Federal Register / Vol. 74, No. 70 / Tuesday, April 14, 2009 / Notices 17197 

Dated: March 7, 2009. 

Jeffrey Shuren, 

Associate Commissioner for Policy and 

Planning. 

[FR Doc. E9–8524 Filed 4–13–09; 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, 

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. 

Insect Salivary Proteins as Potent 

Adjuvants for Enhancing Immune 

Responses 

Description of Technology: This 

invention relates to the discovery that 

specific sand fly salivary proteins have 

marked effects on the outcome of 

Leishmania infection. These proteins 

have the ability to stimulate strong Th1 

and Th2 responses. The Th1 responses 

with one protein, PpSP15, result in 

immune protection while the Th2 

responses to another protein, PpSP44, 

exacerbate infection. The protective 

protein enhanced a specific immune 

response to the infection, suggesting 

that it acts as an adjuvant to alter the 

environment and presentation of the 

parasite antigens. 

These immunogenic salivary proteins, 

capable of driving Th1 or Th2 

responses, can be used as adjuvants in 

vaccine development for a broad 

spectrum of diseases that require 

different immune responses. They may 

therefore be used to enhance immune 

responses to pathogens other than 

Leishmania parasites. They are also very 

potent in their effect, and small doses 

are sufficient to elicit a strong immune 

response. This potency can reduce the 

need to use chemical adjuvants, which 

often require large mounts of material 

and can have deleterious side effects. 

Applications: 

• Vaccine for Leishmania parasite 

and other pathogenic infections. 

• Potent adjuvant for a broad 

spectrum of diseases. 

Advantages: Efficient, potent, and less 

toxic than many chemical adjuvants. 

Development Status: Early Stage. 

Market: 

• 88 countries with an estimated 2 

million people affected each year. 

• Estimated 350 million at risk 

worldwide. 

Inventors: Jesus G. Valenzuela et al. 

(NIAID). 

Publication: F Oliveira, PG Lawyer, S 

Kamhawi, JG Valenzuela. Immunity to 

distinct sand fly salivary proteins 

primes the anti-Leishmania immune 

response towards protection or 

exacerbation of disease. PLoS Negl Trop 

Dis. 2008 Apr 16;2(4):e226. 

Patent Status: U.S. Provisional 

Application No. 61/089,884 filed 08 

Aug 2008 (HHS Reference No. E–303– 

2008/0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Jeffrey A. James 

PhD; 301–435–5474; 

jeffreyja@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 the Insect Salivary 

Proteins as potent immune response 

adjuvants. Please contact Charles 

Rainwater at crainwater@niaid.nih.gov 

or 301/496–2644 for more information. 

Anti-Cancer Oligodeoxynucleotides 

Description of Technology: A majority 

of human cancers originate from 

epithelial tissue. A common cancer of 

epithelial cell origin is non-melanoma 

skin cancer (NMSC), including basal 

cell carcinoma (BCC) and squamous cell 

carcinoma (SCC), with more than seven 

hundred thousand (700,000) new cases 

diagnosed each year in the United States 

alone. BCC is rarely life-threatening 

because it is slow growing and is mostly 

localized. Unlike BCC, SCC metastasizes 

at a rate of two (2) to six (6) percent over 

several years after the initial diagnosis. 

A highly malignant form invades and 

destroys tissue, and then metastasizes, 

initially to a regional lymph node before 

more distant organs such as the lungs or 

brain are affected. SCC is commonly 

encountered in a number of epithelial 

tissues, including the oral cavity, 

esophagus, larynx, bronchi, intestines, 

colon, genital tract, and skin. 

This application relates to 

suppressive CpG oligodeoxynucleotides 

(ODNs). This application claims 

suppressive ODN compositions and 

their use to prevent or delay the 

formation of a tumor, reducing the risk 

of developing a tumor, treating a tumor, 

preventing conversion of a benign to a 

malignant lesion, or preventing 

metastasis. Topical application of the 

ODNs of this invention in preclinical 

studies resulted in significantly fewer 

animals developing papillomas and 

fewer papillomas/animal. The invention 

also relates to use of suppressive ODNs 

to prevent/delay cancer when 

administered systemically as well as 

locally. 

Application: Development of anticancer vaccines, therapeutics and 

diagnostics. 

Development Status: ODNs have been 

synthesized and preclinical studies have 

been performed. 

Inventors: Dennis M. Klinman and 

Hidekazu Ikeuchi (NCI) 

Patent Status: U.S. Provisional 

Application No. 61/119,998 filed 04 Dec 

2008 (HHS Reference No. E–296–2008/ 

0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Peter A. Soukas, 

J.D.; 301–435–4646; 

soukasp@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute, 

Laboratory of Experimental 

Immunology, is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize this technology. Please 

contact John D. Hewes, PhD at 301–435– 

3121 or hewesj@mail.nih.gov for more 

information. 

