Patents Assigned to Uniqure IP B.V.
  • Publication number: 20240093231
    Abstract: The present invention relates to the production of adeno-associated viral vectors in insect cells. The insect cells therefore comprise a first nucleotide sequence encoding the adeno-associated virus (AAV) capsid proteins, whereby the initiation codon for translation of the AAV VP1 capsid protein is an AUG. Upstream of the VP1 open reading frame an alternative out of frame start codon is placed such that translation initiation of the VP1 protein is modified, i.e. reduced, to allow production of VP1:VP2:VP3 in a good stoichiometry resulting in AAV with high potency.
    Type: Application
    Filed: May 3, 2023
    Publication date: March 21, 2024
    Applicant: uniQure IP B.V.
    Inventors: David Johannes Francois Du Plessis, Olivier Ter Brake, Sebastiaan Menno Bosma, Harald Peter Albert Petry, Jacek Lubelski
  • Publication number: 20230416778
    Abstract: The present invention relates nucleic acid constructs for the production of recombinant parvoviral (e.g. adeno-associated viral) vectors in insect cells, to insect cells comprising such constructs and to methods wherein the cells are used to produce recombinant parvoviral virions. The insect cells preferably comprise a first nucleotide sequence encoding the parvoviral rep proteins whereby the initiation codon for translation of the parvoviral Rep78 protein is a suboptimal initiation codon that effects partial exon skipping upon expression in insect cells. The insect cell further comprises a second nucleotide sequence comprising at least one parvoviral (AA V) inverted terminal repeat (ITR) nucleotide sequence and a third nucleotide sequence comprising a sequences coding for the parvoviral capsid proteins.
    Type: Application
    Filed: March 7, 2023
    Publication date: December 28, 2023
    Applicant: uniQure IP B.V.
    Inventors: Wilhelmus Theodorus Johannes Maria Christiaan Hermens, Saskia Jacoba Petronella Haast, Dennis Johan Biesmans, Andrew Christian Bakker
  • Patent number: 11780886
    Abstract: The present invention relates to production of parvoviral vectors to produce adeno-associated virus (AAV) for gene therapy. In particular the invention relates to improvements in parvoviral vectors that increase the packaging capacity, production efficiency, and infectivity of AAV virions that is necessary for large scale manufacturing of AAV for clinical purposes.
    Type: Grant
    Filed: June 24, 2020
    Date of Patent: October 10, 2023
    Assignee: uniQure IP B.V.
    Inventor: David Johannes Francois Du Plessis
  • Patent number: 11667931
    Abstract: The present invention relates to the production of adeno-associated viral vectors in insect cells. The insect cells therefore comprise a first nucleotide sequence encoding the adeno-associated virus (AAV) capsid proteins, whereby the initiation codon for translation of the AAV VP1 capsid protein is an AUG. Upstream of the VP1 open reading frame an alternative out of frame start codon is placed such that translation initiation of the VP1 protein is modified, i.e. reduced, to allow production of VP1:VP2:VP3 in a good stoichiometry resulting in AAV with high potency.
    Type: Grant
    Filed: January 15, 2020
    Date of Patent: June 6, 2023
    Assignee: uniQure IP B.V.
    Inventors: David Johannes Francois Du Plessis, Olivier Ter Brake, Sebastiaan Menno Bosma, Harald Peter Albert Petry, Jacek Lubelski
  • Publication number: 20230119344
    Abstract: The present invention provides for a double stranded RNA comprising a first RNA sequence and a second RNA sequence wherein the first and second RNA sequence are substantially complementary, wherein the first RNA sequence has a sequence length of at least 19 nucleotides and is substantially complementary to SEQ ID NO. 1. Said double stranded RNA is for use in inducing RNAi against Huntingtin exon 1 sequences. The double stranded RNA of to the invention was capable of reducing neuronal cell death and huntingtin aggregates in an animal model.
    Type: Application
    Filed: May 24, 2022
    Publication date: April 20, 2023
    Applicant: Uniqure IP B.V.
    Inventors: Pavlina Stefanova KONSTANTINOVA, Jana MINARIKOV√Ā
  • Patent number: 11613765
    Abstract: The present invention relates nucleic acid constructs for the production of recombinant parvoviral (e.g. adeno-associated viral) vectors in insect cells, to insect cells comprising such constructs and to methods wherein the cells are used to produce recombinant parvoviral virions. The insect cells preferably comprise a first nucleotide sequence encoding the parvoviral rep proteins whereby the initiation codon for translation of the parvoviral Rep78 protein is a suboptimal initiation codon that effects partial exon skipping upon expression in insect cells. The insect cell further comprises a second nucleotide sequence comprising at least one parvoviral (AA V) inverted terminal repeat (ITR) nucleotide sequence and a third nucleotide sequence comprising a sequences coding for the parvoviral capsid proteins.
    Type: Grant
    Filed: December 14, 2020
    Date of Patent: March 28, 2023
    Assignee: UNIQURE IP B.V.
