Mouse Patents (Class 800/18)
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Publication number: 20140120582Abstract: 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: ApplicationFiled: November 14, 2013Publication date: May 1, 2014Applicant: Kymab LimitedInventors: Allan Bradley, E-Chiang Lee, Qi Liang, Wei Wang, Anais Legent, Ian Kirby
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Publication number: 20140115729Abstract: The present application relates to apoptotic anti-IgE antibodies, nucleic acid encoding the same, therapeutic compositions thereof, and their use in the treatment of IgE-mediated disorders.Type: ApplicationFiled: December 20, 2013Publication date: April 24, 2014Applicant: Genentech, Inc.Inventors: Lawren Wu, Mercedesz Balazs, Hans Brightbill, Andrew Chan, Yvonne Chen, Anan Chuntharapai, Mark Dennis, Terence Wong
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Patent number: 8704037Abstract: The present invention provides compositions and methods for studying neuropathy. The compositions and methods provided herein are particularly useful for screening agents of therapeutic and/or diagnostic potential.Type: GrantFiled: December 21, 2011Date of Patent: April 22, 2014Assignee: Case Western Reserve UniversityInventors: Stephen M. Selkirk, Robert H. Miller
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Patent number: 8703485Abstract: 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: GrantFiled: May 30, 2008Date of Patent: April 22, 2014Assignee: OMT, Inc.Inventor: Roland Buelow
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Patent number: 8697939Abstract: The present invention relates to Glycine N-methyltransferase (GNMT) animal model and use thereof.Type: GrantFiled: June 16, 2011Date of Patent: April 15, 2014Assignee: National Yang Ming UniversityInventors: Yi-Ming Chen, Ching-Ping Yang
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Patent number: 8692052Abstract: A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mII2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/II2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.Type: GrantFiled: September 14, 2012Date of Patent: April 8, 2014Assignees: Regeneron Pharmaceuticals, Yale University, Institute for Research in Biomedicine (IRB)Inventors: Sean Stevens, Andrew J. Murphy, Richard Flavell, Elizabeth Eynon, Jorge Galan, Tim Willinger, Markus Manz, Anthony Rongvaux, George D. Yancopoulos
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Publication number: 20140075586Abstract: Non-human totipotent or pluripotent cells are provided comprising at a genomic locus a self-excisable, recombinase expression cassette flanked with recombination recognition sites, wherein a recombinase gene is operably linked to a promoter that is active in a post-meiotic spermatid stage when cytoplasmic bridging occurs between spermatids. Compositions and methods are provided for making cassette-deleted F1 non-human animals, wherein the methods comprise employing totipotent or pluripotent cells containing a self-excisable, recombinase expression cassette.Type: ApplicationFiled: November 13, 2013Publication date: March 13, 2014Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Guochun Gong, Ka-Man Venus Lai, David Frendewey, David M. Valenzuela
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Publication number: 20140068797Abstract: The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.Type: ApplicationFiled: March 15, 2013Publication date: March 6, 2014Applicants: UNIVERSITY OF VIENNA, THE REGENTS OF THE UNIVERSITY OF CALIFORNIAInventors: Jennifer A. Doudna, Martin Jinek, Emmanuelle Charpentier, Krzysztof Chylinski, James Harrison Doudna Cate, Wendell Lim, Lei Qi
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Patent number: 8658854Abstract: The instant invention relates to the use of 24-hydroxylated vitamin D compounds as therapeutics in mammalian bone fracture repair. In addition, the instant invention relates to novel 24-hydroxylated vitamin D compound receptors which can be employed in the development of compounds capable of facilitating fracture repair in animals. The instant invention also relates to nucleic acids encoding such receptors as well as vectors, host cells, transgenic animals comprising such nucleic acids and screening assays employing such receptors.Type: GrantFiled: May 30, 2013Date of Patent: February 25, 2014Assignee: Shriners Hospital For ChildrenInventor: Rene St-Arnaud
