14568 Federal Register / Vol. 74, No. 60 / Tuesday, March 31, 2009 / Notices 

expected to rise as patients with HCV 

infection age and progress to more 

serious liver diseases (McHutchison HG, 

et al. Chronic Hepatitis C: An Age Wave 

of Disease Burden 2005. American 

Journal of Managed Care. 11: S286– 

S295). From 2010–2019, it is estimated 

that direct medical expenditures for 

HCV will be $10.7 billion; the costs of 

decompensated HCV infection (cirrhosis 

and hepatocellular carcinoma) are 

estimated to be $21.3 billion; and 

indirect costs associated with the loss of 

life under age 65 are estimated to be 

$54.2 billion (McHutchison HG, et al. 

2005). 

Chronic hepatitis C is a serious 

disease that can result in long-term 

health problems, including liver 

damage, liver failure, liver cancer, or 

even death. It is the leading cause of 

cirrhosis and liver cancer and the most 

common reason for liver transplantation 

in the United States. Approximately 

8,000–10,000 people die every year from 

hepatitis C related liver disease. 

Of every 100 people infected with the 

hepatitis C virus, about 75–85 people 

will develop chronic hepatitis C virus 

infection; of those, 

• 60–70 people will go on to develop 

chronic liver disease. 

• 5–20 people will go on to develop 

cirrhosis over a period of 20–30 years. 

• 1–5 people will die from cirrhosis 

or liver cancer. 

In spite of the urgent public health 

need for effective drugs and vaccines 

against HCV as discussed above, and in 

spite of the huge market potential for 

such medical remedies, there are no 

effective drugs or vaccines in existence 

as of yet due to technical difficulties, 

one of them, as mentioned at the outset, 

is the difficulties in growing and 

culturing the virus. The only drugs 

available to treat HCV at the present 

time are Ribavirin and Interferon but 

none constitute a real cure for the 

disease. They also can present severe 

side effects that make the use of them 

prohibitive in many cases. The subject 

technology may therefore present an 

opportunity for drug and vaccine 

companies to accelerate their research 

and development in this area. 

Inventors: Rodney Russell, Jens Bukh, 

Robert H. Purcell, and Suzanne U. 

Emerson (NIAID). 

Publication: RS Russell, JC Meunier, S 

Takikawa, K Faulk, RE Engle, J Bukh, 

RH Purcell, SU Emerson. Advantages of 

a single-cycle production assay to study 

cell culture-adaptive mutations of 

hepatitis C virus. Proc Natl Acad Sci 

USA. 2008 Mar 18;105(11):4370–4375. 

Patent Status: 

• U.S. Provisional Application No. 

60/931,259 filed 21 May 2007 (HHS 

Reference No. E–171–2007/0–US–01). 

• U.S. Provisional Application No. 

61/066,773 filed 22 Feb 2008 (HHS 

Reference No. E–171–2007/1–US–01). 

• PCT Application No. PCT/US2008/ 

063982 filed 16 May 2008, which 

published as WO 2008/147735 on 04 

Dec 2008 (HHS Reference No. E–171– 

2007/2–PCT–01). 

Licensing Status: Available for 

licensing. 

Licensing Contacts: Uri Reichman, 

PhD, MBA; 301–435–4616; 

UR7a@nih.gov; Rung C. Tang, JD, LLM; 

301–435–5031; tangrc@mail.nih.gov. 

Dated: March 24, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–7207 Filed 3–30–09; 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 any 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. 

Mouse Monoclonal Antibodies to 

Human Tristetraprolin (TTP) 

Description of Technology: TTP has 

been implicated in autoimmune and 

inflammatory diseases through its role 

as a regulator of the transcripts encoding 

several pro-inflammatory cytokines, 

including tumor necrosis factor alpha. 

However, it has been difficult to study 

endogenous TTP in man and other 

animals because it is expressed at very 

low levels in most cells and tissues, and 

because of the lack of mouse 

monoclonal antibodies directed at the 

human protein. 

