JP2011511004A - ＰＣＳＫ９遺伝子を標的とするｄｓＲＮＡを送達するための最適化された方法 - Google Patents

ＰＣＳＫ９遺伝子を標的とするｄｓＲＮＡを送達するための最適化された方法 Download PDF

Info

Publication number
JP2011511004A
JP2011511004A JP2010545236A JP2010545236A JP2011511004A JP 2011511004 A JP2011511004 A JP 2011511004A JP 2010545236 A JP2010545236 A JP 2010545236A JP 2010545236 A JP2010545236 A JP 2010545236A JP 2011511004 A JP2011511004 A JP 2011511004A
Authority
JP
Japan
Prior art keywords
dsrna
pcsk9
nucleotides
cholesterol
days
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
JP2010545236A
Other languages
English (en)
Japanese (ja)
Other versions
JP2011511004A5 (enExample
Inventor
ケビン フィッツジェラルド，
フォージェロルズ， アントニン デ
エイキン アキンク，
ビクター イー． コテリアンスキ，
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Alnylam Pharmaceuticals Inc
Original Assignee
Alnylam Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Alnylam Pharmaceuticals Inc filed Critical Alnylam Pharmaceuticals Inc
Publication of JP2011511004A publication Critical patent/JP2011511004A/ja
Publication of JP2011511004A5 publication Critical patent/JP2011511004A5/ja
Pending legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-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
    • C12N15/1137—Non-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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/322—2'-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3515—Lipophilic moiety, e.g. cholesterol
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/35—Special therapeutic applications based on a specific dosage / administration regimen

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Virology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
JP2010545236A 2008-01-31 2009-01-30 ＰＣＳＫ９遺伝子を標的とするｄｓＲＮＡを送達するための最適化された方法 Pending JP2011511004A (ja)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US2496808P 2008-01-31 2008-01-31
US3908308P 2008-03-24 2008-03-24
US7654808P 2008-06-27 2008-06-27
US18876508P 2008-08-11 2008-08-11
PCT/US2009/032743 WO2009134487A2 (en) 2008-01-31 2009-01-30 Optimized methods for delivery of dsrna targeting the pcsk9 gene

Publications (2)

Publication Number Publication Date
JP2011511004A true JP2011511004A (ja) 2011-04-07
JP2011511004A5 JP2011511004A5 (enExample) 2013-03-14

Family

ID=41255636

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2010545236A Pending JP2011511004A (ja) 2008-01-31 2009-01-30 ＰＣＳＫ９遺伝子を標的とするｄｓＲＮＡを送達するための最適化された方法

Country Status (8)

Country Link
US (2) US20100010066A1 (enExample)
EP (1) EP2245039A4 (enExample)
JP (1) JP2011511004A (enExample)
AU (1) AU2009241591A1 (enExample)
BR (1) BRPI0907008A2 (enExample)
CA (1) CA2713379A1 (enExample)
MX (1) MX2010008394A (enExample)
WO (1) WO2009134487A2 (enExample)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012530143A (ja) * 2009-06-15 2012-11-29 アルナイラム ファーマシューティカルズ， インコーポレイテッド Ｐｃｓｋ９遺伝子を標的とする、脂質で製剤化されたｄｓｒｎａ
KR20150003344A (ko) * 2012-04-26 2015-01-08 알닐람 파마슈티칼스 인코포레이티드 ＳＥＲＰＩＮＣ1 ｉＲＮＡ 조성물 및 그의 이용 방법
KR20150013159A (ko) * 2012-04-10 2015-02-04 알닐람 파마슈티칼스 인코포레이티드 Ａｌａｓ1 유전자의 발현을 억제하기 위한 조성물 및 방법
JP2016506240A (ja) * 2012-12-05 2016-03-03 アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． ＰＣＳＫ９ｉＲＮＡ組成物及びその使用方法
JP2016523094A (ja) * 2013-06-27 2016-08-08 ロシュ イノベーション センター コペンハーゲン エーエス Ｐｃｓｋ９を標的とするアンチセンスオリゴマーおよびコンジュゲート
WO2024248146A1 (ja) * 2023-05-31 2024-12-05 国立大学法人北海道大学 ｐＨ感受性カチオン性脂質及び脂質ナノ粒子
USRE50996E1 (en) 2021-08-06 2026-08-18 Genzyme Corporation Serpinc1 iRNA compositions and methods of use thereof