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Patent number: 8658853Abstract: Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion of the endogenous low affinity Fc?R locus, and wherein the mouse is capable of expressing a functional FcR?-chain. Genetically modified mice are described, including mice that express low affinity human Fc?R genes from the endogenous Fc?R locus, and wherein the mice comprise a functional FcR?-chain. Genetically modified mice that express up to five low affinity human Fc?R genes on accessory cells of the host immune system are provided.Type: GrantFiled: May 8, 2012Date of Patent: February 25, 2014Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Lynn Macdonald, Naxin Tu, Cagan Gurer, Sean Stevens, Andrew J Murphy
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Publication number: 20140053287Abstract: This invention relates to polypeptides having aldolase activity, including pyruvate activity such as, without limitation, HMG and/or KHG aldolase activity, polynucleotides encoding these polypeptides, and methods of making and using these polynucleotides and polypeptides. In some embodiments, the invention is directed to polypeptides having aldolase activity, including pyruvate activity such as, without limitation, HMG and/or KHG aldolase activity, including thermostable and thermotolerant activity, and polynucleotides encoding these enzymes, and making and using these polynucleotides and polypeptides. The polypeptides in accordance with the invention can be used in a variety of pharmaceutical, agricultural and industrial contexts.Type: ApplicationFiled: August 14, 2013Publication date: February 20, 2014Applicant: VERENIUM CORPORATIONInventors: David P. WEINER, Lishan ZHAO, Peter LUGINBUHL, Ellen BURKE, Toby H. RICHARDSON, Paula M. HICKS
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Publication number: 20140053288Abstract: The present invention relates to a model animal spontaneously developing anemia. More specifically, the invention relates to a transgenic non-human mammal spontaneously developing anemia associated with a postnatal decrease in production of erythropoietin (Epo), Epo-producing cells prepared from the transgenic non-human mammal, and a screening method using the Epo-producing cells.Type: ApplicationFiled: March 29, 2012Publication date: February 20, 2014Applicant: TOHOKU TECHNO ARCH CO., LTD.Inventors: Masayuki Yamamoto, Naoko Minegishi, Shun Yamazaki
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Patent number: 8653324Abstract: Mice comprising a human p16 transgene operably linked to an inducible promoter and capable of controlled expression of p16 are provided. Also provided are cells, tissues, and organs obtainable from such mice, and methods for producing p16 transgenic mice.Type: GrantFiled: June 10, 2011Date of Patent: February 18, 2014Assignee: Fox Chase Cancer CenterInventor: Greg H. Enders
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Publication number: 20140047572Abstract: Disclosed are transgenic non-human mammals, which useful for the screening of thrombopoietin mimetics, thrombopoietin receptor agonists, or thrombopoietin receptor antagonists active on the human thrombopoietin receptor. The transgenic non-human mammal has a genome that comprises a stably integrated transgene construct comprising a polynucleotide sequence encoding a humanized thrombopoietin receptor wherein said transgenic non-human mammal has a baseline blood platelet count corresponding to a physiological blood platelet count of a matched non-transgenic non-human mammal. The chimeric thrombopoietin receptor comprises either the transmembrane domain of a human thrombopoietin receptor or both the extracellular and transmembrane domains of a human thrombopoietin receptor operably coupled to a cytoplasmic domain of a non-human thrombopoietin receptor.Type: ApplicationFiled: March 15, 2013Publication date: February 13, 2014Applicant: University of RochesterInventors: Yuhchyau CHEN, J.H. David WU, Jane L. LIESVELD, Lin GAN
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Publication number: 20140041068Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.Type: ApplicationFiled: October 4, 2013Publication date: February 6, 2014Applicant: REGENERON PHARMACEUTICALS, INC.Inventors: ANDREW J. MURPHY, GEORGE D. YANCOPOULOS, MARGARET KAROW, LYNN MACDONALD, SEAN STEVENS
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Publication number: 20140033337Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.Type: ApplicationFiled: October 4, 2013Publication date: January 30, 2014Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Andrew J. Murphy, George D. Yancopoulos, Margaret Karown, Lynn Macdonald, Sean Stevens
