Federal Register / Vol. 73, No. 168 / Thursday, August 28, 2008 / Notices 50829 

more deaths, with 24 percent in the 

U.S., than any other cause. 

• Cerebral ischemia is the third 

leading cause of death after heart 

diseases and cancer. 

• Decreased blood flow underlies a 

significant number of chronic diseases 

that account for the majority of 

morbidity and mortality for elderly 

adults in this country. 

• Cancer patients and traumatic 

injury victims requiring reconstructive 

surgery. 

• Burn patients requiring skin 

transplants. 

• Organ transplant patients. 

Development Status: Early-stage of 

development (in vivo data available in 

mice and pigs). 

Inventors: Jeff S. Isenberg et al. (NCI). 

Patent Status: PCT Application No. 

PCT/US2007/080647 filed 5 Oct 2007, 

which published as WO 2008/060785 

on 22 May 2008 (HHS Reference No. 

E–227–2006/5–PCT–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Charlene A. 

Sydnor, PhD; 301–435–4689; 

sydnorc@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute Center for 

Cancer Research, Laboratory of 

Pathology is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize therapeutics targeting 

CD47 or thrombospondin-1. Please 

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

3121 or hewesj@mail.nih.gov for more 

information. 

Total Synthesis of Northebaine, 

Normorphine, Noroxymorphone 

Enantiomers and Derivatives via N-Nor 

Intermediates 

Description of Technology: A new 

synthetic process has been found in 

which nordihydrocodeinone, an early 

intermediate in the total synthesis of 

codeine and related compounds, is 

easily formed into a number of N-nor 

compounds. These N-nor compounds 

can be used as precursors in the 

formation of narcotics, narcotic 

antagonists, or narcotic agonistantagonists. 

The manufacture of drugs of this type, 

such as northebaine or normorphine, 

can now be done without the use of 

thebaine as starting material. The 

syntheses have fewer steps than 

previous methods, and also have high 

yields. In addition, very significant 

simplification of existing thebaine based 

processes for the manufacture of opiates 

can be expected. 

Applications: Potential new 

methodology for the synthesis of 

intermediates for drugs including 

naloxone, naltrexone, percodan and 

nalbuphine. 

Market: 

• More than a quarter of Americans 

suffer daily pain, a condition that costs 

the U.S. about $60 billion a year in lost 

productivity. 

• Americans spent about $2.6 billion 

in over-the-counter pain medications 

and another nearly $14 billion on 

outpatient analgesics in 2004. 

• Worldwide, nearly 300 million 

people are believed to suffer from 

chronic pain. 

Inventors: Kenner C. Rice et al. 

(NIDDK) 

Patent Status: 

HHS Reference No. E–012–1986/1—

• Australian Patent 642447 issued 15 

Feb 1994. 

• Japanese Patent 2694156 issued 12 

Sept 1997. 

• Canadian Patent 2067200 issued 30 

Jun 1998. 

• European Patent 0496830 issued 31 

Mar 1999 in Austria, Switzerland, 

Germany, Denmark, Greece, 

Luxembourg, Spain, Belgium, The 

Netherlands, Sweden, France, Italy and 

United Kingdom. 

HHS Reference No. E–012–1986/2—

• United States Patent 5,668,285 

issued 16 Sept 1997. 

Licensing Status: Available for 

licensing. 

Licensing Contact: Charlene A. 

Sydnor, PhD; 301–435–4689; 

sydnorc@mail.nih.gov. 

Dated: August 18, 2008. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E8–19914 Filed 8–27–08; 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. 

Botulinum Toxoid 

Description of Technology: 

Vaccination is the only approach that 

can be used to prevent botulism. A 

pentavalent botulinum toxoid 

comprised of formalin-detoxified 

botulinum neurotoxin (BoNT) BoNT/A, 

B, C, D and E hemagglutinin (Hmg) 

complexes has been used to immunize 

laboratory and military personnel since 

1961, but this has never been licensed 

by the United States Food and Drug 

Administration (FDA). Vaccination 

immediately after toxin exposure has no 

protective benefit because the immune 

response is relatively slow compared to 

the rate of intoxication. The only 

treatment that is available upon 

intoxication is antibody therapy, which 

entails the injection of equine-derived 

botulinum antitoxin (BAT) or humanderived botulinum immunoglobulin 

(BIG) to remove toxin from the blood. 

Antibody therapy does not alleviate 

symptoms of botulism, but can limit the 

amount of toxin that enters nerve 

terminals and thus may lessen the 

severity and shorten the duration of 

paralysis. 

Since a vaccine can be used to either 

protect a human population or produce 

a BAT or BIG product, it is important to 

have reliable methods to evaluate the 

antigenic integrity of botulinum 

vaccines. An in vitro assay that can 

serve in this capacity would be useful 

for evaluating the consistency of the 

antigen throughout the manufacturing 

process, as well as generating data that 

may reduce in vivo testing. 

Available for licensing are a variety of 

new toxoids useful as botulinum 

vaccine antigens, for BAT or BIG 

production, or for development of tests 

to evaluate antigenicity of botulinum 

vaccines. The toxoids of the invention 

are derived from the Serotype A and B 

150 kDa neurotoxin proteins. The 

resulting toxoids are antigenically 

identical to the native toxin as measured 

by inhibition ELISA in spite of showing 


jlentini on PROD1PC65 with NOTICES
50830 Federal Register / Vol. 73, No. 168 / Thursday, August 28, 2008 / Notices 

a reduction of toxicity by more than 

100,000-fold. Sandwich ELISA analysis 

indicated that the featured toxoids were 

two- to three-fold less antigenic than the 

native neurotoxin compared to 

commercially available toxoids, which 

were about 100-fold less antigenic. 

