[Federal Register Volume 72, Number 179 (Monday, September 17, 2007)]
[Notices]
[Pages 52887-52889]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-18189]


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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.

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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.

Suppression of Allergic Asthma by Ascaris Antigens

    Description of Technology: Available for licensing and commercial 
development are compositions and methods for suppressing allergic 
reactions, as well as Th-1 and Th-2 associated immunological diseases, 
by administering any of the two identified Ascaris polypeptide 
antigens, or active fragments or variants thereof, to the affected 
subject.
    Allergic asthma is characterized by antigen-specific IgE 
production, reversible airway hyper-reactivity and eosinophilic 
infiltration of the airways. There is a dramatic increase in the 
prevalence of allergic disorders in emerging and industrialized 
countries and studies suggest that the hygienic environment in those 
countries may not provide allergy-protective mechanisms associated with 
some forms of infection. Recent studies have found that helminth 
infection may suppress the development of allergic disease. Helminth 
infections currently affect over 2 billion people worldwide, causing 
significant morbidity. The most successful geohelminths are members of 
the Ascaris species, including A. lumbricoides and A. suum, which are 
known to infect 1.5 billion people. The inventors studied the 
modulation of allergic disease mediated by a chronic A. suum infection 
in their murine model of ragweed-induced allergic conjunctivitis and 
allergic asthma, and demonstrated that the infection prevents allergic 
inflammation in sites distal from larval migration. This protection was 
due, in part, to the induction of immunoregulatory cytokines such as 
IL-10. In further studies, they demonstrated that a cocktail of 
antigens from the pseudocoelomic fluid (PCF) of A. suum, administered 
during ragweed sensitization, significantly reduced the eosinophil 
migration into the conjunctiva, pulmonary eosinophilic inflammation, 
and total lung pathology induced by the ragweed. PCF exposure also 
reduced the secretion of the pro-allergic cytokines IL-5 and IL-13 in 
the broncho-alveolar lavage fluid after ragweed exposure. All findings 
suggest PCF is capable of suppressing the allergic response to a 
traditional allergen and at multiple tissue sites.
    In further studies, the inventors determined that the protection 
conferred by PCF to allergic inflammation was through a specific first 
antigenic protein isolated from PCF, results that were confirmed by 
using the recombinant form of the first antigen.

[[Page 52888]]

    Furthermore, it is known that Toll-like receptors (TLRs) on 
dendritic cells (DCs) and other antigen presenting cells recognize 
specific molecular patterns on invading pathogens, leading to the 
development of host immunity. A number of pathogens, including 
helminths, have used pattern recognition by TLRs to modulate host 
immunity and inflammation to establish a chronic infection. In further 
studies, the inventors identified a second specific antigenic protein, 
also isolated from PCF, which can modulate activation of bone marrow 
derived DCs in response to stimuli with bacterial lipopolysaccharide 
(LPS); and to stimulate DCs to produce significant increases in IL-10 
but not IL-12 upon co-stimulation with LPS. Studies in various 
genetically deficient mice suggested that this second antigen augments 
the IL-10 production dependent on one of the TLRs, TLR4. In further 
studies with the cloned and expressed form of the second antigen, as 
well as its two domains, the inventors showed that the activity is 
dependent on domain 2 but not domain 1. The purified second antigen 
exhibits different properties than unfractionated PCF. PCF 
administration prevents an initial response from occurring, as it 
inhibits the initiation of the inflammatory cascade. By contrast, the 
second antigen can activate DCs and alter cells such that they 
ultimately suppress responses through the production of IL-10 and can 
therefore act on the effector phase of the inflammatory response (i.e., 
modulate a response that is already occurring).
    Applications: Suppression of allergic responses to traditional 
allergens by administering the identified Ascaris polypeptide antigens, 
or active fragments or variants thereof, to the affected subjects. The 
inventions provide different ways to treat allergic diseases or prevent 
allergic reactions, rather than merely ameliorating the symptoms. The 
inventions are also applicable to other Th-1 and Th-2 associated 
immunological diseases.
    Development Status: The technologies are currently in the pre-
clinical stage of development.
    Inventors: Andrea Keane-Myers et al. (NIAID).
    Relevant Publications: Manuscripts describing the above 
technologies will be available as soon as they are accepted for 
publication.
    Patent Status:
    U.S. Provisional Application No. 60/902,506 filed 22 February 2007 
(HHS Reference No. E-126-2007/0-US-01).
    U.S. Provisional Application No. 60/924,537 filed 18 May 2007 (HHS 
Reference No. E-174-2007/0-US-01).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Cristina Thalhammer-Reyero, Ph.D, MBA; 301/435-
4507; [email protected].