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Publication number: 20140024066Abstract: An animal model includes a photo-activatable fluorescent protein that can conditionally label the mitochondria throughout the animal or in selective animal cells and tissues, allowing for effective studying of the mitochondria and tracking of mitochondrial dynamics.Type: ApplicationFiled: June 20, 2013Publication date: January 23, 2014Inventors: David C. Chan, Anh H. Pham
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Patent number: 8633348Abstract: The present invention provides a genetically-modified non-human animal whose somatic and germ cells contain an exogenous gene encoding a recombinant fusion protein, wherein the presence, and expression, of said recombinant fusion protein renders said genetically-modified non-human animal sterile. Tools for generating such sterile genetically-modified non-human animal as well as methods of use thereof are also provided.Type: GrantFiled: August 26, 2010Date of Patent: January 21, 2014Assignees: Novartis Forschungsstiftung, Zweigniederlassung, Friedrich Miescher Institute for Biomedical Research, Universität ZürichInventors: Pawel Pelczar, Thorsten Buch, Antoine Peters
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Publication number: 20140020124Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.Type: ApplicationFiled: September 25, 2013Publication date: January 16, 2014Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Andrew J. Murphy, George D. Yancopoulos, Margaret Karow, Lynn Macdonald, Sean Stevens
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Publication number: 20140020125Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.Type: ApplicationFiled: September 25, 2013Publication date: January 16, 2014Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Andrew J. Murphy, George D. Yancopoulos, Margaret Karow, Lynn Macdonald, Sean Stevens
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Patent number: 8629318Abstract: The invention relates to the generation of non-human transgenic animals comprising a reporter construct for producing a detectable amount of a reporter molecule operably linked to a transcriptional regulatory nucleic acid molecule from the human CYP3A4 gene located between the initiation of transcription site of the gene and a position located 13,000 nucleotides upstream from the site. The invention also relates to the use of these animals for determining the effect of a compound, particularly, but not exclusively, a xenobiotic or steroid, on the regulation of expression of the CYP3A4 gene in a human.Type: GrantFiled: August 12, 2010Date of Patent: January 14, 2014Assignee: University of SydneyInventors: Christopher Liddle, Bryan James Goodwin, Graham Robertson
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Publication number: 20140010833Abstract: The present invention relates to immunogenic peptides and their various applications. In particular the invention relates to immunogenic peptides derived from the PASD1 protein and their use in therapeutic, diagnostic and prognostic methods.Type: ApplicationFiled: July 10, 2013Publication date: January 9, 2014Inventors: Karen Pulford, Alison Banham, Amanda Anderson, Kamel Ait-Tahar
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Publication number: 20140013456Abstract: A genetically modified non-human animal is provided, wherein the non-human animal expresses an antibody repertoire capable of pH dependent binding to antigens upon immunization. A genetically modified non-human animal is provided that expresses human immunoglobulin light chain variable domains derived from a limited repertoire of human immunoglobulin light chain variable gene segments that comprise histidine modifications in their germline sequence. Methods of making non-human animals that express antibodies comprising histidine residues encoded by histidine codons introduced into immunoglobulin light chain nucleotide sequences are provided.Type: ApplicationFiled: September 18, 2013Publication date: January 9, 2014Applicant: Regeneron Pharmaceuticals, Inc.Inventors: John MCWHIRTER, Lynn MACDONALD, Andrew J. MURPHY
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Patent number: 8624079Abstract: The present invention relates to transgenic non-human animals, tissues or cells derived therefrom and methods of producing them. The transgenic non-human animals or tissues or cells derived therefrom provide a system capable of expressing human proteins responsible for drug metabolism in place of the homologous endogenous non-human animal proteins and for the controlled expression of human genes introduced into the animal so that the expression of the human genes is regulated in a manner more closely analogous to that seen in vivo in humans. One aspect of the invention relates to the use of a human DNA sequence comprising at least part of introns 6 and/or 7 of the human PXR gene.Type: GrantFiled: June 4, 2008Date of Patent: January 7, 2014Assignee: ITI Scotland LimitedInventors: Charles Roland Wolf, Nico Scheer
