JP2016522172A - Ｈｃｖを治療するのに有用な重水素化されたヌクレオシドプロドラッグ - Google Patents

Ｈｃｖを治療するのに有用な重水素化されたヌクレオシドプロドラッグ Download PDF

Info

Publication number
JP2016522172A
JP2016522172A JP2016507703A JP2016507703A JP2016522172A JP 2016522172 A JP2016522172 A JP 2016522172A JP 2016507703 A JP2016507703 A JP 2016507703A JP 2016507703 A JP2016507703 A JP 2016507703A JP 2016522172 A JP2016522172 A JP 2016522172A
Authority
JP
Japan
Prior art keywords
alkyl
compound
deuterium
hydrogen
salt according
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
JP2016507703A
Other languages
English (en)
Japanese (ja)
Other versions
JP2016522172A5 (OSRAM
Inventor
ミリンド、デシュパンデ
ジェイソン、アラン、ワイルス
本 彰 宏 橋
本 彰 宏 橋
アビナッシュ、パドケー
Original Assignee
アキリオン ファーマシューティカルズ，インコーポレーテッド
アキリオン ファーマシューティカルズ，インコーポレーテッド
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 アキリオン ファーマシューティカルズ，インコーポレーテッド, アキリオン ファーマシューティカルズ，インコーポレーテッド filed Critical アキリオン ファーマシューティカルズ，インコーポレーテッド
Publication of JP2016522172A publication Critical patent/JP2016522172A/ja
Publication of JP2016522172A5 publication Critical patent/JP2016522172A5/ja
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C07B59/005—Sugars; Derivatives thereof; Nucleosides; Nucleotides; Nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/22—Amides of acids of phosphorus
    • C07F9/24—Esteramides
    • C07F9/2404—Esteramides the ester moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/2429—Esteramides the ester moiety containing a substituent or a structure which is considered as characteristic of arylalkanols
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/22—Amides of acids of phosphorus
    • C07F9/24—Esteramides
    • C07F9/2454—Esteramides the amide moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/2458—Esteramides the amide moiety containing a substituent or a structure which is considered as characteristic of aliphatic amines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576—Six-membered rings
    • C07F9/58—Pyridine rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06—Pyrimidine radicals
    • C07H19/067—Pyrimidine radicals with ribosyl as the saccharide radical
    • Y—GENERAL 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
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Virology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
JP2016507703A 2013-04-12 2014-04-14 Ｈｃｖを治療するのに有用な重水素化されたヌクレオシドプロドラッグ Pending JP2016522172A (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361811464P 2013-04-12 2013-04-12
US61/811,464 2013-04-12
PCT/US2014/034021 WO2014169280A2 (en) 2013-04-12 2014-04-14 Deuterated nucleoside prodrugs useful for treating hcv

Publications (2)

Publication Number Publication Date
JP2016522172A true JP2016522172A (ja) 2016-07-28
JP2016522172A5 JP2016522172A5 (OSRAM) 2017-06-01

Family

ID=50686233

Family Applications (2)

Application Number Title Priority Date Filing Date
JP2016507703A Pending JP2016522172A (ja) 2013-04-12 2014-04-14 Ｈｃｖを治療するのに有用な重水素化されたヌクレオシドプロドラッグ
JP2016507702A Ceased JP2016518359A (ja) 2013-04-12 2014-04-14 Ｈｃｖを治療するための高活性のヌクレオシド誘導体

Family Applications After (1)

Application Number Title Priority Date Filing Date
JP2016507702A Ceased JP2016518359A (ja) 2013-04-12 2014-04-14 Ｈｃｖを治療するための高活性のヌクレオシド誘導体

Country Status (11)

Country Link
US (2) US20140309164A1 (OSRAM)
EP (2) EP2984098A2 (OSRAM)
JP (2) JP2016522172A (OSRAM)
KR (2) KR20160003700A (OSRAM)
CN (2) CN105377868A (OSRAM)
AU (2) AU2014250764A1 (OSRAM)
BR (2) BR112015025716A2 (OSRAM)
CA (2) CA2909270A1 (OSRAM)
ES (1) ES2623287T3 (OSRAM)
RU (2) RU2015148006A (OSRAM)
WO (2) WO2014169278A1 (OSRAM)

