Mouse Patents (Class 800/18)
  • Patent number: 10820580
    Abstract: The present disclosure relates to the genetically modified non-human animals that have a disruption at the endogenous CD132 gene (e.g., CD132 knockout), and methods of use thereof.
    Type: Grant
    Filed: June 7, 2019
    Date of Patent: November 3, 2020
    Assignee: Beijing Biocytogen Co., Ltd
    Inventors: Yuelei Shen, Yang Bai, Meiling Zhang, Jiawei Yao, Rui Huang, Yanan Guo
  • Patent number: 10785968
    Abstract: Genetically modified non-human animals are provided that may be used to model human hematopoietic cell development, function, or disease. The genetically modified non-human animals comprise a nucleic acid encoding human IL-6 operably linked to an IL-6 promoter. In some instances, the genetically modified non-human animal expressing human IL-6 also expresses at least one of human M-CSF, human IL-3, human GM-CSF, human SIRPa or human TPO. In some instances, the genetically modified non-human animal is immunodeficient. In some such instances, the genetically modified non-human animal is engrafted with healthy or diseased human hematopoietic cells. Also provided are methods for using the subject genetically modified non-human animals in modeling human hematopoietic cell development, function, and/or disease, as well as reagents and kits thereof that find use in making the subject genetically modified non-human animals and/or practicing the subject methods.
    Type: Grant
    Filed: November 6, 2017
    Date of Patent: September 29, 2020
    Assignees: Regeneron Pharmaceuticals, Inc., Yale University, Institute for Research in Biomedicine (IRB)
    Inventors: Richard Flavell, Till Strowig, Markus G. Manz, Chiara Borsotti, Madhav Dhodapkar, Andrew J. Murphy, Sean Stevens, George D. Yancopoulos
  • Patent number: 10774155
    Abstract: The invention discloses methods for the generation of chimaeric human—non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.
    Type: Grant
    Filed: April 9, 2018
    Date of Patent: September 15, 2020
    Assignee: Kymab Limited
    Inventors: Allan Bradley, E-Chiang Lee, Wei Wang, Dominik Spensberger, Hui Liu, Jasper Clube, Qi Liang
  • Patent number: 10767175
    Abstract: The present invention relates to guide RNAs having chemical modifications and their use in CRISPR-Cas systems. The chemically modified guide RNAs have enhanced specificity for target polynucleotide sequences. The present invention also relates to methods of using chemically modified guide RNAs for cleaving or nicking polynucleotides, and for high specificity genome editing.
    Type: Grant
    Filed: April 20, 2017
    Date of Patent: September 8, 2020
    Assignee: AGILENT TECHNOLOGIES, INC.
    Inventors: Douglas J Dellinger, Daniel E Ryan, Subhadeep Roy, Jeffrey R Sampson
  • Patent number: 10765093
    Abstract: This present invention relates to transgenic animals useful to study human diseases. Specifically, the invention relates to transgenic animals expressing at least two human proteins (optionally in replacement of the counterpart proteins in the animal) whereas a first human protein interacts with a second human protein. The transgenic animals can then be used for evaluating drugs or building disease models that are related to the expressed human proteins in the animals. The animals and methods disclosed herein reduce the possibility identifying a false-positive compound—the compound that show an effect in a naturally-occurring, non-transgenic animal but may not necessarily work or be therapeutic in human, since the compound may only interrupt the interaction between two animal proteins not necessarily two related human proteins.
    Type: Grant
    Filed: November 28, 2011
    Date of Patent: September 8, 2020
    Inventor: James Zhu
  • Patent number: 10752906
    Abstract: Stably immunized cells and methods of making stably immunized cells are provided. Methods of altering the microbiota of an ecological environment are provided. Methods of modifying target chromosomes are provided. Methods of delivering genetic material to target cells are provided.
