[Federal Register Volume 76, Number 87 (Thursday, May 5, 2011)]
[Notices]
[Pages 25697-25699]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-11055]


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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.

Improved Standard for Immune System Recovery Assay

    Description of Invention: Monitoring an immune system that has been 
depleted by infection (e.g., HIV), chemotherapy, or progenitor cell 
transplantation is vital to assessing individual's recovery status. 
This technology provides a new plasmid standard to be used as part of 
the existing TREC assay. This new plasmid has a shorter insert than the 
commercially available one, which means it now matches the PCR product 
generated in the qPCR reaction in the TREC assay. Additionally, the new 
plasmid is easier to grow up than the existing standard.
    Applications: TREC assay for T-cell concentration measurements.
    Advantages:
     The insert of standard plasmid is shorter and directly 
matches the PCR product generated in the qPCR reaction.
     The standard plasmid is easy to grow up.
    Development Status: Fully developed.
    Inventors: Daniel C. Douek, Richard A. Koup, Brenna J. Hill 
(NIAID.)
    Relevant Publications:
    1. Douek et al. Changes in thymic function with age and during the 
treatment of HIV infection. Nature 1998 Dec 17;396(6712):690-695. 
[PubMed: 9872319.]
    2. Douek et al. Assessment of thymic output in adults after 
haematopoietic stem-cell transplantation and prediction of T-cell 
reconstitution. Lancet 2000 May 27;355(9218):1875-1881. [PubMed: 
10866444.]
    Patent Status: HHS Reference No. E-067-2011/0--Research Material. 
Patent protection is not being pursued for this technology.
    Licensing Status: Research tool available for non-exclusive 
licensing.
    Licensing Contact: Susan Ano, Ph.D.; 301-435-5515; 
[email protected].

Glucocerebrosidase Activators as a Treatment for Gaucher Disease

    Description of Invention: This technology is a collection of small 
molecule activators of a genetically defective version of the enzyme 
called glucocerebrosidase (GCase), which causes Gaucher disease. 
Gaucher disease is a rare disease affecting 1 in 40,000 babies born. 
Ashkenazi Jews of eastern European descent (about 1 in 800 live births) 
are at particular risk of carrying this genetic defect. It is caused by 
inherited genetic mutations in the gene that encodes GCase, which 
result in reduced activity of the enzyme. This enzyme is normally made 
and then transported to an organelle called a lysosome, which is 
dedicated to the degradation and disposal of molecules the cell no 
longer needs. GCase is responsible for the breakdown of a fatty 
material called glucocerebroside (or glucosylceramide). The 
accumulation of this lipid occurs inside specific cells called 
macrophages and macrophage-derived cells. The disease has been 
categorized into three types: neuronopathic (types 2, 3) and non-
neuronopathic (type 1) with mild to severe symptoms that can appear at 
anytime from infancy to adulthood. Clinical manifestations can include 
an enlarged spleen and liver, anemia, decreased platelets, bone disease 
and neurodegeneration, with varying severity depending on the type of 
disease and time of diagnosis. The deficient GCase activity has been 
attributed to insufficient GCase enzyme in the lysosome. After 
production in the endoplasmic reticulum (ER), defective GCase does not 
fold properly and is therefore degraded in the ER and not transported 
to the lysosome where it would hydrolyze glucocerebroside. The small 
molecule activators may act by increasing the concentration of GCase 
that reaches the lysosome by facilitating the proper folding of GCase 
so that it can be released from the ER and transported to lysosomes. 
Thus, these small molecules could be acting like ``chaperones,'' 
because they facilitate proper folding which results in some active 
enzyme. Prior failed attempts to use small molecule chaperones to 
improve GCase folding and transport were made with inhibitors of GCase, 
which ironically properly folded active GCase that was subsequently 
transported to the lysosome, but the molecule also inhibited the GCase 
co that it could not break down glucocerebroside. On the other hand, 
these proposed small molecules were

[[Page 25698]]

screened for their ability to activate defective GCase in the presence 
of a fluorogenic mimic of glucocerebroside, and their ability to 
facilitate translocation of defective GCase to lysosomes as well. This 
creates the opportunity to induce proper folding, while avoiding 
inhibition of enzyme function.
    Application: Treatment of Gaucher Disease.
    Development Status: Early development.
    Inventors: Juan Marugan, Noel T. Southall, Ehud M. Goldin, Wei 
Zheng, Samarjit Patnaik, Ellen Sidransky, Omid Motabar, Wendy Westbroek 
(NHGRI.)
    Related Publications: None.
    Patent Status: U.S. Provisional Application No. 61/420,946, filed 
December 8, 2010, (HHS Reference No. E-257-2010/0-US-01.)
    Licensing Status: Available for licensing.
    Licensing Contact: Steve Standley, PhD; 301-435-4074; 
[email protected].

