Mouse Patents (Class 800/18)
  • Patent number: 11174506
    Abstract: Labeled probes, and methods of use thereof, comprise a Cas polypeptide conjugated to gRNA that is specific for target nucleic acid sequences, including genomic DNA sequences. The probes and methods can be used to label nucleic acid sequences without global DNA denaturation. The presently-disclosed subject matter meets some or all of the above identified needs, as will become evident to those of ordinary skill in the art after a study of information provided in this document.
    Type: Grant
    Filed: October 16, 2015
    Date of Patent: November 16, 2021
    Assignee: HOWARD HUGHES MEDICAL INSTITUTE
    Inventors: Robert Singer, Wulan Deng, Timothee Lionnet
  • Patent number: 11130955
    Abstract: Methods, compositions, and kits for high throughput DNA assembly reactions in vitro. Modular CRISPR DNA constructs comprising modular insert DNA parts flanked by cloning tag segments comprising pre-validated CRISPR protospacer/protospacer adjacent motif sequence combinations. High throughput methods of CRISPRi and CRISPRa.
    Type: Grant
    Filed: August 15, 2019
    Date of Patent: September 28, 2021
    Assignee: Zymergen Inc.
    Inventors: Brian Chaikind, Hendrik M. Van Rossum, Aaron Miller, Paul Perkovich, Shawn Szyjka, Kedar Patel
  • Patent number: 11124773
    Abstract: The purpose of the present invention is to provide: a cancer stem cell mass from which cells incapable of forming cancer are substantially removed and which has a characteristic property of reproducing a layered structure of a cancer tissue; a process for producing the cancer stem cell mass; and use of the cancer stem cell mass. For achieving the purpose, the present inventors grew a human cancer tissue repeatedly in a NOG mouse, separated cancer cells from the grown cancer tissue, and made a comparison of various cancer cell culture processes with each other. As a result, a cancer stem cell composition which is homogeneous and is substantially free of the coexistence of cells capable of forming cancer and cells incapable of forming cancer in a mixed state can be produced successively by employing an attached culture process using a serum-free stem cell culture medium rather than a generally employed floating culture process, and consequently the present invention has been accomplished.
    Type: Grant
    Filed: October 6, 2011
    Date of Patent: September 21, 2021
    Assignee: CHUGAI SEIYAKU KABUSHIKI KAISHA
    Inventors: Tatsumi Yamazaki, Hisafumi Okabe, Shinta Kobayashi, Yu Jau Chen, Atsuhiko Kato, Masami Suzuki, Koichi Matsubara
  • Patent number: 11102962
    Abstract: Mice that comprise a replacement of endogenous mouse IL-6 and/or IL-6 receptor genes are described, and methods for making and using the mice. Mice comprising a replacement at an endogenous IL-6R? locus of mouse ectodomain-encoding sequence with human ectodomain-encoding sequence is provided. Mice comprising a human IL-6 gene under control of mouse IL-6 regulatory elements is also provided, including mice that have a replacement of mouse IL-6-encoding sequence with human IL-6-encoding sequence at an endogenous mouse IL-6 locus.
    Type: Grant
    Filed: July 3, 2019
    Date of Patent: August 31, 2021
    Assignee: REGENERON PHARMACEUTICALS, INC.
    Inventors: Li-Hsien Wang, Anthony T. Dore, Jr., Sean Stevens, Andrew J. Murphy
  • Patent number: 11065285
    Abstract: The invention disclosed herein describes biomarkers useful for prognosis, selection and monitoring of oncolytic virus therapy for patients with various types of cancer. In particular, the present invention provides identification of proteins whose expression patterns are strongly predictive of the outcome of oncolytic virus therapy in a patient with cancer. The present invention provides a method for identifying and selecting cancer patients who are likely to be non-responsive to onocolytic virus therapy. These patients can be co-administered an agent that stimulates a cell-mediated immune response in the patient with the oncolytic virus or can be administered a therapy other than oncolytic virus therapy.
