27150 Federal Register / Vol. 74, No. 108 / Monday, June 8, 2009 / Notices 

site. Submit a single copy of electronic 

comments or two paper copies of any 

mailed comments, except that 

individuals may submit one paper copy. 

Comments are to be identified with the 

docket number found in brackets in the 

heading of this document. The 

guidance, notices, and received 

comments may be seen in the Division 

of Dockets Management between 9 a.m. 

and 4 p.m., Monday through Friday. 

IV. Electronic Access 

Persons with access to the Internet 

may obtain the document at either 

http://www.fda.gov/cder/guidance/ 

index.htm or http:// 

www.regulations.gov. 

Dated: May 27, 2009. 

Jeffrey Shuren, 

Associate Commissioner for Policy and 

Planning. 

[FR Doc. E9–13261 Filed 6–5–09; 8:45 am] 

BILLING CODE 4160–01–S 

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. 

Interactive Venn Diagram Software 

Designed for Microarray Analysis 

Description of Technology: Multiple 

conditions from any source, but 

designed for experiments involving 

microarrays, will produce (significant 

gene lists for arrays) lists from each 

condition, thus multiple lists. This 

Java® based software provides 

investigators with a method of 

displaying multiple conditions in a 

single graphic along with producing a 

text output of genes that are the product 

of these conditional intersections along 

with each conditions unique list. A 

standard Venn diagram is limited to 

only display three (3) comparisons; this 

software can display any number of 

comparisons and will automatically 

create lists from all intersections even if 

not able to be displayed along with each 

conditions unique list. 

Applications: 

• Microarray analysis. 

• Genomics. 

• Bioinformatics. 

• Any environment creating multiple 

lists (Business, Accounting, Inventory 

Control, etc.). 

Inventor: Daniel E. Sturdevant 

(NIAID). 

Patent Status: HHS Reference No. E– 

189–2009/0—Research Tool. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: Available for 

licensing. 

Licensing Contact: Michael A. 

Shmilovich, Esq.; 301–435–5019; 

shmilovm@mail.nih.gov. 

Axenically-Produced Coxiella 

burnetii and Methods for Producing 

Axenic Coxiella burnetii 

Description of Technology: Coxiella 

burnetii is the causative agent of Q 

(Query) fever. Currently, there is a need 

for a safe Q fever vaccine. It is 

anticipated that axenically-produced C. 

burnetii, which is free of host cell 

related impurities, could provide either 

the basis for a whole-cell Q fever 

vaccine or advance the development of 

a safe recombinant Q fever vaccine. 

Currently, there are no licensed Q-fever 

vaccines except for a whole-cell, 

formalin inactivated, vaccine which is 

available in Australia (Q–Vax). 

Individuals with a previous exposure to 

C. burnetii may, however, have a severe 

allergic reaction to this vaccine and 

other individuals may experience a 

headache or flu-like symptoms after 

vaccination. It is anticipated that 

axenically-produced C. burnetii could 

provide the basis for a less reactogenic 

whole-cell vaccine or facilitate the 

development of a recombinant vaccine 

that does not cause an allergic reaction. 

Additionally, the inability to propagate 

obligate intracellular pathogens under 

axenic (host cell-free) culture conditions 

imposes severe experimental constraints 

that have negatively impacted progress 

in understanding pathogen virulence 

and disease mechanisms. 

Q fever is a zoonotic disease and farm 

animals, pets, and rodents are 

significant reservoirs for C. burnetii. C. 

burnetii persists in the soil for a long 

time and typically humans are exposed 

to Q fever by the inhalation of the 

bacterium deposited with animal waste 

such as urine, feces, and amniotic fluid. 