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Publication number: 20130347138Abstract: The invention provides improved non-human vertebrates and non-vertebrate cells capable of expressing antibodies, eg, comprising human variable region sequences. The invention provides for enhanced AID and/or AID homologue spectra, thereby providing for the increased diversity as a result of somatic hypermutation and/or class-switch recombination during in vivo antibody generation. The invention also provides methods of generating antibodies using such vertebrates, as well as the antibodies per se, therapeutic compositions thereof and uses.Type: ApplicationFiled: May 8, 2013Publication date: December 26, 2013Applicant: Kymab LimitedInventor: Kymab Limited
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Publication number: 20130347134Abstract: The present invention provides, inter alia, transgenic non-human animals, such as transgenic mice. The animals contain in their genome a polynucleotide encoding a von Willebrand factor (VWF) polypeptide, which polypeptide forms a thrombus when in the presence of human platelets. Nucleic acid sequences and vectors for generating the transgenic non-human animals, and methods for using the transgenic non-human animals are provided as well. Chimeric VWF proteins are also provided.Type: ApplicationFiled: June 20, 2013Publication date: December 26, 2013Inventors: Thomas Diacovo, Jianchun Chen
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Publication number: 20130340105Abstract: The invention relates generally to compositions and methods of using transgenic non-human animals expressing human SIRP? that are engrafted with a human hematopoietic system. In various embodiments, the human hematopoietic system engrafted, human SIRP? transgenic non-human animals of the invention are useful as systems for the in vivo evaluation of the growth and differentiation of hematopoietic and immune cells, for the in vivo assessment of an immune response, for the in vivo evaluation of vaccines and vaccination regimens, for in vivo production and collection of immune mediators, including human antibodies, and for use in testing the effect of agents that modulate hematopoietic and immune cell function.Type: ApplicationFiled: September 20, 2011Publication date: December 19, 2013Applicant: Yale UniversityInventors: Richard A. Flavell, Till Strowig, Elizabeth Eynon, William Philbrick, Markus Manz
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Publication number: 20130340104Abstract: 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: ApplicationFiled: March 12, 2013Publication date: December 19, 2013Applicant: Regeneron Pharmaceuticals, Inc.Inventor: Andrew J. Murphy
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Patent number: 8609927Abstract: The present invention embraces a transgenic mouse whose genome harbors a nucleic acid molecule encoding caveolin-1 fused in-frame with a reporter. To control expression of the Cav1-reporter, the nucleic acid molecule further includes a selectable marker expression cassette flanked by recombinase target sites in such a manner that, upon exposure to recombinase, said selectable marker expression cassette is excised from said nucleic acid molecule.Type: GrantFiled: May 21, 2010Date of Patent: December 17, 2013Assignee: Trustees of Dartmouth CollegeInventor: Radu V. Stan
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Publication number: 20130333057Abstract: Mice, embryos, cells, and tissues having a restricted immunoglobulin heavy chain locus and an ectopic sequence encoding one or more ADAM6 proteins are provided. In various embodiments, mice are described that have humanized endogenous immunoglobulin heavy chain loci and are capable of expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof that is functional in a male mouse. Mice, embryos, cells, and tissues having an immunoglobulin heavy chain locus characterized by a single human VH gene segment, a plurality of human DH gene segments and a plurality of human JH gene segments and capable expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof are also provided.Type: ApplicationFiled: March 7, 2013Publication date: December 12, 2013Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Lynn Macdonald, John McWhirter, Naxin Tu, Sean Stevens, Andrew J. Murphy