    Type: Grant
    Filed: June 30, 2020
    Date of Patent: July 20, 2021
    Assignees: DNATRIX, INC., BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM
    Inventors: Frank Tufaro, Charles Conrad, Juan Fueyo-Margareto, Frederick Lang, Jr., Candelaria Gomez-Manzano, W.K. Alfred Yung, Amy Heimberger
  • Patent number: 11060114
    Abstract: Provided is a kit or a system including two elements or components. The first component (i) is a selective component including a nucleic acid sequence and at least one proto-spacer. The second component (ii) includes at least one sensitizing component including at least one cas gene and at least one CRISPR array. At least one spacer of the CRISPR targets a proto-spacer included within a pathogenic gene of a bacterium so as to specifically inactivate said pathogenic gene in said bacterium and wherein at least one spacer of said CRISPR targets a proto-spacer included within said selective component of (i) so as to specifically inactivate said selective component. Further provided is a method using the components or kits of the invention for interference with a horizontal transfer of a pathogenic gene between bacteria and for preventing a pathologic condition in a mammalian subject caused by a bacterial infection.
    Type: Grant
    Filed: May 25, 2017
    Date of Patent: July 13, 2021
    Assignee: TECHNOLOGY INNOVATION MOMENTUM FUND (ISRAEL) LIMITED PARTNERSHIP
    Inventors: Ehud Qimron, Ido Yosef, Miriam Manor
  • Patent number: 11041017
    Abstract: Pharmaceutical composition comprising antibodies or antigen binding fragments thereof that bind to stage-specific embryonic antigen 4 (SSEA-4) are disclosed herein, as well as methods of use thereof. Methods of use include, without limitation, cancer therapies and diagnostics. The antibodies of the disclosure can bind to certain cancer cell surfaces. Exemplary targets of the antibodies disclosed herein can include carcinomas, such as breast cancer, lung cancer, esophageal cancer, rectal cancer, biliary cancer, liver cancer, buccal cancer, gastric cancer, colon cancer, nasopharyngeal cancer, kidney cancer, prostate cancer, ovarian cancer, cervical cancer, endometrial cancer, pancreatic cancer, testicular cancer, bladder cancer, head and neck cancer, oral cancer, neuroendocrine cancer, adrenal cancer, thyroid cancer, bone cancer, skin cancer, basal cell carcinoma, squamous cell carcinoma, melanoma, and/or brain tumor.
    Type: Grant
    Filed: March 29, 2017
    Date of Patent: June 22, 2021
    Assignee: OBI Pharma, Inc.
    Inventors: Cheng-Der Tony Yu, Jiann-Shiun Lai, I-Ju Chen, Chiu-Chun Lin
  • Patent number: 11033009
    Abstract: This disclosure provides, among other things, a transgenic animal and a method of using the same to make antibodies that have a common light chain. In certain embodiments, the transgenic animal may comprising a genome comprising a common light chain transgene, wherein the common light chain transgene comprises a non-immunoglobulin light-chain promoter and a common light-chain coding sequence. In certain embodiments, the common light chain is constitutively expressed.
    Type: Grant
    Filed: August 24, 2016
    Date of Patent: June 15, 2021
    Assignee: CRYSTAL BIOSCIENCE INC.
    Inventors: William Don Harriman, Robert Etches, Philip A. Leighton
  • Patent number: 11026407
    Abstract: A genetically modified mouse is provided, wherein the mouse expresses an immunoglobulin light chain repertoire characterized by a limited number of light chain variable domains. Mice are provided that present a choice of two human light chain variable gene segments such that the immunoglobulin light chains expresses by the mouse comprise one of the two human light chain variable gene segments. Methods for making bispecific antibodies having universal light chains using mice as described herein, including human light chain variable regions, are provided. Methods for making human variable regions suitable for use in multispecific binding proteins, e.g., bispecific antibodies, and host cells are provided.
    Type: Grant
    Filed: August 2, 2019
    Date of Patent: June 8, 2021
    Assignee: Regeneran Pharmaceuticals, Inc.
    Inventors: John McWhirter, Lynn Macdonald, Sean Stevens, Andrew J. Murphy
  • Patent number: 11019810
    Abstract: Genetically modified non-human animals and methods and compositions for making and using the same are provided, wherein the genetic modification comprises a humanization of an endogenous signal-regulatory protein gene, in particular a humanization of a SIRP? gene. Genetically modified mice are described, including mice that express a human or humanized SIRP? protein from an endogenous SIRP? locus.