The epidemiology of Q fever is diverse 

and the disease does not discriminate 

between developed and developing 

countries. Additionally, urban outbreaks 

have been known to occur due to 

windborne C. burnetii. C. burnetii is 

listed as a select agent by the 

Department of Health and Human 

Services (HHS) because of its potential 

as an agent of bioterrorism. Deployed 

military personnel are also at risk of 

contracting Q fever and thousands of 

cases of Q fever have been reported 

among military personnel since the 

disease was first reported in the 1930s. 

Advantages: 

• The ability to propagate, previously 

unpropagatable, C. burnetii without a 

hostcell. 

• The ability to study C. burnetii 

virulence using axenic conditions or 

conditions free of host cell-related 

impurities. 

• This technology is ready for use in 

drug/vaccine discovery, production, and 

development. 

• Potential licensees of this invention 

include companies that are: 1) seeking 

vaccine production platforms based on 

host cell-free (axenic) media, 2) seeking 

to develop recombinant vaccines for 

obligate, intracellular, bacteria; or 3) 

seeking to lower costs and ease scale-up 

would be potential licensees of this 

technology. 

Development Status: This technology 

has been demonstrated with C. burnetii. 

Currently, the inventors are testing this 

technology for support of axenic growth 

of other obligate, intracellular, bacteria 

of public health significance. 

Inventors: Robert A. Heinzen, Anders 

Omsland, Diane C. Cockrell, Dale Howe 

(NIAID). 

Publication: A Omsland et al. Host 

cell-free growth of the Q fever bacterium 

Coxiella burnetii. Proc Natl Acad Sci 

USA. 2009 Mar 17;106(11):4430–4434. 

Patent Status: U.S. Provisional 

Application No. 61/154,330 filed 20 Feb 

2009 (HHS Reference No. E–114–2009/ 

0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Peter A. Soukas, 

J.D.; 301–435–4646; 

soukasp@mail.nih.gov. 


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Federal Register / Vol. 74, No. 108 / Monday, June 8, 2009 / Notices 27151 

Self-Expanding Stent for Valve 

Replacement 

Description of Technology: Aortic 

stenosis and aortic regurgitation are the 

most common types of aortic valvular 

diseases. Such diseased aortic valves in 

the body are traditionally replaced with 

valve prosthesis by an open surgical 

implantation. Available for licensing 

and commercial development is 

intellectual property covering stents for 

use with valve prostheses. One possible 

embodiment of the invention includes a 

self-expandable stent with an elastic 

tubular latticework having radial and 

longitudinal direction. The stent 

geometry and mechanical parameters 

provide more anatomically-correct 

placement and the flexible scaffolding 

of the valve (using an interconnected 

four-sided polygons and longitudinal 

rods comprising a self-expanding stent 

with a plurality of struts connecting a 

plurality of rods) allow for secure 

implantation with adaptable apposition 

of the prosthesis in the aorta. 

Applications: Cardiac Surgery; 

Cardiology; Surgery; Stent implantation. 

Inventors: Keith Horvath, Dumitru 

Mazilu, Ming Li (NHLBI). 

Publications: 

1. M Li, D Mazilu, KA Horvath. 

Robotic system for transapical aortic 

valve replacement with MRI guidance. 

Med Image Comput Comput Assist 

Interv Int Conf Med Image Comput 

Comput Assist Interv. 2008;11(Pt 

2):476–484. 

2. KA Horvath, M Li, D Mazilu, MA 

Guttman, ER McVeigh. Real-time 

magnetic resonance imaging guidance 

for cardiovascular procedures. Semin 

Thorac Cardiovasc Surg. 2007 

Winter;19(4):330–335. Review. 

Patent Status: U.S. Provisional 

Application No. 61/172,568 filed 24 Apr 

2009 (HHS Reference No. E–337–2008/ 

0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Michael A. 

Shmilovich, Esq.; 301–435–5019; 

shmilovm@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Heart, Lung, and Blood 

Institute, Cardiothoracic Surgery 

Research Program, is seeking statements 

of capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize this technology. Please 

contact Peg Koelbe at 301–594–4095 or 

koelblep@nhlbi.nih.gov for more 

information. 

