Mouse Patents (Class 800/18)
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Patent number: 9648857Abstract: Novel methods of testing the immunogenicity of variant antigens are provided. In particular, methods based on the use of transgenic animals are provided, wherein the transgenic animal is tolerized to a particular antigen and is then exposed to variants of the antigen and immune responses are determined. In one embodiment the transgenic animal is a mouse which is transgenic for human MHC class II molecules and the immunogenicity of libraries of variant antibodies are tested.Type: GrantFiled: November 23, 2005Date of Patent: May 16, 2017Assignee: Antitope LimitedInventor: Matthew Baker
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Patent number: 9637546Abstract: The invention relates to PD-1 antibodies and PD-L1 antibodies and uses thereof.Type: GrantFiled: May 20, 2014Date of Patent: May 2, 2017Inventors: Daniel Olive, Nacer-Eddine Serriari, Jacques Nunes, Marguerite Ghiotto
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Patent number: 9629347Abstract: 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: GrantFiled: December 5, 2014Date of Patent: April 25, 2017Assignee: REGENERON PHARMACEUTICALS, INC.Inventors: John McWhirter, Cagan Gurer, Lynn Macdonald, Andrew J. Murphy
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Patent number: 9585373Abstract: The invention provides genetically modified non-human animals that express a humanized MHC II protein (humanized MHC II ? and ? polypeptides), as well as embryos, cells, and tissues comprising the humanized MHC II protein. Also provided are constructs for and methods of making the genetically modified non-human animals. Methods of using the genetically modified non-human animals to study various aspects of the human immune system are provided.Type: GrantFiled: August 8, 2014Date of Patent: March 7, 2017Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Lynn Macdonald, Andrew J Murphy, Naxin Tu, Cagan Gurer, Vera Voronina, Sean Stevens
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Patent number: 9574211Abstract: Methods and compositions for treatment of a genetic disease are provided.Type: GrantFiled: May 13, 2015Date of Patent: February 21, 2017Assignee: Sangamo BioSciences, Inc.Inventors: Philip D. Gregory, Michael C. Holmes
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Patent number: 9565840Abstract: The present invention provides a non-human animal IKK? which shows fibrosis of tissue, since it lacks IKK? gene in a myofibroblast- and/or smooth muscle cell-specific manner. Since the non-human animal shows pathology highly similar to scleroderma, it is extremely useful as an animal model of scleroderma.Type: GrantFiled: October 31, 2013Date of Patent: February 14, 2017Assignees: KYOTO UNIVERSITY, THE REGENTS OF THE UNIVERSITY OF CALIFORNIAInventors: Noboru Ashida, Masayuki Yokode, Michael Karin, Dat Nguyen Tien
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Patent number: 9554563Abstract: 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 mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/Il2rg 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: October 14, 2013Date of Patent: January 31, 2017Assignees: Regeneron Pharmaceuticals, Inc., 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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Patent number: 9540452Abstract: 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: November 17, 2015Date of Patent: January 10, 2017Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Lynn Macdonald, Sean Stevens, Cagan Gurer, Andrew J. Murphy, Karolina A. Meagher
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Patent number: 9493759Abstract: The present invention relates to isolated polypeptides having aspartic endopeptidase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.Type: GrantFiled: December 10, 2009Date of Patent: November 15, 2016Assignee: Novozymes, Inc.Inventors: Beth Nelson, Alfredo Lopez de Leon, Michael Rey
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Patent number: 9494603Abstract: The invention relates to a method for diagnosing, staging and/or monitoring a hemoglobin-related disorder such as ?-thalassemia or a treatment against said hemoglobin-related disorder in a subject in need thereof based on the detection and/or quantification the presence of free ?-Hb pool in a biological sample obtained from said subject.Type: GrantFiled: June 24, 2015Date of Patent: November 15, 2016Assignees: Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud, Assistance Publique—Hopitaux de Paris, Universite Paris Est Creteil Val de MarneInventors: Veronique Baudin-Creuza, Corinne Vasseur, Frederic Galacteros