Citrobacter freundii WR7011 as a Vaccine Strain or Source of Vi 
Capsular Antigen for Protection Against Typhoid Fever

    Description of Invention: According to the WHO, typhoid fever 
remains a serious public health problem throughout the world, with an 
estimated 16-33 million cases and 500,000 to 600,000 deaths annually. 
The Vi capsule of S. typhi, the causative agent of typhoid fever, is a 
surface-bound carbohydrate polymer to which antibodies have been shown 
to protect against typhoid fever. Purification of this polymer from 
virulent S. typhi strains poses a danger to those handling the live 
organisms. However, an unusual strain of Citrobacter freundii, WR7004 
was mutated by the inventors to create a strain (WR7011) that makes Vi 
polysaccharide on its surface. Specifically, the strain was mutated 
using nitrosoguanidine. C. freundii WR7011 makes several times as much 
Vi polysaccharide as strains of S. typhi, is nonpathogenic, and is much 
safer to work with for Vi production or use as a vaccine strain. The 
inventors anticipate that this strain of C. freundii will reduce costs 
of purifying the Vi polysaccharide and also provide an increased level 
of safety during manufacture of the polysaccharide.
    Applications and Modality: Synthesis of S. typhi Vi polysaccharide.
    Market: Research tool useful for vaccine studies and/or vaccine 
production.
    Development Status: The technology is a research tool.
    Inventors: Dennis Kopecko and DeQi Xu (CBER/FDA).
    Pertinent References:
    1. NJ Snellings et al. Genetic regulation of variable Vi antigen 
expression in a strain of Citrobacter freundii. J Bacteriol. 1981 
Feb;145(2):1010-1017.
    2. H-S Houng et al. Expression of Vi antigen in Escherichia coli K-
12: characterization of ViaB from Citrobacter freundii and identity of 
ViaA with RcsB. J Bacteriol. 1992 Sep;174(18):5910-5915.
    3. JT Ou et al. Specific insertion and deletion of insertion 
sequence 1-like DNA element causes the reversible expression of the 
virulent capsular antigen Vi of Citrobacter freundii in Escherichia 
coli. Proc Natl Sci USA. 1988 June;85(12):4402-4405.
    4. SC Szu et al. Vi capsular polysaccharide-protein conjugates for 
prevention of typhoid fever. J Exp Med. 1987 Nov 1;166(5):1510-24.
    Patent Status: HHS Reference No. E-004-2007/0--Research Tool.
    Licensing Status: This technology is not patented. The mouse model 
will be transferred through a Biological Materials License.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].
    Collaborative Research Opportunity: The FDA-CBER Laboratory of 
Enteric and Sexually Transmitted Diseases is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize Vi 
polysaccharide from Citrobacter freundii. Please contact Dr. Dennis J. 
Kopecko at 301-496-1893 or ([email protected]) for more 
information.

Catalytic Domains of [beta](1,4)-galactosyltransferase I Having Altered 
Donor and Acceptor Specificities, Domains That Promote In Vitro Protein 
Folding, and Methods for Their Use

