[Federal Register Volume 73, Number 206 (Thursday, October 23, 2008)]
[Notices]
[Pages 63167-63169]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-25221]


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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.

Gene Expression Profiling for Prognosis of a Non-Hodgkin Lymphoma

    Description of Technology: Diffuse large B cell lymphoma (DLBCL) is 
a quickly progressing cancer of the white blood cells, which is the 
most common type of non-Hodgkin lymphoma. Most commonly, DLBCL is 
treated aggressively with combination chemotherapy referred to as R-
CHOP. Fortunately, with this treatment more than half of these patients 
can be cured or show remission. However, other patients do not respond 
to treatment and succumb to the disease. Therefore, it would be helpful 
to predict which patients are likely not to respond to R-CHOP and would 
benefit from alternate treatments.
    This invention provides gene microarrays and method of use claims 
for a survival predictor calculated for DLBCL patients undergoing 
combination therapy. By measuring the

[[Page 63168]]

gene expression of genes from cancer biopsies it is possible to 
identify patients that are unlikely to be cured by R-CHOP and could 
benefit from alternative treatments like anti-angiogenic drugs.
    Applications: Diagnostic test for managing treatment of DLBCL 
patients; Design and analysis of clinical trials in DLBCL.
    Market: About 16,000 new cases per year of DLBCL in U.S.; Affects 
mostly the middle-aged but it can afflict children.
    Development Status: Clinical data is available.
    Inventors: Louis M. Staudt (NCI).
    Publication: A Rosenwald et al. The use of molecular profiling to 
predict survival after chemotherapy for diffuse large-B-cell lymphoma. 
N Engl J Med. 2002 Jun 20;346(25):1937-1947.
    Patent Status: U.S. Provisional Application No. 61/059,678 filed 06 
Jun 2008 (HHS Reference No. E-256-2008/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Sabarni Chatterjee, PhD; 301-435-5587; 
[email protected].

A Simple Genetic Test for Kidney Disease

    Description of Technology: This technology relates to methods of 
diagnosing a predisposition to diseases that cause chronic kidney 
disease (CKD) and end-stage kidney disease (ESKD). Variations in a 
gene, non-muscle myosin IIA (MYH9), are associated with 79% of the risk 
of focal segmental glomerulosclerosis (FSGS), the disease that causes 
ESKD, in African Americans with HIV, and 56% of African Americans as a 
whole. The variants are also associated with a 2-3 fold increased risk 
for end-stage kidney disease (ESKD) associated with hypertension. The 
variations are also present among European Americans, however they are 
less common.
    A simple genetic screening test has been developed that identifies 
single nucleotide polymorphisms (SNP) and haplotypes in the non-muscle 
myosin gene MYH9. These variants confer genetic risk for the following 
kidney diseases: FSGS, collapsing glomerulopathy, HIV-associated 
nephropathy, hypertensive kidney disease, sickle cell nephropathy, 
lupus nephropathy, and possibly other kidney diseases.
    Applications:
     Facilitate rigorous population (i.e. all individuals) 
screening for early kidney disease.
     Screen individuals with hypertension, to identify 
individuals who might benefit from more intensive therapy.
     Screen kidney donors for MYH9 risk alleles to improve 
renal allograft survival.
     Screen patients with sickle cell disease to identify those 
at increased risk for CKD.
     Screen patients with lupus nephritis to identify those at 
increased risk for CKD.
     Screen patients with HIV-1 infection to identify those at 
increased risk for kidney disease.
     Screen patient with other kidney diseases, including 
idiopathic and secondary kidney disease, where MYH9 mutations may alter 
the propensity to develop kidney disease or the rate of progressive 
renal function decline.
     Pharmaceutical agents might be developed that reverse the 
susceptibility phenotype, reducing propensity to CKD. These agents 
might alter non-muscle myosin IIA function or its interactions with 
critical molecular partners.
    Market: An estimated 26 millions have CKD, with impaired glomerular 
filtration rate and approximately 100,000 individuals in the United 
States develop ESKD every year. The lifetime risk for ESKD is 7.5% of 
individuals of African American descent and 2.1% for individuals of 
European descent. Early identification of individuals with MYH9 
variants who are at increased risk for CKD might substantially reduce 
morbidity and mortality in this population, as impaired kidney function 
is associated with death from cardiovascular disease even in patients 
who do not progress to ESKD.
    Development Status: Early-stage development for clinical 
applications, including diagnostic testing and therapeutic 
intervention.
    Inventors: Cheryl A. Winkler (SAIC/NCI), George W. Nelson (SAIC/
NCI), Jeffrey B. Kopp (NIDDK), Michael W. Smith (SAIC/NCI), Randall C. 
Johnson (SAIC/NCI).
    Publication: JB Kopp et al. MYH9 is a major-effect risk gene for 
focal segmental glomerulosclerosis. Nat Genet. 2008 Oct;40(10):1175-
1184.
    Patent Status: U.S. Provisional Application No. 61/024,863 filed 30 
Jan 2008 (HHS Reference No. E-090-2008/0-US-01); U.S. Provisional 
Application No. 61/095,590 filed 09 Sep 2008 (HHS Reference No. E-090-
2008/1-US-01).
    Licensing Status: Available for non-exclusive and exclusive 
licensing.
    Licensing Contact: Steve Standley, PhD; 301-435-4074; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Laboratory of Genomic Diversity, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize genetic testing for MYH9. Please 
contact John D. Hewes, PhD at 301-435-3121 or [email protected] for 
more information.