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Patent number: 9488652Abstract: The present invention relates to the detection of tumor stem cells and tumor cells in epithelial-mesenchymal transition and uses of such methods. According to the present invention said method comprises a selecting step for selection or enrichment of said predetermined cells from the sample wherein the sample is contacted with the solid surface for preferential binding of said predetermined cells to the solid surface and then the sample is removed d from the solid surface in a washing step. The inventive method is characterized in that the sample contains a polyol at least during one of contacting the sample with the solid surface and the washing step and in a detection step detecting in said cells, preferentially selected or enriched by said selecting step, the presence or absence of expression of at least one marker associate with at least one the group comprising tumor stem cells and tumor cells in epithelial-mesenchymal transition.Type: GrantFiled: October 10, 2013Date of Patent: November 8, 2016Assignee: ADNAGEN GMBHInventors: Siegfried Hauch, Winfried Albert
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Patent number: 9462794Abstract: 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: GrantFiled: October 14, 2015Date of Patent: October 11, 2016Assignee: REGENERON PHARMACEUTICALS, INC.Inventors: Andrew J. Murphy, O. Gavin Thurston, Bindu Varghese, Cagan Gurer
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Patent number: 9453227Abstract: In one embodiment, a single modality cancer immunotherapy regimen that includes a therapeutic composition is provided. Such a therapeutic composition may include a Salmonella strain comprising a plasmid that expresses an shRNA molecule that suppresses the expression of an immunosuppressive target and suppresses tumor growth. In some aspects, the Salmonella strain is an attenuated Salmonella typhimurium strain. In other aspects, the immunosuppressive target is STAT3, IDO1, IDO2, Arginase 1, iNOS, CTLA-4, TGF-?, IL-10, pGE2 or VEGF. In one embodiment, the immunosuppressive target is IDO1 or Arg1 and the shRNA molecule is any one of SEQ ID NO:5-14.Type: GrantFiled: October 28, 2013Date of Patent: September 27, 2016Assignee: CITY OF HOPEInventors: Don J. Diamond, Edwin Manuel, Fernanda V. V. Castro
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Patent number: 9434779Abstract: The technology described herein relates to treatments for, e.g., diastolic heart failure, cardiac hypertrophy, and related conditions.Type: GrantFiled: March 11, 2013Date of Patent: September 6, 2016Assignees: The Brigham and Women's Hospital, Inc., President and Fellows of Harvard CollegeInventors: Richard T. Lee, Francesco Loffredo, James Pancoast, Matthew Steinhauser, Amy Wagers
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Patent number: 9426970Abstract: 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: GrantFiled: July 24, 2014Date of Patent: August 30, 2016Assignees: E. R. SQUIBB & SONS, L.L.C., KYOWA HAKKO KIRIN CO., LTD.Inventors: Kazuma Tomizuka, Isao Ishida, Nils Lonberg, Edward L. Halk
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Patent number: 9402376Abstract: A transgenic, non-human animal model for accelerated aging and/or age-related symptom, recombinant nucleic acid molecules, cells and methods that can be used to make such animal model and cells, methods of using the animal model and cells, to descendants of the transgenic non-human animal, obtained by breeding with the same or with another phenotype, and to a cell line or primary cell culture or to an organotypic brain slice culture, derived from the transgenic non-human animal or its descendants are disclosed.Type: GrantFiled: January 11, 2013Date of Patent: August 2, 2016Assignee: ADVANCED GENOMIC TECHNOLOGY, LLCInventor: Eugenia Wang
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Patent number: 9402377Abstract: 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: GrantFiled: September 20, 2011Date of Patent: August 2, 2016Assignee: Yale UniversityInventors: Richard A. Flavell, Till Strowig, Elizabeth Eynon, William Philbrick, Markus Manz
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Patent number: 9399683Abstract: 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: November 17, 2015Date of Patent: July 26, 2016Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Lynn Macdonald, Sean Stevens, Cagan Gurer, Andrew J. Murphy, Karolina A. Meagher
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Patent number: 9392777Abstract: 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: GrantFiled: June 10, 2015Date of Patent: July 19, 2016Assignee: REGENERON PHARMACEUTICALS, INC.Inventors: Li-Hsien Wang, Anthony T. Dore, Jr., Sean Stevens, Andrew J. Murphy
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Patent number: 9394373Abstract: 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: December 5, 2014Date of Patent: July 19, 2016Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Lynn Macdonald, Sean Stevens, Cagan Gurer, Andrew J. Murphy, Karolina A. Meagher