Method of Diagnosing Multidrug 

Resistant Tuberculosis 

Description of Technology: The 

invention can be used to develop tests 

that are much more rapid than 

conventional tests for determining drug 

resistance. It relates to the discovery 

that a putative gene of Mycobacterium 

tuberculosis (MTb) with no previously 

identified function is responsible for the 

ability of the bacteria to activate a class 

of second line thioamide drugs used for 

MTb infections. The gene, termed 

‘‘etaA,’’ codes for the synthesis of a 

monooxygenase, the enzyme 

responsible for the oxidative activation 

of the drugs. Mutation in the etaA gene 

leads to the expression of mutated, 

inactivated enzyme, thus resulting in 

thioamide drug-resistant bacteria. The 

significance of this discovery is that 

now, resistance to the class of thioamide 

drugs in clinical isolates can be 

identified in a relatively short time, 

eliminating the need to perform lengthy 

culturing procedures. 

The invention claims test methods for 

determining resistance to thioamide 

drugs by detecting gene mutation. These 

include (a) amplifying the etaA gene or 

a portion of it containing the mutation, 

with a set of primers which provide 

amplified product, and sequencing the 

amplified product to compare the 

sequence with a known sequence of the 

wild-type etaA; a difference in sequence 

patterns indicates mutation; (b) 

subjecting the amplified gene product to 

digestion by restriction enzymes and 

comparing the cleaved DNA gel pattern 

to the one obtained from digestion of the 

wild-type etaA gene; a difference 

indicates mutation in etaA; and (c) 

detecting the mutations by probe 

hybridization techniques, where the 

amplified product hybridizes to a 

nucleic acid of known sequence under 

stringent conditions, and the hybridized 

product is detected. In addition to the 

above, the invention proposes other 

detection methods such as commonly 

used for SNPs. Other methods claimed 

in the invention are immunoassay (i.e., 

ELISA) for the etaA gene product or 

mutated versions of it, or immunoassay 

and chemical analysis of the drug 

metabolites, whereby the absence of the 

metabolites indicates gene mutation and 

impaired activating ability. 

Applications: Infectious diseases, 

diagnostics (bacterial); Infectious 

diseases, therapeutics (anti-bacterial). 

Advantages: Novel methods for 

diagnosing multidrug resistant 

tuberculosis that are much more rapid 

than conventional tests. 

Inventors: Clifton E. Barry III (NIAID), 

Andrea E. DeBarber (NIAID), Khisimuzi 

Mdluli (NIAID), et al. 

Publication: AE DeBarber et al. 

Ethionamide activation and sensitivity 

in multidrug-resistant Mycobacterium 

tuberculosis. Proc Natl Acad Sci U S A. 

2000 Aug 15;97(17):9677–9682. 

Patent Status: 

• U.S. Patent No. 6,905,822 issued 14 

Jun 2005 (HHS Reference No. E–093– 

2000/0–US–02). 

• U.S. Patent Application No. 11/ 

058,484 filed 14 Feb 2005 and allowed 

17 Feb 2009 (HHS Reference No. E–093– 

2000/0–US–03). 

Licensing Status: Available for 

licensing. 

Licensing Contact: RC Tang, JD, LLM; 

301–435–5031; tangrc@mail.nih.gov 

A Novel Chimeric Protein for 

Prevention and Treatment of HIV 

Infection 

Description of Technology: This 

invention relates to bifunctional fusion 

proteins effective in HIV neutralization. 

Specifically, the invention is a 

genetically engineered chimeric protein 

composed of a soluble extracellular 

region of human CD4 (sCD4) attached 

via a flexible polypeptide linker to a 

single-chain construct of a human 

monoclonal antibody directed against a 

CD4-induced, highly conserved gp120 

determinant involved in co-receptor 

interaction and virus entry. 

