Mouse Patents (Class 800/18)
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Patent number: 9023841Abstract: This disclosure provides methods for treating asthma or an associated disorder in a patient in need thereof, by administering to the patient an effective amount of an autophagy inducing agent, thereby treating the asthma or the associated disorder. Disorders that can be treated include, allergic asthma, chronic obstructive pulmonary disease, lung inflammation, respiratory tolerance and a lung infection or disorder.Type: GrantFiled: August 2, 2012Date of Patent: May 5, 2015Assignee: University of Southern CaliforniaInventor: Omid Akbari
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Patent number: 9018437Abstract: The invention discloses novel model of transgenic mammal, a method of crossbreeding transgenic mammal and the use of the transgenic mammal for assessing prevention and/or treatment methods for cardiovascular and other diseases related to lipoprotein(a). The transgenic mammal expresses human apolipoprotein (a) (apo(a)) and human apolipoprotein B-100 (apo B-100) genes and produces human lipoprotein (a), apo (a) and apo B-100 and produces no vitamin C. This novel dual transgenic mammal is the ideal model for testing pharmaceutical compounds for efficacy and usefulness in the prevention and/or treatment of human diseases.Type: GrantFiled: September 12, 2013Date of Patent: April 28, 2015Inventors: Matthias W Rath, Aleksandra Niedzwiecki, John Chang-Eun Cha
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Patent number: 9018440Abstract: The present invention relates to compositions and methods useful for detecting and/or measuring, e.g., intracellular signaling in vivo. More particularly, compositions and methods are provided, which include transgenic animals, that are useful in mapping and examining, e.g., calcium fluctuations in vivo between and within populations of cells in real time. Methods for screening for candidate compounds that effect, e.g., intracellular calcium signaling are also provided.Type: GrantFiled: October 24, 2007Date of Patent: April 28, 2015Assignee: Stowers Institute for Medical ResearchInventors: Congrong (Ron) Yu, Limei Ma
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Patent number: 9018441Abstract: Hairless, immunodeficient mice on a non-obese diabetic (NOD) background and methods for their production are disclosed herein. The mice are hairless and have multiple immunodeficiencies, including B-cell and T-cell deficiencies, as well as impaired macrophage and complement function. The mice also have a further deficit in natural killer and dendritic cells of the immune system. The mice are useful for biomedical research, for example, in studies involving xenograft transplantation, spontaneous tumors, cancer cell tumorigenesis, tumor angiogenesis, tumor metastatic potential, tumor suppression therapy, carcinogenesis regulation, and tumor imaging.Type: GrantFiled: April 14, 2011Date of Patent: April 28, 2015Assignee: Harlan Laboratories, Inc.Inventor: Sheryl Wildt
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Publication number: 20150113669Abstract: 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: September 25, 2014Publication date: April 23, 2015Inventors: Allan Bradley, E-Chiang Lee, Qi Liang, Wei Wang
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Publication number: 20150113668Abstract: The invention relates to polynucleotides, particularly chimeric polynucleotides useful for optimal production of functional immunoglobulins with human idiotypes in rodents. The invention further relates to rodents comprising such polynucleotides.Type: ApplicationFiled: October 17, 2014Publication date: April 23, 2015Inventors: Marianne BRUGGEMANN, Roland BUELOW, Michael J. OSBORN, Biao MA
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Patent number: 9012717Abstract: 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: GrantFiled: June 22, 2011Date of Patent: April 21, 2015Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Lynn Macdonald, Sean Stevens, Cagan Gurer, Andrew J. Murphy, Karolina A. Hosiawa
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Patent number: 9006511Abstract: 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: GrantFiled: July 18, 2013Date of Patent: April 14, 2015Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Lynn Macdonald, Sean Stevens, Cagan Gurer, Andrew J. Murphy, Karolina A. Meagher
