Patents by Inventor Carl H. June

Carl H. June has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Altering Gene Expression in Modified T Cells and Uses Thereof
    Publication number: 20180312848
    Abstract: The present invention relates to compositions and methods for generating a modified T cell with a nucleic acid capable of downregulating endogenous gene expression selected from the group consisting of TCR ? chain, TCR ? chain, beta-2 microglobulin and FAS further comprising a nucleic acid encoding a modified T cell receptor (TCR) comprising affinity for a surface antigen on a target cell or an electroporated nucleic acid encoding a chimeric antigen receptor (CAR). Also included are methods and pharmaceutical compositions comprising the modified T cell for adoptive therapy and treating a condition, such as an autoimmune disease.
    Type: Application
    Filed: April 25, 2018
    Publication date: November 1, 2018
    Inventors: Yangbing Zhao, Jiangtao Ren, Xiaojun Liu, Carl H. June
  • Methods and Compositions for Cells Expressing a Chimeric Intracellular Signaling Molecule
    Publication number: 20180282693
    Abstract: The present invention relates to compositions and methods for enhancing T cell metabolism and activity for more effective adoptive T cell therapy. By expressing an intracellular signaling molecule in T cells, the T cells are metabolically enhanced with improved cytotoxicity and resistance to immunosuppression imposed by tumor microenvironments. One aspect includes a modified T cell and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity.
    Type: Application
    Filed: August 25, 2016
    Publication date: October 4, 2018
    Inventors: Carl H. June, Michael Milone, Yangbing Zhao, Lawrence G. Lum, Archana Thakur
  • USE OF CART19 TO DEPLETE NORMAL B CELLS TO INDUCE TOLERANCE
    Publication number: 20180271907
    Abstract: The present invention provides compositions and methods for inducing tolerance in a human. The invention includes administering a genetically modified T cell expressing a CAR wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain.
    Type: Application
    Filed: June 4, 2018
    Publication date: September 27, 2018
    Inventors: Carl H. June, Bruce L. Levine, Michael D. Kalos
  • Compositions and Methods for Treatment of Cancer
    Publication number: 20180258391
    Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell to express a CAR wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain.
    Type: Application
    Filed: September 6, 2017
    Publication date: September 13, 2018
    Inventors: Carl H. June, Bruce L. Levine, David L. Porter, Michael D. Kalos, Michael C. Milone
  • CAR T CELL THERAPIES WITH ENHANCED EFFICACY
    Publication number: 20180258149
    Abstract: The invention provides compositions and methods improved CAR T cell therapies. Specifically, the invention provides cells with reduced Tet, e.g., Tet2 function or expression, and methods of use therefore. The invention further provides Tet2 inhibitors and methods of use therefore in connection with CAR T cells.
    Type: Application
    Filed: September 16, 2016
    Publication date: September 13, 2018
    Applicants: Novartis AG, The Trustees of the University of Pennsylvania
    Inventors: Gregory Motz, Frederic Dixon Bushman, Joseph A. Fraietta, Carl H. June, Jan J. Melenhorst, Christopher Loren Nobles, Regina M. Young
  • Toxicity Management for Anti-Tumor Activity of CARs
    Publication number: 20180256712
    Abstract: The present invention provides compositions and methods for treating cancer in a patient. In one embodiment, the method comprises a first-line therapy comprising administering to a patient in need thereof a genetically modified T cell expressing a CAR wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain and monitoring the levels of cytokines in the patient post T cell infusion to determine the type of second-line of therapy appropriate for treating the patient as a consequence of the presence of the CAR T cell in the patient.
    Type: Application
    Filed: May 7, 2018
    Publication date: September 13, 2018
    Inventors: Carl H. June, Bruce L. Levine, Michael D. Kalos, Stephan Grupp
  • Modified Monocytes/Macrophage Expressing Chimeric Antigen Receptors and Uses Thereof
    Publication number: 20180244748
    Abstract: The present invention includes methods and compositions for treating cancer, whether a solid tumor or a hematologic malignancy. By expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells. One aspect includes a modified cell and pharmaceutical compositions comprising the modified cell for adoptive cell therapy and treating a disease or condition associated with immunosuppression.