Scientists at the NIH have developed 

three mouse monoclonal antibodies 

(TTP–16, TTP–214 and TTP–409) that 

react to different regions of the human 

TTP to allow for the identification and 

localization of the TTP protein by 

standard protocols. Although validation 

has only been conducted at the level of 

western blotting to date, they do not 

appear to cross-react with other human 

members of the TTP protein family. 

Potential Applications: Mouse 

monoclonal antibodies to human TTP 

will be useful in both clinical and basic 

research on a variety of inflammatory 

diseases and studies of mRNA 

destabilization. They can be used to 

identify or isolate TTP in cells or tissues 

by Western blotting, 

immunoprecipitation, 

immunohistochemistry, 

immunofluorescence, flow cytometry, 

and RNA super-shift assays, and can 

also be used in cross-linking and 

immunoprecipitation protocols. 

Inventors: Elizabeth A. Kennington 

and Perry J. Blackshear (NIEHS). 

Patent Status: HHS Reference No. E– 

123–2009/0—Research Tool. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: Available for 

licensing. 

Licensing Contact: Fatima Sayyid, 

M.H.P.M.; 301–435–4521; 

Fatima.Sayyid@hhs.nih.gov. 

Use of Anthrax Lethal Factor To Treat 

Cancer and Screening Methods for 

MAPK Kinase Protease Activity 

Description of Technology: Anthrax 

toxin, produced by Bacillus anthracis, is 

composed of three proteins; protective 

antigen (PA), edema factor (EF), and 

lethal factor (LF). PA by itself has little 

or no toxic effect upon cells, but serves 

to bind cell surface receptors and 

mediate the entry of EF and LF into the 

cell. EF has been identified as an 

adenylate cyclase and together with PA 

forms a toxin (edema toxin; EdTx) 

which can induce edema formation 

when injected subcutaneously. LF and 

PA together form a toxin (lethal toxin; 

LeTx) which can cause rapid lysis of 

certain macrophage-derived cell lines in 

vitro as well as death when injected 

intravenously. 

Indirect evidence had suggested that 

LF was a metalloprotease. However, the 


tjames on PRODPC61 with NOTICES
Federal Register / Vol. 74, No. 60 / Tuesday, March 31, 2009 / Notices 14569 

intracellular target of LF remained 

unknown until recently when NIH 

scientists discovered that LF 

proteolytically inactivates mitogen 

activated protein kinase kinase 1 and 2 

(MAPKK1, 2). Using oocytes of the frog 

Xenopus laevis as well as tumor derived 

NIH3T3 (490) cells expressing an 

effector domain mutant form of the 

human V12HaRas oncogene these 

scientists demonstrated that LF induced 

proteolysis of MAPKK 1 and 2, resulting 

in their irreversible inactivation. 

MAPKK 1 and 2 are components of the 

mitogen activated protein kinase 

(MAPK) signal transduction pathway, 

an evolutionarily conserved pathway 

that controls cell proliferation and 

differentiation in response to 

extracellular signals and also plays a 

crucial role in regulating oocyte meiotic 

maturation. Further, the MAPK pathway 

has been shown to be constitutively 

activated in many primary human as 

well as in tumor-derived cell lines. 

Consistent with this, treatment of 

V12Ha-Ras transformed NIH 3T3 cells 

with LeTx inhibits cell proliferation and 

causes their reversion to a nontransformed phenotype. 

This invention specifically relates to 

in vitro and ex vivo methods of 

screening for modulators, homologues, 

and mimetics of LF mitogen activated 

protein kinase kinase (MAPKK) protease 

activity. Applications for this 

technology could be: 

• A novel tool (LF) for the study of 

the cellular role of the MAPK pathway 

in normal or tumor cells. 

• Investigation of LF for developing 

inhibitors for cancer therapy. By 

analyzing structural-functional 

relationships, additional compounds 

with improved specificity, increased 

potency, and reduced toxicity can be 

generated. Mimetics which block 

MAPKK activity or the determination of 

mechanisms of regulation of proteases 

that target MAPKK at or near the same 

site targeted by LF could be developed. 

• A protease-based assay for LF by 

using a peptide to test for LF cleavage. 

There is no commercial test for anthrax. 

This assay could be used for testing 

soldiers for anthrax exposure. 