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Patent number: 9005981Abstract: The present invention is in the field of identification and characterization of novel insecticidal target sites and, in particular, relates to host cells, assays and antibodies thereto.Type: GrantFiled: December 22, 2009Date of Patent: April 14, 2015Assignee: Dow AgroSciences LLCInventors: Nailah Orr, Gerald B. Watson, Gary D. Gustafson, James M. Hasler, Chaoxian Geng, Scott Chouinard, Kevin R. Cook, Vincent L. Salgado
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Patent number: 8993833Abstract: A modified non-human warm-blooded vertebrate animal in which a biologically active human APP polypeptide is expressed, and in which function of its inducible Nitric Oxide Synthase (iNOS) protein is reduced as compared to a non-modified animal, methods of making the animal, and methods of testing a candidate composition for activity in the treatment of Alzheimer's Disease using the animal.Type: GrantFiled: August 14, 2008Date of Patent: March 31, 2015Assignee: Duke UniversityInventors: Carol Anne Colton, Michael Peter Vitek, Judianne Davis, William E. VanNostrand
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Publication number: 20150089679Abstract: 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: ApplicationFiled: October 17, 2014Publication date: March 26, 2015Applicant: REGENERON PHARMACEUTICALS, INC.Inventors: Andrew J. Murphy, O. Gavin Thurston, Bindu Varghese, Cagan Gurer
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Publication number: 20150089680Abstract: 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: December 5, 2014Publication date: March 26, 2015Inventors: Lynn Macdonald, Sean Stevens, Cagan Gurer, Andrew J. Murphy, Karolina A. Meagher
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Publication number: 20150082466Abstract: The present invention relates to humanisation of antibodies in vivo. The invention provides non-human vertebrates, cells, populations and methods useful for humanising chimaeric antibodies in vivo. Using the present invention it is possible straightforwardly and rapidly to obtain antigen-specific antibodies that are fully human (ie, comprising human variable and constant regions) and have undergone recombination, junctional diversification, affinity maturation and isotype switching in vivo in a non-human vertebrate system. Furthermore, such antibodies are humanised (eg, totally human)—and selected—totally in vivo, and as such the present invention harnesses in vivo filtering for expressibility, affinity and biophysical characteristics in the context of the desired human variable and constant region pairings. This is avoids problems of down-grading antibody characteristics when humanising the constant region of chimaeric antibodies in vitro.Type: ApplicationFiled: September 26, 2014Publication date: March 19, 2015Inventor: Jasper Clube
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Publication number: 20150082470Abstract: Methods and compositions are provided for translational profiling and molecular phenotyping of specific tissues, cells and cell subtypes of interest. The methods provided herein facilitate the analysis of gene expression in the selected subset present within a heterogeneous sample.Type: ApplicationFiled: November 25, 2014Publication date: March 19, 2015Inventors: Nathaniel HEINTZ, Paul GREENGARD, Myriam HEIMAN, Anne SCHAEFER, Joseph P. DOYLE, Joseph D. DOUGHERTY
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Publication number: 20150082469Abstract: 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: November 24, 2014Publication date: March 19, 2015Applicant: Regeneron Pharmaceuticals, Inc.Inventor: Andrew J. Murphy
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Patent number: 8981179Abstract: The present invention relates generally to transgene constructs, transgenic non-human animals comprising transgene constructs, methods of making and methods of using the transgenic non-human animals comprising transgene constructs. An embodiment of the invention relates to methods of assaying the activation of GPCR ligands non-invasively in whole animals, tissue slices, or in native cells using a transgenic model containing a bioluminescent transgene reporter system that is responsive to pathway modulation following ligand binding of GPCR receptors.Type: GrantFiled: December 17, 2010Date of Patent: March 17, 2015Assignee: SanofiInventors: Holly Dressler, Kyriakos D. Economides, Zhen Pang, Harry Gregory Polites
