Government-Owned Inventions; Availability for Licensing, 34756-34762 [E8-13669]
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Federal Register / Vol. 73, No. 118 / Wednesday, June 18, 2008 / Notices
In compliance with the requirements
of Section 3506(c)(2)(A) of the
Paperwork Reduction Act of 1995, the
Administration for Children and
Families is soliciting public comment
on the specific aspects of the
information collection described above.
Copies of the proposed collection of
information can be obtained and
comments may be forwarded by writing
to the Administration for Children and
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and Evaluation, 370 L’Enfant
Promenade, SW., Washington, DC
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The Department specifically requests
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Consideration will be given to
comments and suggestions submitted
within 60 days of this publication.
Dated: June 11, 2008.
Brendan C. Kelly,
OPRE Reports Clearance Officer.
[FR Doc. E8–13658 Filed 6–17–08; 8:45 am]
BILLING CODE 4184–01–M
DEPARTMENT OF HEALTH AND
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Administration for Children and
Families
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prepared in response to the enactment
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forth in Title II of Pub. L. 108 36, Child
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Amendments of 2003, and in the
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direction to the States and Territories to
accomplish the purposes of (1)
supporting community-based efforts to
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better strengthen and support families to
reduce the likelihood of child abuse and
neglect, and; (2) fostering an
understanding, appreciation, and
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Program Instruction contains
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201; 202; 203; 205; 206; 207; and
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provide training and technical
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Respondents: State Governments.
ANNUAL BURDEN ESTIMATES
Number of respondents
Number of responses per
respondent
Average burden hours per
response
Application .......................................................................................................
Annual Report ..................................................................................................
52
52
1
1
40
24
2,080
1,248
Estimated Total Annual Burden Hours .....................................................
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3,328
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Instrument
Additional Information:
Copies of the proposed collection may
be obtained by writing to the
Administration for Children and
Families, Office of Administration,
Office of Information Services, 370
L’Enfant Promenade, SW., Washington,
DC 20447, Attn: ACF Reports Clearance
Officer. All requests should be
identified by the title of the information
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Office of Management and Budget,
Paperwork Reduction Project. Fax: 202–
395–6974. Attn: Desk Officer for the
Administration for Children and
Families.
Dated: June 11, 2008.
Janean Chambers,
Reports Clearance Officer.
[FR Doc. E8–13661 Filed 6–17–08; 8:45 am]
BILLING CODE 4184–01–M
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
National Institutes of Health,
Public Health Service, HHS.
AGENCY:
ACTION:
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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.
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.
ADDRESSES:
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Use of Amyloid Proteins as Vaccine
Scaffolds
Description of Technology: Amyloid
proteins are composed of peptides
whose chemical properties are such that
they spontaneously aggregate in vitro or
in vivo, assuming parallel or antiparallel
beta sheet configurations. Amyloid
proteins can arise from peptides which,
though differing in primary amino acid
sequences, assume the same tertiary and
quaternary structures. The amyloid
structure presents a regular array of
accessible N–termini of the peptide
molecules.
Claimed in this application are
compositions and methods for use of
amyloid proteins as vaccine scaffolds,
on which peptide determinants from
microorganisms or tumors may be
presented to more efficiently generate
and produce a sustained neutralizing
antibody response to prevent infectious
diseases or treat tumors. The inventors
have arrayed peptides to be optimally
immunogenic on the amyloid protein
scaffold by presenting antigen using
three different approaches. First, the Nterminal ends of the amyloid forming
peptides can be directly modified with
the peptide antigen of interest; second,
the N-termini of the amyloid forming
peptides are modified with a linker to
which the peptide antigens of interest
are linked; and third, the scaffold
amyloid may be modified to create a
chimeric molecule.
Aside from stability and enhanced
immunogenicity, the major advantages
of this approach are the synthetic nature
of the vaccine and its low cost. Thus,
concerns regarding contamination of
vaccines produced from cellular
substrates, as are currently employed for
some vaccines, are eliminated; the
robust stability allows the amyloid
based vaccine to be stored at room
temperature for prolonged periods of
time; and the inexpensive synthetic
amino acid starting materials, and their
rapid spontaneous aggregation in vitro
should provide substantial cost savings
over the resource and labor-intensive
current vaccine production platforms.
Application: Immunization to prevent
infectious diseases or treat chronic
conditions or cancer.
Development Status: Vaccine
candidates have been synthesized and
preclinical studies have been
performed.
Inventors: Amy Rosenberg (CDER/
FDA), James E. Keller (CBER/FDA),
Robert Tycko (NIDDK).
Patent Status: PCT Application No.
PCT/US2008/059499 filed 04 Apr 2008,
claiming priority to 06 Apr 2007 (HHS
Reference No. E–106–2007/0–PCT–02).
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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, Division of Therapeutic
Proteins (CDER) and Office of Vaccines,
Division of Bacterial Products (CBER) is
seeking statements of capability or
interest from parties interested in
collaborative research to further
develop, evaluate, or commercialize
amyloid based vaccines for prevention
of infectious disease or treatment of
malignant states. Please contact Amy
Rosenberg at
amy.rosenberg@fda.hhs.gov or (301)
827–1794 for more information.
Immunostimulatory Combinations of
TLR Ligands and Methods of Use
Description of Technology: New drugs
or therapies that act by stimulating the
immune system, or alternatively
inhibiting certain aspects of the immune
system, may be useful for treating
various diseases or disorders, for
example viral diseases, neoplasias, and/
or allergies, and may also have use as
vaccine adjuvants. However, although
adjuvants have been suggested for use in
vaccine compositions, there is an unmet
need for adjuvants that can effectively
enhance immune response.
Development of innate and adaptive
immunity critically depends on the
engagement of pattern recognition
receptors (PRRs), which specifically
detect microbial components named
pathogen-or microbe-associated
molecular patterns (PAMPs or MAMPs)
(1–4). Toll-like receptors (TLRs)
represent an important group of PRRs
that can sense PAMPs or MAMPs once
in the body. TLRs are widely expressed
by many types of cells, for example cells
in the blood, spleen, lung, muscle and
intestines.
The present invention claims
immunostimulatory combinations of
TLR ligands and therapeutic and/or
prophylactic methods that include
administering an immunostimulatory
combination to a subject. In general, the
immunostimulatory combinations can
provide an increased immune response
compared to other immunostimulatory
combinations and/or compositions.
More specifically, combinations of TLR
2, 3 and 9 are claimed. The application
also describes a novel mechanism for
TLR synergy in terms of both signaling
pathways and cytokine combinations.
Application: Development of
improved adjuvants and/or synergistic
combinations of adjuvants for vaccines.
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Development Status: Compositions
have been synthesized and preclinical
studies have been performed.
Inventors: Jay Berzofsky and Qing Zhu
(NCI).
Patent Status: U.S. Provisional
Application No. 60/995,212 filed 24 Sep
2007 (HHS Reference No. E–298–2007/
0–US–01).
Licensing Status: Available for
exclusive or nonexclusive licensing.
Licensing Contact: Peter A. Soukas,
J.D.; 301/435–4646;
soukasp@mail.nih.gov.
Collaborative Research Opportunity:
The National Cancer Institute’s Vaccine
Branch is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize this invention of
synergistic combinations of TLR
ligands. Please contact John D. Hewes,
PhD at 301–435–3121 or
hewesj@mail.nih.gov 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, Nacetylglucosamine, 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)-Nacetylglucosamine 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)galactosyltransferases of the invention
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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 Status: 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;
soukasp@mail.nih.gov.
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, Ph.D. at
301–435–3121 or hewesj@mail.nih.gov
for more information.
Methods of Glycosylation and
Bioconjugation
Description of Technology: Eukaryotic
cells express several classes of
oligosaccharides attached to proteins or
lipids. Animal glycans can be N-linked
via beta-GlcNAc to Asn (N-glycans),
O-linked via -GalNAc to Ser/Thr
(O-glycans), or can connect the carboxyl
end of a protein to a
phosphatidylinositol unit (GPI-anchors)
via a common core glycan structure.
Beta (1,4)-galactosyltransferase I
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catalyzes the transfer of galactose from
the donor, UDP-galactose, to an
acceptor, N-acetylglucosamine, to form
a galactose-beta (1,4)-Nacetylglucosamine bond, and allows
galactose to be linked to an Nacetylglucosamine that may itself be
linked to a variety of other molecules.
