Abstract: The present invention provides compositions and methods for generating a genetically modified T cells comprising a chimeric antigen receptor (CAR) having an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the T cell exhibits prolonged exponential expansion in culture that is ligand independent and independent of the addition of exogenous cytokines or feeder cells.
Type:
Grant
Filed:
February 22, 2013
Date of Patent:
August 7, 2018
Assignee:
The Trustees of the University of Pennsylvania
Inventors:
Matthew J. Frigault, Yangbing Zhao, John Scholler, Carl H. June
Abstract: Provided in the present invention is a method for positioning and integrating transgene and a use thereof. Specifically provided is a variant loxP element. The sequence “ATAAT” of an reverse repeated sequence in a wild type loxp locus is mutated into “CACCT”, i.e., a variant loxp element. Also provided in the present invention are a construct comprising the variant loxP element, a vector or host cell comprising the construct and a method for preparing a transgenic animal using the vector and the host cell.
Type:
Grant
Filed:
September 28, 2013
Date of Patent:
July 31, 2018
Assignees:
SHANGHAI GENON BIOENGINEERING CO., LTD, SHANGHAI TRANSGENIC RESEARCH CENTER
Inventors:
Guoxiang Cheng, Jianquan Chen, Siguo Liu
Abstract: This invention provides a method of producing a primordial germ cell-like cell (PGCLC) from an epiblast isolated from an embryo or an epiblast-like cell (EpiLC) induced from a pluripotent stem cell (PSC), which comprises allowing the epiblast or EpiLC to express exogenous transcription factor(s) selected from the group consisting of: (i) Blimp1, Prdm14 and Tfap2c; ii) Blimp1 and Prdm14; (iii) Blimp1 and Tfap2c; (iv) Prdm14 and Tfap2c; and (v) Prdm14; thereby inducing the epiblast or EpiLC into a PGC state without acquiring transient mesodermal program.
Abstract: The presently disclosed subject matter relates to compositions and methods directed to cancer theranostic nucleic acid constructs that permit simultaneous cancer-specific viral replication, expression of a diagnostic gene product, and expression of a therapeutic gene.
Type:
Grant
Filed:
June 4, 2014
Date of Patent:
June 12, 2018
Assignees:
The Johns Hopkins University, Virginia Commonwealth University
Inventors:
Paul B. Fisher, Swadesh K. Das, Mitchell E. Menezes, Devanand Sarkar, Martin G. Pomper
Abstract: A transgenic non-human animal is provided. In certain embodiments, the animal comprises a genome comprising an immunoglobulin heavy chain locus comprising: a) a transcribed gene encoding a fusion protein comprising, from N-terminus to C-terminus: i. a scaffold comprising a first binding domain; and ii. a heavy chain constant region operably linked to the scaffold; wherein the scaffold is capable of specifically binding to a target in the absence of additional polypeptides; and b) a plurality of pseudogenes that are operably linked to the transcribed gene and that donate, by gene conversion, nucleotide sequence to the part of the transcribed gene that encodes the binding domain.
Abstract: A method for inducing tailored pluripotent stem cells by reprogramming differentiated cells of an adult by using an extract of plant stem cells and plant dedifferentiated stem cells (callus); pluripotent stem cells produced by means of the method; and a cell therapy agent comprising the pluripotent stem cells are disclosed. It is possible to overcome ethical problems since eggs are not used in the making of pluripotent stem cells having abilities like embryonic stem cells. It is possible to produce pluripotent stem cells of ensured safety because a plant stem cell extract which above all has been verified to be harmless to the body is used. It is possible to develop an immunocompatible cell therapy agent tailored to different individuals.
Type:
Grant
Filed:
January 28, 2014
Date of Patent:
May 22, 2018
Assignee:
SNU R&DB FOUNDATION
Inventors:
Yoo-Wook Kwon, Young-Bae Park, Hyo-Soo Kim, Jae-Seung Paek
Abstract: The present invention relates inter alia to improvements in the production of chimaeric antibodies in non-human transgenic vertebrates such as mice and rats bearing one or more chimaeric antibody transgenes. In particular, the invention provides for improved non-human vertebrates and cells in which VpreB has been species-matched with the variable region of the chimaeric antibodies. Also, embodiments also provide for species-matching of the entire surrogate light chain for efficient pairing with chimaeric heavy chains during B-cell development in vivo in a non-human transgenic vertebrate setting.