Families Citing this family (111)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2423060T3 (es) 2004-03-12 2013-09-17 Alnylam Pharmaceuticals, Inc. Agentes iRNA que tienen como diana al VEGF
US7605251B2 (en) 2006-05-11 2009-10-20 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the PCSK9 gene
JOP20080381B1 (ar) * 2007-08-23 2023-03-28 Amgen Inc بروتينات مرتبطة بمولدات مضادات تتفاعل مع بروبروتين كونفيرتاز سيتيليزين ككسين من النوع 9 (pcsk9)
EP3643782A1 (en) 2008-02-11 2020-04-29 Phio Pharmaceuticals Corp. Modified rnai polynucleotides and uses thereof
EP2937418B1 (en) 2008-10-20 2017-10-18 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of transthyretin
US9493774B2 (en) 2009-01-05 2016-11-15 Rxi Pharmaceuticals Corporation Inhibition of PCSK9 through RNAi
CA2754043A1 (en) * 2009-03-12 2010-09-16 Alnylam Pharmaceuticals, Inc. Lipid formulated compositions and methods for inhibiting expression of eg5 and vegf genes
US9051567B2 (en) 2009-06-15 2015-06-09 Tekmira Pharmaceuticals Corporation Methods for increasing efficacy of lipid formulated siRNA
US9187746B2 (en) 2009-09-22 2015-11-17 Alnylam Pharmaceuticals, Inc. Dual targeting siRNA agents
US8846631B2 (en) 2010-01-14 2014-09-30 Regulus Therapeutics Inc. MicroRNA compositions and methods
CA2794189C (en) 2010-03-24 2022-01-11 Rxi Pharmaceuticals Corporation Rna interference in dermal and fibrotic indications
US9095504B2 (en) 2010-03-24 2015-08-04 Rxi Pharmaceuticals Corporation RNA interference in ocular indications
US9290760B2 (en) 2010-09-15 2016-03-22 Alnylam Pharmaceuticals, Inc. Modified iRNA agents
WO2012058210A1 (en) 2010-10-29 2012-05-03 Merck Sharp & Dohme Corp. RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACIDS (siNA)
WO2012058693A2 (en) * 2010-10-29 2012-05-03 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibition of pcsk9 genes
KR102104401B1 (ko) * 2011-03-29 2020-04-27 알닐람 파마슈티칼스 인코포레이티드 Tmprss6 유전자의 발현을 억제하기 위한 조성물 및 방법
WO2012174224A2 (en) * 2011-06-17 2012-12-20 Calando Pharmaceuticals, Inc. Methods for administering nucleic acid-based therapeutics
CA2839573A1 (en) 2011-06-21 2012-12-27 Alnylam Pharmaceuticals, Inc. Angiopoietin-like 3 (angptl3) irna compositions and methods of use thereof
EP2723861A4 (en) * 2011-06-21 2014-12-10 Alnylam Pharmaceuticals Inc COMPOSITIONS AND METHODS FOR INHIBITING HEPCIDINE ANTIMICROBIAL PEPTIDE (HAMP) OR THE ASSOCIATED GENE EXPRESSION
US10023861B2 (en) 2011-08-29 2018-07-17 Ionis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
UA118649C2 (uk) 2011-11-18 2019-02-25 Елнілем Фармасьютікалз, Інк. ДВОЛАНЦЮГОВИЙ ЗАСІБ ДЛЯ PHKі ТА ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ ДЛЯ ІНГІБУВАННЯ ЕКСПРЕСІЇ ТРАНСТИРЕТИНУ (TTR)
US9796974B2 (en) 2011-11-18 2017-10-24 Alnylam Pharmaceuticals, Inc. Modified RNAi agents
DE21212055T1 (de) 2011-12-07 2022-08-04 Alnylam Pharmaceuticals, Inc. Biologisch abbaubare lipide zur freisetzung von wirkstoffen
EP3919620A1 (en) * 2012-05-02 2021-12-08 Sirna Therapeutics, Inc. Short interfering nucleic acid (sina) compositions
US9255154B2 (en) 2012-05-08 2016-02-09 Alderbio Holdings, Llc Anti-PCSK9 antibodies and use thereof
AR091462A1 (es) 2012-06-15 2015-02-04 Genentech Inc Anticuerpos anti-pcsk9, formulaciones, dosificacion y metodos de uso
PT2970974T (pt) * 2013-03-14 2017-11-29 Alnylam Pharmaceuticals Inc Composições de irna de componente do complemento c5 e métodos para a sua utilização
PL2992098T3 (pl) 2013-05-01 2019-09-30 Ionis Pharmaceuticals, Inc. Kompozycje i sposoby modulowania ekspresji hbv i ttr