    Type: Grant
    Filed: August 15, 2019
    Date of Patent: June 1, 2021
    Assignee: REGENERON PHARMACEUTICALS, INC.
    Inventors: Andrew J. Murphy, O. Gavin Thurston, Bindu Varghese, Cagan Gurer
  • Patent number: 11000020
    Abstract: Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise a humanized B-cell activating factor gene. Non-human animals and cells that express a human or humanized B-cell activating factor protein from an endogenous B-cell activating factor locus are described.
    Type: Grant
    Filed: January 8, 2019
    Date of Patent: May 11, 2021
    Assignee: REGENERON PHARMACEUTICALS, INC.
    Inventors: John McWhirter, Cagan Gurer, Lynn Macdonald, Andrew J. Murphy
  • Patent number: 10993420
    Abstract: 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: Grant
    Filed: March 14, 2014
    Date of Patent: May 4, 2021
    Assignee: ERASMUS UNIVERSITY MEDICAL CENTER
    Inventors: Franklin Gerardus Grosveld, Richard Wilhelm Janssens
  • Patent number: 10986820
    Abstract: 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: Grant
    Filed: October 19, 2018
    Date of Patent: April 27, 2021
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: John McWhirter, Lynn Macdonald, Sean Stevens, David R. Buckler, Andrew J. Murphy
  • Patent number: 10980222
    Abstract: The present disclosure relates to genetically modified non-human animals (e.g., genetically-modified mice) that express a human or chimeric (e.g., humanized) CD27. The present disclosure also relates to methods of generating the genetically-modified animals (e.g., genetically modified mice), and methods of using the genetically modified non-human animals (e.g., genetically modified mice) described herein.
    Type: Grant
    Filed: June 7, 2019
    Date of Patent: April 20, 2021
    Assignee: Biocytogen Pharmaceuticals (Beijing) Co., Ltd.
    Inventors: Yuelei Shen, Yang Bai, Rui Huang, Chengzhang Shang, Yanan Guo, Meiling Zhang
  • Patent number: 10973842
    Abstract: The described invention provides a method for reducing progression of lung fibrosis after a lung injury comprising administering a therapeutic amount of a therapeutic agent, wherein the therapeutic amount is effective: (a) to modulate expression of a T-box transcription factor in a population of cells in lung; and (b) to reduce proliferation of the population of cells in lung expressing the T-box transcription factor. According to some embodiments the T-box transcription factor is Tbx4.
    Type: Grant
    Filed: November 1, 2016
    Date of Patent: April 13, 2021
    Assignee: CEDARS-SINAI MEDICAL CENTER
    Inventors: Paul W. Noble, Dianhua Jiang, Ting Xie, Carol Jiurong Liang
  • Patent number: 10954300
    Abstract: Methods of treating a PD-1-resistant cancer are provided and comprise administering to a subject in need thereof a therapeutically effective amount of a c-Rel inhibitor and a therapeutically effective amount of a PD-1 inhibitor. A pharmaceutical combination comprising a therapeutically effective amount of a c-Rel inhibitor, and a therapeutically effective amount of a PD-1 inhibitor is also provided. Finally, methods of treating a cancer such as a CTLA-4-resistant cancer, a CD137-resistant cancer, and an OX-4-resistant cancer are provided and comprise administering to a subject in need thereof a therapeutically effective amount of a c-Rel inhibitor and a therapeutically effective amount of a CLTA-4, CD137 or OX-4 inhibitor, respectively.
    Type: Grant
    Filed: September 28, 2016
    Date of Patent: March 23, 2021
    Assignee: THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK
    Inventors: Sankar Ghosh, Yenkel Grinberg-Bleyer
  • Patent number: 10947433
    Abstract: Proteins with antibacterial properties may be used in additive compositions, fluid compositions, and methods for decreasing or removing sulfur-containing compounds and/or acid-containing compounds from recovered downhole fluids and/or the subterranean reservoir wellbore from which the downhole fluid was recovered. The fluid composition may include at least protein and a base fluid. The protein(s) may be or include a labiase, a lysozyme, a lysostaphin, a hexose oxidase, a cecropin, a thermolysin, a serine protease, a cysteine protease, and combinations thereof. The base fluid may be or include a drilling fluid, a servicing fluid, a production fluid, a completion fluid, an injection fluid, a refinery fluids, and combinations thereof.
