Patents Examined by David A. Montanari
  • Patent number: 10781425
    Abstract: The generation of complex organ tissues from human embryonic and pluripotent stem cells (PSCs) remains a major challenge for translational studies. It is shown that PSCs can be directed to differentiate into intestinal tissue in vitro by modulating the combinatorial activities of several signaling pathways in a step-wise fashion, effectively recapitulating in vivo fetal intestinal development. The resulting intestinal “organoids” were three-dimensional structures consisting of a polarized, columnar epithelium surrounded by mesenchyme that included a smooth muscle-like layer. The epithelium was patterned into crypt-like SOX9-positive proliferative zones and villus-like structures with all of the major functional cell types of the intestine. The culture system is used to demonstrate that expression of NEUROG3, a pro-endocrine transcription factor mutated in enteric anendocrinosis is sufficient to promote differentiation towards the enteroendocrine cell lineage.
    Type: Grant
    Filed: June 20, 2017
    Date of Patent: September 22, 2020
    Assignee: Children's Hospital Medical Center
    Inventors: James M. Wells, Aaron M. Zorn, Jason R. Spence, Noah F. Shroyer
  • Patent number: 10767164
    Abstract: Human pluripotent stem cells (hPSCs) are promising cell source to produce therapeutic endocrine cells for diabetes treatment. A gel solution made by decellularized tissue-specific extracellular matrix (dpECM) significantly promotes three-dimensional (3D) islet-like organogenesis during induced hPSC differentiation into endocrine lineages. Islet organoids are self-organized even in a two-dimensional (2D) culture mode. Cells derived from hPSCs differentiated on such ECM coated substrates exhibit similar cellular composition to native pancreatic islets. These cells express islet signature markers insulin, PDX-1, C-peptide, MafA, glucagon, somatostatin, and pancreatic polypeptide, and secrete more insulin in response to glucose level compared to a traditional matrix substrate (Matrigel). The dpECM facilitates generating more C-peptide+/glucagon? cells rather than C-peptide+/glucagon+ cells. Remarkably, dpECM also facilitated intra-organoid vascularity by generating endothelial cells and pericytes.
    Type: Grant
    Filed: December 13, 2017
    Date of Patent: September 8, 2020
    Assignee: The Research Foundation for The State University of New York
    Inventors: Sha Jin, Kaiming Ye, Huanjing Bi
  • Patent number: 10765728
    Abstract: The present invention pertains to engineered immune cells, method for their preparation and their use as medicament, particularly for immunotherapy. The engineered immune cells of the present invention are characterized in that at least one gene selected from a gene encoding GCN2 and a gene encoding PRDM1 is inactivated or repressed. Such modified Immune cells are resistant to an arginine and/or tryptophan depleted microenvironment caused by, e.g., tumor cells, which makes the immune cells of the invention particularly suitable for immunotherapy. The invention opens the way to standard and affordable adoptive immunotherapy strategies using immune cells for treating different types of malignancies.
    Type: Grant
    Filed: April 10, 2015
    Date of Patent: September 8, 2020
    Assignee: CELLECTIS
    Inventors: Laurent Poirot, Mathieu Simon
  • Patent number: 10738324
    Abstract: Disclosed is a vector, preferably a viral vector, containing a treatment factor and/or a nucleic acid encoding a cytotoxic factor under control of an Aurora kinase promoter. Also disclosed is a virus vector in which the promoter of a nucleic acid encoding a factor necessary to the replication or assembly of at least one virus is substituted by the Aurora kinase promoter. Also disclosed are a disease treatment agent, in particular a cancer treatment agent, which contains the aforementioned vector, and a clinical diagnostic agent, in particular a cancer diagnostic agent, which contains the vector containing the Aurora kinase promoter.
    Type: Grant
    Filed: September 29, 2011
    Date of Patent: August 11, 2020
    Assignee: KAGOSHIMA UNIVERSITY
    Inventor: Ken-ichiro Kosai
  • Patent number: 10738355
    Abstract: The present invention relates to the provision of vaccines which are specific for a patient's tumor and are potentially useful for immunotherapy of the primary tumor as well as tumor metastases. In one aspect, the present invention relates to a method for providing an individualized cancer vaccine comprising the steps: (a) identifying cancer specific somatic mutations in a tumor specimen of a cancer patient to provide a cancer mutation signature of the patient; and (b) providing a vaccine featuring the cancer mutation signature obtained in step (a). In a further aspect, the present invention relates to vaccines which are obtainable by said method.
