Federal Register / Vol. 74, No. 77 / Thursday, April 23, 2009 / Notices 18585 

4 p.m.–5 p.m., May 13, 2009. 

Place: Holiday Inn Amarillo Hotel, 1911 I– 

40 East, Amarillo, TX 79102; Phone: (806) 

372–8741; Fax: (806) 372–7045. Audio 

Conference Call via FTS Conferencing. The 

USA toll-free dial-in number is 1–866–659– 

0537 with a pass code of 9933701. 

Status: Open to the public, limited only by 

the space available. The meeting space 

accommodates approximately 100 people. 

Background: The Advisory Board was 

established under the Energy Employees 

Occupational Illness Compensation Program 

(EEOICP) Act of 2000 to advise the President 

on a variety of policy and technical functions 

required to implement and effectively 

manage the new compensation program. Key 

functions of the Advisory Board include 

providing advice on the development of 

probability of causation guidelines which 

have been promulgated by the Department of 

Health and Human Services (HHS) as a final 

rule; advice on methods of dose 

reconstruction which have also been 

promulgated by HHS as a final rule; advice 

on the scientific validity and quality of dose 

estimation and reconstruction efforts being 

performed for purposes of the compensation 

program, and advice on petitions to add 

classes of workers to the Special Exposure 

Cohort (SEC). 

In December 2000, the President delegated 

responsibility for funding, staffing, and 

operating the Advisory Board to HHS, which 

subsequently delegated this authority to the 

CDC. NIOSH implements this responsibility 

for CDC. The charter was issued on August 

3, 2001, renewed at appropriate intervals, 

and will expire on August 3, 2009. 

Purpose: This Advisory Board is charged 

with (a) providing advice to the Secretary, 

HHS, on the development of guidelines 

under Executive Order 13179; (b) providing 

advice to the Secretary, HHS, on the 

scientific validity and quality of dose 

reconstruction efforts performed for this 

program; and (c) upon request by the 

Secretary, HHS, advise the Secretary on 

whether there is a class of employees at any 

Department of Energy facility who were 

exposed to radiation but for whom it is not 

feasible to estimate their radiation dose, and 

on whether there is reasonable likelihood 

that such radiation doses may have 

endangered the health of members of this 

class. 

Matters To Be Discussed: The agenda for 

the Advisory Board meeting includes: NIOSH 

Program Status Update; Department of Labor 

(DOL) Update; Department of Energy (DOE) 

Update; Board Security Plan; Special 

Exposure Cohort (SEC) Petitions for: Linde 

Ceramics Plant (Residual Period); Standard 

Oil Development Company of New Jersey; 

Blockson Chemical Company (radon-related 

dose reconstruction); and Dow Chemical 

Company (Madison, Illinois); Special 

Exposure Cohort (SEC) Petition Status 

Updates; Work Group reports; Reports of the 

Subcommittees on Dose Reconstruction 

Reviews and Procedures Reviews; and Board 

Future Plans and Meetings. 

The agenda is subject to change as 

priorities dictate. 

In the event an individual cannot attend, 

written comments may be submitted 

according to the policy provided below. Any 

written comments received will be provided 

at the meeting and should be submitted to 

the contact person below well in advance of 

the meeting. 

Policy on Redaction of Board Meeting 

Transcripts (Public Comment), (1) if a person 

making a comment gives his or her name, no 

attempt will be made to redact that name. (2) 

NIOSH will take reasonable steps to ensure 

that individuals making public comment are 

aware of the fact that their comments 

(including their name, if provided) will 

appear in a transcript of the meeting posted 

on a public Web site. Such reasonable steps 

include: (a) A statement read at the start of 

each public comment period stating that 

transcripts will be posted and names of 

speakers will not be redacted; (b) A printed 

copy of the statement mentioned in (a) above 

will be displayed on the table where 

individuals sign up to make public comment; 

(c) A statement such as outlined in (a) above 

will also appear with the agenda for a Board 

Meeting when it is posted on the NIOSH Web 

site; (d) A statement such as in (a) above will 

appear in the Federal Register Notice that 

announces Board and Subcommittee 

meetings. (3) If an individual in making a 

statement reveals personal information (e.g., 

medical information) about themselves that 

information will not usually be redacted. The 

NIOSH FOIA coordinator will, however, 

review such revelations in accordance with 

the Freedom of Information Act and the 

Federal Advisory Committee Act and if 

deemed appropriate, will redact such 

information. (4) All disclosures of 

information concerning third parties will be 

redacted. (5) If it comes to the attention of the 

Designated Federal Officer (DFO) that an 

individual wishes to share information with 

the Board but objects to doing so in a public 

forum, the DFO will work with that 

individual, in accordance with the Federal 

Advisory Committee Act, to find a way that 

the Board can hear such comments. 