    Type: Grant
    Filed: August 10, 2015
    Date of Patent: March 16, 2021
    Assignee: Baker Hughes Holdings LLC
    Inventors: Prasad D. Dhulipala, Charles D. Armstrong
  • Patent number: 10945418
    Abstract: This disclosure relates to genetically modified animal expressing human or chimeric (e.g., humanized) programmed death-ligand 1 (PD-L1, PDL1, or B7-H1), and methods of use thereof. In one aspect, the disclosure relates to genetically-modified, non-human animals whose genome comprises at least one chromosome comprising a sequence encoding a human or chimeric programmed death-ligand 1 (PD-L1).
    Type: Grant
    Filed: May 31, 2019
    Date of Patent: March 16, 2021
    Assignee: Biocytogen Pharmaceuticals (Beijing) Co., Ltd.
    Inventors: Yuelei Shen, Yang Bai, Yanan Guo, Rui Huang, Xiaofei Zhou, Chaoshe Guo
  • Patent number: 10920221
    Abstract: CRISPR/Cas Systems are provided where guide RNAs include one or more selected RNA sequences for delivery to a target nucleic acid sequence.
    Type: Grant
    Filed: May 13, 2016
    Date of Patent: February 16, 2021
    Assignee: President and Fellows of Harvard College
    Inventors: John L. Rinn, David M. Shechner
  • Patent number: 10893666
    Abstract: Methods and compositions are provided for generating F0 fertile XY female animals. The methods and compositions involve making XY pluripotent or totipotent animal cells, in vitro cell cultures, or embryos that are capable of producing a fertile female XY animal in an F0 generation. Such cells, embryos, and animals can be made by silencing a region of the Y chromosome. Optionally, the cells can also be cultured in feminizing medium such as a low-osmolality medium and/or can be modified to decrease the level and/or activity of an Sry protein. Methods and compositions are also provided for silencing a region of the Y chromosome in an XY pluripotent or totipotent animal cell, or in vitro cell cultures, embryos, or animals derived therefrom, by maintaining an XY pluripotent or totipotent animal cell in a feminizing medium.
    Type: Grant
    Filed: September 16, 2016
    Date of Patent: January 19, 2021
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: Jennifer Schmahl, David Frendewey, Junko Kuno, Chia-Jen Siao, Gustavo Droguett, Yu Bai, Wojtek Auerbach
  • Patent number: 10881086
    Abstract: Non-human animals, methods and compositions for making and using the same, are provided, wherein said non-human animals comprise a humanization of a Cluster of Differentiation 274 (CD274) gene. Such non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous CD274 gene so that said non-human animals express a Programmed cell death ligand 1 (PD-L1) polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).
    Type: Grant
    Filed: January 30, 2018
    Date of Patent: January 5, 2021
    Assignee: REGENERON PHARMACEUTICALS, INC.
    Inventors: Elena Burova, Yajun Tang, Ka-Man Venus Lai, Andrew J. Murphy
  • Patent number: 10876100
    Abstract: Disclosed and claimed are mutation(s) or modification(s) of the CRISPR enzyme, for example a Cas enzyme such as a Cas9, which obtain an improvement, for instance a reduction, as to off-target effects of a CRISPR-Cas or CRISPR-enzyme or CRISPR-Cas9 system or complex containing or including such a mutated or modified Cas or CRISPR enzyme or Cas9. Methods for making and using and uses of such mutated or modified Cas or CRISPR enzyme or Cas9 and systems or complexes containing the same and products from such methods and uses are also disclosed and claimed.
    Type: Grant
    Filed: December 16, 2017
    Date of Patent: December 29, 2020
    Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Linyi Gao, Bernd Zetsche, Ian Slaymaker
  • Patent number: 10869465
    Abstract: Provided are a non-human model animal of a retinal vascular disease that can favorably show symptoms similar to those of human retinal vascular diseases such as human diabetic retinopathy, and a method for producing the non-human model animal. In particular, provided are a non-human model animal that is suitable for establishing a method for treating, preventing, or diagnosing retinal edema, which causes highly impaired vision, and a method for producing the non-human model animal. A method for screening a drug for treating and preventing a retinal vascular disease, the method using a non-human model animal, is provided. Provided are a non-human model animal of a retinal vascular disease in which constitutively active Akt is expressed, a method for producing a non-human model animal of a retinal vascular disease in which constitutively active Akt is expressed, and a method for screening a drug for treating or preventing a retinal vascular disease.
