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 (https=
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)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Virology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Urology & Nephrology (AREA)
  • Heart & Thoracic Surgery (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 (https=) 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 (https=)
EP (1) EP2245039A4 (https=)
JP (1) JP2011511004A (https=)
AU (1) AU2009241591A1 (https=)
BR (1) BRPI0907008A2 (https=)
CA (1) CA2713379A1 (https=)
MX (1) MX2010008394A (https=)
WO (1) WO2009134487A2 (https=)

Cited By (6)

* 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

Families Citing this family (108)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2005222902B2 (en) 2004-03-12 2010-06-10 Alnylam Pharmaceuticals, Inc. iRNA agents targeting VEGF
ES2874149T3 (es) 2006-05-11 2021-11-04 Alnylam Pharmaceuticals Inc Composiciones y métodos para inhibir la expresión del gen PCSK9
JOP20080381B1 (ar) * 2007-08-23 2023-03-28 Amgen Inc بروتينات مرتبطة بمولدات مضادات تتفاعل مع بروبروتين كونفيرتاز سيتيليزين ككسين من النوع 9 (pcsk9)
US10131904B2 (en) 2008-02-11 2018-11-20 Rxi Pharmaceuticals Corporation Modified RNAi polynucleotides and uses thereof
EA036772B1 (ru) 2008-10-20 2020-12-18 Элнилэм Фармасьютикалз, Инк. Композиции и способы для ингибирования экспрессии транстиретина
US9493774B2 (en) 2009-01-05 2016-11-15 Rxi Pharmaceuticals Corporation Inhibition of PCSK9 through RNAi
AU2010223967B2 (en) * 2009-03-12 2015-07-30 Alnylam Pharmaceuticals, Inc. Lipid formulated compositions and methods for inhibiting expression of Eg5 and VEGF genes
WO2010147992A1 (en) 2009-06-15 2010-12-23 Alnylam Pharmaceuticals, Inc. Methods for increasing efficacy of lipid formulated sirna
US9187746B2 (en) 2009-09-22 2015-11-17 Alnylam Pharmaceuticals, Inc. Dual targeting siRNA agents
WO2011088309A1 (en) 2010-01-14 2011-07-21 Regulus Therapeutics Inc. Microrna compositions and methods
BR112012024049A2 (pt) 2010-03-24 2017-03-01 Rxi Pharmaceuticals Corp interferência de rna em indicações dérmicas e fibróticas
CN106074591B (zh) 2010-03-24 2020-01-14 菲奥医药公司 眼部症候中的rna干扰
CA2812046A1 (en) * 2010-09-15 2012-03-22 Alnylam Pharmaceuticals, Inc. Modified irna agents
WO2012058693A2 (en) * 2010-10-29 2012-05-03 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibition of pcsk9 genes
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)
KR102365961B1 (ko) * 2011-03-29 2022-02-23 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
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
ES2923573T3 (es) 2011-06-21 2022-09-28 Alnylam Pharmaceuticals Inc Composiciones de ARNi de proteína 3 de tipo angiopoyetina (ANGPTL3) y métodos de uso de las mismas
EP3453761A1 (en) 2011-08-29 2019-03-13 Ionis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
HUE048622T2 (hu) * 2011-11-18 2020-08-28 Alnylam Pharmaceuticals Inc RNSi szerek, készítmények és alkalmazási eljárások transztiretin (TTR) asszociált betegségek kezelésére
