Patents by Inventor Kenneth R. Chien

Kenneth R. Chien 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).

  • Publication number: 20200140819
    Abstract: The present invention provides methods for isolating human cardiac ventricular progenitor cells (HVPs), wherein cultures of day 5-7 cardiac progenitor cells are negatively selected for one or more first markers expressed on human pluripotent stem cells, such as TRA-1-60, to thereby isolate HVPs. The methods can further include positive selection for expression of a second marker selected from the group consisting of JAG1, FZD4, LIFR, FGFR3 and TNFSF9. Large populations, including clonal populations, of isolated HVPs that are first marker negative/second marker positive are also provided. Methods of in vivo use of the HVPs for cardiac repair or to improve cardiac function are also provided. Methods of using the HVPs for cardiac toxicity screening of test compounds are also provided.
    Type: Application
    Filed: October 29, 2019
    Publication date: May 7, 2020
    Inventors: Kenneth R. CHIEN, Jonathan CLARKE, Miia LEHTINEN, Kylie FOO, Chuen Yan LEUNG
  • Patent number: 10612094
    Abstract: The present invention provides genetic markers for identifying engraftable human cardiac ventricular progenitor cells. The engraftment markers of the invention include angiogenic markers and extracellular matrix markers. Human ventricular progenitor cells expressing these markers are capable of forming ventricular tissue in vivo that is vascularized and supported by an extracellular matrix. Methods of engrafting human cardiac ventricular progenitor cells by transplanting into a subject progenitor cells that express the engraftment markers are also provided.
    Type: Grant
    Filed: February 15, 2017
    Date of Patent: April 7, 2020
    Assignee: Procella Therapeutics AB
    Inventors: Chuen Yan Leung, Jonathan Clarke, Jiejia Xu, Federica Santoro, Makoto Sahara, Kenneth R. Chien
  • Patent number: 10596200
    Abstract: The present invention provides LIFR and FGFR3 as cell surface markers for isolating human cardiomyogenic ventricular progenitor cells, in particular progenitor cells that preferentially differentiate into cardiac ventricular muscle cells. Thus, the invention provides human ventricular progenitor (HVP) cells. The invention provides in vitro methods of the separation of Islet 1+ LIFR+ ventricular progenitor cells and/or Islet 1+/FGFR3+ ventricular progenitor cells and/or Islet 1+/LIFR+/FGFR3+ ventricular progenitor cells, and the large scale expansion and propagation thereof. Large clonal populations of isolated LIFR+ and/or FGFR3+ ventricular progenitor cells are also provided. Methods of in vivo use of LIFR+ and/or FGFR3+ ventricular progenitor cells for cardiac repair or to improve cardiac function are also provided. Methods of using the LIFR+ and/or FGFR3+ ventricular progenitor cells for cardiac toxicity screening of test compounds are also provided.
    Type: Grant
    Filed: December 30, 2015
    Date of Patent: March 24, 2020
    Assignee: Procella Therapeutics AB
    Inventors: Kenneth R. Chien, Xiaojun Lance Lian
  • Patent number: 10597637
    Abstract: The present invention provides Jagged 1 and Frizzled 4 as cell surface markers for isolating human cardiomyogenic ventricular progenitor cells, in particular progenitor cells that preferentially differentiate into cardiac ventricular muscle cells. Thus, the invention provides human ventricular progenitor (HVP) cells. The invention provides in vitro methods of the separation of Islet 1+ Jagged 1+ ventricular progenitor cells and/or Islet 1+/Frizzled 4+ ventricular progenitor cells and/or Islet 1+/Jagged 1+/Frizzled 4+ ventricular progenitor cells, and the large scale expansion and propagation thereof. Large clonal populations of isolated Jagged 1+ and/or Frizzled 4+ventricular progenitor cells are also provided. Methods of in vivo use of Jagged 1+ and/or Frizzled 4+ ventricular progenitor cells for cardiac repair or to improve cardiac function are also provided. Methods of using the Jagged 1+ and/or Frizzled 4+ ventricular progenitor cells for cardiac toxicity screening of test compounds are also provided.
    Type: Grant
    Filed: August 21, 2015
    Date of Patent: March 24, 2020
    Assignee: Procella Therapeutics AB
    Inventors: Kenneth R. Chien, Xiaojun Lian
  • Publication number: 20200000881
    Abstract: Aspects of the invention described herein relate to synthetic, modified RNAs and their use in vivo to modulate gene expression. Aspects of the invention further relate to the use of these synthetic, modified RNAs in myocytes, cardiomyoctes, and tumors.
