[Federal Register Volume 76, Number 193 (Wednesday, October 5, 2011)]
[Notices]
[Pages 61714-61717]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-25734]


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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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[[Page 61715]]

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.

Platform Technology Using Ubiquitin To Improve the Delivery and 
Efficacy of Cytosolic Targeted Toxins

    Description of Technology: Targeted toxins (TT) are hybrid protein 
drugs consisting of ligands that bind to the surface of cancer cells 
and deliver polypeptide toxins that kill malignant cells by 
inactivating cytosolic protein synthesis and inducing cell death. A 
major challenge in the construction of targeted toxins is reducing the 
nonspecific binding of the toxin moiety to normal tissues and 
increasing the cytotoxicity of the treatment.
    To address these issues, the NIH inventors have identified that the 
protein ubiquitin, a small protein in eukaryotic cells that plays a 
role in protein recycling, can separate the targeting moiety and the 
catalytic moiety of a TT in the cytosol of cells. By decoupling the two 
moieties, the cytotoxicity of the TT treatment can be greatly increased 
since the catalytic domain remains longer in the cytosol. This 
technology would be highly useful for all TT and immunotoxins that 
access the cytosol to either affect cytosolic targets or traffic to 
further sites of action. To validate this approach, the inventors have 
tested ubiquitin variants within a TT consisting of anthrax toxin 
lethal factor N-terminus (LFn) and Pseudomonas exotoxin A catalytic 
domain (PEIII). Here, they show that the intracellular release of the 
PEIII (catalytic moiety) is achievable and that ubiquitination of the 
TT controls the persistence of the TTs in the cytosol and thus controls 
the observed cytotoxicity.
    Potential Commercial Applications:
     Chimeric or fusion molecules for increasing the efficacy 
and cytotoxicity of targeted toxins and immunotoxins.
     Methods for cytosol delivery of targeted toxins to target 
cells.
    Competitive Advantages:
     Broadly applicable to all cytotoxic immunoconjugates.
     Increased stability and cytotoxicity of the TT without 
affecting the delivery or specificity of the treatment.
     Therapeutic access to the cytosol and/or trafficking to 
further sites of action such as the nucleus.
     Rapid cytosolic release of the catalytic moiety and 
degradation of the targeting moiety.
    Development Stage:
     Pre-clinical
     In vitro data available
    Inventors: Christopher Bachran (NIAID), Stephen Leppla (NIAID), 
Shi-hui Liu (NIAID), Thomas Morley
    Publications:
    1. Tcherniuk S, et al. Construction of tumor-specific toxins using 
ubiquitin fusion technique. Mol Ther. 2005 Feb;11(2):196-204. [PMID 
15668131]
    2. Wang F. Selective cytotoxicity to HER2-positive tumor cells by a 
recombinant e23sFv-TD-tBID protein containing a furin cleavage 
sequence. Clin Cancer Res. 2010 Apr 15;16(8):2284-2294. [PMID 20371697]
    3. Heisler I. A cleavable adapter to reduce nonspecific 
cytotoxicity of recombinant immunotoxins. Int J Cancer. 2003 Jan 
10;103(2):277-282. [PMID 12455044]
    Intellectual Property: HHS Reference No. E-150-2011/0--U.S. 
Provisional Application No. 61/473,450 filed 08 April 2011
    Related Technologies:
     HHS Reference No. E-293-1999--Mutated Anthrax Toxin 
Protective Antigen Proteins That Specifically Target Cells Containing 
High Amounts of Cell-Surface Metalloproteinases or Plasminogen 
Activator Receptors (Leppla/NIAID)
     HHS Reference No. E-070-2007--Human Cancer Therapy Using 
Engineered Metalloproteinase-Activated Anthrax Lethal Toxin That Target 
Tumor Vasculature (Leppla/NIAID)
     HHS Reference No. E-059-2004--Multimeric Protein Toxins to 
Target Cells Having Multiple Identifying Characteristics (Leppla/NIAID)
    Licensing Contact: Whitney Hastings; 301-451-7337; 
[email protected]

