Patents by Inventor David M. Valenzuela
David M. Valenzuela 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: 11932859Abstract: Methods are provided herein for assembling at least two nucleic acids using a sequence specific nuclease agent (e.g., a gRNA-Cas complex) to create end sequences having complementarity and subsequently assembling the overlapping complementary sequences. The nuclease agent (e.g., a gRNA-Cas complex) can create double strand breaks in dsDNA in order to create overlapping end sequences or can create nicks on each strand to produce complementary overhanging end sequences. Assembly using the method described herein can assemble any nucleic acids having overlapping sequences or can use a joiner oligo to assemble sequences without complementary ends.Type: GrantFiled: March 11, 2020Date of Patent: March 19, 2024Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Chris Schoenherr, John McWhirter, Corey Momont, Caitlin L. Goshert, Lynn Macdonald, Gregg S. Warshaw, Jose F. Rojas, Ka-Man Venus Lai, David M. Valenzuela, Andrew J. Murphy
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Publication number: 20240052365Abstract: Compositions and methods are provided for modifying a genomic locus of interest in a eukaryotic cell, a mammalian cell, a human cell or a non-human mammalian cell using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Further methods combine the use of the LTVEC with a CRISPR/Cas system. Compositions and methods for generating a genetically modified non-human animal comprising one or more targeted genetic modifications in their germline are also provided.Type: ApplicationFiled: October 11, 2023Publication date: February 15, 2024Applicant: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Wojtek Auerbach, Ka-Man Venus Lai, David M. Valenzuela, George D. Yancopoulos
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Patent number: 11820997Abstract: Compositions and methods are provided for modifying a genomic locus of interest in a eukaryotic cell, a mammalian cell, a human cell or a non-human mammalian cell using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Further methods combine the use of the LTVEC with a CRISPR/Cas system. Compositions and methods for generating a genetically modified non-human animal comprising one or more targeted genetic modifications in their germline are also provided.Type: GrantFiled: June 3, 2020Date of Patent: November 21, 2023Assignee: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Wojtek Auerbach, Ka-Man Venus Lai, David M. Valenzuela, George D. Yancopoulos
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Publication number: 20230332185Abstract: Compositions and methods are provided for creating and promoting biallelic targeted modifications to genomes within cells and for producing non-human animals comprising the modified genomes. Also provided are compositions and methods for modifying a genome within a cell that is heterozygous for an allele to become homozygous for that allele. The methods make use of Cas proteins and two or more guide RNAs that target different locations within the same genomic target locus. Also provided are methods of identifying cells with modified genomes.Type: ApplicationFiled: May 15, 2023Publication date: October 19, 2023Applicant: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Ka-Man Venus Lai, Wojtek Auerbach, Gustavo Droguett, Anthony Gagliardi, David M. Valenzuela, Vera Voronina, Lynn Macdonald, Andrew J. Murphy, George D. Yancopoulos
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Patent number: 11697828Abstract: Compositions and methods are provided for creating and promoting biallelic targeted modifications to genomes within cells and for producing non-human animals comprising the modified genomes. Also provided are compositions and methods for modifying a genome within a cell that is heterozygous for an allele to become homozygous for that allele. The methods make use of Cas proteins and two or more guide RNAs that target different locations within the same genomic target locus. Also provided are methods of identifying cells with modified genomes.Type: GrantFiled: September 16, 2019Date of Patent: July 11, 2023Assignee: Regeneran Pharmaceuticals, Inc.Inventors: David Frendewey, Ka-Man Venus Lai, Wojtek Auerbach, Gustavo Droguett, Anthony Gagliardi, David M. Valenzuela, Vera Voronina, Lynn Macdonald, Andrew J. Murphy, George D. Yancopoulos
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Publication number: 20230189771Abstract: Genetically modified non-human animals are provided that exhibit a functional lack of one or more IncRNAs. Methods and compositions for disrupting, deleting, and/or replacing IncRNA-encoding sequences are provided. Genetically modified mice that age prematurely are provided. Also provided are cells, tissues and embryos that are genetically modified to comprise a loss-of-function of one or more IncRNAs.Type: ApplicationFiled: November 16, 2022Publication date: June 22, 2023Inventors: Ka-Man Venus Lai, Guochun Gong, John Rinn, David Frendewey, David M. Valenzuela
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Patent number: 11547101Abstract: A non-human animal model for neurodegenerative and/or inflammatory diseases is provided, which non-human animal comprises a disruption in a C9ORF72 locus. In particular, non-human animals described herein comprise a deletion of an entire coding sequence of a C9ORF72 locus. Methods of identifying therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative (e.g., amyotrophic lateral sclerosis (ALS, also referred to as Lou Gehrig's disease) and frontotemporal dementia (FTD)), autoimmune and/or inflammatory diseases (e.g., SLE, glomerulonephritis) are also provided.Type: GrantFiled: March 27, 2019Date of Patent: January 10, 2023Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Amanda Atanasio, Burcin Ikiz, Guochun Gong, Michael L. Lacroix-Fralish, Ka-Man Venus Lai, David M. Valenzuela
