[Federal Register Volume 71, Number 207 (Thursday, October 26, 2006)]
[Notices]
[Pages 62598-62601]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-17966]


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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

[[Page 62599]]

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.

Manganese Superoxide Dimutase VAL16ALA Polymorphism Predicts Resistance 
to Doxorubicin Cancer Therapy

    Description of Technology: Cancer is the second leading cause of 
death in the United States and it is estimated that there will be 
approximately 600,000 deaths caused by cancer in 2006. Major drawbacks 
of the existing cancer therapies are the interindividial differences in 
the response and the cytotoxic side-effects that are associated with 
them. Thus, there is a need to develop new therapeutic approaches to 
optimize treatment and increase patient survival.
    This technology describes the identification of a manganese 
superoxide dismutase (MnSOD) polymorphism as a novel biomarker for the 
prognosis of doxorubicin therapeutic response in breast cancer 
patients, wherein a Val16Ala polymorphism of MnSOD is indicative of 
patient survival. More specifically, patients undergoing doxorubicin 
combination therapy with Val/Val, Val/Ala, and Ala/Ala genotypes had 
95.2%, 79%, and 45.5% survival rates, respectively, in a case study of 
70 unselected breast cancer patients. Carriers of the Ala/Ala genotype 
had a highly significantly poorer breast cancer-specific survival in a 
multivariate Cox regression analysis than carriers of the Val/Val 
genotype. This technology can be developed into an assay to screen for 
breast cancer patients who will be responsive to doxorubicin treatment. 
Further, as the MnSOD polymorphism is common in the population (15% to 
20% of patients have the Ala/Ala genotype), it is a common risk factor 
for doxorubicin therapy. This technology can potentially be utilized as 
a screening tool applicable for all cancer types treated with 
doxorubicin.
    Applications: (1) A novel genetic marker that can predict breast 
cancer patient survival with doxorubicin treatment; (2) A screening 
test based on MnSOD Val16Ala genotype that predicts patient response to 
doxorubicin cancer therapy, wherein treatment can be subsequently 
individualized according to patient MnSOD genotype.
    Development Status: Future studies include determining the 
mechanism in which the polymorphism modulates doxorubicin toxicity.
    Inventors: Stefan Ambs and Brenda Boersma (NCI).
    Patent Status: U.S. Provisional Application No. 60/799,788 filed 11 
May 2006 (HHS Reference No. E-137-2006/0-US-01).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Jennifer Wong; 301/435-4633; 
[email protected].
    Collaborative Research Opportunity: The Laboratory of Human 
Carcinogenesis, Center for Cancer Research, National Cancer Institute, 
National Institutes of Health, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize MnSOD genotyping assays to assess a 
patient's response to doxorubicin combination therapy. Please contact 
Betty Tong, Ph.D. at 301-594-4263 or [email protected] for more 
information.

A Novel Magnetic Resonance Radio-Frequency Coil Array that Eliminates 
Inductive Coupling

    Description of Technology: Parallel magnetic resonance imaging 
(MRI) techniques employ RF coil arrays for faster data acquisition, and 
have been shown to reduce the overall length of MRI procedures, improve 
signal-to-noise ratio (SNR) and image quality, thus making MRI more 
attractive and less costly. Elimination of inductive coupling is an 
essential step in designing RF coil arrays for parallel MRI. If mutual 
inductance remains among coils in the RF coil array, the MR signal 
obtained from one coil may disturb the flux in another coil, making it 
difficult to match the impedance of each individual element to the 
input impedance its preamplifier. This non-optimal matching can lead to 
degradation of MR signal thereby yielding images with low quality. The 
most common strategy for inductive decoupling involves the use of 
preamplifiers with very low input impedance and decoupling networks 
with lumped elements. However, the construction of preamplifiers with 
low input impedance is not easy to accomplish, and these preamplifiers 
impose technical restrictions on coil design, requiring the use of 
overlapping loops to further minimize the amount of mutual inductance 
between the coils.
    The present invention describes a novel RF coil circuitry scheme to 
remove inductive coupling and to overcome the limitations of having to 
use overlapping geometries and low-impedance preamplifiers. The coil 
array employs a transformer to match the input impedance of the 
preamplifier. The signal that reaches the preamplifier is coupled in an 
inductive fashion to the RF coil decoupling network through the 
transformer's primary coil. Because primary and secondary coils in the 
transformer are isolated, the preamplifier circuit (and the MRI scanner 
electronics) is electrically isolated from the MR pickup coil. This 
arrangement provides a perfect electrical balance and isolation between 
the array channels, thus making it unnecessary to use traps and balluns 
in the circuit. At 7T, a 4-channel small animal coil array implementing 
the novel circuitry provided images with excellent SNR and demonstrated 
isolation of all individual RF coils and immunity to standing waves and 
other parasitic signals.
    Applications: (1) MR imaging of humans, including imaging of brain; 
(2) MR imaging of animals, including non-human primates and rodents; 
(3) Functional imaging of humans and animals.
    Advantages: (1) Allows for increased flexibility of coil design 
including geometries that require array with overlapping receiver coil 
loops; (2) Can provide high level of mutual inductance decoupling 
within coils in the array; (3) Isolates the grounds from coil to coil, 
and cancels all ground loops related to the coil array; (4) Greatly 
increases the signal to noise ratio in MR imaging.
    Development Status: Early stage; Working model made and tested, 
improved model for animals under testing.
    Inventors: George C. Nascimento and Afonso C. Silva (NINDS).
    Patent Status: U.S. Provisional Application No. 60/789,934 filed 30 
Mar 2006 (HHS Reference No. E-099-2006/0-US-01).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Chekesha S. Clingman, Ph.D.; 301/435-5018; 
[email protected].

