Patents by Inventor Stefan Wildt
Stefan Wildt 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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Patent number: 8697394Abstract: The present invention relates to eukaryotic host cells, especially lower eukaryotic host cells, having modified oligosaccharides which may be modified further by heterologous expression of a set of glycosyltransferases, sugar and sugar nucleotide transporters to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. The process provides an engineered host cell which can be used to express and target any desirable gene(s) involved in glycosylation. Host cells with modified lipid-linked oligosaccharides are created or selected. N-glycans made in the engineered host cells exhibit GnTIII, GnTIV, GnTV, GnT VI or GnTIX activity, which produce bisected and/or multiantennary N-glycan structures and may be modified further by heterologous expression of one or more enzymes, e.g., glycosyltransferases, sugar, sugar nucleotide transporters, to yield human-like glycoproteins.Type: GrantFiled: February 20, 2004Date of Patent: April 15, 2014Assignee: Glycofi, Inc.Inventors: Piotr Bobrowicz, Stephen R. Hamilton, Tillman U. Gerngross, Stefan Wildt, Byung-Kwon Choi, Juergen Hermann Nett, Robert C. Davidson
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Publication number: 20130295608Abstract: Lower eukaryotic host cells have been recombinantly engineered to produce glycoprotein having human-like O-glycosylation. The glycoproteins are useful for the production of glycoprotein compositions with advantages for the production of human therapeutics.Type: ApplicationFiled: February 20, 2012Publication date: November 7, 2013Inventors: Piotr Bobrowicz, William J. Cook, Stephen Hamilton, Juergen Nett, Terrance A. Stadheim, Stefan Wildt
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Publication number: 20130217067Abstract: The present invention relates to eukaryotic host cells having modified oligosaccharides which may be modified further by heterologous expression of a set of glycosyltransferases, sugar transporters and mannosidases to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. The invention provides nucleic acid molecules and combinatorial libraries which can be used to successfully target and express mammalian enzymatic activities such as those involved in glycosylation to intracellular compartments in a eukaryotic host cell. The process provides an engineered host cell which can be used to express and target any desirable gene(s) involved in glycosylation. Host cells with modified oligosaccharides are created or selected. N-glycans made in the engineered host cells have a Man5GlcNAc2 core structure which may then be modified further by heterologous expression of one or more enzymes, e.g.Type: ApplicationFiled: February 29, 2012Publication date: August 22, 2013Applicant: GlycoFi, Inc.Inventors: TILLMAN U. GERNGROSS, Stefan Wildt, Byung-kwon Choi, Juergen Hermann Nett, Piotr Bobrowicz, Stephen R. Hamilton, Robert C. Davidson
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Patent number: 8445227Abstract: The present invention relates to eukaryotic host cells having modified oligosaccharides which may be modified further by heterologous expression of a set of glycosyltransferases, sugar transporters and mannosidases to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. The process provides an engineered host cell which can be used to express and target any desirable gene(s) involved in glycosylation. Host cells with modified lipid-linked oligosaccharides are created or selected. N-glycans made in the engineered host cells exhibit GnTIII activity, which produce bisected N-glycan structures and may be modified further by heterologous expression of one or more enzymes, e.g., glycosyltransferases, sugar transporters and mannosidases, to yield human-like glycoproteins. For the production of therapeutic proteins, this method may be adapted to engineer cell lines in which any desired glycosylation structure may be obtained.Type: GrantFiled: August 13, 2009Date of Patent: May 21, 2013Assignee: Merck Sharp & DohmeInventors: Piotr Bobrowicz, Stephen R. Hamilton, Tillman U. Gerngross, Stefan Wildt, Byung-Kwon Choi, Juergen Hermann Nett, Robert C. Davidson
