[Federal Register Volume 74, Number 96 (Wednesday, May 20, 2009)]
[Notices]
[Pages 23727-23729]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-11706]


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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.

A549 Cells: A Well-Characterized Lung Carcinoma Cell Line Utilized for 
a Variety of Scientific Studies, Including Adenovirus Production and 
Testing

    Description of Technology: Scientists at the National Institutes of 
Health have developed a cell line designated A549 that was derived from 
explanted cultures of human lung cancer tissue. The A549 cell line has 
been tested under the guidance of the United States Food and Drug 
Administration (FDA) so, under current Good Manufacturing Practices 
(GMP), these cells may be suitable for use in manufacturing constructs 
for use in clinical trials. The A549 cell line has also been found to 
be suitable for adenovirus production, most notably replicating 
adenovirus constructs that do not require complementation by the viral 
oncogene, early region 1A (E1A), which is responsible for viral gene 
transcription. This cell line is further utilized as a negative control 
in assays to measure the replication of adenoviruses that lack E1A and 
as a target cell line to detect replication competent adenoviruses 
(RCA). A549 cells have been well characterized through their use in a 
wide variety of molecular studies, such as anti-tumor drug permeability 
and

[[Page 23728]]

efficacy analysis, infection assays, respiratory immunotoxicity tests, 
cell senescence studies, and cytokine expression profiling. These cells 
can also be utilized to study a variety of molecular characteristics 
for human tumors in culture.
    Application:
     Cell bank tested under cGMP-compliance regulations and 
used to produce adenoviruses for use in clinical trials.
     Research tool to analyze the efficacy of potential anti-
cancer agents to devise better cancer treatments for malignancies, such 
as non-small cell lung cancer (NSCLC).
     Research tool to study the infectivity of viruses that 
cause asthma in order to develop better asthma treatments.
     Standard research tool to analyze a variety of molecular 
biology procedures, for example, cell senescence, cytokine induction, 
protein expression, apoptosis, and receptor-ligand interactions.
    Advantages:
     A549 cells are a well-characterized standard among the 
human lung carcinoma/alveolar cell lines used in molecular biology.
     The A549 cells stored at the NIH were tested under the 
guidance of the FDA's cGMP regulations.
     The A549 cells stored at the NIH may be suitable for 
producing adenoviruses that can be used in clinical trials and 
analyzing adenoviral-based therapies and vaccine strategies.
    Inventors: Wade P. Parks, Donald J. Giard, and Stuart Aaronson (all 
formerly NCI).
    Publication: DJ Giard et al. In vitro cultivation of human tumors: 
Establishment of cell lines derived from a series of solid tumors. J 
Natl Cancer Inst. 1973 Nov; 51(5):1417-1423.
    Patent Status: HHS Reference No. E-129-2009/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for licensing under a Biological 
Materials License Agreement.
    Licensing Contact: Samuel E. Bish, PhD; 301-435-5282; 
[email protected].

Mobilizing the Body to Fight Cancer: T Cell Receptors Specific for the 
Tumor Antigen Survivin