    Type: Grant
    Filed: November 5, 2014
    Date of Patent: August 25, 2020
    Assignee: President and Fellows of Harvard College
    Inventors: Kevin M. Esvelt, Stephanie Yaung
  • Patent number: 10738278
    Abstract: Provided are engineered cells for adoptive therapy, including NK cells and T cells. Also provided are compositions for engineering and producing the cells, compositions containing the cells, and methods for their administration to subjects. In some aspects, features of the cells and methods provide specificity and/or efficacy. In some embodiments, the cells contain genetically engineered antigen receptors that specifically bind to antigens, such as chimeric antigen receptors (CARs) and costimulatory receptors. In some embodiments, the cells include receptors targeting multiple antigens. In some embodiments, the cells include repression of one or more gene product, for example, by disruption of a gene encoding the gene product. In some embodiments, a gene encoding an antigen recognized by the engineered antigen receptor is disrupted, reducing the likelihood of targeting of the engineered cells.
    Type: Grant
    Filed: July 15, 2015
    Date of Patent: August 11, 2020
    Assignee: Juno Therapeutics, Inc.
    Inventors: Kendall M. Mohler, Hyam I. Levitsky
  • Patent number: 10730930
    Abstract: The invention relates to the provision of antibody therapeutics and prophylactics that are tailored specifically for human use. The present invention provides libraries, vertebrates and cells, such as transgenic mice or rats or transgenic mouse or rat cells. Furthermore, the invention relates to methods of using the vertebrates to isolate antibodies or nucleotide sequences encoding antibodies. Antibodies, heavy chains, polypeptides, nucleotide sequences, pharmaceutical compositions and uses are also provided by the invention.
    Type: Grant
    Filed: July 21, 2017
    Date of Patent: August 4, 2020
    Assignee: Kymab Limited
    Inventors: Allan Bradley, Glenn Friedrich, E-Chiang Lee, Mark Strivens, Nicholas England
  • Patent number: 10694724
    Abstract: A transgenic animal model that is suitable for the cell or tissue specific assessing of thyroid hormone (TH) action in vivo is described. The recombinant DNA construct and methods suitable to generate such an animal are also provided. The assessment of TH action is based on a reporter that is dependent on an endogenously expressed thyroid hormone receptor (TR) and coregulators of said receptor.
    Type: Grant
    Filed: November 30, 2015
    Date of Patent: June 30, 2020
    Assignee: Kisérleti Orvostudoányi Kutatóintézet
    Inventors: Csaba Fekete, Balázs Gereben, Petra Mohácsik, Ferenc Erdélyi, Gábor Szabó
  • Patent number: 10687520
    Abstract: Duchenne muscular dystrophy (DMD), which affects 1 in 5,000 male births, is one of the most common genetic disorders of children. This disease is caused by an absence or deficiency of dystrophin protein in striated muscle. The major DMD deletion “hot spots” are found between exon 6 to 8, and exons 45 to 53. Here, a “humanized” mouse model is provided that can be used to test a variety of DMD exon skipping strategies. Among these are, CRISPR/Cas9 oligonucleotides, small molecules or other therapeutic modalities that promote exon skipping or micro dystrophin mini genes or cell based therapies. Methods for restoring the reading frame of exon 44 deletion via CRISPR-mediated exon skipping in the humanized mouse model, in patient-derived iPS cells and ultimately, in patients using various delivery systems are also contemplated. The impact of CRISPR technology on DMD is that gene editing can permanently correct mutations.
    Type: Grant
    Filed: March 7, 2018
    Date of Patent: June 23, 2020
    Assignee: The Board of Regents of the University of Texas System
    Inventors: Yi-Li Min, Rhonda Bassel-Duby, Eric Olson
  • Patent number: 10667501
    Abstract: The invention relates, in one aspect, generally to novel concept of guided selection of antibody variable domains, combination and expression entirely in vivo. An application is to produce multivalent polypeptides. The present invention relates to multivalent (eg, multispecific) antibodies, antibody chains and polypeptides, as well as heavy chain-only antibodies (H2 antibodies) that are devoid of light chains. The invention further relates to the selection, maturation and production of these in vivo in non-human vertebrates and non-human vertebrate cells. To this end the invention also relates to such non-human vertebrates and cells. The invention also relates to the provision of means to produce and select heavy chain-only antibodies and heavy chains comprising variable domains that have undergone affinity maturation.