Families Citing this family (61)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5767643B2 (ja) 2009-09-21 2015-08-19 ギリード・サイエンシズ・インコーポレーテッド １’−置換カルバヌクレオシド類似体の調製のためのプロセスおよび中間体
PE20130400A1 (es) 2010-07-22 2013-04-10 Gilead Sciences Inc Metodos y compuestos para tratar infecciones virales por paramyxoviridae
HUE029038T2 (en) 2012-05-25 2017-01-30 Janssen Sciences Ireland Uc Uracil spirooxetan nucleosides
US10034893B2 (en) 2013-02-01 2018-07-31 Enanta Pharmaceuticals, Inc. 5, 6-D2 uridine nucleoside/tide derivatives
BR112016028119A2 (pt) 2014-06-06 2017-08-22 Res Triangle Inst Agonistas receptores de apelina (apj) e usos dos mesmos
US9603864B2 (en) * 2014-06-24 2017-03-28 Alios Biopharma, Inc. Substituted nucleosides, nucleotides and analogs thereof
US20160016986A1 (en) * 2014-07-21 2016-01-21 Milind Deshpande Stabilized nucleotides for medical treatment
US20170218006A1 (en) * 2014-07-31 2017-08-03 Sandoz Ag Synthesis of Phosphoramidates
WO2016023522A2 (en) * 2014-08-15 2016-02-18 Merck Sharp & Dohme Corp. Substituted phosphoramidate compounds and uses thereof
WO2016033164A1 (en) 2014-08-26 2016-03-03 Enanta Pharmaceuticals, Inc. Nucleoside and nucleotide derivatives
US10118941B2 (en) 2014-09-15 2018-11-06 Medivir Ab Methods for the preparation of diastereomerically pure phosphoramidate prodrugs
TWI698444B (zh) * 2014-10-29 2020-07-11 美商基利科學股份有限公司 製備核糖苷的方法
WO2016073756A1 (en) * 2014-11-06 2016-05-12 Enanta Pharmaceuticals, Inc. Deuterated nucleoside/tide derivatives
US9732110B2 (en) 2014-12-05 2017-08-15 Enanta Pharmaceuticals, Inc. Nucleoside and nucleotide derivatives
WO2016099982A2 (en) 2014-12-15 2016-06-23 Emory University Phosphoramidates for the treatment of hepatitis b virus
WO2016098123A2 (en) * 2014-12-16 2016-06-23 Laurus Labs Private Ltd A recycling process for preparing (s)-2-[(substituted-phenoxy)-phenoxy- phosphorylamino] propionic acid isopropyl ester diastereomers
MA41441A (fr) * 2014-12-19 2017-12-12 Alios Biopharma Inc Nucléosides substitués, nucléotides et analogues de ceux-ci
CN118286245A (zh) 2014-12-26 2024-07-05 埃莫里大学 N4-羟基胞苷和衍生物及与其相关的抗病毒用途
WO2016134058A1 (en) * 2015-02-18 2016-08-25 Abbvie Inc. Combinations useful to treat hepatitis c virus
WO2016134053A1 (en) * 2015-02-18 2016-08-25 Abbvie Inc. Anti-viral compounds
HK1247829A1 (zh) 2015-03-06 2018-10-05 Atea Pharmaceuticals, Inc. 用於治疗HCV的β-D-2'-脱氧-2'Α-氟-2'-β-C-取代-2-改性N6-取代的嘌呤核苷酸
CN108350016B (zh) 2015-09-02 2021-07-27 艾伯维公司 抗病毒四氢呋喃衍生物
PT3349758T (pt) 2015-09-16 2022-07-13 Gilead Sciences Inc Métodos para o tratamento de infeções pelo vírus arenaviridae
BR112018006206A2 (pt) * 2015-09-29 2018-10-09 Achillion Pharmaceuticals Inc composição, uso de uma combinação, forma de dosagem fixa farmacêutica, combinação de dosagem fixa, embalagem, e, uso de uma combinação de dose fixa
CN108602806B (zh) 2015-12-09 2022-07-12 研究三角协会 改进的爱帕琳肽受体(apj)激动剂及其用途
CN108473525A (zh) * 2016-01-04 2018-08-31 上海长森药业有限公司 氘代HCV NS5b抑制剂核苷酸衍生物及其用途
CA3029315A1 (en) 2016-06-24 2017-12-28 Emory University Phosphoramidates for the treatment of hepatitis b virus
LU100724B1 (en) 2016-07-14 2018-07-31 Atea Pharmaceuticals Inc Beta-d-2'-deoxy-2'-alpha-fluoro-2'-beta-c-substituted-4'-fluoro-n6-substituted-6-amino-2-substituted purine nucleotides for the treatment of hepatitis c virus infection
WO2018031818A2 (en) * 2016-08-12 2018-02-15 Alios Biopharma, Inc. Substituted nucleosides, nucleotides and analogs thereof
CN107759632A (zh) * 2016-08-19 2018-03-06 正大天晴药业集团股份有限公司 一种手性磷酸酯的制备方法
EP3512863B1 (en) 2016-09-07 2021-12-08 ATEA Pharmaceuticals, Inc. 2'-substituted-n6-substituted purine nucleotides for rna virus treatment