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Publication number: 20150074837Abstract: The invention discloses novel model of transgenic mammal, a method of crossbreeding transgenic mammal and the use of the transgenic mammal for assessing prevention and/or treatment methods for cardiovascular and other diseases related to lipoprotein(a). The transgenic mammal expresses human apolipoprotein (a) (apo(a)) and human apolipoprotein B-100 (apo B-100) genes and produces human lipoprotein (a), apo (a) and apo B-100 and produces no vitamin C. This novel dual transgenic mammal is the ideal model for testing pharmaceutical compounds for efficacy and usefulness in the prevention and/or treatment of human diseases.Type: ApplicationFiled: September 12, 2013Publication date: March 12, 2015Inventors: MATTHIAS W RATH, Aleksandra Niedzwiecki, JOHN CHANG-EUN CHA
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Patent number: 8962912Abstract: 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: GrantFiled: March 24, 2011Date of Patent: February 24, 2015Assignees: Baxter International Inc., Baxter Healthcare SAInventors: Maria Sasgary, Maria Schuster, Hans-Peter Schwarz, Birgit Maria Reipert, Gerhard Antoine, Hartmut Ehrlich
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Patent number: 8962913Abstract: 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: GrantFiled: March 12, 2013Date of Patent: February 24, 2015Assignee: Regeneron Pharmaceuticals, Inc.Inventor: Andrew J. Murphy
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Publication number: 20150047065Abstract: The present invention relates to a binding molecule that specifically binds to two different epitopes of an antigen expressed on tumor cells, wherein the binding molecule comprises: (a) a first binding (poly)peptide that specifically binds to a first epitope of said antigen expressed on tumor cells, wherein said first binding (poly)peptide is a Fyn SH3-derived polypeptide; and (b) a second binding (poly)peptide that specifically binds to a second epitope of said antigen expressed on tumor cells. The present invention further relates to a nucleic acid molecule encoding the binding molecule of the invention, a vector comprising said nucleic acid molecule as well as a host cell or a non-human host transformed with said vector. The invention further relates to a method of producing a binding molecule of the invention as well as to pharmaceutical and diagnostic composition.Type: ApplicationFiled: March 8, 2013Publication date: February 12, 2015Inventors: Simon Brack, Frédéric Mourlane, Isabella Toller, Richard Woods, Julian Bertschinger, Dragan Grabulovski, Babette Schade, Kristina Klupsch, Helen Hachemi
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Patent number: 8952213Abstract: The disclosed invention provides compositions and methods for the identification of cells that are functionally activated after stimulation or during an activity while maintaining the viability of the identified cells.Type: GrantFiled: April 25, 2003Date of Patent: February 10, 2015Assignee: The Board of Trustees of the Leland Stanford Junior UniversityInventor: Alison L. Barth
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Patent number: 8952214Abstract: A nonhuman transgenic mammal is described whose genome comprises a promoter construct operably linked to a heterologous DNA encoding an epithelial sodium channel ? subunit, wherein said promoter construct directs expression of the epithelial sodium channel ? subunit in lung epithelial cells of said animal, and wherein said transgenic mammal has increased lung mucus retention as compared to the corresponding wild-type mammal. The animal is useful in screening compounds for activity in treating lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease.Type: GrantFiled: June 25, 2010Date of Patent: February 10, 2015Assignee: The University of North Carolina at Chapel HillInventors: Richard C. Boucher, Jr., Wanda O'Neal, Barbara Grubb, Marcus Mall
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Publication number: 20150040250Abstract: 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: October 16, 2014Publication date: February 5, 2015Inventors: Allan Bradley, E-Chiang Lee, Qi Liang, Wei Wang, Glenn Friedrich
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Publication number: 20150040253Abstract: 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: ApplicationFiled: August 8, 2014Publication date: February 5, 2015Inventors: Lynn Macdonald, Andrew J. Murphy, Naxin Tu, Cagan Gurer, Vera Voronina, Sean Stevens
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Patent number: 8946504Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.Type: GrantFiled: July 3, 2013Date of Patent: February 3, 2015Assignee: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Guochun Gong, Ka-Man Venus Lai, David M. Valenzuela
