[Federal Register Volume 76, Number 120 (Wednesday, June 22, 2011)]
[Notices]
[Pages 36551-36553]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-15492]


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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.

Monoclonal Antibodies to Glypican-3 Protein and Heparin Sulfate for 
Treatment of Cancer

    Description of Technology: Hepatocellular carcinoma (HCC) is the 
most common form of liver cancer, and is among the more deadly cancers 
in the world due to its late detection and poor prognosis. HCC is often 
associated with liver disease, curtailing traditional chemotherapy as a 
treatment option. While surgical resection offers the best method for 
long term treatment of the disease, only a small portion of HCC 
patients are eligible for this procedure. As a result, there is a need 
for new treatments that can be successfully applied to a large 
population of HCC patients.
    Glypican-3 (GPC3) is a cell surface protein that is preferentially 
expressed on HCC cells. Evidence has demonstrated that a soluble form 
of GPC3 that is incapable of cell signaling has the ability to inhibit 
the growth of HCC cells. This suggested that blocking GPC3 signaling 
could serve as a therapeutic approach for treating HCC.
    This invention concerns monoclonal antibodies against GPC3 and 
their use, either by themselves or as the targeting domain for an 
immunotoxin, for the treatment of GPC3-expressing cancers such as HCC. 
Specifically, the inventors have generated two distinct monoclonal 
antibodies to GPC3. The first monoclonal antibody (HN3) binds to a 
conformational epitope on the cell surface domain of GPC3. The second 
monoclonal antibody (HS20) binds specifically to heparin sulfate chains 
on GPC3.
    By blocking GPC3 function, these antibodies can inhibit the growth 
of HCC cells, thereby decreasing the ability of tumors to grow and 
metastasize. Furthermore, by using the antibodies to target a toxin to 
only those cells that express GPC3, cancer cells can be eliminated 
while allowing healthy, essential cells to remain unharmed. Thus, 
monoclonal antibodies to GPC3 (and corresponding immunotoxins) 
represent a novel therapeutic candidate for treatment of HCC, as well 
as other cancers associated with the differential expression of GPC3.
    Applications:
     Therapeutic candidates against cancers that overexpress 
GPC3;
     Antibodies for killing cancer cells by inhibiting GPC3-
based cell signaling, thereby inhibiting tumor cell growth;
     Immunotoxins for killing cancer cells through the action 
of a toxic agent;
     Diagnostics for detecting cancers associated with GPC3 
overexpression;
     Specific cancers include hepatocellular cancer (HCC), 
melanoma, thyroid cancer, lung squamous cell carcinoma, Wilms' tumor, 
neuroblastoma, hepatoblastoma, and testicular germ-cell tumors.
    Advantages:
     Monoclonal antibodies create a level of specificity that 
can reduce deleterious side-effects;
     Multiple treatment strategies available including the 
killing of cancer cells with a toxic agent or by inhibiting cell 
signaling;
     Non-invasive and potentially non-liver toxic alternative 
to current HCC treatment strategies.
    Development Status: Preclinical stage of development; cell culture 
data with HCC cells.
    Inventors: Mitchell Ho (NCI) et al.
    Patent Status: U.S. provisional application 61/477,020 (HHS 
technology reference E-130-2011/0-US-01).
    For more information, see:
     M Feng et al. Recombinant soluble glypican 3 protein 
inhibits the growth of hepatocellular carcinoma in vitro. Int J Cancer 
2011 May1;128(9):2246-2247, doi 10.1002/ijc.25549. [PMID: 20617511].
     SI Zitterman et al. Soluble glypican 3 inhibits the growth 
of hepatocellular

[[Page 36552]]

carcinoma in vitro and in vivo. Int J Cancer 2010 Mar 15;126(6):1291-
1301. [PMID: 19816934].
    Licensing Status: Available for licensing.
    Licensing Contact: David A. Lambertson, PhD; 301-435-4632; 
[email protected].
    Collaborative Research Opportunity: The Center for Cancer Research, 
Laboratory of Molecular Biology, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize human monoclonal antibodies or 
immunoconjugates such as immunotoxins and antibody-drug conjugates 
against GPC3, soluble GPC3 and its immunoconjugates such as Fc fusion 
proteins, large scale antibody production, and HCC xenograft mouse 
models. Please contact John Hewes, PhD at 301-435-3121 or 
[email protected] for more information.

