3620 Federal Register / Vol. 74, No. 12 / Wednesday, January 21, 2009 / Notices 

functions, such as signaling and cell-tocell interactions. Glucosylceramide 

synthase—encoded by the Ugcg gene— 

controls the first committed step in the 

major pathway of glycosphingolipid 

synthesis. Global disruption of the Ugcg 

gene in mice is lethal during 

gastrulation. The inventors have 

established a Ugcg allele flanked by 

loxP sites (floxed). When cre 

recombinase was expressed in the 

nervous system under control of the 

nestin promoter, the floxed gene 

underwent recombination, resulting in a 

substantial reduction of Ugcg expression 

and of glycosphingolipid ganglio-series 

levels. The mice deficient in Ugcg 

expression in the nervous system show 

a striking loss of Purkinje cells and 

abnormal neurologic sphingo-lipid 

behavior. 

The Research Tools available are mice 

with a floxed Ugcg allele that can be 

deleted in a conditional manner. These 

mice carrying floxed Ugcg alleles will be 

useful for delineating the functional 

roles of glycosphingolipid synthesis in 

the nervous system and in other 

physiologic systems. 

Applications 

• Study of the functional roles of 

glycosphingolipid synthesis in the 

nervous system and other physiologic 

systems. 

• The floxed Ugcg allele will facilitate 

analysis of the function of 

glycosphingolipids in development, 

physiology, and in diseases such as 

diabetes and cancer. 

Development Status: Ready to Use. 

Inventors: Richard L. Proia (NIDDK). 

Publication: T Yamashita, ML 

Allende, DN Kalkofen, N Werth, K 

Sandhoff, RL Proia. Conditional LoxPflanked glucosylceramide synthase 

allele controlling glycosphingolipid 

synthesis. Genesis 2005 Dec;43(4):175– 

180. 

Patent Status: HHS Reference No. E– 

320–2007/0—Research Material. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: Available for 

licensing under a Biological Materials 

license agreement. 

Licensing Contact: Suryanarayana 

(Sury) Vepa, PhD, J.D.; 301–435–5020; 

vepas@mail.nih.gov. 

Collaborative Research Opportunity: 

The NIDDK Genetics of Development 

and Disease Branch is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize the sphingolipid 

metabolism in physiology and disease. 

Please contact Dr. Proia at 

proia@nih.gov for more information. 

Mutant Nuclear Orphan Receptor for 

Drug Metabolism Assays 

Description of Technology: The 

constitutively active nuclear orphan 

receptor (CAR) activates transcription of 

genes encoding various drugmetabolizing enzymes, such as 

cytochrome P450, in response to drug 

exposure. While the direct activation of 

CAR in response to various drugs has 

been observed in vivo, CAR is always 

active in cell-based transfection assays, 

even in the absence of activating drugs. 

This constitutive activity of CAR makes 

it difficult to perform accurate in vitro 

assays to measure drug metabolism. 

The NIH has obtained patent 

protection for modified CAR proteins 

that can be directly activated by drugs 

in vitro. This technology may 

potentially be used in the development 

of more efficient and cost-effective cellbased drug metabolism assays. 

Applications: Development of 

improved in vitro assays to measure 

drug metabolism. 

Inventors: Masahiko Negishi et al. 

(NIEHS). 

Publications 

1. T Sueyoshi, T Kawamoto, I Zelko, 

P Honkakoski, M Negishi. The repressed 

nuclear receptor CAR responds to 

phenobarbital in activating the human 

CYP2B6 gene. J Biol Chem. 1999 Mar 

5;274(10):6043–6046. 

2. T Kawamoto, S Kakizaki, K 

Yoshinari, M Negishi. Estrogen 

activation of the nuclear orphan 

receptor CAR (constitutive active 

receptor) in induction of the mouse 

Cyp2b10 gene. Mol Endocrinol. 2000 

Nov;14(11):1897–1905. 

Patent Status: U.S. Patent No. 

7,365,160 issued 29 Apr 2008 (HHS 

Reference No. E–034–2002/0–US–03). 

Licensing Status: Available for 

exclusive and non-exclusive licensing. 

Licensing Contact: Tara L. Kirby, PhD; 

301–435–4426; tarak@mail.nih.gov. 

Dated: January 8, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–978 Filed 1–16–09; 8:45 am] 

BILLING CODE 4140–01–P 

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. 

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 alphaherpesvirus lytic infection. After an 

initial lytic infection, alphaherpesviruses 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 

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Federal Register / Vol. 74, No. 12 / Wednesday, January 21, 2009 / Notices 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: 

• Prevention and treatment of 

recurrent Herpes simplex virus 

outbreaks. 

• Prevention and treatment of 

recurrent Varicella zoster infection. 

• Treatment of HSV encephalitis. 

• 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: 

• U.S. Provisional Application No. 

