Patents Assigned to Research Corporation Technologies, Inc.
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Patent number: 9359628Abstract: The present invention provides genetically engineered strains of Pichia capable of producing proteins with reduced glycosylation. In particular, the genetically engineered strains of the present invention are capable of expressing either or both of an ?-1,2-mannosidase and glucosidase II. The genetically engineered strains of the present invention can be further modified such that the OCH1 gene is disrupted. Methods of producing glycoproteins with reduced glycosylation using such genetically engineered stains of Pichia are also provided.Type: GrantFiled: January 10, 2014Date of Patent: June 7, 2016Assignees: VIB, VZW, Research Corporation Technologies, Inc., Universiteit GentInventors: Roland Contreras, Nico L.M. Callewaert, Steven C.J. Geysens
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Patent number: 9156917Abstract: Novel CH2 domain template molecules wherein donor loops from a database of domains are transferred to a CH2 domain scaffold. At least one or up to three loops from a donor are transferred to the CH2 domain. The donor loops may be chosen based on length, e.g., the donor loop may have a length that is similar to that of a structural loop in the CH2 domain scaffold.Type: GrantFiled: February 10, 2012Date of Patent: October 13, 2015Assignee: RESEARCH CORPORATION TECHNOLOGIES, INC.Inventors: David Bramhill, Gopalan Raghunathan
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Publication number: 20150267212Abstract: Disclosed herein are novel Pichia pastoris strains for expression of exogenous proteins with substantially homogeneous N-glycans. The strains are genetically engineered to include a mutant OCH1 allele which is transcribed into an mRNA coding for a mutant OCH1 gene product (i.e., ?-1,6-mannosyltransferase, or “OCH1 protein”). The mutant OCH1 protein contains a catalytic domain substantially identical to that of the wild type OCH1 protein, but lacks an N-terminal sequence necessary to target the OCH1 protein to the Golgi apparatus. The strains disclosed herein are robust, stable, and transformable, and the mutant OCH1 allele and the ability to produce substantially homogeneous N-glycans are maintained for generations after rounds of freezing and thawing and after subsequent transformations.Type: ApplicationFiled: October 23, 2013Publication date: September 24, 2015Applicant: RESEARCH CORPORATION TECHNOLOGIES, INC.Inventors: Kurt R. Gehlsen, Thomas G. Chappell
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Patent number: 9068186Abstract: Viable Gram-negative bacteria or components thereof comprising outer membranes that substantially lack a ligand, such as Lipid A or 6-acyl lipidpolysaccharide, that acts as an agonist of TLR4/MD2. The bacteria may comprise reduced activity of arabinose-5-phosphate isomerases and one or more suppressor mutations, for example in a transporter thereby increasing the transporters capacity to transport Lipid IVA or in membrane protein YhjD. One or more genes (e.g., IpxL, IpxM, pagP, IpxP, and/or eptA) may be substantially deleted and/or one or more enzymes (e.g., LpxL, LpxM, PagP, LpxP, and/or EptA) may be substantially inactive. The bacteria may be competent to take up extracellular DNA, may be donor bacteria, or may be members of a library. The present invention also features methods of creating and utilizing such bacteria.Type: GrantFiled: March 11, 2011Date of Patent: June 30, 2015Assignee: RESEARCH CORPORATION TECHNOLOGIES, INC.Inventors: David Bramhill, Uwe Mamat
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Patent number: 9051357Abstract: The present invention provides modified fibronectin type III (Fn3) molecules, and nucleic acid molecules encoding the modified Fn3 molecules. Also provided are methods of preparing these molecules, and kits to perform the methods.Type: GrantFiled: July 23, 2012Date of Patent: June 9, 2015Assignee: Research Corporation Technologies, Inc.Inventor: Shohei Koide
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Patent number: 8883445Abstract: The present invention provides genetically engineered strains of methylotrophic yeast including Pichia and especially Pichia pastoris capable of producing proteins with reduced or modified glycosylation. Methods of producing glycoproteins with reduced and/or modified glycosylation using such genetically engineered strains of Pichia are also provided. Vectors, which comprise coding sequences for ?-1,2-mannosidase I, glucosidase II, GlcNAc-tranferase I and mannosidase II or comprising OCH1 disrupting sequence, for transforming methylotrophic yeasts are contemplated by the present invention. Kit for providing the comtemplated vectors are also included in this invention.Type: GrantFiled: July 13, 2007Date of Patent: November 11, 2014Assignees: Research Corporation Technologies, Inc., Universiteit Gent, Vib, VZWInventors: Roland Contreras, Nico L. M. Callewaert, Steven C. J. Geysens, Vladimir Kaigorodov, Vervecken Wouter