Mouse Xenograft Model for Mesothelioma

    Description of Technology: Malignant mesothelioma is a cancer that 
presents itself in the protective lining of several organs (e.g., lung, 
heart, testis, etc.). The primary cause for mesothelioma is direct or 
indirect exposure to asbestos, although the disease can present without 
any prior exposure. Mesothelioma is relatively rare, but the prognosis 
for patients is poor, indicating a need to better understand and treat 
the disease. Current treatments often involve chemotherapy and 
radiation therapy, although recent studies have employed the use of 
therapeutic antibodies and antibody-targeted toxins.
    This invention involves the creation of a new mouse model for 
mesothelioma. By creating xenografts with mesothelioma cells that 
express GFP-Luciferase fusion proteins, the xenografts can be detected 
to a high degree of sensitivity, and monitored for several months 
following implantation. The high level of detection sensitivity 
improves the ability to monitor disease progression in response to 
therapeutic candidates, thereby allowing more efficient drug screening 
and evaluation. This has already been demonstrated by using the mouse 
to evaluate an anti-mesothelioma immunotoxin known as SS1P, a drug 
candidate that is currently being evaluated for clinical effectiveness.
    Applications:
     Animal model for screening compounds as potential 
therapeutics for mesothelioma;
     Animal model for studying the effectiveness of potential 
therapeutics for mesothelioma;
     Animal model for studying the pathology of mesothelioma.
    Advantages:
     The model is created using well characterized, art-
accepted mesothelioma cells;
     The model exhibits the classical clinical progression of 
mesothelioma, demonstrating its accuracy as a model;
     The use of GFP-Luciferase fusion proteins allow for non-
invasive evaluation of mesothelioma progression and response to drug 
candidates;
     The use of GFP-Luciferase fusion proteins allow the use of 
highly sensitive detection systems such as bioluminescence.
    Benefits:
     The convenient and efficient identification and evaluation 
of mesothelioma drug candidates.
    Inventor: Mitchell Ho (NCI).
    Patent Status: HHS Reference No. E-302-2009/0 -- Research Tool. 
Patent protection is not being pursued for this technology.
    For more information, see:
     M. Feng et al. In vivo imaging of human malignant 
mesothelioma grown orthotopically in the peritoneal cavity of nude 
mice. J Cancer. 2011 Mar 1;2:123-131. [PMID: 21479131];
     PCT Patent Application WO 2010/065044 (HHS technology 
reference E-336-2008/0-PCT-02);
     U.S. Patent 7,081,518 (HHS technology reference E-139-
1999/0-US-07).
    Licensing Status: The technology is available for non-exclusive 
licensing as a Biological material/Research tool.
    Licensing Contact: David A. Lambertson, PhD; 301-435-4632; 
[email protected].
    Collaborative Research Opportunity: The Center for Cancer Research, 
Laboratory of Molecular Biology, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize monoclonal antibodies and 
immunoconjugates targeting malignant mesotheliomas. Please contact John 
Hewes, PhD at 301-435-3121 or [email protected] for more information.

Increased Therapeutic Effectiveness of Immunotoxins Through the Use of 
Less Immunogenic Toxin Domains

    Description of Technology: Targeted toxins (e.g., immunotoxins) are 
therapeutics that have at least two important components: (1) A toxin 
domain that is capable of killing cells and (2) a targeting domain that 
is capable of selectively localizing the toxic domain to only those 
cells which should be killed. By selecting a targeting domain that 
binds only to certain diseased cells (e.g., a cell which only expresses 
a cell surface receptor when in a diseased state), targeted toxins can 
kill the diseased cells while allowing healthy, essential cells to 
survive. As a result, patients receiving a targeted toxin are less 
likely to experience the deleterious side-effects associated with non-
discriminate therapies such as chemotherapy or radiation therapy.
    A particular toxin that has been used in targeted toxins is 
Pseudomonas exotoxin A (PE). The effectiveness of PE-containing 
targeted toxins has been demonstrated against various forms of cancer, 
including hairy cell leukemia (HCL) and pediatric acute lymphocytic 
leukemia (pALL). Although early variations these targeted toxins have 
demonstrated efficacy upon first administration, the continued 
administration of a targeted toxin often leads to a reduced patient 
response. The primary cause of the reduced response is the formation of 
neutralizing antibodies against PE by the patient.
    Several variations of PE have been created to reduce the 
immunogenicity of PE as a means of increasing the therapeutic 
effectiveness of targeted toxins through multiple rounds of drug 
administration. This technology involves the identification of two 
important B-cell epitopes on PE, and the elimination of those epitopes 
by mutation. These new PE variants retain a sufficient cell killing 
activity while increasing their therapeutic effectiveness toward 
patients that receive multiple administrations. By further combining 
these new mutations with previously identified modifications that also 
improve the efficacy of PE-based targeted toxins, it may be possible to 
treat any disease characterized by cells that express a particular cell 
surface receptor when in a disease state.
    Applications:
     Essential component of a targeted toxin, such as an 
immunotoxin (antibody-targeted toxin) or ligand-targeted toxin;
     Treatment of diseases that are associated with the 
increased expression of a cell surface receptor;
     Applicable to any disease associated with cells that 
preferentially express a specific cell surface receptor;
     Relevant diseases include various cancers, including lung, 
ovarian, breast, head and neck, and hematological cancers.
    Advantages:

[[Page 36553]]

     Less immunogenic targeted toxin results in improved 
efficacy during multiple administrations;
     Targeted therapy decreases non-specific killing of 
healthy, essential cells, resulting in fewer side-effects and healthier 
patients.
    Development Status: Preclinical stage of development.
    Inventors: Pastan (NCI) et al.
    Patent Status:
     U.S. provisional application 61/241,620 (HHS technology 
reference E-269-2009/0-US-01);
     PCT patent application PCT/US2010/048504 (HHS technology 
reference E-269-2009/0-PCT-02).
    For more information, see:
     U.S. Patent Publication US 20100215656 A1 (HHS technology 
reference E-292-2007/0-US-06);
     U.S. Patent Publication US 20090142341 A1 (HHS technology 
reference E-262-2005/0-US-06);
     U.S. Patent 7,777,019 (HHS technology reference E-129-
2001/0-US-07).
    Licensing Status: Available for licensing.
    Licensing Contact: David A. Lambertson, PhD; 301-435-4632; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Molecular Biology Section, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize this technology. Please contact 
John Hewes, PhD at 301-435-3121 or [email protected] for more 
information.

    Dated: June 15, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2011-15492 Filed 6-21-11; 8:45 am]
BILLING CODE 4140-01-P