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Patent number: 9359446Abstract: The present invention relates to an antibody binding to a carbonic anhydrase, wherein the antibody comprises (a) the amino acid sequences SEQ ID NOS. 1 (CDR 1), 2 (CDR 2) and 3 (CDR 3) determining the CDRs of the VH region, and the amino acid sequences SEQ ID NOS. 4 (CDR 1), 5 (CDR 2) and 6 (CDR 3) determining the CDRs of the VL region; or (b) the amino acids sequences of (a), wherein at least one amino acid is conservatively substituted in any one of the amino acid sequences SEQ ID NOS. 1 to 6.Type: GrantFiled: May 2, 2011Date of Patent: June 7, 2016Assignee: Hemholtz Zentrum Munchen—Deutches Forschungszentrum Fur Gesundheit Und Umwelt (GmbH)Inventors: Reinhard Zeidler, Christina Battke, Elisabeth Kremmer, Andrew Flatley, Claudiu Supuran
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Patent number: 9347936Abstract: The present invention provides an inactive Ca2+/calmodulin-dependent protein kinase II? (CaMKII?) knockin animal in which only the protein kinase activity of CaMKII? has been specifically impaired. Since CaMKII? is considered to be involved in higher brain functions including learning and memory, and inhibit epileptic seizure and brain disorders caused by ischemia, the inactive CaMKII? knockin animal of the present invention is widely usable for various studies of the brain and nerve, such as the studies of mechanisms of learning disability, dysmnesia, epileptic seizure and brain disorders.Type: GrantFiled: March 24, 2005Date of Patent: May 24, 2016Assignee: JAPAN SCIENCE AND TECHNOLOGY AGENCYInventors: Yoko Yamagata, Yuchio Yanagawa
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Patent number: 9340794Abstract: Described is a method of introducing multiple nucleic acid molecules into the genome of a cell. The method includes providing a plurality of nucleic acid molecules, each of the plurality of nucleic acid molecules containing (a) a nucleic acid sequence operatively linked to a promoter sequence at the 5? end of the nucleic acid molecule, and (b) an overlapping sequence at the 3? end of the nucleic acid molecule.Type: GrantFiled: August 31, 2012Date of Patent: May 17, 2016Assignee: Academia SinicaInventors: Jui-Jen Chang, Feng-Ju Ho, Cheng-Yu Ho, Wen-Hsiung Li, Ming-Che Shih, Chieh-Chen Huang
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Patent number: 9328169Abstract: The present invention relates to antibodies, including human antibodies, and antigen-binding portions thereof that specifically bind to MAdCAM, preferably human MAdCAM, and inhibit MAdCAM. The antibodies comprise the CDRs or variable domains derived from an antibody produced by the hybridoma cell line 7.16.6 (ECACC Accession No. 03090909) or from an antibody comprising the amino acid sequences of SEQ ID NOs.: 34 and 36. The invention also relates to nucleic acid molecules encoding such antibodies and antigen-binding portions thereof, methods of making and using the antibodies and portions, and compositions comprising these antibodies and portions.Type: GrantFiled: January 7, 2005Date of Patent: May 3, 2016Assignees: Pfizer Inc., Amgen Fremont Inc.Inventors: Nicholas Pullen, Elizabeth Molloy, Sirid-Aimée Kellermann, Larry L. Green, Mary Haak-Frendscho
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Patent number: 9314005Abstract: This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of tumor suppressor gene(s) or gene product(s). In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human cancer and methods of their use.Type: GrantFiled: July 1, 2010Date of Patent: April 19, 2016Assignee: Transposagen Biopharmaceuticals, Inc.Inventors: Eric M. Ostertag, John Stuart Crawford, Joseph Ruiz
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Patent number: 9279117Abstract: A myeloid-specific c-fms-rtTA/(TetO)7-CMV-MMP12 bitransgenic mouse model was created. Induction of MMP12 abnormally elevated frequencies and numbers of common myeloid progenitor (CMP) and granulocyte/macrophage progenitor (GMP) populations, and decreased the frequency and number of the megakaryocyte/erythrocyte progenitor (MEP) population in bone marrow. CD11b+/Gr-1+ immature cell population increased in multiple organs. An immunosuppressive function on T cell proliferation and function by CD11b+/Gr-1+ immature cells was seen in vitro and in vivo from MMP12 over-expression. MMP12 stimulated (Lin?) progenitor cells to differentiate into CD11b+/Gr-1+ immature cells showing immunosuppression on T cell proliferation and function in vitro. Regulatory T cells were increased. In the lung, concentration of interleukin (IL)-6 was increased, which activated oncogenic signal transducer and increased expression of Stat3 downstream genes in epithelial tumor progenitor cells.Type: GrantFiled: January 18, 2012Date of Patent: March 8, 2016Assignee: Indiana University Research and Technology CorporationInventors: Cong Yan, Hong Du
