[Federal Register Volume 76, Number 147 (Monday, August 1, 2011)]
[Notices]
[Pages 45838-45839]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-19378]


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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, Public Health Service, 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. 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.

Combination Cancer Therapy Using an IL13-Targeted Toxin and a Vaccine

    Description of Technology: Typical cancer treatments such as 
chemotherapy, radiation therapy and surgical resection are non-specific 
processes that kill healthy cells as well as diseased cells, ultimately 
resulting in discomfort and undesirable side-effects for patients. In 
an effort to reduce the burden on cancer patients, a tremendous effort 
has been placed on developing ways to increase the specificity of 
cancer treatments. One way to increase specificity is to identify 
proteins which are present on the surface of cancer cells but absent on 
normal healthy cells, and use that protein as a target for delivering a 
therapeutic agent. Because the therapeutic agent only reaches the 
diseased cell, patients are less likely to experience non-specific 
side-effects, reducing their pain burden during treatment.
    IL13-receptor-alpha-2 (IL13-R[alpha]2) is a cell surface protein 
that is selectively expressed on certain diseased cells, including 
cancer cells. IL13-R[alpha]2 binds to the cytokine IL13, suggesting 
that a therapeutic agent fused to IL13 can target and kill only those 
cancer cells which express IL13-R[alpha]2. Our inventors previously 
constructed fusion proteins comprising (1) IL13 and (2) an active 
fragment of the bacterial toxin Pseudomonas exotoxin A (PE). These 
IL13-PE fusion proteins demonstrated the ability to selectively kill 
cancer cells that overexpressed IL13-R[alpha]2, as well as other types 
of diseased cells (asthma, pulmonary fibrosis) which overexpressed 
IL13-R[alpha]2. This suggested that IL13-PE fusion proteins were 
excellent candidates for new therapeutic agents.
    The inventors recently sought methods to increase the effectiveness 
of these IL13-PE fusion proteins in the treatment of disease. This 
technology is directed to a combination therapy comprising (a) a DNA 
vaccine against IL13-R[alpha]2 and (b) an IL13-PE fusion protein. By 
combining these therapeutic approaches it is possible to kill certain 
cell types that express IL13-R[alpha]2 at high levels (such as cancer 
cells), making this combinatorial approach an attractive potential 
therapeutic.
    Applications:
     Treatment of diseases associated with the increased 
expression of IL13-R[alpha]2
     Relevant diseases include pulmonary fibrosis, asthma and 
cancers such as pancreatic cancer, glioblastoma multiforme and other 
head and neck cancers
    Advantages:
     The DNA vaccine only affects cells where IL13-R[alpha]2 
expression is increased, limiting their effects to diseased cells
     IL13-PE fusion proteins also only kill cells that 
overexpress IL13-R[alpha]2, allowing specific targeting of treatment
     Targeted treatment decreases non-specific killing of 
healthy, essential cells, resulting in fewer side-effects and healthier 
patients
    Development Status: Preclinical stage of development.
    Inventors: Puri et al. (FDA).
    Patent Status: US provisional application 61/451,331 (HHS reference 
E-104-2011/0-US-01).
    For more information, see:
     US Patents 5,614,191, 5,919,456 and 6,518,061 (HHS 
technology reference E-266-1994/0)
     US Patent Publication US 20040136959 A1 (HHS technology 
reference E-032-2000/0)
     US Patent 7,541,040 (HHS technology reference E-296-2001/
0)
    Licensing Status: Available for licensing.
    Licensing Contact: David A. Lambertson, PhD; 301-435-4632; 
[email protected].

