[Federal Register Volume 74, Number 12 (Wednesday, January 21, 2009)]
[Notices]
[Pages 3620-3622]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-979]


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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.

Use of Mono-Amine Oxidase Inhibitors To Prevent Herpes Virus Infections 
and Reactivation From Latency

    Description of Technology: Available for licensing are methods of 
using Monoamine Oxidase Inhibitors (MAOIs) to prevent alpha-herpesvirus 
lytic infections, such as those caused by Herpes simplex virus (HSV-1 
or HSV-2) and Varicella zoster virus (VZV), and to possibly prevent the 
periodic reactivation of these viruses from latency. MAOIs have been 
historically used to treat depression, hypertension, and related 
diseases. The invention describes how MAOIs can also inhibit LSD1, a 
histone/protein demethylase that is required for initiation of alpha-
herpesvirus lytic infection. After an initial lytic infection, alpha-
herpesviruses establish latent infections in sensory neurons and 
undergo periodic reactivation that results in disease ranging from mild 
lesions to life threatening encephalitis. Investigators have determined 
that MAOIs may also block the reactivation process. Due to the nature 
of the target LSD1 and its role in modulating chromatin modifications, 
these drugs could also prevent infection by or reactivation of other 
nuclear viruses.
    Alpha-herpesviruses infections are common worldwide, with 57% to 
80% of adults being seropositive for HSV. Recurrent labial herpes 
affects roughly one third of the U.S. population, and these patients 
typically experience 1 to 6 episodes per year. Genital herpes can 
result from infection with either HSV type and HSV-1 has become an 
important cause of genital herpes in

[[Page 3621]]

some developed countries. HSV keratitis is the most frequent cause of 
corneal blindness in the United States, is a leading indication for 
corneal transplantation, and is the most common cause of infectious 
blindness in the Western world.
    Applications:
    <bullet> Prevention and treatment of recurrent Herpes simplex virus 
outbreaks.
    <bullet> Prevention and treatment of recurrent Varicella zoster 
infection.
    <bullet> Treatment of HSV encephalitis.
    <bullet> Treatment of Herpes keratitis.
    Development Status: The investigators intend to do a series of in 
vivo animal studies on the efficacy of MAOIs in preventing primary 
infection and/or reactivation of herpes simplex virus in a mouse model 
system.
    Inventors: Thomas M. Kristie et al. (NIAID).
    Patent Status:
    <bullet> U.S. Provisional Application No. 61/083,304 filed 24 Jul 
2008 (HHS Reference No. E-275-2008/0-US-01).
    <bullet> U.S. Provisional Application No. 61/111,019 filed 04 Nov 
2008 (HHS Reference No. E-275-2008/1-US-01).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Christina Thalhammer-Reyero, PhD; 301-435-4507; 
<a href="/cdn-cgi/l/email-protection#acd8c4cdc0c4cdc1cfecc1cdc5c082c2c5c482cbc3da"><span class="__cf_email__" data-cfemail="16627e777a7e777b75567b777f7a38787f7e38717960">[email protected]</span></a>
    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 
the use of MAOIs to prevent herpes virus infections and reactivation 
from latency. Please contact Marguerite J. Miller at 301-435-8619 or 
<a href="/cdn-cgi/l/email-protection#6e030702020b1c030f1c092e00070f070a4000070640090118"><span class="__cf_email__" data-cfemail="1a777376767f68777b687d5a74737b737e34747372347d756c">[email protected]</span></a> for more information.

Method of Treating Pneumoconiosis With Oligodeoxynucleotides

    Description of Technology: The inhalation of dust containing 
crystalline silica particles causes silicosis, an incurable lung 
disease that progresses even after dust exposure ceases. The World 
Health Organization estimates that over a million U.S. workers are 
exposed to silica dust annually, and that thousands worldwide die each 
year from silicosis. The pulmonary inflammation caused by silica 
inhalation is characterized by a cellular infiltrate and the 
accumulation of chemokines, cytokines (including TNF-alpha, IL-1, and 
IL-6), and Reactive Oxygen Species (ROS) in bronchoalveolar lavage 
(BAL) fluid.
    Macrophages are the predominant immune cell type present in 
alveolar spaces where they play an important role in the lung pathology 
associated with silica inhalation. The uptake of silica particles by 
macrophages triggers the production of ROS (including hydrogen 
peroxide) via the oxidative stress pathway, which in turn contributes 
to pulmonary damage and macrophage death.
    One potential strategy for limiting the production of 
proinflammatory cytokines and ROS after silica exposure involves 
treatment with ``suppressive'' oligonucleotides (ODN). Suppressive ODN 
express motifs based on the repetitive TTAGGG hexamers present at high 
frequency in the telomeric ends of self DNA. Previous studies showed 
that these motifs (released by injured host cells) block Th1 and 
proinflammatory cytokine production in vitro and down-modulate over-
exuberant/pathologic immune responses in vivo (such as those found in 
septic shock and autoimmune diseases).
    This application claims methods for treating, preventing or 
reducing the risk of developing occupational lung diseases using. 
Preclinical in vivo studies show that pretreatment with suppressive 
(but not control) ODN reduces silica-dependent pulmonary inflammation. 
Preclinical in vivo studies also showed that treatment with suppressive 
ODN also reduced disease severity and improved the survival of mice 
exposed to silica.
    Application: Development of ODN-based therapeutics for the 
treatment of pneumoconiosis.
    Development Status: ODNs have been synthesized and preclinical 
studies in the murine model of acute silicosis have been performed.
    Inventors: Dennis M. Klinman (NCI), Takashi Sato (NCI), et al.
    Publication: T Sato et al. Suppressive oligodeoxynucleotides 
inhibit silica-induced pulmonary inflammation. J Immunol. 2008 Jun 
1;180(11):7648-7654.
    Patent Status: U.S. Provisional Application No. 61/055,102 filed 21 
May 2008 (HHS Reference No. E-182-2008/0-US-01)
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; 
<a href="/cdn-cgi/l/email-protection#d8abb7adb3b9aba898b5b9b1b4f6b6b1b0f6bfb7ae"><span class="__cf_email__" data-cfemail="b6c5d9c3ddd7c5c6f6dbd7dfda98d8dfde98d1d9c0">[email protected]</span></a>.
    Collaborative Research Opportunity: The National Cancer Institute, 
Laboratory of Experimental Immunology, is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize Method of 
Treating Pneumoconiosis With Oligodeoxynucleotides. Please contact John 
D. Hewes, Ph.D. at 301-435-3121 or <a href="/cdn-cgi/l/email-protection#721a1705170118321f131b1e5c1c1b1a5c151d04"><span class="__cf_email__" data-cfemail="335b5644564059735e525a5f1d5d5a5b1d545c45">[email protected]</span></a> for more 
information.

