Notice (A): Government-Owned Inventions; Availability for Licensing

Federal Register: November 12, 2009 (Volume 74, Number 217)          
                  Page 58295-58298

AGENCY: National Institutes of Health, Public Health Service, HHS.

ACTION: Notice.

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.

A Method of Identifying Cdk5/p35 Modulators, and Possible Diagnostic or 
Therapeutic Uses for Neurodegenerative Diseases

    Description of Invention: Cyclin-dependent kinase 5 (Cdk5) is a 
serine/threonine cyclin-dependent kinase that is highly expressed in 
the central nervous system and controls many biological processes that 
impact learning and memory, as well as pain and drug addiction. Studies 
have indicated that abnormal Cdk5 activity may be associated with the 
onset of neurodegenerative diseases, such as Alzheimer's disease, 
Parkinson's disease, and amyotrophic lateral sclerosis (ALS). The 
kinase activity of Cdk5 is turned on when it binds to one of the two 
proteins considered to be neuronal activators, p35 and p39.
    Scientists at the NIH designed a cell-based assay to screen for p35 
transcriptional regulators that work as upstream regulators of Cdk5. 
This technology may be useful for assessing the presence and risk of 
conditions associated with atypical Cdk5 kinase activity or for finding 
drug modulators that could be promising drug targets.
    Applications:

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     Diagnostic tool for assessing risk of conditions 
associated with abnormal Cdk5 kinase activity.
     Tool for screening Cdk5 modulators.
    Development Status: Early stage.
    Inventors: Ashok B. Kulkarni and Elias S. Utreras Puratich (NIDCR).
    Patent Status: U.S. Provisional Application No. 61/198,246 filed 03 
Nov 2008 (HHS Reference No. E-012-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Charlene Sydnor, Ph.D.; 301-435-4689; 
sydnorc@mail.nih.gov.
    Collaborative Research Opportunity: The National Institute of 
Dental and Craniofacial Research, Laboratory of Cell and Developmental 
Biology, Functional Genomics Section, is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize this 
technology. Please contact David W. Bradley, Ph.D. at 301-402-0540 or 
bradleyda@nidcr.nih.gov for more information.

A Phantom for Diffusion MRI: A Method of Enhancing Performance and 
Reliability

    Description of Invention: The technology offered for licensing is 
in the field of Diffusion Magnetic Resonance Imaging (Diffusion MRI). 
Specifically, a novel imaging phantom is described and claimed. Such a 
phantom is specifically optimized for Diffusion MRI and is expected to 
enhance the performance and reliability of this now widespread imaging 
technology.
    The phantom provided in this invention comprises a stable aqueous 
solution with a concentration of at least 30%, by weight, of a mixture 
of a high molecular-weight polymer or copolymer and a low molecular-
weight polymer or copolymer, the aqueous solution having a resulting 
water diffusivity from about 2 x 10-4 mm2/s to 
about 3 x 10-3 mm2/s. Polyvinyl Pyrrolidone (PVP) 
is the polymer of choice used in this invention. The phantoms of this 
invention are uniquely stable, non-toxic, and transportable, and have 
shown to maintain constant water diffusivity after two years.
    Applications: Combining a Diffusion MRI phantom with a resolution 
phantom would allow the same device to be used to calibrate an MR 
scanner's image quality and the accuracy and precision of its diffusion 
measurements. This would be useful particularly for Radiological QA and 
for use in assuring data quality in longitudinal and multi-subject 
studies.
    Advantages:
     The imaging phantoms provided in the invention are 
optimized specifically for Diffusion MRI. They possess the following 
features and characteristics:

--Made of non-toxic, non-hazardous, non-flammable and easily 
transportable materials.
--Possess diffusivities similar to those of water in biological 
tissues, particular brain parenchyma.
--Possess stable diffusion properties over time. No appreciable change 
in water diffusivity was detectable after two years.
--Offers option to tailor diffusiveness of the phantoms to different 
applications by varying the ratios of the chemical components.