[[Page 45839]]

Combination Cancer Therapy Using an IL13-Targeted Toxin and an HDAC 
Inhibitor

    Description of Technology: Typical cancer treatments such as 
chemotherapy, radiation therapy and surgical resection are non-specific 
processes that kill healthy cells as well as diseased cells, ultimately 
resulting in discomfort and undesirable side-effects for patients. In 
an effort to reduce the burden on cancer patients, a tremendous effort 
has been placed on developing ways to increase the specificity of 
cancer treatments. One way to increase specificity is to identify 
proteins which are present on the surface of cancer cells but absent on 
normal healthy cells, and use that protein as a target for delivering a 
therapeutic agent. Because the therapeutic agent only reaches the 
diseased cell, patients are less likely to experience non-specific 
side-effects, reducing their pain burden during treatment.
    IL13-receptor-alpha-2 (IL13-R[alpha]2) is a cell surface protein 
that is selectively expressed on certain diseased cells, including 
cancer cells. IL13-R[alpha]2 binds to the cytokine IL13, suggesting 
that a therapeutic agent fused to IL13 can target and kill only those 
cancer cells which express IL13-R[alpha]2. Our inventors previously 
constructed fusion proteins comprising (1) IL13 and (2) an active 
fragment of the bacterial toxin Pseudomonas exotoxin A (PE). These 
IL13-PE fusion proteins demonstrated the ability to selectively kill 
cancer cells that overexpressed IL13-R[alpha]2, as well as other types 
of diseased cells (asthma, pulmonary fibrosis) which overexpressed 
IL13-R[alpha]2. This suggested that IL13-PE fusion proteins were 
excellent candidates for new therapeutic agents.
    In an effort to increase the effectiveness of these IL13-PE fusion 
proteins, the inventors sought ways to increase the expression of IL13-
R[alpha]2 on cancer cells, thereby increasing the rate at which the 
therapeutic agent could kill the diseased cell. Histone deacetylase 
(HDAC) inhibitors have been employed as anti-cancer agents for several 
years, and a number of HDAC inhibitors are currently in clinical 
trials. Although the exact mechanism by which HDAC inhibitors function 
is unclear, it is believed that the ability of these molecules to 
increase the expression of anti-cancer genes is behind their 
therapeutic effect.
    This invention concerns a means of improving specific cancer 
therapy through the combination of (a) IL13-PE fusion proteins and (b) 
HDAC inhibitors. The inventors surprisingly found that the expression 
of IL13-R[alpha]2 increased in several types of pancreatic cancer cells 
in response to HDAC inhibitors, whereas normal, healthy cells did not 
experience such an increase in IL13-R[alpha]2 expression. The use of 
IL13-PE fusion proteins in combination with HDAC inhibitors improved 
specific killing of pancreatic cancer cells relative to the use of 
IL13-PE fusion proteins in the absence of the HDAC inhibitors. This 
suggested that the use of IL13-PE fusion proteins along with HDAC 
inhibitors was a strong candidate combinatorial therapeutic for the 
treatment of various cancers (e.g., pancreatic, glioblastoma 
multiforme) and other diseases characterized by overexpression of IL13-
R[alpha]2 (e.g., asthma, pulmonary fibrosis).
    Applications:
     Treatment of diseases associated with the increased 
expression of IL13-R[alpha]2
     Relevant diseases include pulmonary fibrosis, asthma and 
cancers such as pancreatic cancer, glioblastoma multiforme and other 
head and neck cancers
    Advantages:
     HDAC inhibitors only increased IL13-R[alpha]2 expression 
in diseased cells, leaving normal healthy cells unaltered
     IL13-PE fusion proteins only kill cells that overexpress 
IL13-R[alpha]2, allowing specific targeting of treatment
     Targeted treatment decreases non-specific killing of 
healthy, essential cells, resulting in fewer side-effects and healthier 
patients
    Development Status: Preclinical stage of development
    Inventors: Puri et al. (FDA)
    Patent Status: US provisional application 61/494,779 (HHS reference 
E-107-2011/0-US-01)
    For more information, see:
     US Patents 5,614,191, 5,919,456 and 6,518,061 (HHS 
technology reference E-266-1994/0)
     US Patent Publication US 20040136959 A1 (HHS technology 
reference E-032-2000/0)
     US Patent 7,541,040 (HHS technology reference E-296-2001/
0)
    Licensing Status: Available for licensing
    Licensing Contact: David A. Lambertson, PhD; 301-435-4632; 
[email protected]

    Dated: July 26, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2011-19378 Filed 7-29-11; 8:45 am]
BILLING CODE 4140-01-P