    Description of Technology: [beta](1,4)-galactosyltransferase I 
catalyzes the transfer of galactose from the donor, UDP-galactose, to 
an acceptor, N-acetylglucosamine, to form a galactose-[beta](1,4)-N-
acetylglucosamine bond. This reaction allows galactose to be linked to 
an N-acetylglucosamine that may itself be linked to a variety of other 
molecules. The reaction can be used to make many types of molecules 
having great biological significance. For example, galactose-
[beta](1,4)-N-acetylglucosamine linkages are very important for 
cellular recognition and binding events as well as cellular 
interactions with pathogens, such as viruses. Therefore, methods to 
synthesize these types of bonds have many applications in research and 
medicine to develop pharmaceutical agents and improved vaccines that 
can be used to treat disease.
    The present invention is based on the surprising discovery that the 
enzymatic activity of [beta](1,4)-galactosyltransferase can be altered 
such that the enzyme can make chemical bonds that are very difficult to 
make by other methods. These alterations involve mutating the enzyme 
such that the mutated enzyme can transfer many different types of 
sugars from sugar nucleotide donors to many different types of 
acceptors. Therefore, the mutated [beta](1,4)-

[[Page 52889]]

galactosyltransferases of the invention can be used to synthesize a 
variety of products that, until now, have been very difficult and 
expensive to produce.
    The invention also provides amino acid segments that promote the 
proper folding of a galactosyltransferase catalytic domain and 
mutations in the catalytic domain that enhance folding efficiency and 
make the enzyme stable at room temperature. The amino acid segments may 
be used to properly fold the galactosyltransferase catalytic domains of 
the invention and thereby increase their activity. The amino acid 
segments may also be used to increase the activity of 
galactosyltransferases that are produced recombinantly. Accordingly, 
use of the amino acid segments according to the invention allows for 
production of [beta](1,4)-galactosyltransferases having increased 
enzymatic activity relative to [beta](1,4)-galactosyltransferases 
produced in the absence of the amino acid segments.
    Applications: Synthesis of polysaccharide antigens for conjugate 
vaccines, glycosylation of monoclonal antibodies, and as research 
tools.
    Development Stage: The enzymes have been synthesized and 
preclinical studies have been performed.
    Inventors: Pradman K. Qasba, Boopathy Ramakrishnan, Elizabeth 
Boeggeman (NCI).
    Patent Status: U.S. and Foreign Rights Available (HHS Reference No. 
E-230-2002/2).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute's 
Nanobiology Program is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize the use of galactose and modified galactose 
to be linked to an N-acetylglucosamine that may itself be linked to a 
variety of other molecules. Please contact John D. Hewes, PhD. at 301-
435-3121 or [email protected] for more information.

Rapid Motion Perception MRI Navigator Method

    Description of Technology: Available for licensing and commercial 
development is a non-breathhold flow sensitive navigator technique for 
reducing respiratory motion artifacts in magnetic resonance (MR) 
images. The method, called Rapid Motion Perception (RaMP), tracks bulk 
translational motion of the heart in real-time. The position of the 
blood volume is a direct representation of the heart position. RaMP 
tracks fast-moving blood volume during systole as a marker for the 
heart position, while suppressing stationary or slow moving spins. This 
approach allows cardiac navigation in two orthogonal directions 
simultaneously, eliminates the need to obtain empirical correlations 
between the diaphragm and the heart, and increases tracking reliability 
among individual patients. The method uses a spoiled-Fast Low Angle 
Shot (FLASH) navigator and incorporates an alternating pair of bipolar 
velocity-encoding gradients. Data at 1.5T indicate that RaMP is capable 
of correcting bulk motion of the heart over multiple cardiac cycles to 
within +/-1.43 mm in the superior-inferior direction and +/-0.84 mm in 
the anterior-posterior direction.
    Applications:
    Reduction of MR image artifacts due to respiration motion.
    Real-time tracking of cardiac motion.
    Market: Magnetic Resonance Imaging.
    Development Status: Late-stage technology.
    Inventors: Vinay M. Pai and Han Wen (NHLBI).
    Patent Status: U.S. Patent Application No. 10/244,903 filed 16 Sep 
2002 (HHS Reference No. E-164-2002/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Chekesha S. Clingman, Ph.D.; 301/435-5018; 
[email protected].
    Collaborative Research Opportunity: The NHLBI is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize this 
technology. Please contact Lili Portilla at 301-594-4273 or via e-mail 
at [email protected] for more information.

    Dated: September 7, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E7-18189 Filed 9-14-07; 8:45 am]
BILLING CODE 4140-01-P