    Type: Application
    Filed: July 23, 2019
    Publication date: January 2, 2020
    Applicants: THE GENERAL HOSPITAL CORPORATION, CHILDREN'S MEDICAL CENTER CORPORATION
    Inventors: Kenneth R. Chien, Leon M. Ptaszek, Kathy Oi-Lan Lui, Lior Zangi, Wataru Ebina, Derrick J. Rossi
  • Patent number: 10508263
    Abstract: The present invention provides methods for isolating human cardiac ventricular progenitor cells (HVPs), wherein cultures of day 5-7 cardiac progenitor cells are negatively selected for one or more first markers expressed on human pluripotent stem cells, such as TRA-1-60, to thereby isolate HVPs. The methods can further include positive selection for expression of a second marker selected from the group consisting of JAG1, FZD4, LIFR, FGFR3 and TNFSF9. Large populations, including clonal populations, of isolated HVPs that are first marker negative/second marker positive are also provided. Methods of in vivo use of the HVPs for cardiac repair or to improve cardiac function are also provided. Methods of using the HVPs for cardiac toxicity screening of test compounds are also provided.
    Type: Grant
    Filed: November 7, 2017
    Date of Patent: December 17, 2019
    Assignee: Procella Therapeutics AB
    Inventors: Kenneth R. Chien, Jonathan Clarke, Miia Lehtinen, Kylie Foo, Chuen Yan Leung
  • Publication number: 20190117733
    Abstract: Aspects of the invention described herein relate to synthetic, modified RNAs and their use in vivo to modulate gene expression. Aspects of the invention further relate to the use of these synthetic, modified RNAs in myocytes, cardiomyoctes, and tumors.
    Type: Application
    Filed: June 22, 2018
    Publication date: April 25, 2019
    Applicants: THE GENERAL HOSPITAL CORPORATION, CHILDREN'S MEDICAL CENTER CORPORATION
    Inventors: Kenneth R. Chien, Leon M. Ptaszek, Oi-Lan Lui, Lior Zangi, Wataru Ebina, Derrick J. Rossi
  • Publication number: 20190062696
    Abstract: The present invention provides NRP1 as a cell surface marker for isolating human cardiomyogenic ventricular progenitor cells (HVPs), in particular progenitor cells that preferentially differentiate into cardiac ventricular muscle cells. Additional HVP cell surface markers identified by single cell sequencing are also provided. The invention provides in vitro methods of the separation of NRP1+ ventricular progenitor cells, and the large scale expansion and propagation thereof. Large clonal populations of isolated NRP1+ ventricular progenitor cells are also provided. Methods of in vivo use of NRP1+ ventricular progenitor cells for cardiac repair or to improve cardiac function are also provided. Methods of using the NRP1+ ventricular progenitor cells for cardiac toxicity screening of test compounds are also provided.
    Type: Application
    Filed: August 22, 2018
    Publication date: February 28, 2019
    Inventors: Kenneth R. CHIEN, Jonathan CLARKE, Chuen Yan LEUNG
  • Patent number: 10086043
    Abstract: Aspects of the invention described herein relate to synthetic, modified RNAs and their use in vivo to modulate gene expression. Aspects of the invention further relate to the use of these synthetic, modified RNAs in myocytes, cardiomyoctes, and tumors.
    Type: Grant
    Filed: March 12, 2012
    Date of Patent: October 2, 2018
    Assignees: THE GENERAL HOSPITAL CORPORATION, CHILDREN'S MEDICAL CENTER CORPORATION
    Inventors: Kenneth R. Chien, Leon M. Ptaszek, Oi-Lan Lui, Lior Zangi, Wataru Ebina, Derrick J. Rossi
  • Publication number: 20180148691
    Abstract: The present invention provides methods for isolating human cardiac ventricular progenitor cells (HVPs), wherein cultures of day 5-7 cardiac progenitor cells are negatively selected for one or more first markers expressed on human pluripotent stem cells, such as TRA-1-60, to thereby isolate HVPs. The methods can further include positive selection for expression of a second marker selected from the group consisting of JAG1, FZD4, LIFR, FGFR3 and TNFSF9. Large populations, including clonal populations, of isolated HVPs that are first marker negative/second marker positive are also provided. Methods of in vivo use of the HVPs for cardiac repair or to improve cardiac function are also provided. Methods of using the HVPs for cardiac toxicity screening of test compounds are also provided.
    Type: Application
    Filed: November 7, 2017
    Publication date: May 31, 2018
    Inventors: Kenneth R. CHIEN, Jonathan CLARKE, Miia LEHTINEN, Kylie FOO, Chuen Yan LEUNG
  • Publication number: 20170240964
    Abstract: The present invention provides genetic markers for identifying engraftable human cardiac ventricular progenitor cells. The engraftment markers of the invention include angiogenic markers and extracellular matrix markers. Human ventricular progenitor cells expressing these markers are capable of forming ventricular tissue in vivo that is vascularized and supported by an extracellular matrix. Methods of engrafting human cardiac ventricular progenitor cells by transplanting into a subject progenitor cells that express the engraftment markers are also provided.
