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
9014 Federal Register / Vol. 72, No. 39 / Wednesday, February 28, 2007 / Notices 

opportunity for public comment on 

proposed collections of information, the 

Substance Abuse and Mental Health 

Services Administration (SAMHSA) 

will publish periodic summaries of 

proposed projects. To request more 

information on the proposed projects or 

to obtain a copy of the information 

collection plans, call the SAMHSA 

Reports Clearance Officer on (240) 276–

1243. 

Comments are invited on: (a) Whether 

the proposed collections of information 

are necessary for the proper 

performance of the functions of the 

agency, including whether the 

information shall have practical utility; 

(b) the accuracy of the agency’s estimate 

of the burden of the proposed collection 

of information; (c) ways to enhance the 

quality, utility, and clarity of the 

information to be collected; and (d) 

ways to minimize the burden of the 

collection of information on 

respondents, including through the use 

of automated collection techniques or 

other forms of information technology. 

Proposed Project: Underage Drinking 

Prevention: Town Hall Meeting 

Feedback Form—New 

The Substance Abuse and Mental 

Health Services Administration’s 

(SAMHSA), Center for Substance Abuse 

Prevention (CSAP) is proposing the 

project the 2008 Underage Drinking 

Prevention: Town Hall Meetings (THM) 

Initiative. In 2006, approximately 1,510 

THMs were held in 1,262 communitybased organizations (CBO) throughout 

the Nation. Each of the THMs strived to 

increase the understanding and 

awareness of underage alcohol use and 

its consequences by encouraging 

individuals, families, and communities 

to address the problem. The local THMs 

gave communities the opportunity to 

come together to learn more about the 

new research on underage alcohol use 

and its impact on both the individuals 

and the community. They also 

discussed how their communities can 

best prevent underage alcohol use. 

To help guide decision making and 

planning for future THMs, SAMHSA/ 

CSAP plans to conduct a process 

assessment of the THMs to be held in 

2008. CBOs who agree to participate in 

this initiative will be asked to provide 

feedback about the implementation and 

results of the THMs in their community. 

This information collection is being 

implemented under the authority of 

Section 501(d) (4) of the Public Health 

Service Act (42 U.S.C. 290aa). 

The contractor conducting this 

information collection will distribute a 

brief feedback form to all participating 

organizations. The form includes 14 

items about the THM, including where, 

when, and who conducted the meeting, 

number of attendees, format of meeting, 

participants in the presentations, 

actions planned, media coverage of the 

meeting, composition of the audience, 

responses of the attendees, materials 

provided in the town hall meetings, and 

indications of increased awareness and 

increased involvement. In addition to 

distributing the feedback form, the 

contractor will be responsible for 

collecting, compiling, analyzing, and 

reporting on information requested 

through this feedback form. 

The feedback form will be completed 

by an estimated 1,200 employees from 

CBOs. The paper form will take an 

average of 10 minutes (.167 hours) to 

review instructions, complete the form, 

and mail it in a self-addressed, stamped 

envelope. This burden estimate is based 

on comments from several potential 

respondents who reviewed the form and 

provided comments on how long it 

would take them to complete it. 

Form name Number of 

respondents 

Responses 

per 

respondent 

Hours per 

response 

Total hour 

burden 

Feedback Form ................................................................................................ 1,200 1 .167 120 

Send comments to Summer King, 

SAMHSA Reports Clearance Officer, 

Room 7–1044, One Choke Cherry Road, 

Rockville, MD 20857. Written comments 

should be received within 60 days of 

this notice. 

Dated: February 22, 2007. 

Elaine Parry, 

Acting Director, Office of Program Services. 

[FR Doc. E7–3468 Filed 2–27–07; 8:45 am] 

BILLING CODE 4162–20–P 

DEPARTMENT OF HOMELAND 

SECURITY 

Bureau of Customs and Border 

Protection 

Notice of Issuance of Final 

Determination Concerning Digital 

Color Multifunctional Systems 

AGENCY: U.S. Customs and Border 

Protection, Department of Homeland 

Security. 

ACTION: Notice of final determination. 

SUMMARY: This document provides 

notice that the Bureau of Customs and 

Border Protection (CBP) has issued a 

final determination concerning the 

country of origin of certain digital color 

multifunctional systems to be offered to 

the United States Government under an 

undesignated government procurement 

contract. Based on the facts presented, 

the final determination found that Japan 

is the country of origin of the subject 

digital color multifunctional systems for 

purposes of U.S. government 

procurement. 

DATES: The final determination was 

issued on February 8, 2007. A copy of 

the final determination is attached. Any 

party-at-interest as defined in 19 CFR 

177.22(d), may seek judicial review of 

this final determination within 30 days 

of February 28, 2007. 

FOR FURTHER INFORMATION CONTACT: 

Daniel Cornette, Valuation and Special 

Programs Branch, Office of International 

Trade; telephone (202) 572–8731. 

SUPPLEMENTARY INFORMATION: Notice is 

hereby given that on February 8, 2007, 

pursuant to subpart B of part 177, 

Customs Regulations (19 CFR part 177, 

subpart B), CBP issued a final 

determination concerning the country of 

origin of certain digital color 

multifunctional systems to be offered to 

the United States Government under an 

undesignated government procurement 

contract. The CBP ruling number is HQ 

563491. This final determination was 

issued at the request of Sharp 

Electronics Corporation under 

procedures set forth at 19 CFR part 177, 

subpart B, which implements Title III of 

the Trade Agreements Act of 1979, as 

amended (19 U.S.C. 2511–18). 

The final determination concluded 

that, based upon the facts presented, the 

assembly in Japan of Japanese and 

foreign components to create the subject 

digital color multifunctional systems 

substantially transformed the foreign 

components into a product of Japan. 

Section 177.29, CBP Regulations (19 

CFR 177.29), provides that notice of 

final determinations shall be published 

in the Federal Register within 60 days 

of the date the final determination is 


sroberts on PROD1PC70 with NOTICES