[Federal Register Volume 75, Number 166 (Friday, August 27, 2010)]
[Notices]
[Pages 52756-52758]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-21347]


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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.

System and Method for Producing Nondiffracting Light Sheets that 
Improves the Performance of Selective Plane Illumination Microscopy 
(SPIM)

    Description of Invention: The technology offered for licensing 
relates to a system and method of producing nondiffracting beams of 
light that spatially overlap, but do not interfere with each other when 
intersecting the detection plane of an optical arrangement. The system 
includes an illumination source (i.e. ultrafast laser) for transmitting 
a beam of light through the optical arrangement that includes a 
diffraction grating for diffracting the light beam to produce beams of 
light having different wavelengths, which are then passed through an 
annular aperture that transforms the beams of light into nondiffracting 
beams having different wavelengths. The method can be readily utilized 
in Selective Plane Illumination Microscopy (SPIM), a system that 
provides optical sectioning of a sample that is labeled with 
fluorescent dyes. SPIM can provide quantitative three-dimensional maps 
of the distribution of a flurophore within the sample with high 
spatiotemporal resolution and an excellent signal-to-noise ratio. The 
standard SPIM technique however produces nonuniform axial resolution, 
which is caused by the diffraction of the laser beam through the 
sample, causing degradation in the optical sectioning, and forcing a 
compromise between field of view and axial resolution. Techniques for 
decoupling field of view and axial resolution have previously utilized 
nondiffracting beams (e.g. Bessel beams) for sample illumination. The 
resulting interference from multiple nondiffracting beams degrades the 
quality of optical sectioning and the quality of the image. The present 
technology utilizing nondiffracting noninterfering beams is intended to 
alleviate the problems associated with the currently used SPIM 
techniques.
    Applications: In Selective Plane Illumination Microscopy (SPIM) 
used for optical sectioning and imaging of biological samples.
    Development Status: Proof of concept has been demonstrated.

[[Page 52757]]

    Inventors: Andrew York, Yicong Wu, Hari Shroff (NIBIB)

Relevant Publications

    1. Durnin J, Micheli J Jr, Eberly JH. Diffraction-free beams. Phys 
Rev Lett. 1987 Apr 13;58(15):1499-1501.
    2. Greger K, Swoger J, Stelzer EH. Basic building units and 
properties of a fluorescence single plane illumination microscope. Rev 
Sci Instrum. 2007 Feb;78(2):023705. [PubMed: 17578115]
    3. Fahrbach F, Rohrbach A. Microscopy with Non-diffracting Beams. 
Abstract at 2009 Focus on Microscopy Conference, http://www.focusonmicroscopy.org/2009/PDF/28l_Fahrbach.pdf.
    4. Rohrbach A. Artifacts resulting from imaging in scattering 
media: a theoretical prediction. Opt Lett. 2009 Oct 1;34(19):3041-3043. 
[PubMed: 19794809]
    Patent Status: U.S. Provisional Application No. 61/360,352 filed 30 
Jun 2010, entitled ``System and Method of Producing Nondiffracting 
Light Sheets by a Multiplicity of Spatially Overlapping, Minimally 
Interfering Nondiffracting Optical Beams'' (HHS Reference No. E-118-
2010/0-US-01).
    Licensing Status: Available for licensing.

Licensing Contacts

     Uri Reichman, Ph.D., MBA; 301-435-4616; [email protected].
     Michael Shmilovich, Esq.; 301-435-5019; 
[email protected].
    Collaborative Research Opportunity: The NIBIB Section on High 
Resolution Optical Imaging is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize the nondiffracting Light Sheets for 
SPIM. Please contact Hari Shroff at 301-435-1995 or [email protected] 
for more information.

Method of Producing Immortalized Primary Human Keratinocytes for HPV 
Investigation, Testing of Therapeutics, and Skin Graft Generation

    Description of Invention: One of the major limitations of using 
cultured keratinocytes for research studies is that primary 
keratinocytes senesce after a few passages. Keratinocytes from specific 
anatomical sites are also difficult to culture. Scientists at the NIH 
have demonstrated that primary keratinocytes, from several anatomical 
sites, when treated with a small-molecule inhibitor of the ROCK protein 
maintain a proliferative state and become immortal without genetic 
modification to the cells. Keratinocytes are also the host cells for 
human papillomaviruses (HPVs) and other viruses and this technology 
enables the study of those viruses that do not immortalize cells. In 
addition, this technology may enhance the quantity of material 
available for skin grafts, as current grafting techniques are limited 
by the amount of donor material immediately available. Thus, this 
technology may provide an ideal model environment for producing large 
quantities of both normal and diseased primary human keratinocytes from 
small numbers of primary cells from individual hosts or anatomical 
sites for research purposes, testing of therapeutics, skin graft 
generation and HPV investigation.

