9012 Federal Register / Vol. 72, No. 39 / Wednesday, February 28, 2007 / Notices 

time, should be directed to the: Office 

of Management and Budget, Office of 

Regulatory Affairs, New Executive 

Office Building, Room 10235, 

Washington, DC 20503, Attention: Desk 

Officer for NIH. To request more 

information on the proposed project or 

to obtain a copy of the data collection 

plans and instruments, contact: Michele 

M. Doody, Radiation Epidemiology 

Branch, National Cancer Institute, 

Executive Plaza South, Room 7040, 

Bethesda, MD 20892–7238, or call nontoll-free at 301–594–7203 or e-mail your 

request, including your address to: 

doodym@mail.nih.gov. 

Comments Due Date: Comments 

regarding this information collection are 

best assured of having their full effect if 

received within 30 days of the date of 

this publication. 

Dated: February 16, 2007. 

Rachelle Ragland-Greene, 

NCI Project Clearance Liaison, National 

Institutes of Health. 

[FR Doc. E7–3435 Filed 2–27–07; 8:45 am] 

BILLING CODE 4104–01–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. 

Methods of Determining the Prognosis 

of Hepatocellular Carcinoma 

Description of Technology: 

Hepatocellular carcinoma (HCC) 

represents an extremely poor prognostic 

cancer that remains one of the most 

common and aggressive malignancies 

worldwide. A major hallmark of HCC is 

intrahepatic metastasis and postsurgical reoccurrence. With current 

diagnostic methods, HCC patients are 

often diagnosed with end-stage cancer 

and have poor survival. Thus, there is 

a need for an accurate method to 

identify HCC and its proclivity for 

metastases/relapse, particularly at early 

stages of this disease. 

The inventors have discovered a 

unique set of microRNA (miRNA) 

biomarkers that are associated with HCC 

metastasis/recurrence. This miRNA 

signature was validated in an 

independent cohort of 110 HCC samples 

as an independent predictor of HCC 

prognosis and likelihood of metastasis 

and relapse. In particular, the inventors 

provide evidence that these miRNA 

markers can predict HCC metastasis in 

the early stages of cancer. This 

methodology may enable clinicians to 

effectively stratify patients for 

appropriate cancer treatment and 

prioritize liver transplantation 

candidates. 

Applications: (1) Method to prognose 

HCC, patient survival and likelihood of 

HCC metastasis/relapse; (2) Diagnostic 

tool to aid clinicians in determining 

appropriate cancer treatment; (3) 

Compositions that inhibit miRNA HCC 

biomarkers such as siRNA; (4) Method 

to treatment HCC patients with 

inhibitory miRNA compositions. 

Market: (1) Primary liver cancer 

accounts for about 2% of cancers in the 

U.S., but up to half of all cancers in 

some undeveloped countries; (2) Postoperative five year survival rate of HCC 

patients is 30–40%. 

Development Status: This technology 

is currently in the pre-clinical stage of 

development. 

Inventors: Xin Wei Wang et al. (NCI). 

Publication: Budhu et al. A Unique 

Metastasis-related MicroRNA 

Expression Signature Predicts Survival 

and Recurrence in Hepatocellular 

Carcinoma, manuscript in preparation. 

Patent Status: U.S. Provisional 

Application No. 60/884,052 filed 09 Jan 

2007 (HHS Reference No. E–050–2007/ 

0–US–01). 

Licensing Availability: Available for 

exclusive or non-exclusive licensing. 

Licensing Contact: Jennifer Wong; 

301/435–4633; wongje@mail.nih.gov. 

A Varicella-Zoster Virus Mutant that is 

Markedly Impaired for Latent Infection 

Available for the Development of 

Shingles Vaccines and Diagnostics 

Description of Technology: 

Reactivation of latent Varicella-Zoster 

virus (VZV) infection is the cause of 

shingles, which is prominent in adults 

over the age of 60 and individuals who 

have compromised immune systems, 

due to HIV infection, cancer treatment 

and/or transplant. Shingles is a 

worldwide health concern that affects 

approximately 600,000 Americans each 

year. The incidence of shingles is also 

high in Europe, South America, and 

India; the latter having an estimated two 

million individuals affected, yearly. 

Recent research studies show that VZV 

vaccines have a significant effect on 

decreasing the incidence of shingles in 

elderly. 