     In addition, the inventors established a procedure to make 
concentrated solutions (up to 80 wt% polymer content) from mixtures of 
different molecular weight polyvinyl pyrrolidone (PVP) polymer and/or 
vinylpyrrolidone-based copolymers in water in the presence of 
physiologically relevant ions and gadolinium-based MRI contrast agents. 
In general, preparation of homogeneous polymer solutions from 
hydrophilic glassy polymers with high solute content is problematic due 
to the inter- and intra-molecular interactions (e.g., hydrogen bonds) 
leading to formation of entanglements and gelation. This discovery 
indicates that at certain PVP-water compositions the new preparation 
procedure gives rise to disengagement of polymer chains and 
considerably improves polymer solubility. Moreover, the addition of 
lower molecular weight PVP and/or vinylpyrrolidone-based copolymers 
decreases the intra molecular association among the polymer molecules 
without significantly affecting the diffusive and relaxation properties 
of the solvent (water) in the MRI phantom.
    Development Status: The invention is fully developed.
    Market:
     The market for medical imaging equipment industry is 
approximately $9.0 billion dollars now and has been growing by 
approximately 7.6% annually. MRI instrumentation constitutes a 
significant portion of this market.
     Diffusion MRI is now a mature technology that has received 
FDA approval; Diffusion MRI methods are ``made, used and sold'' by all 
major MRI manufacturers. The installed base of clinical scanners using 
Diffusion MRI methods, including DTI, must now be in the thousands, 
worldwide.
     Imaging phantoms are necessary components of any imaging 
system as they provide the means for the systems' standardization and 
quality control, and are thus a required components for their reliable 
performance. Commercial success of these phantoms described in the 
invention is therefore expected, in particular in view of the unique 
characteristics possessed by these phantoms as outlined above. Due to 
these properties they can be stored in a medical facility without 
special permits or requirements.
     The phantoms described in this invention could be sold 
with new MRI scanners supporting DTI and other diffusion MRI methods or 
for existing MRI scanners that support diffusion MRI applications. 
These phantoms could be used by MRI companies internally for product 
sequence testing and development as well as to ensure that MRI scanners 
shipped to users operate properly and to within ``specs'' following 
installation. The phantoms should be of interest to medical physicists, 
technicians and bioengineers charged with the responsibility of 
assuring quality and reproducibility in their routine and research 
scans.
    Inventors: Ferenc Horkay, Carlo Pierpaoli, Peter Basser (NICHD).
    Patent Status: U.S. Provisional Application No. 61/147,314 filed 26 
Jan 2009 (HHS Reference No. E-249-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contacts: Uri Reichman, Ph.D., MBA; 301-435-4616; 
UR7a@nih.gov; John Stansberry, Ph.D.; 301-435-5236; 
stansbej@mail.nih.gov.
    Collaborative Research Opportunity: The Eunice Kennedy Shriver 
National Institute of Child Health and Human Development's Section on 
Tissue Biophysics & Biomimetics (STBB) is seeking statements of 
capability or interest from outside parties who are interested in 
entering into a Collaborative Research and Development Agreement 
(CRADA) to develop and commercialize the Diffusion MRI Phantom 
described above. Please contact Alan Hubbs, Ph.D. at 301-594-4263 or 
hubbsa@mail.nih.gov for more information.

Viral Inactivation Using Crosslinkers and Detergents

    Description of Invention: The subject technology is a method of 
inactivating enveloped viruses by hydrophobic photoactivatable chemical 
crossing-linking compounds and detergent treatment. The inactivated 
viruses may be used as vaccines against the diseases caused by those 
viruses or as reagents in experimental procedures that require

[[Page 58297]]

inactivated viral particles. The compounds diffuse into the lipid 
bilayer of biological membranes and upon UV irradiation will bind to 
proteins and lipids in this domain, thereby inactivating fusion of 
enveloped viruses with their corresponding target cells. Furthermore, 
the selective binding of these chemical crosslinking agents to protein 
domains in the lipid bilayer may preserve the structural integrity and 
therefore immunogenicity of proteins on the exterior of the inactivated 
virus. The additional detergent step effectively eliminates the 
infectivity of any residual viral particles that are not adequately 
crosslinked.
    Applications:
     Vaccines for enveloped viruses.
     Vaccine for Human Immunodeficiency Virus.
    Advantages:
     Novel method of inactivating enveloped viruses.
     May maintain native conformational structures and viral 
epitopes for generating an effective immune response.
    Development Status: In vitro data can be provided upon request.
    Market: Vaccines.
    Patent Status: International Patent Application PCT/US2009/000623 
filed 30 Jan 2009 (HHS Reference No. E-331-2007/2-PCT-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Kevin W. Chang, Ph.D.; 301-435-5018; 
changke@mail.nih.gov.
    Collaborative Research Opportunity: The National Cancer Institute, 
Center for Cancer Research, Nanobiology Program is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize the use of 
hydrophobic crosslinkers for their use in vaccine development. 
Interested collaborators are also invited to provide statements for 
proposed in vitro or in vivo studies using various enveloped viruses. 
Please contact John D. Hewes, Ph.D. at 301-435-3121 or 
hewesj@mail.nih.gov for more information.