    Type: Grant
    Filed: November 17, 2014
    Date of Patent: June 2, 2020
    Assignee: Kymab Limited
    Inventors: Volker Germaschewski, E-Chiang Lee, Hanif Ali, Jasper Clube
  • Patent number: 10662255
    Abstract: The invention provides non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing transgenic cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.
    Type: Grant
    Filed: March 20, 2017
    Date of Patent: May 26, 2020
    Assignee: Ablexis, LLC
    Inventors: Larry Green, Hiroaki Shizuya
  • Patent number: 10640789
    Abstract: Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.
    Type: Grant
    Filed: February 22, 2016
    Date of Patent: May 5, 2020
    Assignee: President and Fellows of Harvard College
    Inventors: George M. Church, Prashant G. Mali, Kevin M. Esvelt
  • Patent number: 10626188
    Abstract: The invention provides non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing transgenic cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.
    Type: Grant
    Filed: March 20, 2017
    Date of Patent: April 21, 2020
    Assignee: ABLEXIS, LLC
    Inventors: Larry Green, Hiroaki Shizuya
  • Patent number: 10618977
    Abstract: The invention provides non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing transgenic cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.
    Type: Grant
    Filed: March 20, 2017
    Date of Patent: April 14, 2020
    Assignee: ABLEXIS, LLC
    Inventors: Larry Green, Hiroaki Shizuya
  • Patent number: 10604587
    Abstract: The invention provides non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing transgenic cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.
    Type: Grant
    Filed: March 20, 2017
    Date of Patent: March 31, 2020
    Assignee: ABLEXIS, LLC
    Inventors: Larry Green, Hiroaki Shizuya
  • Patent number: 10575505
    Abstract: An object of the present invention is to provide a mouse that enables the functions of human NK cell to be studied. A DNA consisting of a nucleotide sequence represented by SEQ ID NO: 1, which is a gene region comprising a DNA in which a cDNA sequence encoding interleukin 15 (IL-15) is operably ligated to a cDNA sequence encoding the signal peptide of human interleukin (IL-2), is inserted to immunodeficient mouse cDNA. In NOD-scid, IL-2r?null-hIL-15 Tg mice thus generated, hCD56+ cell having a concentration sufficient for conducting in vivo study on human mature NK cell are detected for at least 6 months after transplantation.
    Type: Grant
    Filed: April 20, 2016
    Date of Patent: March 3, 2020
    Assignee: Central Institute for Experimental Animals
    Inventors: Mamoru Ito, Ikumi Katano
  • Patent number: 10555506
    Abstract: The invention provides knock-in non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing knock-in cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.
    Type: Grant
    Filed: April 11, 2016
    Date of Patent: February 11, 2020
    Assignee: ABLEXIS, LLC
    Inventors: Larry Green, Hiroaki Shizuya
  • Patent number: 10526630
    Abstract: 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: Grant
    Filed: October 4, 2013
    Date of Patent: January 7, 2020
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: Andrew J. Murphy, George D. Yancopoulos, Margaret Karow, Lynn Macdonald, Sean Stevens, Aris N. Economides, David M. Valenzuela
  • Patent number: 10526420
    Abstract: The invention provides non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing transgenic cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.