The current technology describes 

compositions, cells and methods related 

to the production and use of a mutant 

VZV and the development of vaccines 

against the infectious agent. Latent VZV 

expresses a limited repertoire of viral 

genes including the following six open 

reading frames (ORFs): 4, 21, 29, 62, 63, 

and 66. The present invention describes 

an ORF29 mutant VZV that 

demonstrates a weakened ability to 

establish latency in animal studies. The 

current technology provides methods 

for using the mutant in the development 

of live vaccines and diagnostic tools. A 

related invention is described in PCT/ 

US05/021788 (publication number 

WO2006012092). 

Applications: Development of 

vaccines and diagnostics for prevention 

of shingles. 

Development Status: Pre-clinical 

studies have been performed to 

demonstrate the reduced latency of the 

ORF29 mutant VZV in animals. 

Inventors: Jeffrey Cohen (NIAID) and 

Lesley Pesnicak (NIAID). 

Patent Status: U.S. Provisional 

Application No. 60/857,766 filed 09 

Nov 2006 (HHS Reference No. E–029–

2007/0–US–01). 

Licensing Availability: Available for 

licensing and commercial development. 

Licensing Contact: Chekesha 

Clingman, Ph.D.; 301/435–5018; 

clingmac@mail.nih.gov. 

Collaborative Research Opportunity: 

The NIAID Laboratory of Clinical 

Infectious Diseases is seeking statements 

of capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize vaccine strains of VZV 

vaccine with impaired latency. Please 

contact Kelly Murphy, J.D., M.S., at 301/ 

451–3523 or murphykt@niaid.nih.gov 

for more information. 


sroberts on PROD1PC70 with NOTICES
Federal Register / Vol. 72, No. 39 / Wednesday, February 28, 2007 / Notices 9013 

Highly Soluble Pyrimido-DioneQuinoline Compounds: Small 

Molecules That Stabilize and Activate 

p53 in Transformed Cells 

Description of Technology: The 

tumor-suppressor p53 protein plays a 

major role in tumor development. Most 

human cancers ail to normally activate 

p53, which is at least partly responsible 

for the unregulated growth of cancer 

cells and their failure to undergo 

apoptosis. While many 

chemotherapeutics enhance p53 levels, 

their non-specific DNA damage 

(genotoxicity) causes unfavorable side 

effects. 

This invention reports the 

composition and function of a 

pyrimido-dione-quinoline that was 

found to inhibit HDM2’s ubiquitin 

ligase (E3) activity without the 

accompanying genotoxicity of current 

therapeutic drugs. Like the HLI98 family 

of compounds reported previously (see 

reference below), the subject of the 

current invention stabilizes p53 in cells, 

inhibiting its ubiquitin-mediated 

proteasomal degradation. Unlike the 

HLI98 compound, the pyrimido-dionequinoline reported here induces a 

robust p53 response, and is highly 

water-soluble. Thus, these pyrimidodione-quinoline compounds have the 

potential to stabilize p53 and activate a 

p53 response in tumors. 

Applications and Modality: Watersoluble with improved potency in 

stabilizing p53 and activating a p53 

response; Inhibits unregulated growth of 

cancer cells; Reduced genotoxicity 

compared to many chemotherapeutics. 

Market: Small molecule-based cancer 

therapeutics for tumors expressing wild 

type p53, which comprises 

approximately 50% of cancers. 

Development Status: The technology 

is currently in the pre-clinical stage of 

development. 

Inventors: Allan M. Weissman and 

Yili Yang (NCI). 

Related Publication: Y Yang et al. 

Small molecule inhibitors of HDM2 

ubiquitin ligase activity stabilize and 

activate p53 in cells. Cancer Cell 2005 

Jun;7(6):547–559. 

Patent Status: U.S. Provisional 

Application No. 60/813,946 filed 14 Jun 

2006 (HHS Reference No. E–138–2006/ 

0–US–01). 

Availability: Available for exclusive 

and non-exclusive licensing. 

Licensing Contact: Thomas P. Clouse, 

J.D.; 301/435–4076; 

clousetp@mail.nih.gov. 

Collaborative Research Opportunity: 

The Laboratory of Protein Dynamics and 

Signaling (LPDS) at the National Cancer 

Institute, NIH, is seeking a collaborative 

partner under a Cooperative Research 

and Development Agreement (CRADA) 

to develop therapeutics approaches 

utilizing inhibitors of the ubiquitin 

system such as described in this 

invention. Please contact John D. 

