Patents by Inventor Arie Pieter Otte
Arie Pieter Otte 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: 10563223Abstract: The present invention relates to nucleic acid fragments and constructs comprising genomic nucleotide sequences, which are present upstream of Rb1 and p15C that are associated with intergenic transcription, for the production of a gene product of interest in a eukaryotic, preferably mammalian, host cell in the presence of a stringent selectable marker. The invention further relates to host cells comprising the nucleic acid constructs, to methods for generating the host cells and to methods for producing a gene product of interest using the host cells.Type: GrantFiled: September 29, 2017Date of Patent: February 18, 2020Assignee: CellaGenics B.V.Inventors: Arie Pieter Otte, Michel Siep, John Antonius Verhees, Femke Hoeksema, Henricus Johannes Maria Van Blokland
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Patent number: 10106799Abstract: The present invention relates to nucleic acid constructs comprising selectable marker genes in a multicistronic transcription unit for use in the generation and selection of eukaryotic host cells for expression of a gene product of interest. For increased stringency of selection, the coding sequence of the selectable marker may be directed preceded by a relatively short functional open reading frame to reduce the efficiency of translation of the selectable marker, and/or the amino acid sequence of the selectable marker may comprise one or more mutations that reduce the level of resistance provide by the mutated marker as compared to its wild type counterpart. The invention further relates to methods for generating eukaryotic host cells for expression of a gene product of interest, wherein these nucleic acid constructs are used, and to methods for producing a gene product of interest wherein thus generated host cells are applied.Type: GrantFiled: February 8, 2016Date of Patent: October 23, 2018Assignee: CELLAGENICS B.V.Inventors: Arie Pieter Otte, Henricus Johannes Maria Van Blokland, John Antonius Verhees
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Publication number: 20180030476Abstract: The present invention relates to nucleic acid fragments and constructs comprising genomic nucleotide sequences, which are present upstream of Rb1 and p15C that are associated with intergenic transcription, for the production of a gene product of interest in a eukaryotic, preferably mammalian, host cell in the presence of a stringent selectable marker. The invention further relates to host cells comprising the nucleic acid constructs, to methods for generating the host cells and to methods for producing a gene product of interest using the host cells.Type: ApplicationFiled: September 29, 2017Publication date: February 1, 2018Applicant: CellaGenics B.V.Inventors: Arie Pieter OTTE, Michel SIEP, John Antonius VERHEES, Femke HOEKSEMA, Henricus Johannes Maria VAN BLOKLAND
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Patent number: 9790517Abstract: The present invention relates to nucleic acid fragments and constructs comprising genomic nucleotide sequences, which are present upstream of Rb1 and p15C that are associated with intergenic transcription, for the production of a gene product of interest in a eukaryotic, preferably mammalian, host cell in the presence of a stringent selectable marker. The invention further relates to host cells comprising the nucleic acid constructs, to methods for generating the host cells and to methods for producing a gene product of interest using the host cells.Type: GrantFiled: June 15, 2011Date of Patent: October 17, 2017Assignee: CellaGenics B.V.Inventors: Arie Pieter Otte, Michel Siep, John Antonius Verhees, Femke Hoeksema, Henricus Johannes Maria Van Blokland
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Patent number: 9650630Abstract: The present invention relates to nucleic acid fragments and constructs comprising genomic nucleotide sequences from the promoter region of a 60S ribosomal protein L32 gene (RPL32), for the production of a gene product of interest in a eukaryotic, preferably mammalian, host cell in the presence of a stringent selectable marker. The invention further relates to host cells comprising the nucleic acid constructs, to methods for generating the host cells and to methods for producing a gene product of interest using the host cells.Type: GrantFiled: August 31, 2011Date of Patent: May 16, 2017Assignee: CellaGenics B.V.Inventors: Arie Pieter Otte, Femke Hoeksema, John Antonius Verhees, Henricus Johannes Maria Van Blokland