Type:
Grant
Filed:
March 26, 2014
Date of Patent:
May 8, 2018
Assignee:
Kymab Limited
Inventors:
Allan Bradley, E-Chiang Lee, Qi Liang, Dominik Spensberger, Nicholas England
Abstract: A root canal filling material for a tooth extraction or tooth non-extraction process can be used clinically because of its easy availability and can efficiently enhance dental tissue regeneration; a method for regenerating dental tissue using the filling material is also provided. A root canal filling material 200 including mesenchymal stem cells 220 excluding dental pulp stem cells, which are inserted into the apical side of a root canal subjected to pulp extirpation or to root canal enlargement and cleaning of an infected root canal and including an extracellular matrix 210 is provided, and a method for regenerating dental tissue, through a tooth extracting or tooth non-extracting process, including a step of injecting the root canal filling material into the apical side of a root canal of a non-extracted tooth subjected to pulp extirpation or to root canal enlargement and cleaning of an infected root canal is provided.
Type:
Grant
Filed:
January 31, 2012
Date of Patent:
May 8, 2018
Assignee:
National Center for Geriatrics and Gerontology
Abstract: The present invention provides a mouse with liver damage, having a high degree of damage against the mouse's original hepatocytes while having a uPA gene in a heterozygous form, and a method for efficiently preparing the mouse. Specifically, the method for preparing a mouse with liver damage having the uPA gene in a heterozygous form comprises the following steps of: (i) transforming mouse ES cells with a DNA fragment containing a liver-specific promoter/enhancer and cDNA that encodes a urokinase-type plasminogen activator operably linked under the control thereof; (ii) injecting the transformed mouse ES cells obtained in step (i) into a host embryo; (iii) transplanting the host embryo obtained in step (ii) via the injection of the ES cells into the uterus of a surrogate mother mouse, so as to obtain a chimeric mouse; and (iv) crossing the chimeric mice obtained in step (iii), so as to obtain a transgenic mouse in which the DNA fragment is introduced in a heterozygous form.
Type:
Grant
Filed:
April 25, 2013
Date of Patent:
May 1, 2018
Assignees:
TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, CHUGAI SEIYAKU KABUSHIKI KAISHA, PHOENIXBIO CO., LTD.
Abstract: Provided herein are methods of treatment of an individual having amyotrophic lateral sclerosis, comprising administering to the individual a therapeutically effective amount of placental stem cells, e.g., tissue culture surface-adherent placental stem cells (PDACs). In one aspect, provided herein is a method of treating amyotrophic lateral sclerosis (ALS) comprising administering to an individual having ALS a therapeutically effective amount of placental stem cells. In certain embodiments, “therapeutically effective” means an amount effective to reduce or ameliorate one or more symptoms of ALS.
Abstract: Adult stem cells are reprogrammed to form pacemaker cells and Purkinje cells through the sequential activation of SHOX2>TBX5>HCN2. These Purkinje cells spontaneously surround and connect with the larger pacemaker cells, thus forming an induced sinoatrial body that produces funny current and can make cardiovascular tissues beat in a manner similar to a natural sinoatrial node.
Type:
Grant
Filed:
December 28, 2015
Date of Patent:
March 13, 2018
Assignees:
InGeneron Inc., Alliance of Cardiovascular Research
Abstract: This disclosure describes, in one aspect, a composition that includes a transgenic pathogen that expresses a heterologous pathogen associated molecular pattern (PAMP). In some embodiments, the pathogen may be attenuated. In some embodiments, the pathogen can include T. cruzi. In another aspect, this disclosure describes a method of treating an infection in a subject. Generally, the method includes administering to the subject, in an amount effective to treat the infection, a pathogen genetically modified to express a pathogen-associated molecular pattern (PAMP) not natively expressed by the pathogen.
