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).
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Publication number: 20150159175Abstract: 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 19, 2014Publication date: June 11, 2015Inventors: David Frendewey, Wojtek Auerbach, Ka-Man Venus Lai, Alexander O. Mujica, Jeffrey D. Lee, Gustavo Droguett, Sean Trzaska, Charleen Hunt, Anthony Gagliardi, Junko Kuno, David M. Valenzuela, George D. Yancopoulos
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Publication number: 20150106961Abstract: Genetically modified non-human animals comprising a humanized interleukin-15 (IL-15) gene. Cells, embryos, and non-human animals comprising a human IL-15 gene. Rodents that express humanized or human IL-15 protein.Type: ApplicationFiled: October 15, 2014Publication date: April 16, 2015Applicant: REGENERON PHARMACEUTICALS, INC.Inventors: Jose F. Rojas, Ka-Man Venus Lai, Andrew J. Murphy
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Publication number: 20150099296Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.Type: ApplicationFiled: December 16, 2014Publication date: April 9, 2015Inventors: David Frendewey, Guochun Gong, Ka-Man Venus Lai, David M. Valenzuela
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Publication number: 20150047062Abstract: 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: ApplicationFiled: August 7, 2014Publication date: February 12, 2015Inventors: Ka-Man Venus Lai, Guochun Gong, John Rinn, David Frendewey, David M. Valenzuela
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Patent number: 8946505Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.Type: GrantFiled: July 3, 2013Date of Patent: February 3, 2015Assignee: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Guochun Gong, Ka-Man Venus Lai, David M. Valenzuela
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Patent number: 8946504Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.Type: GrantFiled: July 3, 2013Date of Patent: February 3, 2015Assignee: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Guochun Gong, Ka-Man Venus Lai, David M. Valenzuela
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Publication number: 20140310828Abstract: 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: April 16, 2014Publication date: October 16, 2014Inventors: Jeffrey D. Lee, Alexander O. Mujica, Wojtek Auerbach, Ka-Man Venus Lai, David M. Valenzuela, George D. Yancopoulos
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Publication number: 20140309487Abstract: 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, 2014Publication date: October 16, 2014Inventors: Jeffrey D. Lee, Alexander O. Mujica, Wojtek Auerbach, Ka-Man Venus Lai, David M. Valenzuela, George D. Yancopoulos
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Publication number: 20140235933Abstract: 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 inhibitor 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: February 20, 2014Publication date: August 21, 2014Inventors: Jeffrey D. Lee, Wojtek Auerbach, David Heslin, David Frendewey, Ka-Man Venus Lai, David M. Valenzuela
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Publication number: 20140221734Abstract: Genetically modified somatic cells of a non-human animal are provided that are engineered to contain a self-excisable, recombinase expression cassette comprising a site-specific recombinase gene operably linked to an ES cell-specific promoter. Compositions and methods for producing a genetically modified, cloned non-human animal that is free of a selective marker gene and a recombinase gene are provided, wherein a targeting construct comprising a self-excisable recombinase gene operably linked to an ES cell-specific promoter is introduced into differentiated somatic cells. The genetically modified genome of the somatic cells is transferred into an enucleated host oocyte. The artificially created zygote is then cultured in vitro until the blastocyst embryonic stage and subsequently implanted into a uterus of a surrogate mother to form a genetically modified, cloned non-human animal free of selective marker and recombinase genes.Type: ApplicationFiled: November 26, 2013Publication date: August 7, 2014Inventors: Guochun Gong, Ka-Man Venus Lai, David M. Valenzuela
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Publication number: 20140199761Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.Type: ApplicationFiled: March 18, 2014Publication date: July 17, 2014Applicant: REGENERON PHARMACEUTICALS, INC.Inventors: David Frendewey, Guochun Gong, Ka-Man Venus Lai, David M. Valenzuela
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Publication number: 20140189900Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.Type: ApplicationFiled: February 10, 2014Publication date: July 3, 2014Applicant: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, David Jonathan Heslin, Ka-Man Venus Lai, David M. Valenzuela
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Patent number: 8697851Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.Type: GrantFiled: December 3, 2012Date of Patent: April 15, 2014Assignee: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, David Jonathan Heslin, Ka-Man Venus Lai, David M. Valenzuela
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Publication number: 20140075586Abstract: Non-human totipotent or pluripotent cells are provided comprising at a genomic locus a self-excisable, recombinase expression cassette flanked with recombination recognition sites, wherein a recombinase gene is operably linked to a promoter that is active in a post-meiotic spermatid stage when cytoplasmic bridging occurs between spermatids. Compositions and methods are provided for making cassette-deleted F1 non-human animals, wherein the methods comprise employing totipotent or pluripotent cells containing a self-excisable, recombinase expression cassette.Type: ApplicationFiled: November 13, 2013Publication date: March 13, 2014Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Guochun Gong, Ka-Man Venus Lai, David Frendewey, David M. Valenzuela
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Publication number: 20130312128Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.Type: ApplicationFiled: July 3, 2013Publication date: November 21, 2013Applicant: Regeneron Pharmaceuticals, Inc.Inventors: David FRENDEWEY, Guochun GONG, Ka-Man Venus LAI, David M. VALENZUELA
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Publication number: 20130312129Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.Type: ApplicationFiled: July 3, 2013Publication date: November 21, 2013Applicant: Regeneron Pharmaceuticals, Inc.Inventors: David FRENDEWEY, Guochun GONG, Ka-Man Venus LAI, David M. VALENZUELA
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Patent number: 8518392Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.Type: GrantFiled: August 13, 2010Date of Patent: August 27, 2013Assignee: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Guochun Gong, Ka-Man Venus Lai, David M. Valenzuela
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Patent number: 8354389Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.Type: GrantFiled: August 13, 2010Date of Patent: January 15, 2013Assignee: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, David Jonathan Heslin, Ka-Man Venus Lai, David M. Valenzuela
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Publication number: 20110041196Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.Type: ApplicationFiled: August 13, 2010Publication date: February 17, 2011Applicant: Regeneron Pharmaceuticals, Inc.Inventors: David FRENDEWEY, David Jonathan HESLIN, Ka-Man Venus LAI, David M. VALENZUELA
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Publication number: 20110041197Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.Type: ApplicationFiled: August 13, 2010Publication date: February 17, 2011Applicant: REGENERON PHARMACEUTICALS, INC.Inventors: DAVID FRENDEWEY, GUOCHUN GONG, KA-MAN VENUS LAI, DAVID M. VALENZUELA