Patents Assigned to Geron Corporation
  • Patent number: 10494398
    Abstract: This invention relates to antisense oligonucleotides comprising at least one N3??P5? phosphorodiamidate linkage (NPN) in the backbone, useful for modulating gene expression involved in the pathogenesis of a disease. Compounds useful as building blocks of said antisense oligonucleotides and methods of preparing building block compounds including NPN linkages are provided.
    Type: Grant
    Filed: June 7, 2017
    Date of Patent: December 3, 2019
    Assignee: Geron Corporation
    Inventors: Krisztina Pongracz, Mahesh Ramaseshan
  • Patent number: 10392418
    Abstract: The present disclosure provides a solid phase method of making oligonucleotides via sequential coupling cycles including at least one coupling of a dinucleotide dimer subunit to a free 3?-terminal group of a growing chain. The oligonucleotides include at least two nucleoside subunits joined by a N3??P5? phosphoramidate linkage. The method may include the steps of (a) deprotecting the protected 3? amino group of a terminal nucleoside attached to a solid phase support, said deprotecting forming a free 3? amino group; (b) contacting the free 3? amino group with a 3?-protected amino-dinucleotide-5?-phosphoramidite dimer in the presence of a nucleophilic catalyst to form an internucleoside N3??P5? phosphoramidite linkage; and (c) oxidizing (e.g., sulfurizing) the linkage. The compositions produced by the subject methods may include a reduced amount of one or more (N?x) oligonucleotide products. Also provided are pharmaceutical compositions including the subject oligonucleotide compositions.
    Type: Grant
    Filed: September 14, 2017
    Date of Patent: August 27, 2019
    Assignee: Geron Corporation
    Inventor: Premchandran H. Ramiya
  • Patent number: 10358459
    Abstract: Oligonucleotides with a novel sugar-phosphate backbone containing at least one 2?-arabino-fluoronucleoside and an internucleoside 3?-NH—P(—O)(OR)—O-5? linkage, where R is a positively charged counter ion or hydrogen, and methods of synthesizing and using the inventive oligonucleotides are provided. The inventive phosphoramidate 2?-arabino-fluorooligonucleotides have a high RNA binding affinity to complementary nucleic acids and are base and acid stable.
    Type: Grant
    Filed: August 16, 2017
    Date of Patent: July 23, 2019
    Assignee: Geron Corporation
    Inventors: Sergei M. Gryaznov, Ronald G. Schultz
  • Patent number: 10196677
    Abstract: The invention provides methods for determining the susceptibility of cancer patients to developing adverse reactions if treated with a telomerase inhibitor drug by measurement of telomere length in appropriate cells of the patient prior to initiation of the telomerase inhibitor treatment.
    Type: Grant
    Filed: February 28, 2017
    Date of Patent: February 5, 2019
    Assignee: Geron Corporation
    Inventors: Calvin B. Harley, Laurence Elias, Jennifer Smith, Mark J. Ratain, Fabio Benedetti
  • Patent number: 10196641
    Abstract: Compounds comprising an oligonucleotide moiety covalently linked to a lipid moiety are disclosed. The oligonucleotide moiety comprises a sequence that is complementary to the RNA component of human telomerase. The compounds inhibit telomerase activity in cells with a high potency and have superior cellular uptake characteristics.
    Type: Grant
    Filed: June 27, 2016
    Date of Patent: February 5, 2019
    Assignee: Geron Corporation
    Inventors: Sergei Gryaznov, Krisztina Pongracz
  • Patent number: 10035814
    Abstract: This invention relates to compounds useful for inhibiting telomere elongation. More specifically, the invention provides nucleotide analogs that are incorporated into telomeres by telomerase thereby inhibiting elongation of telomeres. The compounds are use in treating cancer and other cell proliferative diseases.
    Type: Grant
    Filed: January 30, 2017
    Date of Patent: July 31, 2018
    Assignee: Geron Corporation
    Inventors: Sergei M. Gryaznov, Ronald A. Pruzan, Krisztina Pongracz
  • Patent number: 10035815
    Abstract: Orthogonally protected 3?-amino nucleoside monomers and efficient methods for their synthesis are described. The methods employ selective protection of the 3?-amino group in the presence of the unprotected nucleoside base.
