[Federal Register Volume 73, Number 206 (Thursday, October 23, 2008)]
[Notices]
[Pages 63169-63171]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-25222]


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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; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute's 
Nanobiology Program is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize the use of galactose and modified galactose 
to be linked to an N-acetylglucosamine that may itself be linked to a 
variety of other molecules. Please contact John D. Hewes, PhD, at 301-
435-3121 or [email protected] for more information.

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; 
[email protected].
    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 
[email protected] 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; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute's 
Nanobiology Program is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize structure-based design of novel 
glycosyltransferases. Please contact John D. Hewes, PhD, at 301-435-
3121 or [email protected] 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; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute's 
Nanobiology Program is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize glycosyltransferases. Please contact John D. 
Hewes, PhD, at 301-435-3121 or [email protected].

    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