Neutralization of Hepatitis C Virus 

(HCV) 

Description of Technology: Available 

for licensing and commercial 

development are compositions and 

methods for preventing and/or treating 

infection caused by hepatitis C virus 

(HCV). The invention is based on 

mapping studies conducted by the 

inventors of two epitopes within HCV 

E2: epitope I and epitope II. It has been 

discovered that epitope I is involved in 

virus neutralization but that epitope II 

mediates antibody interference, 

17198 Federal Register / Vol. 74, No. 70 / Tuesday, April 14, 2009 / Notices 

probably an adaptation of the virus to 

obfuscate the immune system. In an 

effort to attenuate or disable the 

interference effect of HCV–E2 epitope II, 

the present invention is directed to a 

HCV E2 polypeptide substitution/ 

deletion of native amino acids LFY in 

epitope II, a HCV E2 polypeptide 

insertion of amino acids between the 

native LFY in epitope II, or the use of 

epitope II as a molecular decoyant or to 

affinity-purify an immune globulin to 

deplete interfering antibodies from, and 

enrich neutralizing antibodies in, the 

preparation. 

Applications: HCV vaccines; HCV 

therapeutics. 

Advantages: Improved HCV vaccines 

and therapeutics. 

Development Status: The technology 

is currently in the preclinical stage of 

development. 

Inventors: Pei Zhang, Marian Major, 

Stephen Feinstone (FDA). 

Publications: 

1. P Zhang et al. Hepatitis C virus 

epitope-specific neutralizing antibodies 

in Igs prepared from human plasma. 

Proc Natl Acad Sci USA. 2007 May 

15;104(20):8449–8454. 

2. MY Yu et al. Neutralizing 

antibodies to hepatitis C virus (HCV) in 

immune globulins derived from antiHCV-positive plasma. Proc Natl Acad 

Sci USA. 2004 May 18;101(20):7705– 

7710. 

Patent Status: 

U.S. Provisional Application No. 61/ 

002,031 filed 06 Nov 2007 (HHS 

Reference No. E–276–2007/0–US–01). 

PCT Application No. PCT/US2008/ 

082368 filed 04 Nov 2008 (HHS 

Reference No. E–276–2007/1–PCT–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: RC Tang, JD, LLM; 

301–435–5031; tangrc@mail.nih.gov. 

Collaborative Research Opportunity: 

The FDA Center for Biologics 

Evaluation and Research, Laboratory of 

Plasma Derivatives, is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize this technology. Please 

contact Alice Welch, PhD at 301–827– 

0359 or Alice.Welch@fda.hhs.gov for 

more information. 

Live-Attenuated West Nile Virus 

Vaccines with Improved Immune 

Responses 

Description of Technology: West Nile 

virus (WNV), the etiologic agent of West 

Nile virus fever and encephalitis, is an 

emerging human and veterinary 

pathogen in North America. WNV also 

periodically poses a serious threat to 

public health in Africa, Australia, 

Europe, the Middle East, and Asia. 

There is no vaccine available. WNV 

strains are phylogenetically grouped 

into two distinct lineages based 

primarily on differences within the 

envelope (Env) protein gene segment. 

The highly virulent strains recently 

emergent on the North American 

continent are of lineage I. Lineage I 

viruses are primarily also isolated in the 

Middle East, Europe, and parts of 

Africa. Lineage II viruses are mostly 

isolated in Africa. Both lineages include 

highly neurovirulent as well as 

relatively attenuated strains of WNV. 

WN vaccine viruses developed by 

others are chimeric live attenuated WN 

vaccine viruses. The genomes of these 

viruses encode the C and NS proteins of 

dengue or yellow fever virus, 

respectively, along with the WNV prM 

and Env proteins, which are the major 

targets of the humoral immune response 

to flaviviruses. These chimeric live 

attenuated WN vaccines have been 

successful in animal testing and some 

are currently in clinical trials. However, 

these vaccines have two potential 

disadvantages due to their 

heterogeneous genetic composition: (i) 

Animal host range may be different from 

that of wild-type WNV, rendering the 

vaccines less than optimal for 

immunization of some at-risk species 

and (ii) the elicited immune response 

may be suboptimal in duration or 

quality, due to the absence from these 

vaccines of homologous WN NS 

proteins. 

FDA’s technology that is available for 

licensing comprises live attenuated 

West Nile viruses that are not chimeric, 

but instead have one or more mutations 

in the 3′ terminal stem loop secondary 

structure, resulting in decreased 

neurovirulence. The related patent 

application also claims methods of 

making the viruses claimed in the 

application and methods for using these 

viruses to prevent or treat WN infection. 

