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28 August 2008

[Federal Register: August 28, 2008 (Volume 73, Number 168)]
[Page 50829-50830]
From the Federal Register Online via GPO Access []



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 human-derived 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

[[Page 50830]]

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 formalin-detoxified 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 
    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 Contact: Peter A. Soukas, J.D.; 301-435-4646;
    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 for more 

Magnetic Resonance Imaging Methods and Systems for Estimating Cone of 

    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).
    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;
    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 for more 

    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]