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Publication number: 20130330771Abstract: A transgenic non-human mammal containing a heterologous lambda light chain gene locus, and/or a heterologous kappa light chain gene locus, and/or a heterologous heavy chain gene locus, each of which can re-arrange so that immunoglobulin heavy and light chain genes are formed and expressed in B-cells following antigen challenge.Type: ApplicationFiled: March 14, 2013Publication date: December 12, 2013Applicant: Erasmus University Medical CenterInventors: Roger Kingdon Craig, Franklin Gerardus Grosveld, Richard Wilhelm Janssens, Mariuns Johannes Van Haperen
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Publication number: 20130323235Abstract: The present invention provides a high affinity, antigen-specific, soluble heavy chain-only antibody which: lacks hallmark camelid-related amino acid substitutions and has FR2 substitutions which are not found in antibodies which comprise heavy and light chain; shows increased net hydrophobicity within CDR1 and an increased number of charged amino acids present in CDR3; and comprises one or more amino acid substitutions within the framework ?-pleated sheet leading to increased net hydrophobicity within FR1 and increased number of charged amino acids present in FR3. Also provided are VH domains having the same properties, gene segments for their production, methods for their production, transgenic animals and uses of the antibody of the VH domains in therapy.Type: ApplicationFiled: March 15, 2013Publication date: December 5, 2013Applicant: ERASMUS UNIVERSITY MEDICAL CENTERInventors: Roger Kingdon Craig, Franklin Gerardus Grosveld, Richard Wilhelm Janssens, Dubravka Drabek
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Publication number: 20130326647Abstract: 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: ApplicationFiled: July 18, 2013Publication date: December 5, 2013Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Lynn Macdonald, Sean Stevens, Cagan Gurer, Andrew J. Murphy, Karolina A. Meagher
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Patent number: 8598409Abstract: This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to a novel ecdysone receptor/chimeric retinoid X receptor-based inducible gene expression system and methods of modulating gene expression in a host cell for applications such as gene therapy, large-scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms.Type: GrantFiled: August 24, 2007Date of Patent: December 3, 2013Assignee: Intrexon CorporationInventors: Marianna Zinovievna Kapitskaya, Subba Reddy Palli
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Patent number: 8597615Abstract: The present embodiments relate to methods of identifying and creating human or humanized antibodies that possess a reduced risk of inducing a Human Anti-Human Antibody (HAHA) response when they are applied to a human host. Other methods are directed to predicting the likelihood of a HAHA response occurring. Methods for screening for anti-HAHA compounds are also included. Methods for determining if various conditions for administering an antibody to a subject enhance or suppress a HAHA response are also included.Type: GrantFiled: May 8, 2012Date of Patent: December 3, 2013Assignee: Amgen Fremont Inc.Inventors: Sirid-Aimee Kellermann, Larry L. Green, Wouter Korver
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Publication number: 20130318643Abstract: 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: ApplicationFiled: January 14, 2013Publication date: November 28, 2013Inventors: Allan Bradley, E-Chiang Lee, Qi Liang, Wei Wang, Anais Legent, Ian Kirby
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Publication number: 20130318640Abstract: The invention relates to a novel polypeptide vitamin K epoxide recycling polypeptide (VKORC1) as a target for coumarin and its derivatives. The invention further provides methods for identifying coumarin derivatives, and also claims VKORC1 polypeptides and VKORC1 nucleic acids containing a sequence abnormality associated with a VKORC1 associated deficiency such as warfarin resistance, wherein the VKORC1 polypeptides and VKORC1 nucleic acids can be used for diagnosing these deficiencies. Moreover, the invention relates to methods for identifying coumarin derivatives usable in pest control of rodents.Type: ApplicationFiled: December 10, 2012Publication date: November 28, 2013Applicants: Baxter International Inc., Baxter Healthcare SAInventors: Baxter Healthcare SA, Baxter International Inc.
