Method Of Making A Transgenic Nonhuman Animal Patents (Class 800/21)
  • Patent number: 10213282
    Abstract: A mammalian in vitro system for culturing an embryo includes a collagen or fibrin matrix and endometrial and/or stromal cells. The in vitro platforms and methods according to embodiments of the invention allow for in vitro embryonic development (including implantation) prior to transfer of the embryo complex in vivo for further development.
    Type: Grant
    Filed: April 28, 2015
    Date of Patent: February 26, 2019
    Assignee: California Institute of Technology
    Inventors: Samuel Ojosnegros Martos, Carol Readhead, Ayelet Lesman
  • Patent number: 10194645
    Abstract: The present invention provides in a first aspect a mouse in which the ? (lambda) light chain locus has been functionally silenced. In one embodiment, the mouse ? light chain locus was functional silenced by deletion of gene segments coding for the ? light chain locus. In a further aspect, a mouse containing functionally silenced ? and ? (kappa) L chain loci was produced. The invention is useful for the production of antibodies, for example heterologous antibodies, including heavy chain only antibodies.
    Type: Grant
    Filed: August 8, 2016
    Date of Patent: February 5, 2019
    Assignee: Crescendo Biologics Limited
    Inventors: Marianne Brüggemann, Xiangang Zou
  • Patent number: 10169653
    Abstract: A method, system and computer program product are disclosed for tagging a resource. In one embodiment, the method comprises receiving a given number of unique electronic tags for tagging a specified resource; for a harvested one of the specified resources, generating image data representing an image of the harvested resource, and selecting one of the electronic tags for the harvested resource; and sending the image data and data identifying the selected electronic tag to a specified entity to register the harvested resource. In an embodiment, the given number of unique physical tags are generated for the specified resource, and the generated image data include data representing one of the physical tags. In an embodiment, a mobile computing device is used to receive the electronic tags, to generate the image data, and to transmit the image data to the specified entity.
    Type: Grant
    Filed: August 23, 2016
    Date of Patent: January 1, 2019
    Assignee: International Business Machines Corporation
    Inventors: Gregory J. Boss, David R. Burns, Andrew R. Jones, Kevin C. McConnell
  • Patent number: 10072069
    Abstract: The invention relates to transgenic animals lacking endogenous Ig and capable of producing transgenic antibodies, as well as methods of making the same. The invention further relates to methods for producing transgenic antibodies in such animals, and transgenic antibodies so produced.
    Type: Grant
    Filed: July 8, 2016
    Date of Patent: September 11, 2018
    Inventor: Roland Buelow
  • Patent number: 9926558
    Abstract: The present invention develops a novel method for controlling mosquito populations. Culicinae mosquitoes carrying one or more loci of transformant Tra-2 RNAi constructs which target to mosquito Transformer-2 locus in respective or none respective Culicinae mosquitoes. Tra-2 sequences used to assemble Tra-2 RNAi recombinant constructs are Tra-2 gene sequences of Culicinae mosquitoes and can be derived from endogenous or exogenous sequences. The Tra-2 RNAi expression is conditional, wherein the expression causing a knockdown effect into the endogenous Tra-2 gene results in mortality of X (m) chromosome bearing sperms and produces maleness mosquito population in the nature environmental of the species.
    Type: Grant
    Filed: December 29, 2011
    Date of Patent: March 27, 2018
    Inventors: Duong Thanh Hoang, Kim Phuc Hoang
  • Patent number: 9743647
    Abstract: Non-human animals comprising a human or humanized IL-4 and/or IL-4R? nucleic acid sequence are provided. Non-human animals that comprise a replacement of the endogenous IL-4 gene and/or IL-4R? gene with a human IL-4 gene and/or IL-4R? gene in whole or in part, and methods for making and using the non-human animals, are described. Non-human animals comprising a human or humanized IL-4 gene under control of non-human IL-4 regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4-encoding sequence with human IL-4-encoding sequence at an endogenous non-human IL-4 locus. Non-human animals comprising a human or humanized IL-4R? gene under control of non-human IL-4R? regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4R?-encoding sequence with human or humanized IL-4R?-encoding sequence at an endogenous non-human C IL-4R? locus.