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Publication number: 20160160221Abstract: The present invention relates to nucleic acid constructs comprising selectable marker genes in a multicistronic transcription unit for use in the generation and selection of eukaryotic host cells for expression of a gene product of interest. For increased stringency of selection, the coding sequence of the selectable marker may be directed preceded by a relatively short functional open reading frame to reduce the efficiency of translation of the selectable marker, and/or the amino acid sequence of the selectable marker may comprise one or more mutations that reduce the level of resistance provide by the mutated marker as compared to its wild type counterpart. The invention further relates to methods for generating eukaryotic host cells for expression of a gene product of interest, wherein these nucleic acid constructs are used, and to methods for producing a gene product of interest wherein thus generated host cells are applied.Type: ApplicationFiled: February 8, 2016Publication date: June 9, 2016Applicant: CellaGenics B.V.Inventors: Arie Pieter OTTE, Henricus Johannes Maria VAN BLOKLAND, John Antonius VERHEES
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Patent number: 9284563Abstract: The present invention relates to nucleic acid constructs comprising selectable marker genes in a multicistronic transcription unit for use in the generation and selection of eukaryotic host cells for expression of a gene product of interest. For increased stringency of selection, the coding sequence of the selectable marker may be directed preceded by a relatively short functional open reading frame to reduce the efficiency of translation of the selectable marker, and/or the amino acid sequence of the selectable marker may comprise one or more mutations that reduce the level of resistance provide by the mutated marker as compared to its wild type counterpart. The invention further relates to methods for generating eukaryotic host cells for expression of a gene product of interest, wherein these nucleic acid constructs are used, and to methods for producing a gene product of interest wherein thus generated host cells are applied.Type: GrantFiled: June 15, 2010Date of Patent: March 15, 2016Assignee: CELLAGENICS B.V.Inventors: Arie Pieter Otte, Henricus Johannes Maria Van Blokland, John Antonius Verhees
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Patent number: 9228004Abstract: Described is a DNA molecule comprising an open reading frame sequence encoding a selectable marker polypeptide, wherein the DNA molecule in the coding strand comprises a translation start sequence for the selectable marker polypeptide having a GTG or TTG start codon, and wherein the ORF sequence that encodes the selectable marker protein has been mutated to replace at least half of its CpG dinucleotides as compared to the native ORF sequence that encodes the selectable marker protein. Further provided are such DNA molecules wherein the ORF sequence that encodes a selectable marker polypeptide is part of a multicistronic transcription unit that further comprises an open reading frame sequence encoding a polypeptide of interest. Also described are methods for obtaining host cells expressing a polypeptide of interest, wherein the host cells comprise the DNA molecules described herein.Type: GrantFiled: November 15, 2013Date of Patent: January 5, 2016Assignee: ChromaGenics B.V.Inventors: Arie Pieter Otte, Henricus J.M. van Blokland, Theodorus Hendrikus Jacobus Kwaks, Richard George Antonius Bernardus Sewalt
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Publication number: 20140186890Abstract: Provided is a DNA molecule comprising a multicistronic transcription unit coding for i) a selectable marker polypeptide functional in a eukaryotic host cell, and for ii) a polypeptide of interest, the polypeptide of interest having a translation initiation sequence separate from that of the selectable marker polypeptide, wherein the coding sequence for the polypeptide of interest is downstream from the coding sequence for the selectable marker in the multicistronic transcription unit, and the nucleic acid sequence coding for the selectable marker polypeptide comprises a mutation that decreases the translation efficiency of the selectable marker in a eukaryotic host cell. Also provided are methods for obtaining host cells expressing a polypeptide of interest, the host cells comprising the described DNA molecules. Further provided is the production of polypeptides of interest, comprising culturing host cells comprising the DNA molecules hereof.Type: ApplicationFiled: January 27, 2014Publication date: July 3, 2014Applicant: CHROMAGENICS B.V.Inventors: Arie Pieter OTTE, Henricus J.M. VAN BLOKLAND, Theodorus Hendrikus Jacobus KWAKS, Richard George Antonius Bernardus SEWALT