    Type: Grant
    Filed: March 20, 2017
    Date of Patent: January 7, 2020
    Assignee: ABLEXIS, LLC
    Inventors: Larry Green, Hiroaki Shizuya
  • Patent number: 10494620
    Abstract: The present disclosure provides compositions and methods for binding and/or cleaving a single stranded target nucleic acid. Subject compositions include a Cas9 polypeptide, a guide nucleic acid, and a PAMmer. A subject PAMmer is a single stranded oligonucleotide having a protospacer adjacent motif (PAM) sequence and at least one of: a specifity segment positioned 5? of the PAM sequence, and an orientation segment positioned 3? of the PAM sequence. In some embodiments, the Cas9 polypeptide is a variant Cas9 polypeptide having reduced nuclease activity relative to a corresponding wild type Cas9 polypeptide. In some cases, methods of binding are for visualizing single stranded target nucleic acids using a detectable label. In some cases, methods of binding are for isolating, collecting, and/or analyzing at least one of: (i) bound single stranded target nucleic acids; and (ii) polypeptides associated with bound single stranded target nucleic acids.
    Type: Grant
    Filed: June 7, 2018
    Date of Patent: December 3, 2019
    Assignee: The Regents of the University of California
    Inventors: Jennifer A. Doudna, Samuel H. Sternberg, Mitchell O'Connell, Benjamin Oakes
  • Patent number: 10492476
    Abstract: The invention provides knock-in non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing knock-in cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.
    Type: Grant
    Filed: April 11, 2016
    Date of Patent: December 3, 2019
    Assignee: ABLEXIS, LLC
    Inventors: Larry Green, Hiroaki Shizuya
  • Patent number: 10487147
    Abstract: The present application relates to anti-PD-L1 antibodies or antigen binding fragments thereof, nucleic acid encoding the same, therapeutic compositions thereof, and their use to enhance T-cell function to upregulate cell-mediated immune responses and for the treatment of T cell dysfunctional disorders, such as tumor immunity, for the treatment of and cancer.
    Type: Grant
    Filed: March 9, 2017
    Date of Patent: November 26, 2019
    Assignee: Merck Patent GmbH
    Inventors: Horacio G. Nastri, Christel Iffland, Olivier Leger, Qi An, Mark Cartwright, Sean D. McKenna
  • Patent number: 10466233
    Abstract: A nanosensor for detecting and quantifying lactate in different types of samples, such as tissues, intra-cellular and subcellular compartments, with high spatial and temporal resolution is disclosed. Methods comprising use of the nanosensor for quantifying the activity of lactate transporters, rates of cellular lactate production and cellular lactate consumption, and rate of mitochondrial pyruvate consumption are also disclosed. Methods for quantifying the transformation in energy metabolism that characterizes cancer cells with single-cell resolution and for detecting interference of candidate drugs with mitochondrial energetics are additionally disclosed.
    Type: Grant
    Filed: April 13, 2012
    Date of Patent: November 5, 2019
    Assignees: CENTRO DE ESTUDIOS CIENTIFICOS DE VALDIVIA, CARNEGIE INSTITUTION OF WASHINGTON
    Inventors: Luis Felipe Barros Olmedo, Alejandro San Martin, Sebastian Ceballo Charpentier, Wolf B. Frommer
  • Patent number: 10463029
    Abstract: This disclosure relates to a rodent model of Steel Syndrome. Disclosed herein are genetically modified rodent animals that carry a mutation in an endogenous rodent Col27a1 gene, equivalent to a mutation in humans causing Steel Syndrome.
    Type: Grant
    Filed: June 7, 2018
    Date of Patent: November 5, 2019
    Assignee: REGENERON PHARMACEUTICALS, INC.
    Inventors: Claudia Gonzaga-Jauregui, Chia-Jen Siao, Harikiran Nistala, Kalyan C. Nannuru
  • Patent number: 10450584
    Abstract: The present invention is directed to methods and compositions comprising novel CRISPR polypeptides and polynucleotides for site-specific cleavage and nicking of nucleic acids, transcriptional control and genome editing.