    Type: Grant
    Filed: July 6, 2015
    Date of Patent: August 29, 2017
    Assignee: REGENERON PHARMACEUTICALS, INC.
    Inventors: Li-Hsien Wang, Yingzi Xue, Andrew Murphy, Sean Stevens
  • Patent number: 9598721
    Abstract: The present invention provides a universally applicable lysis buffer comprising a chaotropic 5 agent, a reducing agent, and a proteolytic enzyme suitable for processing a wide variety of different sample types, such as different types of bodily samples relevant for the diagnosis of a respiratory disease. Furthermore, the present invention provides the use of a chaotropic agent, a reducing agent, and a proteolytic enzyme for the lysis of a broad spectrum of bodily samples. Moreover, the present invention provides a method for processing bodily samples which is universally applicable to the lysis of a variety of different types of bodily samples. Furthermore, the present invention provides methods for analyzing a bodily sample or for detecting the presence of a pathogen in a bodily sample, preferably, for diagnosing a respiratory disease, such as pneumonia or tuberculosis.
    Type: Grant
    Filed: May 9, 2011
    Date of Patent: March 21, 2017
    Assignee: Curetis GmbH
    Inventors: Matthias Klein, Gerd Lüdke, Andreas Boos
  • Patent number: 9592306
    Abstract: Provided herein are mitochondrial-nuclear exchanged cells and animals comprising mitochondrial DNA (mtDNA) from one subject and nuclear DNA (nDNA) from a different subject. Methods for producing a mitochondrial-nuclear exchanged animal and animals made by the methods are provided. Also provided are methods of screening for agents useful for treating a disease or disorder using mitochondrial-nuclear exchanged animals or cells, tissues or organs thereof.
    Type: Grant
    Filed: April 27, 2015
    Date of Patent: March 14, 2017
    Assignee: The UAB Research Foundation
    Inventors: Scott Webster Ballinger, Danny R. Welch, Robert Allen Kesterson, Larry W. Johnson
  • Patent number: 9573997
    Abstract: The present invention relates to a compound which is an antagonist of IL-1 beta or an inhibitor of IL-1 beta expression for use in the treatment or the prevention of aneurysm. In another embodiment, the invention relates to a pharmaceutical composition for use in the treatment or the prevention of aneurysm comprising an antagonist of IL-1 beta or an inhibitor of IL-1 beta expression.
    Type: Grant
    Filed: March 15, 2013
    Date of Patent: February 21, 2017
    Assignees: INSERM (Institut National de la Sante et de la Recherche Medicale), Universite Paris Descartes
    Inventors: Ziad Mallat, Soraya Taleb, Alain Tedgui
  • Patent number: 9447167
    Abstract: Disclosed is a novel means that enables mass production of highly safe fibrinogen at low cost. The transgenic silkworm of the present invention expresses the fibrinogen subunit A?, B? and ? chains in the silk gland cells and produces fibrinogen having coagulation activity in the cocoon filament. Preferably, the transgenic silkworm expresses the subunits in the middle silk gland cells and produces fibrinogen in the sericin layer of the cocoon filament. By recovering fibrinogen from the cocoon of the transgenic silkworm of the present invention, highly safe fibrinogen can be mass-produced at low cost.
    Type: Grant
    Filed: March 2, 2012
    Date of Patent: September 20, 2016
    Assignee: IMMUNO-BIOLOGICAL LABORATORIES CO., LTD
    Inventors: Satoshi Sekiguchi, Manabu Takahisa, Masahiro Tomita
  • Patent number: 9428767
    Abstract: The present invention provides polynucleotide vectors for high expression of heterologous genes, and methods for constructing such vectors. Some vectors further comprise novel transposons and transposases that further improve expression. Further disclosed are vectors that can be used in a gene transfer system for stably introducing nucleic acids into the DNA of a cell. The gene transfer systems can be used in methods, for example, but not limited to, gene expression, gene therapy, insertional mutagenesis, or gene discovery.