Mechanistically, the binding of the 

sCD4 moiety to the HIV gp120 Env 

glycoprotein induces a conformational 

change that enables the antibody moiety 

to bind, thereby blocking Env function 

and virus entry. This novel design 

provides the protein with unique 

characteristics that enable its extremely 

strong binding to gp120, thus rendering 

it a potential effective antiviral agent 

against HIV. Recent studies indicate that 

this novel bispecific protein displays 

extremely broad neutralizing activity 

against genetically diverse primary 

HIV–1 isolates, with breadth much 

greater than previously described (Dey 

et al. J. Virology 2003). The potency is 

generally at least 10-fold greater than 

the best described HIV–1 neutralizing 

monoclonal antibodies, and the protein 

is highly active against many HIV–1 

isolates that are refractory to 

neutralization by these antibodies. 

Importantly, the protein is composed of 

almost entirely human sequences. 

The chimeric protein of this invention 

has considerable potential for 

prevention of HIV–1 infection, both as 

a topical microbicide and as a systemic 

agent to protect during and after acute 

exposure (e.g. vertical transmission, 

post exposure prophylaxis). It also has 

potential utility for treatment of chronic 

infection, including gene therapy 

strategies involving hematopoietic stem 

cells and/or viral vectors. Such proteins, 

nucleic acid molecules encoding them, 

and their production and use in 


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27152 Federal Register / Vol. 74, No. 108 / Monday, June 8, 2009 / Notices 

preventing or treating viral infections 

are claimed in the patents issued for this 

invention. 

Applications: 

• Prophylactic and/or therapeutic 

treatment for HIV infection. 

• Topical microbicide treatment to 

protect against HIV infection. 

• Imaging of HIV infected cells in 

tissues. 

Advantages: 

• High neutralization efficiency due 

to unique bifunctional binding 

characteristics. 

• Potentially minimally immunogenic 

or toxic (human sequences and possibly 

low treatment doses). 

• Broad neutralizing activity. 

• Mechanism of action less 

susceptible to resistance. 

Development Status: 

• Reproducible production and scaleup of chimeric protein has been 

demonstrated. 

• Potent and broad neutralization of 

genetically diverse HIV–1 clinical 

isolates was demonstrated. 

Market: The race to develop effective 

antiviral strategies against HIV infection 

is ongoing. The problems exhibited by 

conventional drugs (i.e. toxicity and 

resistance) have triggered the pursuit of 

alternative approaches to HIV/AIDS 

prevention and treatment. One of the 

new approaches is the development of 

neutralizing antibodies against the HIV 

envelope proteins. This approach has 

not yet yielded any commercially viable 

treatment. It is believed that the 

approach presented in the subject 

invention will circumvent many of the 

shortcomings of the existing drugs and 

other pursued approaches. If this 

approach is successful the commercial 

rewards will be huge because of the 

global magnitude of HIV epidemics. 

Inventor: Edward A. Berger (NIAID). 

Publication: B Dey, CS Del Castillo, 

EA Berger. Neutralization of human 

immunodeficiency virus type 1 by 

sCD4–17b, a single-chain chimeric 

protein, based on sequential interaction 

of gp120 with CD4 and coreceptor. J 

Virol. 2003 March;77(5):2859–2865. 

Patent Status: 

HHS Reference No. E–039–1999/0— 

• U.S. Patent No. 7,115,262, issued 03 

October 2006. 

• U.S. Application No. 11/535,957, 

filed 27 September 2006, published 18 

October 2007 as 20070243208. 

• Australian Patent No. 765218, 

issued 30 July 2003. 

• Applications pending in Canada, 

France, Germany, Great Britain, Italy, 

Japan, Spain. 

Licensing Status: Available for 

licensing. 

Licensing Contacts: Uri Reichman, 

Ph.D, MBA; 301–435–4616; 

ur7a@nih.gov; RC Tang, JD, LLM; 301– 

435–5031; tangrc@mail.nih.gov. 