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Patent number: 11547100Abstract: Genetically modified non-human animals are provided that exhibit a functional lack of one or more lncRNAs. Methods and compositions for disrupting, deleting, and/or replacing lncRNA-encoding sequences are provided. Genetically modified mice that age prematurely are provided. Also provided are cells, tissues and embryos that are genetically modified to comprise a loss-of-function of one or more lncRNAs.Type: GrantFiled: November 30, 2016Date of Patent: January 10, 2023Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Ka-Man Venus Lai, Guochun Gong, John Rinn, David Frendewey, David M. Valenzuela
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Publication number: 20210301301Abstract: Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and/or the rat Rag2/Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.Type: ApplicationFiled: March 9, 2021Publication date: September 30, 2021Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Jeffrey D. Lee, Alexander O. Mujica, Wojtek Auerbach, Ka-Man Venus Lai, David M. Valenzuela, George D. Yancopoulos
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Publication number: 20210130846Abstract: Compositions and methods are provided for making rat pluripotent and totipotent cells, including rat embryonic stem (ES) cells. Compositions and methods for improving efficiency or frequency of germline transmission of genetic modifications in rats are provided. Such methods and compositions comprise an in vitro culture comprising a feeder cell layer and a population of rat ES cells or a rat ES cell line, wherein the in vitro culture conditions maintain pluripotency of the ES cell and comprises a media having mouse leukemia inhibitory factor (LIF) or an active variant or fragment thereof. Various methods of establishing such rat ES cell lines are further provided. Methods of selecting genetically modified rat ES cells are also provided, along with various methods to generate a transgenic rat from the genetically modified rat ES cells provided herein. Various kits and articles of manufacture are further provided.Type: ApplicationFiled: December 10, 2020Publication date: May 6, 2021Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Jeffrey D. Lee, Wojtek Auerbach, David Heslin, David Frendewey, Ka-Man Venus Lai, David M. Valenzuela
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Patent number: 10988776Abstract: Methods of creating mutations in genomic exons by inserting introns into the genomic exons via homologous recombination. Also, methods are provided for introducing modifications into genomic exons by inserting introns into the genomic exons via homologous recombination such that a mature mRNA transcript produced from a genomic region of the genome comprising the genomic exon does not contain the modification are provided. The methods provide for a rapid method for introducing mutations and/or modifications of any type into a mammalian cell genome.Type: GrantFiled: August 29, 2018Date of Patent: April 27, 2021Assignee: REGENERON PHARMACEUTICALS, INC.Inventors: Aris N. Economides, David M. Valenzuela, Samuel Davis, George Yancopoulos
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Patent number: 10975390Abstract: Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and/or the rat Rag2/Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.Type: GrantFiled: June 25, 2019Date of Patent: April 13, 2021Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Jeffrey D. Lee, Alexander O. Mujica, Wojtek Auerbach, Ka-Man Venus Lai, David M. Valenzuela, George D. Yancopoulos
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Patent number: 10894965Abstract: Compositions and methods are provided for making rat pluripotent and totipotent cells, including rat embryonic stem (ES) cells. Compositions and methods for improving efficiency or frequency of germline transmission of genetic modifications in rats are provided. Such methods and compositions comprise an in vitro culture comprising a feeder cell layer and a population of rat ES cells or a rat ES cell line, wherein the in vitro culture conditions maintain pluripotency of the ES cell and comprises a media having mouse leukemia inhibitory factor (LIF) or an active variant or fragment thereof. Various methods of establishing such rat ES cell lines are further provided. Methods of selecting genetically modified rat ES cells are also provided, along with various methods to generate a transgenic rat from the genetically modified rat ES cells provided herein. Various kits and articles of manufacture are further provided.Type: GrantFiled: May 2, 2019Date of Patent: January 19, 2021Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Jeffrey D. Lee, Wojtek Auerbach, David Heslin, David Frendewey, Ka-Man Venus Lai, David M. Valenzuela
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Publication number: 20200370054Abstract: A non-human animal (e.g., a rodent) model for diseases associated with a C9ORF72 heterologous hexanucleotide repeat expansion sequence is provided, which non-human animal comprises a heterologous hexanucleotide repeat (GGGGCC) in an endogenous C9ORF72 locus. A non-human animal disclosed herein comprising a heterologous hexanucleotide repeat expansion sequence comprising at least one instance, e.g., repeat, of a hexanucleotide (GGGGCC) sequence may further exhibit a characteristic and/or phenotype associated with one or more neurodegenerative disorders (e.g., amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD), etc.). Methods of identifying therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative (e.g., amyotrophic lateral sclerosis (ALS, also referred to as Lou Gehrig's disease) and frontotemporal dementia (FTD)) are also provided.Type: ApplicationFiled: August 5, 2020Publication date: November 26, 2020Inventors: David Heslin, Roxanne Ally, Chia-Jen Siao, Ka-Man Venus Lai, David M. Valenzuela, Chunguang Guo, Michael LaCroix-Fralish, Lynn Macdonald, Aarti Sharma-Kanning, Daisuke Kajimura, Gustavo Droguett, David Frendewey, Alexander O. Mujica