    Inventors: Wilhelmus Theodorus Johannes Maria Christiaan Hermens, Saskia Jacoba Petronella Haast, Dennis Johan Biesmans, Andrew Christian Bakker
  • Publication number: 20220395545
    Abstract: The present invention relates to means and method for AAV based gene therapies in humans. In particular, the present invention relates to the treatment of human patients that may be suspected to have antibodies directed against the AAV intended for use in the treatment.
    Type: Application
    Filed: June 30, 2022
    Publication date: December 15, 2022
    Applicant: uniQure IP B.V.
    Inventors: Bart Antonius NIJMEIJER, Valerie FERREIRA
  • Patent number: 11452749
    Abstract: The present invention relates to means and method for AAV based gene therapies in humans. In particular, the present invention relates to the treatment of human patients that may be suspected to have antibodies directed against the AAV intended for use in the treatment.
    Type: Grant
    Filed: July 10, 2018
    Date of Patent: September 27, 2022
    Assignee: UNIQURE IP B.V.
    Inventors: Bart Antonius Nijmeijer, Valerie Ferreira
  • Publication number: 20220251520
    Abstract: The present invention relates to production of proteins in insect cells whereby repeated coding sequences are used in baculoviral vectors. In particular the invention relates to the production of parvoviral vectors that may be used in gene therapy and to improvements in expression of the viral rep proteins that increase the productivity of parvoviral vectors.
    Type: Application
    Filed: April 15, 2022
    Publication date: August 11, 2022
    Applicant: uniQure IP B.V.
    Inventors: Andrew Christian BAKKER, Wilhelmus Theodorus Johannes Maria Christiaan HERMENS
  • Patent number: 11371044
    Abstract: The present invention provides for a double stranded RNA comprising a first RNA sequence and a second RNA sequence wherein the first and second RNA sequence are substantially complementary, wherein the first RNA sequence has a sequence length of at least 19 nucleotides and is substantially complementary to SEQ ID NO. 1. Said double stranded RNA is for use in inducing RNAi against Huntingtin exon 1 sequences. The double stranded RNA of to the invention was capable of reducing neuronal cell death and huntingtin aggregates in an animal model.
    Type: Grant
    Filed: July 15, 2020
    Date of Patent: June 28, 2022
    Assignee: UNIQURE IP B.V.
    Inventors: Pavlina Stefanova Konstantinova, Jana Miniarikov√°
  • Patent number: 11306291
    Abstract: The present invention relates to production of proteins in insect cells whereby repeated coding sequences are used in baculoviral vectors. In particular the invention relates to the production of parvoviral vectors that may be used in gene therapy and to improvements in expression of the viral rep proteins that increase the productivity of parvoviral vectors.
    Type: Grant
    Filed: December 11, 2018
    Date of Patent: April 19, 2022
    Assignee: UNIQURE IP B.V.
    Inventors: Andrew Christian Bakker, Wilhelmus Theodorus Johannes Maria Christiaan Hermens
  • Publication number: 20210353776
    Abstract: Upon administration of rAAV vectors the humoral immune response (neutralizing antibodies) is the first barrier that needs to be overcome. Surprisingly it was found that by using immunoadsorption for depletion of immunoglobulins from the blood (plasma), subjects can be highly efficiently treated with rAAV vectors, i.e. obtain highly efficient transduction after rAAV vector administration, in spite of the presence of high levels of nAb.
    Type: Application
    Filed: June 3, 2021
    Publication date: November 18, 2021
    Applicant: uniQure IP B.V.
    Inventor: Valerie FERREIRA
  • Publication number: 20210332447
    Abstract: The current invention relates to nucleic acid impurities in a composition comprising a parvoviral vector. In particular, the current invention shows that DNA impurities are not randomly encapsulated within a parvoviral virion. The invention therefore relates to a method for identifying and quantifying a nucleic acid impurity in a composition comprising a parvoviral vector. Finally, the current invention relates to method of determining whether a composition comprising a parvoviral vector is regarded as clinically pure.
    Type: Application
    Filed: May 6, 2021
    Publication date: October 28, 2021
    Applicant: uniQure IP B.V.
    Inventors: Jacek LUBELSKI, Wilhelmus Theodorus Johannes Maria Christiaan HERMENS
  • Publication number: 20210222198
    Abstract: The present invention relates to the production of adeno-associated viral vectors in insect cells. The insect cells therefore comprise a first nucleotide sequence encoding the adeno-associated virus (AAV) capsid proteins, whereby the initiation codon for translation of the AAV VP1 capsid protein is a non-ATG, suboptimal initiation codon and wherein the coding sequence for one or more amino acid residues have been inserted between the suboptimal translation initiation codon and the codon encoding the amino acid residue that corresponds to the amino acid residue at position 2 of the wild type capsid amino acid sequence of which the first amino acid residue is alanine, glycine, valine, aspartic acid or glutamic acid.
