[Federal Register: October 23, 2008 (Volume 73, Number 206)]
[Notices]
[Page 63169-63171]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr23oc08-69]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions; Availability for Licensing
AGENCY: National Institutes of Health, Public Health Service, HHS.
ACTION: Notice.
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[[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