    Type: Grant
    Filed: May 23, 2012
    Date of Patent: August 11, 2020
    Assignees: TRON-Translationale Onkologie an der Universitätsmedizin der Johannes Gutenberg-Universität Mainz gGmbH, BioNTech RNA Pharmaceuticals GmbH
    Inventors: Ugur Sahin, Sebastian Kreiter, Mustafa Diken, Jan Diekmann, Michael Koslowski, Cedrik Britten, John Christopher Castle, Martin Lower, Bernhard Renard, Tana Omokoko, Johannes Hendrikus De Graaf
  • Patent number: 10736933
    Abstract: The invention relates to a peptide capable of activating NK cell-mediated immunity, the peptide comprising or consisting of the amino acid sequence XnAX2X1, Wherein Xn is an amino acid sequence of between 5 and 12 residues, and X1 is any amino acid; or leucine or phenylalanine; and X2 is alanine, threonine or serine. The invention further relates to an MHC class I molecule and the peptide, nucleic acids encoding the peptide, activated NK cells, and related compositions and methods, including use in methods of treatment.
    Type: Grant
    Filed: November 9, 2016
    Date of Patent: August 11, 2020
    Assignee: University of Southampton
    Inventor: Salim Iqbal Khakoo
  • Patent number: 10724002
    Abstract: Methods and compositions of erythroid cells that produce adult ?-hemoglobin, generated by culturing CD31+, CD31+/CD34+ or CD34+ cells from embryonic stem cells under serum-free culture conditions.
    Type: Grant
    Filed: April 5, 2018
    Date of Patent: July 28, 2020
    Assignee: WISCONSIN ALUMNI RESEARCH FOUNDATION
    Inventors: Igor I. Slukvin, James A. Thomson, Maksym A. Vodyanyk, Maryna E. Gumenyuk
  • Patent number: 10711249
    Abstract: A method for producing hepatocytes from hepatoblasts is provided. The method includes the step of culturing the hepatoblasts in a medium containing a compound selected from the group consisting of pregnenolone and an adrenergic agonist. The hepatoblasts can be obtained by culturing endodermal cells in a medium containing DMSO, and the endodermal cells can be obtained by culturing pluripotent stem cells in a medium containing Activin A and a GSK-3? inhibitor. Accordingly, a method for producing hepatocytes from pluripotent stem cells is also provided by employing the method of the present invention.
    Type: Grant
    Filed: December 25, 2015
    Date of Patent: July 14, 2020
    Assignee: KYOTO UNIVERSITY
    Inventors: Kenji Osafune, Maki Kotaka
  • Patent number: 10711285
    Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in prokaryotic and eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity.
    Type: Grant
    Filed: December 17, 2015
    Date of Patent: July 14, 2020
    Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Feng Zhang, Patrick Hsu, Chie-yu Lin, Fei Ran
  • Patent number: 10704025
    Abstract: The present invention provides methods to promote the differentiation of pluripotent stem cells into insulin producing cells. In particular, the present invention provides a method to produce cells expressing markers characteristic of the pancreatic endocrine lineage that co-express NKX6.1 and insulin and minimal amounts of glucagon.
    Type: Grant
    Filed: March 13, 2017
    Date of Patent: July 7, 2020
    Assignee: Janssen Biotech, Inc.
    Inventor: Jean Xu
  • Patent number: 10696983
    Abstract: This invention provides methods for transducing a ciliated cell with a recombinant serotype 2 adeno-associated virus (AAV) vector. Additionally, the invention provides methods of treating diseases associated with a mutated gene by transducing a ciliated cell with a recombinant serotype 2 AAV vector containing a corrective transgene.
    Type: Grant
    Filed: May 30, 2008
    Date of Patent: June 30, 2020
    Assignee: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
    Inventors: Jean Bennett, Joshua Lipschutz
  • Patent number: 10696986
    Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems, wherein the guide sequence is modified by secondary structure to increase the specificity of the CRISPR-Cas system and whereby the secondary structure can protect against exonuclease activity and allow for 5? additions to the guide sequence.