WO2014182661A2 (en) 2013-05-06 2014-11-13 Alnylam Pharmaceuticals, Inc Dosages and methods for delivering lipid formulated nucleic acid molecules
TWI664187B (zh) * 2013-05-22 2019-07-01 阿尼拉製藥公司 絲胺酸蛋白酶抑制因子Ａ１ ｉＲＮＡ組成物及其使用方法
WO2015051318A1 (en) 2013-10-04 2015-04-09 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the alas1 gene
WO2015085113A1 (en) 2013-12-04 2015-06-11 Rxi Pharmaceuticals Corporation Methods for treatment of wound healing utilizing chemically modified oligonucleotides
CA2947270A1 (en) 2014-04-28 2015-11-05 Rxi Pharmaceuticals Corporation Methods for treating cancer using nucleic acids targeting mdm2 or mycn
US9926556B2 (en) 2014-04-28 2018-03-27 Ionis Pharmaceuticals, Inc. Linkage modified oligomeric compounds
CR20160554A (es) 2014-05-01 2017-03-07 Ionis Pharmaceuticals Inc Composiciones y métodos para modular la expresión del factor b del complemento
HUE052709T2 (hu) 2014-05-01 2021-05-28 Ionis Pharmaceuticals Inc Módosított antiszensz oligonukleotidok konjugátumai és azok alkalmazása PKK expressziójának módosítására
CA2947619A1 (en) 2014-05-01 2015-11-05 Rxi Pharmaceuticals Corporation Methods for treatment of disorders in the front of the eye utilizing nucleic acid molecules
WO2015168589A2 (en) 2014-05-01 2015-11-05 Isis Pharmaceuticals, Inc. Compositions and methods for modulating angiopoietin-like 3 expression
WO2015168618A2 (en) 2014-05-01 2015-11-05 Isis Pharmaceuticals, Inc. Compositions and methods for modulating growth hormone receptor expression
US10570169B2 (en) 2014-05-22 2020-02-25 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
EP3188799B1 (en) 2014-09-05 2022-07-06 Phio Pharmaceuticals Corp. Methods for treating aging and skin disorders using nucleic acids targeting tyr or mmp1
WO2016040748A1 (en) 2014-09-12 2016-03-17 Ionis Pharmaceuticals, Inc. Compositions and methods for detection of smn protein in a subject and treatment of a subject
US10307491B2 (en) 2015-01-30 2019-06-04 The Regents Of The University Of Michigan Liposomal particles comprising biological molecules and uses thereof
AU2016238290B9 (en) 2015-03-25 2019-06-13 The Regents Of The University Of Michigan Compositions and methods for delivery of biomacromolecule agents
BR112017021053A2 (en) 2015-04-13 2018-08-14 Alnylam Pharmaceuticals, Inc. angiopoietin type 3 (angpt13) irna compositions and methods of use thereof
US10808247B2 (en) 2015-07-06 2020-10-20 Phio Pharmaceuticals Corp. Methods for treating neurological disorders using a synergistic small molecule and nucleic acids therapeutic approach
US11001845B2 (en) 2015-07-06 2021-05-11 Phio Pharmaceuticals Corp. Nucleic acid molecules targeting superoxide dismutase 1 (SOD1)
CA2991894A1 (en) 2015-07-10 2017-01-19 Ionis Pharmaceuticals, Inc. Modulators of diacyglycerol acyltransferase 2 (dgat2)
LT3329002T (lt) 2015-07-31 2021-01-11 Alnylam Pharmaceuticals, Inc. Transtiretino (ttr) irnr kompozicijos ir jų naudojimo būdai, skirti naudoti su ttr susijusių ligų gydymui arba prevencijai
EP3340994A1 (en) 2015-08-25 2018-07-04 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating a proprotein convertase subtilisin kexin (pcsk9) gene-associated disorder
WO2017048620A1 (en) * 2015-09-14 2017-03-23 Alnylam Pharmaceuticals, Inc. Polynucleotide agents targeting patatin-like phospholipase domain containing 3 (pnpla3) and methods of use thereof
HK1251624A1 (zh) 2015-09-24 2019-02-01 Ionis Pharmaceuticals, Inc. Kras表达的调节剂
US11021707B2 (en) 2015-10-19 2021-06-01 Phio Pharmaceuticals Corp. Reduced size self-delivering nucleic acid compounds targeting long non-coding RNA