EP2780454A2 (en) 2011-11-18 2014-09-24 Alnylam Pharmaceuticals, Inc. Modified rnai agents
EP2788006B1 (en) 2011-12-07 2026-01-07 Alnylam Pharmaceuticals, Inc. Biodegradable lipids for the delivery of active agents
WO2013165816A2 (en) 2012-05-02 2013-11-07 Merck Sharp & Dohme Corp. SHORT INTERFERING NUCLEIC ACID (siNA) COMPOSITIONS
US9255154B2 (en) 2012-05-08 2016-02-09 Alderbio Holdings, Llc Anti-PCSK9 antibodies and use thereof
EP2861624A1 (en) 2012-06-15 2015-04-22 F. Hoffmann-La Roche AG Anti-pcsk9 antibodies, formulations, dosing, and methods of use
CA3216595A1 (en) * 2013-03-14 2014-10-02 Kevin Fitzgerald Complement component c5 irna compositions and methods of use thereof
DK2991656T3 (da) 2013-05-01 2020-03-23 Ionis Pharmaceuticals Inc Sammensætninger og fremgangsmåder til modulering af apolipoprotein c-iii-ekspression
WO2014182661A2 (en) 2013-05-06 2014-11-13 Alnylam Pharmaceuticals, Inc Dosages and methods for delivering lipid formulated nucleic acid molecules
TW201936624A (zh) * 2013-05-22 2019-09-16 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
TWI768330B (zh) 2013-10-04 2022-06-21 美國西奈山伊坎醫學院 抑制alas1基因表現的組合物及方法
EP3077050B1 (en) 2013-12-04 2020-10-21 Phio Pharmaceuticals Corp. Methods for treatment of wound healing utilizing chemically modified oligonucleotides
US11279934B2 (en) 2014-04-28 2022-03-22 Phio Pharmaceuticals Corp. Methods for treating cancer using nucleic acids targeting MDM2 or MYCN
DK3137476T3 (da) 2014-04-28 2019-11-18 Ionis Pharmaceuticals Inc Linker-modificerede oligomerforbindelser
WO2015168605A1 (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
SG11201608502TA (en) 2014-05-01 2016-11-29 Ionis Pharmaceuticals Inc Compositions and methods for modulating complement factor b expression
EP3862362A3 (en) 2014-05-01 2021-10-27 Ionis Pharmaceuticals, Inc. Conjugates of modified antisense oligonucleotides and their use for modulating pkk expression
CN110903337A (zh) 2014-05-01 2020-03-24 Ionis制药公司 用于调节生长激素受体表达的组合物和方法
PT3137605T (pt) 2014-05-01 2020-12-18 Ionis Pharmaceuticals Inc Composições e métodos para modulação da expressão de angiopoietina de tipo 3
US10570169B2 (en) 2014-05-22 2020-02-25 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
KR102506169B1 (ko) 2014-09-05 2023-03-08 피오 파마슈티칼스 코프. Tyr 또는 mmp1을 표적화하는 핵산을 사용한 노화 및 피부 장애의 치료 방법
BR112017004056A2 (pt) 2014-09-12 2017-12-05 Biogen Ma Inc composições e métodos para detecção da proteína smn em um indivíduo e tratamento de um indivíduo
WO2016123365A1 (en) 2015-01-30 2016-08-04 The Regents Of The University Of Michigan Liposomal particles comprising biological molecules and uses thereof
WO2016154544A1 (en) 2015-03-25 2016-09-29 The Regents Of The University Of Michigan Compositions and methods for delivery of biomacromolecule agents
EA201792263A1 (ru) 2015-04-13 2018-08-31 Элнилэм Фармасьютикалз, Инк. КОМПОЗИЦИИ НА ОСНОВЕ iRNA ПРОТИВ АНГИОПОЭТИН-ПОДОБНОГО БЕЛКА 3 (ANGPTL3) И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
CN108135923B (zh) 2015-07-06 2021-03-02 菲奥医药公司 靶向超氧化物歧化酶1（sod1）的核酸分子
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
