EA034882B9 - Способ синтеза полинуклеотида - Google Patents

Способ синтеза полинуклеотида

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Publication number
EA034882B9
EA034882B9 EA201691786A EA201691786A EA034882B9 EA 034882 B9 EA034882 B9 EA 034882B9 EA 201691786 A EA201691786 A EA 201691786A EA 201691786 A EA201691786 A EA 201691786A EA 034882 B9 EA034882 B9 EA 034882B9
Authority
EA
Eurasian Patent Office
Prior art keywords
protected
phosphoramidite
amino group
group
independently
Prior art date
Application number
EA201691786A
Other languages
English (en)
Other versions
EA201691786A1 (ru
EA034882B1 (ru
Inventor
Премчандран Х. Рамия
Original Assignee
Джерон Корпорейшн
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Publication date
Application filed by Джерон Корпорейшн filed Critical Джерон Корпорейшн
Publication of EA201691786A1 publication Critical patent/EA201691786A1/ru
Publication of EA034882B1 publication Critical patent/EA034882B1/ru
Publication of EA034882B9 publication Critical patent/EA034882B9/ru

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/04Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1137Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12PFERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P19/00Preparation of compounds containing saccharide radicals
    • C12P19/26Preparation of nitrogen-containing carbohydrates
    • C12P19/28N-glycosides
    • C12P19/30Nucleotides
    • C12P19/34Polynucleotides, e.g. nucleic acids, oligoribonucleotides
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y207/00Transferases transferring phosphorus-containing groups (2.7)
    • C12Y207/07Nucleotidyltransferases (2.7.7)
    • C12Y207/07049RNA-directed DNA polymerase (2.7.7.49), i.e. telomerase or reverse-transcriptase
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    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/11Antisense
    • C12N2310/113Antisense targeting other non-coding nucleic acids, e.g. antagomirs
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/31Chemical structure of the backbone
    • C12N2310/314Phosphoramidates
    • C12N2310/3145Phosphoramidates with the nitrogen in 3' or 5'-position
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/31Chemical structure of the backbone
    • C12N2310/315Phosphorothioates
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    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/35Nature of the modification
    • C12N2310/351Conjugate
    • C12N2310/3515Lipophilic moiety, e.g. cholesterol
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02PCLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00Technologies relating to chemical industry
    • Y02P20/50Improvements relating to the production of bulk chemicals
    • Y02P20/55Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biochemistry (AREA)
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  • Microbiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Virology (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Предложен способ синтеза полинуклеотида, включающий стадии: (a) снятие защиты с защищенной 3'-аминогруппы концевого нуклеозида, присоединенного к твердофазной подложке, причем указанное снятие защиты приводит к образованию свободной 3'-аминогруппы; (b) приведение в контакт свободной 3'-аминогруппы с димером 3'-защищенного аминодинуклеотид-фосфорамидат-5'-фосфорамидита в присутствии нуклеофильного катализатора с образованием межнуклеозидной N3'P5'-фосфорамидитной связи и (c) окисление указанной связи. Кроме того, предложено динуклеотидное тиофосфорамидатное соединение формулы (II)где Bи B, каждый независимо, представляет собой пурин, защищенный пурин, пиримидин или защищенный пиримидин; Rпредставляет собой фосфорамидитную группу и Rи R, каждый независимо, представляет собой защитную группу; или его соль.
EA201691786A 2014-05-01 2015-04-29 Способ синтеза полинуклеотида EA034882B9 (ru)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201461987396P 2014-05-01 2014-05-01
US201562151909P 2015-04-23 2015-04-23
PCT/US2015/028327 WO2015168310A1 (en) 2014-05-01 2015-04-29 Oligonucleotide compositions and methods of making the same

Publications (3)

Publication Number Publication Date
EA201691786A1 EA201691786A1 (ru) 2017-04-28
EA034882B1 EA034882B1 (ru) 2020-04-01
EA034882B9 true EA034882B9 (ru) 2020-07-13

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
EA201691786A EA034882B9 (ru) 2014-05-01 2015-04-29 Способ синтеза полинуклеотида

Country Status (32)