A Novel Strategy for Development of an Effective HIV/AIDS Vaccine

    Description of Invention: The invention offered for licensing and 
commercial development relates to the field of HIV/AIDS Vaccines. More 
specifically, the invention describes a novel strategy that can be 
useful in effective vaccination and treatment of HIV/AIDS infected 
persons. In this strategy (called `trigger-and-neutralize' strategy) 
the infected subject is primed with HIV trimeric gp 120 immunogen to 
induce the production of CD4i (CD4-induced) antibodies. The patient is 
then treated with a compound that stabilizes the `open' conformation of 
the gp120 of the HIV virus, at which conformation the gp120 epitope is 
better exposed and effectively neutralized by the CD4i antibodies.
    Applications: Vaccination and treatment of HIV/AIDS infected 
patients.
    Advantages: The unique strategy of eliciting CD4i antibodies in 
vivo and ensuring their neutralizing effect by stabilizing the gp120 
open conformation, will provide more effective treatment compared to 
other published methods that utilize neutralizing antibodies to treat 
HIV/AIDS.
    Development Status: The subject matter of the invention continues 
to be researched. Proof-of-principle of some of the aspects of the 
invention have been demonstrated.
    Market: Although there are currently many commercial drugs 
available for treatment of HIV/AIDS, there still exists an urgent need 
to develop vaccines against the disease. This need (no approved vaccine 
is available yet) is particularly important because of the resistance 
developed by many patients to commercial drugs and thus the need for 
the use of drug cocktails, as well as the severe side effects that many 
of the drugs exhibit. At present, the World Health Organization 
estimates that over 30 million people are infected with HIV and that 
over 25 million individuals have died from AIDS-related illnesses. The 
potential market for HIV vaccines is therefore huge and thus this 
invention may be commercially attractive for vaccine and drug 
manufacturers.
    Inventors: Sriram Subramaniam (NCI.)
    Relevant Publications:
    1. Liu J, Bartesaghi A, Borgnia MJ, Sapiro G, Subramaniam S. 
Molecular architecture of native HIV-1 gp120 trimers. Nature. 2008 Sep 
4;455(7209):109-113. [PubMed: 18668044.]
    2. White TA, Bartesaghi A, Borgnia MJ, Meyerson JR, M. de la Cruz 
MJ, Bess JW, Nandwani R, Hoxie JA, Lifson JD, Milne JL, Subramaniam S. 
Molecular architectures of trimeric SIV and HIV-1 envelope 
glycoproteins on intact viruses: strain dependent variation in 
quaternary structure. PLoS Pathog. 2010 Dec 23;6(12):e1001249. [PubMed: 
21203482.]
    3. Felts RL, Narayan K, Estes JD, Shi D, Trubey CM, Fu J, Hartnell 
LM, Ruthel GT, Schneider DK, Nagashima K, Bess JW Jr, Bavari S, 
Lowekamp BC, Bliss D, Lifson JD, Subramaniam S. 3D visualization of HIV 
transfer at the virological synapse between dendritic cells and T-
cells. Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13336-13341. 
[PubMed: 20624966.]
    Patent Status: U.S. Provisional Application No. 61/356,326 filed 18 
Jun 2010 (HHS Reference No. E-201-2010/0-US-01), entitled ``Immunogenic 
Compositions Derived from Structural Alteration of HIV Envelope 
Proteins.''
    Licensing Status: Available for licensing and commercial 
development.
    Licensing Contacts:

     Uri Reichman, PhD, MBA; 301-435-4616; [email protected].
     John Stansberry, PhD; 301-435-5236; [email protected].
    Collaborative Research Opportunity: The Center for Cancer Research, 
NCI/NIH is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, produce, 
evaluate, or commercialize trimeric gp120 immunogens. Please contact 
John Hewes, PhD at 301-435-3121 or [email protected] for more 
information.

Epoxy-guaiane Cancer Inhibitors: New Class of Natural Products Isolated 
From the African Plant Phyllanthus englerii

