Mouse Patents (Class 800/18)
  • Patent number: 11559049
    Abstract: Described are transgenic, non-human animals comprising a nucleic acid encoding an immunoglobulin light chain, whereby the immunoglobulin light chain is human, human-like, or humanized. The nucleic acid is provided with a means that renders it resistant to DNA rearrangements and/or somatic hypermutations. In one embodiment, the nucleic acid comprises an expression cassette for the expression of a desired molecule in cells during a certain stage of development in cells developing into mature B cells. Further provided is methods for producing an immunoglobulin from the transgenic, non-human animal.
    Type: Grant
    Filed: January 12, 2018
    Date of Patent: January 24, 2023
    Assignee: Merus N.V.
    Inventors: Ton Logtenberg, Mark Throsby, Robert A. Kramer, Rui D. Pinto, Cornelis A. De Kruif, Erwin Houtzager
  • Patent number: 11555187
    Abstract: Isolation or in vitro assembly of the Cas9-crRNA complex of the Streptococcus thermophilus CRISPR3/Cas system and use for cleavage of DNA bearing a nucleotide sequence complementary to the crRNA and a proto-spacer adjacent motif. Methods for site-specific modification of a target DNA molecule in vitro or in vivo using an RNA-guided DNA endonuclease comprising RNA sequences and at least one of an RuvC active site motif and an HNH active site motif; for conversion of Cas9 polypeptide into a nickase cleaving one strand of double-stranded DNA by inactivating one of the active sites (RuvC or HNH) in the polypeptide by at least one point mutation; for assembly of active polypeptide-polyribonucleotides complex in vivo or in vitro; and for re-programming a Cas9-crRNA complex specificity in vitro and using a cassette containing a single repeat-spacer-repeat unit.
    Type: Grant
    Filed: December 7, 2017
    Date of Patent: January 17, 2023
    Assignee: Vilnius University
    Inventors: Virginijus {hacek over (S)}ik{hacek over (s)}nys, Giedrius Gasiunas, Tautvydas Karvelis, Arvydas Lubys, Lolita Zaliauskiene, Monika Gasiuniene, Anja Smith
  • Patent number: 11470826
    Abstract: An object of the present invention is to provide a method of conveniently producing a genetically modified non-human mammal with high efficiency using a CRISPR-Cas9 system and particularly a production method whereby gene knock-in can be achieved with high efficiency regardless of the gene size. The method of producing a genetically modified non-human mammal comprises introducing a Cas9 protein, a crRNA fragment comprising a nucleotide sequence complementary to a target DNA region, and a tracrRNA fragment into a non-human mammalian oocyte to genetically modify the target DNA.
    Type: Grant
    Filed: October 6, 2015
    Date of Patent: October 18, 2022
    Assignee: NATIONAL UNIVERSITY CORPORATION TOKYO MEDICAL AND DENTAL UNIVERSITY
    Inventors: Kohichi Tanaka, Tomomi Aida, Yusaku Wada
  • Patent number: 11473082
    Abstract: Disclosed are compositions and methods for directing proteins to specific loci in the genome and uses thereof. In one aspect, the disclosed methods allow for directing proteins to specific loci in the genome of an organism, including the steps of providing a fusion protein comprising a DNA localization component and an effector molecule. Preferred embodiments of the disclosure include, but are not limited to, the following fusion proteins: dSaCas9-Clo051, dCas9-Clo051, Xanthomonas-TALE-Clo051, and Ralstonia-TALE-Clo051.
    Type: Grant
    Filed: June 16, 2016
    Date of Patent: October 18, 2022
    Assignee: Poseida Therapeutics, Inc.
    Inventors: Eric Ostertag, Tseten Yeshi, Xianghong Li
  • Patent number: 11466290
    Abstract: Described herein are donor vectors and systems for use in in vivo dual recombinase-mediated cassette exchange. Also described are animal models for consistent, rigorous, and facile investigation of transgene expression. Further described are methods of screening for therapeutic drugs using these animal models, and methods of treatment.
    Type: Grant
    Filed: December 30, 2016
    Date of Patent: October 11, 2022
    Assignee: Cedars-Sinai Medical Center
    Inventors: Joshua Breunig, Moise Danielpour, Gi Bum Kim
  • Patent number: 11464217
    Abstract: Disclosed herein are rodents (such as mice and rats) genetically modified at an endogenous Scn9a locus to comprise an exogenous Scn nucleotide sequence such as the coding sequence of a human SCN2A gene. Also disclosed are methods and compositions useful for making such rodents, and methods of using such rodents for generating anti-NaV1.7 antibodies.