    Type: Application
    Filed: February 15, 2017
    Publication date: August 24, 2017
    Inventors: Chuen Yan LEUNG, Jonathan CLARKE, Jiejia XU, Federica SANTORO, Makoto SAHARA, Kenneth R. CHIEN
  • Publication number: 20160108363
    Abstract: The present invention provides LIFR and FGFR3 as cell surface markers for isolating human cardiomyogenic ventricular progenitor cells, in particular progenitor cells that preferentially differentiate into cardiac ventricular muscle cells. Thus, the invention provides human ventricular progenitor (HVP) cells. The invention provides in vitro methods of the separation of Islet 1+ LIFR+ ventricular progenitor cells and/or Islet 1+/FGFR3+ ventricular progenitor cells and/or Islet 1+/LIFR+/FGFR3+ ventricular progenitor cells, and the large scale expansion and propagation thereof. Large clonal populations of isolated LIFR+ and/or FGFR3+ ventricular progenitor cells are also provided. Methods of in vivo use of LIFR+ and/or FGFR3+ ventricular progenitor cells for cardiac repair or to improve cardiac function are also provided. Methods of using the LIFR+ and/or FGFR3+ ventricular progenitor cells for cardiac toxicity screening of test compounds are also provided.
    Type: Application
    Filed: December 30, 2015
    Publication date: April 21, 2016
    Inventors: Kenneth R. CHIEN, Xiaojun Lance LIAN
  • Publication number: 20160053229
    Abstract: The present invention provides Jagged 1 and Frizzled 4 as cell surface markers for isolating human cardiomyogenic ventricular progenitor cells, in particular progenitor cells that preferentially differentiate into cardiac ventricular muscle cells. Thus, the invention provides human ventricular progenitor (HVP) cells. The invention provides in vitro methods of the separation of Islet 1+ Jagged 1+ ventricular progenitor cells and/or Islet 1+/Frizzled 4+ ventricular progenitor cells and/or Islet 1+/Jagged 1+/Frizzled 4+ ventricular progenitor cells, and the large scale expansion and propagation thereof. Large clonal populations of isolated Jagged 1+ and/or Frizzled 4+ventricular progenitor cells are also provided. Methods of in vivo use of Jagged 1+ and/or Frizzled 4+ ventricular progenitor cells for cardiac repair or to improve cardiac function are also provided. Methods of using the Jagged 1+ and/or Frizzled 4+ ventricular progenitor cells for cardiac toxicity screening of test compounds are also provided.
    Type: Application
    Filed: August 21, 2015
    Publication date: February 25, 2016
    Inventors: Kenneth R. CHIEN, Xiaojun LIAN
  • Patent number: 8765117
    Abstract: The present invention relates to the generation of vascularized human heart tissue from human primordial Islet1-positive (ISL1+) progenitors, and more particularly the generation of vascularized human heart tissue from human primordial Islet1+ cardiovascular stem cells which are positive for markers ISL1+/NKX2.5?/KDR?. One aspect of the invention relates to isolation of human ISL1+ primordial cells from human pluripotent cells, such as human ES cells or other human pluripotent stem cell sources, wherein the human ISL1+ primordial cells can differentiate into three different lineages; cardiomyocyte lineages, endothelial lineages and smooth muscle lineages. Another aspect relates to use and implantation of the human primordial ISL1+ progenitors into an animal model to generate human vascularized heart tissue, and more particularly, the production of an in vivo humanized model of vascular disease.
    Type: Grant
    Filed: June 10, 2010
    Date of Patent: July 1, 2014
    Assignee: The General Hospital Corporation
    Inventors: Kenneth R. Chien, Lei Bu, Xin Jiang, Kathy Oi Lan Lui, Jolanta Chmielowiec
  • Publication number: 20140073687
    Abstract: Aspects of the invention described herein relate to synthetic, modified RNAs and their use in vivo to modulate gene expression. Aspects of the invention further relate to the use of these synthetic, modified RNAs in myocytes, cardiomyoctes, and tumors.
    Type: Application
    Filed: March 12, 2012
    Publication date: March 13, 2014
    Applicants: IMMUNE DISEASE INSTITUTE, INC., THE GENERAL HOSPITAL CORPORATION
    Inventors: Kenneth R. Chien, Leon M. Ptaszek, Kathy Oi-Lan Lui, Lior Zangi, Wataru Ebina, Derrick J. Rossi
  • Publication number: 20120135051
    Abstract: The present invention relates to the generation of vascularized human heart tissue from human primordial Islet1-positive (ISL1+) progenitors, and more particularly the generation of vascularized human heart tissue from human primordial Islet1+ cardiovascular stem cells which are positive for markers ISL1+/NKX2.5?/KDR?. One aspect of the invention relates to isolation of human ISL1+ primordial cells from human pluripotent cells, such as human ES cells or other human pluripotent stem cell sources, wherein the human ISL1+ primordial cells can differentiate into three different lineages; cardiomyocyte lineages, endothelial lineages and smooth muscle lineages. Another aspect relates to use and implantation of the human primordial ISL1+ progenitors into an animal model to generate human vascularized heart tissue, and more particularly, the production of an in vivo humanized model of vascular disease.