Examples of these molecules include
other sugars and proteins. The reaction
can be used to make many types of
molecules having great biological
significance. For example, galactosebeta (1,4)-N-acetylglucosamine linkages
are important for many recognition
events that control how cells interact
with each other in the body, and how
cells interact with pathogens. In
addition, numerous other linkages of
this type are also 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 invention provides in vitro
folding methods for a polypeptidylalpha-N-acetylgalactosaminyltransferase
(pp-GalNAc-T) that transfers GalNAc to
Ser/Thr residue on a protein. The
application claims that this in vitrofolded recombinant ppGalNAc-T
enzyme transfers modified sugar with a
chemical handle to a specific site in the
designed C-terminal polypeptide tag
fused to a protein. The invention
provides methods for engineering a
glycoprotein from a biological substrate,
and methods for glycosylating a
biological substrate for use in
glycoconjugation. Also included in the
invention are diagnostic and therapeutic
uses.
Application: Enzymes and methods
are provided that can be used to
promote the chemical linkage of
biologically important molecules that
have previously been difficult to link.
Development Status: Enzymes have
been synthesized and characterization
studies have been performed.
Inventors: Pradman Qasba and
Boopathy Ramakrishnan (NCI).
Patent Status: U.S. Provisional
Application No. 60/930,294 filed 14
May 2007 (HHS Reference No. E–204–
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 National Cancer Institute is seeking
statements of capability or interest from
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parties interested in collaborative
research to further develop, evaluate, or
commercialize this technology. Please
contact John D. Hewes, Ph.D. at 301–
435–3121 or hewesj@mail.nih.gov for
more information.
Alpha 1–3 N–
Acetylgalactosaminyltransferases With
Altered Donor and Acceptor
Specificities, Compositions, and
Methods of Use
Description of Technology: The
present invention relates to the field of
glycobiology, specifically to
glycosyltransferases. The present
invention provides structure-based
design of novel glycosyltransferases and
their biological applications.
The structural information of
glycosyltransferases has revealed that
the specificity of the sugar donor in
these enzymes is determined by a few
residues in the sugar-nucleotide binding
pocket of the enzyme, which is
conserved among the family members
from different species. This
conservation has made it possible to
reengineer the existing
glycosyltransferases with broader sugar
donor specificities. Mutation of these
residues generates novel
glycosyltransferases that can transfer a
sugar residue with a chemically reactive
functional group to N–
acetylglucosarnine (GlcNAc), galactose
(Gal) and xylose residues of
glycoproteins, glycolipids and
proteoglycans (glycoconjugates). Thus,
there is potential to develop mutant
glycosyltransferases to produce
glycoconjugates carrying sugar moieties
with reactive groups that can be used in
the assembly of bio-nanoparticles to
develop targeted-drug delivery systems
or contrast agents for medical uses.
Accordingly, methods to synthesize
N–acetylglucosamine linkages have
many applications in research and
medicine, including in the development
of pharmaceutical agents and improved
vaccines that can be used to treat
disease.
This application claims compositions
and methods based on the structurebased design of alpha 1–3 N–
Acetylgalactosaminyltransferase (alpha
3 GalNAc–T) mutants from alpha l–
3galactosyltransferase (a3Gal–T) that
can transfer 2′-modified galactose from
the corresponding UDP-derivatives due
to mutations that broaden the alpha
3Gal–T donor specificity and make the
enzyme alpha3 GalNAc–T.
Application: Development of
pharmaceutical agents and improved
vaccines.
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Development Status: Enzymes have
been synthesized and preclinical studies
have been performed.
Inventors: Pradman Qasba, Boopathy
Ramakrishnan, Elizabeth Boeggman,
Marta Pasek (NCI).
Patent Status: PCT Patent Application
filed 22 Aug 2007 (HHS Reference No.
E–279–2007/0–PCT–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 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 structure-based design of
novel glycosyltransferases. Please
contact John D. Hewes, PhD at 301–435–
3121 or hewesj@mail.nih.gov for more
information.
Beta 1,4–Galactosyltransferases With
Altered Donor and Acceptor
Specificities, Compositions and
Methods of Use
Description of Technology: The
present invention relates to the field of
glycobiology, specifically to
glycosyltransferases. The present
invention provides structure-based
design of novel glycosyltransferases and
their biological applications.
The structural information of
glycosyltransferases has revealed that
the specificity of the sugar donor in
these enzymes is determined by a few
residues in the sugar-nucleotide binding
pocket of the enzyme, which is
conserved among the family members
from different species. This
conservation has made it possible to
reengineer the existing
glycosyltransferases with broader sugar
donor specificities. Mutation of these
residues generates novel
glycosyltransferases that can transfer a
sugar residue with a chemically reactive
functional group to N–
acetylglucosarnine (GlcNAc), galactose
(Gal) and xylose residues of
glycoproteins, glycolipids and
proteoglycans (glycoconjugates). Thus,
there is potential to develop mutant
glycosyltransferases to produce
glycoconjugates carrying sugar moieties
with reactive groups that can be used in
the assembly of bio-nanoparticles to
develop targeted-drug delivery systems
or contrast agents for medical uses.
Accordingly, methods to synthesize
N–acetylglucosamine linkages have
many applications in research and
medicine, including in the development
of pharmaceutical agents and improved
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vaccines that can be used to treat
disease.
The invention claims beta (1,4)–
galactosyltransferase I mutants having
altered donor and acceptor and metal
ion specificities, and methods of use
thereof. In addition, the invention
claims methods for synthesizing
oligosaccharides using the beta (1,4)–
galactosyltransferase I mutants and to
using the beta (1,4)–
galactosyltransferase I mutants to
conjugate agents, such as therapeutic
agents or diagnostic agents, to acceptor
molecules. More specifically, the
invention claims a double mutant beta
1,4 galactosyltransferase, human beta–
1,4–Tyr289Leu–Met344His–Gal–T1,
constructed from the individual
mutants, Tyr289Leu–Gal–T1 and
Met344His–Gal–T1, that transfers
modified galactose in the presence of
magnesium ion, in contrast to the wildtype enzyme which requires manganese
ion.
Application: Development of
pharmaceutical agents and improved
vaccines.
Development Status: Enzymes have
been synthesized and preclinical studies
have been performed.
Inventors: Pradman Qasba, Boopathy
Ramakrishnan, Elizabeth Boeggman
(NCI).
Patent Status: PCT Patent Application
filed 22 Aug 2007 (HHS Reference No.
E–280–2007/0–PCT–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 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 glycosyltransferases.
Please contact John D. Hewes, Ph.D.,
Technology Transfer Specialist, NCI, at
(301) 435–3121 or hewesj@nail.nih.gov.
Bioreactor Device and Method and
System for Fabricating Tissue
Description of Technology: Available
for licensing and commercial
development is a millifluidic bioreactor
system for culturing, testing, and
fabricating natural or engineered cells
and tissues. The system consists of a
millifluidic bioreactor device and
methods for sample culture. Biologic
samples that can be utilized include
cells, scaffolds, tissue explants, and
organoids. The system is microchip
controlled and can be operated in
closed-loop, providing controlled
delivery of medium and biofactors in a
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sterile temperature regulated
environment under tabletop or
incubator use. Sample perfusion can be
applied periodically or continuously, in
a bidirectional or unidirectional
manner, and medium re-circulated.
Advantages: The device is small in
size, and of conventional culture plate
format.
Provides the ability to grow larger
biologic samples than microfluidic
systems, while utilizing smaller
medium volumes than conventional
bioreactors. The bioreactor culture
chamber is adapted to contain sample
volumes on a milliliter scale (10 [mu]L
to 1 mL, with a preferred size of 100
[mu]L), significantly larger than
chamber volumes in microfluidic
systems (on the order of 1 [mu]L).
Typical microfluidic systems are
designed to culture cells and not larger
tissue samples.
The integrated medium reservoirs and
bioreactor chamber design provide for,
(1) Concentration of biofactors produced
by the biologic sample, and (2) the use
of smaller amounts of exogenous
biofactor supplements in the culture
medium. The local medium volume
(within the vicinity of the sample) is
less than twice the sample volume. The
total medium volume utilized is small,
preferably 2 ml, significantly smaller
than conventional bioreactors (typically
using 500–1000 mL).
Provides for real-time monitoring of
sample growth and function in response
to stimuli via an optical port and
embedded sensors. The optical port
provides for microscopy and
spectroscopy measurements using
transmitted, reflected, or emitted (e.g.,
fluorescent, chemiluminescent) light.
The embedded sensors provide for
measurement of culture fluid pressure
and sample pH, oxygen tension, and
temperature.