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Patent number: 8946505Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.Type: GrantFiled: July 3, 2013Date of Patent: February 3, 2015Assignee: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Guochun Gong, Ka-Man Venus Lai, David M. Valenzuela
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Publication number: 20150033369Abstract: The present invention is directed to the concept of sectoring antibody gene segment repertoires in order to enable the development of novel, synthetic antibody chain repertoires not seen in nature. The present invention is also directed to the realisation of the inventors that sectoring can also alter gene segment expression by providing new arrangements of gene segment clusters relative to other gene segments and regulatory elements in transgenic immunoglobulin loci, thereby providing for new synthetic antibody chain sequence repertoires. The invention also relates to gene segment inversion.Type: ApplicationFiled: March 19, 2014Publication date: January 29, 2015Applicant: KYMAB LIMITEDInventors: Allan Bradley, E-Chiang Lee
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Publication number: 20150033372Abstract: 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: ApplicationFiled: March 26, 2014Publication date: January 29, 2015Applicant: Kymab LimitedInventors: Allan Bradley, E-Chiang Lee, Qi Liang, Dominik Spensberger, Nicholas England
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Patent number: 8940960Abstract: The human Occludin protein is identified as an essential Hepatitis C Virus (HCV) cell entry factor. Occludin is shown to render murine and other non-human cells infectable with HCV and to be required for HCV-susceptibility of human cells. Associated methods for inhibiting HCV infection, transgenic animal models for HCV pathogenesis, methods of identifying compounds or agents that prevent or mitigate interaction of HCV with Occludin, and HCV inhibitory agents are also disclosed. Kits and cell culture compositions useful for identifying compounds or agents that prevent or mitigate interaction of HCV with Occludin are also provided.Type: GrantFiled: October 1, 2009Date of Patent: January 27, 2015Assignee: The Rockefeller UniversityInventors: Alexander Ploss, Matthew Evans, Charles Rice
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Publication number: 20150026834Abstract: The present invention relates to the field of anastasis, i.e., the process of reversal of apoptosis. More specifically, the present invention provides methods and compositions useful for studying anastasis. In one embodiment, the present invention provides an in vivo biosensor comprising (a) a transcription factor complex comprising the Gal4 transcription factor linked to an enzyme cleavable linker, wherein the transcription factor complex is tethered to the plasma membrane via a transmembrane domain; and (b) a reporter system comprising (1) a first nucleic acid encoding flippase operably linked to the upstream activating sequence that binds Gal4; and (2) a second nucleic acid comprising an FRT-flanked stop codon cassette separating a constitutive promoter and a fluorescent protein open reading frame.Type: ApplicationFiled: March 7, 2013Publication date: January 22, 2015Inventors: Denise Montell, Ho Lam Tang
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Publication number: 20150020223Abstract: 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: ApplicationFiled: September 9, 2014Publication date: January 15, 2015Inventors: Feng Zhang, Randall Jeffrey Platt, Guoping Feng, Yang Zhou
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Publication number: 20150020224Abstract: 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: ApplicationFiled: September 26, 2014Publication date: January 15, 2015Applicant: Regeneron Pharmaceuticals, Inc.Inventors: John McWhirter, Cagan Gurer, Karolina A. Meagher, Lynn Macdonald, Andrew J. Murphy
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Patent number: 8933295Abstract: The method of the invention is useful for evaluating pharmaceutical compositions for treatment of neurological diseases encompassing neurological or neurodegenerative diseases associated with cognitive dysfunction and, in particular, dementia; schizophrenia; anxiety; depression; and pain using a rodent behavioral assay, wherein the method is useful in testing compositions useful in the modulation, amelioration, prevention, or treatment of dementia using a non-human animal carrying at least a transgene for human amyloid-beta protein or human tau and transgenes causing the elevated production of the human amyloid-beta protein in the animal as compared to nontransgenic animals of the same genetic background and the behavior is a nesting behavior.Type: GrantFiled: June 3, 2009Date of Patent: January 13, 2015Assignee: Janssen Biotech, Inc.Inventors: Sun-Yung Jung, Mary Birchler