Applications

     Promotion of sustained primary human keratinocyte 
proliferation in vitro.
     Human skin graft cultures and techniques.
     Immortalization of both normal and diseased cells from 
individual hosts.
     Immortalization of ``difficult to establish'' 
keratinocytes from different anatomical sites.
     In vitro assay for investigating the full life cycle of 
HPV.
     In vitro screen for HPV inhibitors.

Advantages

     Allows culture and immortalization of many types of 
keratinocytes that are difficult to establish and pass in culture.
     Allows isolation of diseased and normal keratinocytes from 
individual hosts for research and therapeutic purposes.
     Current HPV investigations are limited by keratinocyte 
senescence.
     Skin graft generation is currently dependent on slow 
culture of limited quantities of donor material.
    Development Status: Early stage: cell-based assays using primary 
human cells.
    Market: Over 6 million individuals become infected by genital HPV 
every year and over 500,000 new cases of anal and genital warts are 
diagnosed annually in the United States (http://www.cancer.org). At 
least 40,000 American burn victims are hospitalized annually, including 
25,000 admissions to hospitals with specialized burn centers (http://www.ameriburn.org) and skin grafts for diabetic ulcers are increasing. 
Skin disease is very prevalent and is estimated to affect greater than 
50% of individuals in Western countries (Rea et al., British Journal of 
Preventive and Social Medicine 30: 107-14, 1976.
    Inventors: Alison McBride (NIAID), Sandra E. Chapman (NIAID), 
Jonathan C. Vogel (NCI), Atsushi Terunuma (NCI).
    Publication: Chapman S et al. Human keratinocytes are efficiently 
immortalized by a Rho kinase inhibitor. J Clin Invest. 2010 Jul 
1;120(7):2619-26. [PubMed: 20516646].
    Patent Status: PCT Patent Application No. PCT/US2009/066844 filed 
12 Apr 2009, which published as WO/2010/065907 on 10 Jun 2010 (HHS 
Reference No. E-055-2009/0-PCT-02).
    Licensing Status: Available for licensing.
    Licensing Contact: Jeffrey Clark Klein, Ph.D.; 301-594-4697; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Allergy and Infectious Diseases, Laboratory of Viral Diseases is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
methods of producing immortalized primary human keratinocytes. Please 
contact Johanna Schneider, Ph.D. at 301-451-9824 or 
[email protected] for more information.

Novel Drugs for the Treatment of Schizophrenia

    Description of Invention: Because psychosis and cognitive decline 
are among the most common debilitating afflictions of humans, the 
search for new treatments is very important and timely.
    Researchers at the NIH have found that genetic variations on the 
PIK3CD gene are associated with schizophrenia in Caucasian and African 
American families and can affect normal human cognition functions such 
as memory, IQ and executive cognition. The inventors have shown that an 
inhibitor of the phosphatidylinositol 3-kinase p110 delta (PIK3CD) 
enzyme, which is encoded by the PIK3CD gene, significantly improves a 
migratory response that is critically impaired in schizophrenic 
patients. This drug, as well as other PIK3CD inhibitors, could provide 
effective treatments of psychosis and cognitive decline.
    Applications: Novel target for development of therapeutics of CNS 
disorders including schizophrenia, psychosis, and cognitive deficiency.
    Development Status: Early stage: in vivo rodent and in vitro human 
cells.
    Market: According to BioPortfolio, the world schizophrenia market 
was $12 billion in 2004. Schizophrenia affects approximately 0.5% of 
both the U.S. and world populations.
    Inventors: Amanda J. Law and Daniel R. Weinberger (NIMH).
    Publication: In preparation.