AU2016349625B2 (en) 2015-11-06 2022-07-07 Ionis Pharmaceuticals, Inc. Modulating apolipoprotein (a) expression
LT4119569T (lt) 2015-11-06 2024-09-25 Ionis Pharmaceuticals, Inc. Konjuguoti priešprasmiai junginiai, skirti panaudoti terapijoje
IL308717A (en) 2015-12-07 2024-01-01 Genzyme Corp Methods and compositions for treating a serpinc1-associated disorder
JOP20170057B1 (ar) 2016-03-07 2022-03-14 Arrowhead Pharmaceuticals Inc مركبات ترابطية مستهدفة كمركبات علاجية
EP3471778A4 (en) * 2016-06-20 2020-02-19 The Regents of The University of Michigan COMPOSITIONS AND METHOD FOR DELIVERING BIOMACROMOLECOLIC ACTIVE SUBSTANCES
US20190321387A1 (en) 2016-07-15 2019-10-24 Ionis Pharmaceuticals, Inc. Compounds and methods for modulation of transcript processing
PL3484524T3 (pl) 2016-07-15 2023-03-20 Ionis Pharmaceuticals, Inc. Związki i sposoby modulacji smn2
JOP20170056B1 (ar) 2016-09-02 2021-08-17 Arrowhead Pharmaceuticals Inc مركبات ترابطية مستهدفة
WO2018067900A1 (en) 2016-10-06 2018-04-12 Ionis Pharmaceuticals, Inc. Method of conjugating oligomeric compounds
TW202313978A (zh) 2016-11-23 2023-04-01 美商阿尼拉製藥公司 絲胺酸蛋白酶抑制因子Ａ１ ｉＲＮＡ組成物及其使用方法
US20180193270A1 (en) 2016-11-29 2018-07-12 PureTech Health LLC Exosomes for delivery of therapeutic agents
JOP20190215A1 (ar) 2017-03-24 2019-09-19 Ionis Pharmaceuticals Inc مُعدّلات التعبير الوراثي عن pcsk9
US11015198B2 (en) 2017-04-05 2021-05-25 Silence Therapeutics Gmbh Products and compositions
JP7167059B2 (ja) 2017-04-19 2022-11-08 フィオ ファーマシューティカルズ コーポレーション 核酸化合物の局所送達
US11597744B2 (en) 2017-06-30 2023-03-07 Sirius Therapeutics, Inc. Chiral phosphoramidite auxiliaries and methods of their use
EP3684931A1 (en) 2017-09-19 2020-07-29 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating transthyretin (ttr) mediated amyloidosis
CN118291456A (zh) 2017-12-01 2024-07-05 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
WO2019105414A1 (zh) 2017-12-01 2019-06-06 苏州瑞博生物技术有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
HRP20250277T1 (hr) * 2017-12-01 2025-05-09 Suzhou Ribo Life Science Co., Ltd. Dvolančani oligonukleotid, sastav i konjugat koji sadrži dvolančani oligonukleotid, postupak njihove pripreme i upotreba
CN110944675B9 (zh) 2017-12-01 2024-08-09 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
JP7360716B2 (ja) 2017-12-01 2023-10-13 スーチョウ リボ ライフ サイエンス カンパニー、リミテッド 核酸、当該核酸を含む組成物および複合体ならびに調製方法と使用
CN110959011B (zh) 2017-12-29 2023-03-28 苏州瑞博生物技术股份有限公司 缀合物及其制备方法和用途
CA3088522A1 (en) 2018-01-15 2019-07-18 Ionis Pharmaceuticals, Inc. Modulators of dnm2 expression
AU2019218987B2 (en) 2018-02-12 2025-04-24 Ionis Pharmaceuticals, Inc. Modified compounds and uses thereof
IL277970B2 (en) 2018-05-09 2025-03-01 Ionis Pharmaceuticals Inc Oligomeric compounds comprising modified oligonucleotides and conjugated groups for use in the treatment of end-stage renal disease, chronic kidney disease and coronary artery disease
CN108627510A (zh) * 2018-06-06 2018-10-09 临安卡尔生物技术有限公司 高密度脂蛋白胆固醇检测试剂盒
WO2020018558A1 (en) 2018-07-17 2020-01-23 Aronora, Inc. Methods for safely reducing thrombopoietin
EP3833397A4 (en) 2018-08-08 2023-06-14 Arcturus Therapeutics, Inc. COMPOSITIONS AND AGENTS AGAINST NON-ALCOHOLIC STEATOHEPATITIS
WO2020038377A1 (zh) 2018-08-21 2020-02-27 苏州瑞博生物技术有限公司 一种核酸、含有该核酸的药物组合物和缀合物及其用途
TWI869213B (zh) 2018-09-19 2025-01-01 美商Ionis製藥公司 Pnpla3表現之調節劑
JP7376952B2 (ja) 2018-09-30 2023-11-09 スーチョウ リボ ライフ サイエンス カンパニー、リミテッド ｓｉＲＮＡ複合体及びその調製方法と使用
SG11202106378VA (en) 2018-12-21 2021-07-29 Ionis Pharmaceuticals Inc Modulators of hsd17b13 expression