New Derivative of Dextromethorphan for Use in Neuronal Therapy

    Description of Invention: This invention describes a derivative of 
dextromethorphan, which is a non-competitive inhibitor of the nicotinic 
acetylcholine receptor. Dextromethorphan is an antitussive drug used as 
one of the active ingredients to prevent coughs in many over-the-
counter cold and cough medicines. It has also found other uses in 
medicine, ranging from pain relief to psychological applications. The 
disclosed compound may display attractive properties compared to the 
closely related dextromethorphan or other drugs currently in use as 
non-competitive inhibitors of the nicotinic acetylcholine receptors, 
including extended receptor inhibition and reduced side effects.
    The nicotine acetylcholine receptor is a ligand gated ion channel. 
These receptors specifically control rapid permeation of cations 
through the postsynaptic cell membrane, and are key targets in drug 
discovery for a number of diseases such as Alzheimer's and Parkinson's 
disease. This superfamily of receptor proteins is separated into the 
nicotinic receptor superfamily (muscular and neuronal nicotinic), the 
excitatory amino acid superfamily, and the ATP purinergic ligand gated 
ion channels, and they differ only in the number of transmembrane 
domains found in each subunit. This newly discovered derivative of 
dextromethorphan may have potential therapeutic use for several 
conditions involving these nicotinic acetylcholine receptors.
    Advantages:
     Derivative of dextromethorphan may have superior 
properties on target receptors including increased selectivity, potency 
and receptor occupancy.
     Potential other therapeutic uses for the new compound.
    Development Status: Early stage.
    Inventors: Irving W. Wainer et al. (NIA).
    Publication: K Jozwiak et al. Displacement and non-linear 
chromatographic techniques in the investigation of the interaction of 
noncompetitive inhibitors with an immobilized alpha3beta4 nicotinic 
acetylcholine receptor liquid chromatographic stationary phase. Anal 
Chem. 2002 Sep 15;74(18):4618-4624.
    Patent Status: U.S. Patent Application No. 10/820,809 filed 09 Apr 
2004, claiming priority to 11 Apr 2003 (HHS Reference No. E-158-2003/1-
US-02).
    Licensing Status: Available for licensing.
    Licensing Contact: Jeffrey A. James, Ph.D.; 301-435-5474; 
jeffreyja@mail.nih.gov.
    Collaborative Research Opportunity: The National Institute on 
Aging, Laboratory of Clinical Investigation, is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize a series of 
noncompetitive inhibitors of neuronal nicotinic acetylcholine receptors 
based upon the dextromethorphan and levomethorphan scaffolds including 
molecular modeling and synthesis of new derivatives, receptor binding 
and occupancy studies and non-competitive inhibition of nicotinic 
acetylcholine receptors subtypes and related ligand gated ion channels. 
Please contact Nicole Darack, Ph.D. at 301-435-3101 or 
darackn@mail.nih.gov for more information.

Methods and Compositions for the Diagnosis of Neuroendocrine Lung 
Cancer

    Description of Invention: The technology relates to the use of cDNA 
microarrays to facilitate the identification of pulmonary 
neuroendocrine tumors. In order to identify molecular markers that 
could be used to classify pulmonary tumors, the inventors examined the 
gene expression profiles of clinical samples from patients with small 
cell lung cancer (SCLC), large cell neuroendocrine carcinoma (LCNEC), 
and typical carcinoma (TC) tumors by cDNA microarray analysis to detect 
hybridization between cDNA from tumor cells and DNA from a panel of 
8,897 human genes. Gene expression was found to be nonrandom and to 
exhibit highly significant clustering that divided the tumors into 
their assigned World Health Organization (WHO) classification with 100% 
accuracy. The inventors concluded that pulmonary neuroendocrine tumors 
could be classified based on the genome-wide expression profile of the 
clinical samples without further manipulations.
    Applications:
     Method to differentiate three types of pulmonary 
neuroendocrine tumors.
     Method to diagnose pulmonary neuroendocrine cancer.
     Neuroendocrine Microarray.
    Advantages: Accurate, rapid, easy to use diagnostic to stratify 
patients according pulmonary tumors.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Market:
     Cancer is the second leading cause of death in United 
States and it will be responsible for an estimated 562,340 deaths.
     It is estimated that the cancer therapeutic market would 
double to $50 billion a year in 2010 from $25 billion in 2006.
    Inventors: Curtis C. Harris et al. (NCI)
    Publication: P He et al. Identification of carboxypeptidase E and 
gamma-glutamyl hydrolase as biomarkers for pulmonary neuroendocrine 
tumors by