    Type: Grant
    Filed: August 8, 2018
    Date of Patent: December 22, 2020
    Assignee: OSAKA UNIVERSITY
    Inventors: Yoko Fukushima, Kohji Nishida, Toru Nakano
  • Patent number: 10863730
    Abstract: A method for producing a cell in which a target gene is knocked out, the method including the step of: introducing a CRISPR-Cas system into a cell having one or more kinds of target genes, the CRISPR-Cas system being able to produce (i) three or more kinds of guide RNAs for each of the one or more kinds of target genes and (ii) a Cas protein. The present invention can provide a method that enables highly efficient (90% or more) production of whole-body biallelic knockout animals in a single generation.
    Type: Grant
    Filed: December 25, 2015
    Date of Patent: December 15, 2020
    Assignee: RIKEN
    Inventors: Hiroki Ueda, Genshiro Sunagawa, Kenta Sumiyama, Maki Ukai, Dimitri Perrin
  • Patent number: 10851380
    Abstract: The present invention relates to targeted genome editing in eukaryotic cells or organisms. More particularly, the present invention relates to a composition for cleaving a target DNA in eukaryotic cells or organisms comprising a guide RNA specific for the target DNA and Cas protein-encoding nucleic acid or Cas protein, and use thereof.
    Type: Grant
    Filed: April 13, 2015
    Date of Patent: December 1, 2020
    Assignee: TOOLGEN INCORPORATED
    Inventors: Jin-Soo Kim, Seung Woo Cho, Sojung Kim
  • Patent number: 10820580
    Abstract: The present disclosure relates to the genetically modified non-human animals that have a disruption at the endogenous CD132 gene (e.g., CD132 knockout), and methods of use thereof.
    Type: Grant
    Filed: June 7, 2019
    Date of Patent: November 3, 2020
    Assignee: Beijing Biocytogen Co., Ltd
    Inventors: Yuelei Shen, Yang Bai, Meiling Zhang, Jiawei Yao, Rui Huang, Yanan Guo
  • Patent number: 10785968
    Abstract: Genetically modified non-human animals are provided that may be used to model human hematopoietic cell development, function, or disease. The genetically modified non-human animals comprise a nucleic acid encoding human IL-6 operably linked to an IL-6 promoter. In some instances, the genetically modified non-human animal expressing human IL-6 also expresses at least one of human M-CSF, human IL-3, human GM-CSF, human SIRPa or human TPO. In some instances, the genetically modified non-human animal is immunodeficient. In some such instances, the genetically modified non-human animal is engrafted with healthy or diseased human hematopoietic cells. Also provided are methods for using the subject genetically modified non-human animals in modeling human hematopoietic cell development, function, and/or disease, as well as reagents and kits thereof that find use in making the subject genetically modified non-human animals and/or practicing the subject methods.
    Type: Grant
    Filed: November 6, 2017
    Date of Patent: September 29, 2020
    Assignees: Regeneron Pharmaceuticals, Inc., Yale University, Institute for Research in Biomedicine (IRB)
    Inventors: Richard Flavell, Till Strowig, Markus G. Manz, Chiara Borsotti, Madhav Dhodapkar, Andrew J. Murphy, Sean Stevens, George D. Yancopoulos
  • Patent number: 10774155
    Abstract: The invention discloses methods for the generation of chimaeric human—non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.
    Type: Grant
    Filed: April 9, 2018
    Date of Patent: September 15, 2020
    Assignee: Kymab Limited
    Inventors: Allan Bradley, E-Chiang Lee, Wei Wang, Dominik Spensberger, Hui Liu, Jasper Clube, Qi Liang
  • Patent number: 10767175
    Abstract: The present invention relates to guide RNAs having chemical modifications and their use in CRISPR-Cas systems. The chemically modified guide RNAs have enhanced specificity for target polynucleotide sequences. The present invention also relates to methods of using chemically modified guide RNAs for cleaving or nicking polynucleotides, and for high specificity genome editing.