Contact Person for More Information: 

Theodore Katz, M.P.A., Executive Secretary, 

NIOSH, CDC, 1600 Clifton Road, MS E–20, 

Atlanta, GA 30333, Telephone (513)533– 

6800, Toll Free 1(800) CDC–INFO, e-mail 

ocas@cdc.gov. 

The Director, Management Analysis and 

Services Office, has been delegated the 

authority to sign Federal Register notices 

pertaining to announcements of meetings and 

other committee management activities, for 

both CDC and the Agency for Toxic 

Substances and Disease Registry. 

Dated: April 16, 2009. 

Elaine L. Baker, 

Director, Management Analysis and Services 

Office, Centers for Disease Control and 

Prevention. 

[FR Doc. E9–9332 Filed 4–22–09; 8:45 am] 

BILLING CODE 4163–18–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

Public Teleconference Regarding 

Licensing and Collaborative Research 

Opportunities for: A Double-Barreled 

Attack: Azatoxins, A New Hope for 

Treating Cancer 

AGENCY: National Institutes of Health, 

Public Health Service, HHS. 

ACTION: Notice. 

Technology Summary 

This technology describes a novel 

class of Topoisomerase II (top2) 

inhibitors that are useful in treating 

cancer. Drugs that inhibit the top2 

enzyme are among the most active 

anticancer agents discovered. However, 

many of the currently available 

inhibitors produce toxic side effects, 

have poor pharmacokinetics, or 

eventually become ineffective because 

malignant cells readily acquire 

resistance. Therefore, there is a need for 

developing new top2 inhibitor drugs 

that will overcome these limitations. 

Azatoxin and its derivatives, which 

are derived by combining two parent 

compounds etoposide and ellipticine, 

are the first compounds rationally 

designed as inhibitors of top2. 

Azatoxins are also potent inhibitors of 

tubulin polymerization. These two anticancer activities can be successfully 

separated by synthesizing azatoxin 

derivatives to yield compounds which 

can be pharmacologically advantageous 

against tumor proliferation. The 

azatoxin platform represents an 

unexploited class of top2 inhibitors that 

could be developed into especially 

potent chemotherapeutics. 

Competitive Advantage of Our 

Technology 

Currently, several top2 inhibitors are 

approved for clinical use; however, they 

produce serious side effects. Etoposide, 

for example, causes problems with 

myelosuppression, drug resistance, and 

has poor bioavailability. Moreover, it 

appears to have carcinogenic properties 

as it has been linked to the development 

of acute myelogenous leukemia—an 

effect also observed with mitoxantrone. 

Anthracyclines, like doxorubicin, have 

the same limitations as etoposide, but 

they also possess cardiotoxic effects. 

Azatoxins have the potential to be 

developed into chemotherapeutics that 

outperform these currently used top2 

inhibitors. 

Azatoxins have been substantially 

characterized through years of preclinical research demonstrating that 


sroberts on PROD1PC70 with NOTICES
18586 Federal Register / Vol. 74, No. 77 / Thursday, April 23, 2009 / Notices 

they possess properties from both of its 

parental compounds, etoposide and 

ellipticine. They act by stabilizing the 

top2–DNA cleavage complex, like 

etoposide does, instead of inhibiting 

top2 catalytic activity, the mechanism 

by which ellipticine acts. With regard to 

DNA cleavage activity, azatoxins show 

similar activity to etoposide. In addition 

to acting as a top2 inhibitor, azatoxin is 

also a potent inhibitor of tubulin 

polymerization. 

The anti-cancer activity of azatoxins 

has been validated by cell line 

screening. The Developmental 

Therapeutics Program (DTP) of the 

National Cancer Institute (NCI) has 

tested azatoxins in its tumor cell panel 

and established their effectiveness 

against disseminated leukemia and 

localized tumors, such as non-small cell 

lung and colon cancer. These results are 

very encouraging showing that certain 

azatoxin derivatives are 100 times more 

active than etoposide, which is the 

common top2 inhibitor used in 

chemotherapy. Azatoxins are a novel 

class of potent top2 and/or tubulin 

inhibitors that could outperform current 

chemotherapeutic agents. 

Technology Description 

Topoisomerase enzymes are critical 

for normal cell division because they 

prevent tangles and knots from forming 

during DNA replication by cleaving and 

religating DNA. Several compounds 

have been discovered that block 

topoisomerases and stop its ability to 

religate DNA resulting in an increased 

number of double strand DNA breaks 

that kill the cell. These inhibitors are 

especially effective against rapidly 

dividing malignant cells that express 

high levels of top2, which represents a 

main reason these top2 enzymes have 

become an important therapeutic target. 

The problem is that currently used 

drugs are limited by their toxicity, 

insolubility, and their susceptibility to 

induce drug resistance. 

In an effort to produce top2 inhibitors 

with increased therapeutic efficiency, 

well established top2 inhibitors were 

compared by molecular modeling to 

produce a composite top2 inhibitor 

pharmacophore of the diverse 

inhibitors. Based on this model, 

azatoxin was designed as an analogue 

hybrid of etoposide and ellipticine. 