Capable of providing external
stimulation to the biologic sample,
including mechanical forces (e.g., fluid
shear, hydrostatic pressure, matrix
compression, microgravity via
clinorotation), electrical fields (e.g., AC
currents), and biofactors (e.g., growth
factors, cytokines) while monitoring
their effect in real-time via the
embedded sensors, optical port, and
medium sampling port.
Monitoring of biologic sample
response to external stimulation can be
performed non-invasively and nondestructively through the embedded
sensors, optical port, and medium
sampling port. Testing of tissue
mechanical and electrical properties
(e.g., stiffness, permeability, loss
modulus via stress or creep test,
electrical impedance) can be performed
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over time without removing the sample
from the bioreactor device.
The bioreactor sample chamber can be
constructed with multiple levels fed via
separate perfusion circuits, facilitating
the growth and production of
multiphasic tissues.
Application: Cartilage repair and
methods for making tissue-engineered
cartilage.
Development Status: Electrospinning
method is fully developed and cartilage
has been synthesized.
Inventors: Juan M. Taboas (NIAMS),
Rocky S. Tuan (NIAMS), et al.
Patent Status: PCT Application No.
PCT/US2006/028417 filed 20 Jul 2006,
which published as WO 2007/012071
on 25 Jan 2007; claiming priority to 20
Jul 2005 (HHS Reference No. E–042–
2005/0–PCT–02).
Licensing Status: Available for
exclusive or non-exclusive licensing.
Licensing Contact: Peter A. Soukas,
J.D.; 301/435–4646;
soukasp@mail.nih.gov.
Cell-Nanofiber Composite Based
Engineered Cartilage
Description of Technology: Available
for licensing and commercial
development is a tissue-engineered
cartilage derived from a cellular
composite made from a biodegradable,
biocompatible polymeric nanofibrous
matrix having dispersed chondrocytes
or adult mesenchymal stem cells. More
particularly, tissue-engineered cartilage
can be prepared where the cartilage has
a biodegradable and biocompatible
nanofibrous polymer matrix prepared by
electrospinning and a plurality of
chondrocytes or mesenchymal stem
cells dispersed in the pores of the
matrix. The tissue-engineered cartilage
possesses compressive strength
properties similar to natural cartilage.
The electrospinning process is a
simple, economical means to produce
biomaterial matrices or scaffolds of
ultra-fine fibers derived from a variety
of biodegradable polymers (Li WJ, et al.,
J. Biomed. Mater. Res. 2002; 60:613–21).
Nanofibrous scaffolds (NFSs) formed by
electrospinning, by virtue of structural
similarity to natural extracellular matrix
(ECM), may represent promising
structures for tissue engineering
applications. Electrospun threedimensional NFSs are characterized by
high porosity with a wide distribution
of pore diameter, high-surface area to
volume ratio and morphological
similarities to natural collagen fibrils (Li
WJ, et al., J. Biomed. Mater. Res. 2002;
60:613–21). These physical
characteristics promote favorable
biological responses of seeded cells in
vitro and in vivo, including enhanced
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cell attachment, proliferation,
maintenance of the chondrocytic
phenotype (Li WJ, et al., J. Biomed.
Mater. Res. 2003; 67A: 1105–14), and
support of chondrogenic differentiation
(Li WJ, et al., Biomaterials 2005;
26:599–609) as well as other connective
tissue lineage differentiation (Li WJ, et
al., Biomaterials 2005; 26:5158–5166).
The invention based on cell-nanofiber
composite represents a candidate
engineered tissue for cell-based
approaches to cartilage repair.
Application: Cartilage repair and
methods for making tissue-engineered
cartilage.
Development Status: Electrospinning
method is fully developed and cartilage
has been synthesized.
Inventors: Wan-Ju Li and Rocky Tuan
(NIAMS).
Publications: The invention is further
described in:
1. W-J Li et al., Engineering
controllable anisotropy in electrospun
biodegradable nanofibrous scaffolds for
musculoskeletal tissue engineering. J
Biomech. 2007; 40(8):1686–1693.
2. W-J Li et al., Fabrication and
characterization of six electrospun
poly(alpha-hydroxy ester)-based fibrous
scaffolds for tissue engineering
applications. Acta Biomater. 2006 Jul;
2(4):377–385.
3. CK Kuo et al., Cartilage tissue
engineering: its potential and uses. Curr
Opin Rheumatol. 2006 Jan; 18(1):64–73.
Review.
4. W-J Li et al., Multilineage
differentiation of human mesenchymal
stem cells in a three-dimensional
nanofibrous scaffold. Biomaterials. 2005
Sep; 26(25):5158–5166.
Patent Status: PCT Application No.
PCT/US2006/0237477 filed 15 Jun 2006,
claiming priority to 15 Jun 2005 (HHS
Reference No. E–116–2005/0–PCT–02).
Licensing Status: Available for
exclusive or non-exclusive licensing.
Licensing Contact: Peter A. Soukas,
J.D.; 301/435–4646;
soukasp@mail.nih.gov.
Cell-Nanofiber Composite and CellNanofiber Composite Amalgam Based
Engineered Intervertebral Disc
Description of Technology: Diseased
or damaged musculoskeletal tissues are
often replaced by an artificial material,
cadaver tissue or donated, allogenic
tissue. Tissue engineering offers an
attractive alternative whereby a live,
natural tissue is generated from a
construct made up of a patient’s own
cells or an acceptable/compatible cell
source in combination with a
biodegradable scaffold for replacement
of defective tissue.
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Degeneration of the intervertebral disc
(IVD) is a common and significant
source of morbidity in our society.
Approximately 8 of 10 adults at some
point in their life will experience an
episode of significant low back pain,
with the majority improving without
any formal treatment. However, for the
subject requiring surgical management
current interventions focus on fusion of
the involved IVD levels, which
eliminates pain but does not attempt to
restore disc function. Approximately
200,000 spinal fusions were performed
in the United States in 2002 to treat pain
associated with lumbar disc
degeneration. Spinal fusion however is
thought to significantly alter the
biomechanics of the disc and lead to
further degeneration, or adjacent
segment disease. Therefore, in the past
decade there has been mounting interest
in the concept of IVD replacement. The
replacement of the IVD holds
tremendous potential as an alternative
to spinal fusion for the treatment of
degenerative disc disease by offering a
safer alternative to current spinal fusion
practices.
At the present time, several disc
replacement implants are at different
stages of preclinical and clinical testing.
These disc replacement technologies are
designed to address flexion, extension,
and lateral bending motions; however,
they do little to address compressive
forces and their longevity is limited due
to their inability to biointegrate.
Therefore, a cell-based tissue
engineering approach offers the most
promising alternative to replace the
degenerated IVD. Current treatment for
injuries that penetrate subchondral bone
include subchondral drilling, periosteal
tissue grafting, osteochondral
allografting, chondrogenic cell and
transplantation; but are limited due to
suboptimal integration with host
tissues.
The present invention claims tissue
engineered intervertebral discs
comprising a nanofibrous polymer
hydrogel amalgam having cells
dispersed therein, methods of
fabricating tissue engineered
intervertebral discs by culturing a
mixture of stem cells or intervertebral
disc cells and a electrospun nanofibrous
polymer hydrogel amalgam in a suitable
bioreactor, and methods of treatment
comprising implantation of tissue
engineered intervertebral disc into a
subject.
Application: Intervertebral disc bioconstructs and electrospinning methods
for fabrication of the discs.
Development Status: Prototype
devices have been fabricated and
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preclinical studies have been
performed.
Inventors: Wan-Ju Li, Leon Nesti,
Rocky Tuan (NIAMS).
Patent Status: PCT Application No.
PCT/US07/020974 filed 27 Sep 2007,
claiming priority to 27 Sep 2006 (HHS
Reference No. E–309–2006/2–PCT–01).
Licensing Status: Available for
exclusive or non-exclusive licensing.
Licensing Contact: Peter A. Soukas,
J.D.; 301/435–4646;
soukasp@mail.nih.gov.
Methods for Preparing Bacillus
anthracis Protective Antigen for Use in
Vaccines
Description of Technology: This
invention relates to improved methods
of preparing Bacillus anthracis
protective antigen (PA) from a cell or
organism, particularly a recombinant
cell or microorganism, for use in
vaccines. Production and purification
methods of modified PA from a nonsporogenic strain of Bacillus anthracis
are described. Specifically, a scalable
fermentation and purification process is
claimed that is suitable for vaccine
development, and that produces almost
three times more product than earlierreported processes. This is
accomplished using a biologically
inactive protease-resistant PA variant in
a protease-deficient non-sporogenic
avirulent strain of B. anthracis (BH445).