Nanoparticles for Imaging and Treatment of Brain Tumors

    Description of Technology: Malignant brain tumors, whether arising 
within the brain or invading the brain from other tissues, are 
difficult to treat. Conventional chemotherapy drugs do not reach 
therapeutic levels in brain tumor tissue, and do not remain in brain 
tumor tissue for long enough to enter brain tumor cells and kill them. 
As a consequence, these chemotherapy drugs are not effective at 
treating malignant brain tumors growing in patients, even though these 
drugs are effective at killing brain tumor cells growing in culture.
    This invention claims that intravenously administered 
functionalized polyamidoamine (PAMAM) dendrimers of certain sizes can 
selectively cross the blood-brain barrier (BBB) of malignant brain 
tumors, and can accumulate over time within individual brain tumor 
cells. Gadolinium and fluorescent probe conjugated dendrimers with 
these properties can be used for simultaneous magnetic resonance and 
fluorescence imaging of brain tumor cells. Since these nanoparticles 
possess numerous additional surface functional groups, in addition to 
being useful for multi-modality imaging, functionalized dendrimers can 
also be useful for the simultaneous delivery of cytotoxic drugs and 
inhibitors of tumor cell metabolic or migratory pathways.
    Advantages:
     Intravenously administered nanoparticles selectively cross 
the BBB of brain tumors and accumulate within brain tumor cells but not 
normal brain cells.
     Nanoparticles accumulate in and are retained in brain 
tumor tissue for long enough to result in the effective uptake of 
nanoparticles by individual brain tumor cells.
     Nanoparticle size can be adjusted to achieve the desired 
particle blood half-life.
     A wide variety of agents can be attached to the functional 
groups on the nanoparticle exterior.
    Applications:

[[Page 63169]]

     Anatomic and metabolic imaging of brain and spinal cord 
tumors for diagnostic and therapeutic purposes.
     Intravenous treatment of brain and spinal cord tumors.
     Imaging of intravenous drug delivery to brain and spinal 
cord tumors.
     Potential to be used for imaging and treatment of other 
neurological disorders in which the BBB becomes porous.
    Market: In 2008, it is estimated that malignant tumors of the brain 
and spinal cord will account for about 1.5% of all cancers and 2.3% of 
all expected cancer-related deaths.
    Development Status: Early stage development; Pre-clinical data 
available.
    Inventor: Hemant Sarin (CC).
    Patent Status: U.S. Provisional Application No. 61/055,328 filed 22 
May 2008 (HHS Reference No. E-063-2008/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Surekha Vathyam, PhD; 301-435-4076; 
[email protected].

