[Federal Register Volume 72, Number 129 (Friday, July 6, 2007)]
[Notices]
[Pages 37029-37030]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-13128]


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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.

Potential Serum Bio-Markers for Alpha-Fetoprotein (AFP) Negative 
Hepatocellular Carcinoma

    Description of Technology: This technology relates to improved 
methods of detecting hepatocellular carcinoma (HCC) by using new 
biomarkers. The overexpression of Gpc3, Mdk, SerpinI1, PEG-10 and QP-C 
correlates with the presence of HCC, even in small tumors. By comparing 
the expression levels of at least three of these markers in subject 
samples with their expression levels in control samples, the presence 
of HCC can be diagnosed. The method can also be used to monitor the 
progression, and regression of HCC.
    HCC is a common and aggressive cancer with a high mortality rate. 
The high mortality rate stems from an inability to diagnose the cancer 
at an early stage in patients, due to the lack of available biomarkers 
for HCC. Currently, HCC is diagnosed by measuring the levels of serum 
alpha-fetoprotein (AFP); however, AFP is not always present in HCC 
tumors, especially small tumors.
    Applications: Protein markers useful for screening HCC more 
accurately and with increased sensitivity; The proteins can also serve 
as prognostic and therapeutic response biomarkers.
    Advantages: Highly sensitive, secretory markers that can be easily 
identified in patient serum; Markers can identify HCC in patients with 
small tumors that would previously go undetected.
    Benefits: HCC affects 20,000 people in U.S. or over half a million 
worldwide every year and 90% of them die of the disease. Improving the 
quality of life and duration of life for people suffering from this 
disease will depend a lot on early detection of the disease and this 
technology can contribute significantly to that social cause. 
Furthermore, the cancer diagnostic market is estimated to grow to 
almost $10 billion dollars in the next 5 years.
    Inventors: Xin Wei Wang (NCI) et al.
    U.S. Patent Status: Pending PCT Application PCT/US2006/042591, 
published as WO 2007/053659 (HHS Reference No. E-333-2005/0-PCT-02).
    Licensing Contact: David A. Lambertson, PhD; Phone: (301) 435-4632; 
Fax: (301) 402-0220; E-mail: [email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Laboratory of Human Carcinogenesis, is seeking statements of capability 
or interest from parties interested in collaborative research to 
further develop, evaluate, or commercialize new biomarkers for 
hepatocellular carcinoma (HCC). Please contact John D. Hewes, PhD at 
301-435-3121 or [email protected] for more information.

[[Page 37030]]

Modification of Recombinant Anti-Tumor RNase (rapLR1) for Optimal Use 
in the Large Scale Manufacture of Stable and Potent RapLR1-Antibody 
Conjugates

    Description of Technology: This technology involves modified rapLR1 
molecules having an improved capacity for conjugation to targeting 
moieties. Previously, techniques for attaching wild-type rapLR1 to a 
targeting moiety required an excess of RNase, leading to high 
production costs. The inventors have now mutated specific amino acids 
in rapLR1 to allow a more efficient (and therefore less costly) 
conjugation reaction.
    Members of the ribonuclease A (RNase A) superfamily, such as 
rapLR1, have the ability to efficiently kill a wide range of cancer 
cells. Ligand binding moieties such as antibodies or peptides can be 
used to target RNases to a particular cell or cell type that expresses 
a marker, e.g., a marker that is associated with cancer. The current 
invention provides rapLR1 molecules that have been genetically modified 
to contain a cysteine at a specific location that does not interfere 
with the enzymatic activity of the molecule. The inserted cysteine 
provides the advantage of a site-directed and specific attachment of 
rapLR1 to targeting moieties, which results in more efficient 
production of the therapeutic. This significantly reduces the cost of 
bringing rapLR1-related cancer therapeutics to market.
    Applications: Targeted anti-cancer therapy molecules; Targeting 
moiety can be interchanged based on target cancer cells; Targeting any 
disease in which the cell is transformed and presents unique levels of 
cell surface markers.
    Advantages: RapLR1 delivery, specificity and toxicity to cancer 
cells is increased by conjugation to a targeting moiety; Modified 
rapLR1 increases conjugation efficiency, making the preparation of the 
anti-cancer agents more cost effective without sacrificing specificity.
    Benefits: Cancer is the second leading cause of death in the United 
States, with approximately 600,000 cancer-related deaths occurring in 
2006 alone. Because rapLR1 can be used to treat a number of different 
cancers (depending on the targeting moiety), there is a powerful social 
benefit from this technology: Improving the duration and quality of 
life of a wide range of cancer patients. Furthermore, the cancer 
therapeutic market is expected to reach $27 billion by 2009. Because 
rapLR1 can now be efficiently conjugated to targeting moieties, there 
is an opportunity to occupy a significant niche in that predicted 
market, with lower cost to the licensee.
    Inventors: Dianne L. Newton et al. (NCI).
    U.S. Patent Status: Pending PCT Application PCT/US2006/038180, 
published as WO 2007/041361 (HHS Reference No. E-265-2005/0-PCT-02).
    Licensing Contact: David A. Lambertson, PhD; Phone: (301) 435-4632; 
Fax: (301) 402-0220; E-mail: [email protected].