Preclinical studies have been 

performed using the toxoids of the 

invention. Mice were immunized twice, 

on Day Zero (0) and Day Fourteen (14). 

By Day Twenty-Eight (28), relatively 

high toxin-specific IgG titers were 

detected in animals that had received 

any of the in-house toxoids, with greater 

than 99% being IgG1 and the remainder 

IgG2. These immunized mice remained 

asymptomatic after being challenged 

with Fifty (50) to One Million 

(1,000,000) median lethal dose (LD50) 

units of the 900 kDa neurotoxin. In 

contrast, animals immunized with 

several different batches of 

commercially available toxoids did not 

develop measurable toxin-specific 

antibody titers; however, these mice did 

survive neurotoxin challenges with Two 

(2) LD50 units, but died when 

challenged with Six (6) LD50 units. 

This application claims the formalindetoxified botulinum compositions 

described above and an in vitro method 

for characterizing the toxoids. Also 

claimed are methods of making the 

botulinum compositions, and methods 

of producing antitoxin to botulinum 

toxin. 

Applications: ELISA development, 

production of equine or human-derived 

botulinum antitoxin, development of 

next generation botulism vaccines. 

Development Status: Toxoids have 

been prepared and preclinical studies 

have been performed. Standard 

antibody reagents for ELISA assay 

development have been prepared. 

Inventors: James E. Keller (FDA/ 

CBER). 

Publication: JE Keller. 

Characterization of New Formalin 

Botulinum Neurotoxin Toxoids. Clin 

Vaccine Immunol. 2008 Jul 30; Epub 

ahead of print, doi:10.1128/CVI.00117–

08. 

Patent Status: U.S. Provisional 

Application No. 61/036,904 filed 14 Mar 

2008 (HHS Reference No. E–325–2007/ 

0–US–01). 

Licensing Status: Available for 

exclusive or non-exclusive licensing. 

Licensing Contact: Peter A. Soukas, 

J.D.; 301–435–4646; 

soukasp@mail.nih.gov. 

Collaborative Research Opportunity: 

The FDA Center for Biologics 

Evaluation and Research is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize botulinum toxoids. 

Please contact Alice Welch, PhD at 301–

827–0359 or Alice.Welch@fda.hhs.gov 

for more information. 

Magnetic Resonance Imaging Methods 

and Systems for Estimating Cone of 

Uncertainty 

Description of Technology: In 

diffusion tensor MRI imaging it is 

desirable to determine and display the 

fiber tract dispersion, e.g., the 

eigenvectors and the associated 

uncertainties. For example, the unit 

eigenvector may be displayed with a 

cone of uncertainty around its tip. This 

conveys the notion that the direction of 

fiber is not known precisely. However, 

the known methods are directed to 

computation and visualization of a 

circular cone of uncertainty. These 

methods are suitable for practical 

computation and visualization of an 

elliptical cone of uncertainty. The 

current invention overcomes this 

problem by providing (1) a 

reconstruction procedure to construct 

the covariance matrix of a major 

eigenvector for each voxel of a region of 

interest of a subject, (2) a visualization 

technique to visualize the elliptical cone 

of uncertainty of the eigenvector, and (3) 

two reconstruction procedures to 

compute the normalized areal and 

circumferential measures of the 

elliptical cone of uncertainty. The 

methods can be used to diagnose 

medical disorders associated with 

anomalous changes in water diffusion. 

The methods can also be used in 

applications in material science and 

earth science (geomagnetism). 

Applications: Magnetic Resonance 

Imaging; Diagnostics; Material science; 

Earth science (Geomagnetism). 

Inventor: Cheng Guan Koay (NICHD). 

Publications: 

1. CG Koay et al. The elliptical cone 

of uncertainty and its normalized 

measures in diffusion tensor imaging. 

IEEE Trans Med Imaging. 2008 

Jun;27(6):834–846. 

2. CG Koay et al. Error propagation 

framework for diffusion tensor imaging 

via diffusion tensor representations. 

IEEE Trans Med Imaging. 2007 

Aug;26(8):1017–1034. 

3. CG Koay et al. A unifying 

theoretical and algorithmic framework 

for least squares methods of estimation 

in diffusion tensor imaging. J Magn 

Reson. 2006 Sep;182(1):115–125. 

Patent Status: U.S. Provisional 

Application No. 60/996,169 filed 05 

Nov 2007 (HHS Reference No. E–273–

2007/0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Michael A. 

Shmilovich, Esq.; 301–435–5019; 

shmilovm@mail.nih.gov. 

Collaborative Research Opportunity: 

The NICHD, Section on Tissue 

Biophysics and Biomimetics, is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize this technology. Please 

contact Alan E. Hubbs, PhD at 301–594–

4263 or hubbsa@mail.nih.gov for more 

information. 

Dated: August 18, 2008. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E8–19915 Filed 8–27–08; 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. 

Radiotracers for Imaging Cannabinoid 

Sub-Type1 (CB1) Receptor 

Description of Technology: The 

present invention relates to novel 

radiolabeled compounds for imaging 

cannabinoid sub-type 1 (CB1) receptors 

in brains of mammals, particularly 

humans, using positron emission 

tomography (PET) or single photon 

emission computed tomography 


jlentini on PROD1PC65 with NOTICES