AU2017325870B2 (en) 2016-09-16 2021-07-22 Research Traingle Institute Tetrahydroisoquinoline kappa opioid antagonists
AU2017343638B2 (en) 2016-10-12 2021-12-09 Research Triangle Institute Heterocyclic apelin receptor (APJ) agonists and uses thereof
JP7071342B6 (ja) 2016-12-21 2023-12-20 リサーチ トライアングル インスティテュート 改善されたバイオアベイラビリティを有するジアリールプリン誘導体
CN108276463A (zh) * 2017-01-06 2018-07-13 米文君 一类新的化合物及其用途
EP4450129A3 (en) 2017-02-01 2025-03-19 ATEA Pharmaceuticals, Inc. Nucleotide hemi-sulfate salt for the treatment of hepatitis c virus
CN110869028B (zh) 2017-03-14 2023-01-20 吉利德科学公司 治疗猫冠状病毒感染的方法
KR20190141747A (ko) 2017-05-01 2019-12-24 길리애드 사이언시즈, 인코포레이티드 (S)-2-에틸부틸 2-(((S)-(((2R,3S,4R,5R)-5-(4-아미노피롤로[2,1-f] [1,2,4]트리아진-7-일)-5-시아노-3,4-디히드록시테트라히드로푸란-2-일)메톡시)(페녹시) 포스포릴)아미노)프로파노에이트의 결정질 형태
US10675296B2 (en) 2017-07-11 2020-06-09 Gilead Sciences, Inc. Compositions comprising an RNA polymerase inhibitor and cyclodextrin for treating viral infections
CN107987105B (zh) * 2017-11-24 2019-10-01 无锡微色谱生物科技有限公司 一种可用于皮肤敷料的h2s给体化合物、海绵敷料和制备方法
KR102139340B1 (ko) 2017-12-01 2020-07-29 주식회사 엘지생활건강 즉시 주름 개선 및 탄력 증진용 화장료 조성물
US11331331B2 (en) 2017-12-07 2022-05-17 Emory University N4-hydroxycytidine and derivatives and anti-viral uses related thereto
TW202012001A (zh) 2018-04-10 2020-04-01 美商亞堤製藥公司 C型肝炎病毒(hcv)感染硬化之患者的治療
CN110835358B (zh) * 2018-08-16 2022-08-05 上海复星星泰医药科技有限公司 一种索磷布韦中间体的制备方法
US12221447B2 (en) 2018-08-20 2025-02-11 Duke University Methods and compositions for drugs to treat ophthalmic diseases
CN110221064A (zh) * 2019-05-23 2019-09-10 南京农业大学 猪塞尼卡谷病毒elisa抗体检测方法及应用
CN118766947A (zh) 2020-01-27 2024-10-15 吉利德科学公司 用于治疗SARS CoV-2感染的方法
US10874687B1 (en) 2020-02-27 2020-12-29 Atea Pharmaceuticals, Inc. Highly active compounds against COVID-19
WO2021173713A1 (en) 2020-02-27 2021-09-02 Atea Pharmaceuticals, Inc. Highly active compounds against covid-19
CN111233929B (zh) * 2020-02-28 2023-02-28 成都阿奇生物医药科技有限公司 一种核苷类似物的氘代物及其制备方法和用途
CA3169340A1 (en) 2020-03-12 2021-09-16 Pavel R. Badalov Methods of preparing 1'-cyano nucleosides
JP7482250B2 (ja) 2020-04-06 2024-05-13 ギリアード サイエンシーズ， インコーポレイテッド １’－シアノ置換カルバヌクレオシド類似体の吸入製剤
CN111467363A (zh) * 2020-04-07 2020-07-31 中国科学院深圳先进技术研究院 索非布韦在制备预防和治疗冠状病毒的药物中的应用
PL4157272T3 (pl) 2020-05-29 2025-10-20 Gilead Sciences, Inc. Remdesiwir do leczenia zakażeń wirusowych
JP2023531524A (ja) 2020-06-24 2023-07-24 ギリアード サイエンシーズ， インコーポレイテッド １’－シアノヌクレオシド類似体及びその使用
LT4204421T (lt) 2020-08-27 2024-06-25 Gilead Sciences, Inc. Virusinių infekcijų gydymui skirti junginiai ir būdai
CN117500494A (zh) 2021-06-17 2024-02-02 阿堤亚制药公司 有利的抗hcv联合疗法
CN116217632A (zh) * 2021-12-06 2023-06-06 广州谷森制药有限公司 一种氘代胞苷衍生物的制备方法
US20230295172A1 (en) 2022-03-02 2023-09-21 Gilead Sciences, Inc. Compounds and methods for treatment of viral infections
CA3262284A1 (en) 2022-07-21 2024-01-25 Antiva Biosciences, Inc. Pharmaceutical compositions and forms for the treatment of human papillomavirus (HPV) infection and HPV-induced neoplasm
US12357577B1 (en) 2024-02-02 2025-07-15 Gilead Sciences, Inc. Pharmaceutical formulations and uses thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012040127A1 (en) * 2010-09-22 2012-03-29 Alios Biopharma, Inc. Substituted nucleotide analogs
WO2012142523A2 (en) * 2011-04-13 2012-10-18 Gilead Sciences, Inc. 1'-substituted pyrimidine n-nucleoside analogs for antiviral treatment
JP2012527477A (ja) * 2009-05-20 2012-11-08 ギリアド ファーマセット エルエルシー Ｎ−［（２’ｒ）−２’−デオキシ−２’−フルオロ−２’−メチル−ｐ−フェニル−５’−ウリジリル］−ｌ−アラニン１−メチルエチルエステルおよびその製造のためのプロセス