    Type: Application
    Filed: July 28, 2016
    Publication date: August 30, 2018
    Inventors: Saar GILL, Michael KLICHINSKY, Carl H. JUNE
  • Toxicity Management for Anti-Tumor Activity of CARs
    Publication number: 20180243411
    Abstract: The present invention provides compositions and methods for treating cancer in a patient. In one embodiment, the method comprises a first-line therapy comprising administering to a patient in need thereof a genetically modified T cell expressing a CAR wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain and monitoring the levels of cytokines in the patient post T cell infusion to determine the type of second-line of therapy appropriate for treating the patient as a consequence of the presence of the CART cell in the patient.
    Type: Application
    Filed: April 26, 2018
    Publication date: August 30, 2018
    Inventors: Carl H. June, Bruce L. Levine, Michael D. Kalos, Stephan Grupp
  • Methods and Compositions for Cells Expressing a Chimeric Intracellular Signaling Molecule
    Publication number: 20180243341
    Abstract: The present invention relates to compositions and methods for enhancing T cell metabolism and activity for more effective adoptive T cell therapy. By expressing an chimeric antigen receptor and bispecific antibodies in T cells, the T cells are metabolically enhanced with improved cytotoxicity and resistance to immunosuppression imposed by tumor microenvironments. Certain aspects include modified T cells and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity.
    Type: Application
    Filed: August 26, 2016
    Publication date: August 30, 2018
    Inventors: Carl H. June, Michael Milone, Yangbing Zhao, Lawrence G. Lum, Archana Thakur
  • Methods for treating chronic lymphocytic leukemia (CLL)
    Patent number: 10046008
    Abstract: The present invention relates generally to the treatment of PML by infusion of activated and expanded autologous lymphocytes.
    Type: Grant
    Filed: September 10, 2015
    Date of Patent: August 14, 2018
    Assignee: The Trustees of the University of Pennsylvania
    Inventors: Carl H. June, Bruce L. Levine, Anne Chew, Stephen J. Schuster
  • Compositions and methods for generating a persisting population of T cells useful for the treatment of cancer
    Patent number: 10040846
    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
  • ICOS critically regulates the expansion and function of inflammatory human Th17 cells
    Patent number: 9994818
    Abstract: The invention includes compositions and methods for generating and expanding therapeutic Th17 cells. The invention includes contacting T cells with a composition comprising a first agent that is capable of providing a primary activation signal to T cells and a second agent that is capable of activating ICOS on T cells in the presence of Th-17 polarizing agents.
    Type: Grant
    Filed: August 11, 2015
    Date of Patent: June 12, 2018
    Assignee: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
    Inventors: James L. Riley, Chrystal Paulos, Carl H. June, Bruce L. Levine
  • COMBINATION OF CHIMERIC ANTIGEN RECEPTOR THERAPY AND AMINO PYRIMIDINE DERIVATIVES
    Publication number: 20180140602
    Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD19, e.g., by administering a recombinant T cell comprising the CD19 CAR as described herein, in combination with a BTK inhibitor, e.g., an amino pyrimidine derivative described herein. The invention also provides kits and compositions described herein.
    Type: Application
    Filed: April 7, 2016
    Publication date: May 24, 2018
    Inventors: Daniela Angst, John Byrd, Jason Dubovsky, Joseph A. Fraietta, Francois Gessier, Saar Gill, Amy Johnson, Carl H. June, Marcela Maus, Natarajan Muthusamy, David L. Porter, Marco Ruella, Anna Vulpetti, Mariusz Wasik
  • METHODS FOR IMPROVING THE EFFICACY AND EXPANSION OF CHIMERIC ANTIGEN RECEPTOR?EXPRESSING CELLS
    Publication number: 20180133296
    Abstract: The invention provides methods of making immune effector cells (e.g., T cells, NK cells) that can be engineered to express a chimeric antigen receptor (CAR), compositions and reaction mixtures comprising the same, and methods of treatment using the same.
    Type: Application
    Filed: April 15, 2016
    Publication date: May 17, 2018
    Inventors: David Maxwell Barrett, Felipe Bedoya, Saba Ghassemi, Carl H. June, Bruce L. Levine, Jan J. Melenhorst, Michael C. Milone, Daniel J. Powell, Jr., Nathan Amar Singh, Zoe Zheng
  • PHOSPHOGLYCERATE KINASE 1 (PGK) PROMOTERS AND METHODS OF USE FOR EXPRESSING CHIMERIC ANTIGEN RECEPTOR
    Publication number: 20180118834
    Abstract: The invention provides compositions and methods for treating diseases associated with expression of a tumor antigen as described herein. The invention also relates to nucleic acids comprising a truncated PGK promoter operably linked to a chimeric antigen receptor (CAR) specific to a tumor antigen as described herein, vectors encoding the same, and recombinant T cells comprising the CARs of the present invention. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an antigen binding domain that binds to a tumor antigen as described herein.