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Patent number: 9271479Abstract: The present invention relates to a non-human animal deficient in the N-terminal domain of the IL-33 gene. Also provided herein is the use of said non-human animal as an in vivo model of inflammatory diseases, especially with regard to screening methods for anti-inflammatory compounds, and methods for evaluating and optimizing the pharmacological properties of a given anti-inflammatory compound.Type: GrantFiled: September 3, 2014Date of Patent: March 1, 2016Assignee: Hoffmann-La Roche Inc.Inventors: Javier Cote-Sierra, Antonio Iglesias, Claas Aiko Meyer
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Patent number: 9267135Abstract: Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.Type: GrantFiled: June 30, 2014Date of Patent: February 23, 2016Assignee: President and Fellows of Harvard CollegeInventors: George M. Church, Prashant G. Mali, Kevin M. Esvelt
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Patent number: 9260723Abstract: A method of altering a eukaryotic cell is provided including transfecting the eukaryotic cell with a nucleic acid encoding RNA complementary to genomic DNA of the eukaryotic cell, transfecting the eukaryotic cell with a nucleic acid encoding an enzyme that interacts with the RNA and cleaves the genomic DNA in a site specific manner, wherein the cell expresses the RNA and the enzyme, the RNA binds to complementary genomic DNA and the enzyme cleaves the genomic DNA in a site specific manner.Type: GrantFiled: June 30, 2014Date of Patent: February 16, 2016Assignee: President and Fellows of Harvard CollegeInventors: Prashant G. Mali, George M. Church, Luhan Yang
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Patent number: 9238676Abstract: The present invention provides inhibitors and/or antagonists of plasma kallikrein. Also provided are methods of utilizing the inhibitors as therapeutics.Type: GrantFiled: March 14, 2013Date of Patent: January 19, 2016Assignee: RA PHARMACEUTICALS, INC.Inventors: Zhaolin Wang, Ping Ye, Alonso Ricardo, Kristopher Josephson, Paul Anderson, Michelle Denise Arata, Zhong Ma, Nathan Ezekiel Nims, Eberhard Schneider, Gregor Schurmann, Peter Wagner, Douglas A. Treco, Hong Zheng, Daniel Elbaum, Nicolas Cedric Boyer
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Patent number: 9226484Abstract: 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 15, 2015Date of Patent: January 5, 2016Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Lynn Macdonald, Sean Stevens, Cagan Gurer, Andrew J. Murphy, Karolina A. Meagher
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Patent number: 9198982Abstract: The present invention provides methods of identifying candidate agents for treating excitotoxicity-related disorders. The present invention further provides methods for treating excitotoxicity-related disorders.Type: GrantFiled: April 7, 2011Date of Patent: December 1, 2015Assignee: THE J. DAVID GLADSTONE INSTITUTESInventors: Erik Roberson, Lennart Mucke
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Patent number: 9198891Abstract: The present invention relates to a method of identifying compounds useful in inhibiting protein kinase-like endoplasmic reticulum protein kinase (PERK). The method comprises providing a first model comprising PERK active domains, where the said active domains are selected from the group consisting of the peptide spanning from amino acid residue Asp144 to amino acid residue Ser191 of SEQ ID NO: 1 and a peptide comprising the amino acid residue at position 7 of SEQ ID NO: 1, providing one or more candidate compounds, evaluating contact between the candidate compounds and the first model to determine which of the one or more candidate compounds have an ability to bind to and/or fit in the first model, and identifying the compounds which, based on said evaluating, have the ability to bind to and/or fit in the first model as compounds potentially useful for inhibiting PERK.Type: GrantFiled: May 19, 2011Date of Patent: December 1, 2015Assignee: New York UniversityInventors: Timothy Cardozo, Hong Wang, David Ron
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Patent number: 9193977Abstract: 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: GrantFiled: September 23, 2014Date of Patent: November 24, 2015Assignee: REGENERON PHARMACEUTICALS, INC.Inventors: Andrew J. Murphy, O. Gavin Thurston, Bindu Varghese, Cagan Gurer