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Publication number: 20150013025Abstract: 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 the HTNCre was applied.Type: ApplicationFiled: May 7, 2014Publication date: January 8, 2015Inventor: JAMES WEST
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Publication number: 20150007359Abstract: The present invention is directed generally to eukaryotic cells comprising single-celled organisms that are introduced into the eukaryotic cell through human intervention and which transfer to daughter cells of the eukaryotic cell through at least five cell divisions, and methods of introducing such single-celled organisms into eukaryotic cells. The invention also provides methods of using such eukaryotic cells. The invention further provides single-celled organisms that introduce a phenotype to eukaryotic cells that is maintained in daughter cells. The invention additionally provides eukaryotic cells containing magnetotactic bacteria.Type: ApplicationFiled: September 17, 2014Publication date: January 1, 2015Inventors: Caleb B. BELL, III, Alexey Bazarov
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Patent number: 8921642Abstract: Described are transgenic animals for conditional and inducible cell targeting, that express a dimerizable conditional-STOP caspase 3 transgene.Type: GrantFiled: January 12, 2009Date of Patent: December 30, 2014Assignee: Massachusetts Eye and Ear InfirmaryInventors: Albert Edge, Masato Fujioka
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Publication number: 20140380515Abstract: The present invention provides novel transgenic nonhuman mammals capable of producing human sequence antibodies, as well as methods of producing and using these antibodies.Type: ApplicationFiled: July 24, 2014Publication date: December 25, 2014Inventors: KAZUMA TOMIZUKA, ISAO ISHIDA, NILS LONBERG, EDWARD L. HALK
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Patent number: 8907157Abstract: The invention provides methods for the production of transgenic animals comprising a recombinant Ig locus, as well as transgenic antibodies derived therefrom. The methods involve meganuclease cleavage-stimulated homologous recombination in mammalian embryos.Type: GrantFiled: February 5, 2010Date of Patent: December 9, 2014Assignee: OMT, Inc.Inventor: Roland Buelow
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Publication number: 20140359798Abstract: Genetically engineered mice having a corrected Cbr1rd8 mutation and methods for correcting the Cbr1rd8 mutation to produce the genetically engineered mice are provided according to aspects of the present invention. Kits, expression vectors and fusion proteins according to aspects of the invention are provided for use to produce the genetically engineered mice characterized by a corrected Cbr1rd8 mutation.Type: ApplicationFiled: June 3, 2014Publication date: December 4, 2014Applicant: THE JACKSON LABORATORYInventors: Michael V. Wiles, Benjamin E. Low
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Publication number: 20140356907Abstract: 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, 2014Publication date: December 4, 2014Applicant: ERASMUS UNIVERSITY MEDICAL CENTERInventors: FRANKLIN GERARDUS GROSVELD, RICHARD WILHELM JANSSENS, MARINUS JOHANNES VAN HAPEREN, ROGER KINGDON CRAIG, ERNIE DE BOER
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Publication number: 20140356908Abstract: A transgenic non-human mammal containing a heterologous heavy chain gene locus that is capable of producing soluble heavy chain only antibodies and antigen-binding fragments thereof following immunization.Type: ApplicationFiled: March 14, 2014Publication date: December 4, 2014Applicant: ERASMUS UNIVERSITY MEDICAL CENTERInventors: FRANKLIN GERARDUS GROSVELD, RICHARD WILHELM JANSSENS
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Publication number: 20140359797Abstract: 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: ApplicationFiled: March 26, 2014Publication date: December 4, 2014Applicant: Kymab LimitedInventors: Allan Bradley, E-Chiang Lee, Qi Liang, Dominik Spensberger, Nicholas England