    Type: Grant
    Filed: April 9, 2015
    Date of Patent: August 30, 2016
    Assignee: DNA2.0, INC.
    Inventors: Jeremy Minshull, Mark Welch, Sridhar Govindrajan, Kate Caves
  • Patent number: 9204623
    Abstract: The present invention describes a novel transgenic mouse model for the common sporadic form of Alzheimer's disease. More particularly, the invention relates to a nucleotide sequence encoding A? 4-42 in functional linkage with at least a promoter, signal peptide sequence and a polyadenylation signal sequence, a cell and a transgenic non-human animal comprising said nucleotide sequence, and their respective use in screening methods.
    Type: Grant
    Filed: June 8, 2010
    Date of Patent: December 8, 2015
    Assignee: GEORG-AUGUST-UNIVERSITÄT GÖTTINGEN STIFTUNG ÖFFENTLICHEN RECHTS, UNIVERSITÄTSMEDIZIN
    Inventors: Thomas Bayer, Oliver Wirths
  • Patent number: 9198404
    Abstract: The present invention provides Maternal Sterility Constructs (MSC) and methods of producing sterile progeny lacking germ cells. Female animals carrying the MSC transgene will give rise to a sterile generation, as the MSC specifically eliminates Progenitor Germ Cells (PGCs) of her progeny. These females are called lineage ending females. Male animals carrying the MSC transgene, however, give rise to fertile progeny (assuming the male is not derived from an MSC-transgenic female). Thus, MSC transgenic males can be used to propagate the transgenic line. The invention can be advantageously applied to eliminate pest or invasive species, or to provide effective population control and improve culture performance of farmed species, such as fish and shellfish.
    Type: Grant
    Filed: November 23, 2010
    Date of Patent: December 1, 2015
    Assignee: AQUABOUNTY TECHNOLOGIES, INC.
    Inventors: Xavier Lauth, John T. Buchanan
  • Patent number: 9145560
    Abstract: The present invention relates to methods for producing transgenic animals, particularly transgenic rats, using retroviral constructs engineered to carry the transgene(s) of interest.
    Type: Grant
    Filed: January 28, 2008
    Date of Patent: September 29, 2015
    Assignee: California Institute of Technology
    Inventors: David Baltimore, Elizabeth J. Hong, Carlos Lois-Caballe, Shirley Pease
  • Patent number: 9125384
    Abstract: The invention relates to a method of selectively expanding human leukemic cells in a non-adult NOD/SCID/IL2rgnull mouse by transplanting a substance containing a leukemic stem cell derived from a human acute myelogenous leukemia patient to the mouse. In addition, the invention relates to screening for a medicament capable of eradicating leukemic stem cell (LSC), consideration of treatment methods suitable for individual patients, identification of a differentially expressed gene and the like, using a mouse with expanded human leukemic cells.
    Type: Grant
    Filed: October 17, 2008
    Date of Patent: September 8, 2015
    Assignees: RIKEN, The Jackson Laboratory
    Inventors: Fumihiko Ishikawa, Yoriko Saito, Osamu Ohara, Leonard D. Shultz
  • Patent number: 9121036
    Abstract: Promoters active in insects can be enhanced by positive feedback mechanisms and associated with repressible lethal effects.
    Type: Grant
    Filed: July 28, 2004
    Date of Patent: September 1, 2015
    Assignee: Oxitec Limited
    Inventor: Luke Alphey
  • Publication number: 20150143563
    Abstract: The invention is directed to reliable and efficient detection of mRNAs as well as other RNAs in living cells and its use to identify and, if desired, separate cells based on their desired characteristics. Such methods greatly simplify and reduce the time necessary to carry out previously-known procedures, and offers new approaches as well, such as selecting cells that generate a particular protein or antisense oligonucleotide, generating cell lines that express multiple proteins, generating cell lines with knock-out of one or more protein, and others.