More specifically, the inventors 

modified infectious WN DNA such that 

all or segments of the wild-type WN 3′ 

stem loop nucleotide sequence was 

replaced with analogous dengue virus 

serotype 2 3′ stem loop sequences. The 

inventors also created a number of point 

mutations in the nucleotide sequence of 

the WN 3′ stem loop sequence. 

Application: Development of live 

attenuated West Nile Virus vaccines, 

therapeutics and diagnostics. 

Development Status: Vaccine 

candidates have been prepared and 

preclinical (mouse) studies have been 

performed. 

Inventors: Lewis Markoff and Li Yu 

(FDA/CBER). 

Publication: L Yu et al. Attenuated 

West Nile viruses bearing 3′SL and 

envelope gene substitution mutations. 

Vaccine. 2008 Nov 5;26(47):5981–5988. 

Patent Status: 

HHS Reference No. E–022–2004/0— 

• U.S. Provisional Patent Application 

No. 60/579,396 filed 14 Jun 2004. 

• PCT Patent Application No. PCT/ 

US2005/0207327 filed 14 Jun 2005. 

• U.S. Patent Application No. 11/ 

629,560 filed 14 Dec 2006. 

Licensing Status: Available for 

licensing. 

Licensing Contact: Peter A. Soukas, 

J.D.; 301–435–4646; 

soukasp@mail.nih.gov. 

Collaborative Research Opportunity: 

The FDA Office of Vaccines Research & 

Review is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize West Nile Virus 

vaccines. Please contact Alice Y. Welch, 

PhD, at 301–827–0359 or 

Alice.Welch@fda.hhs.gov for more 

information. 

Neuronal Decoding Algorithm for 

Prosthetic Limbs 

Description of Technology: The 

invention is a new algorithm for 

decoding neuronal responses based on 

the discovery that neuronal spike trains 

can be described using order statistics. 

The device has applications in the 

direct control of prosthetic limbs by 

neuronal signals originating from 

electrodes placed in the brain. The 

method allows for decoding neuronal 

responses by monitoring sequences of 

potentials from neurons while specific 

motor tasks are carried out. The 

sequences are then characterized using 

the innovative technique of applying 

order statistics to the spike train, such 

that subsequent action potentials 

representing unidentified motor tasks 

can be decoded to determine the 

unknown task. The invention is of 

substantial importance because it 

appears to have achieved a closed form 

interpretation of neuronal responses 

upon which a motor prosthetic device 

might be based. 

Applications: Direct control of 

prosthetic limbs by neurons; Closed 

form interpretation of neuronal response 

for prosthetic devices. 

Development Status: Early Stage. 

Inventors: Barry J. Richmond and 

Matthew C. Wiener (NIMH). 

Patent Status: U.S. Patent No. 

7,442,212 issued 28 Oct 2008 (HHS 

Reference No. E–038–2001/0–US–03). 

Licensing Status: Available for 

licensing. 

Federal Register / Vol. 74, No. 70 / Tuesday, April 14, 2009 / Notices 17199 

Licensing Contact: Jeffrey A. James, 

PhD; 301–435–5474; 

jeffreyja@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Institute of Mental Health, 

Laboratory of Neuropsychology, is 

seeking statements of capability or 

interest from parties interested in 

collaborative research to further 

develop, evaluate, or commercialize 

decoding algorithm for neuronal 

responses. Please contact Suzanne 

Winfield at winfiels@mail.nih.gov or 

301–402–4324 for more information. 

Dated: April 7, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–8473 Filed 4–13–09; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

Government-Owned Inventions; 

Availability for Licensing: Methods for 

Improvements and Enhancements of 

Diffusion Tensor MRI 

AGENCY: National Institutes of Health, 

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. 

FOR FURTHER INFORMATION CONTACT: 

Licensing information and copies of the 

U.S. patent applications listed below 

may be obtained by contacting either 

Uri Reichman, PhD, MBA (Phone: 301– 

435–4616; Fax: 301–402–0220; E-mail: 

UR7a@nih.gov) or John Stansberry, PhD 

(Phone: 301–435–5236; Fax: 301–402– 

0220; E-mail: stansbej@mail.nih.gov) at 

the Office of Technology Transfer, 

National Institutes of Health, 6011 

Executive Boulevard, Suite 325, 

Rockville, Maryland 20852–3804. A 

signed Confidential Disclosure 

Agreement will be required to receive 

copies of the patent applications. 

SUPPLEMENTARY INFORMATION: The 

technology offered for licensing is in the 

field of Diffusion Magnetic Resonance 

Imaging (MRI). Specifically, three new 

methods have been described and 

claimed that enhance the scope and 

applicability of Diffusion Tensor MRI 

(DTI or DT–MRI). 

