Patents by Inventor Jon S. Thorson
Jon S. Thorson has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Publication number: 20120245054Abstract: The invention provides a rapid, quantitative assay to directly assess the impact of a diverse range of sugars upon the sugar-mediated uptake of corresponding sugar-conjugates into various cell types.Type: ApplicationFiled: May 7, 2012Publication date: September 27, 2012Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATIONInventors: Jon S. Thorson, John R. Fitzgibbon
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Patent number: 8236926Abstract: The present invention generally relates to methods and compositions for generating vancomycin analogs. Specifically the invention relates to generating a vancomycin library through chemoselective ligation of a sugar moiety with a vancomycin aglycon. In particular, the present invention provides a library of vancomycin analogs, where the member of the library comprises at least one vancomycin analog selected from 2?-N-acyldecanoyl-glucosyl vancomycin neoglycoside, 3?-N-acyldecanoyl-glucosyl vancomycin neoglycoside, 4?-N-acyldecanoyl-glucosyl vancomycin neoglycoside, 6?-N-acyldecanoyl-glucosyl vancomycin neoglycoside, 2?-N-acylbiphenyl-glucosyl vancomycin neoglycoside, 3?-N-acylbiphenoyl-glucosyl vancomycin neoglycoside, 4?-N-acylbiphenoyl-glucosyl vancomycin neoglycoside and 6?-N-acylbiphenoyl-glucosyl vancomycin neoglycoside.Type: GrantFiled: September 6, 2007Date of Patent: August 7, 2012Assignee: Wisconsin Alumni Research FoundationInventors: Jon S. Thorson, Byron R. Griffith
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Patent number: 8232254Abstract: Colchicine neoglycosides, method for their synthesis and methods for their use are disclosed. The invention provides analogs of colchicine glycosylated to include a sugar moiety on a colchicine scaffold that is generally unglycosylated in nature. The colchicine neoglycosides disclosed herein are shown to have cytotoxic effects equivalent to at least the known cytotoxins paclitaxel and doxorubicin. Further, the neoglycosides disclosed according to the invention have physiologic effects not previously recognized in the alkaloid family that includes colchicine but recognized in other cytotoxic drug families such as the taxanes which act by stabilizing tubulin formation.Type: GrantFiled: October 8, 2007Date of Patent: July 31, 2012Assignee: Wisconsin Alumni Research FoundationInventors: Jon S. Thorson, Ahmed Aqeel
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Patent number: 8211654Abstract: The invention provides a rapid, quantitative assay to directly assess the impact of a diverse range of sugars upon the sugar-mediated uptake of corresponding sugar-conjugates into various cell types.Type: GrantFiled: February 2, 2009Date of Patent: July 3, 2012Assignee: Wisconsin Alumni Research FoundationInventors: Jon S. Thorson, John R. Fitzgibbon
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Publication number: 20120094946Abstract: A library of glycosylated chlorambucil analogs which are useful as anti-tumor and/or anti-metastatic agents is disclosed. The glycosylated chlorambucil analogs have the general formula wherein represents a reducing sugar moiety.Type: ApplicationFiled: October 17, 2011Publication date: April 19, 2012Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATIONInventors: Jon S. Thorson, Randal D. Goff
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Patent number: 8097443Abstract: The present invention provides mutant RmlA enzymes possessing an increased purine/pyrimidine bias in nucleotide triphosphate substrate specificity as compared to a corresponding non-mutated RmlA enzyme. Such enzymes expand the types of substrates that can be used in enzymatic glycorandomization methods thereby increasing diversity of chemical libraries.Type: GrantFiled: April 16, 2008Date of Patent: January 17, 2012Assignee: Wisconsin Alumni Research FoundationInventor: Jon S. Thorson
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Patent number: 8093028Abstract: The present invention provides engineered glycosyltransferase enzymes and method for making and using the same possessing an expanded substrate specificity as compared to corresponding non-mutated glycosyltransferase enzymes. Such enzymes expand the variety of substrates that can be used in enzymatic glycosylation methods, including enzymatic glycorandomization, thereby providing increased diversity in chemical products.Type: GrantFiled: July 24, 2008Date of Patent: January 10, 2012Assignee: Wisconsin Alumni Research FoundationInventors: Jon S. Thorson, Gavin J. Williams, Richard W. Gantt
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Publication number: 20110306074Abstract: The present invention generally relates to materials and methods for exploiting glycosyltransferase reversibility for nucleotide diphosphate (NDP) sugar synthesis. The present invention provides engineered glycosyltransferase enzymes characterized by improved reaction reversibility and expanded sugar donor specificity as compared to corresponding non-mutated glycosyltransferase enzymes. Such reagents provide advantageous routes to NDP sugars for subsequent use in a variety of biomedical applications, including enzymatic and chemoenzymatic glycorandomization.Type: ApplicationFiled: June 13, 2011Publication date: December 15, 2011Applicant: Wisconsin Alumni Research FoundationInventors: Jon S. Thorson, Richard W. Gantt