    Type: Application
    Filed: January 16, 2015
    Publication date: May 21, 2015
    Inventors: Kambiz Shekdar, Gunter Blobel
  • Publication number: 20150143552
    Abstract: Provided is an arthropod male germline gene expression system suitable for conditional expression of an effector gene in an Arthropod male germline. The system comprises a first expression unit comprising an effector gene and a promoter therefor operably linked thereto; and a second expression unit. Said second unit comprises a coding sequence for a transcription factor and an upstream regulatory element operably linked thereto, the transcription factor being capable of acting upon the promoter in the first expression unit to drive expression of the effector gene. The upstream regulatory element includes a promoter for the transcription factor; and a 5? UTR adjacent a start site for the transcription factor coding sequence. The upstream regulatory element driving sufficient expression of the transcription factor such that the transcription factor protein in turn drives transcription of the effector gene before meiosis.
    Type: Application
    Filed: March 5, 2013
    Publication date: May 21, 2015
    Inventor: Luke Alphey
  • Publication number: 20150143559
    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 a proliferation-inducing ligand gene. Non-human animals and cells that express a human or humanized a proliferation-inducing ligand protein from an endogenous a proliferation-inducing ligand locus are described.
    Type: Application
    Filed: November 10, 2014
    Publication date: May 21, 2015
    Inventors: John McWhirter, Cagan Gurer, Lynn Macdonald, Andrew J. Murphy
  • Publication number: 20150143558
    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: Application
    Filed: November 10, 2014
    Publication date: May 21, 2015
    Inventors: John McWhirter, Cagan Gurer, Lynn Macdonald, Andrew J. Murphy
  • Publication number: 20150143560
    Abstract: The present invention relates to a technique for inducing epilepsy and a non-human animal model of epilepsy. More particularly, the present invention relates to a method for inducing epilepsy in an animal, a non-human animal model of epilepsy, and a method for manufacturing the same.
    Type: Application
    Filed: November 14, 2014
    Publication date: May 21, 2015
    Inventors: JEONG HO LEE, DONG SEOK KIM, JAE SEOK LIM, HOON CHUL KANG
  • Publication number: 20150135346
    Abstract: The subject invention provides materials and method for making a recessive gene dominant. This is accomplished by interfering with the natural mechanisms that inhibit expression of the recessive gene and/or by interfering with the expression of the naturally dominant gene. In a preferred embodiment, the method of the subject invention comprises both reducing inhibition of expression of the recessive gene and increasing inhibition of the dominant gene.
    Type: Application
    Filed: November 8, 2014
    Publication date: May 14, 2015
    Inventor: James WEST
  • Publication number: 20150135345
    Abstract: Rationally-designed LAGLIDADG meganucleases and methods of making such meganucleases are provided. In addition, methods are provided for using the meganucleases to generate recombinant cells and organisms having a desired DNA sequence inserted into a limited number of loci within the genome, as well as methods of gene therapy, for treatment of pathogenic infections, and for in vitro applications in diagnostics and research.
    Type: Application
    Filed: August 19, 2014
    Publication date: May 14, 2015
    Inventors: James Jefferson SMITH, Derek JANTZ, Homme W. HELLINGA
  • Publication number: 20150128298
    Abstract: The present invention provides a mouse with liver damage, having a high degree of damage against the mouse's original hepatocytes while having a uPA gene in a heterozygous form, and a method for efficiently preparing the mouse. Specifically, the method for preparing a mouse with liver damage having the uPA gene in a heterozygous form comprises the following steps of: (i) transforming mouse ES cells with a DNA fragment containing a liver-specific promoter/enhancer and cDNA that encodes a urokinase-type plasminogen activator operably linked under the control thereof; (ii) injecting the transformed mouse ES cells obtained in step (i) into a host embryo; (iii) transplanting the host embryo obtained in step (ii) via the injection of the ES cells into the uterus of a surrogate mother mouse, so as to obtain a chimeric mouse; and (iv) crossing the chimeric mice obtained in step (iii), so as to obtain a transgenic mouse in which the DNA fragment is introduced in a heterozygous form.