    Type: Application
    Filed: November 5, 2020
    Publication date: July 22, 2021
    Applicant: Uniqure IP B.V.
    Inventors: Jacek LUBELSKI, Sebastiaan Bosma, Harald Peter Albert Petry, Wilhelmus Theodorus Johannes Maria Christ Hermens
  • Patent number: 11060070
    Abstract: Nucleic acids encoding Parvoviral Rep proteins with a mutated nuclear localization signal (NLS) are provided. Also provided is a nucleic acid comprising a nucleotide sequence encoding a Parvoviral Rep protein with a mutated zinc finger domain and a nucleic acid comprising a nucleotide sequence encoding a Parvoviral Rep protein comprising an amino acid mutation at position 43, 57, 79, 97, 120, 179, 305, 484, 493 or 571 with reference to SEQ ID NO: 2. Nucleic acid constructs and cells, such as insect cells, comprising the nucleic acids are provided as well as a method for producing a recombinant Parvoviral virion using the nucleic acids.
    Type: Grant
    Filed: July 17, 2019
    Date of Patent: July 13, 2021
    Assignee: UNIQURE IP B.V.
    Inventors: Yvet Noordman, Jacek Lubelski, Andrew Christian Bakker
  • Patent number: 11033639
    Abstract: Upon administration of rAAV vectors the humoral immune response (neutralizing antibodies) is the first barrier that needs to be overcome. Surprisingly it was found that by using immunoadsorption for depletion of immunoglobulins from the blood (plasma), subjects can be highly efficiently treated with rAAV vectors, i.e. obtain highly efficient transduction after rAAV vector administration, in spite of the presence of high levels of nAb.
    Type: Grant
    Filed: April 15, 2019
    Date of Patent: June 15, 2021
    Assignee: UNIQURE IP B.V.
    Inventor: Valerie Ferreira
  • Patent number: 11021762
    Abstract: The current invention relates to nucleic acid impurities in a composition comprising a parvoviral vector. In particular, the current invention shows that DNA impurities are not randomly encapsulated within a parvoviral virion. The invention therefore relates to a method for identifying and quantifying a nucleic acid impurity in a composition comprising a parvoviral vector. Finally, the current invention relates to method of determining whether a composition comprising a parvoviral vector is regarded as clinically pure.
    Type: Grant
    Filed: November 27, 2015
    Date of Patent: June 1, 2021
    Assignee: UNIQURE IP B.V.
    Inventors: Jacek Lubelski, Wilhelmus Theodorus Johannes Maria Christiaan Hermens
  • Publication number: 20210147874
    Abstract: The present invention relates nucleic acid constructs for the production of recombinant parvoviral (e.g. adeno-associated viral) vectors in insect cells, to insect cells comprising such constructs and to methods wherein the cells are used to produce recombinant parvoviral virions. The insect cells preferably comprise a first nucleotide sequence encoding the parvoviral rep proteins whereby the initiation codon for translation of the parvoviral Rep78 protein is a suboptimal initiation codon that effects partial exon skipping upon expression in insect cells. The insect cell further comprises a second nucleotide sequence comprising at least one parvoviral (AA V) inverted terminal repeat (ITR) nucleotide sequence and a third nucleotide sequence comprising a sequences coding for the parvoviral capsid proteins.
    Type: Application
    Filed: December 14, 2020
    Publication date: May 20, 2021
    Applicant: uniQure IP B.V.
    Inventors: Wilhelmus Johannes Theodorus Maria Christiaan Hermens, Saskia Jacoba Petronella Haast, Dennis Johan Biesmans, Andrew Christian Bakker
  • Patent number: 10865423
    Abstract: The present invention relates nucleic acid constructs for the production of recombinant parvoviral (e.g. adeno-associated viral) vectors in insect cells, to insect cells comprising such constructs and to methods wherein the cells are used to produce recombinant parvoviral virions. The insect cells preferably comprise a first nucleotide sequence encoding the parvoviral rep proteins whereby the initiation codon for translation of the parvoviral Rep78 protein is a suboptimal initiation codon that effects partial exon skipping upon expression in insect cells. The insect cell further comprises a second nucleotide sequence comprising at least one parvoviral (AAV) inverted terminal repeat (ITR) nucleotide sequence and a third nucleotide sequence comprising a sequences coding for the parvoviral capsid proteins.
    Type: Grant
    Filed: January 10, 2020
    Date of Patent: December 15, 2020
    Assignee: uniQure IP B.V.
    Inventors: Wilhelmus Theodorus Johannes Maria Christiaan Hermens, Saskia Jacoba Petronella Haast, Dennis Johan Biesmans, Andrew Christian Bakker
  • Publication number: 20200360535
    Abstract: Described herein are saturating agents, AAV gene therapy vectors, and therapeutic agents, as well as methods and kits comprising the same.
    Type: Application
    Filed: June 9, 2020
    Publication date: November 19, 2020
    Applicant: uniQure IP B.V.
    Inventor: Valerie FERREIRA