The invention of DTI represented a 

breakthrough in MRI. It provides a 

method and system for measuring the 

effective diffusion tensor of spin-labeled 

molecules, and for generating images of 

key tensor-derived parameters that 

indicate features of tissue 

microstructure, organization and even 

physiological state. DTI data has 

improved the diagnosis of a large 

number of diseases, disorders, and 

conditions, and is also being used 

therapeutically, for instance, to aid 

neurosurgical planning. 

One of the pioneers in Diffusion MRI, 

Dr. Peter Basser, a Principal Investigator 

in NIH’s Eunice Kennedy Shriver 

National Institute of Child Health and 

Human Development (NICHD), is the 

primary inventor of DTI. Dr. Basser’s 

first contribution in this field is 

described in US Patent #5,539,310 

(issued July 23, 1996), entitled ‘‘Method 

and System for Measuring the Diffusion 

Tensor and for Diffusion Tensor 

Imaging.’’ His new inventions 

(described below) extend the specificity 

and clinical value of diffusion MRI data, 

particularly in elucidating fine 

microstructural details and features that 

are not detectable using DTI. 

Diffusion Tensor and q-Space MRI 

Specimen Characterization 

Description of Technology 

Diffusion Tensor MRI (DTI or DT– 

MRI) provides information primarily 

about how water diffuses in the 

extracellular compartment of tissues, 

where water mobility is hindered (i.e., 

where water diffuses freely but 

encounters barriers from which it is 

reflected). However, DTI does not 

provide a complete characterization of 

diffusion in the intracellular 

compartment of some cells, particularly 

myelinated axons, where water mobility 

is restricted by impermeable membranes 

(i.e., where water is trapped but 

otherwise free to diffuse within the 

cell). 

The subject invention provides a new 

modeling framework that selfconsistently describes 3–D anisotropic 

diffusion within a hindered 

extracellular compartment and within a 

restricted intra-axonal compartment. It 

results in an improved characterization 

and measurement tissue and cell 

microstructure in neuronal tissue, 

which promises to advance diagnosis of 

neurological conditions (e.g., Stroke, 

MS, Alzheimer’s disease), possibly 

cognitive and behavioral disorders (e.g., 

schizophrenia), as well as our ability to 

follow normal development and aging 

processes. 

More specifically, this new in vivo 

diffusion MRI method, especially suited 

for the characterization of brain white 

matter, marries q-space and DTI 

concepts: Diffusion within axons is 

modeled as hindered diffusion parallel 

to the axis of the axon, and restricted 

diffusion perpendicular to the axis. 

Diffusion exterior to axons is modeled 

as hindered diffusion with differing 

diffusivities parallel and perpendicular 

to the nerves’ axis. To practice this 

method, diffusion weighted (DW) MRI 

data are acquired from specimens at 

different q-values (with different 

diffusion gradient magnitudes and 

directions). Parameters associated with 

tissue microstructure, such as the intra 

and extra-axonal principal diffusivities 

and their corresponding principal 

directions, and the volume fractions of 

intra and extra-axonal space are then 

estimated from these data. Improved 

angular resolution of fiber tract 

orientation can be obtained for 

tractography studies and more 

microstructural information can be 

gleaned for both diagnostic and 

therapeutic purposes than from 

conventional DTI. This technology has 

been named CHARMED (Composite 

Hindered and Restricted Model of 

Diffusion). 

Inventors 

Peter J. Basser (NICHD) et al. 

Publications 

1. Y Assaf, RZ Freidlin, GK Rohde, PJ 

Basser. New modeling and experimental 

framework to characterize hindered and 

restricted water diffusion in brain white 

matter. Magn Reson Med. 2004 

Nov;52(5):965–978. 

2. Y Assaf and PJ Basser. Composite 

hindered and restricted model of 

diffusion (CHARMED) MR imaging of 

the human brain. Neuroimage 2005 Aug 

1;27(1):48–58. 

3. L Avram, E O ̈ zarslan, Y Assaf, A 

Bar-Shir, Y Cohen, PJ Basser. Threedimensional water diffusion in 

impermeable cylindrical tubes: theory 

versus experiments. NMR Biomed. 2008 

Oct;21(8):888–898. 

4. A Bar-Shir, L Avram, Y Assaf, PJ 

Basser, Y Cohen. Experimental 

Parameters and Diffraction Patterns at 

High q Diffusion MR: Experiments and 

Theoretical Simulations. Proc Intl Soc 

Mag Reson Med. 2007;15:1530. 

Patent Status 

U.S. Patent Application No. 10/ 

888,917 filed 08 Jul 2004, claiming