CA2991894A1 (en) 2015-07-10 2017-01-19 Ionis Pharmaceuticals, Inc. Modulators of diacyglycerol acyltransferase 2 (dgat2)
CN108138182B (zh) 2015-07-31 2022-08-19 阿尔尼拉姆医药品有限公司 甲状腺素运载蛋白(TTR)iRNA组合物及其治疗或预防TTR相关疾病的使用方法
CN118697894A (zh) 2015-08-25 2024-09-27 阿尔尼拉姆医药品有限公司 用于治疗前蛋白转化酶枯草杆菌蛋白酶kexin(pcsk9)基因相关障碍的方法和组合物
EP3350328A1 (en) * 2015-09-14 2018-07-25 Alnylam Pharmaceuticals, Inc. Polynucleotide agents targeting patatin-like phospholipase domain containing 3 (pnpla3) and methods of use thereof
JP6877414B2 (ja) 2015-09-24 2021-05-26 アイオニス・ファーマシューティカルズ・インコーポレイテッドＩｏｎｉｓ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． Ｋｒａｓ発現のモジュレーター
WO2017070151A1 (en) 2015-10-19 2017-04-27 Rxi Pharmaceuticals Corporation 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
US20190046555A1 (en) 2015-11-06 2019-02-14 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds for use in therapy
FI3386518T3 (fi) 2015-12-07 2025-09-25 Genzyme Corp Menetelmiä ja koostumuksia serpinc1:een liittyvän häiriön hoitamiseksi
KR102515329B1 (ko) 2016-03-07 2023-03-29 애로우헤드 파마슈티컬스 인코포레이티드 치료용 화합물을 위한 표적화 리간드
US12257352B2 (en) 2016-06-20 2025-03-25 The Regents Of The University Of Michigan Compositions and methods for delivery of biomacromolecule agents
ES2935658T3 (es) 2016-07-15 2023-03-09 Ionis Pharmaceuticals Inc Compuestos y métodos para la modulación de SMN2
MX2018009853A (es) 2016-09-02 2018-11-09 Arrowhead Pharmaceuticals Inc Ligandos de direccion.
EP3522898A4 (en) 2016-10-06 2020-05-27 Ionis Pharmaceuticals, Inc. METHOD FOR 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
EP4035659A1 (en) 2016-11-29 2022-08-03 PureTech LYT, Inc. Exosomes for delivery of therapeutic agents
JOP20190215A1 (ar) 2017-03-24 2019-09-19 Ionis Pharmaceuticals Inc مُعدّلات التعبير الوراثي عن pcsk9
JP7155239B2 (ja) 2017-04-05 2022-10-18 サイレンス・セラピューティクス・ゲーエムベーハー 産物及び組成物
WO2018195355A1 (en) 2017-04-19 2018-10-25 Rxi Pharmaceuticals Corporation Topical delivery of nucleic acid compounds
WO2019006455A1 (en) 2017-06-30 2019-01-03 Solstice Biologics, Ltd. AUXILIARIES OF CHIRAL PHOSPHORAMIDITIS AND METHODS OF USE THEREOF
KR20250046363A (ko) 2017-09-19 2025-04-02 알닐람 파마슈티칼스 인코포레이티드 트랜스타이레틴(ttr) 매개 아밀로이드증을 치료하기 위한 조성물 및 방법
CA3083968C (en) 2017-12-01 2024-04-23 Suzhou Ribo Life Science Co., Ltd. Double-stranded oligonucleotide, composition and conjugate comprising double-stranded oligonucleotide, preparation method thereof and use thereof
WO2019105437A1 (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
WO2019105435A1 (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
JP7365052B2 (ja) 2017-12-01 2023-10-19 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
CN110945130B (zh) 2017-12-01 2024-04-09 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
EP3732185B1 (en) 2017-12-29 2025-02-26 Suzhou Ribo Life Science Co., Ltd. Conjugates and preparation and use thereof
BR112020014425A2 (pt) 2018-01-15 2020-12-29 Ionis Pharmaceuticals, Inc. Moduladores de expressão de dnm2
AU2019218987B2 (en) 2018-02-12 2025-04-24 Ionis Pharmaceuticals, Inc. Modified compounds and uses thereof
