockville, MD, Potential Commercial Applications
297,557 (HHS Reference No. E–082–
2015/0–US–01) filed February 19, 2016 20850–9702, Tel. 240–276–5515 or • A more stable cancer therapeutic for
entitled ‘‘SNP-Based Assay to Predict Email ncitechtransfer@mail.nih.gov. A currently used PE-coupled RITs, for
Breast Cancer Survival’’. signed Confidential Disclosure example, anti-mesothelin PE-based
Collaboration Opportunity: Agreement may be required to receive immunotoxins.
Researchers at the NCI seek licensing copies of the patent applications.
Value Proposition
and/or co-development research SUPPLEMENTARY INFORMATION:
collaborations for methods that provide Technology description follows. • Protection of the FCS by a disulfide
significant improvements in examining Title of invention: Immunotoxins with bond results in more stable RIT, which
additional SNPs for improved Increased Stability for Cancer Therapy. can lead to fewer off-target effects.
prognostics, and to evaluate whether the Keywords: Recombinant Development Stage: In-vivo.
SNP signature is associated with overall Immunotoxin, RIT, Antibody, Inventor(s): Ira Pastan M.D. (NCI), et
cancer incidence or effective treatment Mesothelin, Mesothelioma. al.
strategies. Intellectual Property: United States
Description of Technology Provisional Patent Application 62/
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Contact Information: Requests for
copies of the patent application or Recombinant immunotoxins (RITs) 323,668 (NIH Reference E–157–2016/0–
inquiries about licensing, research are fusions of an antibody-based US–01), entitled ‘‘New, More Stable
collaborations, and co-development targeting moiety and a toxin.
1 Fitzgerald DJ, Kreitman R, et al. Int J Med
opportunities should be sent to John D. Pseudomonas exotoxin A (PE) is a
Microbiol. 2004;293:577–582.
Hewes, Ph.D., email hewesj@ bacterial toxin that has been used in 2 Sampson JH, Akabani G, Archer GE, et al. J

mail.nih.gov. several RITs evaluated in clinical Neurooncol. 2003;65(1):27–35.

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Federal Register / Vol. 81, No. 177 / Tuesday, September 13, 2016 / Notices 62917

