[Federal Register Volume 73, Number 160 (Monday, August 18, 2008)]
[Notices]
[Pages 48215-48216]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-18982]


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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.

Extracellular Matrix Gene Chips To Detect Metastatic Tumors

    Description of Technology: Cancer mortality is primarily associated 
with metastatic disease and not the primary tumor. Recent evidence 
suggests that metastatic disease can be an early event and in the 
majority of patients metastasis starts by the time the disease is 
diagnosed. Currently however, approximately one third of patients 
without evidence of tumor dissemination at the time of surgical 
resection of the primary tumor subsequently develop distant metastases 
after the tumor is removed. Therefore there is a need for methods of 
characterizing the early metastatic process for better treatment of 
cancer.
    This invention provides arrays which can be used for detecting the 
metastatic capacity of a tumor. In particular, these gene chips or 
microarrays detect the over-expression of the cancer-related 
extracellular matrix (ECM) modifier proteins Anakin and Bromodomain 4 
(Brd4). It has been shown that ECM gene dysregulation is predictive of 
metastasis in breast cancer and recently Brd4 and Anakin have been 
identified as metastasis modifiers.
    Using the signature profiles of Anakin and Brd4, the inventors have 
demonstrated that these genes predict survival outcome in affymetrix 
and glass slide based microarray experiments. As a result, screening 
for Brd4 and/or Anakin status in tumors could be an important 
prognostic test and may enable physicians to better stratify patients 
based on risk of recurrence and progression to metastatic disease.
    Applications:
     Detecting metastatic disease in patients diagnosed with 
cancer.
     Method of characterizing a tumor or cancer by detecting 
the expression levels of Anakin or Brd4.
     Diagnostic tool to aid clinicians in determining 
appropriate cancer treatment.
    Market:
     Approximately 1,437,180 new cancer cases are expected to 
be diagnosed in 2008.
     Almost 565,650 people in the U.S. are expected to die of 
cancer. This is more than 1,500 people a day.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Kent Hunter and Nigel Crawford (NCI).
    Patent Status: U.S. Provisional Application No. 60/970,400 filed 06 
Sep 2007 (HHS Reference No. E-093-2007/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Whitney A. Hastings; 301-451-7337; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
Metastasis Susceptibility Section of the Laboratory of Cancer Biology 
and Genetics is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize Brd4 and/or RRP1B (Anakin) prognostic tests. 
Please contact John D. Hewes, Ph.D. at 301-435-3121 or 
[email protected] for more information.

NUP98-HOXD13 Transgenic Mice

    Description of Technology: Myelodysplastic syndrome (MDS) is 
collection of closely related blood diseases that arise in the bone 
marrow characterized by anemia, neutropenia, and thrombocytopenia 
resulting from hematopoietic stem cell disorders. A variety of genetic 
aberrations have been associated with MDS, including chromosomal 
translocations of the NUP98 gene. The only current curative therapy for 
MDS is allogeneic bone marrow transplant. Without bone marrow 
transplant, patients either die of progressive pancytopenia or 
following transformation of MDS to acute myeloid leukemia. Progress in 
understanding and treating MDS has been hampered by a lack of an animal 
model that accurately recapitulates all of the features of human MDS. 
Utilizing a NUP98-HOXD13 (hereafter NHD13) fusion gene, a mouse model 
was developed to elucidate the biology of MDS. Genetically engineered 
mice that express an NHD13 transgene display all of the phenotypic 
features of MDS including peripheral blood cytopenia, bone marrow 
dysplasia, and transformation to acute leukemia. These mice provide an 
accurate preclinical model for MDS.
    Applications: Model to study MDS and evaluate MDS therapy.
    Market: 15,000-20,000 new cases of MDS are diagnosed in the U.S.; 
80-90% of patients are older than 60 years old.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Peter D. Aplan et al. (NCI).
    Publications:
    1. YW Lin et al. Notch1 mutations are important for leukemic 
transformation in murine models of precursor-T leukemia/lymphoma. 
Blood. 2006 Mar 15;107(6):2540-2543.

[[Page 48216]]

    2. YW Lin et al., NUP98-HOXD13 transgenic mice develop a highly 
penetrant, severe myelodysplastic syndrome that progresses to acute 
leukemia. Blood. 2005 Jul 1;106(1):287-295.
    Patent Status: HHS Reference No. E-071-2007/0--Research Tool.
    Licensing Status: Available for non-exclusive licensing.
    Licensing Contact: Jennifer Wong; 301-435-4633; 
[email protected].
    Collaborative Research Opportunity: The Leukemia Biology Section, 
Genetics Branch, National Cancer Institute is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize the NHD13 mouse 
model. Please contact John D. Hewes, Ph.D. at 301-435-3121 or 
[email protected] for more information.

