Patents by Inventor Wojtek Auerbach
Wojtek Auerbach 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: 9655351Abstract: 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: GrantFiled: June 22, 2016Date of Patent: May 23, 2017Assignee: REGENERON PHARMACEUTICALS, INC.Inventors: Wojtek Auerbach, Thomas DeChiara, William Poueymirou, David Frendewey, David Valenzuela
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Publication number: 20170079250Abstract: Methods and compositions are provided for generating F0 fertile XY female animals. The methods and compositions involve making XY pluripotent or totipotent animal cells, in vitro cell cultures, or embryos that are capable of producing a fertile female XY animal in an F0 generation. Such cells, embryos, and animals can be made by silencing a region of the Y chromosome. Optionally, the cells can also be cultured in feminizing medium such as a low-osmolality medium and/or can be modified to decrease the level and/or activity of an Sry protein. Methods and compositions are also provided for silencing a region of the Y chromosome in an XY pluripotent or totipotent animal cell, or in vitro cell cultures, embryos, or animals derived therefrom, by maintaining an XY pluripotent or totipotent animal cell in a feminizing medium.Type: ApplicationFiled: September 16, 2016Publication date: March 23, 2017Inventors: Jennifer Schmahl, David Frendewey, Junko Kuno, Chia-Jen Siao, Gustavo Droguett, Yu Bai, Wojtek Auerbach
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Publication number: 20170067078Abstract: 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: November 17, 2016Publication date: March 9, 2017Applicant: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Wojtek Auerbach, Ka-Man Venus Lai, David M. Valenzuela, George D. Yancopoulos
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Publication number: 20170037429Abstract: 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: August 19, 2016Publication date: February 9, 2017Applicant: 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: 9546384Abstract: 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: October 15, 2014Date of Patent: January 17, 2017Assignee: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Wojtek Auerbach, Ka-Man Venus Lai, David M. Valenzuela, George D. Yancopoulos
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Publication number: 20160316728Abstract: 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 FO 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: July 11, 2016Publication date: November 3, 2016Inventors: William Poueymirou, Thomas M. DeChiara, Wojtek Auerbach, Aris N. Economides, Nicholas W. Gale, David Frendewey, David M. Valenzuela
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Publication number: 20160316729Abstract: 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: July 11, 2016Publication date: November 3, 2016Inventors: William Poueymirou, Thomas M. DeChiara, Wojtek Auerbach, David Frendewey, David M. Valenzuela
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Publication number: 20160295841Abstract: 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 22, 2016Publication date: October 13, 2016Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Wojtek Auerbach, Thomas DeChiara, William Poueymirou, David Frendewey, David Valenzuela
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Patent number: 9414575Abstract: 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: June 20, 2014Date of Patent: August 16, 2016Assignee: REGENERON PHARMACEUTICALS, INC.Inventors: William Poueymirou, Thomas M. DeChiara, Wojtek Auerbach, David Frendewey, David M. Valenzuela
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Patent number: 9398762Abstract: 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: GrantFiled: November 11, 2014Date of Patent: July 26, 2016Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Wojtek Auerbach, Thomas DeChiara, William Poueymirou, David Frendewey, David Valenzuela
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Publication number: 20160145646Abstract: 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: November 20, 2015Publication date: May 26, 2016Inventors: David Frendewey, Ka-Man Venus Lai, Wojtek Auerbach, Jeffrey D. Lee, Alexander O. Mujica, Gustavo Droguett, Sean Trzaska, Charleen Hunt, Anthony Gagliardi, David M. Valenzuela, Vera Voronina, Lynn Macdonald, Andrew J. Murphy, George D. Yancopoulos
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Publication number: 20160108369Abstract: 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: October 15, 2015Publication date: April 21, 2016Applicant: REGENERON PHARMACEUTICALS, INC.Inventors: Junko Kuno, Wojtek Auerbach, David M. Valenzuela
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Publication number: 20160108360Abstract: 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: October 30, 2015Publication date: April 21, 2016Applicant: 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: 20160060657Abstract: 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 30, 2015Publication date: March 3, 2016Applicant: REGENERON PHARMACEUTICALS, INC.Inventors: 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: 20160046960Abstract: Methods and compositions are provided for generating targeted genetic modifications on the Y chromosome or a challenging target locus. Compositions include an in vitro culture comprising an XY pluripotent and/or totipotent animal cell (i.e., XY ES cells or XY iPS cells) having a modification that decreases the level and/or activity of an Sry protein; and, culturing these cells in a medium that promotes development of XY F0 fertile females. Such compositions find use in various methods for making a fertile female XY non-human mammal in an F0 generation.Type: ApplicationFiled: October 29, 2015Publication date: February 18, 2016Inventors: David Frendewey, Gustavo Droguett, Anthony Gagliardi, Junko Kuno, Wojtek Auerbach, David M. Valenzuela
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Patent number: 9228208Abstract: 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 19, 2014Date of Patent: January 5, 2016Assignee: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Wojtek Auerbach, Ka-Man Venus Lai, David M. Valenzuela, George D. Yancopoulos
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Publication number: 20150376650Abstract: 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: June 5, 2015Publication date: December 31, 2015Applicant: REGENERON PHARMACEUTICALS, INC.Inventors: Wojtek Auerbach, David Frendewey, Gustavo Droguett, Anthony Gagliardi, Junko Kuno, David M. Valenzuela
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Publication number: 20150376651Abstract: Methods and compositions are provided for generating targeted genetic modifications on the Y chromosome or a challenging target locus. Compositions include an in vitro culture comprising an XY pluripotent and/or totipotent animal cell (i.e., XY ES cells or XY iPS cells) having a modification that decreases the level and/or activity of an Sry protein; and, culturing these cells in a medium that promotes development of XY F0 fertile females. Such compositions find use in various methods for making a fertile female XY non-human mammal in an F0 generation.Type: ApplicationFiled: June 26, 2015Publication date: December 31, 2015Applicant: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Gustavo Droguett, Anthony Gagliardi, Junko Kuno, Wojtek Auerbach, David M. Valenzuela
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Patent number: 9149026Abstract: 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: GrantFiled: June 10, 2011Date of Patent: October 6, 2015Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Wojtek Auerbach, Thomas Dechiara, William Poueymirou, David Frendewey, David Valenzuela
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Publication number: 20150159174Abstract: 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 15, 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