JP7507495B2 (ja) 2018-12-28 2024-06-28 スーチョウ リボ ライフ サイエンス カンパニー、リミテッド 核酸、当該核酸を含む組成物及び複合体ならびに調製方法と使用
CN113286888B (zh) 2019-05-22 2023-12-22 苏州瑞博生物技术股份有限公司 核酸、药物组合物与缀合物及制备方法和用途
JP7610848B2 (ja) 2019-05-22 2025-01-09 スーチョウ リボ ライフ サイエンス カンパニー、リミテッド 核酸、薬物組成物及び複合体ならびに調製方法と使用
CN113227376B (zh) 2019-05-22 2024-04-09 苏州瑞博生物技术股份有限公司 核酸、药物组合物与缀合物及制备方法和用途
CN113795582B (zh) 2019-05-24 2024-05-24 苏州瑞博生物技术股份有限公司 核酸、药物组合物与缀合物及制备方法和用途
CN114728017B (zh) 2019-10-14 2025-10-28 阿斯利康(瑞典)有限公司 Pnpla3表达的调节剂
CA3160657A1 (en) 2019-11-08 2021-05-14 Phio Pharmaceuticals Corp. Chemically modified oligonucleotides targeting bromodomain containing protein 4 (brd4) for immunotherapy
WO2021138537A1 (en) 2019-12-31 2021-07-08 Phio Pharmaceuticals Corp. Chemically modified oligonucleotides with improved systemic delivery
AU2021225957A1 (en) 2020-02-28 2022-09-08 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating SMN2
CA3174708A1 (en) * 2020-03-04 2021-09-10 Verve Therapeutics, Inc. Compositions and methods for targeted rna delivery
US20230183694A1 (en) 2020-03-16 2023-06-15 Argonaute RNA Limited Antagonist of pcsk9
EP4132951A4 (en) 2020-04-09 2025-06-11 Verve Therapeutics, Inc. CHEMICALLY MODIFIED GENE EDITING GUIDE RNAS WITH CAS12B
JP2023522957A (ja) 2020-04-21 2023-06-01 フラッグシップ パイオニアリング， インコーポレイテッド 二機能性分子およびその使用方法
KR20230108728A (ko) 2020-11-18 2023-07-18 아이오니스 파마수티컬즈, 인코포레이티드 앤지오텐시노겐 발현을 조절하기 위한 화합물 및 방법
BR112023017737A2 (pt) 2021-03-04 2023-10-03 Alnylam Pharmaceuticals Inc Composições de irna de angiopoietina-semelhantes 3 (angptl3) e métodos de uso das mesmas
US20230089502A1 (en) * 2021-06-17 2023-03-23 Sirnaomics, Inc. Products and compositions
AR126675A1 (es) 2021-08-03 2023-11-01 Alnylam Pharmaceuticals Inc COMPOSICIONES DE ARNi CONTRA LA TRANSTIRRETINA (TTR) Y SUS MÉTODOS DE USO
EP4380576A4 (en) 2021-08-03 2026-04-29 Verve Therapeutics Inc RNA TARGETED COMPOSITIONS AND ADMINISTRATION METHODS
WO2023015265A2 (en) 2021-08-04 2023-02-09 Phio Pharmaceuticals Corp. Chemically modified oligonucleotides
WO2023015264A1 (en) 2021-08-04 2023-02-09 Phio Pharmaceuticals Corp. Immunotherapy of cancer utilizing natural killer cells treated with chemically modified oligonucleotides
AU2022357561A1 (en) 2021-10-01 2024-04-18 Adarx Pharmaceuticals, Inc. Prekallikrein-modulating compositions and methods of use thereof
US20240401045A1 (en) 2021-10-01 2024-12-05 Adarx Pharmaceuticals, Inc. Angiotensinogen-modulating compositions and methods of use thereof
EP4698652A2 (en) 2023-04-20 2026-02-25 Adarx Pharmaceuticals, Inc. Mapt-modulating compositions and methods of use thereof
WO2024238396A1 (en) 2023-05-12 2024-11-21 Adarx Pharmaceuticals, Inc. Nmda ligand conjugated compounds and uses thereof
WO2024249328A2 (en) 2023-05-26 2024-12-05 Adarx Pharmaceuticals, Inc. Sod1-modulating compositions and methods of use thereof
CN121712891A (zh) 2023-06-20 2026-03-20 阿达尔克斯制药有限公司 Lrrk2调节组合物及其使用方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007134161A2 (en) * 2006-05-11 2007-11-22 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the pcsk9 gene
WO2008011431A2 (en) * 2006-07-17 2008-01-24 Sirna Therapeutics Inc. Rna interference mediated inhibition of proprotein convertase subtilisin kexin 9 (pcsk9) gene expression using short interfering nucleic acid (sina)
JP2008501729A (ja) * 2004-06-07 2008-01-24 プロチバ バイオセラピューティクス インコーポレイティッド カチオン性脂質および使用方法
WO2009127060A1 (en) * 2008-04-15 2009-10-22 Protiva Biotherapeutics, Inc. Novel lipid formulations for nucleic acid delivery