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Publication number: 20140106401Abstract: Described is a DNA molecule comprising an open reading frame sequence encoding a selectable marker polypeptide, wherein the DNA molecule in the coding strand comprises a translation start sequence for the selectable marker polypeptide having a GTG or TTG start codon, and wherein the ORF sequence that encodes the selectable marker protein has been mutated to replace at least half of its CpG dinucleotides as compared to the native ORF sequence that encodes the selectable marker protein. Further provided are such DNA molecules wherein the ORF sequence that encodes a selectable marker polypeptide is part of a multicistronic transcription unit that further comprises an open reading frame sequence encoding a polypeptide of interest. Also described are methods for obtaining host cells expressing a polypeptide of interest, wherein the host cells comprise the DNA molecules described herein.Type: ApplicationFiled: November 15, 2013Publication date: April 17, 2014Applicant: ChromaGenics B.V.Inventors: Arie Pieter Otte, Henricus J.M. van Blokland, Theodorus Hendrikus Jacobus Kwaks, Richard George Antonius Bernardus Sewalt
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Publication number: 20130236956Abstract: The present invention relates to nucleic acid fragments and constructs comprising genomic nucleotide sequences from the promoter region of a 60S ribosomal protein L32 gene (RPL32), for the production of a gene product of interest in a eukaryotic, preferably mammalian, host cell in the presence of a stringent selectable marker. The invention further relates to host cells comprising the nucleic acid constructs, to methods for generating the host cells and to methods for producing a gene product of interest using the host cells.Type: ApplicationFiled: August 31, 2011Publication date: September 12, 2013Inventors: Arie Pieter Otte, Femke Hoeksema, John Antonious Verhees, Henricus Johannes Maria Van Blokland
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Publication number: 20130157312Abstract: The present invention relates to nucleic acid fragments and constructs comprising genomic nucleotide sequences, which are present upstream of Rb1 and p15C that are associated with intergenic transcription, for the production of a gene product of interest in a eukaryotic, preferably mammalian, host cell in the presence of a stringent selectable marker. The invention further relates to host cells comprising the nucleic acid constructs, to methods for generating the host cells and to methods for producing a gene product of interest using the host cells.Type: ApplicationFiled: June 15, 2011Publication date: June 20, 2013Inventors: Arie Pieter Otte, Michel Siep, John Antonius Verhess, Femke Hoeksema
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Patent number: 8263393Abstract: Described are means and methods for providing a cell with a protein expression unit, the method comprising providing a nucleic acid sequence comprising the unit with a nucleic acid sequence encoding a binding site for a member of a chromatin modification system for rendering chromatin more accessible for transcription (opener), wherein the opener is present in the cell. Preferred openers comprise histone modification proteins, chromatin remodeling proteins and trithorax group proteins or equivalents. The cells thus generated and nucleic acid sequences encoding such openers are provided. Openers are preferred in the context of STAR and TRAP sequences.Type: GrantFiled: June 20, 2005Date of Patent: September 11, 2012Assignee: Chromagenics B.V.Inventors: Arie Pieter Otte, Theodorus Hendrikus Jacobus Kwaks, Richard George Antonius Bernardus Sewalt
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Publication number: 20120156672Abstract: The present invention relates to nucleic acid constructs comprising selectable marker genes in a multicistronic transcription unit for use in the generation and selection of eukaryotic host cells for expression of a gene product of interest. For increased stringency of selection, the coding sequence of the selectable marker may be directed preceded by a relatively short functional open reading frame to reduce the efficiency of translation of the selectable marker, and/or the amino acid sequence of the selectable marker may comprise one or more mutations that reduce the level of resistance provide by the mutated marker as compared to its wild type counterpart. The invention further relates to methods for generating eukaryotic host cells for expression of a gene product of interest, wherein these nucleic acid constructs are used, and to methods for producing a gene product of interest wherein thus generated host cells are applied.Type: ApplicationFiled: June 15, 2010Publication date: June 21, 2012Inventors: Arie Pieter Otte, Henricus Johannes Maria Van Blokland, John Antonius Verhees
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Patent number: 8173422Abstract: The present invention relates to the production of proteins in a cell or host cell. The invention uses a TRAnscription Pause (TRAP) sequence to enhance a protein expression characteristic of a protein expression unit. The TRAP sequence is thought to prevent, at least in part, formation of antisense RNA or to, at least in part, prevent transcription to enter the protein expression unit. In one embodiment, the invention provides a method for expression of at least one protein of interest in a cell comprising providing the cell with at least one protein expression unit that comprises a promoter functionally linked to an open reading frame encoding at least one protein of interest, characterized in that the protein expression unit further comprises at least one TRAP sequence and wherein the TRAP sequence is functionally located downstream of the open reading frame and at least in part prevents formation of antisense RNA.Type: GrantFiled: July 11, 2008Date of Patent: May 8, 2012Assignee: Chromagenics B.V.Inventors: Arie Pieter Otte, Henricus Johannes Maria Van Blokland
