Patents by Inventor Ka-Man Venus Lai
Ka-Man Venus Lai 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).
-
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
-
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
-
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
-
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
-
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
-
Patent number: 10412939Abstract: This disclosure provides a rodent model of prostate cancer. The rodents disclosed herein comprise a transgene that provides prostate-specific expression of an oncogenic protein (e.g, an SV40 tumor antigen) under the control of 5? and 3? regulatory regions of a mouse probasin gene. The rodents develop progressive forms of prostate tumor that resemble the development of human prostate cancer.Type: GrantFiled: September 1, 2016Date of Patent: September 17, 2019Assignee: REGENERON PHARMACEUTICALS, INC.Inventors: Chia-Jen Siao, Hoi-Ching Lee, Zhe Li, Ka-Man Venus Lai, Gavin Thurston
-
Patent number: 10390522Abstract: Non-human animals, and methods and compositions for making and using the same, are provided, wherein the non-human animals comprise a humanization of a Programmed cell death 1 (Pdcd1) gene. The non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous Pdcd1 gene so that the non-human animals express a PD-1 polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).Type: GrantFiled: June 19, 2015Date of Patent: August 27, 2019Assignee: REGENERON PHARMACEUTICALS, INC.Inventors: Elena Burova, Alexander O. Mujica, Ka-Man Venus Lai, Andrew J. Murphy
-
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
-
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
-
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
-
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
-
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
-
Patent number: 10285388Abstract: 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: May 26, 2016Date of Patent: May 14, 2019Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Amanda Atanasio, Burcin Ikiz, Guochun Gong, Michael L. Lacroix-Fralish, Ka-man Venus Lai, David M. Valenzuela
-
Publication number: 20190136201Abstract: The invention provides stem cell derived beta-pancreatic cells and animal models of T2D in which cells have been grafted. The stem cells bear a mutated form of SLC30A8 conferring protection or susceptibility to T2D. The cells and animal models can be used for drug screening as well as to provide insights into the mechanism of T2D and potentially new therapeutic and diagnostic targets.Type: ApplicationFiled: November 21, 2018Publication date: May 9, 2019Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Guochun Gong, Ka-Man Venus Lai, David M. Valenzuela
-
Patent number: 10273488Abstract: 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: June 30, 2017Date of Patent: April 30, 2019Assignee: 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
-
Publication number: 20190112619Abstract: 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: December 18, 2018Publication date: April 18, 2019Applicant: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Wojtek Auerbach, Ka-Man Venus Lai, David M. Valenzuela, George D. Yancopoulos
-
Patent number: 10208317Abstract: 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: November 17, 2016Date of Patent: February 19, 2019Assignee: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Wojtek Auerbach, Ka-Man Venus Lai, David M. Valenzuela, George D. Yancopoulos
-
Patent number: 10196613Abstract: The invention provides stem cell derived beta-pancreatic cells and animal models of T2D in which cells have been grafted. The stem cells bear a mutated form of SLC30A8 conferring protection or susceptibility to T2D. The cells and animal models can be used for drug screening as well as to provide insights into the mechanism of T2D and potentially new therapeutic and diagnostic targets.Type: GrantFiled: December 18, 2015Date of Patent: February 5, 2019Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Guochun Gong, Ka-Man Venus Lai, David M. Valenzuela
-
Publication number: 20180206462Abstract: Non-human animals, and methods and compositions for making and using the same, are provided, wherein the non-human animals comprise a humanization of a Programmed cell death 1 (Pdcd1) gene. The non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous Pdcd1 gene so that the non-human animals express a PD-1 polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).Type: ApplicationFiled: March 20, 2018Publication date: July 26, 2018Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Elena Burova, Alexander O. Mujica, Ka-Man Venus Lai, Andrew J. Murphy
-
Publication number: 20180160663Abstract: Non-human animals, methods and compositions for making and using the same, are provided, wherein said non-human animals comprise a humanization of a Cluster of Differentiation 274 (CD274) gene. Such non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous CD274 gene so that said non-human animals express a Programmed cell death ligand 1 (PD-L1) polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).Type: ApplicationFiled: January 30, 2018Publication date: June 14, 2018Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Elena Burova, Yajun Tang, Ka-Man Venus Lai, Andrew J. Murphy