[Federal Register Volume 70, Number 186 (Tuesday, September 27, 2005)]
[Notices]
[Pages 56475-56477]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-19173]


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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.

HIV-Encoded siRNA, microRNA and Suppressor of RNA Silencing

Yamina Bennasser et al. (NIAID)
U.S. Provisional Application No. 60/677,839 filed 05 May 2005 (HHS 
Reference No. E-203-2005/0-US-01).
Licensing Contact: Susan Ano; 301/435-5515; [email protected].

    The present invention relates to virus-encoded siRNA and miRNA 
species and the use of such RNAs in the diagnosis, prevention and/or 
treatment of retroviral infection, especially HIV or SIV infection. 
This invention conveys the first evidence that HIV-1 encodes viral 
siRNA precursors in its genome and that natural HIV-1 infection 
provokes nucleic acid-based immunity in human cells. To overcome this 
cellular defense, the HIV-1 Tat protein has evolved to include a 
suppressor of RNA silencing (SRS) function. Additionally, this 
invention identifies five microRNA (miRNA) precursor candidates that 
regulate cellular gene expression at a post-transcriptional level. The 
five miRNA precursors (21-25 nucleotides in length) are encoded in 
highly conserved regions of HIV such as TAR sequence, gag, pol and nef 
genes. These findings indicate that viruses utilize RNA interference as 
a mechanism to regulate cellular gene expression.
    This technology is further described in: Bennasser et al., ``HIV-1 
encoded candidate micro-RNAs and their cellular targets,'' 
Retrovirology 2004 Dec 15, 1(1):43, doi:10.1186/1742-4690-1-43; and 
Bennasser et al., ``Evidence that HIV-1 encodes an siRNA and a 
suppressor of RNA silencing,'' Immunity 2005 May, 22(5):607-619, 
doi:10.1016/j.immuni.2005.03.010.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Miniature Laser-Induced Fluorescence Detector

Paul Smith, Nicole Morgan, Edward Wellner, Terry Phillips (ORS)
U.S. Provisional Application No. 60/682,847 filed 20 May 2005 (HHS 
Reference No. E-129-2005/0-US-01).
Licensing Contact: Michael Shmilovich; 301/435-5019; 
[email protected].

    Available for licensing and commercial development is a miniature 
laser-induced fluorescence detector having an in-line microfluidic 
detection cell. The detection cell finds application in High 
Performance Liquid Chromatography (HPLC), Capillary Electrophoresis 
(CE) and Mass Spectroscopy (MS) applications, among others. The cell 
for fluorescence measurements can have a measurement volume of 1 nL or 
less and a sample can be excited using two excitation wavelengths. The 
detection cell can include a 5 mm to 5 cm long capillary tube and an 
excitation fiber proximate to the capillary tube. A detection fiber is 
also proximate to the capillary tube, and the detection fiber has a 
diameter the same size or larger than the external diameter of the 
capillary tube. A plurality of both excitation and detection fibers can 
be used.
    In addition to licensing, the technology may be available for 
further development through collaborative research opportunities with 
the inventors.

Cellular Receptor for Varicella-Zoster Virus and Cell-to-Cell Spread of 
Virus

Jeffery Cohen et al. (NIAID)
U.S. Provisional Application No. 60/684,526 filed 26 May 2005 (HHS 
Reference No. E-289-2004/0-US-01).
Licensing Contact: Chekesha S. Clingman; 301/435-5018; 
[email protected].

    This technology relates to identification of insulin degrading 
enzyme (IDE) as a cellular receptor for Varicella-Zoster-Virus (VZV), 
the etiologic agent of varicella (chickenpox) and zoster (shingles). 
Acute infection of VZV is followed by cell-associated viremia and the 
development of varicella rash. The virus establishes life-long latency 
in the nervous system and can reactivate to cause zoster. The mechanism 
of VZV entry into target cells and spread from cell-to-cell is not well 
understood. The inventors have shown that antibodies to IDE and 
recombinant IDE partially inhibit infection with the virus in cell 
culture. Reducing the level of IDE in the cell (with siRNA), or 
blocking the ability of IDE to bind with a VZV glycoprotein, markedly 
diminishes cell-to-cell spread of the virus in cell culture and 
partially inhibits infection of cells with cell-free virus. This 
invention further describes molecules that may have a role in the 
treatment or prevention of VZV infections, including antibodies to IDE, 
peptides that block IDE-VZV interactions, and other molecules that 
block binding activity of IDE.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