    Type: Grant
    Filed: May 16, 2016
    Date of Patent: July 31, 2018
    Assignee: Geron Corporation
    Inventors: Sergei M. Gryaznov, Krisztina Pongracz, Daria Zielinska
  • Patent number: 9951389
    Abstract: Provided herein are methods for identifying individuals diagnosed with a cell proliferative disorder that will benefit from treatment with a telomerase inhibitor compound. Also provided herein are methods for treating these individuals with telomerase inhibitor compounds.
    Type: Grant
    Filed: October 30, 2015
    Date of Patent: April 24, 2018
    Assignee: Geron Corporation
    Inventors: Ekaterina Bassett, Bart Burington, Hui Wang, Kevin Eng
  • Patent number: 9822360
    Abstract: The present disclosure relates to RNA amidates and thioamidates useful for RNA interference applications. The RNA amidates and thioamidates contain at least one internucleoside linkage chosen from ribo-N3??P5? phosphoramidate (NP) and ribo-N3??P5? thiophosphoramidate (NPS) linkages, and optionally further containing at least one covalently conjugated lipid moiety. Compositions comprising the amidates and thioamidates are disclosed, as are methods for their use in modulating gene expression.
    Type: Grant
    Filed: August 6, 2015
    Date of Patent: November 21, 2017
    Assignee: Geron Corporation
    Inventors: Sergei Gryaznov, Krisztina Pongracz
  • Patent number: 9796747
    Abstract: The present disclosure provides a solid phase method of making oligonucleotides via sequential coupling cycles including at least one coupling of a dinucleotide dimer subunit to a free 3?-terminal group of a growing chain. The oligonucleotides include at least two nucleoside subunits joined by a N3??P5? phosphoramidate linkage. The method may include the steps of (a) deprotecting the protected 3? amino group of a terminal nucleoside attached to a solid phase support, said deprotecting forming a free 3? amino group; (b) contacting the free 3? amino group with a 3?-protected amino-dinucleotide-5?-phosphoramidite dimer in the presence of a nucleophilic catalyst to form an internucleoside N3??P5? phosphoramidite linkage; and (c) oxidizing (e.g., sulfurizing) the linkage. The compositions produced by the subject methods may include a reduced amount of one or more (N?x) oligonucleotide products. Also provided are pharmaceutical compositions including the subject oligonucleotide compositions.
    Type: Grant
    Filed: April 29, 2015
    Date of Patent: October 24, 2017
    Assignee: Geron Corporation
    Inventor: Premchandran H. Ramiya
  • Patent number: 9771581
    Abstract: Provided herein are antisense oligonucleotides that can effectively prevent or decrease c-myc protein expression as well as decrease overall rates of cell proliferation in in vitro and mammalian in vivo models of cell proliferative disorders as well as methods for using the same.
    Type: Grant
    Filed: December 2, 2015
    Date of Patent: September 26, 2017
    Assignee: Geron Corporation
    Inventors: Sergei M. Gryaznov, Daria Zielinska, Ronald A. Pruzan, Jeffrey N. Lindquist
  • Patent number: 9765109
    Abstract: Oligonucleotides with a novel sugar-phosphate backbone containing at least one 2?-arabino-fluoronucleoside and an internucleoside 3?-NH—P(—O)(OR)—O-5? linkage, where R is a positively charged counter ion or hydrogen, and methods of synthesizing and using the inventive oligonucleotides are provided. The inventive phosphoramidate 2?-arabino-fluorooligonucleotides have a high RNA binding affinity to complementary nucleic acids and are base and acid stable.
    Type: Grant
    Filed: September 11, 2014
    Date of Patent: September 19, 2017
    Assignee: Geron Corporation
    Inventors: Sergei M. Gryaznov, Ronald G. Schultz
  • Patent number: 9732114
    Abstract: Compounds of the form O-(x-L)n, where O is an oligonucleoside having at least a plurality of N3??P5? thiophosphoramidate (NPS) internucleoside linkages, a conjugated lipid moiety L, and at least one G-rich sequence motif as described, are effective to morphologically alter and reduce adhesion of cancer cells.
