Patents Assigned to GlycoFi, Inc
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Patent number: 7923430Abstract: Cell lines having genetically modified glycosylation pathways that allow them to carry out a sequence of enzymatic reactions, which mimic the processing of glycoproteins in humans, have been developed. The lower eukaryotes, which ordinarily produce high-mannose containing N-glycans, including unicellular and multicellular fungi are modified to produce N-glycans such as Man5GlcNAc2 or other structures along human glycosylation pathways. This is achieved using a combination of engineering and/or selection of strains which: do not express certain enzymes which create the undesirable complex structures characteristic of the fungal glycoproteins, which express exogenous enzymes selected either to have optimal activity under the conditions present in the fungi where activity is desired, or which are targeted to an organelle where optimal activity is achieved, and combinations thereof wherein the genetically engineered eukaryote expresses multiple exogenous enzymes required to produce “human-like” glycoproteins.Type: GrantFiled: October 11, 2005Date of Patent: April 12, 2011Assignee: Glycofi, Inc.Inventor: Tillman U. Gerngross
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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: 20110027831Abstract: The present invention relates to eukaryotic host cells which have been modified to produce sialylated glycoproteins by the heterologous expression of a set of glycosyltransferases, including sialyltransferase and/or trans-sialidase, to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. Novel eukaryotic host cells expressing a CMP-sialic acid biosynthetic pathway for the production of sialylated glycoproteins are also provided. 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 sialylation) 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.Type: ApplicationFiled: October 1, 2010Publication date: February 3, 2011Applicant: GlycoFi, Inc.Inventor: STEPHEN R. HAMILTON
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Publication number: 20110020870Abstract: Cell lines having genetically modified glycosylation pathways that allow them to carry out a sequence of enzymatic reactions, which mimic the processing of glycoproteins in humans, have been developed. Recombinant proteins expressed in these engineered hosts yield glycoproteins more similar, if not substantially identical, to their human counterparts. The lower eukaryotes, which ordinarily produce high-mannose containing N-glycans, including unicellular and multicellular fungi are modified to produce N-glycans such as Man5GlcNAc2 or other structures along human glycosylation pathways.Type: ApplicationFiled: October 11, 2010Publication date: January 27, 2011Applicant: GlycoFi, Inc.Inventor: Tillman U. Gerngross
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Patent number: 7863020Abstract: The present invention relates to eukaryotic host cells which have been modified to produce sialylated glycoproteins by the heterologous expression of a set of glycosyltransferases, including sialyltransferase and/or trans-sialidase, to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. Novel eukaryotic host cells expressing a CMP-sialic acid biosynthetic pathway for the production of sialylated glycoproteins are also provided. 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 sialylation) 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.Type: GrantFiled: May 5, 2006Date of Patent: January 4, 2011Assignee: GlycoFi, Inc.Inventor: Stephen R. Hamilton
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Publication number: 20100279356Abstract: The present invention relates to eukaryotic host cells which have been modified to produce sialylated glycoproteins by the heterologous expression of a set of glycosyltransferases, including sialyltransferase and/or trans-sialidase, to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. Novel eukaryotic host cells expressing a CMP-sialic acid biosynthetic pathway for the production of sialylated glycoproteins are also provided. 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 sialylation) 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.Type: ApplicationFiled: June 21, 2010Publication date: November 4, 2010Applicant: GlycoFi, Inc.Inventor: STEPHEN R. HAMILTON
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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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Patent number: 7713719Abstract: The present invention provides methods to reduce or eliminate ?-mannosidase resistant glycans on glycoproteins in yeast. The reduction or elimination of ?-mannosidase resistant glycans on glycoproteins results from the disruption of the newly isolated P. pastoris AMR2 gene encoding ?1,2-mannosyltransferase. The present invention also discloses novel genes, polypeptides, antibodies, vectors and host cells relating to ?-mannosidase resistance on glycans.Type: GrantFiled: November 7, 2008Date of Patent: May 11, 2010Assignee: GlycoFi, Inc.Inventor: Piotr Bobrowicz