    Type: Grant
    Filed: August 27, 2015
    Date of Patent: October 22, 2019
    Assignee: NORTH CAROLINA STATE UNIVERSITY
    Inventors: Rodolphe Barrangou, Alexandra E. Briner
  • Patent number: 10433528
    Abstract: Mice that comprise a replacement of endogenous mouse IL-6 and/or IL-6 receptor genes are described, and methods for making and using the mice. Mice comprising a replacement at an endogenous IL-6R? locus of mouse ectodomain-encoding sequence with human ectodomain-encoding sequence is provided. Mice comprising a human IL-6 gene under control of mouse IL-6 regulatory elements is also provided, including mice that have a replacement of mouse IL-6-encoding sequence with human IL-6-encoding sequence at an endogenous mouse IL-6 locus.
    Type: Grant
    Filed: June 6, 2018
    Date of Patent: October 8, 2019
    Assignee: REGENERON PHARMACEUTICALS, INC.
    Inventors: Li-Hsien Wang, Anthony T. Dore, Jr., Sean Stevens, Andrew J. Murphy
  • Patent number: 10433527
    Abstract: The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use.
    Type: Grant
    Filed: May 15, 2018
    Date of Patent: October 8, 2019
    Assignees: Regeneron Pharmaceuticals, Inc., Yale University, Institute for Research in Biomedicine (IRB)
    Inventors: Richard Flavell, Markus Manz, Anthony Rongvaux, Till Strowig, Tim Willinger, Andrew J. Murphy, Sean Stevens, George Yancopoulos
  • Patent number: 10426146
    Abstract: Genetically modified non-human animals and methods and compositions for making and using the same are provided, wherein the genetic modification comprises a humanization of an endogenous signal-regulatory protein gene, in particular a humanization of a SIRP? gene. Genetically modified mice are described, including mice that express a human or humanized SIRP? protein from an endogenous SIRP? locus.
    Type: Grant
    Filed: January 3, 2019
    Date of Patent: October 1, 2019
    Assignee: REGENERON PHARMACEUTICALS, INC.
    Inventors: Andrew J. Murphy, O. Gavin Thurston, Bindu Varghese, Cagan Gurer
  • Patent number: 10412940
    Abstract: A genetically modified mouse is provided, wherein the mouse expresses an immunoglobulin light chain repertoire characterized by a limited number of light chain variable domains. Mice are provided that present a choice of two human light chain variable gene segments such that the immunoglobulin light chains expresses by the mouse comprise one of the two human light chain variable gene segments. Methods for making bispecific antibodies having universal light chains using mice as described herein, including human light chain variable regions, are provided. Methods for making human variable regions suitable for use in multispecific binding proteins, e.g., bispecific antibodies, and host cells are provided.
    Type: Grant
    Filed: September 11, 2018
    Date of Patent: September 17, 2019
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: John McWhirter, Lynn Macdonald, Sean Stevens, Andrew J. Murphy
  • Patent number: 10390522
    Abstract: 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: Grant
    Filed: June 19, 2015
    Date of Patent: August 27, 2019
    Assignee: REGENERON PHARMACEUTICALS, INC.
    Inventors: Elena Burova, Alexander O. Mujica, Ka-Man Venus Lai, Andrew J. Murphy
  • Patent number: 10314298
    Abstract: Genetically modified non-human animals comprising a human or humanized interleukin-7 (IL-7) gene. Cells, embryos, and non-human animals comprising a human or humanized IL-7 gene. Rodents that express human or humanized IL-7 protein. Genetically modified mice that comprise a human or humanized IL-7-encoding gene in their germline, wherein the human or humanized IL-7-encoding gene is under control of endogenous mouse IL-7 regulatory sequences.
    Type: Grant
    Filed: April 24, 2018
    Date of Patent: June 11, 2019
    Assignee: REGENERON PHARMACEUTICALS, INC.
    Inventor: Andrew J. Murphy
  • Patent number: 10306874
    Abstract: 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 Lymphocyte activation gene 3 (Lag3). The non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous Lag3 locus so that the non-human animals express a Lag3 polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).
    Type: Grant
    Filed: November 18, 2016
    Date of Patent: June 4, 2019
    Assignee: REGENERON PHARMACEUTICALS, INC.