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Publication number: 20120232007Abstract: Methods for producing proteins and glycoproteins in Pichia pastoris that lack detectable cross binding activity to antibodies made against host cell antigens are described. In particular, methods are described wherein recombinant Pichia pastoris strains that do not display a ?-mannosyltransferase 2 activity with respect to an N-glycan or O-glycan and do not display at least one activity selected from a ?-mannosyltransferase 1, 3, and 4 activity to produce recombinant proteins and glycoproteins. These recombinant Pichia pastoris strains can produce proteins and glycoproteins that lack detectable ?-mannosidase resistant ?-mannose residues thereon and thus, lack cross binding activity to antibodies against host cell antigens. Further described are methods for producing bi-sialylated human erythropoietin in Pichia pastoris that lack detectable cross binding activity to antibodies against host cell antigens.Type: ApplicationFiled: October 11, 2010Publication date: September 13, 2012Applicant: MERCK SHARP & DOHME CORPInventors: Piotr Bobrowicz, Sujatha Gomathinayagam, Stephen Hamilton, Huijuan Li, Natarajan Sethuraman, Terrance A. Stadheim, Stefan Wildt
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Publication number: 20120135461Abstract: A method is described for producing protein compositions having reduced amounts of O-linked glycosylation. The method includes producing the protein in cells cultured in the presence of one or more ?-1,2-mannosidases from Coccidiodes immitis, Coccidiodes posadasii, Penicillium citrinum, Magnaporthe grisea, Aspergillus saitoi, Aspergillus oryzae, and Chaetomiun globosum or a catalytically active fragment of said ?-1,2-mannosidase.Type: ApplicationFiled: July 27, 2011Publication date: May 31, 2012Inventors: WILLIAM JAMES COOK, STEFAN WILDT
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Publication number: 20120121630Abstract: The present invention provides Herpes Simplex Virus (HSV) gD, gC, gB and/or gE recombinant glycoproteins having a particular pre-selected N-linked glycosylation pattern as the predominant N-glycoform. The present invention also provides methods of producing these recombinant glycoproteins in yeast, preferably Pichia pastoris, which may be glycoengineered to provide particular glycosylation patterns. The present invention further provides vaccines comprising gD and gC, and optionally gB and/or gE, at least one of which has a particular pre-selected N-linked glycosylation pattern as the predominant N-glycoform. The recombinant glycoproteins are produced by a method which, in one embodiment, comprises transforming a yeast of the genus Pichia with an expression vector containing a DNA encoding an HSV glycoprotein, which is under regulation of a promoter functional in a yeast of the genus Pichia, culturing the yeast in a medium, and recovering the recombinant glycoprotein from the obtained culture.Type: ApplicationFiled: July 21, 2010Publication date: May 17, 2012Inventors: Janine T. Bryan, John W. Ballet, Jessica A. Flynn, Danilo R. Casimiro, Robert C. Davidson, Victoria Copeland, Sandra E. Rios, Byung-Kwon Choi, Stefan Wildt
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Publication number: 20120052530Abstract: The present invention relates to eukaryotic host cells having modified oligosaccharides which may be modified further by heterologous expression of a set of glycosyltransferases, sugar transporters and mannosidases to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. The invention provides nucleic acid molecules and combinatorial libraries which can be used to successfully target and express mammalian enzymatic activities such as those involved in glycosylation to intracellular compartments in a eukaryotic host cell. The process provides an engineered host cell which can be used to express and target any desirable gene(s) involved in glycosylation. Host cells with modified oligosaccharides are created or selected. N-glycans made in the engineered host cells have a Man5GlcNAc2 core structure which may then be modified further by heterologous expression of one or more enzymes, e.g.Type: ApplicationFiled: June 9, 2011Publication date: March 1, 2012Applicant: GlycoFi, Inc.Inventors: TILLMAN U. GERNGROSS, Stefan Wildt, Byung-kwon Choi, Juergen Hermann Nett, Piotr Bobrowicz, Stephen R. Hamilton, Robert C. Davidson
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Publication number: 20120021948Abstract: Methods for display of recombinant whole immunoglobulins or immunoglobulin libraries on the surface of eukaryote host cells, including yeast and filamentous fungi, are described. The methods are useful for screening libraries of recombinant immunoglobulins in eukaryote host cells to identify immunoglobulins that are specific for an antigen of interest.Type: ApplicationFiled: October 3, 2011Publication date: January 26, 2012Applicant: Merck Sharp & Dohme Corp.Inventors: Bianka Prinz, Natarajan Sethuraman, Dongxing Zha, Stefan Wildt, Piotr Bobrowicz