    Type: Application
    Filed: April 25, 2013
    Publication date: May 7, 2015
    Applicants: TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, PHOENIXBIO CO., LTD., CHUGAI SEIYAKU KABUSHIKI KAISHA
    Inventors: Michinori Kohara, Koichi Jishage, Yosuke Kawase, Chise Mukaidani, Hiroki Oshita, Satoko Hamamura
  • Publication number: 20150128300
    Abstract: The disclosure provides methods and compositions for generating conditional knock-out alleles using donor constructs together with sequence-specific nucleases to generate conditional knock-out alleles. Specifically, the donor construct comprises a 5? homology region, a 5? recombinase recognition site, a donor sequence, a 3? recombinase recognition site, and a 3? homology region. Further disclosed are the donor sequences each comprises a target sequence having at least one neutral mutation. Different sequence-specific nucleases can be used with the donor constructs are further disclosed.
    Type: Application
    Filed: June 12, 2013
    Publication date: May 7, 2015
    Inventors: Soren Warming, Keith R. Anderson
  • Publication number: 20150113669
    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: Application
    Filed: September 25, 2014
    Publication date: April 23, 2015
    Inventors: Allan Bradley, E-Chiang Lee, Qi Liang, Wei Wang
  • Publication number: 20150106964
    Abstract: The methods of producing an organism capable of ingesting and digesting omega-3 rich sources; for producing an organism that desires the consumption of omega-3 rich sources; and for producing an omega-3 enriched hybrid organism are each described. Each method isolates a donor DNA/RNA strand of a donor organism; extracts the donor DNA/RNA strand from the donor organism; and fuses the donor DNA/RNA strand into a receiving DNA/RNA strand of a receiving organism. In the first method, the donor organism is capable of ingesting and digesting omega-3 rich sources, and the receiving organism is incapable of ingesting or digesting omega-3 rich sources. In the second method, the donor organism desires the consumption of omega-3 rich sources, and the receiving organism does not desire the consumption of omega-3 rich sources. In the third method, the donor organism produces omega-3 fatty acids, and the receiving organism is unable to produce omega-3 fatty acids.
    Type: Application
    Filed: December 22, 2014
    Publication date: April 16, 2015
    Inventor: Sadia Ross Barrameda
  • Publication number: 20150106963
    Abstract: Novel mutations in cytochrome P450C17 (CYP17) and cytochrome b5 (CYB5) affecting 16-androstene steroid synthesis are disclosed. The novel mutations result in alterations in production of critical intermediaries in the synthesis of 16-androstene steroids. Altering the activity of these enzymes may be useful in enhancing reducing androstenone synthesis and reducing boar taint. The identification of these novel mutations also allows for the development of transgenic pigs bearing mutations in these enzymes or for genetic screening to identify pigs on the basis of their CYP17 and/or CYB5 genotype. Pigs having these mutations may be selected and bred to produce pigs that have a lower incidence of boar taint.
    Type: Application
    Filed: October 13, 2014
    Publication date: April 16, 2015
    Inventor: E. James Squires
  • Publication number: 20150106961
    Abstract: 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: Application
    Filed: October 15, 2014
    Publication date: April 16, 2015
    Applicant: REGENERON PHARMACEUTICALS, INC.
    Inventors: Jose F. Rojas, Ka-Man Venus Lai, Andrew J. Murphy
  • Publication number: 20150089678
    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: Application
    Filed: September 23, 2014
    Publication date: March 26, 2015
    Applicant: REGENERON PHARMACEUTICALS, INC.