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Patent number: 8592643Abstract: An object of the present invention is to provide a method for introducing a gene into an embryo for production of a human disease model primate animal using a non-human primate animal such as a marmoset. The present invention relates to a method for introducing a foreign gene into an early embryo of a non-human primate animal, which comprises placing early embryos of a non-human primate in a 0.2 M to 0.3 M sucrose solution, so as to increase the volume of the perivitelline spaces, and then injecting a viral vector containing a human foreign gene operably linked to a promoter into the perivitelline spaces of the early embryos.Type: GrantFiled: December 9, 2008Date of Patent: November 26, 2013Assignees: Central Institute for Experimental Animals, Keio UniversityInventors: Erika Sasaki, Hideyuki Okano
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Publication number: 20130312129Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.Type: ApplicationFiled: July 3, 2013Publication date: November 21, 2013Applicant: Regeneron Pharmaceuticals, Inc.Inventors: David FRENDEWEY, Guochun GONG, Ka-Man Venus LAI, David M. VALENZUELA
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Publication number: 20130312128Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.Type: ApplicationFiled: July 3, 2013Publication date: November 21, 2013Applicant: Regeneron Pharmaceuticals, Inc.Inventors: David FRENDEWEY, Guochun GONG, Ka-Man Venus LAI, David M. VALENZUELA
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Publication number: 20130312130Abstract: Provided are methods for producing a reprogrammed fibroblast or epithelial cell. The methods include growing a plurality of fibroblasts or epithelial cells in monolayer culture to confluency; and disrupting the monolayer culture to place at least a fraction of the plurality of fibroblasts or epithelial cells into suspension culture under conditions sufficient to form one or more embryoid body-like spheres, wherein the one or more embryoid body-like spheres comprise one or more reprogrammed fibroblasts or epithelial cells that express one or more markers not expressed prior to the disrupting step. Also provided are reprogrammed fibroblasts or epithelial cells produced by the disclosed methods, formulations that include reprogrammed fibroblasts or epithelial cells, methods for using the reprogrammed fibroblasts or epithelial cells, methods for producing chimeric non-human mammals that include one or more sphere-induced Pluripotent Cells (siPS), and chimeric non-human mammals produced thereby.Type: ApplicationFiled: September 23, 2011Publication date: November 21, 2013Applicant: UNIVERSITY OF LOUISVILLEInventors: Douglas Dean, Yongqing Liu
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Publication number: 20130305396Abstract: Provided herein are rodents that express the human endosialin gene. In preferred embodiments, the rodent is a mouse. Preferably, the human endosialin gene is integrated into the native or endogenous endosialin gene locus. More preferably, the host rodent is null for the endogenous endosialin gene product. The human endosialin gene is preferably expressed in a similar development and disease response pattern as that of the native endosialin gene product in parental or wild type rodents. This feature makes these rodents useful for studying the effects of test agents to positively or negatively affect endosialin biology for therapeutic use. Use of human endosialin expressing rodents lacking native endosialin gene product (HUE rodents) is proposed as a strategy for developing agents that can positively or negatively affect the endosialin pathway and also serve as a screening tool to identify those agents that may be useful as human therapies.Type: ApplicationFiled: September 28, 2011Publication date: November 14, 2013Inventors: Luigi Grasso, Jian Min Lin, Yuhong Zhou, Brian E. Tomkowicz, Nicholas C. Nicolaides, Philip M. Sass
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Publication number: 20130302836Abstract: A genetically modified mouse is provided, wherein the mouse is incapable of rearranging and expressing an endogenous mouse immunoglobulin light chain variable sequence, wherein the mouse expresses only one or two human light chain variable domains encoded by human immunoglobulin sequences operably linked to the mouse kappa (?) constant gene at the endogenous mouse ? locus, wherein the mouse expresses a reverse chimeric antibody having a light chain variable domain derived from one of only two human light chain variable region gene segments and a mouse ? constant domain, and a human heavy chain variable domain and a mouse heavy chain constant domain, from an endogenous mouse heavy chain locus. Bispecific epitope-binding proteins that are fully human are provided, comprising two different heavy chains that associate with an identical light chain that comprises a variable domain derived from one of two different human light chain variable region gene segments.Type: ApplicationFiled: July 23, 2013Publication date: November 14, 2013Inventors: John McWhirter, Lynn Macdonald, Sean Stevens, Samuel Davis, David R. Buckler, Andrew J. Murphy