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Publication number: 20140221251Abstract: Viable Gram-negative bacteria or components thereof comprising outer membranes that substantially lack a ligand, such as Lipid A or 6-acyl lipidpolysaccharide, that acts as an agonist of TLR4/MD-2. The bacteria may comprise reduced activity of arabinose-5-phosphate isomerases and one or more suppressor mutations, for example in a transporter thereby increasing the transporter's capacity to transport lipid IVA or in membrane protein YhjD. One or more genes (e.g., lpxL, lpxM, pagP, lpxP, and/or eptA) may be substantially deleted and/or one or more enzymes (e.g., LpxL, LpxM, PagP, LpxP, and/or EptA) may be substantially inactive. The bacteria may be competent to take up extracellular DNA, may be donor bacteria, or may be members of a library. The present invention also features methods of creating and utilizing such bacteria.Type: ApplicationFiled: September 7, 2012Publication date: August 7, 2014Applicant: RESEARCH CORPORATION TECHNOLOGIES, INC.Inventors: David Bramhill, Uwe Mamat
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Publication number: 20140154738Abstract: The present invention provides genetically engineered strains of Pichia capable of producing proteins with reduced glycosylation. In particular, the genetically engineered strains of the present invention are capable of expressing either or both of an ?-1,2-mannosidase and glucosidase II. The genetically engineered strains of the present invention can be further modified such that the OCH1 gene is disrupted. Methods of producing glycoproteins with reduced glycosylation using such genetically engineered stains of Pichia are also provided.Type: ApplicationFiled: January 10, 2014Publication date: June 5, 2014Applicants: VIB, VZW, UNIVERSITEIT GENT, RESEARCH CORPORATION TECHNOLOGIES, INC.Inventors: Roland Contreras, Nico L.M. Callewaert, Steven C.J. Geysens
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Patent number: 8663971Abstract: The present invention provides genetically engineered strains of Pichia capable of producing proteins with reduced glycosylation. In particular, the genetically engineered strains of the present invention are capable of expressing either or both of an ?-1,2-mannosidase and glucosidase II. The genetically engineered strains of the present invention can be further modified such that the OCH1 gene is disrupted. Methods of producing glycoproteins with reduced glycosylation using such genetically engineered stains of Pichia are also provided.Type: GrantFiled: April 16, 2009Date of Patent: March 4, 2014Assignees: VIB, VZW, Research Corporation Technologies, Inc., Universiteit GentInventors: Roland Contreras, Nico L. M. Callewaert, Steven C. J. Geysens
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Publication number: 20130316953Abstract: The present invention is directed to the use of compounds of the formula: for treating pain, in particular neuropathic pain, bipolar disease and migraine headaches.Type: ApplicationFiled: July 29, 2013Publication date: November 28, 2013Applicant: RESEARCH CORPORATION TECHNOLOGIES, INC.Inventor: Robert H. Harris
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Patent number: 8519183Abstract: The present invention is directed to the use of compounds of the formula: for treating pain, in particular neuropathic pain, bipolar disease and migraine headaches.Type: GrantFiled: July 1, 2010Date of Patent: August 27, 2013Assignee: Research Corporation Technologies, Inc.Inventor: Robert H. Harris
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Publication number: 20130189247Abstract: The present invention relate to small binding proteins comprising two or more protein domains derived from a CH2 domain or CH2-like domain of an immunoglobulin in which the CH2 domains have been altered to recognize one or more target proteins and, in some embodiments, retain, or have modified, certain secondary effector functions.Type: ApplicationFiled: February 11, 2011Publication date: July 25, 2013Applicant: RESEARCH CORPORATION TECHNOLOGIES, INC.Inventors: David Bramhill, Kurt R. Gehlsen, Dimiter S. Dimitrov, Rui Gong
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Patent number: 8440456Abstract: The present invention provides the genome sequence of Pichia pastoris and manually curated annotation of protein-coding genes. The invention provides novel nucleic acids, proteins, and related expression vectors useful for genetic engineering of methylotrophic yeast strains, as well as engineered methylotrophic yeast strains particularly Pichia pastsoris, and use thereof for recombinant production of heterologous proteins including glycoproteins suitable for use in mammals including humans.Type: GrantFiled: May 21, 2010Date of Patent: May 14, 2013Assignees: VIB, VZW, Universiteit Gent, Research Corporation Technologies, Inc.Inventors: Nico Callewaert, Kristof De Schutter, Petra Tiels, Yao-Cheng Lin