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Patent number: 8067551Abstract: The present invention relates to eukaryotic host cells having modified oligosaccharides which may be modified further by heterologous expression of a set of glycosyltransferases, sugar transporters and mannosidases to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. The invention provides nucleic acid molecules and combinatorial libraries which can be used to successfully target and express mammalian enzymatic activities such as those involved in glycosylation to intracellular compartments in a eukaryotic host cell. The process provides an engineered host cell which can be used to express and target any desirable gene(s) involved in glycosylation. Host cells with modified oligosaccharides are created or selected. N-glycans made in the engineered host cells have a Man5GlcNAc2 core structure which may then be modified further by heterologous expression of one or more enzymes, e.g.Type: GrantFiled: November 7, 2008Date of Patent: November 29, 2011Assignee: Glycofi, Inc.Inventors: Tillman U. Gerngross, Stefan Wildt, Byung-Kwon Choi, Juergen Hermann Nett, Piotr Bobrowicz, Stephen R Hamilton, Robert C. Davidson
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Patent number: 8067339Abstract: Methods for display of recombinant whole immunoglobulins or immunoglobulin libraries on the surface of eukaryote host cells, including yeast and filamentous fungi, are described. The methods are useful for screening libraries of recombinant immunoglobulins in eukaryote host cells to identify immunoglobulins that are specific for an antigen of interest.Type: GrantFiled: June 23, 2009Date of Patent: November 29, 2011Assignee: Merck Sharp & Dohme Corp.Inventors: Bianka Prinz, Natarajan Sethuraman, Dongxing Zha, Stefan Wildt, Piotr Bobrowicz
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Patent number: 7935513Abstract: The present invention relates to eukaryotic host cells having modified oligosaccharides which may be modified further by heterologous expression of a set of glycosyltransferases, sugar transporters and mannosidases to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. The invention provides nucleic acid molecules and combinatorial libraries which can be used to successfully target and express mammalian enzymatic activities such as those involved in glycosylation to intracellular compartments in a eukaryotic host cell. The process provides an engineered host cell which can be used to express and target any desirable gene(s) involved in glycosylation. Host cells with modified oligosaccharides are created or selected. N-glycans made in the engineered host cells have a Man5GlcNAc2 core structure which may then be modified further by heterologous expression of one or more enzymes, e.g.Type: GrantFiled: June 5, 2008Date of Patent: May 3, 2011Assignee: Glycofi, Inc.Inventors: Tillman U. Gerngross, Stefan Wildt, Byung-Kwon Choi, Juergen Hermann Nett, Piotr Bobrowicz, Stephen R. Hamilton, Robert C. Davidson
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Publication number: 20110086054Abstract: Lower eukaryotic host cells have been engineered to produce glycoprotein having at least one terminal ?-galactosyl epitope. The glycoproteins are useful for the production of highly antigenic glycoprotein compositions with advantages for the production of vaccines.Type: ApplicationFiled: December 3, 2009Publication date: April 14, 2011Inventors: Natarajan Sethuraman, Robert C. Davidson, Terrance A. Stadheim, Stefan Wildt
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Publication number: 20110053214Abstract: The present invention provides a novel lower eukaryotic host cell producing human-like glycoproteins characterized as having a terminal ?-galactose residue and essentially lacking fucose and sialic acid residues. The present invention also provides a method for catalyzing the transfer of a galactose residue from UDP-galactose onto an acceptor substrate in a recombinant lower eukaryotic host cell, which can be used as a therapeutic glycoprotein.Type: ApplicationFiled: July 21, 2010Publication date: March 3, 2011Applicant: GLYCOFI, INC.Inventors: Robert Collier Davidson, Tillman Ulf Gerngross, Stefan Wildt, Byung-Kwon Choi, Juergen Hermann Nett, Piotr Bobrowicz, Stephen Robin Hamilton
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Publication number: 20100331192Abstract: Methods for display of recombinant proteins or protein libraries on the surface of lower eukaryotes such as yeast and filamentous fungi are described. The methods are useful for screening libraries of recombinant proteins in lower eukaryotes to identify particular proteins with desired properties from the array of proteins in the libraries. The methods are particularly useful for constructing and screening antibody libraries in lower eukaryotes.Type: ApplicationFiled: February 20, 2009Publication date: December 30, 2010Inventors: Dongxing Zha, Stefan Wildt