A Novel Amplification Method Permits Pathogens To Be Detected With 
Microarrays

Michael J. Brownstein, Charles Xiang, and Zhi-Qing Qi (NIMH)
U.S. Provisional Application No. 60/635,239 filed 09 Dec 2004 (DHHS 
Reference No. E-184-2004/0-US-01).
Licensing Contact: Cristina Thalhammer-Reyero; 301/435-4507; 
[email protected].

[[Page 56476]]

    Available for licensing and commercial development is a high 
throughput, microarray-based multiplex method of detecting target 
nucleic acids in a sample. In particular, PCR is coupled with 
microarrays for the qualitative identification of multiple target 
nucleic acids, with primers specific for a target sequence, and used to 
detect genomic nucleic acids of pathogens of interest, or transcripts 
derived therefrom. Also claimed are oligonucleotide microarrays for use 
in such methods.
    The present method is distinguished from other multiplex PCR assays 
by the additional steps to ensure specificity and sensitivity, so that 
a larger number of probes can be detected simultaneously in each single 
reaction. An important application of this method, for which it was 
developed, is the detection of multiple ``Category A List'' agents for 
the purpose of differential diagnosis in case of bioterrorism attacks. 
The method comprises: (a) screening the genomes of the desired 
infectious agents to find sequences specific for each of them and 
distinct from human sequences; (b) designing 60 base long 
oligonucleotide targets, to print on microarrays; and (c) including in 
the microarrays both sense and antisense versions of each, as well 
multiple targets per virus, to increase reliability.
    Other methods, such as PCR amplification followed by separation and 
characterization of DNA products by gel electrophoresis, are simple and 
sensitive, but they have a number of inherent shortcomings. Highly 
sensitive PCR amplification tends to generate nonspecific DNA products, 
which complicate interpretation of the results. Additionally, in a 
typical method for detecting pathogens in a sample, PCR reactions for 
each pathogen must be run separately from one another due to 
differences in amplification conditions. Furthermore, in cases where 
multiplex PCR coupled with a microarray is used for the qualitative 
detection of several pathogens, the generation of nonspecific DNA 
products can be a significant problem. The current method is a rapid, 
high-throughput method for qualitative identification of multiple 
target nucleic acids that is sensitive, highly discriminating and 
robust.

Methods for Treating Viral-Associated Tumors With LFA-1 Inhibiting 
Statins

Jeffrey Cohen et al. (NIAID)
U.S. Provisional Application No. 60/515,013 filed 28 Oct 2003 (HHS 
Reference No. E-312-2003/0-US-01); PCT Application No. PCT/US2004/
035829 (publication WO2005/042710) filed 28 Oct 2004 (HHS Reference No. 
E-312-2003/0-PCT-02).
Licensing Contact: Susan Ano; 301/435-5515; [email protected].

    This technology describes the use of certain natural and synthetic 
statins, including simvastatin, other leukocyte function antigen-1 
(LFA-1) inhibiting statins, and compounds derived from LFA-1 inhibiting 
statins and statin-like compounds, for treatment or prevention of 
Epstein-Barr Virus (EBV) associated tumors, including lymphomas that 
express LFA-1 and transforming proteins. Such compounds could also be 
used to treat tumors associated with other viruses that express LFA-1. 
Cancers associated with EBV that could be treated with the statins by 
methods described herein include gastric carcinoma (the second leading 
cause of cancer deaths worldwide), nasopharyngeal carcinoma, Hodgkin's 
disease, lymphoproliferative disease, T-cell lymphoma, and non-
Hodgkin's lymphoma. These compounds could potentially be used as 
chemotherapeutics with possibly less severe side effects than currently 
employed chemotherapies.
    This technology is further described in: Katano et al., 
``Simvastatin induces apoptosis of Epstein-Barr virus (EBV)-transformed 
lymphoblastoid cell lines and delays development of EBV lymphomas,'' 
PNAS, 2004 Apr 6, 101(14):4966-4971, doi 10.1073/pnas.0401064101.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Attenuated Human Parainfluenza Virus (PIV) for Use as Live, Attenuated 
Vaccines and as Vector Vaccines