[[Page 52758]]

    Patent Status: PCT Application No. PCT/US2009/66867 filed 04 Dec 
2009 (HHS Reference No. E-054-2009/0-PCT-02).
    Licensing Status: Available for licensing.
    Licensing Contact: Charlene Sydnor, Ph.D.; 301-435-4689; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Mental Health Clinical Brain Disorders Branch is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize the development 
of PIK3CD inhibitors for the treatment of CNS disorders including 
schizophrenia, psychosis, and cognitive deficiency. Please contact 
Amanda Law at [email protected] for more information.

Fast Electron Paramagnetic Resonance Imaging (EPRI) Using CW-EPR 
Spectrometer With Sinusoidal Rapid-Scan and Digital Signal Processing

    Description of Invention: Electron Paramagnetic Resonance (EPR) 
Imaging is an indispensable tool that may be applied to a variety of 
disciplines for evaluation of chemical species having unpaired 
electrons such as free radicals and transition metal ions. In 
Continuous Wave (CW)-EPR the sample is continuously irradiated with 
weak RF radiation while sweeping the magnetic field relatively slowly. 
Existing CW-EPR techniques utilize a signal detection method known as 
phase-sensitive detection which results in data acquisition times that 
are too long for in vivo applications. The present technology 
represents significant improvements on conventional CW-EPR.
    The subject technology includes three approaches to collecting 
image data with increased spatial, temporal and spectral resolution and 
improved sensitivity. Spectral data acquisition is performed by a 
direct detection strategy involving mixing a signal to base-band and 
acquiring data with a fast-digitizer. Projection data is acquired using 
a sinusoidal magnetic field sweep under gradient magnetic fields. Data 
collection times are decreased with the utility of rotating gradients.
    Further improvement to the present technology includes optimized 
DSP (digital signal processing) transmit and receive systems that 
decrease the analog background noise and allow optimizing the extent of 
signal averaging for improved image quality.
    Increased speed and sensitivity make CW-EPR a potentially useful 
and complementary tool to proton Magnetic Resonance Imaging for in vivo 
imaging. The presently described improvements to CW-EPR will allow 
changes of blood perfusion and oxygenation in tumors to be observed in 
nearly real-time, while improved resolution will permit angiogenesis in 
and around tumors to be monitored in a non-invasive manner. 
Additionally, rapid scan imaging provides excellent temporal resolution 
and will help quantify pharmaco-kinetics and metabolic degradation 
kinetics of bioactive and redox sensitive free radicals such as 
nitroxides.

Applications

     Enhanced spatial, temporal, and spectral resolution of 
Continuous Wave-Electron Paramagnetic Resonance Imaging.
     Real-time assessment of changes in blood perfusion and 
oxygenation.
    Development Status: Preliminary experiments have been conducted and 
the technology has been tested for feasibility.
    Inventors: Sankaran Subramanian et al. (NCI).
    Relevant Publication: Subramanian S, Koscielniak JW, Devasahayam N, 
Pursley RH, Pohida TJ, Krishna MC. A new strategy for fast 
radiofrequency CW EPR imaging: Direct detection with rapid scan and 
rotating gradients. J Magn Reson. 2007 Jun; 186(2):212-219. [PubMed: 
17350865].

Patent Status

     U.S. Provisional Application No. 60/818,052 filed 30 Jun 
2006 (HHS Reference No. E-221-2005/0-US-01).
     PCT Application No. PCT/US07/00072371 filed 02 Jul 2007, 
which published as WO 2008/091365 on 31 Jul 2008 (HHS Reference No. E-
221-2005/1-PCT-01).
     U.S. Patent Application No. 12/306,514 filed 23 Dec 2008 
(HHS Reference No. E-221-2005/1-US-02).
     U.S. Patent Application No. 12/564,006 filed 21 Sep 2009 
(HHS Reference No. E-221-2005/2-US-01).
    Licensing Status: Available for licensing.

Licensing Contacts

     Uri Reichman, PhD, MBA; 301-435-4616; [email protected].
     John Stansberry, PhD; 301-435-5236; [email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Radiation Biology Branch, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop improved hardware in terms of higher gradient & sweep 
frequencies and compatible AC amplifiers and evaluate, or commercialize 
the above rapid scan-rotating gradients strategy for performing routine 
in vivo radiofrequency CW EPR imaging in small animals. Please contact 
John D. Hewes, PhD, at 301-435-3121 or [email protected] for more 
information.

    Dated: August 20, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-21347 Filed 8-26-10; 8:45 am]
BILLING CODE 4140-01-P