    Type: Grant
    Filed: February 21, 2020
    Date of Patent: October 11, 2022
    Assignee: Regeneron Pharmaceuticals, Inc.
    Inventors: Nicole Alessandri-Haber, Andrew J. Murphy, Lynn Macdonald
  • Patent number: 11459570
    Abstract: Methods for treating, and for identifying novel treatments for, neurodegenerative diseases, as well as animal and cellular models.
    Type: Grant
    Filed: June 14, 2019
    Date of Patent: October 4, 2022
    Assignee: The General Hospital Corporation
    Inventors: Mark William Albers, Steven Rodriguez
  • Patent number: 11445710
    Abstract: Described are transgenic, non-human animals comprising a nucleic acid encoding an immunoglobulin light chain, whereby the immunoglobulin light chain is human, human-like, or humanized. The nucleic acid is provided with a means that renders it resistant to DNA rearrangements and/or somatic hypermutations. In one embodiment, the nucleic acid comprises an expression cassette for the expression of a desired molecule in cells during a certain stage of development in cells developing into mature B cells. Further provided is methods for producing an immunoglobulin from the transgenic, non-human animal.
    Type: Grant
    Filed: January 12, 2018
    Date of Patent: September 20, 2022
    Assignee: Merus N.V.
    Inventors: Ton Logtenberg, Mark Throsby, Robert A. Kramer, Rui D. Pinto, Cornelis A. De Kruif, Erwin Houtzager
  • Patent number: 11427636
    Abstract: Described herein are novel anti-PD1 antibody reagents (e.g., antibodies, antigen-binding fragments thereof, and/or chimeric antigen receptors). Also described herein antibody-drug conjugates or kits comprising the disclosed antibody reagents, as well as methods of treating cancer by administering the disclosed antibody reagents.
    Type: Grant
    Filed: May 1, 2018
    Date of Patent: August 30, 2022
    Assignee: THE CHILDREN'S MEDICAL CENTER CORPORATION
    Inventors: Frederick W. Alt, Ming Tian, Hwei-Ling Cheng
  • Patent number: 11427837
    Abstract: The present disclosure provides methods and compositions for enhanced editing of genomic DNA. For example, in some embodiments, a subject method is a method of editing genomic DNA of a eukaryotic cell and the method includes introducing into a eukaryotic cell a composition comprising: (a) a linearized non-homologous DNA composition and (b) a genome targeting composition (which includes a genome editing endonuclease, or a nucleic acid encoding the genome editing endonuclease). In some cases in which the genome editing endonuclease is a CRISPR/Cas endonuclease, the genome targeting composition can also include a corresponding CRISPR/Cas guide RNA.
    Type: Grant
    Filed: January 11, 2017
    Date of Patent: August 30, 2022
    Assignee: The Regents of the University of California
    Inventors: Jacob Corn, Christopher D. Richardson, Graham Jordan Ray
  • Patent number: 11396665
    Abstract: The present invention relates to the field of molecular biology and cell biology. More specifically, the present invention relates to a CRISPR-CAS system for a filamentous fungal host cell.
    Type: Grant
    Filed: January 6, 2016
    Date of Patent: July 26, 2022
    Assignee: DSM IP ASSETS B.V.
    Inventors: Bernard Meijrink, René Verwaal, Bianca Elisabeth Maria Gielesen, Johannes Andries Roubos, Carsten Pohl, Arnold Jacob Mattieu Driessen, Roelof Ary Lans Bovenberg, Yvonne Irene Nygård
  • Patent number: 11384344
    Abstract: The present application provides systems, methods and compositions used for targeted gene modification, targeted insertion, perturbation of gene transcripts, nucleic acid editing. Novel nucleic acid targeting systems comprise components of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) systems and transposable elements.
    Type: Grant
    Filed: December 17, 2019
    Date of Patent: July 12, 2022
    Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Jonathan Strecker, Alim Ladha
  • Patent number: 11384354
    Abstract: The present disclosure relates to a method of generating an antibody library, not limiting to a human naïve antibody gene expression library encompassing a pool of nucleic acid sequences derived from a natural antibody repertoire comprising humoral immunity from healthy and genetically diverse human populations. More specifically, the method employs a combination of phage and/or yeast antibody surface display concept which allows to screen large antibody library size and facilitates better folding of antibody structure. The present disclosure also relates to a human naïve antibody library generated by employing the process of the present disclosure, a set of primers employed in the method and application(s) of said antibody library.
