Patents by Inventor David Frendewey
David Frendewey 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: 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: 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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Publication number: 20140178879Abstract: 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: ApplicationFiled: February 28, 2014Publication date: June 26, 2014Applicant: Regeneron Pharmaceuticals, Inc.Inventors: ARIS N. ECONOMIDES, Andrew J. Murphy, David M. Valenzuela, David Frendewey, George D. Yancopoulos
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Patent number: 8759105Abstract: 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: June 1, 2007Date of Patent: June 24, 2014Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Aris N. Economides, Andrew J. Murphy, David M. Valenzuela, David Frendewey, George D. Yancopoulos
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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: 20130309670Abstract: 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: ApplicationFiled: April 25, 2013Publication date: November 21, 2013Applicant: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Wojtek Auerbach, David M. Valenzuela, George D. Yancopoulos
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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: 20110307968Abstract: Methods and compositions are described for making phenotypically female fertile animals from XY donor cells and suitable host embryos. Culture media and methods are provided for maintaining XY donor cells in culture that after introduction into a host embryo and gestation in a suitable host will result in fertile XY female animals. Methods and compositions are described for making fertile female animals in an F0 generation from a donor XY cell and a host embryo, as are methods for making F1 progeny that are homozygous for a modification from a heterozygous F0 fertile male and a heterozygous F0 fertile female sibling.Type: ApplicationFiled: June 10, 2011Publication date: December 15, 2011Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Wojtek AUERBACH, Thomas DeChiara, William Poueymirou, David Frendewey, David 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
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Patent number: 7659442Abstract: Methods of generating modified embryos and mammals by introduction of donor cells into an early stage embryo are provided, such that the resulting embryo and animal generated therefrom has a significant contribution to all tissues from the donor cells and is capable of transmitting the donor cell DNA.Type: GrantFiled: September 27, 2007Date of Patent: February 9, 2010Assignee: Regeneron Pharmaceuticals, Inc.Inventors: William Poueymirou, Thomas M. DeChiara, Wojtek Auerbach, David Frendewey, David M. Valenzuela
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Publication number: 20090271884Abstract: Genetically modified mice and nucleic acid constructs for making the genetically modified mice are described. A first mouse having a gene encoding an activator (such as a Cre recombinase) operably linked to a developmentally-regulated promoter (such as a Nanog promoter) is provided. A second mouse having a toxic responder gene (such as a gene encoding diphtheria toxin A) is provided, where the toxic gene is expressed only in the presence of an activator, Embryos from a mating of the first and the second mouse are provided as host embryos suitable for generating mice from donor cells introduced into the host embryos. Ablating the ICM of a mouse embryo physically, chemically, or genetically is described, as well as making F0 generation mice that are substantially or in full derived from donor cells, employing a host mouse embryo with an ablated or nonproliferating ICM.Type: ApplicationFiled: March 6, 2009Publication date: October 29, 2009Applicant: Regeneron Pharmaceuticals, Inc.Inventors: William POUEYMIROU, Thomas M. DECHIARA, Wojtek AUERBACH, Aris N. ECONOMIDES, Nicholas W. GALE, David FRENDEWEY, David M. VALENZUELA
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Patent number: 7576259Abstract: Methods of generating modified embryos and mammals by introduction of donor cells into an early stage embryo are provided, such that the resulting embryo and animal generated therefrom has a significant contribution to all tissues from the donor cells and is capable of transmitting the donor cell DNA.Type: GrantFiled: September 27, 2007Date of Patent: August 18, 2009Assignee: Regeneron Pharmaceuticals, Inc.Inventors: William Poueymirou, Thomas M. DeChiara, Wojtek Auerbach, David Frendewey, David M. Valenzuela
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Publication number: 20090055943Abstract: 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: ApplicationFiled: June 1, 2007Publication date: February 26, 2009Inventors: Aris N. Economides, Andrew J. Murphy, David M. Valenzuela, David Frendewey, George D. Yancopoulos
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Publication number: 20080078000Abstract: Methods of generating modified embryos and mammals by introduction of donor cells into an early stage embryo are provided, such that the resulting embryo and animal generated therefrom has a significant contribution to all tissues from the donor cells and is capable of transmitting the donor cell DNA.Type: ApplicationFiled: September 27, 2007Publication date: March 27, 2008Applicant: Regeneron Pharmaceuticals, Inc.Inventors: William Poueymirou, Thomas Dechiara, Wojtek Auerbach, David Frendewey, David Valenzuela