Methods for Expression and Purification of Immunotoxins

    Description of Technology: The invention concerns immunotoxins and 
methods of making the immunotoxins. Targeting of the immunotoxins 
occurs via an antibody that is specific to T cells. This allows the 
specific ablation of malignant T cells and resting T cells. The 
transient ablation of resting T cells can ``reset'' the immune system 
by accentuating tolerizing responses. As a result, the immunotoxin can 
be used to treat autoimmune disease, malignant T cell-related cancers, 
and graft-versus-host disease. The toxin portion of the immunotoxin is 
engineered to maintain bioactivity when produced in yeast, specifically 
Pichia pastoris. This system allows the production of dimeric antibody 
fragments with increased binding affinity and potency.
    Applications: Immunotoxins produced by this method can be used for 
the treatment of autoimmune diseases such as multiple sclerosis, lupus, 
type I diabetes, aplastic anemia; Immunotoxins produced by this method 
can be used for treatment of T-cell leukemias and lymphomas such as 
cutaneous T cell leukemia/lymphoma (CTCL); Immunotoxins produced by 
this method can be used for increasing immune tolerance in patients 
requiring transplants/grafts.
    Advantages: Method produces GMP quality immunotoxin and can be 
scaled up to industry scales; Modified toxin moiety has reduced 
glycosylation in this system, resulting in a more effective and 
efficient immunotoxin; Immunotoxin doesn't produce the deleterious 
side-effects seen with other methods of treating autoimmune disease, 
malignant T cell leukemia/lymphoma and graft-versus-host disease.
    Benefits: New methods and compositions with limited side-effects 
have the potential to revolutionize treatment of autoimmune disease; 
provides an opportunity to capture a significant market share for the 
millions of people who suffer from an autoimmune disease.
    Inventors: David Neville et al. (NIMH)
    Patent Status: U.S. Patent Application No. 10/566,886 filed 01 Feb 
2006, which published as U.S. 2006/0216782 on 28 Sep 2006 (HHS 
Reference No. E-043-1997/2-US-03); U.S. Patent No. 6,632,928 issued 14 
Oct 2003 (HHS Reference No. E-044-1997/0-US-07); U.S. Patent 
Application No. 10/435,567 filed 09 May 2003, which published as 2003/
0185825 on 02 Oct 2003 (HHS Reference No. E-044-1997/0-US-08); U.S. 
Patent Application No. 10/296,085 filed 18 Nov 2002, which published as 
2004/0127682 on 01 Jul 2004 (HHS Reference No. E-044-1997/1-US-06); 
Foreign rights are also available.
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: David A. Lambertson, PhD; 301/435-4632; 
[email protected]. 
    Collaborative Research Opportunity: The National Institute of 
Mental Health, Laboratory of Molecular Biology, is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize methods of 
expression and purification of immunotoxins. Please contact David 
Neville at [email protected] for more information.

    Dated: June 28, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E7-13128 Filed 7-5-07; 8:45 am]
BILLING CODE 4140-01-P