Collaborative Research Opportunity: 

The NIAID Office of Technology 

Development is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize ‘‘A Novel Chimeric 

Protein for Prevention and Treatment of 

HIV Infection.’’ Please contact Rick 

Williams at 301–402–0960 for more 

information. 

Dated: June 1, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–13284 Filed 6–5–09; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2009–D–0217] 

Guidance for Industry on Medication 

Guides—Adding a Toll-Free Number 

for Reporting Adverse Events; 

Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of a guidance for industry 

entitled ‘‘Medication Guides—Adding a 

Toll-Free Number for Reporting Adverse 

Events.’’ Beginning July 1, 2009, 

manufacturers of prescription drug 

products approved under the Federal 

Food, Drug, and Cosmetic Act (the act) 

that are required to have a Medication 

Guide must add a verbatim statement to 

their Medication Guides containing 

FDA’s toll-free number for reporting 

side effects. These manufacturers are 

also required to report to FDA that they 

have complied with this requirement. 

This guidance explains what statement 

to add to Medication Guides, where to 

add it, and how to notify the agency that 

such a statement has been added. 

DATES: Submit written or electronic 

comments on agency guidances at any 

time. 

ADDRESSES: Submit written requests for 

single copies of this draft guidance to 

the Division of Drug Information, Center 

for Drug Evaluation and Research, Food 

and Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, rm. 2201, 

Silver Spring, MD 20993–0002. Send 

one self-addressed adhesive label to 

assist that office in processing your 

requests. Submit written comments on 

the draft guidance to the Division of 

Dockets Management (HFA–305), Food 

and Drug Administration, 5630 Fishers 

Lane, rm. 1061, Rockville, MD 20852. 

Submit electronic comments to http:// 

www.regulations.gov. See the 

SUPPLEMENTARY INFORMATION section for 

electronic access to the guidance 

document. 

FOR FURTHER INFORMATION CONTACT: 

Nancy Clark, Center for Drug Evaluation 

and Research, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Silver Spring, MD 20993, 301– 

796–5400, Nancy.Clark@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a guidance for industry entitled 

‘‘Medication Guides—Adding a TollFree Number for Reporting Adverse 

Events.’’ On September 27, 2007, the 

President signed into law the Food and 

Drug Administration Amendments Act 

(FDAAA) (Public Law 110–85). Among 

other things, FDAAA reauthorized the 

Best Pharmaceuticals for Children Act 

(BPCA) (Public Law 107–109). When 

enacted in 2001, the BPCA directed 

FDA to issue a final rule requiring the 

labeling of each human drug product for 

which an application is approved under 

section 505 of the act (21 U.S.C. 355) to 

include: (1) A toll-free number 

maintained by FDA for the purpose of 

receiving reports of adverse events 

regarding drugs and (2) a statement that 

the number is to be used for reporting 

purposes only, not to receive medical 

advice. The BPCA stated that the final 

rule must reach the broadest consumer 

audience and minimize the cost to the 

pharmacy profession. As required, FDA 

issued a proposed rule entitled ‘‘TollFree Number for Reporting Adverse 

Events on Labeling for Human Drug 

Products’’ (69 FR 21778, April 22, 

2004), which would require, among 

other things, that a side effects 

statement be included in FDA-approved 

Medication Guides for drug products 

approved under section 505 of the act. 

FDA received 22 comments on this 

proposed rule and was in the process of 

analyzing the comments and conducting 

research on consumer comprehension of 

the side effects statement when FDAAA 

was enacted. Section 502(f) of FDAAA 

stated that ‘‘the proposed rule * * * 

entitled ‘Toll-Free Number for Reporting 

Adverse Events on Labeling for Human 

Drug Products’ * * * shall take effect 

on January 1, 2008,’’ unless FDA issues 

a final rule before that date. FDA did not 

issue a final rule by January 1, 2008, so 


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