Subsequently, several modifications of 

azatoxin have been synthesized to 

generate derivatives, such as 

anilinoazatoxins, which have improved 

pharmacological profiles. 

Market 

Despite further discoveries leading to 

a greater understanding and treating of 

cancer, it continues to be a burden to 

the public health. After heart disease, 

cancer is the most common cause of 

death in the United States. In 2008, it 

was estimated that about 565,650 

Americans were expected to die of 

cancer. Although, the incidence of 

cancer has been dropping over the 

years, it was estimated that over 1.4 

million Americans would be diagnosed 

with cancer in 2008. 

Cancer is not only a health burden but 

also a financial burden to the country. 

The NIH estimated the overall cost of 

cancer in 2007 to be $219.2 billion 

dollars with $89 billion attributable to 

direct medical costs. It is expected that 

cancer will continue to be a public 

health problem for the foreseeable 

future which prompts the need for the 

development of new therapeutics. 

Chemotherapy is still the standard 

approach for treating cancers even 

though there were high expectations 

that targeted therapeutics would become 

the preferred drugs in cancer treatment. 

Current topoisomerase inhibitors have 

demonstrated to be effective 

chemotherapy drugs and they continue 

being developed for use in combination 

therapy with targeted therapeutics. 

However, top2 inhibitors need to be 

improved in order to overcome their 

limitations. A next-generation top2 

inhibitor like azatoxins has potential in 

meeting this need. 

Patent Estate 

The National Institutes of Health 

holds a substantial portfolio of patents 

in U.S., Europe, Canada, and Australia 

which claim compositions of azatoxin 

and its derivatives, pharmaceutical 

formulations, and methods of use for 

chemotherapy. 

The portfolio includes the following 

issued patents: 

I. United States Patent No. 5,622,960 

entitled ‘‘Topoisomerase II inhibitors 

and therapeutic uses therefor’’ issued 

April 22, 1997 (HHS Ref. No. E–119– 

1992/1–US–01). 

II. United States Patent No. 5,747,520 

entitled ‘‘Topoisomerase II inhibitors 

and therapeutic uses therefor’’ issued 

May 5, 1998 (HHS Ref. No. E–119–1992/ 

1–US–17). 

III. European Patent No. 0665846 

entitled ‘‘Topoisomerase II inhibitors 

and therapeutic uses therefor’’ issued 

July 29, 1998 (HHS Ref. No. E–119– 

1992/1–EP–10) validated in Austria, 

Belgium, Denmark, France, Germany, 

Great Britain, Ireland, Italy, 

Luxembourg, Switzerland, and The 

Netherlands. 

IV. Canadian Patent No. 2147608 

entitled ‘‘Topoisomerase II inhibitors 

and therapeutic uses therefor’’ issued 

December 12, 2006 (HHS Ref. No. E– 

119–1992/1–CA–06). 

V. Australian Patent No. 676511 

entitled ‘‘Topoisomerase II inhibitors 

and therapeutic uses therefor’’ issued 

June 13, 1997 (HHS Ref. No. E–119– 

1992/1–AU–04). 

Next Step: Teleconference 

There will be a teleconference where 

the principal investigator, Dr. Yves 

Pommier, will explain this technology. 

Licensing and collaborative research 

opportunities will also be discussed. If 

you are interested in participating in 

this teleconference please call or e-mail 

Samuel Bish; (301) 435–5282; 

bishse@mail.nih.gov. The NIH Office of 

Technology Transfer (OTT) will then email you the date, time, and number for 

the teleconference. 

Dated: April 16, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–9344 Filed 4–22–09; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HOMELAND 

SECURITY 

U.S. Customs and Border Protection 

[Docket No. USCBP–2006–0037] 

Expansion of Global Entry Pilot 

Program 

AGENCY: U.S. Customs and Border 

Protection; Department of Homeland 

Security. 

ACTION: General notice. 

SUMMARY: U.S. Customs and Border 

Protection (CBP) is currently conducting 

an international trusted traveler pilot 

program, referred to as Global Entry, at 

seven U.S. airports. This document 

announces that pursuant to an 

arrangement between the United States 

and the Netherlands, CBP is expanding 

eligibility for participation in the Global 

Entry pilot to include citizens of the 

Netherlands who participate in Privium, 

an expedited travel program in the 

Netherlands, and who otherwise satisfy 

the requirements for participation in 

Global Entry. Currently, eligibility is 

limited to U.S. citizens, U.S. nationals, 

and U.S. lawful permanent residents 

(LPRs). Pursuant to this same 

arrangement, U.S. citizens who 

participate in the Global Entry pilot will 

have the option to also apply for 

participation in Privium. 

DATES: Effective Dates: Applications for 

the Global Entry pilot are currently 


sroberts on PROD1PC70 with NOTICES