    Type: Grant
    Filed: December 21, 2015
    Date of Patent: July 12, 2022
    Assignee: ZUMUTOR BIOLOGICS INC.
    Inventors: Sohang Chatterjee, Kavitha Iyer Rodrigues, Maloy Ghosh, Sunit Maity, Divya Unnikrishnan, Yogendra Manjunath Bangalore Muniraju, Sathyabalan Murugesan, Pavithra Mukunda, Bhargav Prasad, Veeresha Kamanagowda, Sanghamitra Bhattacharjee, Pravin Kumar Dakshinamurthy, Vivek Halan, Sankaranarayanan Srinivasan, Anuradha Hora, Bairavabalakumar Natarajan, Karthika Nair, Aswini Thanigaivel, Amol Maliwalave, Bharath Ravindra Shenoy, Sahana Bhima Rao, Subhra Prakash Chakrabarty, Ashvini Kumar Dubey, Amir Khan, Anurag Tiwari, Santosh Kumar, Shivani Patel, Nikitha M
  • Patent number: 11365429
    Abstract: 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: Grant
    Filed: April 29, 2019
    Date of Patent: June 21, 2022
    Assignee: President and Fellows of Harvard College
    Inventors: George M. Church, Prashant G. Mali, Luhan Yang
  • Patent number: 11360061
    Abstract: Provided are methods for determining the amount of lacosamide in a sample using mass spectrometry. The methods generally involve ionizing lacosamide in a sample and detecting and quantifying the amount of the ion to determine the amount of lacosamide in the sample.
    Type: Grant
    Filed: July 13, 2020
    Date of Patent: June 14, 2022
    Assignee: Quest Diagnostics Investments Incorporated
    Inventors: Beatrisa Boyadzhyan, Karin Thomassian, Anita Dermartirosian, Lou Jambor
  • Patent number: 11359211
    Abstract: 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: Grant
    Filed: April 29, 2019
    Date of Patent: June 14, 2022
    Assignee: President and Fellows of Harvard College
    Inventors: George M. Church, Prashant G. Mali, Luhan Yang
  • Patent number: 11337409
    Abstract: This disclosure provides, among other things, strategies for minimizing antibody diversification in a transgenic animal that uses gene conversion for antibody diversification. In some embodiments, the animal may comprise a genome comprising an endogenous immunoglobulin light chain locus comprising: (a) a functional immunoglobulin light chain gene comprising a nucleic acid encoding a light chain variable region; and (b) a plurality of pseudogenes that are operably linked to the functional immunoglobulin light chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding a light chain variable region, wherein the pseudogenes are upstream or downstream of the functional immunoglobulin light chain gene and encode the same amino acid sequence as the light chain variable region of the functional immunoglobulin light chain gene of (a). In other embodiments, the locus may have a tandem array of coding sequences for the light chain.
    Type: Grant
    Filed: June 5, 2019
    Date of Patent: May 24, 2022
    Assignee: CRYSTAL BIOSCIENCE INC.
    Inventors: Philip A. Leighton, William Don Harriman, Robert Etches
  • Patent number: 11306308
    Abstract: Provided herein is an improved method for performing CRISPR/Cas based screening that is not dependent on viral cloning methods.
    Type: Grant
    Filed: November 11, 2016
    Date of Patent: April 19, 2022
    Assignees: Massachusetts Institute of Technology, The Brigham and Women's Hospital, Inc.
    Inventors: David K. Gifford, Nisha Rajagopal, Richard Irving Sherwood
  • Patent number: 11274302
    Abstract: The invention provides specific synthetic chimeric xenonucleic acid guide RNA; s(XNA-gRNA) for enhancing crispr mediated genome editing efficiency. The invention also provides methods and compositions for inducing CRISPR/Cas-based gene editing/regulation (e.g., genome editing or gene expression) of a target nucleic acid (e.g., target DNA or target RNA) in a cell. The methods include using single guide RNAs (sgRNAs) that have been chemically modified with xeno nucleic acids which enhance gene regulation of the target nucleic acid in a primary cell for use in ex vivo therapy or in a cell in a subject for use in in vivo therapy. Additionally, provided herein are methods for preventing or treating a genetic disease in a subject by administering a sufficient amount of a sgRNA that has been chemically modified with xeno nucleic acids to correct a mutation in a target gene associated with the genetic disease.