Family Cites Families (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6054299A (en) * 1994-04-29 2000-04-25 Conrad; Charles A. Stem-loop cloning vector and method
US6271359B1 (en) * 1999-04-14 2001-08-07 Musc Foundation For Research Development Tissue-specific and pathogen-specific toxic agents and ribozymes
EP1261620A2 (en) * 2000-02-07 2002-12-04 Roche Diagnostics Corporation Cationic amphiphiles for use in nucleic acid transfection
CN100523215C (zh) * 2000-12-01 2009-08-05 马普科技促进协会 介导rna干涉的小rna分子
EP1386004A4 (en) * 2001-04-05 2005-02-16 Ribozyme Pharm Inc MODULATION OF GENE EXPRESSION ASSOCIATED WITH INFLAMMATORY PROLIFERATION AND GROWTH OF NEURITIES BY METHODS INVOLVING NUCLEIC ACID
US20070173473A1 (en) * 2001-05-18 2007-07-26 Sirna Therapeutics, Inc. RNA interference mediated inhibition of proprotein convertase subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA)
US20080249040A1 (en) * 2001-05-18 2008-10-09 Sirna Therapeutics, Inc. RNA interference mediated inhibition of sterol regulatory element binding protein 1 (SREBP1) gene expression using short interfering nucleic acid (siNA)
US20040009216A1 (en) * 2002-04-05 2004-01-15 Rodrigueza Wendi V. Compositions and methods for dosing liposomes of certain sizes to treat or prevent disease
US7923547B2 (en) * 2002-09-05 2011-04-12 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
EP2305813A3 (en) * 2002-11-14 2012-03-28 Dharmacon, Inc. Fuctional and hyperfunctional sirna
AU2004257373B2 (en) * 2003-07-16 2011-03-24 Arbutus Biopharma Corporation Lipid encapsulated interfering RNA
CA2569664C (en) * 2004-06-07 2013-07-16 Protiva Biotherapeutics, Inc. Lipid encapsulated interfering rna
US20060134189A1 (en) * 2004-11-17 2006-06-22 Protiva Biotherapeutics, Inc siRNA silencing of apolipoprotein B
CA2597724A1 (en) * 2005-02-14 2007-08-02 Sirna Therapeutics, Inc. Cationic lipids and formulated molecular compositions containing them
US7915230B2 (en) * 2005-05-17 2011-03-29 Molecular Transfer, Inc. Reagents for transfection of eukaryotic cells
EP1948674A4 (en) * 2005-11-02 2009-02-04 Protiva Biotherapeutics Inc MODIFIED SIRNA MOLECULES AND APPLICATIONS THEREOF
WO2007056861A1 (en) * 2005-11-18 2007-05-24 Protiva Biotherapeutics, Inc. Sirna silencing of influenza virus gene expression
CA3144493A1 (en) * 2006-10-03 2008-04-10 Arbutus Biopharma Corporation Lipid containing formulations
JOP20080381B1 (ar) * 2007-08-23 2023-03-28 Amgen Inc بروتينات مرتبطة بمولدات مضادات تتفاعل مع بروبروتين كونفيرتاز سيتيليزين ككسين من النوع 9 (pcsk9)
US9006191B2 (en) * 2007-12-27 2015-04-14 Protiva Biotherapeutics, Inc. Silencing of polo-like kinase expression using interfering RNA
EP3100718B1 (en) * 2008-01-02 2019-11-27 Arbutus Biopharma Corporation Improved compositions and methods for the delivery of nucleic acids
EP2373382B1 (en) * 2008-12-10 2017-02-15 Alnylam Pharmaceuticals, Inc. Gnaq targeted dsrna compositions and methods for inhibiting expression
KR20220038506A (ko) * 2009-06-10 2022-03-28 알닐람 파마슈티칼스 인코포레이티드 향상된 지질 조성물
NZ597504A (en) * 2009-06-15 2013-10-25 Alnylam Pharmaceuticals Inc Lipid formulated dsrna targeting the pcsk9 gene