    Type: Grant
    Filed: April 20, 2017
    Date of Patent: September 8, 2020
    Assignee: AGILENT TECHNOLOGIES, INC.
    Inventors: Douglas J Dellinger, Daniel E Ryan, Subhadeep Roy, Jeffrey R Sampson
  • Patent number: 10765093
    Abstract: This present invention relates to transgenic animals useful to study human diseases. Specifically, the invention relates to transgenic animals expressing at least two human proteins (optionally in replacement of the counterpart proteins in the animal) whereas a first human protein interacts with a second human protein. The transgenic animals can then be used for evaluating drugs or building disease models that are related to the expressed human proteins in the animals. The animals and methods disclosed herein reduce the possibility identifying a false-positive compound—the compound that show an effect in a naturally-occurring, non-transgenic animal but may not necessarily work or be therapeutic in human, since the compound may only interrupt the interaction between two animal proteins not necessarily two related human proteins.
    Type: Grant
    Filed: November 28, 2011
    Date of Patent: September 8, 2020
    Inventor: James Zhu
  • Patent number: 10752906
    Abstract: Stably immunized cells and methods of making stably immunized cells are provided. Methods of altering the microbiota of an ecological environment are provided. Methods of modifying target chromosomes are provided. Methods of delivering genetic material to target cells are provided.
    Type: Grant
    Filed: November 5, 2014
    Date of Patent: August 25, 2020
    Assignee: President and Fellows of Harvard College
    Inventors: Kevin M. Esvelt, Stephanie Yaung
  • Patent number: 10738278
    Abstract: Provided are engineered cells for adoptive therapy, including NK cells and T cells. Also provided are compositions for engineering and producing the cells, compositions containing the cells, and methods for their administration to subjects. In some aspects, features of the cells and methods provide specificity and/or efficacy. In some embodiments, the cells contain genetically engineered antigen receptors that specifically bind to antigens, such as chimeric antigen receptors (CARs) and costimulatory receptors. In some embodiments, the cells include receptors targeting multiple antigens. In some embodiments, the cells include repression of one or more gene product, for example, by disruption of a gene encoding the gene product. In some embodiments, a gene encoding an antigen recognized by the engineered antigen receptor is disrupted, reducing the likelihood of targeting of the engineered cells.
    Type: Grant
    Filed: July 15, 2015
    Date of Patent: August 11, 2020
    Assignee: Juno Therapeutics, Inc.
    Inventors: Kendall M. Mohler, Hyam I. Levitsky
  • Patent number: 10730930
    Abstract: The invention relates to the provision of antibody therapeutics and prophylactics that are tailored specifically for human use. The present invention provides libraries, vertebrates and cells, such as transgenic mice or rats or transgenic mouse or rat cells. Furthermore, the invention relates to methods of using the vertebrates to isolate antibodies or nucleotide sequences encoding antibodies. Antibodies, heavy chains, polypeptides, nucleotide sequences, pharmaceutical compositions and uses are also provided by the invention.
    Type: Grant
    Filed: July 21, 2017
    Date of Patent: August 4, 2020
    Assignee: Kymab Limited
    Inventors: Allan Bradley, Glenn Friedrich, E-Chiang Lee, Mark Strivens, Nicholas England
  • Patent number: 10694724
    Abstract: A transgenic animal model that is suitable for the cell or tissue specific assessing of thyroid hormone (TH) action in vivo is described. The recombinant DNA construct and methods suitable to generate such an animal are also provided. The assessment of TH action is based on a reporter that is dependent on an endogenously expressed thyroid hormone receptor (TR) and coregulators of said receptor.
    Type: Grant
    Filed: November 30, 2015
    Date of Patent: June 30, 2020
    Assignee: Kisérleti Orvostudoányi Kutatóintézet
    Inventors: Csaba Fekete, Balázs Gereben, Petra Mohácsik, Ferenc Erdélyi, Gábor Szabó
  • Patent number: 10687520
    Abstract: Duchenne muscular dystrophy (DMD), which affects 1 in 5,000 male births, is one of the most common genetic disorders of children. This disease is caused by an absence or deficiency of dystrophin protein in striated muscle. The major DMD deletion “hot spots” are found between exon 6 to 8, and exons 45 to 53. Here, a “humanized” mouse model is provided that can be used to test a variety of DMD exon skipping strategies. Among these are, CRISPR/Cas9 oligonucleotides, small molecules or other therapeutic modalities that promote exon skipping or micro dystrophin mini genes or cell based therapies. Methods for restoring the reading frame of exon 44 deletion via CRISPR-mediated exon skipping in the humanized mouse model, in patient-derived iPS cells and ultimately, in patients using various delivery systems are also contemplated. The impact of CRISPR technology on DMD is that gene editing can permanently correct mutations.
