Government-Owned Inventions; Availability for Licensing, 63169-63171 [E8-25222]
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• Anatomic and metabolic imaging of
brain and spinal cord tumors for
diagnostic and therapeutic purposes.
• Intravenous treatment of brain and
spinal cord tumors.
• Imaging of intravenous drug
delivery to brain and spinal cord
tumors.
• Potential to be used for imaging and
treatment of other neurological
disorders in which the BBB becomes
porous.
Market: In 2008, it is estimated that
malignant tumors of the brain and
spinal cord will account for about 1.5%
of all cancers and 2.3% of all expected
cancer-related deaths.
Development Status: Early stage
development; Pre-clinical data
available.
Inventor: Hemant Sarin (CC).
Patent Status: U.S. Provisional
Application No. 61/055,328 filed 22
May 2008 (HHS Reference No. E–063–
2008/0–US–01).
Licensing Status: Available for
exclusive or non-exclusive licensing.
Licensing Contact: Surekha Vathyam,
PhD; 301–435–4076;
vathyams@mail.nih.gov.
Induced Internalization of Surface
Receptors
Description of Technology: Cellsurface receptors are responsible for the
biological activities of many molecules.
Specific ligands bind to them, causing
the cell-surface receptors to internalize
or bring the receptor and ligand inside
the cell. A number of diseases,
including cancer, metabolic disorders,
and viral infections are known to
require the expression of cell-surface
receptors for critical pathogenetic steps.
This has prompted significant research
efforts towards the development of
pharmaceutical agents that block the
signals from cell-surface receptors.
While this current research shows great
promise, there is a strong need for new
therapeutic strategies that utilize the
mechanistic properties of cell-surface
receptors.
This technology describes a strategy
for artificially inducing the
internalization of surface receptors, and
thereby blocking the effects of the
ligands associated with that receptor.
This method employs bifunctional
ligands that bind to both a scavenger
receptor and a target receptor. As proof
of concept, the inventors Drs. Narazaki
and Tosato have shown that a ligand
capable of binding to the scavenger
receptor SREC–1 and the neuropilin-1
receptor NRP1 induces the
internalization of NRP1 and inhibits
NRP1 signaling. The inventors propose
that this strategy can be used to inhibit
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signaling from any target receptor if an
appropriate bifunctional ligand is used.
For example, the concept could be
expanded to other receptors, such as
HDL and LDL receptors. Likewise the
bifunctional ligand could include
specific antibodies or modified ligands
that recognize cell surface receptors of
biological importance. Accordingly, this
approach could be used to limit tumor
angiogenesis, limit tumor growth, block
metastasis formation, block
inflammation, block viral infection, and
treat just about any disease where we
identify a cell surface receptor as the
molecular basis for disease.
Applications:
• Method of inducing the
internalization of target receptors.
• Inhibiting diseases or conditions
associated with target receptors, such as
HIV infection, cancer, or angiogenesis.
• Treating diseases or conditions
associated with target receptors, such as
cancer, viral infections, or HIV
infections.
Market:
• Cancer is one of the leading causes
of death in the United States and it is
estimated that there will be more than
half a million deaths caused by cancer
in 2008.
• It is estimated that over one million
people in the U.S. are living with HIV/
AIDS and approximately 50,000 new
infections occur each year.
Development Status: The technology
is currently in the pre-clinical stage of
development.
Inventors: Masashi Narazaki and
Giovanna Tosato (NCI).
Patent Status: U.S. Provisional
Application No. 61/023,397 filed 24 Jan
2008 (HHS Reference No. E–250–2007/
0–US–01).
Licensing Status: Available for
licensing.
Licensing Contact: Whitney A.
Hastings; 301–451–7337;
hastingw@mail.nih.gov.
Collaborative Research Opportunity:
The National Cancer Institute,
Laboratory of Cellular Oncology, is
seeking statements of capability or
interest from parties interested in
collaborative research to further
develop, evaluate, or commercialize the
technology aimed at promoting selective
receptor internalization as a means to
neutralize ligand function and receptor
signaling. Please contact John D. Hewes,
PhD at 301–435–3121 or
hewesj@mail.nih.gov for more
information.
Methods of Determining the Prognosis
of an Adenocarcinoma
Description of Technology: Available
for licensing and commercial
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63169
development is a novel method for
determining the prognosis of a subject
with adenocarcinoma in an organ, such
as the lung, and to aid in the selection
of a specific therapeutic regimen. Lung
adenocarcinoma (AC) is the
predominant histological subtype of
lung cancer, which is the leading cause
of cancer deaths worldwide. The risk of
metastasis remains substantial in AC
patients, even when a curative resection
of early-stage AC is performed. The
prognosis includes the determination of
the likelihood of survival, the likelihood
of metastasis, or both. The method
includes quantization of the expression
of a plurality of Th1 and Th2 cytokines
of interest in the adenocarcinoma and in
non-cancerous tissue in the organ.
Altered expression of one or more of the
Th1 and Th2 cytokines in the
adenocarcinoma as compared to the
non-cancerous tissue determines the
prognosis for the subject. The method is
capable of distinguishing patients with
lymph node metastasis versus those
with short term survival. Furthermore,
methods are provided for evaluating the
effectiveness of anti-cancer agents.
Applications: Prognosis of
adenocarcinoma, aid in the selection of
specific therapeutic regimens and
evaluation of the effectiveness of anticancer agents.