NOX5 Immunogenic Peptides and Monoclonal Antibodies for the Detection 
of Cancer and Inflammatory Responses

    Description of Technology: The membrane-associated NADPH oxidase 5 
(NOX5) protein is expressed in various fetal tissues, uterus, testis, 
spleen, lymph nodes and endothelial cells. In addition, the reactive 
oxygen species (ROS) generated by NOX5 have been shown to participate 
in signaling cascades regulating proliferation in several cancers and 
pre-cancerous conditions, such as hairy cell leukemia, melanoma, 
prostate cancer, and Barret's esophagus. Further, excess ROS produced 
by NOX5 has been associated with coronary artery disease, inflammation, 
and atherosclerosis.
    The present invention discloses the identification and 
characterization of a purified monoclonal antibody against NOX5 
protein. This NOX5 antibody can detect endogenous levels of NOX5 in 
human cells and could aid in studies and diagnostic tests of NOX5-based 
redox signaling involved in cancer, cell growth and differentiation, as 
well as angiogenic and inflammatory responses. In addition, the NOX5 
antibody may have therapeutic applications (e.g. anti-inflammatory, 
antiangiogenic, or antiproliferative activity) by interfering with NOX5 
activation at the cell surface.
    Potential Commercial Applications:
     Diagnostic for the detection of NOX5 in human cells and 
NOX5-based redox signaling
     Antibody can be used in ELISA, Western Blot, 
Immunofluorescence, Immunoprecipitation and Immunohistochemistry
     Tool to aid in the understanding of NOX5's functional 
significance in human physiology and pathophysiology
     Possible therapeutic for the treatment of various human 
diseases associated with NOX5 and/or ROS
    Competitive Advantages:
     Antibody is the only mouse monoclonal commercially 
available to the best of our knowledge
     Antibody is highly specific in recognizing the NOX5 
protein with greater efficiency and the accurate detection compared to 
other Nox5 antibodies
    Development Stage: Pre-clinical
    Inventors: James H. Doroshow, Krishnendu K. Roy, Smitha Antony 
(NCI)
    Publications:
    1. Kamiguti AS, et al. Expression and activity of NOX5 in the 
circulating malignant B cells of hairy cell leukemia. J Immunol. 2005 
Dec 15;175(12):8424-8430. [PMID: 16339585]
    2. Brar SS, et al. NOX5 NAD(P)H oxidase regulates growth and 
apoptosis in DU 145 prostate cancer cells. Am J Physiol Cell Physiol. 
2003 Aug;285(2):C353-C369. [PMID: 12686516]

[[Page 61716]]

    3. Hong J, et al. Bile acid reflux contributes to development of 
esophageal adenocarcinoma via activation of phosphatidylinositol-
specific phospholipase Cgamma2 and NADPH oxidase NOX5-S. Cancer Res. 
2010 Feb 1;70(3):1247-1255. [PMID: 20086178]
    Intellectual Property: HHS Reference No. E-149-2011/0--U.S. 
Provisional Application No. 61/471,596 filed 04 April 2011
    Licensing Contact: Whitney Hastings; 301-451-7337; 
[email protected]