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Patent number: 7795002Abstract: The present invention provides a novel lower eukaryotic host cell producing human-like glycoproteins characterized as having a terminal ?-galactose residue and essentially lacking fucose and sialic acid residues. The present invention also provides a method for catalyzing the transfer of a galactose residue from UDP-galactose onto an acceptor substrate in a recombinant lower eukaryotic host cell, which can be used as a therapeutic glycoprotein.Type: GrantFiled: April 15, 2005Date of Patent: September 14, 2010Assignee: Glycofi, Inc.Inventors: Robert Davidson, Tillman Ulf Gerngross, Stefan Wildt, Byung-Kwon Choi, Juergen Hermann Nett, Piotr Bobrowicz, Stephen Robin Hamilton
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Publication number: 20100184143Abstract: The present invention relates to immunoglobulin glycoprotein compositions having predominant N-glycan structures on an immunoglobulin glycoprotein which confer a specific effector function. Additionally, the present invention relates to pharmaceutical compositions comprising an antibody having a particular enriched N-glycan structure, wherein said N-glycan structure is Man3GlcNAc2.Type: ApplicationFiled: October 9, 2008Publication date: July 22, 2010Inventors: Tillman U. Gerngross, Huijuan Li, Stefan Wildt
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Publication number: 20100016561Abstract: The present invention relates to eukaryotic host cells having modified oligosaccharides which may be modified further by heterologous expression of a set of glycosyltransferases, sugar transporters and mannosidases to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. The process provides an engineered host cell which can be used to express and target any desirable gene(s) involved in glycosylation. Host cells with modified lipid-linked oligosaccharides are created or selected. N-glycans made in the engineered host cells exhibit GnTIII activity, which produce bisected N-glycan structures and may be modified further by heterologous expression of one or more enzymes, e.g., glycosyltransferases, sugar transporters and mannosidases, to yield human-like glycoproteins. For the production of therapeutic proteins, this method may be adapted to engineer cell lines in which any desired glycosylation structure may be obtained.Type: ApplicationFiled: August 13, 2009Publication date: January 21, 2010Applicant: GlycoFi, Inc.Inventors: Piotr Bobrowicz, Stephen R. Hamilton, Tillman U. Gerngross, Stefan Wildt, Byung-Kwon Choi, Juergen Hermann Nett, Robert C. Davidson
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Publication number: 20100016555Abstract: The present invention relates to eukaryotic host cells having modified oligosaccharides which may be modified further by heterologous expression of a set of glycosyltransferases, sugar transporters and mannosidases to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. The process provides an engineered host cell which can be used to express and target any desirable gene(s) involved in glycosylation. Host cells with modified lipid-linked oligosaccharides are created or selected. N-glycans made in the engineered host cells exhibit GnTIII activity, which produce bisected N-glycan structures and may be modified further by heterologous expression of one or more enzymes, e.g., glycosyltransferases, sugar transporters and mannosidases, to yield human-like glycoproteins. For the production of therapeutic proteins, this method may be adapted to engineer cell lines in which any desired glycosylation structure may be obtained.Type: ApplicationFiled: August 13, 2009Publication date: January 21, 2010Applicant: GlycoFi, Inc.Inventors: Piotr Bobrowicz, Stephen R. Hamilton, Tillman U. Gerngross, Stefan Wildt, Byung-Kwon Choi, Juergen H. Nett, Robert C. Davidson
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Publication number: 20100009866Abstract: Methods for display of recombinant whole immunoglobulins or immunoglobulin libraries on the surface of eukaryote host cells, including yeast and filamentous fungi, are described. The methods are useful for screening libraries of recombinant immunoglobulins in eukaryote host cells to identify immunoglobulins that are specific for an antigen of interest.Type: ApplicationFiled: June 23, 2009Publication date: January 14, 2010Inventors: Bianka Prinz, Natarajan Sethuraman, Dongxing Zha, Stefan Wildt, Piotr Bobrowicz