    Inventors: Alexander O. Mujica, Elena Burova, Andrew J. Murphy
  • Patent number: 10299467
    Abstract: The present invention relates to the use of a genetically modified non-human animal as an animal model for obesity or obesity-related disorders, wherein the amount of Lysine-specific Demethylase 1 (LSD1) in at least one tissue or at least one cell type of said animal is reduced.
    Type: Grant
    Filed: October 31, 2013
    Date of Patent: May 28, 2019
    Assignee: UNIVERSITAETSKLINIKUM FREIBURG
    Inventors: Roland Schüle, Delphine Duteil, Eric Metzger, Thomas Günther
  • Patent number: 10266803
    Abstract: Genetically modified mice are provided that express human ? variable (hV?) sequences, including mice that express hV? sequences from an endogenous mouse ? light chain locus, mice that express hV? sequences from an endogenous mouse ? light chain locus, and mice that express hV? sequences from a transgene or an episome wherein the hV? sequence is linked to a mouse constant sequence. Mice are provided that are a source of somatically mutated human ? variable sequences useful for making antigen-binding proteins. Compositions and methods for making antigen-binding proteins that comprise human ? variable sequences, including human antibodies, are provided.
    Type: Grant
    Filed: November 13, 2017
    Date of Patent: April 23, 2019
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: Lynn Macdonald, Sean Stevens, Cagan Gurer, Andrew J. Murphy, Karolina A. Meagher
  • Patent number: 10251378
    Abstract: A transgenic mouse has a genome that includes the entire gene region of human transforming growth factor beta-1 (human TGF?1) located downstream of a mouse Podocin promoter such that expression of the human TGF?1 is controlled by the mouse Podocin promoter. The human TGF?1 contains 7 exons and 6 introns, the human TGF?1 is expressed in a kidney of the mouse as non-active TGF?1 and becomes active TGF?1 extracellularly, and the transgenic mouse spontaneously develops renal fibrosis.
    Type: Grant
    Filed: June 24, 2015
    Date of Patent: April 9, 2019
    Assignee: MIE UNIVERSITY
    Inventors: Yutaka Yano, Esteban C. Gabazza, Corina Gabazza
  • Patent number: 10251376
    Abstract: This document relates to methods and materials involved in the removal of senescent cells within a mammal. For example, transgenic non-human animals that can be induced to delete senescent cells are provided.
    Type: Grant
    Filed: April 2, 2018
    Date of Patent: April 9, 2019
    Assignee: MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH
    Inventors: James L. Kirkland, Tamar Tchkonia, Jan M. A. van Deursen, Darren J. Baker
  • Patent number: 10226033
    Abstract: The invention discloses methods for the generation of chimaeric human—non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanized antibodies; compositions comprising the antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in the methods.
    Type: Grant
    Filed: August 29, 2017
    Date of Patent: March 12, 2019
    Assignee: Kymab Limited
    Inventors: Allan Bradley, E-Chiang Lee, Qi Liang, Wei Wang, Dominik Spensberger, Hui Liu, Jasper Clube
  • Patent number: 10219494
    Abstract: Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise a humanized B-cell activating factor gene. Non-human animals and cells that express a human or humanized B-cell activating factor protein from an endogenous B-cell activating factor locus are described.
    Type: Grant
    Filed: March 15, 2017
    Date of Patent: March 5, 2019
    Assignee: REGENERON PHARMACEUTICALS, INC.
    Inventors: John McWhirter, Cagan Gurer, Lynn Macdonald, Andrew J. Murphy
  • Patent number: 10219493
    Abstract: The invention provides genetically modified non-human animals that express a humanized MHC II protein (humanized MHC II ? and ? polypeptides), as well as embryos, cells, and tissues comprising the humanized MHC II protein. Also provided are constructs for and methods of making said genetically modified non-human animals. Methods of using the genetically modified non-human animals to study various aspects of the human immune system are provided.
