Patents Assigned to Research Corporation Technologies, Inc.
  • Patent number: 10329572
    Abstract: 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: Grant
    Filed: February 28, 2017
    Date of Patent: June 25, 2019
    Assignee: Research Corporation Technologies, Inc.
    Inventors: Kurt R. Gehlsen, Thomas G. Chappell
  • Publication number: 20180346551
    Abstract: 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: Application
    Filed: August 13, 2018
    Publication date: December 6, 2018
    Applicant: Research Corporation Technologies, Inc.
    Inventor: Shohei Koide
  • Patent number: 10113164
    Abstract: This disclosure relates to novel Pichia pastoris display systems, e.g., display systems featuring the Pichia pastoris strains (such as SuperMan5) with substantially homogeneous N-glycans displayed on cell surface proteins.
    Type: Grant
    Filed: December 16, 2014
    Date of Patent: October 30, 2018
    Assignee: Research Corporation Technologies, Inc.
    Inventors: Kurt R. Gehlsen, Thomas G. Chappell
  • Patent number: 9976131
    Abstract: The present application relates to modified T cell epitopes derived from fungal ribotoxins, including ?-sarcin, clavin, gigantin, mitogillin, and restrictocin, as well as modified ribotoxin molecules comprising one or more of the modified epitopes. The modified ribotoxin molecules inhibit protein synthesis, like the wild type ribotoxins, but exhibit reduced immunogenicity as compared to the corresponding wild type ribotoxin. Another aspect relates to a fusion protein which comprises a modified ribotoxin fused or conjugated or otherwise linked to a targeting molecule that is effective for binding a target of interest. Another aspect relates to the use of the modified ribotoxin or fusion protein for treating or managing a disease or condition.
    Type: Grant
    Filed: February 13, 2017
    Date of Patent: May 22, 2018
    Assignee: RESEARCH CORPORATION TECHNOLOGIES, INC.
    Inventors: Kurt R. Gehlsen, Timothy David Jones, Francis Joseph Carr, Arron Hearn
  • Publication number: 20170369555
    Abstract: 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: Application
    Filed: February 16, 2016
    Publication date: December 28, 2017
    Applicant: Research Corporation Technologies, Inc.
    Inventor: Shohei Koide
  • Patent number: 9803210
    Abstract: This disclosure features fusion proteins comprising a base protein linked to or incorporated in a CH2 scaffold of IgG. The CH2 scaffold can derive from the macaque CH2 domain of IgG. The fusion proteins can effectively bind a single or multiple targets, and can be engineered to regulate effector functions as desired. The fusion proteins can have an increased serum half-life, solubility, stability, protease resistance, and/or expression as compared to the scaffolds alone and/or as compared to the base protein alone. This disclosure also features fusion proteins comprising a base protein, a CH2 scaffold and a discrete polyethylene glycol (dPEG) linked to the scaffold via a serine, tyrosine, cysteine, lysine, or a glycosylation site of the scaffold. This disclosure additionally features scaffolds linked to a discrete polyethylene glycol (dPEG) via a serine, tyrosine, cysteine, or lysine of the scaffolds or a glycosylation site of the scaffold.
    Type: Grant
    Filed: February 8, 2013
    Date of Patent: October 31, 2017
    Assignee: Research Corporation Technologies, Inc.
    Inventors: David Bramhill, Kurt R. Gehlsen
  • Publication number: 20170298369
    Abstract: This disclosure features fusion proteins comprising a base protein linked to or incorporated in a CH2 scaffold of IgG. The CH2 scaffold can derive from the macaque CH2 domain of IgG. The fusion proteins can effectively bind a single or multiple targets, and can be engineered to regulate effector functions as desired. The fusion proteins can have an increased serum half-life, solubility, stability, protease resistance, and/or expression as compared to the scaffolds alone and/or as compared to the base protein alone. This disclosure also features fusion proteins comprising a base protein, a CH2 scaffold and a discrete polyethylene glycol (dPEG) linked to the scaffold via a serine, tyrosine, cysteine, lysine, or a glycosylation site of the scaffold. This disclosure additionally features scaffolds linked to a discrete polyethylene glycol (dPEG) via a serine, tyrosine, cysteine, or lysine of the scaffolds or a glycosylation site of the scaffold.
    Type: Application
    Filed: February 8, 2013
    Publication date: October 19, 2017
    Applicant: RESEARCH CORPORATION TECHNOLOGIES, INC.