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Patent number: 9181340Abstract: Antibodies that specifically bind TEM8 protein, and conjugates thereof, are disclosed herein. In some examples the conjugates and antibodies are useful for methods of detecting and treating pathogenic angiogenesis. In other examples the conjugates and antibodies are useful for methods of detecting and treating cancer. In additional examples, the conjugates and antibodies are useful for methods of decreasing binding of Anthrax protective antigen to a cell.Type: GrantFiled: June 13, 2012Date of Patent: November 10, 2015Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services, Novartis AGInventors: Brad St. Croix, Tony Fleming, Amit Chaudhary, Saurabh Saha, Xiaoyan Michelle Zhang, Rou-fun Kwong, Mary Beth Hilton
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Patent number: 9155290Abstract: 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: GrantFiled: October 15, 2014Date of Patent: October 13, 2015Assignee: REGENERON PHARMACEUTICALS, INC.Inventors: Jose F. Rojas, Ka-Man Venus Lai, Andrew J. Murphy
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Patent number: 9149026Abstract: Methods and compositions are described for making phenotypically female fertile animals from XY donor cells and suitable host embryos. Culture media and methods are provided for maintaining XY donor cells in culture that after introduction into a host embryo and gestation in a suitable host will result in fertile XY female animals. Methods and compositions are described for making fertile female animals in an F0 generation from a donor XY cell and a host embryo, as are methods for making F1 progeny that are homozygous for a modification from a heterozygous F0 fertile male and a heterozygous F0 fertile female sibling.Type: GrantFiled: June 10, 2011Date of Patent: October 6, 2015Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Wojtek Auerbach, Thomas Dechiara, William Poueymirou, David Frendewey, David Valenzuela
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Patent number: 9139638Abstract: Recombinant non-human mammals having reduced or no expression of vesicular acetylcholine transporter protein (VAChT) as compared to the corresponding wild-type mammal are provided. The mammal may have, e.g., impaired performance in object and social recognition and/or impaired neuromuscular performance and/or alterations in autonomic nervous system function as compared to the corresponding wild-type mammal. Methods of screening a compound for cholinergic activity or activity in treating a cholinergic neurotransmission disorder are also provided. In addition, a cell such as a nerve cell isolated from a mammal as described herein is provided, along with cell cultures, which are useful in vitro for screening the activity of candidate compounds for their effect on cholinergic neurotransmission, and for their activity in treating cholinergic neurotransmission disorders.Type: GrantFiled: August 21, 2007Date of Patent: September 22, 2015Assignees: Duke University, Universidade Federal de Minas GeraisInventors: Marc G. Caron, Vania F. Prado, Marco A. Prado, Raul Gainetdinov, Grace S. Pereira, Braulio M. Castro, Cristina M. Silva, Ivan A. Izquierdo
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Patent number: 9125386Abstract: 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: GrantFiled: September 19, 2014Date of Patent: September 8, 2015Assignee: REGENERON PHARMACEUTICALS, INC.Inventors: Li-Hsien Wang, Anthony T. Dore, Jr., Sean Stevens, Andrew J. Murphy
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Patent number: 9127292Abstract: 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: GrantFiled: October 17, 2014Date of Patent: September 8, 2015Assignee: REGENERON PHARMACEUTICALS, INC.Inventors: Andrew J. Murphy, O. Gavin Thurston, Bindu Varghese, Cagan Gurer
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Patent number: 9096672Abstract: The present invention relates to novel antibodies, particularly antibodies directed against deletion mutants of epidermal growth factor receptor and particularly to the type III deletion mutant, EGFRvIII. The invention also relates to human monoclonal antibodies directed against deletion mutants of epidermal growth factor receptor and particularly to EGFRvIII. Diagnostic and therapeutic formulations of such antibodies, and immunoconjugates thereof, are also provided.Type: GrantFiled: March 2, 2009Date of Patent: August 4, 2015Assignee: Amgen Fremont Inc.Inventors: Richard Weber, Xiao Feng, Orit Foord, Larry Green, Jean M. Gudas, Bruce Keyt, Ying Liu, Palaniswami Rathanaswami, Robert Raya, Xiao Dong Yang, Jose Corvalan, Ian Foltz, Xiao-Chi Jia, Jaspal S. Kang, Chadwick T. King, Scott L. Klakamp, Qiaojuan Jane Su