Conjugates of Ligand, Linker, and Cytotoxic Agent and Related 
Compositions and Methods of Use

    Description of Technology: Systemic toxicity of drugs is one of the 
most serious problems in cancer chemotherapy and frequently is dose 
limiting. Specific delivery of cytotoxic drugs to cancer cells remains 
among the most intractable problems of cancer therapy. Targeted 
delivery of anti-proliferation drugs through the cell surface receptors 
that are over expressed on cancer cells can reduce systemic toxicity 
and increase effectiveness of a treatment.
    The present invention describes cytotoxic compounds with an 
intracellular target that can selectively enter tumor cells through 
specific receptors on the cell surface. The invention also describes a 
conjugate comprising a cytotoxic agent, a linker arm and a ligand 
capable of delivering a cytotoxic agent in a cell specific manner. Such 
conjugates of a cytotoxic agent and a ligand (delivery moiety) have 
increased selectivity for tumor cells. The toxic moiety and the ligand 
are joined by a linker arm that is stable in circulation, but is easily 
cleaved in lysosomes upon internalization of the conjugate. A panel of 
compounds comprised of a variety of cytotoxic warheads, against various 
intracellular targets linked to an assortment of ligands, has been 
developed and tested in a model system. Ligand moieties of these 
conjugates are capable of specific delivery of cytotoxic agents to 
receptors that are frequently over expressed in gastric, colon, lung, 
breast, ovarian and pancreatic tumors. These compounds have the 
potential to be highly effective anti-tumor agents with considerably 
little negative effect. This disclosed technology could provide new and 
exciting methodologies to treat cancer.
    Applications: Anti-tumor agent for gastric, colon, lung, breast, 
ovarian and pancreatic tumors.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Nadya I. Tarasova et al. (NCI).
    Patent Status: U.S. Patent Application No. 10/505,239 filed 19 Aug 
2004, claiming priority to 27 Feb 2002 (HHS Reference No. E-057-2002/2-
US-02).
    Licensing Contact: Adaku Nwachukwu, J.D.; 301/435-5560; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
Structural Biophysics Laboratory is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize Conjugates of Ligand, Linker, and 
Cytotoxic Agent and Related Compositions and Methods of Use. Please 
contact John D. Hewes, Ph.D. at 301-435-3121 or [email protected] for 
more information.

SH2 Domain Binding Inhibitors

    Description of Technology: Signal transduction processes underlie 
the transfer of extracellular information to the interior of the cell 
and ultimately to the nucleus. A variety of signal transduction 
processes are critical for normal cellular homeostasis, with protein-
tyrosine kinases (PTKs) playing central roles in many of these 
pathways. Examples of such PTKs include the PDGF receptor, the FGF 
receptor, the HGF receptor, members of the EGF receptor family, such as 
the EGF receptor, erb-B2, erb-B3 and erb-B4, the src kinase family, Fak 
kinase and the Jak kinase family. Protein-tyrosine phosphorylation that 
results from the action of PTKs can modulate the activity of certain 
target enzymes as well as facilitate the formation of specific multi-
protein signaling complexes through the actions of homologous protein 
modules termed Src homology 2 (SH2) domains, which recognize specific 
phosphotyrosyl containing sequences. A malfunction in this system 
through tyrosine kinase overexpression and/or deregulation can be 
manifested by various oncogenic and hyperproliferative disorders, 
including cancers, inflammation, autoimmune disease, hyperproliferative 
skin disorders, psoriasis and allergy/asthma, etc. The disclosed 
compounds, e.g. peptides, preferably, macrocyclic peptides, are Grb2 
SH2 domain signaling antagonists with enhanced binding affinity. The 
claims of the current application are directed to compositions of 
matter and methods of use which provide for the diagnosis, testing and 
treatment of the aforementioned disease states.
    Applications: For treatment of cancer, inflammation, autoimmune 
diseases, hyperproliferative skin disorders, psoriasis and asthma.
    Development Status: The technology is currently in an early pre-
clinical stage of development.
    Inventors: Terrence R. Burke, Jr., et al. (NCI).
    Patent Status:
     U.S. Patent No. 6,977,241 issued 20 Dec 2005 (HHS 
Reference No. E-262-2000/0-US-03).
     U.S. Patent Application No. 10/517,717 filed 17 Mar 2005, 
allowed (HHS Reference No. E-262-2000/1-US-03).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Adaku Nwachukwu, J.D.; 301-435-5560; 
[email protected].

    Dated: August 7, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E8-18982 Filed 8-19-08; 8:45 am]
BILLING CODE 4140-01-P