    Inventors: David BRAMHILL, Kurt R. Gehlsen
  • Publication number: 20170166910
    Abstract: 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 OCH1protein 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: Application
    Filed: February 28, 2017
    Publication date: June 15, 2017
    Applicant: Research Corporation Technologies, Inc.
    Inventors: Kurt R. Gehlsen, Thomas G. Chappell
  • Patent number: 9617550
    Abstract: 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: Grant
    Filed: October 23, 2013
    Date of Patent: April 11, 2017
    Assignee: Research Corporation Technologies, Inc.
    Inventors: Kurt R. Gehlsen, Thomas G. Chappell
  • Patent number: 9603911
    Abstract: The present application relates to modified T cell epitopes derived from fungal ribotoxins, including a-sarcin, clavin, gigantin, mitogillin, and restrictocin, as well as modified ribotoxin molecules comprising one or more of the modified epitopes. The modified ribotoxin molecules inhibit protein synthesis, like the wild type ribotoxins, but exhibit reduced immunogenicity as compared to the corresponding wild type ribotoxin. Another aspect relates to a fusion protein which comprises a modified ribotoxin fused or conjugated or otherwise linked to a targeting molecule that is effective for binding a target of interest. Another aspect relates to the use of the modified ribotoxin or fusion protein for treating or managing a disease or condition.
    Type: Grant
    Filed: March 3, 2014
    Date of Patent: March 28, 2017
    Assignee: RESEARCH CORPORATION TECHNOLOGIES, INC.
    Inventors: Kurt R. Gehlsen, Timothy David Jones, Francis Joseph Carr, Arron Hearn
  • Patent number: 9458454
    Abstract: 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: Grant
    Filed: September 7, 2012
    Date of Patent: October 4, 2016
    Assignee: Research Corporation Technologies, Inc.
    Inventors: David Bramhill, Uwe Mamat
  • Patent number: 9359628
    Abstract: 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: Grant
    Filed: January 10, 2014
    Date of Patent: June 7, 2016
    Assignees: VIB, VZW, Research Corporation Technologies, Inc., Universiteit Gent
    Inventors: Roland Contreras, Nico L.M. Callewaert, Steven C.J. Geysens
  • Patent number: 9156917
    Abstract: 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: Grant
    Filed: February 10, 2012
    Date of Patent: October 13, 2015
    Assignee: RESEARCH CORPORATION TECHNOLOGIES, INC.
    Inventors: David Bramhill, Gopalan Raghunathan
  • Publication number: 20150267212
    Abstract: 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: Application
    Filed: October 23, 2013
    Publication date: September 24, 2015
    Applicant: RESEARCH CORPORATION TECHNOLOGIES, INC.
    Inventors: Kurt R. Gehlsen, Thomas G. Chappell
  • Patent number: 9068186
    Abstract: 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: Grant
    Filed: March 11, 2011
    Date of Patent: June 30, 2015
    Assignee: RESEARCH CORPORATION TECHNOLOGIES, INC.
    Inventors: David Bramhill, Uwe Mamat
  • Patent number: 9051357
    Abstract: 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: Grant
    Filed: July 23, 2012
    Date of Patent: June 9, 2015
    Assignee: Research Corporation Technologies, Inc.
    Inventor: Shohei Koide
  • Patent number: 8883445
    Abstract: 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: Grant
    Filed: July 13, 2007
    Date of Patent: November 11, 2014
    Assignees: Research Corporation Technologies, Inc., Universiteit Gent, Vib, VZW
    Inventors: Roland Contreras, Nico L. M. Callewaert, Steven C. J. Geysens, Vladimir Kaigorodov, Vervecken Wouter
  • Publication number: 20140221251
    Abstract: 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: Application
    Filed: September 7, 2012
    Publication date: August 7, 2014
    Applicant: RESEARCH CORPORATION TECHNOLOGIES, INC.
    Inventors: David Bramhill, Uwe Mamat
  • Publication number: 20140154738
    Abstract: 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: Application
    Filed: January 10, 2014
    Publication date: June 5, 2014
    Applicants: VIB, VZW, UNIVERSITEIT GENT, RESEARCH CORPORATION TECHNOLOGIES, INC.
    Inventors: Roland Contreras, Nico L.M. Callewaert, Steven C.J. Geysens
  • Patent number: 8663971
    Abstract: 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: Grant
    Filed: April 16, 2009
    Date of Patent: March 4, 2014
    Assignees: VIB, VZW, Research Corporation Technologies, Inc., Universiteit Gent
    Inventors: Roland Contreras, Nico L. M. Callewaert, Steven C. J. Geysens