Patents by Inventor Brian Zambrowicz
Brian Zambrowicz 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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Publication number: 20240093316Abstract: Methods and compositions are provided herein for assessing CRISPR/Cas-mediated non-homologous end joining (NHEJ) activity and/or CRISPR/Cas-induced recombination of a target genomic locus with an exogenous donor nucleic acid in vivo and ex vivo. The methods and compositions employ cells and non-human animals comprising a Cas expression cassette such as a genomically integrated Cas expression cassette so that the Cas protein can be constitutively available or available in a tissue-specific or temporal-specific manner. Methods and compositions are also provided for making and using these non-human animals, including use of these non-human animals to assess CRISPR/Cas activity in vivo via adeno-associated virus (AAV)-mediated delivery of guide RNAs to the non-human animals.Type: ApplicationFiled: November 27, 2023Publication date: March 21, 2024Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Guochun Gong, Charleen Hunt, Daisuke Kajimura, Suzanne Hartford, Brian Zambrowicz
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Publication number: 20240084293Abstract: Cas-protein-ready tau biosensor cells, CRISPR/Cas synergistic activation mediator (SAM)-ready tau biosensor cells, and methods of making and using such cells to screen for genetic modifiers of tau seeding or aggregation are provided. Reagents and methods for sensitizing such cells to tau seeding activity or tau aggregation or for causing tau aggregation are also provided.Type: ApplicationFiled: November 6, 2023Publication date: March 14, 2024Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Marine Prissette, Matthew Koss, Wen Fury, Brian Zambrowicz
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Publication number: 20240076613Abstract: BANF1, PPP2CA, and ANKLE2 were identified as genes that promote tau aggregation when disrupted. Improved tauopathy models such as cells, tissues, or animals having mutations in or inhibition of expression of BANF1 and/or PPP2CA and/or ANKLE2 are provided. Methods of using such improved tauopathy models for assessing therapeutic candidates for the treatment of a tauopathy, methods of making the improved tauopathy models, and methods of accelerating or exacerbating tau aggregation in a tauopathy model are also provided.Type: ApplicationFiled: November 6, 2023Publication date: March 7, 2024Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Marine Prissette, Matthew Koss, Mathieu Desclaux, John McWhirter, Arijit Bhowmick, David Frendewey, Brian Zambrowicz, Claudia Racioppi
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Patent number: 11891618Abstract: Non-human animal cells and non-human animals comprising a humanized TTR locus comprising a beta-slip mutation and methods of using such non-human animal cells and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized TTR locus comprising a beta-slip mutation express a human transthyretin protein or a chimeric transthyretin protein, fragments of which are from human transthyretin. Methods are provided for using such non-human animals comprising a humanized TTR locus to assess in vivo efficacy of human-TTR-targeting reagents such as nuclease agents designed to target human TTR.Type: GrantFiled: June 3, 2020Date of Patent: February 6, 2024Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Jeffery Haines, Keith Crosby, Meghan Drummond Samuelson, David Frendewey, Brian Zambrowicz, Andrew J. Murphy
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Patent number: 11866794Abstract: Methods and compositions are provided herein for assessing CRISPR/Cas-mediated non-homologous end joining (NHEJ) activity and/or CRISPR/Cas-induced recombination of a target genomic locus with an exogenous donor nucleic acid in vivo and ex vivo. The methods and compositions employ cells and non-human animals comprising a Cas expression cassette such as a genomically integrated Cas expression cassette so that the Cas protein can be constitutively available or available in a tissue-specific or temporal-specific manner. Methods and compositions are also provided for making and using these non-human animals, including use of these non-human animals to assess CRISPR/Cas activity in vivo via adeno-associated virus (AAV)-mediated delivery of guide RNAs to the non-human animals.Type: GrantFiled: August 24, 2021Date of Patent: January 9, 2024Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Guochun Gong, Charleen Hunt, Daisuke Kajimura, Suzanne Hartford, Brian Zambrowicz
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Publication number: 20230416728Abstract: Cas-protein-ready tau biosensor cells, CRISPR/Cas synergistic activation mediator (SAM)-ready tau biosensor cells, and methods of making and using such cells to screen for genetic vulnerability associated with tau aggregation are provided.Type: ApplicationFiled: August 31, 2023Publication date: December 28, 2023Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Marine Prissette, Matthew Koss, Yu Bai, Brian Zambrowicz
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Patent number: 11845931Abstract: Cas-protein-ready tau biosensor cells, CRISPR/Cas synergistic activation mediator (SAM)-ready tau biosensor cells, and methods of making and using such cells to screen for genetic modifiers of tau seeding or aggregation are provided. Reagents and methods for sensitizing such cells to tau seeding activity or tau aggregation or for causing tau aggregation are also provided.Type: GrantFiled: March 17, 2020Date of Patent: December 19, 2023Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Marine Prissette, Matthew Koss, Wen Fury, Brian Zambrowicz