Characterization of the interaction 

between LF and MAPKK at the amino 

acid level may lead to the generation of 

inhibitors which may prove useful in 

treating anthrax. 

Inventors: Nicholas S. Duesbery (NCI), 

Craig Webb (NCI), Stephen H. Leppla 

(NIDCR), George F. Vande Woude (NCI). 

Patent Status: 

U.S. Patent 6,485,925 issued 26 Nov. 

2002 (HHS Reference No. E–066–1998/ 

0–US–06). 

U.S. Patent 6,893,835 issued 17 May 

2005 (HHS Reference No. E–066–1998/ 

0–US–07). 

U.S. Patent 6,911,203 issued 28 June 

2005 (HHS Reference No. E–066–1998/ 

0–US–08). 

U.S. Patent 7,056,693 issued 06 June 

2006 (HHS Reference No. E–066–1998/ 

0–US–10). 

U.S. Patent 7,183,071 issued 27 Feb. 

2007 (HHS Reference No. E–066–1998/ 

0–US–11). 

International rights available. 

Licensing Status: Available for 

licensing. 

Licensing Contact: Surekha Vathyam, 

PhD; 301–435–4076; 

vathyams@mail.nih.gov. 

This abstract updates the version 

published in the Federal Register on 

Friday, March 13, 2009 (74 FR 10947– 

10948), to correct the reference numbers 

from E–068–1998 to E–066–1998. 

Dated: March 25, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–7223 Filed 3–30–09; 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. 

Vaccine for Shigella sonnei 

Description of Technology: 

Shigellosis, an inflammatory enteric 

infection is on the World Health 

Organization’s priority list of disease to 

be prevented. It can be prevented by Ospecific polysaccharide (O-SP)-protein 

conjugate vaccines in adults. But the 

highest incidence and severity of S. 

sonnei shigellosis is in young children 

and the O-SP-protein conjugate that was 

effective in adults cannot overcome the 

age-related immunogenicity of vaccines 

in this age group. Thus, a better 

immunogen is needed. 

The immunogen claimed in this 

application uses O-SP formed by 

isolation of low molecular mass of OSP-core fragments from the native 

product that allows a conjugate to be 

formed with a ‘‘sun’’ configuration as 

opposed to ‘‘lattice’’ type conjugates 

made previously, based on a synthetic 

saccharide conjugate of S. dysenteriae 

type 1 that induced significantly higher 

antibody levels than the ‘‘lattice’’ type 

conjugate. IgG antibody levels induced 

in young outbred mice with the ‘‘sun’’ 

configuration S. sonnei conjugate were 

higher than conjugates made with the 

full length O-SP. 

This application claims the vaccine 

compositions described above, methods 

of making the vaccine compositions of 

the technology, and methods of 

preventing and/or treating Shigellosis. 

Application: Development of Shigella 

sonnei vaccines and diagnostics. 

Advantages: Known regulatory path 

for conjugate vaccines, potential 

reduction in number of doses of 

vaccine, pediatric vaccine. 

Development Status: Vaccine 

candidates have been synthesized and 

preclinical studies have been 

performed. 

Inventors: John B. Robbins (NICHD), 

Rachel Schneerson (NICHD), Joanna 

Kubler-Kielb (NICHD), Christopher P. 

Mocca (NICHD), et al. 

Publications: 

1. J Kubler-Kielb et al. The elucidation 

of the structure of the core part of the 

LPS from Plesiomonas shigelloides 

serotype O17 expressing Opolysaccharide chain identical to the 

Shigella sonnei O-chain. Carbohydr Res. 

2008 Dec 8;343(18):3123–3127. 

2. JB Robbins et al. Shigella sonnei Ospecific oligosaccharide-core-protein 

conjugates: synthesis, characterization 

and immunogenicity in mice. Proc Natl 

Acad Sci. 2009; doi 10.1073/ 

pnas.0900891106. 

Patent Status: U.S. Provisional 

Application No. 61/089,394 filed 15 

Aug 2008 (HHS Reference No. E–308– 

2008/0–US–01) 


tjames on PRODPC61 with NOTICES