JP7438135B2 (ja) 2018-05-09 2024-02-26 アイオーニス ファーマシューティカルズ， インコーポレーテッド Ｆｘｉの発現を低下させるための化合物及び方法
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
EP3823725A4 (en) 2018-07-17 2023-05-10 Aronora, Inc. METHODS FOR SAFELY REDUCING THROMBOPOIETIN
US20210292768A1 (en) 2018-08-08 2021-09-23 Arcturus Therapeutics, Inc. Compositions and agents against nonalcoholic steatohepatitis
US11918600B2 (en) 2018-08-21 2024-03-05 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition and conjugate containing nucleic acid, and use thereof
TWI856973B (zh) 2018-09-19 2024-10-01 美商Ionis製藥公司 Pnpla3表現之調節劑
EP3862024A4 (en) 2018-09-30 2022-08-17 Suzhou Ribo Life Science Co., Ltd. SIRNA CONJUGATE, METHOD FOR ITS PRODUCTION AND ITS USE
EP3899024A4 (en) 2018-12-21 2023-05-31 Ionis Pharmaceuticals, Inc. Modulators of hsd17b13 expression
US12496347B2 (en) 2018-12-28 2025-12-16 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, composition and conjugate containing nucleic acid, preparation method therefor and use thereof
AU2020280438B2 (en) 2019-05-22 2025-03-06 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition, conjugate, preparation method, and use
JP7610268B2 (ja) 2019-05-22 2025-01-08 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
WO2020233680A1 (zh) 2019-05-22 2020-11-26 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
EP3978609A4 (en) 2019-05-24 2024-02-07 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition, conjugate, preparation method, and use
EP4045062A1 (en) 2019-10-14 2022-08-24 Astrazeneca AB Modulators of pnpla3 expression
CN115135765A (zh) 2019-11-08 2022-09-30 菲奥医药公司 用于免疫治疗的靶向含布罗莫结构域之蛋白4(brd4)的经化学修饰的寡核苷酸
WO2021138537A1 (en) 2019-12-31 2021-07-08 Phio Pharmaceuticals Corp. Chemically modified oligonucleotides with improved systemic delivery
CR20220485A (es) 2020-02-28 2022-11-10 Ionis Pharmaceuticals Inc Compuestos y métodos para modular smn2
KR20230011913A (ko) * 2020-03-04 2023-01-25 버브 테라퓨틱스, 인크. 표적화된 rna 전달을 위한 조성물 및 방법
US20230183694A1 (en) 2020-03-16 2023-06-15 Argonaute RNA Limited Antagonist of pcsk9
AU2021260934A1 (en) 2020-04-21 2022-11-24 Flagship Pioneering, Inc. Bifunctional molecules and methods of using thereof
EP4136092B1 (en) 2020-11-18 2024-07-31 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating angiotensinogen expression
IL305442A (en) 2021-03-04 2023-10-01 Alnylam Pharmaceuticals Inc Angiopoietin-like 3 (ANGPTL3) IRNA compositions and methods of using them
US20230089502A1 (en) * 2021-06-17 2023-03-23 Sirnaomics, Inc. Products and compositions
CA3227852A1 (en) 2021-08-03 2023-02-09 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof
JP2024530647A (ja) 2021-08-03 2024-08-23 ヴァーヴ・セラピューティクス，インコーポレーテッド 標的ｒｎａ送達のための組成物および方法
WO2023015264A1 (en) 2021-08-04 2023-02-09 Phio Pharmaceuticals Corp. Immunotherapy of cancer utilizing natural killer cells treated with chemically modified oligonucleotides
JP2024529025A (ja) 2021-08-04 2024-08-01 フィオ ファーマシューティカルズ コーポレーション 化学修飾されたオリゴヌクレオチド
MX2024004011A (es) 2021-10-01 2024-07-01 Adarx Pharmaceuticals Inc Composiciones moduladoras de precalicreína y métodos de uso de estas.
