[Federal Register Volume 72, Number 25 (Wednesday, February 7, 2007)]
[Notices]
[Pages 5726-5728]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-1931]


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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.

Extended Transgene Expression for a Non-Integrating Adenoviral Vector 
Containing Retroviral Elements

    Description of Technology: Anthrax lethal toxin (LeTx) consists of 
two components: The protective antigen (PrAg) and the lethal factor 
(LF). PrAg binds to the cell surface where it is activated by furin 
protease, followed by the formation of a PrAg heptamer. LF is then 
translocated into the cytosol of a cell via this heptamer, where it 
acts as a metalloprotease on all but one mitogen-activated protein 
kinase kinase (MAPKK). Approximately 70% of human melanomas contain a 
mutation (B-RAF V600E) that constitutively activates a MAPKK pathway, 
and LeTx has been shown to have significant toxicity towards cells 
which have this mutation. This suggested a potential use for LeTx in 
cancer therapy. Unfortunately, native LeTx is toxic to normal cells, 
detracting from its in vivo applicability.
    PrAg has been engineered to be activated by a matrix 
metalloprotease (MMP), instead of by furin protease. Because MMPs are 
highly expressed in tumor cells, this modification increases 
selectivity towards cancer cells. Surprisingly, mouse data shows that 
the modified LeTx (denoted PrAg-L1/LF) is less cytotoxic to ``normal'' 
cells in vivo, when compared to wild-type LeTx. Significantly, PrAg-L1/
LF maintained its high toxicity toward human tumors in mouse xenograft 
models of human tumors, including melanomas. However, this toxicity 
applied not only to tumors having mutations that constitutively 
activate MAPKKs, but also to other tumor types such as lung and colon 
carcinomas. The absence of toxicity to ``normal'' cells coupled to its 
effectiveness on a wide range of cancer

[[Page 5727]]

cell types suggests that PrAg-L1/LF may represent a novel cancer 
therapeutic.
    Applications: PrAg-L1/LF has applications as a human cancer 
therapeutic; Applicability extends beyond melanomas, including lung and 
colon carcinomas.
    Market: The worldwide market for melanoma therapeutics is 
approximately $437M, and is predicted to reach $680M by the year 2009. 
Approximately 2.4 million people are afflicted with melanoma, with 
around 150,000 new cases each year. Demonstration of effectiveness in 
vivo for lung and colon carcinomas will increase the market for this 
technology.
    Development Status: The technology is at the preclinical stage.
    Inventors: Stephen H. Leppla (NIAID), Shi-hui Liu (NIAID), Thomas 
H. Bugge (NIDCR), John R. Basile (NIDCR), Brooke Currie (NIDCR).
    Related Publications:
    1. S Liu et al. Intermolecular complementation achieves high-
specificity tumor targeting by anthrax toxin. Nat Biotechnol. 2005 
Jun;23(6):725-730.
    2. RJ Abi-Habib et al. A urokinase-activated recombinant anthrax 
toxin is selectively cytotoxic to many human tumor cell types. Mol 
Cancer Ther. 2006 Oct;5(10):2556-2562.
    Patent Status: U.S. Provisional Application No. 60/870,050 filed 14 
Dec 2006 (HHS Reference E-070-2007/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: David A. Lambertson, Ph.D.; 301/435-4632; 
[email protected].
    Collaborative Research Opportunity: The NIAID Laboratory of 
Bacterial Diseases is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize PrAg-L1/LF as a novel cancer therapeutic. 
Please contact Stephen H. Leppla, Ph.D. at 301/594-2865 and/or 
[email protected] for more information.

A Novel Combination of CXCR-4 Antagonist T22 With Conventional 
Immunotherapy Improves Treatment Efficacy in Established Tumors

    Description of Technology: Immunotherapy for cancer rarely results 
in complete responses, possibly due to chemokine receptor mediated 
activation of prosurvival pathways in cancer cells. CXCR4, is one such 
receptor that is expressed in a variety of cancers, including melanoma. 
Inhibiting these chemokine receptors may circumvent the ability of 
cancer to protect themselves from immunological attack.
    This invention provides a method of treating cancers that expresses 
the chemokine receptor CXCR4 by a novel combination therapeutic 
approach. More specifically, the invention claims methods and 
compositions for the improved treatment of metastatic tumors by using a 
CXCR4 antagonist in conjunction with conventional monoclonal antibody 
based immunotherapy (e.g., anti-CTLA4 mAb) or immunostimulatory 
chemotherapeutics (e.g., cyclophosphamide). The invention clearly 
demonstrates that treatment of in vivo experimental lung cancer models 
with T22, a CXCR4 antagonist, followed by anti-Cytotoxic lymphocyte 
antigen (CTLA)-4 monoclonal antibody (or cyclophosphamide) treatment 
synergistically reduced the total tumor burden compared with the 
reduction of tumor burden when either agent is used alone. T22 
treatment alone is not cytotoxic and has no demonstrated ability to 
increase non-specific host autoimmunity when used in combination with 
anti-CTLA4 mAb or cyclophosphamide. This invention has significant 
potential as a new, effective combination immunotherapy.
    Applications and Modality: (1) A new method of combination therapy 
for cancer based on immunotherapeutics, including adoptive transfer of 
anti-tumor lymphocytes and treatment with immunostimulatory agents 
(monoclonal antibodies or chemotherapy); (2) A new therapeutic method 
for the treatment of CXCR4 chemokine receptor expressing cancers; (3) A 
new therapeutic method exploiting the role of chemokine receptor CXCR4 
that potentially renders immunotherapy more effective without further 
increasing risks of patient autoimmunity.
    Market: Chemokine receptor CXCR4 has a proven role in cancer 
metastasis in several cancers. The anti-cancer market is projected to 
reach sales of $60 billion by 2010.
    Development Status: The technology is currently in the pre-clinical 
stage of development. Animal data is available.
    Inventor: Sam T. Hwang (NCI).
    Publications:
    1. CH Lee et al. Sensitization of B16 tumor cells with a CXCR4 
antagonist increases the efficacy of immunotherapy for established lung 
metastases. Mol Cancer Ther. 2006 Oct;5(10):2592-2599.
    2. T Kakinuma and ST Hwang. Chemokines, chemokine receptors, and 
cancer metastasis. J Leukoc Biol. 2006 Apr;79(4): 639-651.
    3. T Murakami et al. Expression of CXC chemokine receptor-4 
enhances the pulmonary metastatic potential of murine B16 melanoma 
cells. Cancer Res. 2002 Dec 15;62(24):7328-7334.
    Patent Status: U.S. Provisional Application No. 60/840,216 filed 25 
Aug 2006, entitled ``Combination Therapy for the Treatment of Cancer'' 
(HHS Reference No. E-267-2006/0-US-01).
    Licensing Status: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: John Stansberry, Ph.D.; 301/435-5236; 
[email protected].