    Inventors: Andrew J. Murphy, O. Gavin Thurston, Bindu Varghese, Cagan Gurer
  • Patent number: 8986743
    Abstract: In a method for preparing an animal model for the human immune system in a non-human mammal, human stem cells with hematopoietic potential are transplanted into a non-human mammal. The non-human mammal is conditioned with cell culture supernatant of a culture of human cell lines, cells and/or tissue. The cell culture supernatant is derived from cell lines producing cytokines and other molecular mediators.
    Type: Grant
    Filed: May 17, 2006
    Date of Patent: March 24, 2015
    Assignee: Universität Leipzig
    Inventors: Frank Emmrich, Manja Kamprad, Manuela Ackermann
  • Publication number: 20150067900
    Abstract: The present invention relates to polypeptides and more particularly to Transcription Activator-Like Effector derived proteins that allow to efficiently target and/or process nucleic acids. The present invention also concerns methods to use these proteins. The present invention also relates to vectors, compositions and kits in which RVD domains and Transcription Activator-Like Effector (TALE) proteins of the present invention are used.
    Type: Application
    Filed: March 15, 2013
    Publication date: March 5, 2015
    Applicant: Cellectis, S.A.
    Inventors: Philippe Duchateau, Alexandre Juillerat, Claudia Bertonati
  • Publication number: 20150056636
    Abstract: The present invention provides a transgenic mouse which comprises a deficiency for murine T lymphocytes, B lymphocytes and NK cells, a deficiency for murine MHC class I and MHC class II molecules, and a functional xenogenic SIRP? transgene. This mouse is useful for in vivo screening of various compounds, including immuno-therapeutic agents and vaccines. The said mouse is also useful for testing the in vivo metabolism of xenobiotic compounds.
    Type: Application
    Filed: March 26, 2013
    Publication date: February 26, 2015
    Inventors: Sylvie Garcia, Malika Serra-Hassoun
  • Patent number: 8962912
    Abstract: The present invention relates, in general, to development of non-human transgenic animals expressing a human blood clotting factor, such as Factor VIII, Factor VII, Factor IX and von Willebrand factor. The invention further provides methods of detecting immunogenic events against human blood clotting factor using the transgenic animals described.
    Type: Grant
    Filed: March 24, 2011
    Date of Patent: February 24, 2015
    Assignees: Baxter International Inc., Baxter Healthcare SA
    Inventors: Maria Sasgary, Maria Schuster, Hans-Peter Schwarz, Birgit Maria Reipert, Gerhard Antoine, Hartmut Ehrlich
  • Patent number: 8962913
    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: March 12, 2013
    Date of Patent: February 24, 2015
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventor: Andrew J. Murphy
  • Publication number: 20150052625
    Abstract: The present invention provides embryonic stem cells obtainable from an embryo of an immunodeficient mouse which is deficient in both Rag2 and Jak3 genes by culture in the presence of a GSK3 inhibitor and an MEK inhibitor, as well as a transgenic mouse, which is created with the use of these embryonic stem cells.
    Type: Application
    Filed: March 27, 2012
    Publication date: February 19, 2015
    Applicants: Trans Genic Inc., National University Corporation Kumamoto University
    Inventors: Ken-ichi Yamamura, Kimi Araki, Seiji Okada, Akihiko Shimono
  • Publication number: 20150047060
    Abstract: A non-human transgenic animal having a polynucleotide encoding a PTN polypeptide, which polynucleotide is operably linked to a promoter, wherein said transgenic animal has greater than wild-type expression of the PTN polypeptide in at least one brain region, as well as related vectors, methods of producing transgenic animals, in vitro and in vivo screening methods for potential therapeutic agents, and methods for treating and diagnosing neuropsychiatric illnesses, particularly anxiety and depression, are disclosed.
    Type: Application
    Filed: March 14, 2013
    Publication date: February 12, 2015
    Applicant: BRAINCO BIOPHARMA, S.L.