One of the PA variants described in the
patent application lacks the furin and
chymotrypsin cleavage sites.
Advantages: Bacillus anthracis
protective antigen is a major component
of the currently licensed human vaccine
(Anthrax Vaccine Adsorbed, AVA).
Although the current human vaccine
has been shown to be effective against
cutaneous anthrax infection in animals
and humans and against inhalation
anthrax in rhesus monkeys, the licensed
vaccine has several limitations: (1) AVA
elicits a relatively high degree of local
and systemic adverse reactions,
probably mediated by variable amounts
of undefined bacterial products, making
standardization difficult; (2) the
immunization schedule requires
administration of six doses within an
eighteen (18) month period, followed by
annual boosters; (3) there is no defined
vaccine-induced protective level of
antibody to PA by which to evaluate
new lots of vaccines; and (4) AVA is
comprised of a wild-type PA. Thus a
vaccine comprising a modified purified
recombinant PA would be effective,
safe, allow precise standardization, and
require fewer injections.
The invention also relates to PA
variants, and/or compositions thereof,
which are useful for eliciting an
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immunogenic response in mammals,
particularly humans, including
responses that provide protection
against, or reduce the severity of,
infections caused by B. anthracis. The
vaccines claimed in this application are
intended for active immunization for
prevention of B. anthracis infection, and
for preparation of immune antibodies.
Application: Improved B. anthracis
vaccines.
Development Status: Phase I clinical
studies are being performed.
Inventors: Joseph Shiloach (NIDDK),
Stephen Leppla (NIDCR), Delia Ramirez
(NIDDK), Rachel Schneerson (NICHD),
John Robbins (NICHD).
Publication: DM Ramirez et. al.
Production, recovery and
immunogenicity of the protective
antigen from a recombinant strain of
Bacillus anthracis. J Ind Microbiol
Biotechnol. 2002 Apr;28(4):232–238.
Patent Status: U.S. Patent Application
No. 10/290,712 filed 08 Nov 2002 (HHS
Reference No. E–023–2002/0–US–02).
Licensing Status: Available for
exclusive or nonexclusive licensing.
Licensing Contact: Peter A. Soukas,
J.D.; 301/435–4646;
soukasp@mail.nih.gov.
Collaborative Research Opportunity:
The National Institutes of Health is
seeking statements of capability or
interest from parties interested in
collaborative research to further
develop, evaluate, or commercialize
methods of preparing Bacillus anthracis
protective antigen (PA) from a cell or
organism, particularly a recombinant
cell or microorganism, for use in
vaccines. Please contact Rochelle S.
Blaustein, J.D., at 301/451–3636 or
Rochelle.Blaustein@nih.gov for
additional information.
Recombinant Modified Bacillus
anthracis Protective Antigen for Use in
Vaccines
Description of Technology: This
invention relates to improved methods
of preparing Bacillus anthracis
protective antigen (PA) for use in
vaccines. PA is a secreted, non-toxic
protein with a molecular weight of 83
KDa. PA is a major component of the
currently licensed human vaccine
(Anthrax Vaccine Adsorbed, AVA).
Although the licensed human vaccine
has been shown to be effective against
cutaneous anthrax infection in animals
and humans and against inhalation
anthrax in rhesus monkeys, the licensed
vaccine has several limitations: (1) AVA
elicits a relatively high degree of local
and systemic adverse reactions,
probably mediated by variable amounts
of undefined bacterial products, making
standardization difficult; (2) the
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34761
immunization schedule requires
administration of six doses within an
eighteen (18) month period, followed by
annual boosters; (3) there is no defined
vaccine-induced protective level of
antibody to PA by which to evaluate
new lots of vaccines; and (4) AVA is
comprised of a wild-type PA. It has been
suggested that a vaccine comprising a
modified purified recombinant PA
would be effective, safe, allow precise
standardization, and require fewer
injections.
This invention claims methods of
producing and recovering PA from a cell
or organism, particularly a recombinant
cell or microorganism. The invention
claims production and purification of
modified PA from a non-sporogenic
strain of Bacillus anthracis. In contrast
to other previously described methods,
greater quantities of PA are obtainable
from these cells or microorganisms.
Specifically, a scalable fermentation and
purification process is claimed that is
suitable for vaccine development, and
that produces almost three times more
product than earlier-reported processes.
This is accomplished using a
biologically inactive protease-resistant
PA variant in a protease-deficient nonsporogenic avirulent strain of B.
anthracis (BH445). One of the PA
variants described in the patent
application lacks the furin and
chymotrypsin cleavage sites.
The invention relates to improved
methods of producing and recovering
sporulation-deficient B. anthracis
mutant strains, and for producing and
recovering recombinant B. anthracis
protective antigen (PA), especially
modified PA which is protease resistant,
and to methods of using of these PAs or
nucleic acids encoding these PAs for
eliciting an immunogenic response in
humans, including responses which
provide protection against, or reduce the
severity of, B. anthracis bacterial
infections and which are useful to
prevent and/or treat illnesses caused by
B. anthracis, such as inhalation anthrax,
cutaneous anthrax and gastrointestinal
anthrax.
Application: Improved B. anthracis
vaccines.
Development Status: Phase I clinical
studies are being performed.
Inventors: Stephen Leppla (NIDCR),
M. J. Rosovitz (NIDCR), John Robbins
(NICHD), Rachel Schneerson (NICHD).
Patent Status: U.S. Patent No.
7,261,900 issued 28 Aug 2007 (HHS
Reference No. E–268–2002/0–US–02);
U.S. Patent Application No. 11/831,860
filed 31 Jul 2007 (HHS Reference No. E–
268–2002/0–US–03).
Licensing Status: Available for
exclusive or nonexclusive licensing.
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34762
Federal Register / Vol. 73, No. 118 / Wednesday, June 18, 2008 / Notices
Licensing Contact: Peter A. Soukas,
J.D.; 301/435–4646;
soukasp@mail.nih.gov.
rwilkins on PROD1PC63 with NOTICES
gPGA Conjugates for Eliciting Immune
Responses Directed Against Bacillus
anthracis and Other Bacilli
Description of Technology: This
invention claims immunogenic
conjugates of a poly-g-glutamic acid
(gPGA) of B. anthracis, or of another
bacillus that expresses a gPGA that elicit
a serum antibody response against B.
anthracis, in mammalian hosts to which
the conjugates are administered. The
invention also relates methods which
are useful for eliciting an immunogenic
response in mammals, particularly
humans, including responses which
provide protection against, or reduce the
severity of, infections caused by B.
anthracis. The vaccines claimed in this
application are intended for active
immunization for prevention of B.
anthracis infection, and for preparation
of immune antibodies. The vaccines of
this invention are designed to confer
specific immunity against infection with
B. anthracis, and to induce antibodies
specific to B. anthracis gPGA. The B.
anthracis vaccine is composed of nontoxic bacterial components, suitable for
infants, children of all ages, and adults.
Inventors: Rachel Schneerson
(NICHD), Stephen Leppla (NIAID), John
Robbins (NICHD), Joseph Shiloach
(NIDDK), Joanna Kubler-Kielb (NICHD),
Darrell Liu (NIDCR), Fathy Majadly
(NICHD).
Publication: R Schneerson et al.
Poly(gamma-D-glutamic acid) protein
conjugates induce IgG antibodies in
mice to the capsule of Bacillus
anthracis: a potential addition to the
anthrax vaccine. Proc Natl Acad Sci
USA. 2003 Jul 22;100(15):8945–8950.
Patent Status: U.S. Patent Application
No. 10/559,825 filed 02 Dec 2005,
claiming priority to 05 Jun 2003 (HHS
Reference No. E–343–2002/0–US–04).
Licensing Status: Available for
licensing.
Licensing Contact: Peter A. Soukas,
J.D.; 301/435–4646;
soukasp@mail.nih.gov.
Methods for Conjugation of
Oligosaccharides or Polysaccharides to
Protein Carriers Through Oxime
Linkages Via 3-Deoxy-D-MannoOctulsonic Acid
Description of Technology: This
technology comprises new methods for
the conjugation of O-specific
polysaccharides/oligosaccharides (OSP/OS) derived from bacterial
lipooligosaccharides/
lipopolysaccharides (LOS/LPS), after
their cleavage from Lipid A, to carrier
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proteins, to serve as potential vaccines.
