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
14570 Federal Register / Vol. 74, No. 60 / Tuesday, March 31, 2009 / Notices 

Licensing Status: Available for 

licensing. 

Licensing Contact: Peter A. Soukas, 

J.D.; 301–435–4646; 

soukasp@mail.nih.gov 

Radiotracers for Imaging Pglycoprotein Transporter Function 

Description of Technology: This 

invention offers technology to help treat 

certain brain diseases, such as 

Alzheimer’s disease and Parkinson’s, 

and may lead to more effective and 

personalized treatments. P-glycoprotein 

transporter (P-gp) acts as a pump at the 

blood-brain barrier to exclude a wide 

range of xenobiotics (e.g., toxins, drugs, 

etc.) from the brain and is also 

expressed in a tumor in response to 

exposure to established/prospective 

chemotherapeutics (a phenomenon 

known as multidrug resistance; MDR). 

The instant invention relates to 

compounds that are avid substrates for 

P-gp, and their preparation and use as 

radiotracers for imaging P-gp function in 

vitro and in vivo. 

Applications: These radiotracers have 

potential application for investigating 

the function of P-gp at the blood-brain 

barrier for human subjects and patients 

in relation to neuropsychiatric disorders 

and in cancer. Their application may 

lead to a better general understanding of 

the role of P-gp in the unfolding of 

certain brain diseases (e.g., Alzheimer’s 

disease, Parkinson’s disease), and 

ultimately to more effective and 

personalized treatment. Likewise, these 

radiotracers may be applied in oncology 

to help understand MDR and its clinical 

manifestation, and to help seek out 

cancer therapies that avoid MDR. 

Advantages: This class of radiotracer, 

typified by the described [11C]dLop, is 

designed to restrict the formation of 

radiometabolites that would obstruct the 

measurement of P-gp function at the 

blood-brain barrier or at tumors. In this 

sense these radiotracers are vastly 

superior to progenitors (e.g., 

[11C]verapamil, [11C]loperamide), 

which can only give qualitative not 

quantitative information. 

Development Status: Radiotracer 

studies in human subjects are in 

progress. Longer-lived versions of the 

radiotracers are in development. 

Market: These radiotracers may be of 

interest to those wishing to market and/ 

or apply such radiotracers in the 

medical imaging field. 

Inventors: Victor W. Pike, Robert B. 

Innis, Sami S. Zoghbi, and Neva 

Lazarova (NIMH). 

Publications: 

1. SS Zoghbi, JS Liow, F Yasuno, J 

Hong, E Tuan, N Lazarova, RL Gladding, 

VW Pike, RB Innis. 11C–Loperamide 

and its N-desmethyl radiometabolite are 

avid substrates for brain P-glycoprotein 

efflux. J Nucl Med. 2008 Apr;49(4):649– 

656. 

2. N Lazarova, SS Zoghbi, J Hong, N 

Seneca, E Tuan; RL Gladding, JS Liow, 

A Taku, RB Innis, VW Pike. Synthesis 

and evaluation of [N-methyl-11C]Ndesmethyl-loperamide as a new and 

improved PET radiotracer for imaging Pgp function. J Med Chem. 2008 Oct 

9;51(19):6034–6043. 

3. JS Liow, W Kreisl, SS Zoghbi, N 

Lazarova, N Seneca, RL Gladding, A 

Taku, P Herscovitch, VW Pike, RB Innis. 

P-glycoprotein function at the bloodbrain barrier imaged using 11C–Ndesmethyl-loperamide in monkeys. J 

Nucl Med. 2009 Jan;50(1):108–115. 

Patent Status: U.S. Patent Application 

No. 12/112,994 filed 30 Apr 2008 (HHS 

Reference No. E–318–2007/0–US–01) 

Licensing Status: Available for 

licensing. 

Licensing Contact: RC Tang, JD, LLM; 

301–435–5031; tangrc@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Institute of Mental Health 

Molecular Imaging Branch is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize radiotracers for imaging 

P-gp function. Please contact Victor Pike 

at pikev@mail.nih.gov for more 

information. 

Dated: March 24, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–7213 Filed 3–30–09; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

Center for Scientific Review; Notice of 

Closed Meetings 

Pursuant to section 10(d) of the 

Federal Advisory Committee Act, as 

amended (5 U.S.C. Appendix 2), notice 

is hereby given of the following 

meetings. 

The meetings will be closed to the 

public in accordance with the 

provisions set forth in sections 

552b(c)(4) and 552b(c)(6), Title 5 U.S.C., 

as amended. The grant applications and 

the discussions could disclose 

confidential trade secrets or commercial 

property such as patentable material, 

and personal information concerning 

individuals associated with the grant 

applications, the disclosure of which 

would constitute a clearly unwarranted 

invasion of personal privacy. 

Name of Committee: Center for Scientific 

Review Special Emphasis Panel; Molecular 

Neuroscience. 

Date: April 20–21, 2009. 

Time: 9 a.m. to 3 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: National Institutes of Health, 6701 

Rockledge Drive, Bethesda, MD 20892 

(Virtual Meeting). 

Contact Person: Deborah L. Lewis, PhD, 

Scientific Review Officer, Center for 

Scientific Review, National Institutes of 

Health, 6701 Rockledge Drive, Room 4118, 

MSC 7850, Bethesda, MD 20892, (301) 435– 

1224, lewisdeb@csr.nih.gov. 

Name of Committee: Center for Scientific 

Review Special Emphasis Panel; Topics in 

Developmental, Cellular and Molecular 

Biology. 

Date: April 20, 2009. 

Time: 2 p.m. to 4 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: National Institutes of Health, 6701 

Rockledge Drive, Bethesda, MD 20892 

(Telephone Conference Call). 

Contact Person: Sherry L. Dupere, PhD, 

Scientific Review Officer, Center for 

Scientific Review, National Institutes of 

Health, 6701 Rockledge Drive, Room 5136, 

MSC 7843, Bethesda, MD 20892, (301) 435– 

1021, duperes@csr.nih.gov. 

Name of Committee: Center for Scientific 

Review Special Emphasis Panel; Member 

Conflict Review for UKDG Study Section. 

Date: April 27, 2009. 

Time: 1 p.m. to 3 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: National Institutes of Health, 6701 

Rockledge Drive, Bethesda, MD 20892 

(Telephone Conferece Call). 

Contact Person: Rass M. Shayiq, PhD, 

Scientific Review Officer, Center for 

Scientific Review, National Institutes of 

Health, 6701 Rockledge Drive, Room 2182, 

MSC 7818, Bethesda, MD 20892, (301) 435– 

2359, shayiqr@csr.nih.gov. 

Name of Committee: Center for Scientific 

Review Special Emphasis Panel. Member 

Conflict: Memory and Neuroendocrinology. 

Date: April 29, 2009. 

Time: 3 p.m. to 5 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: National Institutes of Health, 6701 

Rockledge Drive, Bethesda, MD 20892 

(Virtual Meeting). 

Contact Person: Edwin C. Clayton, PhD, 

Scientific Review Officer, Center for 

Scientific Review, National Institutes of 

Health, 6701 Rockledge Drive, Room 50950, 

MSC 7844, Bethesda, MD 20892, (301) 402– 

1304, claytone@csr.nih.gov. 

(Catalogue of Federal Domestic Assistance 

Program Nos. 93.306, Comparative Medicine; 

93.333, Clinical Research, 93.306, 93.333, 

93.337, 93.393–93.396, 93.837–93.844, 

93.846–93.878, 93.892, 93.893, National 

Institutes of Health, HHS) 


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