Attenuated Salmonella as a Delivery System for siRNA-Based Tumor 
Therapy

    Description of Technology: The discovery that genes vectored by 
bacteria can be functionally transferred to mammalian cells has 
suggested the possible use of bacterial vectors as vehicles for gene 
therapy. Genetically modified, nonpathogenic bacteria have been used as 
potential antitumor agents, either to elicit direct tumoricidal effects 
or to deliver tumoricidal molecules. Bioengineered attenuated strains 
of Salmonella enterica serovar typhimurium (S. typhimurium) have been 
shown to accumulate preferentially greater than one-thousand fold in 
tumors than in normal tissues and to disperse homogeneously in tumor 
tissues. Preferential replication allows the bacteria to produce and 
deliver a variety of anticancer therapeutic agents at high 
concentrations directly within the tumor, while minimizing toxicity to 
normal tissues. These attenuated bacteria have been found to be safe in 
mice, pigs, and monkeys when administered intravenously, and certain 
live attenuated Salmonella strains have been shown to be well tolerated 
after oral administration in human clinical trials. The S. typhimurium 
phoP/phoQ operon is a typical bacterial two-component regulatory system 
composed of a membrane-associated sensor kinase (PhoQ) and a 
cytoplasmic transcriptional regulator. phoP/phoQ is required for 
virulence, and its deletion results in poor survival of this bacterium 
in macrophages and a marked attenuation in mice and humans. phoP/phoQ 
deletion strains have been employed as effective vaccine delivery 
vehicles. More recently, attenuated salmonellae have been used for 
targeted delivery of tumoricidal proteins.
    This technology comprises live, attenuated Salmonella strains as a 
delivery system for small interfering double-stranded RNA (siRNA)-based 
tumor therapy. The inventors' data provide the first convincing 
evidence that Salmonella can be used for delivering plasmid-based 
siRNAs into tumors growing in vivo. Claimed in the related patent 
application are methods of inhibiting the growth or reducing the volume 
of solid cancer tumors using the si-RNA constructs directed against 
genes that promote tumor survival and cancer cell growth. The Stat3-
siRNAs carried by an attenuated S. typhimurium

[[Page 3622]]

described in the application exhibit tumor suppressive effects not only 
on the growth of the primary tumor but also on the development of 
metastases, suggesting that an appropriate attenuated S. typhimurium 
combined with the RNA interference (RNAi) approach may offer a 
clinically feasible method for cancer therapy.
    Application: Development of live attenuated bacterial cancer 
vaccines, cancer therapeutics and diagnostics.
    Development Status: Vaccines have been prepared and preclinical 
studies have been performed.
    Inventors: Dennis Kopecko (FDA/CBER), DeQi Xu (FDA/CBER), et al.
    Related Publications:
    1. L Zhang et al. Intratumoral delivery and suppression of prostate 
tumor growth by attenuated Salmonella enterica serovar typhimurium 
carrying plasmid-based small interfering RNAs. Cancer Res. 2007 Jun 
15;67(12):5859-5864.
    2. L Zhang et al. Effects of plasmid-based Stat3-specific short 
hairpin RNA and GRIM-19 on PC-3M tumor cell growth. Clin Cancer Res. 
2008 Jan 15;14(2):559-568.
    Patent Status:
    <bullet> Chinese Patent Application No. 200610017045.5 filed 26 Jul 
2006 (HHS Reference No. E-278-2007/0-CN-01).
    <bullet> PCT Patent Application No. PCT/US2007/074272 filed 24 Jul 
2007, which published as WO 2008/091375 on 31 Jul 2008 (HHS Reference 
No. E-278-2007/0-PCT-02).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; 
<a href="/cdn-cgi/l/email-protection#b6c5d9c3ddd7c5c6f6dbd7dfda98d8dfde98d1d9c0"><span class="__cf_email__" data-cfemail="2c5f4359474d5f5c6c414d454002424544024b435a">[email protected]</span></a>.
    Collaborative Research Opportunity: FDA-CBER Division of Bacterial, 
Parasitic, and Allergenic Products is seeking statements of capability 
or interest from parties interested in collaborative research to 
further develop, evaluate, or commercialize Salmonella-delivered anti-
tumor therapies or Salmonella-vectored vaccines. Please contact Alice 
Welch at <a href="/cdn-cgi/l/email-protection#c485a8ada7a1ea93a1a8a7ac84a2a0a5eaacacb7eaa3abb2"><span class="__cf_email__" data-cfemail="d697babfb5b3f881b3bab5be96b0b2b7f8bebea5f8b1b9a0">[email protected]</span></a> for more information.

    Dated: January 8, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E9-979 Filed 1-16-09; 8:45 am]
BILLING CODE 4140-01-P


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