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Patent number: 11845957Abstract: BANF1, PPP2CA, and ANKLE2 were identified as genes that promote tau aggregation when disrupted. Improved tauopathy models such as cells, tissues, or animals having mutations in or inhibition of expression of BANF1 and/or PPP2CA and/or ANKLE2 are provided. Methods of using such improved tauopathy models for assessing therapeutic candidates for the treatment of a tauopathy, methods of making the improved tauopathy models, and methods of accelerating or exacerbating tau aggregation in a tauopathy model are also provided.Type: GrantFiled: June 12, 2020Date of Patent: December 19, 2023Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Marine Prissette, Matthew Koss, Mathieu Desclaux, John McWhirter, Arijit Bhowmick, David Frendewey, Brian Zambrowicz, Claudia Racioppi
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Publication number: 20230337645Abstract: Nuclease-mediated methods for expanding repeats already present at a genomic locus are provided. Non-human animal genomes, non-human animal cells, and non-human animals comprising a heterologous hexanucleotide repeat expansion sequence inserted at an endogenous C9orf72 locus and methods of making such non-human animal cells and non-human animals through nuclease-mediated repeat expansion are also provided. Methods of using the non-human animal cells or non-human animals to identify therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative disorders associated with repeat expansion at the C9orf72 locus are also provided.Type: ApplicationFiled: May 12, 2023Publication date: October 26, 2023Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Daisuke Kajimura, Aarti Sharma-Kanning, Brittany Dubose, Gustavo Droguett, Chia-Jen Siao, Junko Kuno, David Frendewey, Brian Zambrowicz
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Patent number: 11781131Abstract: Cas-protein-ready tau bio sensor cells, CRISPR/Cas synergistic activation mediator (SAM)-ready tau biosensor cells, and methods of making and using such cells to screen for genetic vulnerability associated with tau aggregation are provided.Type: GrantFiled: March 17, 2020Date of Patent: October 10, 2023Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Marine Prissette, Matthew Koss, Yu Bai, Brian Zambrowicz
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Publication number: 20230293727Abstract: Provided herein are methods of inhibiting tau aggregation in a cell or a subject, comprising administering a LEM domain-containing protein 2 (LEMD2), a charged multivesicular body protein 7 (CHMP7), or an inner nuclear membrane protein Man 1 (LEMD3) or a nucleic acid encoding the LEMD2, the CHMP7, or the LEMD3 to the cell or the subject. Also provided herein are methods of treating or preventing a tauopathy in a subject, comprising administering LEMD2, CHMP7, or LEMD3 or a nucleic acid encoding the LEMD2, the CHMP7, or the LEMD3 to the subject, wherein the LEMD2, the CHMP7, or the LEMD3 inhibits tau aggregation in a cell in the subject. Also provided are nucleic acids encoding LEMD2, CHMP7, or LEMD3 (e.g., in an expression construct and operably linked to a heterologous promoter).Type: ApplicationFiled: October 26, 2022Publication date: September 21, 2023Inventors: Marine Prissette, Wen Fury, Daria Fedorova, Claudia Racioppi, Brian Zambrowicz
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Publication number: 20230232797Abstract: Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized albumin (ALB) locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized albumin locus express a human albumin protein or a chimeric albumin protein, fragments of which are from human albumin. Methods are provided for using such non-human animals comprising a humanized albumin locus to assess in vivo efficacy of human-albumin-targeting reagents such as nuclease agents designed to target human albumin.Type: ApplicationFiled: February 27, 2023Publication date: July 27, 2023Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Qing Fang, Chia-Jen Siao, Dan Chalothorn, KehDih Lai, Leah Sabin, Rachel Sattler, Brian Zambrowicz, Lori Morton
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Patent number: 11690362Abstract: Nuclease-mediated methods for expanding repeats already present at a genomic locus are provided. Non-human animal genomes, non-human animal cells, and non-human animals comprising a heterologous hexanucleotide repeat expansion sequence inserted at an endogenous C9orf72 locus and methods of making such non-human animal cells and non-human animals through nuclease-mediated repeat expansion are also provided. Methods of using the non-human animal cells or non-human animals to identify therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative disorders associated with repeat expansion at the C9orf72 locus are also provided.Type: GrantFiled: December 13, 2019Date of Patent: July 4, 2023Assignee: Regeneran Pharmaceuticals, Inc.Inventors: Daisuke Kajimura, Aarti Sharma-Kanning, Brittany Dubose, Gustavo Droguett, Chia-Jen Siao, Junko Kuno, David Frendewey, Brian Zambrowicz