Conjugation is performed between the
carbonyl group on the terminal reducing
end of the saccharide and the aminooxy
group of a bifunctional linker bound
further to the protein.
The inventors have carried out the
reaction under mild conditions and in a
short time resulting in binding 3-deoxyD-manno-octulosonic acid (KDO) on the
sacchride to the protein. These
conjugates preserve the external nonreducing end of the sacchride, are
recognized by antisera, and induce
immune responses in mice to both
conjugate components (i.e., the OS and
the associated carrier protein).
Application: Cost effective and
efficient manufacturing of conjugate
vaccines.
Inventors: Joanna Kubler-Kielb
(NICHD), Vince Pozsgay (NICHD), Gil
Ben-Menachem (NICHD), Rachel
Schneerson (NICHD), et al.
Patent Status: PCT Application No.
PCT/US2007/016373 filed 18 Jul 2007,
which published as WO 2008/013735
on 31 Jan 2008; claiming priority to 21
Jul 2006 (HHS Reference No. E–183–
2005/0–PCT–02).
Licensing Status: Available for
exclusive or non-exclusive licensing.
Licensing Contact: Peter A. Soukas,
J.D.; 301/435–4646;
soukasp@mail.nih.gov.
Dated: June 10, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E8–13669 Filed 6–17–08; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
National Institutes of Health,
Public Health Service, HHS.
ACTION: Notice.
AGENCY:
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.
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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.
ADDRESSES:
Construction of Recombinant
Baculoviruses Carrying the Gene
Encoding the Major Capsid Protein,
VP1, From Calicivirus Strains
(Including Norovirus Strains Toronto,
Hawaii, Desert Shield, Snow Mountain,
and MD145–12)
Description of Technology: The
noroviruses (known as ‘‘Norwalk-like
viruses’’) are associated with an
estimated 23,000,000 cases of acute
gastroenteritis in the United States each
year. Norovirus illness often occurs in
outbreaks, affecting large numbers of
individuals, illustrated recently by wellpublicized reports of gastroenteritis
outbreaks on several recreational cruise
ships and in settings such as hospitals
and schools. Norovirus disease is clearly
important in terms of medical costs and
missed workdays, and accumulating
data support its emerging recognition as
important agents of diarrhea-related
morbidity.
Because the noroviruses cannot be
propagated by any means in the
laboratory, an important strategy in their
study is the development of molecular
biology-based tools. This invention
reports the development of recombinant
baculoviruses carrying the capsid gene
from several caliciviruses associated
with human disease. Growth of these
baculovirus recombinants in insect cells
results in the expression of virus-like
particles (VLPs) that are antigenically
indistinguishable from the native
calicivirus particle. These VLPs can be
purified in large quantities for use as
diagnostic reagents and potential
vaccine candidates.
Inventors: Kim Y. Green, Judy F. Lew,
Adriene D. King, Stanislav V.
Sosnovtsev, Gael M. Belliot (NIAID).
Publication: An example of the
application of these materials is further
described in KY Green et al., ‘‘A
predominant role for Norwalk-like
viruses as agents of epidemic
gastroenteritis in Maryland nursing
homes for the elderly,’’ J. Infect. Dis.
2002 Jan. 15;185(2):133–146.
Patent Status: HHS Reference No. E–
198–2003/0—Research Material.
Licensing Status: The materials
embodied in this invention are available
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]]>Agencies
[Federal Register Volume 73, Number 118 (Wednesday, June 18, 2008)]
[Notices]
[Pages 34756-34762]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E8-13669]
-----------------------------------------------------------------------
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.
[[Page 34757]]
Use of Amyloid Proteins as Vaccine Scaffolds
Description of Technology: Amyloid proteins are composed of
peptides whose chemical properties are such that they spontaneously
aggregate in vitro or in vivo, assuming parallel or antiparallel beta
sheet configurations. Amyloid proteins can arise from peptides which,
though differing in primary amino acid sequences, assume the same
tertiary and quaternary structures. The amyloid structure presents a
regular array of accessible N-termini of the peptide molecules.
Claimed in this application are compositions and methods for use of
amyloid proteins as vaccine scaffolds, on which peptide determinants
from microorganisms or tumors may be presented to more efficiently
generate and produce a sustained neutralizing antibody response to
prevent infectious diseases or treat tumors. The inventors have arrayed
peptides to be optimally immunogenic on the amyloid protein scaffold by
presenting antigen using three different approaches. First, the N-
terminal ends of the amyloid forming peptides can be directly modified
with the peptide antigen of interest; second, the N-termini of the
amyloid forming peptides are modified with a linker to which the
peptide antigens of interest are linked; and third, the scaffold
amyloid may be modified to create a chimeric molecule.
Aside from stability and enhanced immunogenicity, the major
advantages of this approach are the synthetic nature of the vaccine and
its low cost. Thus, concerns regarding contamination of vaccines
produced from cellular substrates, as are currently employed for some
vaccines, are eliminated; the robust stability allows the amyloid based
vaccine to be stored at room temperature for prolonged periods of time;
and the inexpensive synthetic amino acid starting materials, and their
rapid spontaneous aggregation in vitro should provide substantial cost
savings over the resource and labor-intensive current vaccine
production platforms.
Application: Immunization to prevent infectious diseases or treat
chronic conditions or cancer.
Development Status: Vaccine candidates have been synthesized and
preclinical studies have been performed.
Inventors: Amy Rosenberg (CDER/FDA), James E. Keller (CBER/FDA),
Robert Tycko (NIDDK).
Patent Status: PCT Application No. PCT/US2008/059499 filed 04 Apr
2008, claiming priority to 06 Apr 2007 (HHS Reference No. E-106-2007/0-
PCT-02).
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, Division of
Therapeutic Proteins (CDER) and Office of Vaccines, Division of
Bacterial Products (CBER) is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate, or commercialize amyloid based vaccines for
prevention of infectious disease or treatment of malignant states.
Please contact Amy Rosenberg at amy.rosenberg@fda.hhs.gov or (301) 827-
1794 for more information.
Immunostimulatory Combinations of TLR Ligands and Methods of Use
Description of Technology: New drugs or therapies that act by
stimulating the immune system, or alternatively inhibiting certain
aspects of the immune system, may be useful for treating various
diseases or disorders, for example viral diseases, neoplasias, and/ or
allergies, and may also have use as vaccine adjuvants. However,
although adjuvants have been suggested for use in vaccine compositions,
there is an unmet need for adjuvants that can effectively enhance
immune response.
Development of innate and adaptive immunity critically depends on
the engagement of pattern recognition receptors (PRRs), which
specifically detect microbial components named pathogen-or microbe-
associated molecular patterns (PAMPs or MAMPs) (1-4). Toll-like
receptors (TLRs) represent an important group of PRRs that can sense
PAMPs or MAMPs once in the body. TLRs are widely expressed by many
types of cells, for example cells in the blood, spleen, lung, muscle
and intestines.
The present invention claims immunostimulatory combinations of TLR
ligands and therapeutic and/or prophylactic methods that include
administering an immunostimulatory combination to a subject. In
general, the immunostimulatory combinations can provide an increased
immune response compared to other immunostimulatory combinations and/or
compositions. More specifically, combinations of TLR 2, 3 and 9 are
claimed. The application also describes a novel mechanism for TLR
synergy in terms of both signaling pathways and cytokine combinations.
Application: Development of improved adjuvants and/or synergistic
combinations of adjuvants for vaccines.
Development Status: Compositions have been synthesized and
preclinical studies have been performed.
Inventors: Jay Berzofsky and Qing Zhu (NCI).
Patent Status: U.S. Provisional Application No. 60/995,212 filed 24
Sep 2007 (HHS Reference No. E-298-2007/0-US-01).
Licensing Status: Available for exclusive or nonexclusive
licensing.
Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646;
soukasp@mail.nih.gov.
Collaborative Research Opportunity: The National Cancer Institute's
Vaccine Branch is seeking statements of capability or interest from
parties interested in collaborative research to further develop,
evaluate, or commercialize this invention of synergistic combinations
of TLR ligands. Please contact John D. Hewes, PhD at 301-435-3121 or
hewesj@mail.nih.gov 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)-galactosyltransferases of
the invention
[[Page 34758]]
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 Status: 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;
soukasp@mail.nih.gov.
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, Ph.D. at 301-
435-3121 or hewesj@mail.nih.gov for more information.