    Type: Grant
    Filed: January 24, 2017
    Date of Patent: March 5, 2019
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: Lynn Macdonald, Andrew J. Murphy, Naxin Tu, Cagan Gurer, Vera Voronina, Sean Stevens
  • Patent number: 10206379
    Abstract: Genetically modified non-human animals and methods and compositions for making and using the same are provided, wherein the genetic modification comprises a humanization of an endogenous signal-regulatory protein gene, in particular a humanization of a SIRP? gene. Genetically modified mice are described, including mice that express a human or humanized SIRP? protein from an endogenous SIRP? locus.
    Type: Grant
    Filed: January 10, 2018
    Date of Patent: February 19, 2019
    Assignee: REGENERON PHARMACEUTICALS, INC.
    Inventors: Andrew J. Murphy, O. Gavin Thurston, Bindu Varghese, Cagan Gurer
  • Patent number: 10202619
    Abstract: The invention relates to engineered CRISPR/Cas9 systems for genomic modification in mammalian cells. The present specification describes the design and testing of a polynucleotide encoding the Streptococcus pyogenes (S. pyogenes) Cas9 protein, where the nucleotide sequence has been optimized for expression in mammalian cells. The specification also describes all-in-one systems for RNA-guided genome engineering in mammalian cells, including human cells.
    Type: Grant
    Filed: October 5, 2015
    Date of Patent: February 12, 2019
    Assignee: SYSTEM BIOSCIENCES, LLC
    Inventor: Fangting Wu
  • Patent number: 10202589
    Abstract: Engineered CRISPR-Cas9 nucleases with altered and improved PAM specificities and their use in genomic engineering, epigenomic engineering, and genome targeting.
    Type: Grant
    Filed: March 3, 2016
    Date of Patent: February 12, 2019
    Assignee: The General Hospital Corporation
    Inventors: J. Keith Joung, Benjamin Kleinstiver
  • Patent number: 10172931
    Abstract: A recombinant baculovirus displaying on its envelop a fusion protein is disclosed. The fusion protein comprises a heterologous antigen, and a C-terminal region of baculovirus envelope GP64 protein, which has at least 100 amino acid residues in length and lacks a B12D5 binding epitope located within the central basic region of the GP64 protein. The genome of the recombinant baculovirus comprises a transgene encoding a fusion protein that comprises a signal peptide, the heterologous antigen, and the C-terminal region of the baculovirus envelope GP64 protein, in which the antigen is located between the signal peptide and the C-terminal region of the GP64 protein. Methods for eliciting an antigen-specific immunogenic response in a subject in need thereof are also disclosed.
    Type: Grant
    Filed: May 13, 2016
    Date of Patent: January 8, 2019
    Assignee: REBER GENETICS CO., LTD.
    Inventors: Chia-Jung Chang, Yan-Chiou Liao, Wei-I Chou, Hsiu-Kang Chang
  • Patent number: 10167344
    Abstract: A genetically modified mouse is provided, wherein the mouse expresses an immunoglobulin light chain repertoire characterized by a limited number of light chain variable domains. Mice are provided that present a choice of two human light chain variable gene segments such that the immunoglobulin light chains expresses by the mouse comprise one of the two human light chain variable gene segments. Methods for making bispecific antibodies having universal light chains using mice as described herein, including human light chain variable regions, are provided. Methods for making human variable regions suitable for use in multispecific binding proteins, e.g., bispecific antibodies, and host cells are provided.
    Type: Grant
    Filed: September 11, 2017
    Date of Patent: January 1, 2019
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: John McWhirter, Lynn Macdonald, Sean Stevens, Andrew J. Murphy
  • Patent number: 10159227
    Abstract: The present invention relates to a vector comprising a nucleic acid sequence that encodes the APP protein and/or the PS1 protein or variants thereof. The invention also relates to a method for inducing the Alzheimer's disease in an animal using the vector of the invention and to animal model having the Alzheimer's disease obtained by said method.