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Publication number: 20230123787Abstract: This disclosure relates to an animal model of human disease. More specifically, this disclosure relates to a rodent model of mood disorders such as unipolar depression and an anxiety disorder. Disclosed herein are genetically modified rodent animals that carry a humanized G protein-coupled receptor 156 (GPR156) gene that encodes a mutant human GPR156 protein comprising Asp at an amino acid position corresponding to position 533 in a full length wild type human GPR156 protein.Type: ApplicationFiled: August 10, 2022Publication date: April 20, 2023Applicant: REGENERON PHARMACEUTICALS, INC.Inventors: Meghan Drummond Samuelson, Brian Zambrowicz, Ka-Man Venus Lai, Charleen Hunt, Susannah Brydges, Andrew J. Murphy, Claudia Gonzaga-Jauregui, Jose Rojas, Nicole Alessandri-Haber, Robert Breese, Susan D. Croll
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Publication number: 20230123296Abstract: Non-human animal cells and non-human animals comprising CRISPR/Cas synergistic activation mediator system components and methods of making and using such non-human animal cells and non-human animals are provided. Methods are provided for using such non-human animals to increase expression of target genes in vivo and to assess CRISPR/Cas synergistic activation mediator systems for the ability to increase expression of target genes in vivo.Type: ApplicationFiled: November 1, 2022Publication date: April 20, 2023Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Charleen Hunt, Suzanne Hartford, Guochun Gong, Brian Zambrowicz
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Publication number: 20230114649Abstract: The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a human chromosome 9 open reading frame 72 (C9orf72) gene, as well as methods of inhibiting expression of a C9orf72 gene and methods of treating subjects having a C9orf72-associated disease or disorder, e.g., C9orf72 amyotrophic lateral sclerosis/frontotemporal dementia or Huntington-Like Syndrome Due To C9orf72 Expansions, using such dsRNAi agents and compositions.Type: ApplicationFiled: June 9, 2022Publication date: April 13, 2023Inventors: Elane Fishilevich, Stuart Milstein, Kirk Brown, Tracy Zimmermann, James D. McIninch, David Frendewey, Eric Chiao, Aarti Sharma-Kanning, Anthony Gagliardi, Gustavo Droguett, Brittany Dubose, Brian Zambrowicz
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Patent number: 11622547Abstract: Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized albumin (ALB) locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized albumin locus express a human albumin protein or a chimeric albumin protein, fragments of which are from human albumin. Methods are provided for using such non-human animals comprising a humanized albumin locus to assess in vivo efficacy of human-albumin-targeting reagents such as nuclease agents designed to target human albumin.Type: GrantFiled: June 5, 2020Date of Patent: April 11, 2023Assignee: Regeneran Pharmaceuticals, Inc.Inventors: Qing Fang, Chia-Jen Siao, Dan Chalothorn, KehDih Lai, Leah Sabin, Rachel Sattler, Brian Zambrowicz, Lori Morton
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Publication number: 20230102342Abstract: Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized TTR locus comprising a V30M mutation and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized TTR locus express a human TTR protein or a chimeric TTR protein, fragments of which are from human TTR. Methods are provided for using such non-human animals comprising a humanized TTR locus to assess in vivo efficacy of human-TTR-targeting reagents such as nuclease agents designed to target human TTR.Type: ApplicationFiled: March 23, 2021Publication date: March 30, 2023Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Meghan Drummond Samuelson, Jeffery Haines, Charleen Hunt, Guochun Gong, Brian Zambrowicz
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Publication number: 20230078551Abstract: Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized TTR locus and methods of using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized TTR locus express a human transthyretin protein or a chimeric transthyretin protein, fragments of which are from human transthyretin. Methods are provided for using such non-human animals comprising a humanized TTR locus to assess in vivo efficacy of human-TTR-targeting reagents such as nuclease agents designed to target human TTR. Methods are also provided for making such non-human animals comprising a humanized TTR locus.Type: ApplicationFiled: November 22, 2022Publication date: March 16, 2023Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Meghan Drummond Samuelson, Jeffery Haines, Suzanne Hartford, David Frendewey, Brian Zambrowicz, Andrew J. Murphy
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Publication number: 20230001019Abstract: Nucleic acid constructs and compositions that allow insertion and/or expression of a retinoschisin coding sequence are provided. Nuclease agents targeting RS1 loci are provided. Compositions and methods of using such constructs for integration into a target genomic locus and/or expression in a cell are also provided. Methods of treating X-linked juvenile retinoschisis using the nucleic acid constructs and compositions are also provided.Type: ApplicationFiled: November 7, 2020Publication date: January 5, 2023Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Charleen Hunt, Yang Liu, Guochun Gong, Carmelo Romano, Brian Zambrowicz