mGluR5 Tumor Mouse Model

    Description of Technology: Glutamate receptor mGluR5 has been 
reported to function in the brain. There were no prior reports of it 
being involved in melanoma. The NIH investigators have discovered that 
when over expressed in transgenic animals, mGluR5 induces melanoma. The 
establishment of an mGluR5 tumor mouse model will provide a unique 
opportunity to help elucidate the mechanisms underlying tumor 
formation, and allow the study of aggressive melanoma in animals and a 
screen of potential therapeutics. Such an mGluR5 tumor mouse model is 
established at the National Institutes of Health and is available for 
licensing.
    Potential Commercial Applications:
     Drug screening for melanoma therapeutics
     Research Tool
    Competitive Advantage: Tumor mouse model only available from the 
NIH lab.
    Development Stage:
     Prototype
     Pre-clinical
     In vivo data available (animal)
    Inventors: Katherine W. Roche and Kyu Yeong Choi (NINDS)
    Publication: Choi KY, et al. Expression of the metabotropic 
glutamate receptor 5 (mGluR5) induces melanoma in transgenic mice. Proc 
Natl Acad Sci USA 2011; published ahead of print September 6, 2011, 
doi:10.1073/pnas.1107304108.
    Intellectual Property: HHS Reference No. E-123-2010/0--Research 
Tool. Patent protection is not being pursued for this technology.
    Licensing Contact: Betty Tong, Ph.D.; 301-594-6565; 
[email protected]

Monoclonal Antibodies to FCRL5 (CD307e/IRTA2/FcRH5) as Therapeutics and 
Diagnostics for B-cell Cancers

    Description of Technology: The Fc receptor-like (FCRL) genes (also 
known as CD307, IRTA, FcRH, IFGP or SPAP) encode cell membrane proteins 
that are believed to play roles in immunity and B cell differentiation. 
Some FCRL genes have been implicated in B cell lymphomas and multiple 
myelomas. Data suggest that the FCRL1-5 proteins are expressed 
differently on malignant B cells as well as subpopulations of normal B 
cells. Due to this differential expression, FCRL proteins represent 
potential targets for the treatment of cancers of a B cell origin.
    This technology relates to the development of novel monoclonal 
antibodies for a specific member of the FCRL protein family: FCRL5. 
FCRL5 is normally induced on mature B cells upon activation, but its 
expression is deregulated in multiple myeloma and Burkitt's lymphoma. 
Due to the correlation of FCRL5 overexpression and B cell malignancies, 
antibodies to FCRL5 may have value as a therapeutic or diagnostic tool. 
Specifically, the antibodies can be used as therapeutic agents by 
themselves or they can be attached to a cytotoxic agent such as 
Pseudomonas exotoxin A. Alternatively, the antibodies can be used to 
detect the deregulation of FCRL5 as a means of diagnosing B cell 
malignancies.
    Potential Commercial Applications:
     Detection or diagnosis of B cell cancers using monoclonal 
antibodies to FCRL5
     Treatment of B cell cancers using monoclonal antibodies to 
FCRL5 for inducing antibody-dependent cell death
     Treatment of B cell cancers using monoclonal antibodies to 
FCRL5 for targeting cytotoxic agents specifically to cancer cells 
(e.g., immunotoxins)
    Competitive Advantages:
     No cross-reactivity with other FCRL proteins demonstrates 
strong selectivity as both a therapeutic and diagnostic agent
     Targeted therapeutics such as monoclonal antibodies and 
immunotoxins decrease non-specific killing of healthy, essential cells, 
resulting in fewer side-effects and healthier patients
    Development Stage: Pre-clinical
    Inventors: Ira H. Pastan et al. (NCI)
    Publications:
    1. Ise T, et al. Elevation of soluble CD307 (IRTA2/FcRH5) protein 
in the blood and expression on malignant cells of patients with 
multiple myeloma, chronic lymphocytic leukemia, and mantle cell 
lymphoma. Leukemia. 2007 Jan; 21(1):169-174. [PMID 17051241]
    2. Ise T, et al. Immunoglobulin superfamily receptor translocation 
associated 2 protein on lymphoma cell lines and hairy cell leukemia 
cells detected by novel monoclonal antibodies. Clin Cancer Res. 2005 
Jan 1;11(1):87-96. [PMID 15671532]
    Intellectual Property: HHS Reference No. E-287-2004/1--U.S. Patent 
7,999,077 issued 16 Aug 2011
    Licensing Contact: David A. Lambertson, Ph.D.; 301-435-4632; 
[email protected]