Immunotoxin Variants with a Disulfide would constitute a clearly unwarranted American Blvd. West, Suite 990,
Bond Protecting the Furin Cleavage invasion of personal privacy. Bloomington, MN 55437–1458; or by
Site.’’ Name of Committee: National Library of electronic mail to permitsR3ES@fws.gov.
Related Technologies Medicine Special Emphasis Panel; R01/R21/ FOR FURTHER INFORMATION CONTACT:
K01/K99 Conflicts. Carlita Payne, (612) 713–5343.
• NIH Reference E–262–2005, entitled Date: December 2, 2016.
‘‘Mutated Pseudomonas Exotoxins Time: 11:00 a.m. to 4:30 p.m. SUPPLEMENTARY INFORMATION:
with Reduced Antigenicity’’ Agenda: To review and evaluate grant
Background
• NIH Reference E–292–2007, entitled applications.
‘‘Deletions in Domain II of Place: National Library of Medicine, 6705 The Endangered Species Act of 1973
Pseudomonas Exotoxin A that Reduce Rockledge Drive, Suite 301, Bethesda, MD (ESA), as amended (16 U.S.C. 1531 et
Non-Specific Toxicity’’ 20817 (Telephone Conference Call).
seq.), prohibits certain activities with
• NIH Reference E–174–2011, entitled Contact Person: Zoe E. Huang, MD,
Scientific Review Officer, Extramural endangered and threatened species
‘‘Pseudomonas Exotoxin A with Less Programs, National Library of Medicine, NIH, unless the activities are specifically
Immunogenic T-Cell and/or B-Cell 6705 Rockledge Drive, Suite 301, Bethesda, authorized by a Federal permit. The
Epitopes’’ MD 20892–7968, 301–594–4937, huangz@ ESA and our implementing regulations
• NIH Reference E–263–2011, entitled mail.nih.gov. in part 17 of title 50 of the Code of
‘‘Pseudomonas Exotoxin A with Less (Catalogue of Federal Domestic Assistance Federal Regulations (CFR) provide for
Immunogenic B-Cell Epitopes’’ Program No. 93.879, Medical Library the issuance of such permits and require
Collaboration Opportunity: Assistance, National Institutes of Health, that we invite public comment before
Researchers at the NCI seek parties HHS) issuing permits for activities involving
interested in licensing DS–PE24 RITs. Dated: September 7, 2016. endangered species.
Contact Information: Requests for
Michelle Trout, A permit granted by us under section
copies of the patent application or
Program Analyst, Office of the Federal 10(a)(1)(A) of the ESA authorizes the
inquiries about licensing, research
Advisory Committee Policy. permittee to conduct activities with U.S.
collaborations, and co-development
[FR Doc. 2016–21898 Filed 9–12–16; 8:45 am] endangered or threatened species for
opportunities should be sent to John D.
BILLING CODE 4140–01–P scientific purposes, enhancement of
Hewes, Ph.D., email: john.hewes@
propagation or survival, or interstate
nih.gov.
commerce (the latter only in the event
Dated: September 5, 2016. that it facilitates scientific purposes or
DEPARTMENT OF THE INTERIOR
John D. Hewes, enhancement of propagation or
Technology Transfer Specialist, Technology Fish and Wildlife Service survival). Our regulations implementing
Transfer Center, National Cancer Institute. section 10(a)(1)(A) of the ESA for these
[FWS–R3–ES–2016–N153;
[FR Doc. 2016–21906 Filed 9–12–16; 8:45 am]
FXES11130300000–167–FF03E00000]
permits are found at 50 CFR 17.22 for
BILLING CODE 4140–01–P endangered wildlife species, 50 CFR
Endangered and Threatened Wildlife 17.32 for threatened wildlife species, 50
and Plants; Permit Applications CFR 17.62 for endangered plant species,
DEPARTMENT OF HEALTH AND and 50 CFR 17.72 for threatened plant
HUMAN SERVICES AGENCY: Fish and Wildlife Service, species.
Interior.
National Institutes of Health ACTION: Notice of availability; request
Applications Available for Review and
for comments. Comment
National Library of Medicine; Notice of
Closed Meeting We invite local, State, Tribal, and
SUMMARY: We, the U.S. Fish and
Federal agencies and the public to
Wildlife Service, invite the public to
Pursuant to section 10(d) of the comment on the following applications.
comment on the following applications
Federal Advisory Committee Act, as Please refer to the permit number when
for a permit to conduct activities
amended (5 U.S.C. App), notice is you submit comments. Documents and
intended to enhance the survival of
hereby given of the following meeting. other information the applicants have
endangered or threatened species.
The meeting will be closed to the submitted with the applications are
Federal law prohibits certain activities
public in accordance with the available for review, subject to the
with endangered species unless a permit
provisions set forth in sections requirements of the Privacy Act (5
is obtained.
552b(c)(4) and 552b(c)(6), title 5 U.S.C., U.S.C. 552a) and Freedom of
as amended. The grant applications and DATES: We must receive any written Information Act (5 U.S.C. 552).
the discussions could disclose comments on or before October 13,
2016. Permit Applications
confidential trade secrets or commercial
property such as patentable materials, ADDRESSES: Send written comments by Proposed activities in the following
and personal information concerning U.S. mail to the Regional Director, Attn: permit requests are for the recovery and
individuals associated with the grant Carlita Payne, U.S. Fish and Wildlife enhancement of survival of the species
applications, the disclosure of which Service, Ecological Services, 5600 in the wild.
Application Permit
Applicant Species Location Activity Type of take
No. action
Lhorne on DSK30JT082PROD with NOTICES

TE04397C Giorgianna G. Indiana bat (Myotis sodalis), north- Rangewide ... Conduct presence/absence sur- Capture, handle, radio- New.
Auteri. ern long-eared bat (Myotis veys, document habitat use, tag, release.
septentrionalis), gray bat (Myotis conduct population monitoring,
grisescens). evaluate impacts.

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Document Created: 2018-02-09 13:16:48
Document Modified: 2018-02-09 13:16:48

Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Notices
Action		Notice.
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.
FR Citation		81 FR 62916

81 FR 62916 - Government-Owned Inventions; Availability for Licensing

DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

Federal Register Volume 81, Issue 177 (September 13, 2016)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health