    Type: Application
    Filed: January 15, 2016
    Publication date: May 3, 2018
    Inventors: Jennifer Brogdon, Hilmar Erhard Ebersbach, David Glass, Thomas Huber, Julia Jascur, Carl H. June, Jihyun Lee, Joan Mannick, Michael C. Milone, Leon Murphy, Avery D. Posey, Huijuan Song, Yongqiang Wang, Lai Wei, Qilong Wu, Qiumei Yang, Jiquan Zhang
  • Enhancing Activity of CAR T Cells by Co-Introducing a Bispecific Antibody
    Publication number: 20180057609
    Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention includes administering a T cell, genetically modified to express a chimeric antigen receptor (CAR), a bispecific antibody, or a combination thereof to a subject. The CAR and bispecific antibody of the invention can comprise a human antibody, a humanized antibody, or antigen-binding fragments thereof.
    Type: Application
    Filed: August 30, 2017
    Publication date: March 1, 2018
    Inventors: Carl H. June, Yangbing Zhao, Xiaojun Liu
  • CAR-EXPRESSING CELLS AGAINST MULTIPLE TUMOR ANTIGENS AND USES THEREOF
    Publication number: 20180044424
    Abstract: The invention provides compositions and methods for treating cancer by using immune effector cells (e.g., T cells, NK cells) engineered to conditionally express an agent which enhances the immune effector response of an immune effector cell that expresses a Chimeric Antigen Receptor (CAR). The conditional agents described herein include agents that target a cancer associated antigen, e.g., a CAR, agents that inhibit one or more checkpoint inhibitors of the immune response, and a cytokine.
    Type: Application
    Filed: February 1, 2016
    Publication date: February 15, 2018
    Inventors: Carl H. June, Daniel J. Powell, Jr.
  • USE OF THE CD2 SIGNALING DOMAIN IN SECOND-GENERATION CHIMERIC ANTIGEN RECEPTORS
    Publication number: 20180037625
    Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell expressing a CAR having an antigen binding domain, a transmembrane domain, a CD2 signaling domain, and a CD3 zeta signaling domain. The invention also includes incorporating CD2 into the CAR to alter the cytokine production of CAR-T cells in both negative and positive directions.
    Type: Application
    Filed: August 4, 2017
    Publication date: February 8, 2018
    Inventors: Carl H. June, John Scholler, Avery D. Posey, Jr.
  • COMPOSITIONS AND METHODS FOR T CELL DELIVERY OF THERAPEUTIC MOLECULES
    Publication number: 20170360913
    Abstract: The present invention includes compositions and methods for modifying a T cell with a nucleic acid encoding a switch molecule comprising an extracellular domain comprising a membrane receptor or fragment thereof and an intracellular domain comprising a signaling receptor or fragment thereof. In one aspect, a method comprises introducing a nucleic acid encoding a switch molecule and a nucleic acid encoding a soluble fusion protein and/or a nucleic acid encoding a bispecific antibody into a population of cells comprising T cells, wherein the T cells transiently expresses the switch molecule and soluble fusion protein or bispecific antibody. In other aspect, compositions of T cells and methods of treating a disease or condition, such as cancer or an autoimmune disease, are also included.
    Type: Application
    Filed: October 30, 2015
    Publication date: December 21, 2017
    Applicant: The Trustees of the University of Pennsylania
    Inventors: Yangbing ZHAO, Carl H. JUNE, Xiaojun LIU
  • USE OF ICOS-BASED CARS TO ENHANCE ANTITUMOR ACTIVITY AND CAR PERSISTENCE
    Publication number: 20170362295
    Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention includes administering a genetically modified Th17 cell to express a CAR having an antigen binding domain, a transmembrane domain, and an ICOS intracellular signaling domain.
    Type: Application
    Filed: June 29, 2017
    Publication date: December 21, 2017
    Inventors: Carl H. June, Sonia Guedan Carrio, Yangbing Zhao, John Scholler