Type:
Grant
Filed:
January 17, 2014
Date of Patent:
March 6, 2018
Assignee:
University of Georgia Research Foundation, Inc.
Abstract: The present invention is directed to methods of inhibiting tumor growth in a subject. The present invention is further directed to methods of diagnosing cancer in a subject and identifying a suitable course of treatment for the subject based on the diagnosis. The present invention is also directed to an orthotopic animal model of pancreatic cancer.
Type:
Grant
Filed:
August 20, 2012
Date of Patent:
February 27, 2018
Assignee:
New York University
Inventors:
Dafna Bar-Sagi, Yuliya Pylayeva-Gupta, Kyoung Eun Lee
Abstract: Genetically modified cells, tissues, and organs for treating or preventing diseases are disclosed. Also disclosed are methods of making the genetically modified cells and non-human animals.
Abstract: The invention relates to a transgenic non-human mammal comprising human immunoglobulin mu and epsilon heavy-chain constant transgenes C? and C? inserted in place of endogenous mu heavy-chain switch sequence S?, and its use for producing chimeric human immunoglobulin E antibodies specific for an antigen of interest.
Type:
Grant
Filed:
July 3, 2014
Date of Patent:
January 23, 2018
Assignees:
B CELL DESIGN, UNIVERSITE DE LIMOGES
Inventors:
Michel Cogne, Brice Laffleur, Armelle Cuvillier, Marie Bosselut
Abstract: A method of purifying a viral vector is provided. The method includes loading a nonionic density gradient into a continuous flow centrifuge rotor; loading a material including the viral vector into the continuous flow centrifuge rotor; rotating the continuous flow centrifuge rotor in a manner sufficient to separate the viral vector and a predictable contaminate from the material in the nonionic density gradient; and unloading the separated viral vector and the predicable contaminant from the continuous flow centrifuge rotor.
Abstract: The present invention relates to methods and compositions useful for the prevention and/or treatment of PRRS in animals, typically domestic pigs. The invention relates to proteins which comprise fragments of CD163, nucleic acid constructs encoding such proteins, and methods of modifying expression or activity of CD 163 in vivo.
Type:
Grant
Filed:
July 24, 2014
Date of Patent:
January 2, 2018
Assignee:
The University Court of the University of Edinburgh
Inventors:
Tahar Ait-Ali, Simon Lillico, Alan Archibald, Christopher Bruce Alexander Whitelaw
Abstract: The present disclosure provides adeno-associated virus (AAV) virions with altered capsid protein, where the AAV virions exhibit greater infectivity of retinal cells, when administered via intravitreal injection, compared to wild-type AAV. The present disclosure further provides methods of delivering a gene product to a retinal cell in an individual, and methods of treating ocular disease.
Type:
Grant
Filed:
January 27, 2015
Date of Patent:
January 2, 2018
Assignee:
The Regents of the University of California
Inventors:
David V. Schaffer, Ryan R. Klimczak, James T. Koerber, John G. Flannery, Deniz Dalkara Mourot, Meike Visel, Leah C. T. Byrne
Abstract: There is described herein a method of enriching a population of stem cells for hematopoietic progenitors. The method comprises inducing hematopoietic differentiation in a population of human embryonic stem cells or human induced pluripotent stem cells; sorting the population based on expression of CD43 and at least one of CD34, CD31 and CD144; and selecting a fraction that is at least one of CD34+CD43?, CD31+CD43? and CD144+CD43?. Also provided are populations of hematopoietic progenitors obtained by the methods described herein.
Type:
Grant
Filed:
November 21, 2012
Date of Patent:
December 5, 2017
Assignees:
UNIVERSITY HEALTH NETWORK, SUNNYBROOK RESEARCH INSTITUTE
Inventors:
Gordon Keller, Juan Carlos Zuniga-Pflucker, Marion J. Kennedy, Christopher Michael Sturgeon, Andrea Ditadi, Geneve Sheandra Awong