    Type: Grant
    Filed: November 5, 2014
    Date of Patent: December 25, 2018
    Assignees: INSERM (Institut National de la Sante et de la Recherche Medicale), Universite de Paris—Sud, Commissariat a l'Energie Atomique et aux Energies Alternatives, Centre National de la Recherche Scientifique (CNRS), Universite Paris Descartes
    Inventors: Nathalie Cartier-Lacave, Jerome Braudeau, Nicole Deglon, Philippe Hantraye, Mickael Audrain
  • Patent number: 10131712
    Abstract: The present invention concerns compositions and methods of use of bispecific antibodies comprising at least one binding site for a tumor-associated antigen (TAA) and at least one binding site for an antigen expressed on an effector T cell, NK cell, monocyte or neutrophil. The bispecific antibodies are of use for inducing an immune response against a TAA-expressing tumor. The methods may comprising administering the bispecific antibody in combination with one or more therapeutic agents such as antibody-drug conjugates, interferons (preferably interferon-?), and/or checkpoint inhibitor antibodies. The bispecific antibody is capable of targeting effector T cells, NK cells, monocytes or neutrophils to induce leukocyte-mediated cytotoxicity of cancer cells. The cytotoxic immune response is enhanced by co-administration of interferon, checkpoint inhibitor antibody and/or ADC. In preferred embodiments, the checkpoint inhibitor is a chimeric or humanized anti-PD1 antibody as described herein.
    Type: Grant
    Filed: May 24, 2017
    Date of Patent: November 20, 2018
    Assignee: IBC Pharmaceuticals, Inc.
    Inventors: Edmund A. Rossi, Chien-Hsing Chang, David M. Goldenberg
  • Patent number: 10080354
    Abstract: Described herein are nucleic acid constructs, hematopoietic stem cell identifier animals, and methods of using thereof for isolating hematopoietic stem cell populations. Also provided are methods of using the identifier animals and cells isolated from them to screen for agents that affect the growth, proliferation, potency, expansion, or maintenance of the stem cells. Such agents can be used for promoting growth of stem cells in vitro or in vivo, and also for inhibiting cancer cells that have been determined to resemble a stem cell.
    Type: Grant
    Filed: September 6, 2013
    Date of Patent: September 25, 2018
    Assignee: CHILDREN'S MEDICAL CENTER CORPORATION
    Inventors: Derrick J. Rossi, Roi Gazit
  • Patent number: 10047164
    Abstract: A composition comprising a TLR2 antagonistic antibody or antigen binding fragment thereof for use in the treatment or prophylaxis of pancreatic cancer is provided. The antibody or antigen binding fragment may be provided for simultaneous, separate or sequential administration with a secondary chemotherapeutic agent such as gemcitabine, and optionally a tertiary chemotherapeutic agent such as abraxane for enhanced treatment. Also provided is a screening method for the identification of compounds for use in treatment or prevention of pancreatic cancer.
    Type: Grant
    Filed: August 23, 2016
    Date of Patent: August 14, 2018
    Assignee: OPSONA THERAPEUTICS LIMITED
    Inventor: Thorsten Hagemann
  • Patent number: 10004211
    Abstract: Mice that comprise a replacement of endogenous mouse IL-6 and/or IL-6 receptor genes are described, and methods for making and using the mice. Mice comprising a replacement at an endogenous IL-6R? locus of mouse ectodomain-encoding sequence with human ectodomain-encoding sequence is provided. Mice comprising a human IL-6 gene under control of mouse IL-6 regulatory elements is also provided, including mice that have a replacement of mouse IL-6-encoding sequence with human IL-6-encoding sequence at an endogenous mouse IL-6 locus.
    Type: Grant
    Filed: November 14, 2016
    Date of Patent: June 26, 2018
    Assignee: REGENERON PHARMACEUTICALS, INC.
    Inventors: Li-Hsien Wang, Anthony T. Dore, Jr., Sean Stevens, Andrew J. Murphy