U.S. Provisional Application No. 60/643,310 filed 12 Jan 2005 (HHS 
Reference No. E-295-2004/0-US-01)
Sheila M. Nolan et al. (NIAID)
     and
U.S. Provisional Application No. 60/412,053 filed 18 Sep 2002 (HHS 
Reference No. E-092-2002/0-US-01); U.S. Patent Application No. 10/
667,141 filed 18 Sep 2003 (HHS Reference No. E-092-2002/0-US-02; PCT 
Application No. PCT/US03/29685 filed 18 Sep 2003, which published as 
WO2004/027037 on 01 Apr 2004 (HHS Reference No. E-092-2002/0-PCT-03), 
and National Stage filed in Canada, Europe, Japan, Australia, and India
Mario H. Skiadopoulos et al. (NIAID)
Licensing Contact: Susan Ano; 301/435-5515; [email protected].

    The identified technologies describe self-replicating infectious 
recombinant paramyxoviruses with one or more attenuating mutations, 
such as a separate variant polynucleotide encoding a P protein and a 
separate monocistronic polynucleotide encoding a V protein, or at least 
one temperature sensitive mutation and one non-temperature sensitive 
mutation. Compositions and methods for recovering, making and using the 
infectious, recombinant paramyxoviruses as described are also included 
(e.g. recombinant human parainfluenza virus type 2 (HPIV2)). In 
addition, these inventions provide novel tools and methods for 
introducing defined, predetermined structural and phenotypic changes 
into an infectious HPIV2 candidate for use in immunogenic compositions, 
including live attenuated virus vaccines. Furthermore, these inventions 
describe the recombinant HPIV2 P+V can be used to introduce attenuating 
mutations to develop live attenuated virus vaccines. The 
paramyxoviruses of the invention are also useful as vectors for 
expressing heterologous antigens (e.g. RSV, HMPV, measles or mumps 
viruses) in an immunogenic composition. As members of the 
paramyxoviruses, HPIVs are important pathogens causing severe lower 
respiratory tract infections in infants and young children. Despite 
considerable efforts, there are currently no parainfluenza virus 
vaccines available.
    Advantages of the subject technologies to generate live attenuated 
viruses or vectored vaccine candidates via multiple mutations are the 
design of safe and stable viral vaccine candidates. Since two common 
vaccine development approaches (viral subunit vaccines and inactivated 
whole virus preparations) elicited either short-lived, inadequate 
immunity or unfavorable immune responses, the identified technologies 
provide a promising means to develop vaccines against HPIVs and other 
human pathogens. In addition, live attenuated viruses are the most 
promising candidate vaccines because they induce both local and 
systemic immunity and are efficacious even in the presence of passively 
transferred serum antibodies, the very situation found in the target 
population of infants with maternally derived antibodies.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

[[Page 56477]]

Imaging With Positron-Emitting Taxanes as a Guide to Antitumor Therapy

Jerry M. Collins, Raymond W. Klecker, Lawrence Anderson (FDA)
U.S. Provisional Application No. 60/155,061 filed 21 Sep 1999 (HHS 
Reference No. E-263-1998/0-US-01); U.S. Patent Application Nos. 10/
088,561 filed 19 Mar 2002 (HHS Reference No. E-263-1998/0-US-03) and 
10/319,812 filed 16 Dec 2002 (HHS Reference No. E-263-1998/1-US-01) are 
pending.
Licensing Contact: Michael Shmilovich; (301) 435-5019; 
[email protected].

    Available for licensing and commercial development is a method for 
using positron-emitting compounds to label taxane type drugs. This 
invention also describes methods of synthesizing these taxane type 
compounds. Further, methods to guide treatment of solid tumors, with 
labeled taxanes, are also disclosed in the present application. 
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.
    Additional information may be found in: Ravert et al., 
``Radiosynthesis of [ 11C]paclitaxel,'' J Label Compd and 
Radiopharm, 2002, 45(6):471-477.

    Dated: September 15, 2005.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 05-19173 Filed 9-26-05; 8:45 am]
BILLING CODE 4140-01-P