Methods of Glycosylation and Bioconjugation
Description of Technology: Eukaryotic cells express several classes
of oligosaccharides attached to proteins or lipids. Animal glycans can
be N-linked via beta-GlcNAc to Asn (N-glycans), O-linked via -GalNAc to
Ser/Thr (O-glycans), or can connect the carboxyl end of a protein to a
phosphatidylinositol unit (GPI-anchors) via a common core glycan
structure. 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, and allows galactose to be linked to an N-acetylglucosamine that
may itself be linked to a variety of other molecules. Examples of these
molecules include other sugars and proteins. 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
important for many recognition events that control how cells interact
with each other in the body, and how cells interact with pathogens. In
addition, numerous other linkages of this type are also 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 invention provides in vitro folding methods for a polypeptidyl-
alpha-N-acetylgalactosaminyltransferase (pp-GalNAc-T) that transfers
GalNAc to Ser/Thr residue on a protein. The application claims that
this in vitro-folded recombinant ppGalNAc-T enzyme transfers modified
sugar with a chemical handle to a specific site in the designed C-
terminal polypeptide tag fused to a protein. The invention provides
methods for engineering a glycoprotein from a biological substrate, and
methods for glycosylating a biological substrate for use in
glycoconjugation. Also included in the invention are diagnostic and
therapeutic uses.
Application: Enzymes and methods are provided that can be used to
promote the chemical linkage of biologically important molecules that
have previously been difficult to link.
Development Status: Enzymes have been synthesized and
characterization studies have been performed.
Inventors: Pradman Qasba and Boopathy Ramakrishnan (NCI).
Patent Status: U.S. Provisional Application No. 60/930,294 filed 14
May 2007 (HHS Reference No. E-204-2007/0-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 National Cancer Institute
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, Ph.D. at
301-435-3121 or hewesj@mail.nih.gov for more information.
Alpha 1-3 N-Acetylgalactosaminyltransferases With Altered Donor and
Acceptor Specificities, Compositions, and Methods of Use
Description of Technology: The present invention relates to the
field of glycobiology, specifically to glycosyltransferases. The
present invention provides structure-based design of novel
glycosyltransferases and their biological applications.
The structural information of glycosyltransferases has revealed
that the specificity of the sugar donor in these enzymes is determined
by a few residues in the sugar-nucleotide binding pocket of the enzyme,
which is conserved among the family members from different species.
This conservation has made it possible to reengineer the existing
glycosyltransferases with broader sugar donor specificities. Mutation
of these residues generates novel glycosyltransferases that can
transfer a sugar residue with a chemically reactive functional group to
N-acetylglucosarnine (GlcNAc), galactose (Gal) and xylose residues of
glycoproteins, glycolipids and proteoglycans (glycoconjugates). Thus,
there is potential to develop mutant glycosyltransferases to produce
glycoconjugates carrying sugar moieties with reactive groups that can
be used in the assembly of bio-nanoparticles to develop targeted-drug
delivery systems or contrast agents for medical uses.
Accordingly, methods to synthesize N-acetylglucosamine linkages
have many applications in research and medicine, including in the
development of pharmaceutical agents and improved vaccines that can be
used to treat disease.
This application claims compositions and methods based on the
structure-based design of alpha 1-3 N-Acetylgalactosaminyltransferase
(alpha 3 GalNAc-T) mutants from alpha l-3galactosyltransferase (a3Gal-
T) that can transfer 2'-modified galactose from the corresponding UDP-
derivatives due to mutations that broaden the alpha 3Gal-T donor
specificity and make the enzyme alpha3 GalNAc-T.
Application: Development of pharmaceutical agents and improved
vaccines.
[[Page 34759]]
Development Status: Enzymes have been synthesized and preclinical
studies have been performed.
Inventors: Pradman Qasba, Boopathy Ramakrishnan, Elizabeth
Boeggman, Marta Pasek (NCI).
Patent Status: PCT Patent Application filed 22 Aug 2007 (HHS
Reference No. E-279-2007/0-PCT-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 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 structure-based design of novel
glycosyltransferases. Please contact John D. Hewes, PhD at 301-435-3121
or hewesj@mail.nih.gov for more information.
Beta 1,4-Galactosyltransferases With Altered Donor and Acceptor
Specificities, Compositions and Methods of Use
Description of Technology: The present invention relates to the
field of glycobiology, specifically to glycosyltransferases. The
present invention provides structure-based design of novel
glycosyltransferases and their biological applications.
The structural information of glycosyltransferases has revealed
that the specificity of the sugar donor in these enzymes is determined
by a few residues in the sugar-nucleotide binding pocket of the enzyme,
which is conserved among the family members from different species.
This conservation has made it possible to reengineer the existing
glycosyltransferases with broader sugar donor specificities. Mutation
of these residues generates novel glycosyltransferases that can
transfer a sugar residue with a chemically reactive functional group to
N-acetylglucosarnine (GlcNAc), galactose (Gal) and xylose residues of
glycoproteins, glycolipids and proteoglycans (glycoconjugates). Thus,
there is potential to develop mutant glycosyltransferases to produce
glycoconjugates carrying sugar moieties with reactive groups that can
be used in the assembly of bio-nanoparticles to develop targeted-drug
delivery systems or contrast agents for medical uses.
Accordingly, methods to synthesize N-acetylglucosamine linkages
have many applications in research and medicine, including in the
development of pharmaceutical agents and improved vaccines that can be
used to treat disease.
The invention claims beta (1,4)-galactosyltransferase I mutants
having altered donor and acceptor and metal ion specificities, and
methods of use thereof. In addition, the invention claims methods for
synthesizing oligosaccharides using the beta (1,4)-
galactosyltransferase I mutants and to using the beta (1,4)-
galactosyltransferase I mutants to conjugate agents, such as
therapeutic agents or diagnostic agents, to acceptor molecules. More
specifically, the invention claims a double mutant beta 1,4
galactosyltransferase, human beta-1,4-Tyr289Leu-Met344His-Gal-T1,
constructed from the individual mutants, Tyr289Leu-Gal-T1 and
Met344His-Gal-T1, that transfers modified galactose in the presence of
magnesium ion, in contrast to the wild-type enzyme which requires
manganese ion.
Application: Development of pharmaceutical agents and improved
vaccines.
Development Status: Enzymes have been synthesized and preclinical
studies have been performed.
Inventors: Pradman Qasba, Boopathy Ramakrishnan, Elizabeth Boeggman
(NCI).
Patent Status: PCT Patent Application filed 22 Aug 2007 (HHS
Reference No. E-280-2007/0-PCT-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 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 glycosyltransferases. Please contact John D.
Hewes, Ph.D., Technology Transfer Specialist, NCI, at (301) 435-3121 or
hewesj@nail.nih.gov.
Bioreactor Device and Method and System for Fabricating Tissue
Description of Technology: Available for licensing and commercial
development is a millifluidic bioreactor system for culturing, testing,
and fabricating natural or engineered cells and tissues. The system
consists of a millifluidic bioreactor device and methods for sample
culture. Biologic samples that can be utilized include cells,
scaffolds, tissue explants, and organoids. The system is microchip
controlled and can be operated in closed-loop, providing controlled
delivery of medium and biofactors in a sterile temperature regulated
environment under tabletop or incubator use. Sample perfusion can be
applied periodically or continuously, in a bidirectional or
unidirectional manner, and medium re-circulated.
Advantages: The device is small in size, and of conventional
culture plate format.
Provides the ability to grow larger biologic samples than
microfluidic systems, while utilizing smaller medium volumes than
conventional bioreactors. The bioreactor culture chamber is adapted to
contain sample volumes on a milliliter scale (10 [mu]L to 1 mL, with a
preferred size of 100 [mu]L), significantly larger than chamber volumes
in microfluidic systems (on the order of 1 [mu]L). Typical microfluidic
systems are designed to culture cells and not larger tissue samples.
The integrated medium reservoirs and bioreactor chamber design
provide for, (1) Concentration of biofactors produced by the biologic
sample, and (2) the use of smaller amounts of exogenous biofactor
supplements in the culture medium. The local medium volume (within the
vicinity of the sample) is less than twice the sample volume. The total
medium volume utilized is small, preferably 2 ml, significantly smaller
than conventional bioreactors (typically using 500-1000 mL).
Provides for real-time monitoring of sample growth and function in
response to stimuli via an optical port and embedded sensors. The
optical port provides for microscopy and spectroscopy measurements
using transmitted, reflected, or emitted (e.g., fluorescent,
chemiluminescent) light. The embedded sensors provide for measurement
of culture fluid pressure and sample pH, oxygen tension, and
temperature.