    Type: Grant
    Filed: June 12, 2017
    Date of Patent: June 30, 2020
    Assignees: THE BOARD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Feng Zhang, Omar O. Abudayyeh, James E. Dahlman, Patrick Hsu, David A. Scott
  • Patent number: 10662407
    Abstract: The present disclosure relates to a method for controlling the differentiation of embryonic stem cells into adipocytes or kidney precursor cells by regulating SIRT1 (silent mating type information regulation 2 homolog; sirtuin 1) expression, the method, which controls the differentiation of embryonic stem cells into adipocytes by regulating SIRT1 expression, being capable of controlling the inhibition or promotion of adipocyte differentiation in accordance with the timing of a SIRT1 expression inhibitor treatment. Furthermore, kidney precursor cell differentiation can be regulated by a SIRT1 expression inhibitor or promoter treatment. Accordingly, a SIRT1 inhibitor can be selected to be used as an inhibitor or a therapeutic agent for obesity, diabetes accompanying obesity, and renal and metabolic diseases.
    Type: Grant
    Filed: January 22, 2016
    Date of Patent: May 26, 2020
    Assignees: INDUSTRIAL COOPERATION FOUNDATION CHONBUK NATIONAL UNIVERSITY, Chonbuk National University Hospital
    Inventors: Won Kim, Yu Jin Jung
  • Patent number: 10662256
    Abstract: The present invention relates to transgenic mammals that express canine-based immunoglobulins, including transgenic rodents that express canine-based immunoglobulins for the development of canine therapeutic antibodies.
    Type: Grant
    Filed: May 23, 2017
    Date of Patent: May 26, 2020
    Assignee: TRIANNI, INC.
    Inventor: Matthias Wabl
  • 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: 10647997
    Abstract: A modified effector cell includes a non-reversibly produced vector-encoded anti-GD2-BB-? chimeric receptor for use in disialoganglioside GD2-expressing neoplasia, which is inserted in the cell, to obtain an effector cell that stably produces the anti-GD2-BB-? chimeric receptor, the chimeric receptor having two distinct mutually fused portions, i.e. an intra-cytoplasmic portion and an extra-cytoplasmic portion.
    Type: Grant
    Filed: October 25, 2012
    Date of Patent: May 12, 2020
    Assignee: St. Jude Children's Research Hospital, Inc.
    Inventors: Massimo Dominici, Sara Caldrer, Maria Carlotta Spano, Paolo Paolucci, Marco Bestagno, Dario Campana
  • Patent number: 10634666
    Abstract: The invention relates to a novel non-obese diabetic (NOD) mouse and its application. Particularly, the invention relates to a NOD mouse specifically expressing anti-polyethylene glycol membrane antibody reporter (anti-PEG reporter) in the NOD mouse.
    Type: Grant
    Filed: November 29, 2016
    Date of Patent: April 28, 2020
    Assignee: TAIPEI MEDICAL UNIVERSITY
    Inventor: Kuo-Hsiang Chuang
  • Patent number: 10633635
    Abstract: The invention provides for methods of differentiating pancreatic endocrine cells into pancreatic beta cells expressing PDX1, NKX6.1, MAFA, UCN3 and SLC2A. These pancreatic beta cells may be obtained by step-wise differentiation of pluripotent stem cells. The pancreatic beta cells exhibit glucose-dependent mitochondrial respiration and glucose-stimulated insulin secretion similar to islet cells.
    Type: Grant
    Filed: June 14, 2017
    Date of Patent: April 28, 2020
    Assignee: Janssen Biotech, Inc.
    Inventors: Sebastian Rieck, Alireza Rezania
  • 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: 10626417
    Abstract: A transgenic cat with a phenotype characterized by the substantial absence of the major cat allergen, Fel d I. The phenotype is conferred in the transgenic cat by disrupting the coding sequence of the target gene with a specialized construct. The phenotype of the transgenic cat is transmissible to its offspring.
    Type: Grant
    Filed: October 11, 2016
    Date of Patent: April 21, 2020
    Inventors: David B. Avner, James Kehler, Sven Bocklandt