    Inventors: David Arteta, Marcelo Ferrer, Laureano Simon, Antonio Martinez, Maria Uribarri
  • Publication number: 20150047061
    Abstract: Genetically modified mice comprising a nucleic acid sequence encoding a human M-CSF protein are provided. Also provided are genetically modified mice comprising a nucleic acid sequence encoding a human M-CSF protein that have been engrafted with human cells such as human hematopoietic cells, and methods for making such engrafted mice. These mice find use in a number of applications, such as in modeling human immune disease and pathogen infection; in in vivo screens for agents that modulate hematopoietic cell development and/or activity, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to hematopoietic cells; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on hematopoietic cells; in in vivo screens of human hematopoietic cells from an individual to predict the responsiveness of an individual to a disease therapy, etc.
    Type: Application
    Filed: August 26, 2014
    Publication date: February 12, 2015
    Inventors: Andrew J. Murphy, Sean Stevens, Chozhavendan Rathinam, Elizabeth Eynon, Markus Manz, Richard Flavell, George D. Yancopoulos
  • Patent number: 8952215
    Abstract: The present inventors produced transgenic silkworms which comprise a promoter of a DNA encoding a protein specifically expressed in the silk gland and a DNA encoding a recombinant antibody whose expression is regulated directly or indirectly by the promoter, and which secrete the recombinant antibody into the silk gland. The recombinant antibodies produced from the silk gland of the transgenic silkworms were confirmed to be active.
    Type: Grant
    Filed: October 18, 2006
    Date of Patent: February 10, 2015
    Assignees: Nitto Boseki Co., Ltd., National Institute of Agrobiological Sciences
    Inventors: Toshiki Tamura, Isao Kobayashi, Toshio Kanda, Keiro Uchino, Katsuhiro Katayama, Tatsuya Ohashi, Iwao Kiyokawa, Hisae Arai, Noriyuki Funahashi
  • Publication number: 20150040254
    Abstract: Provided is a porcine CD28 receptor molecule, which is: 1) a protein consisting of an amino acid sequence represented by SEQ ID NO:2, or 2) a protein derived from 1) by substitution, deletion or addition of one or several amino acids in the amino acid sequence represented by SEQ ID NO:2 and having equivalent activity with 1). Further provided is a gene for coding the porcine CD28 receptor, the nucleotide sequence of which is shown as SEQ ID NO:1. When the provided co-stimulating receptor CD28 is expressed specifically and highly in a T cell, the activation, proliferation and cell factor secretion activity of the T cell when stimulated by an antigen can be enhanced, thereby enhancing the acquired immune response of a host and enhancing the immune effect of a vaccine. FIG. 8 is selected as the drawing attached to the Abstract.
    Type: Application
    Filed: December 19, 2011
    Publication date: February 5, 2015
    Applicant: CHINA AGRICULTURAL UNIVERSITY
    Inventors: Xun Suo, Xianyong Liu, Huali Su, Xinxin Zhao, Xiaoxi Huang
  • Publication number: 20150040253
    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 same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.
    Type: Application
    Filed: August 8, 2014
    Publication date: February 5, 2015
    Inventors: Lynn Macdonald, Andrew J. Murphy, Naxin Tu, Cagan Gurer, Vera Voronina, Sean Stevens
  • Patent number: 8946504
    Abstract: 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: Grant
    Filed: July 3, 2013
    Date of Patent: February 3, 2015
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: David Frendewey, Guochun Gong, Ka-Man Venus Lai, David M. Valenzuela
  • Patent number: 8946505
    Abstract: 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: Grant
    Filed: July 3, 2013
    Date of Patent: February 3, 2015
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: David Frendewey, Guochun Gong, Ka-Man Venus Lai, David M. Valenzuela
  • Publication number: 20150033372
    Abstract: The present invention relates inter alia to improvements in the production of chimaeric antibodies in non-human transgenic vertebrates such as mice and rats bearing one or more chimaeric antibody transgenes. In particular, the invention provides for improved non-human vertebrates and cells in which VpreB has been species-matched with the variable region of the chimaeric antibodies. Also, embodiments also provide for species-matching of the entire surrogate light chain for efficient pairing with chimaeric heavy chains during B-cell development in vivo in a non-human transgenic vertebrate setting.