Capable of providing external stimulation to the biologic sample,
including mechanical forces (e.g., fluid shear, hydrostatic pressure,
matrix compression, microgravity via clinorotation), electrical fields
(e.g., AC currents), and biofactors (e.g., growth factors, cytokines)
while monitoring their effect in real-time via the embedded sensors,
optical port, and medium sampling port.
Monitoring of biologic sample response to external stimulation can
be performed non-invasively and non-destructively through the embedded
sensors, optical port, and medium sampling port. Testing of tissue
mechanical and electrical properties (e.g., stiffness, permeability,
loss modulus via stress or creep test, electrical impedance) can be
performed
[[Page 34760]]
over time without removing the sample from the bioreactor device.
The bioreactor sample chamber can be constructed with multiple
levels fed via separate perfusion circuits, facilitating the growth and
production of multiphasic tissues.
Application: Cartilage repair and methods for making tissue-
engineered cartilage.
Development Status: Electrospinning method is fully developed and
cartilage has been synthesized.
Inventors: Juan M. Taboas (NIAMS), Rocky S. Tuan (NIAMS), et al.
Patent Status: PCT Application No. PCT/US2006/028417 filed 20 Jul
2006, which published as WO 2007/012071 on 25 Jan 2007; claiming
priority to 20 Jul 2005 (HHS Reference No. E-042-2005/0-PCT-02).
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646;
soukasp@mail.nih.gov.
Cell-Nanofiber Composite Based Engineered Cartilage
Description of Technology: Available for licensing and commercial
development is a tissue-engineered cartilage derived from a cellular
composite made from a biodegradable, biocompatible polymeric
nanofibrous matrix having dispersed chondrocytes or adult mesenchymal
stem cells. More particularly, tissue-engineered cartilage can be
prepared where the cartilage has a biodegradable and biocompatible
nanofibrous polymer matrix prepared by electrospinning and a plurality
of chondrocytes or mesenchymal stem cells dispersed in the pores of the
matrix. The tissue-engineered cartilage possesses compressive strength
properties similar to natural cartilage.
The electrospinning process is a simple, economical means to
produce biomaterial matrices or scaffolds of ultra-fine fibers derived
from a variety of biodegradable polymers (Li WJ, et al., J. Biomed.
Mater. Res. 2002; 60:613-21). Nanofibrous scaffolds (NFSs) formed by
electrospinning, by virtue of structural similarity to natural
extracellular matrix (ECM), may represent promising structures for
tissue engineering applications. Electrospun three-dimensional NFSs are
characterized by high porosity with a wide distribution of pore
diameter, high-surface area to volume ratio and morphological
similarities to natural collagen fibrils (Li WJ, et al., J. Biomed.
Mater. Res. 2002; 60:613-21). These physical characteristics promote
favorable biological responses of seeded cells in vitro and in vivo,
including enhanced cell attachment, proliferation, maintenance of the
chondrocytic phenotype (Li WJ, et al., J. Biomed. Mater. Res. 2003;
67A: 1105-14), and support of chondrogenic differentiation (Li WJ, et
al., Biomaterials 2005; 26:599-609) as well as other connective tissue
lineage differentiation (Li WJ, et al., Biomaterials 2005; 26:5158-
5166). The invention based on cell-nanofiber composite represents a
candidate engineered tissue for cell-based approaches to cartilage
repair.
Application: Cartilage repair and methods for making tissue-
engineered cartilage.
Development Status: Electrospinning method is fully developed and
cartilage has been synthesized.
Inventors: Wan-Ju Li and Rocky Tuan (NIAMS).
Publications: The invention is further described in:
1. W-J Li et al., Engineering controllable anisotropy in
electrospun biodegradable nanofibrous scaffolds for musculoskeletal
tissue engineering. J Biomech. 2007; 40(8):1686-1693.
2. W-J Li et al., Fabrication and characterization of six
electrospun poly(alpha-hydroxy ester)-based fibrous scaffolds for
tissue engineering applications. Acta Biomater. 2006 Jul; 2(4):377-385.
3. CK Kuo et al., Cartilage tissue engineering: its potential and
uses. Curr Opin Rheumatol. 2006 Jan; 18(1):64-73. Review.
4. W-J Li et al., Multilineage differentiation of human mesenchymal
stem cells in a three-dimensional nanofibrous scaffold. Biomaterials.
2005 Sep; 26(25):5158-5166.
Patent Status: PCT Application No. PCT/US2006/0237477 filed 15 Jun
2006, claiming priority to 15 Jun 2005 (HHS Reference No. E-116-2005/0-
PCT-02).
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646;
soukasp@mail.nih.gov.
Cell-Nanofiber Composite and Cell-Nanofiber Composite Amalgam Based
Engineered Intervertebral Disc
Description of Technology: Diseased or damaged musculoskeletal
tissues are often replaced by an artificial material, cadaver tissue or
donated, allogenic tissue. Tissue engineering offers an attractive
alternative whereby a live, natural tissue is generated from a
construct made up of a patient's own cells or an acceptable/compatible
cell source in combination with a biodegradable scaffold for
replacement of defective tissue.
Degeneration of the intervertebral disc (IVD) is a common and
significant source of morbidity in our society. Approximately 8 of 10
adults at some point in their life will experience an episode of
significant low back pain, with the majority improving without any
formal treatment. However, for the subject requiring surgical
management current interventions focus on fusion of the involved IVD
levels, which eliminates pain but does not attempt to restore disc
function. Approximately 200,000 spinal fusions were performed in the
United States in 2002 to treat pain associated with lumbar disc
degeneration. Spinal fusion however is thought to significantly alter
the biomechanics of the disc and lead to further degeneration, or
adjacent segment disease. Therefore, in the past decade there has been
mounting interest in the concept of IVD replacement. The replacement of
the IVD holds tremendous potential as an alternative to spinal fusion
for the treatment of degenerative disc disease by offering a safer
alternative to current spinal fusion practices.
At the present time, several disc replacement implants are at
different stages of preclinical and clinical testing. These disc
replacement technologies are designed to address flexion, extension,
and lateral bending motions; however, they do little to address
compressive forces and their longevity is limited due to their
inability to biointegrate. Therefore, a cell-based tissue engineering
approach offers the most promising alternative to replace the
degenerated IVD. Current treatment for injuries that penetrate
subchondral bone include subchondral drilling, periosteal tissue
grafting, osteochondral allografting, chondrogenic cell and
transplantation; but are limited due to suboptimal integration with
host tissues.
The present invention claims tissue engineered intervertebral discs
comprising a nanofibrous polymer hydrogel amalgam having cells
dispersed therein, methods of fabricating tissue engineered
intervertebral discs by culturing a mixture of stem cells or
intervertebral disc cells and a electrospun nanofibrous polymer
hydrogel amalgam in a suitable bioreactor, and methods of treatment
comprising implantation of tissue engineered intervertebral disc into a
subject.
Application: Intervertebral disc bio-constructs and electrospinning
methods for fabrication of the discs.
Development Status: Prototype devices have been fabricated and
[[Page 34761]]
preclinical studies have been performed.
Inventors: Wan-Ju Li, Leon Nesti, Rocky Tuan (NIAMS).
Patent Status: PCT Application No. PCT/US07/020974 filed 27 Sep
2007, claiming priority to 27 Sep 2006 (HHS Reference No. E-309-2006/2-
PCT-01).
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646;
soukasp@mail.nih.gov.
Methods for Preparing Bacillus anthracis Protective Antigen for Use in
Vaccines
Description of Technology: This invention relates to improved
methods of preparing Bacillus anthracis protective antigen (PA) from a
cell or organism, particularly a recombinant cell or microorganism, for
use in vaccines. Production and purification methods of modified PA
from a non-sporogenic strain of Bacillus anthracis are described.
Specifically, a scalable fermentation and purification process is
claimed that is suitable for vaccine development, and that produces
almost three times more product than earlier-reported processes. This
is accomplished using a biologically inactive protease-resistant PA
variant in a protease-deficient non-sporogenic avirulent strain of B.
anthracis (BH445). One of the PA variants described in the patent
application lacks the furin and chymotrypsin cleavage sites.