PDE11A as a Novel Therapeutic Target for Inherited Form of Cushing 
Syndrome and Endocrine Tumors

    Description of Technology: Cushing Syndrome, a disorder associated 
with excess production of a steroid hormone, cortisol, affects up to 10 
per 15 million people every year. Cushing Syndrome may be caused by 
several reasons such as cortisol-producing endocrine tumors and can be 
inherited in some instances. Surgery of the adrenal tumor is the most 
common method of treatment. New diagnostic and therapeutic approaches

[[Page 62600]]

need to be developed for successful management of the disease.
    This technology describes the clinical identification of a new 
disease termed ``isolated micronodular adrenocortical disease'' (iMAD), 
as well as the role of PDE11A gene in this disease. Additionally, the 
technology also identifies particular sequence variants of the PDE11A 
gene associated with abnormal or altered function of the gene, PDE11A 
as a potential novel drug target for the treatment of bilateral adrenal 
hyperplasia, and possibly other endocrine tumors and malignancies.
    Applications and Modality: (1) Identification of PDE11A gene and 
sequence variants for the diagnosis of ``isolated micronodular 
adrenocortical disease'' (iMAD), a form of Cushing Syndrome and 
endocrine tumors, i.e., as diagnostic tool. (2) Identification of 
PDE11A as a potential novel drug target for the treatment of bilateral 
adrenal hyperplasia and other endocrine and non-endocrine tumors and 
malignancies.
    Market: (1) 5 to 10 per 15 million 10 to 15 million new cases of 
Cushing Syndrome every year; (2) 27,000 new cases of endocrine tumors 
every year; (3) The technology involving PDE11A genes for the diagnosis 
and treatment of endocrine tumors including Cushing syndrome; (4) The 
endocrine drug market is more than 40 billion U.S. dollars.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventor: Dr. Constantine A. Stratakis (NICHD).
    Publication: A Horvath et al. A genome-wide scan identifies 
mutations in the gene encoding phosphodiesterase 11A4 (PDE11A) in 
individuals with adrenocortical hyperplasia. Nat Genet. 2006 
Jul;38(7):794-800. Epub 2006 Jun 11, doi:10.1038/ng1809. [PubMed abs]
    Patent Status: U.S. Provisional Application No. 60/761,446 filed 24 
Jan 2006 entitled ``PDE11A mutations in Adrenal Diseases'' (HHS 
Reference No. E-027-2006/0-US-01).
    Licensing Status: Available for exclusive and non-exclusive 
license.
    Licensing Contact: Mojdeh Bahar; 301/435-2950; [email protected].
    Collaborative Research Opportunity: The NICHD Heritable Disorders 
Branch is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate, or 
commercialize testing for PDE11A genetic or functional defects in 
endocrine disease, and endocrine and other tumors or cancers. Please 
contact Betty Tong, Ph.D. at 301-594-4263 or [email protected] for 
more information.