    Type: Grant
    Filed: October 17, 2017
    Date of Patent: March 15, 2022
    Assignee: DIACARTA LTD
    Inventor: Michael J Powell
  • Patent number: 11267874
    Abstract: Disclosed herein are sensor systems, compositions comprising the sensor systems, and methods of using the same. In particular aspects, disclosed herein are sensor systems for a target intracellular ligand and uses thereof, e.g., in detection assays or in cell manipulation or therapeutic applications.
    Type: Grant
    Filed: April 15, 2016
    Date of Patent: March 8, 2022
    Assignee: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Chung Yiu Jonathan Tang, Constance Cepko, Eugene Drokhlyansky, Sui Wang
  • Patent number: 11267852
    Abstract: Provided herein is a cell line with improved odorant receptor function comprising an activated endogenous RTP1 gene, which further expresses an RTP1 protein. Further provided herein is a method for specifically activating an endogenous RTP1 gene in a eukaryotic cell using a CRISPR/Cas9 derived technique. Also provided herein is a method for identifying compounds with desired effects such as perfume or aroma modulators in said cell line.
    Type: Grant
    Filed: June 9, 2016
    Date of Patent: March 8, 2022
    Assignee: FIRMENICH SA
    Inventors: Hyo-Young Jeong, Patrick Pfister, Matthew Rogers
  • Patent number: 11240996
    Abstract: Mice comprising a transgene encoding a peptide (iBox) inhibitor of Group B p21-activated kinase are provided. Also provided are cells, tissue, and organs obtained from such transgenic mice. Also provided are methods for producing mice comprising an iBox-encoding transgene.
    Type: Grant
    Filed: August 23, 2017
    Date of Patent: February 8, 2022
    Assignee: Institute For Cancer Research
    Inventors: Jonathan Chernoff, Hoi Yee Chow
  • Patent number: 11242409
    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: February 8, 2022
    Assignee: ABLEXIS, LLC
    Inventors: Larry Green, Hiroaki Shizuya
  • Patent number: 11214800
    Abstract: Chromatin 3D structure modulating agents in the context of the present invention are intended to interfere or manipulate the function of loop anchor motifs, such as CTCF motifs. In certain example embodiments, the present invention may block formation of an loop anchor or chromatin domain or induce formation of a loop anchor or chromatin domain at a targeted genomic location. For instance, a loop anchor motif can be altered, such as by mutating (including inverting) a binding motif so as to remove such a motif, or by adding new binding motifs in new locations within a loop domain, so as to reduce the size of an existing loop, so as to modify the size of an existing loop, or combinations thereof. Alternatively, the chromatin 3D structure modulating agent may bind a target region and mask a loop anchor motif, thereby preventing a loop anchor or chromatin domain from forming. The chromatin 3D structure modulating agent may bind a target region and cause a loop anchor of chromatin domain to form.
    Type: Grant
    Filed: August 18, 2016
    Date of Patent: January 4, 2022
    Assignees: THE BROAD INSTITUTE, INC., BAYLOR COLLEGE OF MEDICINE
    Inventors: Erez Lieberman Aiden, Eric S. Lander, Suhas Rao, Su-Chen Huang, Adrian L. Sanborn, Neva C. Durand, Miriam Huntley, Andrew Jewett
  • Patent number: 11214620
    Abstract: The present invention relates to antibody molecules which bind to programmed death-ligand 1 (PD-L1) and lymphocyte-activation gene 3 (LAG-3). The antibody molecules preferably comprise a CDR-based antigen binding site for PD-L1, and a LAG-3 antigen binding site which may be located in two or more structural loops of a CH3 domain of the antibody molecule. The antibody molecules of the invention find application, for example, in cancer therapy.
    Type: Grant
    Filed: June 20, 2017
    Date of Patent: January 4, 2022
    Assignee: F-star Therapeutics Limited
    Inventors: Jamie Campbell, Nikole Sandy, Mihriban Tuna, Francisca Wollerton Van Horck, Katy Louise Everett, Miguel Gaspar, Matthew Kraman, Katarzyna Kmiecik, Mustapha Faroudi, Natalie Fosh, Barbara Hebeis
  • 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: 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: 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: 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