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Publication number: 20110064752Abstract: The present invention relates to, inter alia, extracellular drug conjugates (EDC) in which an antibody or other targeting agent (e.g. a targeting moiety) is linked to a drug through a linker (e.g. a non-cleavable linker). These conjugates are useful in the treatment of disease and/or as a tool in the evaluation of biological systems.Type: ApplicationFiled: September 9, 2010Publication date: March 17, 2011Applicant: CENTROSE, LLCInventors: Charles R. Hutchinson, Jill Hutchinson Bollettieri, James R. Prudent, Jon S. Thorson
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Publication number: 20100267655Abstract: The present invention discloses a set of glycosylated warfarin analogs which are useful as anti-tumor or anti-metastatic agents and as reagents for studying sugar uptake in cells.Type: ApplicationFiled: July 30, 2009Publication date: October 21, 2010Applicant: Wisconsin Alumni Research FoundationInventors: Jon S. Thorson, Shannon C. Timmons
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Publication number: 20100256078Abstract: The present invention provides methods of producing libraries of compounds with enhanced desirable properties and diminished side effects as well as the compounds produced by the methods. In preferred embodiments, methods of the present invention use a universal chemical glycosylation method that employs reducing sugars and requires no protection or activation. In a preferred embodiment, the invention provides a library of neoglycoside digitoxin analogs that includes compounds with significantly enhanced cytotoxic potency toward human cancer cells and tumor-specificity, but are less potent Na+/K+-ATPase inhibitors in a human cell line than digitoxin.Type: ApplicationFiled: June 21, 2010Publication date: October 7, 2010Applicant: Wisconsin Alumni Research FoundationInventors: Jon S. Thorson, Joseph M. Langenhan
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Patent number: 7754874Abstract: The present invention provides methods of producing libraries of compounds with enhanced desirable properties and diminished side effects as well as the compounds produced by the methods. In preferred embodiments, methods of the present invention use a universal chemical glycosylation method that employs reducing sugars and requires no protection or activation. In a preferred embodiment, the invention provides a library of neoglycoside digitoxin analogs that includes compounds with significantly enhanced cytotoxic potency toward human cancer cells and tumor-specificity, but are less potent Na+/K+-ATPase inhibitors in a human cell line than digitoxin.Type: GrantFiled: June 24, 2005Date of Patent: July 13, 2010Assignee: Wisconsin Alumni Research FoundationInventors: Jon S. Thorson, Joseph M. Langenhan
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Publication number: 20090317829Abstract: The invention provides a rapid, quantitative assay to directly assess the impact of a diverse range of sugars upon the sugar-mediated uptake of corresponding sugar-conjugates into various cell types.Type: ApplicationFiled: February 2, 2009Publication date: December 24, 2009Applicant: Wisconsin Alumni Research FoundationInventors: Jon S. Thorson, John R. Fitzgibbon
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Publication number: 20090275485Abstract: The present invention relates to methods of use of glycosyltransferases and related novel compounds. The invention exploits the reversibility of glycosyltransferases to generate new sugars, unnatural biomolecules and numerous one-pot reactions for generation of new biomolecules having varied backbones such as enediynes, vancomycins, bleomycins, anthracyclines, macrolides, pluramycins, aureolic acids, indolocarbazoles, aminglycosides, glycopeptides, polyenes, coumarins, benzoisochromanequinones, calicheamicins, erythromycin, avermectins, ivermectins, angucyclines, cardiac glycosides, steroids or flavinoids. In preferred embodiments, the invention specifically relates to biosynthesis of anticancer (the enediyne calicheamicin, CLM), anthelmintic agents (the macrolides avermectin, ivermectin and erythromycin) and antibiotic (the glycopeptide vancomycin, VCM) natural product-based drugs developed by reversible, bidirectional glycosyltransferase-catalyzed reactions.Type: ApplicationFiled: August 30, 2007Publication date: November 5, 2009Applicant: Wisconsin Alumni Research FoundationInventors: Jon S. Thorson, Changsgeng Zhang, Byron R. Griffith
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Publication number: 20090181854Abstract: The present invention provides engineered glycosyltransferase enzymes and method for making and using the same possessing an expanded substrate specificity as compared to corresponding non-mutated glycosyltransferase enzymes. Such enzymes expand the variety of substrates that can be used in enzymatic glycosylation methods, including enzymatic glycorandomization, thereby providing increased diversity in chemical products.Type: ApplicationFiled: July 24, 2008Publication date: July 16, 2009Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATIONInventors: Jon S. Thorson, Gavin J. Williams, Richard W. Gantt