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Patent number: 8354268Abstract: The present invention provides genetically engineered strains of Pichiacapable of producing proteins with reduced glycosylation. In particular, the genetically engineered strains of the present invention are capable of expressing either or both of an ?-1,2-mannosidase and glucosidase II. The genetically engineered strains of the present invention can be further modified such that the OCH1 gene is disrupted. Methods of producing glycoproteins with reduced glycosylation using such genetically engineered stains of Pichia are also provided.Type: GrantFiled: September 25, 2003Date of Patent: January 15, 2013Assignees: VIB, VZW, Research Corporation Technologies, Inc., Universiteit GentInventors: Roland Contreras, Nico L. M. Callewaert, Steven C. J. Geysens
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Patent number: 8303964Abstract: The present invention provides non-toxic Gram-negative bacteria. In particular, the present invention provides viable Gram-negative bacteria (e.g., E. coli) substantially lacking lipopolysaccharide (LPS, endotoxin) within the outer membrane. The present invention further provides methods of generating viable non-toxic Gram-negative bacteria and uses thereof. The present invention also provides compositions and methods for inducing immune responses and for researching and developing therapeutic agents.Type: GrantFiled: January 19, 2007Date of Patent: November 6, 2012Assignee: Research Corporation Technologies, Inc.Inventors: Ronald Wesley Woodard, Timothy Charles Meredith, Parag Aggarwal
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Patent number: 8263741Abstract: The present invention provides a fibronectin type III (Fn3) molecule, wherein the Fn3 contains a stabilizing mutation. The present invention also provides Fn3 polypeptide monobodies, nucleic acid molecules encoding monobodies, and variegated nucleic acid libraries encoding such monobodies. Also provided are methods of preparing a Fn3 polypeptide monobody, and kits to perform the methods.Type: GrantFiled: July 11, 2001Date of Patent: September 11, 2012Assignee: Research Corporation Technologies, Inc.Inventor: Shohei Koide
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Patent number: 8258265Abstract: The present invention provides modified fibronectin type III (Fn3) molecules, and nucleic acid molecules encoding the modified Fn3 molecules. Also provided are methods of preparing these molecules, and kits to perform the methods.Type: GrantFiled: August 30, 2007Date of Patent: September 4, 2012Assignee: Research Corporation Technologies, Inc.Inventor: Shohei Koide
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METHODS FOR PRODUCING SUBSTANTIALLY HOMOGENEOUS HYBRID OR COMPLEX N-GLYCANS IN METHYLOTROPHIC YEASTS
Publication number: 20120029174Abstract: The present invention provides methods for effectively and efficiently converting methylotrophic yeast's heterogeneous high mannose-type N-glycosylation to mammalian-type N-glycosylation by disruption of an endogenous glycosyltransferase gene (OCH1) and step-wise introduction of heterologous glycosidase and glycosyltransferase activities. Each engineering step includes a number of stages: transformation with an appropriate vector, cultivation of a number of transformants, performance of sugar analysis and heterologous protein expression analysis, and selection of a desirable clone. The selected clone is then subjected to the next engineering step.Type: ApplicationFiled: September 23, 2011Publication date: February 2, 2012Applicants: VIB, VZW, Research Corporation Technologies, Inc., Universiteit GentInventors: Nico Callewaert, David A. Wiersma -
Patent number: 8058053Abstract: The present invention relates to methods and genetically engineered methylotrophic yeast strains for producing glycoproteins with mammalian-like glycosylation. The present invention also relates to vectors useful for generating methylotrophic yeast strains capable of producing glycoproteins with mammalian-like glycosylation. Glycoproteins produced from the genetically engineered methylotrophic yeast strains are also provided.Type: GrantFiled: February 11, 2009Date of Patent: November 15, 2011Assignees: VIB, VZW, Universiteit Gent, Research Corporation Technologies, Inc.Inventors: Roland Contreras, Nico L. M. Callewaert, Wouter Vervecken, Vladimir Kaigorodov
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METHODS FOR PRODUCING SUBSTANTIALLY HOMOGENEOUS HYBRID OR COMPLEX N-GLYCANS IN METHYLOTROPHIC YEASTS
Publication number: 20110092374Abstract: The present invention provides methods for effectively and efficiently converting methylotrophic yeast's heterogeneous high mannose-type N-glycosylation to mammalian-type N-glycosylation by disruption of an endogenous glycosyltransferase gene (OCH1) and step-wise introduction of heterologous glycosidase and glycosyltransferase activities. Each engineering step includes a number of stages: transformation with an appropriate vector, cultivation of a number of transformants, performance of sugar analysis and heterologous protein expression analysis, and selection of a desirable clone. The selected clone is then subjected to the next engineering step.Type: ApplicationFiled: October 18, 2010Publication date: April 21, 2011Applicants: VIB, VZW, UNIVERSITEIT GENT, RESEARCH CORPORATION TECHNOLOGIES, INC.Inventors: Nico Callewaert, David A. Wiersma