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Publication number: 20110300580Abstract: Described is a DNA molecule comprising an open reading frame sequence that encodes a selectable marker polypeptide, wherein the DNA molecule in the coding strand comprises a translation start sequence for the selectable marker polypeptide having a GTG start codon or a TTG start codon, and wherein the ORF sequence that encodes the selectable marker protein has been mutated to replace at least half of its CpG dinucleotides as compared to the native ORF sequence that encodes the selectable marker protein. Further provided are such DNA molecules wherein the ORF sequence that encodes a selectable marker polypeptide is part of a multicistronic transcription unit that further comprises an open reading frame sequence encoding a polypeptide of interest. Also described are methods for obtaining host cells expressing a polypeptide of interest, wherein the host cells comprise the DNA molecules described herein.Type: ApplicationFiled: July 18, 2011Publication date: December 8, 2011Inventors: Arie Pieter Otte, Henricus Johannes Maria Van Blokland, Theodorus Hendrikus Jacobus Kwaks, Richard George Antonius Bernardus Sewalt
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Patent number: 8039230Abstract: The invention provides a DNA molecule comprising an open reading frame sequence that encodes a selectable marker polypeptide, wherein said DNA molecule in the coding strand comprises a translation start sequence for the selectable marker polypeptide having a GTG startcodon or a TTG startcodon, and wherein the open reading frame sequence that encodes the selectable marker protein has been mutated to replace at least half of its CpG dinucleotides as compared to the native open reading frame sequence that encodes the selectable marker protein.Type: GrantFiled: April 24, 2007Date of Patent: October 18, 2011Assignee: Chromagenics B.V.Inventors: Arie Pieter Otte, Henricus J. M. van Blokland, Theodorus H. J. Kwaks, Richard G. A. B. Sewalt
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Patent number: 7968700Abstract: The invention provides recombinant DNA molecules comprising novel expression augmenting DNA fragments and an expression cassette, said expression cassette comprising a heterologous promoter linked to a nucleic acid of interest. The invention further provides uses of the novel expression augmenting DNA fragments. The invention further provides methods for obtaining novel expression augmenting DNA fragments.Type: GrantFiled: March 20, 2007Date of Patent: June 28, 2011Assignee: Chromagenics B.V.Inventors: Arie Pieter Otte, Henricus Johannes Maria Van Blokland, Theodorus Hendrikus Jacobus Kwaks, Richard George Antonius Bernardus Sewalt
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Patent number: 7960143Abstract: Described is the production of proteins in a host cell. Even more specifically, described are methods for improving expression of two or more proteins in a cells or host cell. The methods are suited for production of, for example, recombinant antibodies that can be used in pharmaceutical preparations or as diagnostic tools. In certain embodiments, provided are methods for obtaining a cell that expresses two or more proteins comprising providing the cell with two or more protein expression units encoding two or more proteins, characterized in that at least two of the protein expression units comprise at least one STAR sequence.Type: GrantFiled: October 26, 2007Date of Patent: June 14, 2011Assignee: Chromagenics B.V.Inventors: Arie Pieter Otte, Arthur Leo Kruckeberg, Richard George Antonius Bernardus Sewalt
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Patent number: 7901908Abstract: Described is the production of proteins in a host cell. More specifically, described are methods for improving expression of two or more proteins in a cell or host cell. The methods are suited for production of, for example, recombinant antibodies that can be used in pharmaceutical preparations or as diagnostic tools. In one embodiment, provided is a method for obtaining a cell that expresses two or more proteins comprising providing the cell with two or more protein expression units encoding two or more proteins, characterized in that at least two of the protein expression units comprise at least one STAR sequence.Type: GrantFiled: October 26, 2007Date of Patent: March 8, 2011Assignee: ChromaGenics B.V.Inventors: Arie Pieter Otte, Arthur Leo Kruckeberg, Richard George Antonius Bernardus Sewalt