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Publication number: 20140351960Abstract: Arterial and venous endothelial cells are molecularly distinct from the earliest stages of angiogenesis. This distinction is revealed by expression on arterial cells of a transmembrane ligand, called EphrinB2 whose receptor EphB4 is expressed on venous cells. Targeted disruption of the EphrinB2 gene prevents the remodeling of veins from a capillary plexus into properly branched structures. Moreover, it also disrupts the remodeling of arteries, suggesting that reciprocal interactions between pre-specified arterial and venous endothelial cells are necessary for angiogenesis. This distinction can be used to advantage in methods to alter angiogenesis, methods to assess the effect of drugs on artery cells and vein cells, and methods to identify and isolate artery cells and vein cells, for example.Type: ApplicationFiled: November 22, 2013Publication date: November 27, 2014Applicant: CALIFORNIA INSTITUTE OF TECHNOLOGYInventors: Hai U. Wang, Zhoufeng Chen, David J. Anderson
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Patent number: 8895801Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.Type: GrantFiled: September 25, 2013Date of Patent: November 25, 2014Assignee: Regeneron Pharmaceuticals Inc.Inventors: Andrew J. Murphy, George D. Yancopoulos, Margaret Karow, Lynn Macdonald, Sean Stevens, Aris N. Economides, David M. Valenzuela
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Patent number: 8895802Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.Type: GrantFiled: October 4, 2013Date of Patent: November 25, 2014Assignee: Regeneron Pharmaceuticals Inc.Inventors: Andrew J. Murphy, George D. Yancopoulos, Margaret Karow, Lynn Macdonald, Sean Stevens, Aris N. Economides, David M. Valenzuela
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Publication number: 20140338008Abstract: It is revealed that an organ such as pancreas can be regenerated by utilizing a fact that the deficiency of an organ is complemented by injecting an induced pluripotent stem cell (iPS cell) into a developed blastocyst in a blastocyst complementation method. Thus, the present invention has solved the above-described object. This provides a method for producing a target organ, using an iPS cell, in a living body of a non-human mammal having an abnormality associated with a lack of development of the target organ in a development stage, the target organ produced being derived from a different individual mammal that is an individual different from the non-human mammal.Type: ApplicationFiled: March 5, 2014Publication date: November 13, 2014Applicant: The University of TokyoInventors: Hiromitsu Nakauchi, Toshihiro Kobayashi, Tomoyuki Yamaguchi, Sanae Hamanaka
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Patent number: 8883496Abstract: 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 23, 2011Date of Patent: November 11, 2014Assignee: Regeneron Phamaceuticals, Inc.Inventors: Lynn MacDonald, Naxin Tu, Cagan Gurer, Li-Hsien Wang, Sean Stevens, Andrew J. Murphy
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Patent number: 8883150Abstract: 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: GrantFiled: March 19, 2010Date of Patent: November 11, 2014Assignee: Erasmus University Medical CenterInventors: Roger Kingdon Craig, Franklin Gerardus Grosveld, Richard Wilhelm Janssens, Dubravka Drabek, Tao Chen, Ernie De Boer
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Publication number: 20140331344Abstract: The present invention relates inter alia to fertile non-human vertebrates such as mice and rats useful for producing antibodies bearing human variable regions, in which endogenous immunoglobulin chain expression has been inactivated.Type: ApplicationFiled: May 3, 2013Publication date: November 6, 2014Applicant: Kymab Ltd.Inventor: Kymab Ltd.
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Publication number: 20140331339Abstract: The invention provides Assay Vertebrates comprising a human antigen or epitope knock-in for testing antibodies comprising human variable regions and generated in a related Antibody-Generating Vertebrate. The invention also provides kits and methods involving these vertebrates and antibodies. The invention provides for superior assay models and assay methods of chimaeric and other test antibodies comprising human variable regions.Type: ApplicationFiled: April 28, 2014Publication date: November 6, 2014Applicant: Kymab LimitedInventors: Allan Bradley, E-Chiang Lee, Qi Liang