    Description of Invention: The present invention involves the 
observation of renal selective inhibitory activity by the extracts of 
the African plant Phyllanthus englerii. Bioassay-guided fractionation 
of the purified extracts revealed a series of novel chemical entities 
which are named Englerin A-F. The englerins and their derivatives are 
useful in the treatment of a number of cancers, particularly renal 
cancer. The englerins exhibit selective and potent renal cell 
inhibitory activity in vitro.
    These compounds are recoverable in reasonable yield from natural 
product extracts and are considered to be reasonably tractable for 
synthetic chemistry schemes. Sufficient supply of several analogs had 
been extracted from repository samples for identification and initial 
biological characterization. Subsequent five-dose testing in the NCI60 
screening panel indicated and confirmed impressive renal-selective 
activity.
    Applications: The new chemical entities can be potential cancer 
therapeutics, especially for renal cancer.
    Advantages:
     There is reasonable yield and recovery of the compounds 
from the natural product extracts.
     The synthetic chemistry schemes for synthesis of these 
compounds are considered to be reasonably tractable.
    Development Status: Proof of concept in vitro studies have been 
completed and further in vitro and in vivo animal model studies are 
ongoing.
    Inventors: John A. Beutler et al. (NCI)
    Relevant Publication: S. Sutthivaiyakit et al. A novel 29-nor-3,4-
seco-friedelane triterpene and a new guaiane sesquiterpene from the 
roots of Phyllanthus oxyphyllus. Tetrahedron 2003 Dec 8; 59(50):9991-
9995.
    Patent Status: U.S. Patent Application No. 12/811,245 filed 29 Jul 
2010 (HHS Reference No. E-064-2008/2-US-06) and related international 
filings.
    Licensing Status: Available for licensing.
    Licensing Contact: Surekha Vathyam, PhD; 301-435-4076; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
Molecular Targets Development Program is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize epoxy-guaiane 
cancer inhibitors. Please contact John D. Hewes, PhD at 301-435-3121 or 
[email protected] for more information.

[[Page 25699]]

Imidazoacridones With Anti-Tumor Activity

    Description of Invention: The present invention relates to novel 
bifunctional molecules with potent and selective activity against 
colon, liver and pancreatic tumors. Compounds have low animal toxicity, 
excellent PK/PD characteristics and proved to be very effective in 
several preclinical animal models of cancer. Extensive mechanistic 
studies have demonstrated that compounds inhibit tumor growth through a 
novel mechanism. These agents are composed of an imidazoacridone moiety 
linked by a nitrogen containing aliphatic chain of various length and 
rigidity to another aromatic ring system capable of intercalation to 
DNA.
    Previous studies on related symmetrical bis-imidazoacridones 
revealed that only one planar imidazoacridone moiety intercalates into 
DNA. The second aromatic moiety, which is crucial for biological 
activity, along with the linker resides in DNA minor groove, and is 
believed to interact with DNA-binding proteins (most likely, 
transcription factors and/or repair proteins). The symmetrical bis-
imidazoacridones arrest the growth of sensitive cancers (especially 
colon cancers) but do not kill the tumors. It was hypothesized that the 
growth arrest was due to the inability of the affected tumor cells to 
repair DNA damage caused by the compounds. Remarkably, bis-
imidazoacridones are very well tolerated, are very tissue selective and 
do not appear to damage normal tissues.
    Since the binding of the symmetrical bis-imidazoacridones to DNA 
was unsymmetrical, the inventors have developed unsymmetrical compounds 
in which one imidazoacridone moieties was replaced by other 
intercalating groups, with the expectation that this would enhance 
biological activity while retaining the remarkable tissue selectivity 
and low systemic toxicity. The new compounds contain intercalating 
moieties such as 3-chloro-7-methoxyacridine or naphthalimide along with 
the original imidazoacridones.
    These new compounds, especially those containing naphthalimide 
moiety, are extremely cytotoxic against a variety of tumor cells in 
vitro (IC50 at low nanomolar range) and kill tumor cells by inducing 
apoptosis. In vivo, in nude mice xenografted with human tumors, the 
compounds significantly inhibited the growth of such tumors as colon 
tumor HCT116 and Colo205 as well as pancreatic tumors (lines 6.03 and 
10.05 freshly established from a patient). These compounds are 
extremely potent agents against hepatocellular carcinoma as evidenced 
by their ability to eradicate liver cancer in an orthotopic liver 
cancer model in rats. Remarkably, no toxicity was observed at the 
therapeutic doses. These are among the most potent agents known against 
cancers of the GI tract and appear to be tolerated very well.
    Inventors: Wieslaw M. Cholody et al. (NCI)
    Patent Status:
     U.S. Patent 6,664,263 issued 16 Dec 2003 (HHS Reference 
No. E-289-1999/0-US-07) and related international patents/patent 
applications.
     U.S. Patent 6,541,483 issued 01 Apr 2003 (HHS Reference 
No. E-065-1996/2-US-25) and related international patents/patent 
applications.
    Licensing Status: Available for licensing.
    Licensing Contact: Betty B. Tong, PhD; 301-594-6565; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Center for Cancer Research, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize imidazoacridones as therapeutic 
agents for cancer treatment. Please contact John Hewes, PhD at 301-435-
3121 or [email protected] for more information.

    Dated: April 29, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2011-11055 Filed 5-4-11; 8:45 am]
BILLING CODE 4140-01-P