    Type: Application
    Filed: March 26, 2014
    Publication date: January 29, 2015
    Applicant: Kymab Limited
    Inventors: Allan Bradley, E-Chiang Lee, Qi Liang, Dominik Spensberger, Nicholas England
  • Publication number: 20150026831
    Abstract: This invention relates transgenic animals that overexpress TL1A in a tissue specific manner to model inflammatory bowel disease (IBD), such as colitis, Crohn's disease and ulcerative colitis, fibrosis, and related inflammatory diseases and conditions. TL1A transgenic animals constitutively express both TL1A and GFP in lymphoid and myeloid cell lineages, allowing convenient identification and sorting of immune cells involved in IBD disease progression, such as T-cells, antigen presenting cells (APC), and dendritic cells (DC). TL1A transgenic animals may be induced to exhibit gross fibrosis, or isolated cells may be implanted into immunodeficient mice to establish colitis.
    Type: Application
    Filed: May 8, 2014
    Publication date: January 22, 2015
    Applicant: CEDARS-SINAI MEDICAL CENTER
    Inventors: David Q. Shih, Stephan R. Targan
  • Publication number: 20150020224
    Abstract: Non-human animals, e.g., mammals, e.g., mice or rats, are provided comprising an immunoglobulin heavy chain locus that comprises a rearranged human immunoglobulin heavy chain variable region nucleotide sequence. The rearranged human immunoglobulin heavy chain variable region nucleotide sequence may be operably linked to a heavy or light chain constant region nucleic acid sequence. Also described are genetically modified non-human animals comprising an immunoglobulin light chain locus comprising one or more but less than the wild type number of human immunoglobulin light chain variable region gene segments, which may be operably linked to a light chain constant region nucleic acid sequence. Also provided are methods for obtaining nucleic acid sequences that encode immunoglobulin light chain variable domains capable of binding an antigen in the absence of a heavy chain.
    Type: Application
    Filed: September 26, 2014
    Publication date: January 15, 2015
    Applicant: Regeneron Pharmaceuticals, Inc.
    Inventors: John McWhirter, Cagan Gurer, Karolina A. Meagher, Lynn Macdonald, Andrew J. Murphy
  • Publication number: 20150020223
    Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.
    Type: Application
    Filed: September 9, 2014
    Publication date: January 15, 2015
    Inventors: Feng Zhang, Randall Jeffrey Platt, Guoping Feng, Yang Zhou
  • Patent number: 8933203
    Abstract: A method of using vaults as carrier molecules to deliver one or more than one substance to an organism, or to a specific tissue or to specific cells, or to an environmental medium. A vault-like particle. A method of preventing damage by one or more than one substance to an organism, to a specific tissue, to specific cells, or to an environmental medium, by sequestering the one or more than one substance within a vault-like particle. A method of delivering one or more than one substance or a sensor to an organism, to a specific tissue, to specific cells, or to an environmental medium. According to another embodiment of the present invention, there is provided a method of making vault-like particles, and making vault-like particles comprising one or more than one substance, or one or more than one sensor.
    Type: Grant
    Filed: October 15, 2008
    Date of Patent: January 13, 2015
    Assignee: The Regents of the University of California
    Inventors: Leonard H. Rome, Valerie A. Kickhoefer, Raval-Fernandes Sujna, Phoebe L. Stewart
  • Publication number: 20150013023
    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: Application
    Filed: September 19, 2014
    Publication date: January 8, 2015
    Applicant: REGENERON PHARMACEUTICALS, INC.
    Inventors: Li-Hsien Wang, Anthony T. Dore, JR., Sean Stevens, Andrew J. Murphy
  • Publication number: 20150013022
    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: Application
    Filed: September 19, 2014
    Publication date: January 8, 2015
    Applicant: REGENERON PHARMACEUTICALS, INC.
    Inventors: Li-Hsien Wang, Anthony T. Dore, JR., Sean Stevens, Andrew J. Murphy