Country Link
US (5) US9796747B2 (ru)
EP (2) EP3137479B1 (ru)
JP (6) JP7040892B2 (ru)
KR (3) KR20210130822A (ru)
CN (3) CN111228288B (ru)
AP (1) AP2016009489A0 (ru)
AU (3) AU2015253158B2 (ru)
BR (1) BR112016025196B1 (ru)
CA (1) CA2943888A1 (ru)
CL (4) CL2016002749A1 (ru)
DK (1) DK3137479T3 (ru)
EA (1) EA034882B9 (ru)
ES (1) ES2963740T3 (ru)
FI (1) FI3137479T3 (ru)
HR (1) HRP20231505T1 (ru)
HU (1) HUE064289T2 (ru)
IL (2) IL248044B (ru)
JO (2) JOP20200257A1 (ru)
LT (1) LT3137479T (ru)
MX (2) MX2016014178A (ru)
MY (2) MY178617A (ru)
PE (1) PE20170147A1 (ru)
PH (1) PH12016502080A1 (ru)
PL (1) PL3137479T3 (ru)
PT (1) PT3137479T (ru)
RS (1) RS64860B1 (ru)
SG (2) SG11201608226YA (ru)
SI (1) SI3137479T1 (ru)
TW (2) TWI712413B (ru)
UA (1) UA126108C2 (ru)
WO (1) WO2015168310A1 (ru)
ZA (2) ZA201606624B (ru)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
LT3296312T (lt) 2004-07-02 2021-06-10 Geron Corporation Apsaugotų 3'-amino-5'-fosforamidito nukleozido monomerų sintezė
JOP20200257A1 (ar) 2014-05-01 2017-06-16 Geron Corp تركيبات أوليجو نوكليوتيد وطرق لتحضيرها
TN2017000411A1 (en) 2015-04-23 2019-01-16 Geron Corp Methods of polynucleotide preparation using multivalent cation salt compositions
CA3066968C (en) * 2017-07-10 2023-06-13 Geron Corporation Improved process for preparing imetelstat
MX2022005008A (es) * 2019-10-28 2022-08-08 Geron Corp Sales de 3-(ácido graso amido)-2-hidroxi-1-(hidroxi protegido)-propano succinilada solida amorfa y métodos para elaborarlas.
AU2020375734A1 (en) 2019-10-28 2022-05-26 Geron Corporation Crystalline solids of 3-palmitoyl-amido-1,2-propanediol and 3-palmitoyl-amido-2-hydroxy-1-dimethoxytriphenylmethylether-propane and methods of making and using the same
KR20220123300A (ko) 2020-01-08 2022-09-06 닛토덴코 가부시키가이샤 분절-타입 아미디트(segment-type amidite)를 사용한 핵산 합성 방법

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070037770A1 (en) * 1999-09-10 2007-02-15 Sergei Gryaznov Oligonucleotide N3'-P5' thiophosphoramidates: their synthesis and use
WO2008094640A2 (en) * 2007-01-30 2008-08-07 Geron Corporation Compounds having anti-adhesive effects on cancer cells
US20090175801A1 (en) * 2006-04-24 2009-07-09 Deen Dennis F Cns-tumor treatment method and composition