Induced Internalization of Surface Receptors

    Description of Technology: Cell-surface receptors are responsible 
for the biological activities of many molecules. Specific ligands bind 
to them, causing the cell-surface receptors to internalize or bring the 
receptor and ligand inside the cell. A number of diseases, including 
cancer, metabolic disorders, and viral infections are known to require 
the expression of cell-surface receptors for critical pathogenetic 
steps. This has prompted significant research efforts towards the 
development of pharmaceutical agents that block the signals from cell-
surface receptors. While this current research shows great promise, 
there is a strong need for new therapeutic strategies that utilize the 
mechanistic properties of cell-surface receptors.
    This technology describes a strategy for artificially inducing the 
internalization of surface receptors, and thereby blocking the effects 
of the ligands associated with that receptor. This method employs 
bifunctional ligands that bind to both a scavenger receptor and a 
target receptor. As proof of concept, the inventors Drs. Narazaki and 
Tosato have shown that a ligand capable of binding to the scavenger 
receptor SREC-1 and the neuropilin-1 receptor NRP1 induces the 
internalization of NRP1 and inhibits NRP1 signaling. The inventors 
propose that this strategy can be used to inhibit signaling from any 
target receptor if an appropriate bifunctional ligand is used. For 
example, the concept could be expanded to other receptors, such as HDL 
and LDL receptors. Likewise the bifunctional ligand could include 
specific antibodies or modified ligands that recognize cell surface 
receptors of biological importance. Accordingly, this approach could be 
used to limit tumor angiogenesis, limit tumor growth, block metastasis 
formation, block inflammation, block viral infection, and treat just 
about any disease where we identify a cell surface receptor as the 
molecular basis for disease.
    Applications:
     Method of inducing the internalization of target 
receptors.
     Inhibiting diseases or conditions associated with target 
receptors, such as HIV infection, cancer, or angiogenesis.
     Treating diseases or conditions associated with target 
receptors, such as cancer, viral infections, or HIV infections.
    Market:
     Cancer is one of the leading causes of death in the United 
States and it is estimated that there will be more than half a million 
deaths caused by cancer in 2008.
     It is estimated that over one million people in the U.S. 
are living with HIV/AIDS and approximately 50,000 new infections occur 
each year.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Masashi Narazaki and Giovanna Tosato (NCI).
    Patent Status: U.S. Provisional Application No. 61/023,397 filed 24 
Jan 2008 (HHS Reference No. E-250-2007/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Whitney A. Hastings; 301-451-7337; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Laboratory of Cellular Oncology, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize the technology aimed at promoting 
selective receptor internalization as a means to neutralize ligand 
function and receptor signaling. Please contact John D. Hewes, PhD at 
301-435-3121 or [email protected] for more information.

Methods of Determining the Prognosis of an Adenocarcinoma

    Description of Technology: Available for licensing and commercial 
development is a novel method for determining the prognosis of a 
subject with adenocarcinoma in an organ, such as the lung, and to aid 
in the selection of a specific therapeutic regimen. Lung adenocarcinoma 
(AC) is the predominant histological subtype of lung cancer, which is 
the leading cause of cancer deaths worldwide. The risk of metastasis 
remains substantial in AC patients, even when a curative resection of 
early-stage AC is performed. The prognosis includes the determination 
of the likelihood of survival, the likelihood of metastasis, or both. 
The method includes quantization of the expression of a plurality of 
Th1 and Th2 cytokines of interest in the adenocarcinoma and in non-
cancerous tissue in the organ. Altered expression of one or more of the 
Th1 and Th2 cytokines in the adenocarcinoma as compared to the non-
cancerous tissue determines the prognosis for the subject. The method 
is capable of distinguishing patients with lymph node metastasis versus 
those with short term survival. Furthermore, methods are provided for 
evaluating the effectiveness of anti-cancer agents.
    Applications: Prognosis of adenocarcinoma, aid in the selection of 
specific therapeutic regimens and evaluation of the effectiveness of 
anti-cancer agents.
    Development Status: The technology is in early stage of 
development.
    Inventors: Curtis C. Harris, Masahiro Seike, Xin Wei Wang (NCI).
    Patent Status: PCT Application No. PCT/US2007/073637 filed 16 Jul 
2007, which published as WO 2008/009028 on 17 Jan 2008; claiming 
priority to 14 Jul 2006 (HHS Reference No. E-263-2006/1-PCT-01).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Susan Ano, PhD; 301-435-5515; [email protected].

    Dated: October 14, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E8-25221 Filed 10-22-08; 8:45 am]
BILLING CODE 4140-01-P