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Publication number: 20100062516Abstract: A method for producing human-like glycoproteins by expressing a Class 2 ?-mannosidase having a substrate specificity for Man?1,3 and Man?1,6 glycosidic linkages in a lower eukaryote is disclosed. Hydrolysis of these linkages on oligosaccharides produces substrates for further N-glycan processing in the secretory pathway.Type: ApplicationFiled: August 6, 2009Publication date: March 11, 2010Applicant: GlycoFi, Inc.Inventor: Stephen Hamilton
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Publication number: 20100062523Abstract: A method for producing human-like glycoproteins by expressing a Class 2 ?-mannosidase having a substrate specificity for Man?1,3 and Man?1,6 glycosidic linkages in a lower eukaryote is disclosed. Hydrolysis of these linkages on oligosaccharides produces substrates for further N-glycan processing in the secretory pathway.Type: ApplicationFiled: August 6, 2009Publication date: March 11, 2010Applicant: GlycoFi, Inc.,Inventor: Stephen Hamilton
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Publication number: 20100021991Abstract: Cell lines having genetically modified glycosylation pathways that allow them to carry out a sequence of enzymatic reactions, which mimic the processing of glycoproteins in humans, have been developed. Recombinant proteins expressed in these engineered hosts yield glycoproteins more similar, if not substantially identical, to their human counterparts. The lower eukaryotes, which ordinarily produce high-mannose containing N-glycans, including unicellular and multicellular fungi are modified to produce N-glycans such as Man5GlcNAc2 or other structures along human glycosylation pathways.Type: ApplicationFiled: August 27, 2009Publication date: January 28, 2010Applicant: GlycoFi, Inc.Inventor: Tillman U. Gerngross
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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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Patent number: 7629163Abstract: Cell lines having genetically modified glycosylation pathways that allow them to carry out a sequence of enzymatic reactions, which mimic the processing of glycoproteins in humans, have been developed. Recombinant proteins expressed in these engineered hosts yield glycoproteins more similar, if not substantially identical, to their human counterparts. The lower eukaryotes, which ordinarily produce high-mannose containing N-glycans, including unicellular and multicellular fungi are modified to produce N-glycans such as Man5GlcNAc2 or other structures along human glycosylation pathways.Type: GrantFiled: November 10, 2005Date of Patent: December 8, 2009Assignee: GlycoFi, Inc.Inventor: Tillman U. Gerngross
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Patent number: 7598055Abstract: 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: October 7, 2003Date of Patent: October 6, 2009Assignee: 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: 20090170159Abstract: 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 an inhibitor of Pmt-mediated O-linked glycosylation and/or in the presence of one or more ?-1,2-mannosidases.Type: ApplicationFiled: November 10, 2006Publication date: July 2, 2009Applicant: GLYCOFI, INCInventors: Piotr Bobrowicz, W. James Cook, Warren Kett
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Patent number: 7514253Abstract: A novel gene encoding P. pastoris orotate-phosphoribosyl transferase (URA5) is disclosed. Methods for producing and selecting yeast strains capable of stable genetic integration of heterologous sequences into the host genome are also provided.Type: GrantFiled: June 3, 2003Date of Patent: April 7, 2009Assignee: GlycoFi, Inc.Inventor: Juergen H. Nett
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Patent number: 7479389Abstract: Novel genes encoding P. pastoris ARG1, ARG2, ARG3, HIS1, HIS2, HIS5 and HIS6 are disclosed. A method for inactivating alternately at least two biosynthetic pathways in a methylotrophic yeast is provided. A method for producing and selecting yeast strains characterized as being capable of genetic integration of heterologous sequences into the host genome using the genes involved in the biosynthetic pathways is also disclosed.Type: GrantFiled: March 2, 2005Date of Patent: January 20, 2009Assignee: GlycoFi, Inc.Inventors: Juergen Nett, Tillman Gerngross
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Patent number: 7465577Abstract: The present invention provides methods to reduce or eliminate ?-mannosidase resistant glycans on glycoproteins in yeast. The reduction or elimination of ?-mannosidase resistant glycans on glycoproteins results from the disruption of the newly isolated P. pastoris AMR2 gene encoding ?1,2-mannosyltransferase. The present invention also discloses novel genes, polypeptides, antibodies, vectors and host cells relating to ?-mannosidase resistance on glycans.Type: GrantFiled: April 29, 2005Date of Patent: December 16, 2008Assignee: GlycoFi, Inc.Inventor: Piotr Bobrowicz
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Patent number: 7449308Abstract: 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: February 20, 2003Date of Patent: November 11, 2008Assignee: GlycoFi, Inc.Inventors: Tillman U. Gerngross, Stefan Wildt, Byung-Kwon Choi, Juergen Hermann Nett, Piotr Bobrowicz, Stephen R. Hamilton, Robert C. Davidson