[[Page 58298]]

cDNA microarray. Human Pathol. 2004 Oct;35(10):1196-1209.
    Patent Status: U.S. Patent Application No. 10/533,459 filed 02 May 
2005 (HHS Reference No. E-248-2002/0-US-04).
    Licensing Status: Available for licensing.
    Licensing Contact: Jennifer Wong; 301-435-4633; 
wongje@mail.nih.gov.

Immunotoxin Useful for Treatment of AIDS

    Description of Invention: Human Immunodeficiency Virus (HIV) 
attacks and destroys T cells, leading to the development of Acquired 
Immunodeficiency Syndrome (AIDS) in patients. Although significant 
progress has been made treating patients with AIDS, an effective cure 
has yet to be identified. For example, highly active antiretroviral 
therapy (HAART) has shown dramatic reduction of viral replication while 
allowing recovery of the immune system in HIV patients. However, HAART 
does not directly kill HIV-infected T cells, allowing the virus to 
persist in the body and resume replication and infection of T cells 
after HAART is stopped. This ultimately results in a return to pre-
treatment levels of viral replication and the persistence of the 
disease in patients.
    The current technology concerns an invention that can be used to 
address this limitation of HAART. An immunotoxin has been created that 
targets a toxin (PE38) to the HIV-specific Envelope glycoprotein 
(gp120) that is displayed on the surface of T cells that have been 
infected with the HIV virus. The immunotoxin kills the HIV-infected T 
cells and other infected cell types that serve as a viral reservoirs 
during HAART, thereby reducing the ability of the virus to replicate 
and infect other cells after HAART is stopped. Recent data shows that 
the immunotoxin blocks the spread of HIV-1 in vitro and does not induce 
hepatotoxicity in rhesus monkeys, suggesting the procedure could be 
effective in human patients. By combining the immunotoxin with a 
treatment regimen such as HAART, it may be possible to significantly 
improve treatment of HIV infection.
    Applications:
     Reduction of HIV-1 infected cell populations in patients 
to reduce viral reservoirs.
     Treatment of HIV infection in combination with therapeutic 
regimens such as HAART.
    Advantages:
     Overcomes a limitation of current HIV therapies by 
specifically depleting infected cell reservoirs.
     Specific targeting of HIV-infected cells allows depletion 
of infected cells without affecting uninfected cells.
     Combination therapy combines inhibition of HIV replication 
and selective killing of infected cells that still persist.
    Development Status: Preclinical stage of development.
    Patent Status:
     US Patent Application 09/673,707 (HHS Reference No. E-201-
1998/0-US-06), pending.
     European Patent 1085908 (HHS Reference No. E-201-1998/0-
EP-05).
    For more information, see:
     PE Kennedy et al. Anti-HIV-1 immunotoxin 3B3(Fv)-PE38: 
enhanced potency against clinical isolates in human PBMCs and 
macrophages, and negligible hepatotoxicity in macaques. J Leukoc Biol. 
2006 Nov;80(5):1175-1182.
     TK Bera et al. Specific killing of HIV-infected 
lymphocytes by a recombinant immunotoxin directed against the HIV-1 
envelope glycoprotein. Mol Med. 1998 Jun;4(6):384-391.
    Inventors: Ira Pastan et al. (NCI)
    Licensing Status: Available for licensing.
    Licensing Contact: David A. Lambertson, Ph.D.; 301-435-4632; 
lambertsond@mail.nih.gov.
    Collaborative Research Opportunity: The Center for Cancer Research, 
Laboratory of Molecular Biology, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize this technology. Please contact 
John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more 
information.

    Dated: November 4, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E9-27196 Filed 11-10-09; 8:45 am]

BILLING CODE 4140-01-P