    Description of Technology: A major drawback of current 
chemotherapy-based cancer treatments is the harsh side-effects 
associated with many cancer drugs. Thus, there is an urgent need to 
develop new therapeutic strategies combining fewer side-effects and 
more specific anti-tumor activity. Immunotherapy is a promising new 
cancer therapeutic approach that directs an individual's innate and 
adaptive immune system to fight against specific diseases, including 
cancer.
    T cell receptors (TCRs) are proteins that recognize antigens in the 
context of infected or transformed cells and activate T cells to 
mediate an immune response and destroy abnormal cells. TCRs consist of 
two domains, one variable domain that recognizes the antigen and one 
constant region that helps the TCR anchor to the membrane and transmit 
recognition signals by interacting with other proteins.
    Scientists at the National Institutes of Health (NIH) have 
developed genetically modified T cells, which possess TCRs that 
specifically recognize human survivin, a tumor antigen expressed in 
many adult and pediatric cancers that is absent from most normal 
tissues. Non-human T cells that recognized human survivin peptides with 
high affinity in the context of human leukocyte antigen (HLA) alleles 
were identified. Then, using recombinant DNA technology, the survivin-
specific TCRs from the non-human T cells were fused to human TCR 
backbones and expressed in human T cells. The resulting survivin-
specific human T cells could prove to be powerful new immunotherapeutic 
tools for attacking survivin-expressing tumors after infusion into 
patients.
    Applications:
     Immunotherapeutics to treat and/or prevent the 
reoccurrence of a variety of human cancers that overexpress human 
survivin by inserting survivin-specific TCR sequences into patient T 
cells
     A drug component of a combination immunotherapy regimen 
aimed at targeting the specific tumor-associated antigens expressed by 
cancer cells within individual patients.
    Advantages:
     Survivin is overexpressed in virtually all cancers, 
including lung, colon, breast, pancreatic, stomach, liver, ovarian and 
prostate cancer, as well as in melanoma and hematopoietic malignancies, 
but this antigen is not expressed on normal cells. Thus, survivin is an 
ideal antigen for targeted treatment. Anti-survivin TCR immunotherapy 
could treat a host of cancer types while reducing the side-effects of 
treatment.
     The survivin-specific TCR sequences can be derived in non-
human species in the context of a wide variety of HLA molecules and, 
thus, TCRs specific for each patient's HLA profile can be generated 
rapidly.
     The survivin-specific T cells should not be rejected by a 
patient's immune system since the survivin-specific TCR sequences are 
fused to a human TCR backbone.
    Development Status: This technology is in the pre-clinical stage of 
development. The inventors plan to initiate a clinical trial in the 
next 6-12 months.
    Market: Cancer continues to be a medical and financial burden on 
U.S. public health. According to U.S. estimates, cancer is the second 
leading cause of death with over 565,000 deaths reported in 2008 and 
almost 1.5 million new cases were reported (excluding some skin 
cancers) in 2008. In 2007, the NIH estimated that the overall cost of 
cancer was $219.2 billion dollars and $89 billion went to direct 
medical costs. Despite our increasing knowledge of oncology and cancer 
treatment methods, the fight against cancer will continue to benefit 
from the development of new therapeutics aimed at treating individual 
patients.
    Inventors: Crystal L. Mackall et al. (NCI).
    Publications:
    1. Manuscript in preparation.
    2. CJ Cohen et al. Recognition of fresh human tumor by human 
peripheral blood lymphocytes transduced with a bicistronic retroviral 
vector encoding a murine anti-p53 TCR. J Immunol. 2005 Nov 
1;175(9):5799-5808. (Erratum in: J Immunol. 2006 Oct 15;177(8):5746.)
    3. RA Morgan et al. Cancer regression in patients after transfer of 
genetically engineered lymphocytes. Science 2006 Oct 6;314(5796):126-
129.
    Patent Status: U.S. Provisional Application No. 61/140,338 filed 23 
Dec 2008 (HHS Reference No. E-325-2008/0-US-01)
    Licensing Status: Available for licensing.
    Licensing Contact: Samuel E. Bish, PhD; 301-435-5282; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
Pediatric Oncology Branch is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize genetically engineered lymphocytes 
with specificity for human survivin. Please contact John D. Hewes, PhD 
at 301-435-3121 or [email protected] for more information.

Fused Azepinone Cyclin Dependent Kinase Inhibitors

    Description of Technology: The invention describes a class of 
cyclin dependent kinase (CDK) inhibitors that have anti-proliferative 
activity in human tumor cell lines. CDKs are important in

[[Page 23729]]

the control of the cell cycle and alterations in CDK expression, 
function, or regulation and are associated with diseases characterized 
by cellular proliferation. Increasing CDK activity has been reported in 
many cancers. Likewise, the loss of inhibitory activity has been 
observed in a wide variety of primary human tumors and human tumor-
derived cell lines, including lung, breast, brain, bone, skin, bladder, 
kidney, ovary, liver, colon, and pancreas as well as in leukemia. These 
compounds have also been found to potently inhibit GSK3beta activity 
which has recently been linked to a variety of cellular processes and 
several disparate areas of biology. In particular, GSK3beta activity 
has been strongly implicated in Alzheimer's as well as cardiac failure. 
Thus, the compounds of this invention offer unique opportunities for a 
variety of indications.
    Applications: CDK/GSK3beta inhibitor therapeutics for the treatment 
of several indications including various cancers, neurodegenerative 
diseases, and cardiac conditions.
    Development: Pre-clinical stage of development.
    Inventors: Daniel W. Zaharevitz et al. (NCI).
    Publication: DW Zaharevitz et al. Discovery and initial 
characterization of the paullones, a novel class of small-molecule 
inhibitors of cyclin-dependent kinases. Cancer Res. 1999 Jun 
1;59(11):2566-2569.
    Patent Status: HHS Reference No. E-025-1998/0--
     U.S. Patent No. 6,610,684, issued August 26, 2003;
     Australian Patent Nos. 780528 and 778735, issued March 24, 
2005 and December 16, 2004;
     Canada Patent Application No. 2335115, filed June 16, 
1999;
     Japanese Patent Application No. 2000-554735, filed June 
16, 1999;
     United Kingdom Patent No. 1086105, validated March 01, 
2006 ((E-025-1998/0-GB-09);
     French Patent No. 1086105, validated March 01, 2006 (E-
025-1998/0-FR-10); and
     German Patent No. 69930120.3, validated March 16, 2006 (E-
025-1998/0-DE-11).
    Licensing Status: Available for licensing.
    Licensing Contact: Whitney A. Hastings; 301-451-7337; 
[email protected].

    Dated: May 13, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E9-11706 Filed 5-19-09; 8:45 am]
BILLING CODE 4140-01-P