61/083,304 filed 24 Jul 2008 (HHS 

Reference No. E–275–2008/0–US–01). 

• 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 nonexclusive or exclusive licensing. 

Licensing Contact: Christina 

Thalhammer-Reyero, PhD; 301–435– 

4507; thalhamc@mail.nih.gov 

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 

millermarg@niaid.nih.gov 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 TNFalpha, 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 downmodulate 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 ODNbased 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 silicainduced 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; 

soukasp@mail.nih.gov. 

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 hewesj@mail.nih.gov 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 twocomponent 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 

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3622 Federal Register / Vol. 74, No. 12 / Wednesday, January 21, 2009 / Notices 

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 plasmidbased 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: 

• Chinese Patent Application No. 

200610017045.5 filed 26 Jul 2006 (HHS 

Reference No. E–278–2007/0–CN–01). 

• 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; 

soukasp@mail.nih.gov. 

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 

Alice.Welch@fda.hhs.gov 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 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

National Cancer Institute; Notice of 

Meeting 

Pursuant to section 10(d) of the 

Federal Advisory Committee Act, as 

amended (5 U.S.C. Appendix 2), notice 

is hereby given of the meeting of the 

National Cancer Advisory Board. 

The meeting will be open to the 

public as indicated below, with 

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Individuals who plan to attend and 

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A portion of the meeting will be 

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the grant applications, the disclosure of 

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unwarranted invasion of personal 

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Name of Committee: National Cancer 

Advisory Board; Ad Hoc Subcommittee on 

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Open: February 2, 2009, 6:30 p.m. to 8 p.m. 

Agenda: Discussion on cancer 

communications. 

Place: Bethesda Marriott Suites, 6711 

Democracy Boulevard, Bethesda, Maryland 

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Contact Person: Dr. Paulette S. Gray, 

Executive Secretary, National Cancer 

Institute, National Institutes of Health, 6116 

Executive Boulevard, 8th Floor, Room 8001, 

Bethesda, MD 20892–8327, (301) 496–5147. 

Name of Committee: National Cancer 

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Open: February 3, 2009, 8 a.m. to 4 p.m. 

Agenda: Program reports and 

presentations; business of the Board. 

Place: National Institutes of Health, 9000 

Rockville Pike, Building 31, C Wing, 6th 

Floor, Conference Room 6, Bethesda, MD 

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Contact Person: Dr. Paulette S. Gray, 

Executive Secretary, National Cancer 

Institute, National Institutes of Health, 6116 

Executive Boulevard, 8th Floor, Room 8001, 

Bethesda, MD 20892–8327, (301) 496–5147. 

Name of Committee: National Cancer 

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Closed: February 3, 2009, 4 p.m. to 5 p.m. 

Agenda: Review of grant applications. 

Place: National Institutes of Health, 9000 

Rockville Pike, Building 31, C Wing, 6th 

Floor, Conference Room 6, Bethesda, MD 

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Contact Person: Dr. Paulette S. Gray, 

Executive Secretary, National Cancer 

Institute, National Institutes of Health, 6116 

Executive Boulevard, 8th Floor, Room 8001, 

Bethesda, MD 20892–8327, (301) 496–5147. 

Name of Committee: National Cancer 

Advisory Board. 

Open: February 4, 2009, 8 a.m.to 12 p.m. 

Agenda: Program reports and 

presentations; business of the Board. 

Place: National Institutes of Health, 9000 

Rockville Pike, Building 31, C Wing, 6th 

Floor, Conference Room 6, Bethesda, MD 

20892. 

Contact Person: Dr. Paulette S. Gray, 

Executive Secretary, National Cancer 

Institute, National Institutes of Health, 6116 

Executive Boulevard, 8th Floor, Room 8001, 

Bethesda, MD 20892–8327, (301) 496–5147. 

Any interested person may file written 

comments with the committee by forwarding 

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this notice. The statement should include the 

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applicable, the business or professional 

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In the interest of security, NIH has 

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deainfo.nci.nih.gov/advisory/ncab.htm, 

where an agenda and any additional 

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(Catalogue of Federal Domestic Assistance 

Program Nos. 93.392, Cancer Construction; 

93.393, Cancer Cause and Prevention 

Research; 93.394, Cancer Detection and 

Diagnosis Research; 93.395, Cancer 

Treatment Research; 93.396, Cancer Biology 

Research; 93.397, Cancer Centers Support; 

93.398, Cancer Research Manpower; 93.399, 

Cancer Control, National Institutes of Health, 

HHS) 

Dated: January 9, 2009. 

Jennifer Spaeth, 

Director, Office of Federal Advisory 

Committee Policy. 

[FR Doc. E9–996 Filed 1–16–09; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

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Resources; Notice of Closed Meetings 

Pursuant to section 10(d) of the 

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amended (5 U.S.C. Appendix 2), notice 

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meetings. 

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