Patents by Inventor Henricus Johannes Maria van Blokland
Henricus Johannes Maria van Blokland 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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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: 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: 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: 7825232Abstract: The invention provides a novel anti-repressor element, which is useful for improving expression of nucleic acid in host cells. Methods using the novel anti-repressor element for producing a protein of interest are also provided. The invention also provides new configurations of expression cassettes comprising anti-repressor elements.Type: GrantFiled: July 7, 2005Date of Patent: November 2, 2010Assignee: Chromagenics B.V.Inventors: Arie Pieter Otte, Theodorus Hendrikus Jacobus Kwaks, Richard George Antonius Bernardus Sewalt, Henricus Johannes Maria Van Blokland
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Publication number: 20100190207Abstract: 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: ApplicationFiled: March 20, 2007Publication date: July 29, 2010Inventors: Arie Pieter Otte, Henricus Johannes Maria Van Blokland, Theodorus Hendrikus Jacobus Kwaks, Richard George Antonius Bernardus Sewalt
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Publication number: 20100136616Abstract: The invention provides a DNA molecule comprising a multicistronic transcription unit coding for i) a polypeptide of interest, and for ii) a selectable marker polypeptide functional in a eukaryotic host cell, wherein the polypeptide of interest has a translation initiation sequence separate from that of the selectable marker polypeptide, and wherein the coding sequence for the polypeptide of interest is upstream from the coding sequence for the selectable marker polypeptide in said multicistronic transcription unit, and wherein an internal ribosome entry site (IRES) is present downstream from the coding sequence for the polypeptide of interest and upstream from the coding sequence for the selectable marker polypeptide, and wherein the nucleic acid sequence coding for the selectable marker polypeptide in the coding strand comprises a GTG or a TTG startcodon.Type: ApplicationFiled: February 21, 2007Publication date: June 3, 2010Inventors: Arie Pieter Otte, Henricus Johannes Maria Van Blokland, Theodorus Hendrikus Jacobus Kwaks, Richard George Anotius Bernardus Sewalt
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Publication number: 20090098601Abstract: 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: ApplicationFiled: April 24, 2007Publication date: April 16, 2009Inventors: Arie Pieter Otte, Henricus Johannes Maria Van Blokland, Theodorus Hendrikus Jacobus Kwaks, Richard George Antonius Bernardus Sewalt
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Publication number: 20090011468Abstract: 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: ApplicationFiled: July 11, 2008Publication date: January 8, 2009Applicant: Chromagenics B.V.Inventors: Arie Pieter Otte, Henricus Johannes Maria Van Blokland
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Patent number: 7413896Abstract: 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: June 20, 2005Date of Patent: August 19, 2008Assignee: Chromagenics B.V.Inventors: Arie Pieter Otte, Henricus Johannes Maria van Blokland