Family Cites Families (77)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4046720A (en) 1974-01-17 1977-09-06 California Institute Of Technology Crosslinked, porous, polyacrylate beads
US4394448A (en) 1978-02-24 1983-07-19 Szoka Jr Francis C Method of inserting DNA into living cells
US4678814A (en) 1981-03-30 1987-07-07 California Institute Of Technology Polyacrolein microspheres
US4413070A (en) 1981-03-30 1983-11-01 California Institute Of Technology Polyacrolein microspheres
US4897355A (en) 1985-01-07 1990-01-30 Syntex (U.S.A.) Inc. N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor
US6448392B1 (en) 1985-03-06 2002-09-10 Chimerix, Inc. Lipid derivatives of antiviral nucleosides: liposomal incorporation and method of use
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
US4757141A (en) 1985-08-26 1988-07-12 Applied Biosystems, Incorporated Amino-derivatized phosphite and phosphate linking agents, phosphoramidite precursors, and useful conjugates thereof
US4659774A (en) 1985-11-01 1987-04-21 American Hoechst Corporation Support for solid-phase oligonucleotide synthesis
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
WO1990010448A2 (en) 1989-03-07 1990-09-20 Genentech, Inc. Covalent conjugates of lipid and oligonucleotide
US4958013A (en) 1989-06-06 1990-09-18 Northwestern University Cholesteryl modified oligonucleotides
US5411947A (en) 1989-06-28 1995-05-02 Vestar, Inc. Method of converting a drug to an orally available form by covalently bonding a lipid to the drug
US6395492B1 (en) 1990-01-11 2002-05-28 Isis Pharmaceuticals, Inc. Derivatized oligonucleotides having improved uptake and other properties
US6153737A (en) 1990-01-11 2000-11-28 Isis Pharmaceuticals, Inc. Derivatized oligonucleotides having improved uptake and other properties
US6114513A (en) 1990-01-11 2000-09-05 Isis Pharmaceuticals, Inc. Thiol-derivatized oligonucleotides
AU7759291A (en) 1990-03-29 1991-10-21 Gilead Sciences, Inc. Oligonucleotide-transport agent disulfide conjugates
US5420330A (en) 1990-09-07 1995-05-30 Pharmacia P-L Biochemicals Inc. Lipo-phosphoramidites
US5419966A (en) 1991-06-10 1995-05-30 Microprobe Corporation Solid support for synthesis of 3'-tailed oligonucleotides
US5633360A (en) 1992-04-14 1997-05-27 Gilead Sciences, Inc. Oligonucleotide analogs capable of passive cell membrane permeation
US5629154A (en) 1993-11-12 1997-05-13 Geron Corporation Telomerase activity assays
US5489508A (en) 1992-05-13 1996-02-06 University Of Texas System Board Of Regents Therapy and diagnosis of conditions related to telomere length and/or telomerase activity
US5837453A (en) 1992-05-13 1998-11-17 Geron Corporation Telomerase activity assays
US6235886B1 (en) 1993-09-03 2001-05-22 Isis Pharmaceuticals, Inc. Methods of synthesis and use
US5523389A (en) 1992-09-29 1996-06-04 Isis Pharmaceuticals, Inc. Inhibitors of human immunodeficiency virus
US7067497B2 (en) 1992-09-29 2006-06-27 Isis Pharmaceuticals, Inc. Modulation of telomere length by oligonucleotides having a G-core sequence
US6087491A (en) 1993-01-08 2000-07-11 Hybridon, Inc. Extremely high purity oligonucleotides and methods of synthesizing them using dimer blocks
US5476925A (en) 1993-02-01 1995-12-19 Northwestern University Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups
US6350853B1 (en) 1993-04-26 2002-02-26 Peter E. Nielsen Conjugated peptide nucleic acids having enhanced cellular uptake
DE4331670A1 (de) 1993-09-17 1995-03-23 Hoechst Ag Neue Antisense-Oligonucleotide gegen HSV-1 sowie deren Herstellung
CA2174425A1 (en) 1993-10-18 1995-04-27 Graham Leslie Barrett A method for enhancing neurone survival and agents useful for same
US5863726A (en) 1993-11-12 1999-01-26 Geron Corporation Telomerase activity assays
US5726297A (en) 1994-03-18 1998-03-10 Lynx Therapeutics, Inc. Oligodeoxyribonucleotide N3' P5' phosphoramidates
US5965720A (en) 1994-03-18 1999-10-12 Lynx Therapeutics, Inc. Oligonucleotide N3'→P5' phosphoramidates
US5599922A (en) 1994-03-18 1997-02-04 Lynx Therapeutics, Inc. Oligonucleotide N3'-P5' phosphoramidates: hybridization and nuclease resistance properties
GB9413035D0 (en) 1994-06-29 1994-08-17 Scras Antisense oligonucleeotides
PL181019B1 (pl) 1994-07-07 2001-05-31 Geron Corp Składnik RNA ssaczej telomerazy i sposób wytwarzania rekombinowanego enzymu telomerazy
US5958680A (en) 1994-07-07 1999-09-28 Geron Corporation Mammalian telomerase
US5583016A (en) 1994-07-07 1996-12-10 Geron Corporation Mammalian telomerase
WO1996014277A1 (en) 1994-11-07 1996-05-17 Hybridon, Inc. Synthesis of 35s-labeled oligonucleotides with 3h-1,2-benzodithiol-3-1,1-dioxide
US5656638A (en) 1995-04-18 1997-08-12 Geron Corporation Telomerase inhibitors
US5863936A (en) 1995-04-18 1999-01-26 Geron Corporation Telomerase inhibitors
US5760062A (en) 1995-04-18 1998-06-02 Geron Corporation Telomerase inhibitors
US5840490A (en) 1995-06-07 1998-11-24 Mcmaster University Telomerase activity associated with hematological and colorectal malignancies
US5770613A (en) 1995-09-29 1998-06-23 Geron Corporation Telomerase inhibitors
US5767278A (en) 1995-10-06 1998-06-16 Geron Corporation Telomerase inhibitors
US5859233A (en) 1996-02-21 1999-01-12 Lynx Therapeutics, Inc. Synthons for synthesis of oligonucleotide N3-P5 phosphoramidates
US5684143A (en) 1996-02-21 1997-11-04 Lynx Therapeutics, Inc. Oligo-2'-fluoronucleotide N3'->P5' phosphoramidates
GB9606158D0 (en) 1996-03-23 1996-05-29 Ciba Geigy Ag Chemical compounds
US6015710A (en) 1996-04-09 2000-01-18 The University Of Texas System Modulation of mammalian telomerase by peptide nucleic acids
WO1997037691A1 (en) 1996-04-10 1997-10-16 Lynx Therapeutics, Inc. Telomerase inhibitors
US6111085A (en) 1996-09-13 2000-08-29 Isis Pharmaceuticals, Inc. Carbamate-derivatized nucleosides and oligonucleosides
US6444650B1 (en) 1996-10-01 2002-09-03 Geron Corporation Antisense compositions for detecting and inhibiting telomerase reverse transcriptase
US6261836B1 (en) 1996-10-01 2001-07-17 Geron Corporation Telomerase
US6001991A (en) 1996-10-04 1999-12-14 Isis Pharmaceuticals Inc. Antisense oligonucleotide modulation of MDR P-glycoprotein gene expression
US5846723A (en) 1996-12-20 1998-12-08 Geron Corporation Methods for detecting the RNA component of telomerase
CA2274586A1 (en) 1996-12-20 1998-07-02 Geron Corporation Methods for detecting and inhibiting the rna component of telomerase
US5877309A (en) 1997-08-13 1999-03-02 Isis Pharmaceuticals, Inc. Antisense oligonucleotides against JNK
US5998604A (en) 1997-09-15 1999-12-07 The Perkin-Elmer Corporation Polynucleotide purification method
JP3722630B2 (ja) 1998-10-28 2005-11-30 パイオニア株式会社 記録再生装置
US6656730B1 (en) 1999-06-15 2003-12-02 Isis Pharmaceuticals, Inc. Oligonucleotides conjugated to protein-binding drugs
GB9927674D0 (en) * 1999-11-23 2000-01-19 Aegis Eng Ltd Protective material
US6331399B1 (en) 2000-05-16 2001-12-18 Isis Pharmaceuticals, Inc. Antisense inhibition of tert expression
EP1379689B1 (en) * 2001-03-23 2012-09-26 Geron Corporation Oligonucleotide conjugates
US7563618B2 (en) 2001-03-23 2009-07-21 Geron Corporation Oligonucleotide conjugates
EP1667522B1 (en) 2003-09-09 2018-01-17 Geron Corporation Modified oligonucleotides for telomerase inhibition
US20120329858A1 (en) * 2010-08-04 2012-12-27 Geron Corporation Modified oligonucleotides for telomerase inhibition
LT3296312T (lt) 2004-07-02 2021-06-10 Geron Corporation Apsaugotų 3'-amino-5'-fosforamidito nukleozido monomerų sintezė
WO2006023880A2 (en) * 2004-08-23 2006-03-02 Isis Pharmaceuticals, Inc. Compounds and methods for the characterization of oligonucleotides
JP2008523786A (ja) * 2004-10-18 2008-07-10 コドン デバイシズ インコーポレイテッド 高忠実度合成ポリヌクレオチドのアセンブリ方法
WO2006113470A2 (en) 2005-04-15 2006-10-26 Geron Corporation Cancer treatment by combined inhibition of proteasome and telomerase activities
DK2101789T3 (en) 2006-10-30 2015-03-23 Geron Corp Combined telomerase inhibitor and gemcitabine for the treatment of cancer
US9106103B2 (en) 2011-09-23 2015-08-11 Eaton Corporation Unintteruptible power supply systems and methods employing on-demand energy storage
US9006630B2 (en) 2012-01-13 2015-04-14 Altasens, Inc. Quality of optically black reference pixels in CMOS iSoCs
US9375485B2 (en) 2012-12-07 2016-06-28 Geron Corporation Use of telomerase inhibitors for the treatment of myeloproliferative disorders and myeloproliferative neoplasms
US20150342982A1 (en) 2012-12-07 2015-12-03 Geron Corporation Use of Telomerase Inhibitors for the Treatment of Myeloproliferative Disorders and Myeloproliferative Neoplasms
JOP20200257A1 (ar) 2014-05-01 2017-06-16 Geron Corp تركيبات أوليجو نوكليوتيد وطرق لتحضيرها