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Publication number: 20090137006Abstract: One preferred embodiment of the present invention provides a GalK variant comprising a Y371H, M173L or Y371H-M173L mutation for in vivo and in vitro glycorandomization. In another preferred embodiment, the E. coli GalK variant is mutated at one or more amino acids including R28, E34, D37, D174, Y223, C339, Y371, Y371H, M173, and M173L. The GalK variants display catalytic activity toward a variety of D or L sugars. Another preferred embodiment provides method of phosphorylating sugars comprising the step of incubating a nucleotide triphosphate (NTP) and a D or L sugar in the presence of a GalK variant such that a sugar phosphate is produced. This sugar phosphate may be further incubated with a nucleotidylyltransferase, such that a NDP-sugar is produced. The NDP-sugar may be further incubated with a biomolecule capable of being glycosylated in the presence of a glycosyltransferase, such that a glycosylated biomolecule is produced.Type: ApplicationFiled: January 20, 2009Publication date: May 28, 2009Inventor: Jon S. Thorson
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Patent number: 7479385Abstract: One preferred embodiment of the present invention provides a GalK variant comprising a Y371H, M173L or Y371H-M173L mutation for in vivo and in vitro glycorandomization. In another preferred embodiment, the E. coli GalK variant is mutated at one or more amino acids including R28, E34, D37, D174, Y233, C339, Y371, Y371H, M173, M173L and C353. The GalK variants display catalytic activity toward a variety of D or L sugars. Another preferred embodiment provides method of phosphorylating sugars comprising the step of incubating a nucleotide triphosphate (NTP) and a D or L sugar in the presence of a GalK variant such that a sugar phosphate is produced. This sugar phosphate may be further incubated with a nucleotidylyltransferase, such that a NDP-sugar is produced. The NDP-sugar may be further incubated with a biomolecule capable of being glycosylated in the presence of a glycosyltransferase, such that a glycosylated biomolecule is produced.Type: GrantFiled: December 6, 2004Date of Patent: January 20, 2009Assignee: Wisconsin Alumni Research FoundationInventor: Jon S. Thorson
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Publication number: 20080254509Abstract: The present invention provides mutant Rm1A enzymes possessing an increased purine/pyrimidine bias in nucleotide triphosphate substrate specificity as compared to a corresponding non-mutated Rm1A enzyme. Such enzymes expand the types of substrates that can be used in enzymatic glycorandomization methods thereby increasing diversity of chemical libraries.Type: ApplicationFiled: April 16, 2008Publication date: October 16, 2008Applicant: Wisconsin Alumni Research FoundationInventor: Jon S. Thorson
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Publication number: 20080171787Abstract: Colchicine neoglycosides, method for their synthesis and methods for their use are disclosed. The invention provides analogs of colchicine glycosylated to include a sugar moiety on a colchicine scaffold that is generally unglycosylated in nature. The colchicine neoglycosides disclosed herein are shown to have cytotoxic effects equivalent to at least the known cytotoxins paclitaxel and doxorubicin. Further, the neoglycosides disclosed according to the invention have physiologic effects not previously recognized in the alkaloid family that includes colchicine but recognized in other cytotoxic drug families such as the taxanes which act by stabilizing tubulin formation.Type: ApplicationFiled: October 8, 2007Publication date: July 17, 2008Applicant: Wisconsin Alumni Research FoundationInventors: Jon S. Thorson, Ahmed Aqeel
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Publication number: 20080114157Abstract: The present invention generally relates to methods and compositions for generating vancomycin analogs. Specifically the invention relates to generating a vancomycin library through chemoselective ligation of a sugar moiety with a vancomycin aglycon. In particular, the present invention provides a library of vancomycin analogs, where the member of the library comprises at least one vancomycin analog selected from 2?-N-acyldecanoyl-glucosyl vancomycin neoglycoside, 3?-N-acyldecanoyl-glucosyl vancomycin neoglycoside, 4?-N-acyldecanoyl-glucosyl vancomycin neoglycoside, 6?-N-acyldecanoyl-glucosyl vancomycin neoglycoside, 2?-N-acylbiphenyl-glucosyl vancomycin neoglycoside, 3?-N-acylbiphenoyl-glucosyl vancomycin neoglycoside, 4?-N-acylbiphenoyl-glucosyl vancomycin neoglycoside and 6?-N-acylbiphenoyl-glucosyl vancomycin neoglycoside.Type: ApplicationFiled: September 6, 2007Publication date: May 15, 2008Applicant: Wisconsin Alumni Research FoundationInventors: Jon S. Thorson, Byron R. Griffith