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Patent number: 10781453Abstract: A non-human animal (e.g., a rodent) model for diseases associated with a C9ORF72 heterologous hexanucleotide repeat expansion sequence is provided, which non-human animal comprises a heterologous hexanucleotide repeat (GGGGCC) in an endogenous C9ORF72 locus. A non-human animal disclosed herein comprising a heterologous hexanucleotide repeat expansion sequence comprising at least one instance, e.g., repeat, of a hexanucleotide (GGGGCC) sequence may further exhibit a characteristic and/or phenotype associated with one or more neurodegenerative disorders (e.g., amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD), etc.). Methods of identifying therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative (e.g., amyotrophic lateral sclerosis (ALS, also referred to as Lou Gehrig's disease) and frontotemporal dementia (FTD)) are also provided.Type: GrantFiled: September 29, 2017Date of Patent: September 22, 2020Assignee: Regeneron Pharmaceuticals, Inc.Inventors: David Heslin, Roxanne Ally, Chia-Jen Siao, Ka-Man Venus Lai, David M. Valenzuela, Aarti Sharma-Kanning, Daisuke Kajimura, Gustavo Droguett, David Frendewey, Alexander O. Mujica
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Publication number: 20200291425Abstract: Compositions and methods are provided for modifying a genomic locus of interest in a eukaryotic cell, a mammalian cell, a human cell or a non-human mammalian cell using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Further methods combine the use of the LTVEC with a CRISPR/Cas system. Compositions and methods for generating a genetically modified non-human animal comprising one or more targeted genetic modifications in their germline are also provided.Type: ApplicationFiled: June 3, 2020Publication date: September 17, 2020Applicant: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Wojtek Auerbach, Ka-Man Venus Lai, David M. Valenzuela, George D. Yancopoulos
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Patent number: 10711280Abstract: Compositions and methods are provided for modifying a genomic locus of interest in a eukaryotic cell, a mammalian cell, a human cell or a non-human mammalian cell using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Further methods combine the use of the LTVEC with a CRISPR/Cas system. Compositions and methods for generating a genetically modified non-human animal comprising one or more targeted genetic modifications in their germline are also provided.Type: GrantFiled: December 18, 2018Date of Patent: July 14, 2020Assignee: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Wojtek Auerbach, Ka-Man Venus Lai, David M. Valenzuela, George D. Yancopoulos
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Publication number: 20200208161Abstract: Methods are provided herein for assembling at least two nucleic acids using a sequence specific nuclease agent (e.g., a gRNA-Cas complex) to create end sequences having complementarity and subsequently assembling the overlapping complementary sequences. The nuclease agent (e.g., a gRNA-Cas complex) can create double strand breaks in dsDNA in order to create overlapping end sequences or can create nicks on each strand to produce complementary overhanging end sequences. Assembly using the method described herein can assemble any nucleic acids having overlapping sequences or can use a joiner oligo to assemble sequences without complementary ends.Type: ApplicationFiled: March 11, 2020Publication date: July 2, 2020Applicant: REGENERON PHARMACEUTICALS, INC.Inventors: Chris Schoenherr, John McWhirter, Corey Momont, Caitlin L. Goshert, Lynn Macdonald, Gregg S. Warshaw, Jose F. Rojas, Ka-Man Venus Lai, David M. Valenzuela, Andrew J. Murphy
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Patent number: 10640800Abstract: Provided herein is a mouse that produces hybrid antibodies containing human variable regions and mouse constant regions.Type: GrantFiled: July 19, 2016Date of Patent: May 5, 2020Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Andrew J. Murphy, George D. Yancopoulos, Margaret Karow, Lynn MacDonald, Sean Stevens, Aris N. Economides, David M. Valenzuela
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Patent number: 10626402Abstract: Methods are provided herein for assembling at least two nucleic acids using a sequence specific nuclease agent (e.g., a gRNA-Cas complex) to create end sequences having complementarity and subsequently assembling the overlapping complementary sequences. The nuclease agent (e.g., a gRNA-Cas complex) can create double strand breaks in dsDNA in order to create overlapping end sequences or can create nicks on each strand to produce complementary overhanging end sequences. Assembly using the method described herein can assemble any nucleic acids having overlapping sequences or can use a joiner oligo to assemble sequences without complementary ends.Type: GrantFiled: March 7, 2019Date of Patent: April 21, 2020Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Chris Schoenherr, John McWhirter, Corey Momont, Caitlin L. Goshert, Lynn MacDonald, Gregg S. Warshaw, Jose F. Rojas, Ka-Man Venus Lai, David M. Valenzuela, Andrew J. Murphy