Hewes, Ph.D. at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

Human Cancer Therapy Using 

Engineered Anthrax Lethal Toxin 

Description of Technology: Anthrax 

lethal toxin (LeTx) consists of two 

components: The protective antigen 

(PrAg) and the lethal factor (LF). PrAg 

binds to the cell surface where it is 

activated by furin protease, followed by 

the formation of a PrAg heptamer. LF is 

then translocated into the cytosol of a 

cell via this heptamer, where it acts as 

a metalloprotease on all but one 

mitogen-activated protein kinase kinase 

(MAPKK). Approximately 70% of 

human melanomas contain a mutation 

(B–RAF V600E) that constitutively 

activates a MAPKK pathway, and LeTx 

has been shown to have significant 

toxicity towards cells which have this 

mutation. This suggested a potential use 

for LeTx in cancer therapy. 

Unfortunately, native LeTx is toxic to 

normal cells, detracting from its in vivo 

applicability. 

PrAg has been engineered to be 

activated by a matrix metalloprotease 

(MMP), instead of by furin protease. 

Because MMPs are highly expressed in 

tumor cells, this modification increases 

selectivity towards cancer cells. 

Surprisingly, mouse data shows that the 

modified LeTx (denoted PrAg–L1/LF) is 

less cytotoxic to ‘‘normal’’ cells in vivo, 

when compared to wild-type LeTx. 

Significantly, PrAg–L1/LF maintained 

its high toxicity toward human tumors 

in mouse xenograft models of human 

tumors, including melanomas. However, 

this toxicity applied not only to tumors 

having mutations that constitutively 

activate MAPKKs, but also to other 

tumor types such as lung and colon 

carcinomas. The absence of toxicity to 

‘‘normal’’ cells coupled to its 

effectiveness on a wide range of cancer 

cell types suggests that PrAg–L1/LF may 

represent a novel cancer therapeutic. 

Applications: PrAg–L1/LF has 

applications as a human cancer 

therapeutic; Applicability extends 

beyond melanomas, including lung and 

colon carcinomas. 

Market: The worldwide market for 

melanoma therapeutics is 

approximately $437M, and is predicted 

to reach $680M by the year 2009. 

Approximately 2.4 million people are 

afflicted with melanoma, with around 

150,000 new cases each year. 

Demonstration of effectiveness in vivo 

for lung and colon carcinomas will 

increase the market for this technology. 

Development Status: The technology 

is at the preclinical stage. 

Inventors: Stephen H. Leppla (NIAID), 

Shi-hui Liu (NIAID), Thomas H. Bugge 

(NIDCR), John R. Basile (NIDCR), Brooke 

Currie (NIDCR). 

Related Publications: 

1. S Liu et al. Intermolecular 

complementation achieves highspecificity tumor targeting by anthrax 

toxin. Nat Biotechnol. 2005 

Jun;23(6):725–730. 

2. RJ Abi-Habib et al. A urokinaseactivated recombinant anthrax toxin is 

selectively cytotoxic to many human 

tumor cell types. Mol Cancer Ther. 2006 

Oct;5(10):2556–2562. 

Patent Status: U.S. Provisional 

Application No. 60/870,050 filed 14 Dec 

2006 (HHS Reference E–070–2007/0–

US–01). 

Licensing Status: Available for 

exclusive or non-exclusive licensing. 

Licensing Contact: David A. 

Lambertson, Ph.D.; 301/435–4632; 

lambertsond@od.nih.gov. 

Collaborative Research Opportunity: 

The NIAID Laboratory of Bacterial 

Diseases is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize PrAg–L1/LF as a novel 

cancer therapeutic. Please contact 

Stephen H. Leppla, Ph.D. at 301/594–

2865 and/or sleppla@niaid.nih.gov for 

more information. 

This abstract was originally published 

in the Federal Register on Wednesday, 

February 7, 2007, 72 FR 5726, with an 

incorrect title of ‘‘Extended Transgene 

Expression for a Non-Integrating 

Adenoviral Vector Containing Retroviral 

Elements.’’

Dated: February 20, 2007. 

Steven M. Ferguson, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E7–3436 Filed 2–27–07; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Substance Abuse and Mental Health 

Services Administration 

Agency Information Collection 

Activities: Proposed Collection; 

Comment Request 

In compliance with Section 

3506(c)(2)(A) of the Paperwork 

Reduction Act of 1995 concerning 


sroberts on PROD1PC70 with NOTICES