    Type: Application
    Filed: June 10, 2010
    Publication date: May 31, 2012
    Applicant: The General Hospital Corporation
    Inventors: Kenneth R. Chien, Lei Bu, Xin Jiang, Kathy Oi Lan Lui, Jolanta Chmielowiec
  • Publication number: 20120027807
    Abstract: The present invention generally relates to a population of committed ventricular progenitor (CVP) cells and their use to generate a tissue engineered myocardium, in particular two dimensional tissue engineered myocardium which is comparable to functional ventricular heart muscle. One embodiment of present invention provides a composition and methods for the production of a tissue engineered myocardium which has functional properties of cardiac muscle, such as contractibility (e.g. contraction force) and numerous properties of mature fully functional ventricular heart muscle tissue. In particular, in one embodiment, a composition comprising the tissue engineered myocardium comprises committed ventricular progenitor (CVP) cells seeded on a free-standing biopolymer structure to form functional ventricular myocardium tissue.
    Type: Application
    Filed: October 9, 2009
    Publication date: February 2, 2012
    Applicant: THE GENERAL HOSPITAL CORPORATION
    Inventors: Kenneth R. Chien, Ibrahim J. Domian, Murali Chiravuri, Peter Van Der Meer, Kevin Kit Parker, Adam W. Feinberg
  • Publication number: 20120009158
    Abstract: The present invention generally relates to methods and compositions to generate a secondary iPS (2iPS) cell to produce somatic cells of a rare differentiation cell type fate. In some embodiments, the method relates to an increase in efficiency of differentiation and production of high yields of somatic cells of a rare differentiation cell type fate produced from secondary iPS (2iPS) cells as compared to their differentiation from other pluripotent stem cell sources such as ES cells or primary iPS cells. In some embodiments, the present invention relates to compositions, methods and systems for reprogramming a first somatic cell into a primary iPS cell, where the primary iPS cell is then differentiated along a selected linage to produce a second somatic cell, which is then reprogrammed to a secondary iPS cell (2iPS) cell. The 2iPS cell has a high efficiency of differentiating into a cell of the same cell type as the second somatic cell, e.g.
    Type: Application
    Filed: June 17, 2011
    Publication date: January 12, 2012
    Applicant: THE GENERAL HOSPITAL CORPORATION
    Inventors: Kenneth R. Chien, Huansheng Xu, Byungdoo Alexander Yi
  • Publication number: 20110033430
    Abstract: The present invention relates to methods for the induction and a cell to enter the Islet 1+ (Isl1+) lineage and methods for expansion of cells of islet 1+ lineage. One aspect of the present invention relates to methods to induce a cell to enter the islet 1+ lineage, and more particularly to a method to induce a cell to enter a the Isl1+ lineage to become an Isl1+ progenitor that is capable of differentiating along multiple different lineages such as a endothelial lineage, a smooth muscle lineage or a cardiac lineage. In particular, one embodiment present invention relates to methods to induce a cell to enter the Isl1+ lineage by inhibiting a wnt signalling pathway in the cell. Another aspect of the present invention relates to methods to expand a cell of the Isl1+ lineage, such as a Isl1+ progenitor by activating a wnt signalling pathway in the Isl1+ progenitor.
    Type: Application
    Filed: February 8, 2008
    Publication date: February 10, 2011
    Applicant: THE GENERAL HOSPITAL CORPORATION
    Inventors: Kenneth R Chien, Yibing Qyang, Silvia Martin-Puig
  • Publication number: 20100210713
    Abstract: The present invention relates generally to the field of cardiovascular repair, and more particularly to methods and compositions for the survival of cells in response to mechanical stress and to the proliferation of postnatal cardiomyocytes. The present invention relates to a nuclear form of Creb312(N) polypeptide which when expressed in a cell promotes cell survival in response to stress such as mechanical stretch stress. Another aspect of the invention relates to the expression of the nuclear form of Creb312(N) polypeptide in a cardiomyocyte promotes propagation or regeneration of the cardiomyocyte.
    Type: Application
    Filed: January 14, 2010
    Publication date: August 19, 2010
    Applicant: THE GENERAL HOSPITAL CORPORATION
    Inventors: Kenneth R. Chien, Yuh-Shin Chang