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070037770A1 (en) * 1999-09-10 2007-02-15 Sergei Gryaznov Oligonucleotide N3'-P5' thiophosphoramidates: their synthesis and use
US20090175801A1 (en) * 2006-04-24 2009-07-09 Deen Dennis F Cns-tumor treatment method and composition
WO2008094640A2 (en) * 2007-01-30 2008-08-07 Geron Corporation Compounds having anti-adhesive effects on cancer cells

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CAPALDI, D.C. et al., Highly Efficient Solid Phase Synthesis Of Oligonucleotide Analogs Containing Phosphprodithioate Linkages. Nucleic Acids Res. 01 May 2000, Vol. 28, No. 9; E40; DOI: 10.1093/nar/28.9.e40 *
CHEN, J.J. et al., N2'P3' Phosphoramidate Glycerol Nucleic Acid As A Potential Alternative Genetic System. J. Am. Chem. Soc. 18 February 2009, Vol. 131, No. 6; pages 2119-2121; DOI: 10.1021/ja809069b *
FEARON, K.L. et al., Investigation Of The 'N-1' Impurity In Phosphorothioate Oligodeoxynucleotides Synthesized By The Solid-Phase -Cyanoethyl Phosphoramidate Method Using Stepwise Sulfurization. Nucleic Acids Research. 1995, Vol. 23, No. 14; pages 2754-2761 *

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