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008501729A (ja) * 2004-06-07 2008-01-24 プロチバ バイオセラピューティクス インコーポレイティッド カチオン性脂質および使用方法
WO2007134161A2 (en) * 2006-05-11 2007-11-22 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the pcsk9 gene
WO2008011431A2 (en) * 2006-07-17 2008-01-24 Sirna Therapeutics Inc. Rna interference mediated inhibition of proprotein convertase subtilisin kexin 9 (pcsk9) gene expression using short interfering nucleic acid (sina)
WO2009127060A1 (en) * 2008-04-15 2009-10-22 Protiva Biotherapeutics, Inc. Novel lipid formulations for nucleic acid delivery

Cited By (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012530143A (ja) * 2009-06-15 2012-11-29 アルナイラム ファーマシューティカルズ， インコーポレイテッド Ｐｃｓｋ９遺伝子を標的とする、脂質で製剤化されたｄｓｒｎａ
KR102139451B1 (ko) 2012-04-10 2020-07-31 알닐람 파마슈티칼스 인코포레이티드 Ａｌａｓ1 유전자의 발현을 억제하기 위한 조성물 및 방법
JP7847571B2 (ja) 2012-04-10 2026-04-17 アルナイラム ファーマシューティカルズ， インコーポレイテッド Ａｌａｓ１遺伝子の発現を阻害する組成物および方法
KR20150013159A (ko) * 2012-04-10 2015-02-04 알닐람 파마슈티칼스 인코포레이티드 Ａｌａｓ1 유전자의 발현을 억제하기 위한 조성물 및 방법
JP2015518373A (ja) * 2012-04-10 2015-07-02 アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． Ａｌａｓ１遺伝子の発現を阻害する組成物および方法
JP2024012395A (ja) * 2012-04-10 2024-01-30 アルナイラム ファーマシューティカルズ， インコーポレイテッド Ａｌａｓ１遺伝子の発現を阻害する組成物および方法
JP7417352B2 (ja) 2012-04-10 2024-01-18 アルナイラム ファーマシューティカルズ， インコーポレイテッド Ａｌａｓ１遺伝子の発現を阻害する組成物および方法
JP7377246B2 (ja) 2012-04-10 2023-11-09 アルナイラム ファーマシューティカルズ， インコーポレイテッド Ａｌａｓ１遺伝子の発現を阻害する組成物および方法
JP2022036945A (ja) * 2012-04-10 2022-03-08 アルナイラム ファーマシューティカルズ， インコーポレイテッド Ａｌａｓ１遺伝子の発現を阻害する組成物および方法
JP2019022519A (ja) * 2012-04-10 2019-02-14 アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． Ａｌａｓ１遺伝子の発現を阻害する組成物および方法
KR102139918B1 (ko) 2012-04-26 2020-08-05 젠자임 코포레이션 ＳＥＲＰＩＮＣ1 ｉＲＮＡ 조성물 및 그의 이용 방법
KR20150003344A (ko) * 2012-04-26 2015-01-08 알닐람 파마슈티칼스 인코포레이티드 ＳＥＲＰＩＮＣ1 ｉＲＮＡ 조성물 및 그의 이용 방법
JP2024099663A (ja) * 2012-04-26 2024-07-25 ジェンザイム・コーポレーション Ｓｅｒｐｉｎｃ１ ｉＲＮＡ組成物およびその使用方法
JP2019068848A (ja) * 2012-04-26 2019-05-09 ジェンザイム・コーポレーション Ｓｅｒｐｉｎｃ１ ｉＲＮＡ組成物およびその使用方法
JP2022000022A (ja) * 2012-04-26 2022-01-04 ジェンザイム・コーポレーション Ｓｅｒｐｉｎｃ１ ｉＲＮＡ組成物およびその使用方法
JP7478121B2 (ja) 2012-04-26 2024-05-02 ジェンザイム・コーポレーション Ｓｅｒｐｉｎｃ１ ｉＲＮＡ組成物およびその使用方法
JP2015519047A (ja) * 2012-04-26 2015-07-09 アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． Ｓｅｒｐｉｎｃ１ｉＲＮＡ組成物およびその使用方法
JP2016506240A (ja) * 2012-12-05 2016-03-03 アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． ＰＣＳＫ９ｉＲＮＡ組成物及びその使用方法
JP7670747B2 (ja) 2012-12-05 2025-04-30 アルナイラム ファーマシューティカルズ， インコーポレイテッド ＰＣＳＫ９ ｉＲＮＡ組成物及びその使用方法
JP2019103501A (ja) * 2012-12-05 2019-06-27 アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． ＰＣＳＫ９ ｉＲＮＡ組成物及びその使用方法
JP7239335B2 (ja) 2012-12-05 2023-03-14 アルナイラム ファーマシューティカルズ， インコーポレイテッド ＰＣＳＫ９ ｉＲＮＡ組成物及びその使用方法
JP2023103244A (ja) * 2012-12-05 2023-07-26 アルナイラム ファーマシューティカルズ， インコーポレイテッド ＰＣＳＫ９ ｉＲＮＡ組成物及びその使用方法
JP2018064575A (ja) * 2013-06-27 2018-04-26 ロシュ イノベーション センター コペンハーゲン エーエス Ｐｃｓｋ９を標的とするアンチセンスオリゴマーおよびコンジュゲート
JP2016523094A (ja) * 2013-06-27 2016-08-08 ロシュ イノベーション センター コペンハーゲン エーエス Ｐｃｓｋ９を標的とするアンチセンスオリゴマーおよびコンジュゲート
US11739332B2 (en) 2013-06-27 2023-08-29 Roche Innovation Center Copenhagen A/S Antisense oligomers targeting PCSK9
US9879265B2 (en) 2013-06-27 2018-01-30 Roche Innovation Center Copenhagen A/S Oligonucleotide conjugates
US10443058B2 (en) 2013-06-27 2019-10-15 Roche Innovation Center Copenhagen A/S Antisense oligomers targeting PCSK9
US10385342B2 (en) 2013-06-27 2019-08-20 Roche Innovation Center Copenhagen A/S Methods of treatment using antisense oligomers and conjugates targeting PCSK9
US12421516B2 (en) 2013-06-27 2025-09-23 Roche Innovation Center Copenhagen A/S Antisense oligomers targeting PCSK9
US10370668B2 (en) 2013-06-27 2019-08-06 Roche Innovation Center Copenhagen A/S Manufacture of antisense oligomers and conjugates targeting PCSK9
USRE50996E1 (en) 2021-08-06 2026-08-18 Genzyme Corporation Serpinc1 iRNA compositions and methods of use thereof
WO2024248146A1 (ja) * 2023-05-31 2024-12-05 国立大学法人北海道大学 ｐＨ感受性カチオン性脂質及び脂質ナノ粒子