2-Amino-O4-Substituted Pteridines: Improved Chemotherapy Adjuvants

    Description of Technology: O6-Benzylguanine derivatives, 
some O6-benzylpyrimidines, and related compounds are known 
to be inactivators of the human DNA repair protein O6-
alkylguanine-DNA alkyltransferase (alkyltransferase). This repair 
protein is the primary source of resistance many tumor cells develop 
when exposed to chemotherapeutic agents that modify the O6-
position of DNA guanine residues. Therefore, inactivation of this 
protein can bring about a significant improvement in the therapeutic 
effectiveness of these chemotherapy drugs. The prototype inactivator 
O6-benzylguanine is currently in clinical trials in the 
United States as an adjuvant in combination with the chloroethylating 
agent 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU) and the methylating 
agent temozolomide. A similar alkyltransferase inactivator, 
O6-(4-bromothenyl) guanine is in clinical trials in the UK.
    This technology is directed to the discovery of a new class of 
potent alkyltransferase inactivators, 2-amino-O4-
benzylpteridine derivatives targeted for use in cancer treatment in 
combination with chemotherapeutic agents such as 1, 3-bis (2-
chloroethyl)-1-nitrosurea (BCNU) or temozolomide. The derivatives of 
the present invention inactivate the O6-alkylguanine-DNA-
alkyltransferase repair protein and thus enhance activity of such 
chemotherapeutic agents. Some of the derivatives are water soluble and 
possess tumor cell selectivity in particular by inactivating 
alkyltransferase in tumor cells that overexpress folic acid receptors. 
The 2-amino-O4-benzylpteridine derivatives represent a 
promising new class of alkyltransferase inactivator with 
representatives that may be great candidates as chemotherapy adjuvants.
    Applications and Modality: (1) New small molecules as 
alkyltransferase inactivators based on 2-amino-O4-
benzylpteridine compounds; (2) Promising candidates as chemotherapy 
adjuvants for the treatment of cancer; (3) Therapeutic application for 
drug resistant tumors where acquired resistance is caused by 
O6-alkylguanine-DNA alkyltransferase.
    Market: (1) 600,000 deaths from cancer related diseases estimated 
in 2006; (2) This technology involving small molecule therapeutics for 
the treatment of several cancers has a potential market of several 
billion U.S. dollars.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Robert C. Moschel (NCI) et al.
    Publication: ME Nelson, NA Loktionova, AE Pegg, RC Moschel. 2-
amino-O4-benzylpteridine derivatives: potent inactivators of 
O6-alkylguanine-DNA alkyltransferase. J Med Chem. 2004 Jul 
15;47(15):3887-3891. Epub 2004 Jun 18, doi 10.1021/jm049758+ S0022-
2623(04)09758-4.
    Patent Status: U.S. Provisional Application No. 60/534,519 filed 06 
Jan 2004 (HHS Reference No. E-274-2003/0-US-01); U.S. Patent 
Application No. 10/585,566 filed 06 Jul 2006 (HHS Reference No. E-274-
2003/0-US-03); Foreign equivalents.
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Adaku Madu, J.D.; 301/435-5560; 
[email protected].

Retrovirus-Like Particles as Vaccines and Immunogens

    Description of Technology: This technology describes retrovirus-
like particles and their production from retroviral constructs in which 
the gene encoding all but seven amino acids of the nucleocapsid (NC) 
protein was deleted. NC is critical for both genomic RNA packaging into 
the virion and viral integration into the host cell. Therefore, this 
deletion functionally eliminates two essential steps in retrovirus 
replication, thereby resulting in non-infectious retrovirus-like 
particles that maintain their full complement of antigenic proteins. 
Furthermore, efficient formation of these particles requires inhibition 
of the protease enzymatic activity, either by mutation to the protease 
gene in the construct or by protease inhibitor thereby ensuring the 
production of non-infectious retrovirus-like particles by altering two 
independent targets. These particles can be used in vaccines or 
immunogenic compositions. Specific examples using HIV-1 constructs are 
given.
    Applications: Retroviral vaccine; Immunogenic compositions.
    Development Status: In vitro data available.
    Inventor: David E. Ott (NCI).
    Publications:
    1. DE Ott et al. Elimination of protease activity restores 
efficient virion production to a human immunodeficiency virus type 1 
nucleocapsid deletion mutant. J Virol. 2003 May;77(10):5547-5556. 
[PubMed abs]

[[Page 62601]]

    2. DE Ott et al. Redundant roles for nucleocapsid and matrix RNA-
binding sequences in human immunodeficiency virus type 1 assembly. J 
Virol. 2005 Nov;79(22), 13839-13847. [PubMed abs] Patent Status: U.S. 
Patent Application No. 11/413,614 filed 27 Apr 2006 (HHS Reference No. 
E-236-2003/0-US-02).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Susan Ano, Ph.D.; 301/435-5515; 
[email protected].
    Collaborative Research Opportunity: The NCI, CCR, AIDS Vaccine 
Program is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate, or 
commercialize whole retrovirus-like particle vaccines. Please contact 
Betty Tong, Ph.D. at 301-594-4263 or [email protected] for more 
information.

    Dated: October 19, 2006.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E6-17966 Filed 10-25-06; 8:45 am]
BILLING CODE 4140-01-P