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Patent number: 9097728Abstract: A method for diagnosing and/or staging a hemoglobin disorder such as ?-thalassemia involves contacting a blood sample of a subject with an Alpha-Hemoglobin Stabilizing Protein which may be present on a solid support, and detecting and/or quantifying free ?-Hb. Detection or quantification can be achieved by photometry such as HTRF or immunological procedures such as EIA and ELISA. The free ?-Hb is compared to a reference value, and can be used to correlate with the diagnosis and/or staging of the hemoglobin disorder for the subject.Type: GrantFiled: April 23, 2010Date of Patent: August 4, 2015Assignees: Institut National de la Sante et de la Recherche Medicale (INSERM), Universite Paris-Sud, Assistance Publique-Hopitaux de Paris, Universite Paris Est Creteil Val de MarneInventors: Veronique Baudin-Creuza, Corinne Vasseur, Frederic Galacteros
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Patent number: 9089599Abstract: 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: January 10, 2014Date of Patent: July 28, 2015Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Lynn Macdonald, Naxin Tu, Cagan Gurer, Sean Stevens, Andrew J. Murphy
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Patent number: 9072777Abstract: It is intended to provide an angiogenic agent which contains, as the active ingredient, at least one substance selected from the group consisting of adrenomedullin, a substance inhibiting the activity of adrenomedullin degrading enzyme, an adrenomedullin receptor activity-modifying protein, a calcitonin receptor-like receptor and an adrenomedullin receptor.Type: GrantFiled: March 1, 2006Date of Patent: July 7, 2015Inventor: Takayuki Shindo
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Patent number: 9062113Abstract: The present invention relates to novel antibodies, particularly antibodies directed against deletion mutants of epidermal growth factor receptor and particularly to the type III deletion mutant, EGFRvIII. The invention also relates to human monoclonal antibodies directed against deletion mutants of epidermal growth factor receptor and particularly to EGFRvIII. Diagnostic and therapeutic formulations of such antibodies, and immunoconjugates thereof, are also provided.Type: GrantFiled: November 10, 2008Date of Patent: June 23, 2015Assignee: Amgen Fremont Inc.Inventors: Richard Weber, Xiao Feng, Orit Foord, Larry Green, Jean Gudas, Bruce Keyt, Ying Liu, Palaniswami Rathanaswami, Robert Raya, Xiao Dong Yang, Jose Corvalan, Ian Foltz, Xiao-Chi Jia, Jaspal S. Kang, Chadwick T. King, Scott L. Klakamp, Qiaojuan Jane Su
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Patent number: 9043996Abstract: The invention provides genetically modified non-human animals that express a humanized MHC II protein (humanized MHC II ? and ? polypeptides), as well as embryos, cells, and tissues comprising the humanized MHC II protein. Also provided are constructs for and methods of making the genetically modified non-human animals. Methods of using the genetically modified non-human animals to study various aspects of the human immune system are provided.Type: GrantFiled: March 11, 2013Date of Patent: June 2, 2015Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Lynn MacDonald, Andrew J. Murphy, Naxin Tu, Cagan Gurer, Vera Voronina, Sean Stevens
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Patent number: 9040771Abstract: 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: GrantFiled: January 27, 2012Date of Patent: May 26, 2015Assignee: The UAB Research FoundationInventors: Scott Webster Ballinger, Danny R. Welch, Robert Allen Kesterson, Larry W. Johnson
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Patent number: 9035128Abstract: 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: May 19, 2015Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Lynn MacDonald, Sean Stevens, Cagan Gurer, Andrew J. Murphy, Karolina A. Hosiawa
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Publication number: 20150133641Abstract: The invention relates, in one aspect, generally to novel concept of guided selection of antibody variable domains, combination and expression entirely in vivo. An application is to produce multivalent polypeptides. The present invention relates to multivalent (eg, multispecific) antibodies, antibody chains and polypeptides, as well as heavy chain-only antibodies (H2 antibodies) that are devoid of light chains. The invention further relates to the selection, maturation and production of these in vivo in non-human vertebrates and non-human vertebrate cells. To this end the invention also relates to such non-human vertebrates and cells. The invention also relates to the provision of means to produce and select heavy chain-only antibodies and heavy chains comprising variable domains that have undergone affinity maturation.Type: ApplicationFiled: November 17, 2014Publication date: May 14, 2015Inventors: Volker Germaschewski, E-Chiang Lee, Hanif Ali, Jasper Clube
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Patent number: 9029628Abstract: 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: May 12, 2015Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Lynn Macdonald, Sean Stevens, Cagan Gurer, Andrew J. Murphy, Karolina A. Meagher