    Type: Grant
    Filed: March 7, 2018
    Date of Patent: June 23, 2020
    Assignee: The Board of Regents of the University of Texas System
    Inventors: Yi-Li Min, Rhonda Bassel-Duby, Eric Olson
  • Patent number: 10667501
    Abstract: The invention relates, in one aspect, generally to novel concept of guided selection of antibody variable domains, combination and expression entirely in vivo. An application is to produce multivalent polypeptides. The present invention relates to multivalent (eg, multispecific) antibodies, antibody chains and polypeptides, as well as heavy chain-only antibodies (H2 antibodies) that are devoid of light chains. The invention further relates to the selection, maturation and production of these in vivo in non-human vertebrates and non-human vertebrate cells. To this end the invention also relates to such non-human vertebrates and cells. The invention also relates to the provision of means to produce and select heavy chain-only antibodies and heavy chains comprising variable domains that have undergone affinity maturation.
    Type: Grant
    Filed: November 17, 2014
    Date of Patent: June 2, 2020
    Assignee: Kymab Limited
    Inventors: Volker Germaschewski, E-Chiang Lee, Hanif Ali, Jasper Clube
  • Patent number: 10662255
    Abstract: The invention provides non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing transgenic cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.
    Type: Grant
    Filed: March 20, 2017
    Date of Patent: May 26, 2020
    Assignee: Ablexis, LLC
    Inventors: Larry Green, Hiroaki Shizuya
  • Patent number: 10640789
    Abstract: Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.
    Type: Grant
    Filed: February 22, 2016
    Date of Patent: May 5, 2020
    Assignee: President and Fellows of Harvard College
    Inventors: George M. Church, Prashant G. Mali, Kevin M. Esvelt
  • Patent number: 10626188
    Abstract: The invention provides non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing transgenic cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.
    Type: Grant
    Filed: March 20, 2017
    Date of Patent: April 21, 2020
    Assignee: ABLEXIS, LLC
    Inventors: Larry Green, Hiroaki Shizuya
  • Patent number: 10618977
    Abstract: The invention provides non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing transgenic cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.
    Type: Grant
    Filed: March 20, 2017
    Date of Patent: April 14, 2020
    Assignee: ABLEXIS, LLC
    Inventors: Larry Green, Hiroaki Shizuya
  • Patent number: 10604587
    Abstract: The invention provides non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing transgenic cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.
    Type: Grant
    Filed: March 20, 2017
    Date of Patent: March 31, 2020
    Assignee: ABLEXIS, LLC
    Inventors: Larry Green, Hiroaki Shizuya
  • Patent number: 10575505
    Abstract: An object of the present invention is to provide a mouse that enables the functions of human NK cell to be studied. A DNA consisting of a nucleotide sequence represented by SEQ ID NO: 1, which is a gene region comprising a DNA in which a cDNA sequence encoding interleukin 15 (IL-15) is operably ligated to a cDNA sequence encoding the signal peptide of human interleukin (IL-2), is inserted to immunodeficient mouse cDNA. In NOD-scid, IL-2r?null-hIL-15 Tg mice thus generated, hCD56+ cell having a concentration sufficient for conducting in vivo study on human mature NK cell are detected for at least 6 months after transplantation.
    Type: Grant
    Filed: April 20, 2016
    Date of Patent: March 3, 2020
    Assignee: Central Institute for Experimental Animals
    Inventors: Mamoru Ito, Ikumi Katano
  • Patent number: 10555506
    Abstract: The invention provides knock-in non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing knock-in cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.
    Type: Grant
    Filed: April 11, 2016
    Date of Patent: February 11, 2020
    Assignee: ABLEXIS, LLC
    Inventors: Larry Green, Hiroaki Shizuya
  • Patent number: 10526630
    Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.
