[Federal Register Volume 74, Number 212 (Wednesday, November 4, 2009)]
[Notices]
[Pages 57180-57182]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-26607]


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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.

Live-Attenuated Tularemia Vaccine

    Description of Invention: The invention provides compositions and 
methods of use for a modified strain of Francisella tularensis, the 
causative agent of tularemia, a category A biodefense agent (NIAID 
classification). Currently, no vaccines are available, and the only 
approved therapeutics for tularemia are antibiotics that are only 
effective if delivered early in the infection. The subject invention 
defines and characterizes mutations in Francisella tularensis that 
result in attenuated bacteria capable of inducing strong protective 
immune responses. Thus, these stable mutant strains could be used as 
efficient live vaccines against tularemia.
    Applications: Live-attenuated vaccines against Francisella 
tularensis.
    Advantages:
     Live-attenuated bacteria can be easily produced through 
recombinant technologies
     Live-attenuated vaccines do no require adjuvants
     Immune response to live-attenuated vaccines lasts for 
years and does not require booster
    Development Status: In vitro and in vivo data available.

[[Page 57181]]

    Inventors: Jean A. Celli and Catharine M. Bosio (NIAID).
    Relevant Publications:

1. TD Wehrly et al. Intracellular biology and virulence determinants of 
Francisella tularensis revealed by transcriptional profiling inside 
macrophages. Cell Microbiol. 2009 Jul;11(7): 1128-1150.
2. J Su et al. Genome-wide identification of Francisella tularensis 
virulence determinants. Infect Immun. 2007 Jun;75(6):3089-3101.
3. S Janovsk[aacute] et al. Identification of immunoreactive antigens 
in membrane proteins enriched fraction from Francisella tularensis LVS. 
Immunol Lett. 2007 Feb 15;108(2):151-159.
4. S Janovsk[aacute] et al. Proteomic analysis of antibody response in 
a case of laboratory-acquired infection with Francisella tularensis 
subsp. tularensis. Folia Microbiol (Praha). 2007;52(2):194-198.

    Patent Status: U.S. Provisional Application No. 61/156,173 filed 27 
Feb 2009 (HHS Reference No. E-125-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Sally Hu, Ph.D.; 301-435-5606; [email protected].
    Collaborative Research Opportunity: The NIAID Office of Technology 
Development is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize live vaccine strains of Francisella 
tularensis with defined mutations. Please contact Rosemary Walsh at 
301-496-2644 for more information.

Improved Targeting Precision of Radiotherapy

    Description of Invention: The technology offered for licensing is 
in the field of radiotherapy. The invention provides for improvement in 
the targeting precision of 4D Image-Guided Radiation Therapy (4D IGRT). 
It relates to new methods for (1) predicting the dynamic tidal volume 
of a patient and (2) predicting the motion of the diaphragm and points 
of interest near the diaphragm, by monitoring the external volume 
change of a patient's torso, thereby improving the time-resolved 
computed tomography (4DCT) and motion-compensated radiation therapy 
(4DRT). The method is based on the observation that the change in torso 
volume is representative of the change in lung air volume (expansion 
and contraction) driven by diaphragm displacement, as evidence by the 
high linear relationship between the two with a linear coefficient of 
unity. A model of lung volume expansion and extension within a 
patient's rib cage is presented in this invention to convert the 
external torso volume change (TVC) to relative diaphragm displacement.
    Applications: The method can be integrated with Image-Guided 
Radiation Therapy and related instrumentation to provide improvement in 
targeting precision and thus enhancement in therapeutic ratio and 
radiotherapy outcome.
    Advantage: The invention is advantageous to previous methods 
related to tracking of internal organ motion due to its unique 
observations as follows:
     There is a highly correlated, quantitative linear 
relationship between volume changes of the external torso and the 
internal lung during respiration.
     Based on this external-internal volumetric relationship 
and lung volume compensation model, a patient's diaphragm displacement 
can be predicted with a clinically acceptable accuracy.
    A novel approach based on these observations may therefore offer a 
more accurate and reliable approach for motion tracking during 4D IGRT, 
in comparison to existing methods. In particular, the advantages which 
may be provided by this technology are as follows:
     Minimizing the use of excessive ionization radiation for 
patient imaging. The use of x-ray based imaging techniques can be 
largely avoided.
     Minimizing the use of intrusive implanted fiducials for 
target localization, a method currently used in radiation therapy.
     Torso volume change is more comprehensive indication of 
lung volume change than the fiducial displacement or bellows tension, 
which are both indirect indicators. This approach intrinsically 
eliminates the problems due to sensitivity of marker location, 
reproducibility of marker(s) placement, complexity of data analysis, 
and reliability of motion correlation in the presence of breathing 
irregularity and breathing pattern change.
     The technology may be advantageous to the currently used 
spirometry method, which requires frequent calibration, baseline drift 
calibration and inconvenience.
     The technology can be utilized by modifying existing 
superficial imaging techniques, such as optical camera imaging (OCI) 
systems. Therefore it is highly likely that the technology can be 
integrated into an image guided radiation therapy in the future.
    Development Status: The core of this invention is established. The 
following 2 on-going studies have been initiated: (1) Calculating the 
motion of a tumor anywhere in the lungs using a tumor motion model and 
volumetric boundary conditions, and (2) calculating the volumes using a 
surface imaging system and testing the accuracy based on phantom and 
patient studies. The implementation of this technique after the studies 
should be straightforward in an existing radiotherapy system.
    Market: The commercial market of radiotherapy and related equipment 
is huge. Radiotherapy alone or in combination with chemotherapy is used 
for at least 50% of cancer treatments. According to market research the 
radiation therapy market is growing rapidly with annual cancer rates 
worldwide projected to increase by fifty percent by 2020. Extra-cranial 
stereotactic body radiotherapy (SBRT) using ablative or near ablative 
radiation dose to the tumor has shown significant improvement in local 
control rate, especially in early stage of non-small cell lung cancer 
(NSCLC). The requirement for high precision motion monitoring and 
tracking is critical for SBRT procedures with clinically tolerable 
toxicity to normal tissues.
    Methods of calculating internal organ motion are incorporated into 
radiotherapy systems to enhance their targeting precision and improve 
therapeutic ratio. The market for these methods is therefore vast and 
rapidly growing. In particular, there is a constant need for such 
improved methods that can readily be integrated into existing systems. 
The invention described here has therefore a good potential for 
commercial success.
    Inventors: Guang (George) Li (NCI), Robert W. Miller (NCI), Kevin 
A. Camphausen (NCI), et al.
    Patent Status: U.S. Provisional Application No. 61/145,487 filed 16 
Jan 2009 (HHS Reference No. E-151-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contacts: Uri Reichman, Ph.D., MBA; 301-435-4616; 
[email protected]; John Stansberry, Ph.D.; 301-435-5236; 
[email protected].