    Type: Grant
    Filed: July 21, 2014
    Date of Patent: August 15, 2017
    Assignees: GERON CORPORATION, BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM
    Inventors: Sergei M. Gryaznov, Jerry W. Shay, Woodring Wright
  • Patent number: 9708360
    Abstract: This invention relates to antisense oligonucleotides comprising at least one N3??P5? phosphorodiamidate linkage (NPN) in the backbone, and kits and pharmaceutical compositions thereof, useful for modulating gene expression involved in the pathogenesis of a disease. Also included are compounds useful as building blocks of said antisense oligonucleotides and methods of preparing said antisense oligonucleotides and building block compounds including NPN linkages.
    Type: Grant
    Filed: September 26, 2014
    Date of Patent: July 18, 2017
    Assignee: Geron Corporation
    Inventors: Krisztina Pongracz, Mahesh Ramaseshan
  • Patent number: 9657296
    Abstract: Compounds comprising an oligonucleotide moiety covalently linked to a lipid moiety are disclosed. The oligonucleotide moiety comprises a sequence that is complementary to the RNA component of human telomerase. The compounds inhibit telomerase activity in cells with a high potency and have superior cellular uptake characteristics.
    Type: Grant
    Filed: May 18, 2015
    Date of Patent: May 23, 2017
    Assignee: Geron Corporation
    Inventors: Sergei Gryaznov, Krisztina Pongracz
  • Patent number: 9624542
    Abstract: Methods of reliably quantifying telomere length in cells or tissues that have been formalin fixed and paraffin embedded (FFPE) samples by quantitative polymerase chain reaction protocol and kits for use with such various methods are provided. The methods of the present invention may be used to predetermine an individual's response to treatment with a telomerase inhibitor, a telomere damaging agent or a telomerase activator.
    Type: Grant
    Filed: March 26, 2012
    Date of Patent: April 18, 2017
    Assignee: Geron Corporation
    Inventors: Hui Wang, Ning F. Go, Zhu Zhen Pirot
  • Patent number: 9617583
    Abstract: The invention provides methods for determining the susceptibility of cancer patients to developing adverse reactions if treated with a telomerase inhibitor drug by measurement of telomere length in appropriate cells of the patient prior to initiation of the telomerase inhibitor treatment.
    Type: Grant
    Filed: October 2, 2014
    Date of Patent: April 11, 2017
    Assignee: Geron Corporation
    Inventors: Calvin B. Harley, Laurence Elias, Jennifer Smith, Mark J. Ratain, Fabio Benedetti
  • Patent number: 9593137
    Abstract: This invention relates to compounds useful for inhibiting telomere elongation. More specifically, the invention provides nucleotide analogs that are incorporated into telomeres by telomerase thereby inhibiting elongation of telomeres. The compounds are useful in treating cancer and other cell proliferative diseases.
    Type: Grant
    Filed: December 21, 2012
    Date of Patent: March 14, 2017
    Assignee: Geron Corporation
    Inventors: Sergei M. Gryaznov, Ronald A. Pruzan, Krisztina Pongracz
  • Patent number: 9572891
    Abstract: Oligonucleotide conjugates, where an oligonucleotide is covalently attached to an aromatic system, are provided. In particular embodiments the oligonucleotide is complementary to the RNA component of human telomerase and is covalently attached to a nucleobase via an optional linker. The conjugates inhibit telomerase enzyme activity.
    Type: Grant
    Filed: June 2, 2015
    Date of Patent: February 21, 2017
    Assignee: Geron Corporation
    Inventors: Sergei M. Gryaznov, Krisztina Pongracz, Richard L. Tolman, Gregg B. Morin
  • Patent number: 9404112
    Abstract: Compounds comprising an oligonucleotide moiety covalently linked to a lipid moiety are disclosed. The oligonucleotide moiety comprises a sequence that is complementary to the RNA component of human telomerase. The compounds inhibit telomerase activity in cells with a high potency and have superior cellular uptake characteristics.
    Type: Grant
    Filed: August 21, 2012
    Date of Patent: August 2, 2016
    Assignee: Geron Corporation
    Inventors: Sergei Gryaznov, Krisztina Pongracz