Advantages: Bacillus anthracis protective antigen is a major
component of the currently licensed human vaccine (Anthrax Vaccine
Adsorbed, AVA). Although the current human vaccine has been shown to be
effective against cutaneous anthrax infection in animals and humans and
against inhalation anthrax in rhesus monkeys, the licensed vaccine has
several limitations: (1) AVA elicits a relatively high degree of local
and systemic adverse reactions, probably mediated by variable amounts
of undefined bacterial products, making standardization difficult; (2)
the immunization schedule requires administration of six doses within
an eighteen (18) month period, followed by annual boosters; (3) there
is no defined vaccine-induced protective level of antibody to PA by
which to evaluate new lots of vaccines; and (4) AVA is comprised of a
wild-type PA. Thus a vaccine comprising a modified purified recombinant
PA would be effective, safe, allow precise standardization, and require
fewer injections.
The invention also relates to PA variants, and/or compositions
thereof, which are useful for eliciting an immunogenic response in
mammals, particularly humans, including responses that provide
protection against, or reduce the severity of, infections caused by B.
anthracis. The vaccines claimed in this application are intended for
active immunization for prevention of B. anthracis infection, and for
preparation of immune antibodies.
Application: Improved B. anthracis vaccines.
Development Status: Phase I clinical studies are being performed.
Inventors: Joseph Shiloach (NIDDK), Stephen Leppla (NIDCR), Delia
Ramirez (NIDDK), Rachel Schneerson (NICHD), John Robbins (NICHD).
Publication: DM Ramirez et. al. Production, recovery and
immunogenicity of the protective antigen from a recombinant strain of
Bacillus anthracis. J Ind Microbiol Biotechnol. 2002 Apr;28(4):232-238.
Patent Status: U.S. Patent Application No. 10/290,712 filed 08 Nov
2002 (HHS Reference No. E-023-2002/0-US-02).
Licensing Status: Available for exclusive or nonexclusive
licensing.
Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646;
soukasp@mail.nih.gov.
Collaborative Research Opportunity: The National Institutes of
Health is seeking statements of capability or interest from parties
interested in collaborative research to further develop, evaluate, or
commercialize methods of preparing Bacillus anthracis protective
antigen (PA) from a cell or organism, particularly a recombinant cell
or microorganism, for use in vaccines. Please contact Rochelle S.
Blaustein, J.D., at 301/451-3636 or Rochelle.Blaustein@nih.gov for
additional information.
Recombinant Modified Bacillus anthracis Protective Antigen for Use in
Vaccines
Description of Technology: This invention relates to improved
methods of preparing Bacillus anthracis protective antigen (PA) for use
in vaccines. PA is a secreted, non-toxic protein with a molecular
weight of 83 KDa. PA is a major component of the currently licensed
human vaccine (Anthrax Vaccine Adsorbed, AVA). Although the licensed
human vaccine has been shown to be effective against cutaneous anthrax
infection in animals and humans and against inhalation anthrax in
rhesus monkeys, the licensed vaccine has several limitations: (1) AVA
elicits a relatively high degree of local and systemic adverse
reactions, probably mediated by variable amounts of undefined bacterial
products, making standardization difficult; (2) the immunization
schedule requires administration of six doses within an eighteen (18)
month period, followed by annual boosters; (3) there is no defined
vaccine-induced protective level of antibody to PA by which to evaluate
new lots of vaccines; and (4) AVA is comprised of a wild-type PA. It
has been suggested that a vaccine comprising a modified purified
recombinant PA would be effective, safe, allow precise standardization,
and require fewer injections.
This invention claims methods of producing and recovering PA from a
cell or organism, particularly a recombinant cell or microorganism. The
invention claims production and purification of modified PA from a non-
sporogenic strain of Bacillus anthracis. In contrast to other
previously described methods, greater quantities of PA are obtainable
from these cells or microorganisms. Specifically, a scalable
fermentation and purification process is claimed that is suitable for
vaccine development, and that produces almost three times more product
than earlier-reported processes. This is accomplished using a
biologically inactive protease-resistant PA variant in a protease-
deficient non-sporogenic avirulent strain of B. anthracis (BH445). One
of the PA variants described in the patent application lacks the furin
and chymotrypsin cleavage sites.
The invention relates to improved methods of producing and
recovering sporulation-deficient B. anthracis mutant strains, and for
producing and recovering recombinant B. anthracis protective antigen
(PA), especially modified PA which is protease resistant, and to
methods of using of these PAs or nucleic acids encoding these PAs for
eliciting an immunogenic response in humans, including responses which
provide protection against, or reduce the severity of, B. anthracis
bacterial infections and which are useful to prevent and/or treat
illnesses caused by B. anthracis, such as inhalation anthrax, cutaneous
anthrax and gastrointestinal anthrax.
Application: Improved B. anthracis vaccines.
Development Status: Phase I clinical studies are being performed.
Inventors: Stephen Leppla (NIDCR), M. J. Rosovitz (NIDCR), John
Robbins (NICHD), Rachel Schneerson (NICHD).
Patent Status: U.S. Patent No. 7,261,900 issued 28 Aug 2007 (HHS
Reference No. E-268-2002/0-US-02); U.S. Patent Application No. 11/
831,860 filed 31 Jul 2007 (HHS Reference No. E-268-2002/0-US-03).
Licensing Status: Available for exclusive or nonexclusive
licensing.
[[Page 34762]]
Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646;
soukasp@mail.nih.gov.
[gamma]PGA Conjugates for Eliciting Immune Responses Directed Against
Bacillus anthracis and Other Bacilli
Description of Technology: This invention claims immunogenic
conjugates of a poly-[gamma]-glutamic acid ([gamma]PGA) of B.
anthracis, or of another bacillus that expresses a [gamma]PGA that
elicit a serum antibody response against B. anthracis, in mammalian
hosts to which the conjugates are administered. The invention also
relates methods which are useful for eliciting an immunogenic response
in mammals, particularly humans, including responses which provide
protection against, or reduce the severity of, infections caused by B.
anthracis. The vaccines claimed in this application are intended for
active immunization for prevention of B. anthracis infection, and for
preparation of immune antibodies. The vaccines of this invention are
designed to confer specific immunity against infection with B.
anthracis, and to induce antibodies specific to B. anthracis
[gamma]PGA. The B. anthracis vaccine is composed of non-toxic bacterial
components, suitable for infants, children of all ages, and adults.
Inventors: Rachel Schneerson (NICHD), Stephen Leppla (NIAID), John
Robbins (NICHD), Joseph Shiloach (NIDDK), Joanna Kubler-Kielb (NICHD),
Darrell Liu (NIDCR), Fathy Majadly (NICHD).
Publication: R Schneerson et al. Poly(gamma-D-glutamic acid)
protein conjugates induce IgG antibodies in mice to the capsule of
Bacillus anthracis: a potential addition to the anthrax vaccine. Proc
Natl Acad Sci USA. 2003 Jul 22;100(15):8945-8950.
Patent Status: U.S. Patent Application No. 10/559,825 filed 02 Dec
2005, claiming priority to 05 Jun 2003 (HHS Reference No. E-343-2002/0-
US-04).
Licensing Status: Available for licensing.
Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646;
soukasp@mail.nih.gov.
Methods for Conjugation of Oligosaccharides or Polysaccharides to
Protein Carriers Through Oxime Linkages Via 3-Deoxy-D-Manno-Octulsonic
Acid
Description of Technology: This technology comprises new methods
for the conjugation of O-specific polysaccharides/oligosaccharides (O-
SP/OS) derived from bacterial lipooligosaccharides/ lipopolysaccharides
(LOS/LPS), after their cleavage from Lipid A, to carrier proteins, to
serve as potential vaccines. Conjugation is performed between the
carbonyl group on the terminal reducing end of the saccharide and the
aminooxy group of a bifunctional linker bound further to the protein.
The inventors have carried out the reaction under mild conditions
and in a short time resulting in binding 3-deoxy-D-manno-octulosonic
acid (KDO) on the sacchride to the protein. These conjugates preserve
the external non-reducing end of the sacchride, are recognized by
antisera, and induce immune responses in mice to both conjugate
components (i.e., the OS and the associated carrier protein).
Application: Cost effective and efficient manufacturing of
conjugate vaccines.
Inventors: Joanna Kubler-Kielb (NICHD), Vince Pozsgay (NICHD), Gil
Ben-Menachem (NICHD), Rachel Schneerson (NICHD), et al.
Patent Status: PCT Application No. PCT/US2007/016373 filed 18 Jul
2007, which published as WO 2008/013735 on 31 Jan 2008; claiming
priority to 21 Jul 2006 (HHS Reference No. E-183-2005/0-PCT-02).
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646;
soukasp@mail.nih.gov.
Dated: June 10, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E8-13669 Filed 6-17-08; 8:45 am]
BILLING CODE 4140-01-P
