[Federal Register Volume 70, Number 238 (Tuesday, December 13, 2005)]
[Notices]
[Pages 73779-73781]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E5-7249]


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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.

Tri-Functional Nanospheres

Yun-bo Shi (NICHD) et al.
U.S. Patent Application No. 11/135,380 filed 24 May 2005 (HHS Reference 
No. E-145-2005/0-US-01).
Licensing Contact: Cristina Thalhammer-Reyero; 301/435-4507; 
[email protected].

    Available for licensing and commercial development is an invention 
related to ``biofunctional'' tri-functional nanospheres (TFNs) or 
multi-functional nanospheres (MFNs) obtained by binding one or more 
biomaterials, such as folate, IgG, biotin or streptavidin, to 
fluorescent-magnetic bifunctional nanospheres (BFNs). Unlike other BFNs 
available, which are virtually all based on having a magnetic core, the 
present invention is based on mesoporous BFNs with hydrophobic inner 
cavities. The properties of the TFNs of the subject invention have 
superior qualities for use for the various applications that require 
aqueous solutions.
    Nanospheres are becoming the materials of choice for a rapidly 
increasing number of pharmaceutical and biomedical applications, 
including the use of quantum dots (QDs) and magnetic nanoparticles. 
Materials with the combined function of fluorescent labeling and 
magnetic separation have many applications in biomedical science, 
including those resulting from the encapsulation of both particles in 
polymer microcapsules. However, these related prior technologies are 
predominantly dependent on core-shell type technologies. Typically, a 
magnetic material such as magnetite or a fluorescent particle such as a 
QD is used as a core. Such a core-shell structure is chemically 
unstable and disadvantageous for fluorescence applications because the 
shell tends to absorb either or both of the excitation and emission 
lights, thus dimming the fluorescent signal. The nanoparticles of this 
invention are composed of a mesoporous copolymer, a magnetic material 
embedded into the mesoporous copolymer, a fluorescent nanomaterial 
concurrently embedded into the mesoporous copolymer, and one or more 
biomaterials coupled to the mesoporous copolymer.
    TFNs and MFNs have multiple uses. When the TFNs are labeled by a 
single biomaterial, the nanoparticles may specifically bind to a cell, 
or a protein or any other moiety that to which the biomaterial 
specifically binds. For instance, the biomaterial may be a small 
molecule ligand that is specifically bound by a cell surface receptor. 
MFNs in which two bioagents are coupled to single BFNs allow using one 
bioagent to target a macromolecule or a cell and using the second one 
to alter the function/properties of the macromolecule or cell, e.g., 
using a protein to target a cell and using a toxin or cell death 
protein to kill the targeted cell, or using a chemical or protein to 
target a protein within a complex and another one to alter the function 
of a different component of the complex.
    The technology is further described in ``Biofunctionalization of 
fluorescent-magnetic-biofunctional nanospheres and their 
applications,'' Guo-Ping Wang, Er-Qun Song, Hai-Yan Xie, Zhi-Ling 
Zhang, Zhi-Quan Tian, Chao Zuo, Dai-Wen Pang, Dao-Cheng Wu and Yun-Bo 
Shi; Chemical Communications, 2005, (34), 4276-4278; DOI: 10.1039/
b508075d.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Efficient Growth of Wild-Type Hepatitis A Virus in Cell Culture for 
Development of Live Vaccines

Gerarado Kaplan and Krishnamurthy Konduru (FDA).

[[Page 73780]]

U.S. Provisional Application No. 60/684,526 filed 28 Jun 2005 (HHS 
Reference No. E-151-2004/0-US-01).
Licensing Contact: Chekesha S. Clingman; 301/435-5018; 
[email protected].
    This technology relates to the development of recombinant wild-type 
and attenuated Hepatitis A Virus (HAV) vectors capable of growing in 
cell culture and useful for development of a live HAV vaccine. This 
technology also encompasses HAV vectors coding for markers that allow 
the selection of cell lines that support the efficient growth of wild-
type and attenuated HAV in culture for diagnostic and environmental 
monitoring purposes. The currently available killed HAV vaccines are 
expensive and require a two dose schedule to confer immunity for 
approximately two decades. Inability of wild-type (wt) HAV to grow 
efficiently in cell culture has been the major roadblock to developing 
a live HAV vaccine, which could confer lifelong immunity, be cost-
effective and allow eradication of the virus. The inventors have 
developed recombinant infectious HAV coding for resistance genes 
against antibiotics that inhibits translation in mammalian cells and 
provides a selective phenotype that allows selection of cells 
expressing the phenotype within one week. Also, the inventors have 
created methods of selecting cells permissive for replication of wild-
type and not overly attenuated HAV by utilizing selective or screened 
phenotypes and antibiotic resistant cell techniques.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Internal Control Nucleic Acid Molecule for Real-Time Polymerase Chain 
Reaction

Michael Vickery, Angelo DePaola, George Blackstone (FDA).
U.S. Provisional Application No. 60/471,121 filed 16 May 2003 (HHS 
Reference No. E-213-2003/0-US-01);
PCT Application No. PCT/US04/15175 filed 14 May 2004 (HHS Reference No. 
E-213-2003/0-PCT-02).
Licensing Contact: Michael Shmilovich; 301/435-5019; 
[email protected].