Development Status: The technology
is in early stage of development.
Inventors: Curtis C. Harris, Masahiro
Seike, Xin Wei Wang (NCI).
Patent Status: PCT Application No.
PCT/US2007/073637 filed 16 Jul 2007,
which published as WO 2008/009028
on 17 Jan 2008; claiming priority to 14
Jul 2006 (HHS Reference No. E–263–
2006/1–PCT–01).
Licensing Status: Available for nonexclusive or exclusive licensing.
Licensing Contact: Susan Ano, PhD;
301–435–5515; anos@mail.nih.gov.
Dated: October 14, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E8–25221 Filed 10–22–08; 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:
E:\FR\FM\23OCN1.SGM
23OCN1
63170
Federal Register / Vol. 73, No. 206 / Thursday, October 23, 2008 / Notices
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.
dwashington3 on PRODPC61 with NOTICES
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
can be used to synthesize a variety of
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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. Patent Application
No. 11/178,230 filed 08 Jul 2005,
allowed (HHS Reference No. E–230–
2002/2–US–03); Foreign rights also
available.
Licensing Status: Available for
exclusive or non-exclusive licensing.
Licensing Contact: John Stansberry,
PhD; 301–435–5236;
stansbej@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 Nacetylglucosamine that may itself be
linked to a variety of other molecules.
Please contact John D. Hewes, PhD, 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), Olinked via -GalNAc to Ser/Thr (Oglycans), or can connect the carboxyl
end of a protein to a
phosphatidylinositol unit (GPI-anchors)
via a common core glycan structure.
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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)-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: PCT Application No.
PCT/US2008/006248 filed 14 May 2008,
claiming priority to 14 May 2007 (HHS
Reference No. E–204–2007/0–PCT–02).
Licensing Status: Available for
exclusive or non-exclusive licensing.
Licensing Contact: John Stansberry,
PhD; 301–435–5236;
stansbej@mail.nih.gov.
Collaborative Research Opportunity:
The National Cancer Institute is seeking
E:\FR\FM\23OCN1.SGM
23OCN1
Federal Register / Vol. 73, No. 206 / Thursday, October 23, 2008 / Notices
statements of capability or interest from
parties interested in collaborative
research to further develop, evaluate, or
commercialize this technology. Please
contact John D. Hewes, PhD, at 301–
435–3121 or hewesj@mail.nih.gov for
more information.
dwashington3 on PRODPC61 with NOTICES
Alpha 1-3 NAcetylgalactosaminyltransferases 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 Nacetylglucosarnine (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 NAcetylgalactosaminyltransferase (alpha
3 GalNAc-T) mutants from alpha l3galactosyltransferase (a3Gal-T) that can
transfer 2′-modified galactose from the
corresponding UDP-derivatives due to
mutations that broaden the alpha 3GalT 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 Application No.
PCT/US2007/018678 filed 22 Aug 2007
(HHS Reference No. E–279–2007/0–
PCT–01).
Licensing Status: Available for
exclusive or non-exclusive licensing.
Licensing Contact: John Stansberry,
PhD; 301–435–5236;
stansbej@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 Nacetylglucosarnine (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
PO 00000
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Fmt 4703
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63171
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, 4Tyr289Leu-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 Application No.
PCT/US2007/018656 filed 22 Aug 2007
(HHS Reference No. E–280–2007/0–
PCT–01).
Licensing Status: Available for
exclusive or non-exclusive licensing.
Licensing Contact: John Stansberry,
PhD; 301–435–5236;
stansbej@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, PhD, at
301–435–3121 or hewesj@mail.nih.gov.
Dated: October 15, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E8–25222 Filed 10–22–08; 8:45 am]
BILLING CODE 4140–01–P
E:\FR\FM\23OCN1.SGM
23OCN1
]]>Agencies
[Federal Register Volume 73, Number 206 (Thursday, October 23, 2008)]
[Notices]
[Pages 63169-63171]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E8-25222]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
[[Page 63170]]
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.
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 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. Patent Application No. 11/178,230 filed 08 Jul
2005, allowed (HHS Reference No. E-230-2002/2-US-03); Foreign rights
also available.
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: John Stansberry, PhD; 301-435-5236;
stansbej@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, PhD, 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: PCT Application No. PCT/US2008/006248 filed 14 May
2008, claiming priority to 14 May 2007 (HHS Reference No. E-204-2007/0-
PCT-02).
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: John Stansberry, PhD; 301-435-5236;
stansbej@mail.nih.gov.
Collaborative Research Opportunity: The National Cancer Institute
is seeking
[[Page 63171]]
statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or commercialize
this technology. Please contact John D. Hewes, PhD, at 301-435-3121 or
hewesj@mail.nih.gov for more information.
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.
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 Application No. PCT/US2007/018678 filed 22 Aug
2007 (HHS Reference No. E-279-2007/0-PCT-01).
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: John Stansberry, PhD; 301-435-5236;
stansbej@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 Application No. PCT/US2007/018656 filed 22 Aug
2007 (HHS Reference No. E-280-2007/0-PCT-01).
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: John Stansberry, PhD; 301-435-5236;
stansbej@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, PhD, at 301-435-3121 or hewesj@mail.nih.gov.
Dated: October 15, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E8-25222 Filed 10-22-08; 8:45 am]
BILLING CODE 4140-01-P