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Patent number: 8581022Abstract: A method of identifying a compound for preventing and/or treating an autoimmune disease is described which comprises obtaining a (BTLA?/?) NKT cell from a non-human animal, contacting the (BTLA?/?) NKT cell ex vivo with a test compound, in the presence of an antigen, measuring a response of the (BTLA?/?) NKT cell to the antigen, comparing the response of the (BTLA?/?) NKT cell to the antigen with a response of a (BTLA?/?) NKT cell in control assay, and selecting the compound that reduces the response of the (BTLA?/?) NKT cell in the presence of an antigen compared to a response of a (BTLA?/?) NKT cell in the control assay. Other methods of identifying a compound for preventing and/or treating an autoimmune disease are also described.Type: GrantFiled: March 30, 2010Date of Patent: November 12, 2013Assignee: National University Corporation Chiba UniversityInventors: Norihiko Watanabe, Yoshihiro Oya
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Publication number: 20130298268Abstract: Disclosed are materials and methods for creating customizable traits in animals. In the demonstration of the principle of the subject invention, a keratin-14 specific promoter is used with, red fluorescent protein in the loxp cassette, dominant black (?G23) beta defensin 103 in the pigment cassette, and an SV40 (with intron) polyadenylation sequence. When Cre recombinase (or HTNCre) is applied to the animal's skin in a carrier base (e.g., lipid bilayers), fur is permanently genetically modified to turn black in the shape in which it was applied.Type: ApplicationFiled: July 16, 2013Publication date: November 7, 2013Inventor: JAMES WEST
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Patent number: 8569573Abstract: Described herein is a method of expanding human hepatocytes in vivo using an immunodeficient mouse which is further deficient in fumarylacetoacetate hydrolase (Fah). The method comprises transplanting human hepatocytes into the immunodeficient and Fah-deficient mice, allowing the hepatocytes to expand and collecting the expanded human hepatocytes. The method also allows serial transplantation of the human hepatocytes into secondary, tertiary, quaternary or additional mice. Also provided are mutant mice comprising homozygous deletions or point mutations in the Fah, Rag2 and Il2rg genes.Type: GrantFiled: June 5, 2008Date of Patent: October 29, 2013Assignees: Oregon Health & Science University, The Board of Trustees of the Leland Stanford Junior UniversityInventors: Markus Grompe, Hisaya Azuma, Muhsen Al-Dhalimy, Mark A. Kay
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Publication number: 20130276158Abstract: The present invention provides methods for attenuating gene expression in a cell, especially in a mammalian cell, using gene-targeted double stranded RNA (dsRNA), such as a hairpin RNA. The dsRNA contains a nucleotide sequence that hybridizes under physiologic conditions of the cell to the nucleotide sequence of at least a portion of the gene to be inhibited (the “target” gene).Type: ApplicationFiled: June 18, 2012Publication date: October 17, 2013Applicant: Cold Spring Harbor LaboratoryInventors: Gregory J. HANNON, Patrick Paddison, Emily Bernstein, Amy Caudy, Douglas Conklin, Scott Hammond
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Publication number: 20130276156Abstract: The present invention relates to the field of biotechnology or genetic engineering. More specifically, the present invention relates to a multiple inducible gene regulation system that functions within cells to simultaneously control the quantitative expression of multiple genes.Type: ApplicationFiled: September 13, 2012Publication date: October 17, 2013Applicant: Intrexon CorporationInventors: Tarlochan Singh DHADIALLA, Dean Ervin Cress, Glenn Richard Carlson, Robert Eugene Hormann, Subba Reddy Palli, Arthur John Kudla, Ronald Phillip Herzig, JR., Mohan Philip
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Patent number: 8552253Abstract: Provided is a method of using any mammal except humans, in particular, a mammal as an attention deficit hyperactivity disorder model, wherein genes of G protein-coupled receptor kinase interacting protein 1 (GIT1) as a neuronal synapse protein in the brain are knocked out from the mammal. In addition, disclosed is analysis of GIT1 knock-out mice in aspects of molecular biology, cellular biology, electrical biology and animal behavior and, more particularly, a screening method of novel drug, wherein excessive behavior as an attention deficit hyperactive disorder as well as recovery of theta wave in the frontal lobe are observed by administering a candidate material of the drug, thereby inducing recovery of the attention deficit hyperactivity disorder.Type: GrantFiled: April 13, 2012Date of Patent: October 8, 2013Assignee: Korea Advanced Institute of Science and TechnologyInventors: Eunjoon Kim, Changwon Kang, Won Mah, Hyejung Won, Eun-Kyoung Hahm, Eunjin Kim
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Patent number: 8552254Abstract: The present invention provides novel methods of maintaining genetic stability of non-human animal inbred strains. In the methods, pedigree-tracked cryopreserved embryos or gametes or pre-gametes derived from a foundation colony are produced and used to re-establish the foundation colony at appropriate intervals.Type: GrantFiled: October 26, 2009Date of Patent: October 8, 2013Assignee: The Jackson LaboratoryInventors: Michael V. Wiles, Robert Taft, Eva M. Eicher, Shannon Byers