Lentivirus Based Vector System for Gene Therapy Delivery

    Description of Technology: Gene therapy is a technique based on the 
idea that a genetic disorder can be treated by replacing a 
dysfunctional gene with a functional copy of that gene. Currently, 
retroviral vectors and adenoviral vectors are most frequently used for 
gene therapy clinical trials. Retroviral vectors provide long term gene 
expression and are capable of transferring genes into non-dividing 
cells, unlike their adenoviral counterparts. However, retroviral 
vectors often suffer from weak viral titers and inefficient 
encapsidation of the therapeutic gene, detracting from their 
therapeutic value. Thus, there is a need in the art for improved 
retroviral gene therapy vectors.
    This technology family is directed to a retroviral vector system 
comprising a packaging vector and a transfer vector, and a method of 
using the vectors for gene therapy. The packaging vector is the result 
of an HIV-2 lentiviral vector containing mutations in sequences 
surrounding a splice donor site within the packaging signal. The 
transfer vector comprises mutations that render a splice donor site 
non-functional. These mutations increase the viral titer and 
expression/encapsidation of the transgene, but without a corresponding 
increase in the packaging of viral RNA. Thus, these vectors may address 
some of the pressing concerns with current gene therapy vectors 
systems.
    Applications: Improved lentivirus based vector system with 
practical application in gene therapy/gene transfer; Two vector system 
minimizes possibility of HIV infection; Packaging vector is a result of 
HIV-2 Lentivirus vector; Improved packaging and expression ability 
addresses current low viral titer problem.
    Market: The only gene therapy product currently in the market was 
approved in China in 2004; The R&D market of gene therapy is projected 
to grow to several billion dollars in the next 5 years.

[[Page 5728]]

    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Suresh K. Arya (NCI).
    Publication: SK Arya et al. Human immunodeficiency virus type 2 
lentivirus vectors for gene transfer: expression and potential for 
helper virus-free packaging. Hum Gene Ther. 1998 Jun 10;9(9):1371-1380.
    Patent Status: U.S. Patent No. 6,790,657 issued 14 Sep 2004, 
entitled ``Lentivirus Vector System'' (HHS Reference No. E-231-1998/0-
US-03); U.S. Patent Application No. 10/731,988 filed 09 Dec 2003, now 
allowed, entitled ``Lentivirus Vector System'' (HHS Reference No. E-
231-1998/0-US-04).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: David Lambertson, Ph.D.; 301/435-4632; 
[email protected].

Methods and Compositions of Chemokine-Tumor Antigen Fusion Proteins as 
Cancer Vaccines

    Description of Technology: Tumor cells are known to express tumor 
specific antigens on the cell surface. These antigens are believed to 
be poorly immunogenic, largely because they represent gene products of 
oncogenes or other cellular genes which are normally present in the 
host. As a result, poor immunogenicity of relevant cancer antigens has 
proven to be a major obstacle to successful immunotherapy with tumor 
vaccines. Thus, there is a need for a more potent vaccine to elicit an 
immune response effective in the treatment or prevention of cancer.
    The current invention embodies a fusion protein comprising of a 
chemokine and tumor antigen. The inventors reported in several peer-
reviewed manuscripts that these fusion proteins represent potential 
vaccines for use against cancer. More specifically, the inventors have 
developed a vaccine construct that expresses fusion protein comprising 
human monocyte chemotactic protein-3 fused with tumor antigens, such as 
lymphoma-derived Id or breast cancer Muc-1. Administration of the 
fusion protein, or a nucleic acid encoding the fusion protein, elicits 
a specific immune response directed against the tumor antigen or 
protein, thereby inhibiting the growth of cells expressing this antigen 
or protein.
    Applications and Modality: Potential immunotherapy for cancer.
    Market: 600,000 deaths from cancer related diseases estimated in 
2006.
    Development Status: This technology is currently in the pre-
clinical stage of development.
    Inventors: Larry Kwak (NCI) and Arya Biragyn (NIA).
    Patent Status: U.S. Patent No. 6,562,347 issued 13 May 2003 (HHS 
Reference No. E-107-1998-0-US-03).
    Licensing Status: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: Jennifer Wong; 301/435-4633; 
[email protected].

    Dated: January 31, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E7-1931 Filed 2-6-07; 8:45 am]
BILLING CODE 4140-01-P