A Novel Multimeric CD4 Fusion Protein for Treating HIV Infection

    Description of Invention: This invention could potentially provide 
an alternative to antiretroviral therapy (ART), especially in cases 
where productively-infected cells persist with ART. This multimeric CD4 
fusion protein acts as a decoy to inhibit human immunodeficiency virus 
(HIV-1) entry

[[Page 57182]]

into host cells. More specifically, this multimeric CD4 inhibits the 
interaction between HIV-1 gp120 and CD4 present on the surface of CD4 
T-cells, the major HIV-1 target cell. There is strong evidence that 
binding between gp120, as part of a virion spike, and CD4 on cell 
surface is the first step for HIV entry into host cells. This 
multimeric CD4 provides a number of advantages over inhibitory CD4 
molecules previously developed. First, this CD4 multimer is capable of 
binding at least 10 gp120 simultaneously with high avidity. Second, it 
does not enhance HIV infection at suboptimal concentrations, a 
phenomenon observed with previously developed recombinant CD4 
molecules. Third, it has been demonstrated that this CD4 fusion protein 
hyper-crosslinks CD16 on natural killer (NK) cells and as a consequence 
delivers an exceptionally strong signal to NK cells, promoting potent 
Antibody-Dependent Cellular Cytotoxicity (ADCC) and lysis of HIV-
infected cells. The inventors have shown that this recombinant CD4 
multimer efficiently neutralizes primary isolates from different HIV 
subgroups.
    The invention comprises an immunoglobulin construct having up to 12 
amino terminal domains of CD4 (D1D2), the epitope responsible for HIV-1 
gp120 binding activity. It also comprises domains of a human IgG1 heavy 
chain, as well as the IgA tailpiece that drives its polymerization. The 
two amino terminal domains of CD4 are fused to the CH2CH3 domains 
(which bears the FC receptor recognition epitopes) of a human IgG1 
heavy chain.
    Applications: HIV therapeutics and HIV vaccine development.
    Advantages: Efficient inhibition of HIV-1 viral entry without 
enhancement of infection at suboptimal concentrations. Potent 
activation of Antibody-Dependent Cellular Cytotoxicity (ADCC) and lysis 
of HIV-infected cells.
    Development Status: The anti-HIV activity of this multimeric CD4 
protein has been well characterized in vitro.
    Inventors: James Arthos, Claudia Cicala, Anthony S. Fauci (NIAID).
    Publications:

1. J Arthos et al. Biochemical and biological characterization of a 
dodecameric CD4-Ig fusion protein: implications for therapeutic and 
vaccine strategies. J Biol Chem. 2002 Mar 29;277(13):11456-11464.
2. PD Kwong et al. HIV-1 evades antibody-mediated neutralization 
through conformational masking of receptor-binding sites. Nature. 2002 
Dec 12;420(6916):678-682.
3. N Gupta et al. Targeted lysis of HIV-infected cells by natural 
killer cells armed and triggered by a recombinant immunoglobulin fusion 
protein: implications for immunotherapy. Virology. 2005 Feb 
20;332(2):491-497.
4. T Zhou et al. Structural definition of a conserved neutralization 
epitope on HIV-1 gp120. Nature. 2007 Feb 15;445(7129):732-737.
5. A Bennett et al. A Cryoelectron tomographic analysis of an HIV-
neutralizing protein and its complex with native viral gp120. J Biol 
Chem. 2007 Sep 21;282(38):27754-27759.
    Patent Status: HHS Reference No. E-337-2001/0--
     U.S. Patent No. 7,368,114 issued 06 May 2008
     European Application No. 02799169.4 (recently allowed)
    Licensing Status: Available for licensing.
    Licensing Contact: RC Tang, JD, LLM; 301-435-5031; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Allergy and Infectious Diseases, Laboratory of Immunoregulation, is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
this invention. Please contact William Ronnenberg at 301-451-3522 or 
[email protected] for more information.

    Dated: October 29, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E9-26607 Filed 11-3-09; 8:45 am]
BILLING CODE 4140-01-P