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: 10584364Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.Type: GrantFiled: October 4, 2013Date of Patent: March 10, 2020Assignee: Rgeneron 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: 10526630Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.Type: GrantFiled: October 4, 2013Date of Patent: January 7, 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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Publication number: 20200002731Abstract: 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: September 16, 2019Publication date: January 2, 2020Applicant: 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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Publication number: 20200002730Abstract: 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: September 16, 2019Publication date: January 2, 2020Applicant: 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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Publication number: 20190382730Abstract: Methods and compositions are provided for generating or maintaining human iPS cells in culture. Methods include the use of a low osmolality medium to make human iPS cells, or use of a low osmolality medium to maintain human iPS cells. Methods for making targeted genetic modification to human iPS cells cultured in low osmolality medium are also included. Compositions include human iPS cells cultured and maintained using the low osmolality medium defined herein.Type: ApplicationFiled: August 5, 2019Publication date: December 19, 2019Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Junko Kuno, Wojtek Auerbach, David M. Valenzuela
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Patent number: 10457960Abstract: 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: November 20, 2015Date of Patent: October 29, 2019Assignee: 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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Publication number: 20190323032Abstract: 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: June 25, 2019Publication date: October 24, 2019Applicant: 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: 20190316149Abstract: 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: May 2, 2019Publication date: October 17, 2019Applicant: 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: 10428310Abstract: Methods and compositions are provided for generating or maintaining human iPS cells in culture. Methods include the use of a low osmolality medium to make human iPS cells, or use of a low osmolality medium to maintain human iPS cells. Methods for making targeted genetic modification to human iPS cells cultured in low osmolality medium are also included. Compositions include human iPS cells cultured and maintained using the low osmolality medium defined herein.Type: GrantFiled: October 15, 2015Date of Patent: October 1, 2019Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Junko Kuno, Wojtek Auerbach, David M. Valenzuela
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Patent number: 10385359Abstract: 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: January 19, 2017Date of Patent: August 20, 2019Assignee: 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: 10378040Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.Type: GrantFiled: September 25, 2013Date of Patent: August 13, 2019Assignee: 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: 10378037Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.Type: GrantFiled: September 24, 2013Date of Patent: August 13, 2019Assignee: 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: 10378038Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.Type: GrantFiled: September 25, 2013Date of Patent: August 13, 2019Assignee: 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: 10378039Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.Type: GrantFiled: September 25, 2013Date of Patent: August 13, 2019Assignee: 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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Publication number: 20190225992Abstract: Methods and compositions are provided for modifying one or more target loci in a cell. Such methods comprise providing a cell comprising a first polynucleotide encoding a first selection marker operably linked to a first promoter active in the cell, wherein the first polynucleotide further comprises a first recognition site for a first nuclease agent. A first nuclease agent is introduced into a cell, wherein the first nuclease agent induces a nick or double-strand break at the first recognition site. Further introduced into the cell is a first targeting vector comprising a first insert polynucleotide flanked by a first and a second homology arm that correspond to a first and a second target site located in sufficient proximity to the first recognition site. At least one cell is then identified comprising in its genome the first insert polynucleotide integrated at the target locus.Type: ApplicationFiled: March 29, 2019Publication date: July 25, 2019Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Wojtek Auerbach, David Frendewey, Gustavo Droguett, Anthony Gagliardi, Junko Kuno, David M. Valenzuela
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Publication number: 20190216062Abstract: 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: ApplicationFiled: March 27, 2019Publication date: July 18, 2019Inventors: Amanda Atanasio, Burcin Ikiz, Guochun Gong, Michael L. Lacroix-Fralish, Ka-Man Venus Lai, David M. Valenzuela
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Patent number: 10344299Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.Type: GrantFiled: May 23, 2017Date of Patent: July 9, 2019Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Aris N. Economides, Andrew J. Murphy, David M. Valenzuela, David Frendewey, George D. Yancopoulos
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Publication number: 20190194668Abstract: 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 7, 2019Publication date: June 27, 2019Applicant: REGENERON PHARMACEUTICALS, INC.Inventors: Chris Schoenherr, John McWhirter, Corey Momont, Caitlin Montagna, Lynn Macdonald, Gregg S. Warshaw, Jose F. Rojas, Ka-Man Venus Lai, David M. Valenzuela, Andrew J. Murphy
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Patent number: 10329582Abstract: 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: August 19, 2016Date of Patent: June 25, 2019Assignee: 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: 10301646Abstract: Compositions and methods are provided for making one or more targeted genetic modifications at a target genomic locus by employing homologous recombination facilitated by single or double-strand break at or near the target genomic locus. Compositions and methods for promoting efficiency of homologous recombination between an LTVEC and a target genomic locus in prokaryotic or eukaryotic cells using engineered nucleases are also provided.Type: GrantFiled: October 24, 2017Date of Patent: May 28, 2019Assignee: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Wojtek Auerbach, David M. Valenzuela, George D. Yancopoulos, Ka-Man Venus Lai