    Type: Grant
    Filed: October 4, 2013
    Date of Patent: January 7, 2020
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: Andrew J. Murphy, George D. Yancopoulos, Margaret Karow, Lynn Macdonald, Sean Stevens, Aris N. Economides, David M. Valenzuela
  • Patent number: 10526420
    Abstract: The invention provides non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing transgenic cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.
    Type: Grant
    Filed: March 20, 2017
    Date of Patent: January 7, 2020
    Assignee: ABLEXIS, LLC
    Inventors: Larry Green, Hiroaki Shizuya
  • Patent number: 10492476
    Abstract: The invention provides knock-in non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing knock-in cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.
    Type: Grant
    Filed: April 11, 2016
    Date of Patent: December 3, 2019
    Assignee: ABLEXIS, LLC
    Inventors: Larry Green, Hiroaki Shizuya
  • Patent number: 10494620
    Abstract: The present disclosure provides compositions and methods for binding and/or cleaving a single stranded target nucleic acid. Subject compositions include a Cas9 polypeptide, a guide nucleic acid, and a PAMmer. A subject PAMmer is a single stranded oligonucleotide having a protospacer adjacent motif (PAM) sequence and at least one of: a specifity segment positioned 5? of the PAM sequence, and an orientation segment positioned 3? of the PAM sequence. In some embodiments, the Cas9 polypeptide is a variant Cas9 polypeptide having reduced nuclease activity relative to a corresponding wild type Cas9 polypeptide. In some cases, methods of binding are for visualizing single stranded target nucleic acids using a detectable label. In some cases, methods of binding are for isolating, collecting, and/or analyzing at least one of: (i) bound single stranded target nucleic acids; and (ii) polypeptides associated with bound single stranded target nucleic acids.
    Type: Grant
    Filed: June 7, 2018
    Date of Patent: December 3, 2019
    Assignee: The Regents of the University of California
    Inventors: Jennifer A. Doudna, Samuel H. Sternberg, Mitchell O'Connell, Benjamin Oakes
  • Patent number: 10487147
    Abstract: The present application relates to anti-PD-L1 antibodies or antigen binding fragments thereof, nucleic acid encoding the same, therapeutic compositions thereof, and their use to enhance T-cell function to upregulate cell-mediated immune responses and for the treatment of T cell dysfunctional disorders, such as tumor immunity, for the treatment of and cancer.
    Type: Grant
    Filed: March 9, 2017
    Date of Patent: November 26, 2019
    Assignee: Merck Patent GmbH
    Inventors: Horacio G. Nastri, Christel Iffland, Olivier Leger, Qi An, Mark Cartwright, Sean D. McKenna
  • Patent number: 10463029
    Abstract: This disclosure relates to a rodent model of Steel Syndrome. Disclosed herein are genetically modified rodent animals that carry a mutation in an endogenous rodent Col27a1 gene, equivalent to a mutation in humans causing Steel Syndrome.
    Type: Grant
    Filed: June 7, 2018
    Date of Patent: November 5, 2019
    Assignee: REGENERON PHARMACEUTICALS, INC.
    Inventors: Claudia Gonzaga-Jauregui, Chia-Jen Siao, Harikiran Nistala, Kalyan C. Nannuru
  • Patent number: 10466233
    Abstract: A nanosensor for detecting and quantifying lactate in different types of samples, such as tissues, intra-cellular and subcellular compartments, with high spatial and temporal resolution is disclosed. Methods comprising use of the nanosensor for quantifying the activity of lactate transporters, rates of cellular lactate production and cellular lactate consumption, and rate of mitochondrial pyruvate consumption are also disclosed. Methods for quantifying the transformation in energy metabolism that characterizes cancer cells with single-cell resolution and for detecting interference of candidate drugs with mitochondrial energetics are additionally disclosed.
    Type: Grant
    Filed: April 13, 2012
    Date of Patent: November 5, 2019
    Assignees: CENTRO DE ESTUDIOS CIENTIFICOS DE VALDIVIA, CARNEGIE INSTITUTION OF WASHINGTON
    Inventors: Luis Felipe Barros Olmedo, Alejandro San Martin, Sebastian Ceballo Charpentier, Wolf B. Frommer