    The invention provides a PCR internal control system for use in 
both real-time PCR (also known as kinetic or Q-PCR) and conventional 
PCR. This flexible system has a number of novel design qualities which 
make it universally adaptable for use in virtually any real-time or 
conventional PCR assay, including RT-PCR and multiplex PCR 
applications, regardless of the organism/gene/nucleic acid being 
targeted. It provides the user/assay developer a choice of control 
product sizes, fluorogenic probe reporting systems, and thermal cycling 
options, allowing ease of incorporation into various assay formats and 
instrument platforms. This unique internal control also can be readily 
incorporated into virtually any existing quantitative multiplex real-
time PCR assay. The invention also provides methods of using the 
internal control system and kits of the invention.
    Additional information may be found in Vickery et al., ``Detection 
and Quantification of Total and Potentially Virulent Vibrio 
parahaemolyticus Using a 4-Channel Multiplex Real-Time PCR Targeting 
the tl, tdh, and trh Genes and a Novel PCR Internal Control,'' 
published abstract, 103rd General Meeting of the American Society for 
Microbiology, May 18-23, 2003, Washington, DC.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Bisubstrate Inhibitors of Acetyltransferases

Dr. David Klein et al. (NICHD).
HHS Reference No. E-205-1999/0-PCT-02 filed 08 Aug 2000.
Licensing Contact: Marlene Shinn-Astor; 301/435-4426; 
[email protected].

    The present invention provides methods of inhibiting 
acetyletransferase enzymes, such as arylalkylamine-N-acetyltransferase 
(AANAT), by producing a bisubstrate inhibitor in a cell. AANAT 
catalyzes the transfer of acetyl groups from Acetyl coenzyme A (AcCoA) 
to substrates such as serotonin. Bisubstrate inhibitors are compounds 
which share characteristics of AcCoA and of the specific acetyl group 
acceptors. A highly potent bisubstrate inhibitor of AANAT is CoA-S-N-
acetyltryptamine. That inhibitor may be formed in vitro by the reaction 
of alkylating derivatives of the acetyl acceptor and AcCoA. However, 
the inhibitor thus formed does not cross the cell membranes and is 
expensive to produce using AcCoA.
    The present invention is based on the surprising discovery that a 
bisubstrate inhibitor which is specific for a particular 
acetyltransferase can be formed in a cell by introducing into the cell 
an alkylating derivative of an acetyl acceptor. Formation of the 
bisubstrate inhibitor occurs efficiently at very low concentrations of 
introduced drug because the enzyme to be inhibited positions and 
catalyzes the reactants favorably to form the inhibitor. The 
bisubstrate inhibitor is likely to accumulate in the cell because it is 
stable, highly charged and thus will not pass through cell membranes. 
The targeted acetyltransferase will thus be inhibited and therapeutic 
actions realized.
    The varied actions of acetyltransferases in biochemical processes 
offer many potential therapeutic targets. Acetylation inactivates drugs 
and endogenous ligands so inhibitors could, for example, enhance the 
effectiveness of antibiotics where antibiotic resistance is due to a 
high level of acetylation. In the case of AANAT, acetylation 
inactivates serotonin and is the rate limiting step in the formation of 
melatonin. Inhibition of AANAT will thus decrease melatonin production 
and increase serotonin levels. Melatonin is a pineal hormone that has 
endocrinological, neurophysiological, and behavioral functions. Since 
melatonin and serotonin are implicated in several types of mood 
disorders, inhibition of AANAT could have valuable therapeutic uses. 
Specific inhibitors of melatonin synthesis are not yet available and 
serotonin antagonists have unacceptable side effects in many patients.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Imaging With Positron-Emitting Taxanes, Camptothecins, and Other Drugs 
as a Guide to Antitumor Therapy

Jerry M. Collins, Raymond W. Klecker, Lawrence Anderson (FDA).
U.S. Patent Application No. 10/088,561 filed 19 Mar 2002 (HHS Reference 
No. E-263-1998/0-US-03);
U.S. Patent Application No. 10/319,812 filed 16 Dec 2002 (HHS Reference 
No. E-263-1998/1-US-01).
Licensing Contact: Michael Shmilovich; 301/435-5019; 
[email protected].

    Available for licensing and commercial development is a method for 
using of positron-emitting compounds to label taxane type drugs. This 
invention also relates to the use, synthesis and structure of three 
radio-labeled probe molecules, \11\C-SN-38, \11\C-imatinib, and \11\C-
mitoxantrone. SN-38 is a major active metabolite of Camptosar, a 
product marketed by Pharmacia for the treatment of colorectal cancer. 
Imatinib is a compound that is used to treat chronic myeloid leukemia 
(CML) and is

[[Page 73781]]

marketed under the tradename Gleevec. Mitoxantrone is also used to 
treat certain types of cancers and multiple sclerosis. For all of these 
compounds the FDA approved new and expanded uses and there is intense 
interest in determining whether and where each of the compounds 
actually collects in the body, and especially whether they are taken up 
by the targeted tumor. Traditional approaches to determine drug uptake 
and retention have been invasive. Advantages of using this technology 
include: (1) Avoidance of exposing patients to toxic drugs that have no 
potential for benefit; (2) ability to rapidly determine whether a given 
tumor will be likely to respond to a particular drug; and (3) the 
ability to monitor the impact of various dosages, schedules, and 
modulators for delivery, in situ, at the actual tumor under treatment 
conditions. Further, methods to guide treatment of solid tumors, with 
labeled taxanes, are also disclosed in the present application.
    Additional information may be found in: Ravert et al., 
``Radiosynthesis of [11C]paclitaxel,'' J Label Compd and Radiopharm, 
2002, 45(6):471-477.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

    Dated: December 1, 2005.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E5-7249 Filed 12-12-05; 8:45 am]
BILLING CODE 4140-01-P