Potent Inhibitory RNAs for Non-Surgical Treatment of Salivary Gland 
Cancers

    Description of Technology: In the U.S., approximately 40,000 cases 
of head and neck cancer, including salivary gland tumors, are diagnosed 
each year. Surgery with post-operative radiotherapy is the most common 
treatment for salivary gland tumors. However, complete removal is 
difficult due to the three-dimensional growth pattern of these tumors 
which impedes a surgeon's ability to determine once the tumor has been 
fully removed. Both surgeons and patients desire minimal surgical 
approaches for cosmetic reasons, as well as to preserve nerve function 
in the facial area. Thus a significant need exists for non-surgical 
approaches to treating salivary gland tumors.
    Researchers at the National Cancer Institute, NIH, have discovered 
that mucoepidermoid (MEC) salivary gland tumors arise from a 
chromosomal rearrangement which generates a fusion oncogene, Mect1-
Maml2, that functions to alter Notch and CREB signaling pathways. An 
RNAi vector has been developed that selectively suppresses the oncogene 
and inhibits growth of certain MEC tumor cell lines containing the 
oncogene by at least 90%. The RNAi vector has no effect on cells that 
do not express the oncogene. This ability of the RNAi vectors to block 
the ``gain-of-function'' activity of the acquired Mect1-Maml2 oncogene 
suggests new possibilities for the diagnosis and therapy of these 
cancers.
    Potential Commercial Applications:
     Diagnosis of MEC salivary gland tumors
     Treatment of MEC salivary gland tumors
    Competitive Advantages:
     Non-surgical
     Selective
     Potent
     Can be used in combination with other known treatments, 
such as radiation and chemotherapy
    Development Stage:
     Pre-clinical
     In vitro data available
    Inventors: Frederic Kaye (formerly NCI), Takefumi Komiya (NCI)
    Publications:
    1. Tonon G, et al. t(11;19)(q21;p13) translocation in 
mucoepidermoid carcinoma creates a novel fusion

[[Page 61717]]

product that disrupts a Notch signaling pathway. Nat Genet. 2003 
Feb;33(2):208-213. [PMID 12539049]
    2. Martins C, et al. A study of MECT1-MAML2 in mucoepidermoid 
carcinoma and Warthin's tumor of salivary glands. J Mol Diagn. 2004 
Aug;6(3):205-210. [PMID 15269296]
    3. Coxon A, et al. Mect1-Maml2 fusion oncogene linked to the 
aberrant activation of cyclic AMP/CREB regulated genes. Cancer Res. 
2005 Aug 15;65(16):7137-7144. [PMID 16103063]
    4. Komiya T, et al. Sustained expression of Mect1-Maml2 is 
essential for tumor cell growth in salivary gland cancers carrying the 
t(11;19) translocation. Oncogene. 2006 Oct 5;25(45):6128-6132. [PMID 
16652146]
    5. Kaye FJ. Emerging biology of malignant salivary gland tumors 
offers new insights into the classification and treatment of 
mucoepidermoid cancer. Clin Cancer Res. 2006 Jul 1;12(13):3878-3881. 
[PMID 16818681]
    6. Tirado Y, et al. CRTC1/MAML2 fusion transcript in high grade 
mucoepidermoid carcinomas of salivary and thyroid glands and Warthin's 
tumors: implications for histogenesis and biologic behavior. Genes 
Chromosomes Cancer. 2007 Jul;46(7):708-715. [PMID 17437281]
    7. Komiya T, et al. Enhanced activity of the CREB co-activator 
Crtc1 in LKB1 null lung cancer. Oncogene. 2010 Mar 18;29(11):1672-1680. 
[PMID 20010869]
    Intellectual Property: HHS, Reference No. E-086-2003/0 --
     U.S. Patent No. 7,553,822 issued 30 June 2009
     U.S. Patent Application No. 12/493,901 filed 29 June 2009
    Licensing Contact: Patrick McCue, Ph.D.; 301-435-5560; 
[email protected]

    Dated: September 29, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2011-25734 Filed 10-4-11; 8:45 am]
BILLING CODE 4140-01-P