Also Published As

Publication number Publication date
EP2245039A4 (en) 2012-06-06
WO2009134487A2 (en) 2009-11-05
EP2245039A2 (en) 2010-11-03
WO2009134487A3 (en) 2010-02-04
AU2009241591A1 (en) 2009-11-05
MX2010008394A (es) 2010-11-12
US20120016009A1 (en) 2012-01-19
CA2713379A1 (en) 2009-11-05
US20100010066A1 (en) 2010-01-14
BRPI0907008A2 (pt) 2015-07-07

Similar Documents

Publication Publication Date Title
JP7806130B2 (ja) トランスチレチンの発現を阻害するための組成物および方法
JP6669905B2 (ja) トランスチレチン（ＴＴＲ）関連眼アミロイドーシスのためのｓｉＲＮＡ療法
JP5530933B2 (ja) 第ｖｉｉ因子遺伝子発現阻害のための組成物及び方法
KR102096014B1 (ko) PCSK9 iRNA 조성물 및 그 사용 방법
JP5723378B2 (ja) トランスサイレチン（ｔｔｒ）を阻害する脂質製剤化組成物及び方法
US20120016009A1 (en) Optimized Methods For Delivery Of DSRNA Targeting The PCSK9 Gene
JP5570806B2 (ja) Ｐｃｓｋ９遺伝子の発現を阻害するための組成物および方法
JP5529142B2 (ja) 血清アミロイドａ遺伝子の発現を阻害するための脂質製剤組成物および方法
JP2019213535A (ja) アポリポタンパク質ｃ−ｉｉｉ（ａｐｏｃ３）の発現を阻害するための組成物及び方法
JP2017012176A (ja) Ｐｃｓｋ９遺伝子の阻害のための組成物および方法
AU2021203272B2 (en) Compositions and methods for inhibiting expression of transthyretin
EA037110B1 (ru) КОМПОЗИЦИИ С иРНК К PCSK9 И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20120124

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20120124

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20130116

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20130620

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20130919

A602 Written permission of extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A602

Effective date: 20130927

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20131018

A602 Written permission of extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A602

Effective date: 20131025

A02 Decision of refusal

Free format text: JAPANESE INTERMEDIATE CODE: A02

Effective date: 20140304