WO2024220930A2 (en) 2023-04-20 2024-10-24 Adarx Pharmaceuticals, Inc. Mapt-modulating compositions and methods of use thereof
CN121398851A (zh) 2023-05-12 2026-01-23 阿达尔克斯制药有限公司 Nmda配体缀合的化合物及其用途
IL324720A (en) 2023-05-26 2026-01-01 Adarx Pharmaceuticals Inc SOD1 modulators and methods of using them
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
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
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

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
WO2001057064A2 (en) * 2000-02-07 2001-08-09 Roche Diagnostics Corporation Cationic amphiphiles for use in nucleic acid transfection
WO2002081628A2 (en) * 2001-04-05 2002-10-17 Ribozyme Pharmaceuticals, Incorporated Modulation of gene expression associated with inflammation proliferation and neurite outgrowth, using nucleic acid based technologies
US20040259247A1 (en) * 2000-12-01 2004-12-23 Thomas Tuschl Rna interference mediating small rna molecules
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
US7956176B2 (en) * 2002-09-05 2011-06-07 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
EP2305812A3 (en) * 2002-11-14 2012-06-06 Dharmacon, Inc. Fuctional and hyperfunctional sirna
ES2559828T3 (es) * 2003-07-16 2016-02-16 Protiva Biotherapeutics Inc. ARN de interferencia encapsulado en lípidos
US7799565B2 (en) * 2004-06-07 2010-09-21 Protiva Biotherapeutics, Inc. Lipid encapsulated interfering RNA
CA2587411A1 (en) * 2004-11-17 2006-05-26 Protiva Biotherapeutics, Inc. Sirna silencing of apolipoprotein b
JP5042863B2 (ja) * 2005-02-14 2012-10-03 サーナ・セラピューティクス・インコーポレイテッド 生物学的に活性な分子をデリバリーするための脂質ナノ粒子系組成物および方法
US7915230B2 (en) * 2005-05-17 2011-03-29 Molecular Transfer, Inc. Reagents for transfection of eukaryotic cells
US8101741B2 (en) * 2005-11-02 2012-01-24 Protiva Biotherapeutics, Inc. Modified siRNA molecules and uses thereof
WO2007056861A1 (en) * 2005-11-18 2007-05-24 Protiva Biotherapeutics, Inc. Sirna silencing of influenza virus gene expression
EP3192788A1 (en) * 2006-10-03 2017-07-19 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)
WO2009082817A1 (en) * 2007-12-27 2009-07-09 Protiva Biotherapeutics, Inc. Silencing of polo-like kinase expression using interfering rna
WO2009086558A1 (en) * 2008-01-02 2009-07-09 Tekmira Pharmaceuticals 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
MX342785B (es) * 2009-06-10 2016-10-12 Alnylam Pharmaceuticals Inc Formulacion mejorada de lipido.
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 (31)

* 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
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
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
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
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
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
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
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
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
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
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
KR102139918B1 (ko) 2012-04-26 2020-08-05 젠자임 코포레이션 ＳＥＲＰＩＮＣ1 ｉＲＮＡ 조성물 및 그의 이용 방법
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
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
KR20150003344A (ko) * 2012-04-26 2015-01-08 알닐람 파마슈티칼스 인코포레이티드 ＳＥＲＰＩＮＣ1 ｉＲＮＡ 조성물 및 그의 이용 방법
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
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
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
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
US10443058B2 (en) 2013-06-27 2019-10-15 Roche Innovation Center Copenhagen A/S Antisense oligomers targeting PCSK9
US11739332B2 (en) 2013-06-27 2023-08-29 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
US10370668B2 (en) 2013-06-27 2019-08-06 Roche Innovation Center Copenhagen A/S Manufacture of antisense oligomers and conjugates targeting PCSK9
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
US9879265B2 (en) 2013-06-27 2018-01-30 Roche Innovation Center Copenhagen A/S Oligonucleotide conjugates
US12421516B2 (en) 2013-06-27 2025-09-23 Roche Innovation Center Copenhagen A/S Antisense oligomers targeting PCSK9
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

Also Published As

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

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
JP2011511004A (ja) 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
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
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
JP2013545736A (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