Family Cites Families (120)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3480613A (en) 1967-07-03 1969-11-25 Merck & Co Inc 2-c or 3-c-alkylribofuranosyl - 1-substituted compounds and the nucleosides thereof
US3792039A (en) 1971-12-27 1974-02-12 Miles Lab Poly 2'-fluoro-2'-deoxyuridylic acid
US5449664A (en) 1988-11-21 1995-09-12 Syntex (U.S.A.) Inc. Antiviral agents
US6423489B1 (en) 1992-09-10 2002-07-23 Isis Pharmaceuticals, Inc. Compositions and methods for treatment of Hepatitis C virus-associated diseases
US6391542B1 (en) 1992-09-10 2002-05-21 Isis Pharmaceuticals, Inc. Compositions and methods for treatment of Hepatitis C virus-associated diseases
JPH08506479A (ja) 1992-09-10 1996-07-16 財団法人化学及血清療法研究所 Ｃ型肝炎ウイルス関連疾患の治療のための組成物および方法
US6433159B1 (en) 1992-09-10 2002-08-13 Isis Pharmaceuticals, Inc. Compositions and methods for treatment of Hepatitis C virus associated diseases
US6174868B1 (en) 1992-09-10 2001-01-16 Isis Pharmaceuticals, Inc. Compositions and methods for treatment of hepatitis C virus-associated diseases
EP0719273B1 (en) 1993-09-17 2010-11-03 Gilead Sciences, Inc. Nucleotide analogs
US5798340A (en) 1993-09-17 1998-08-25 Gilead Sciences, Inc. Nucleotide analogs
US5656745A (en) 1993-09-17 1997-08-12 Gilead Sciences, Inc. Nucleotide analogs
CA2267279A1 (en) 1996-10-16 1998-04-23 Devron Averett Monocyclic l-nucleosides, analogs and uses thereof
US6316612B1 (en) 1997-08-22 2001-11-13 Ribozyme Pharmaceuticals, Inc. Xylofuranosly-containing nucleoside phosphoramidites and polynucleotides
US6054576A (en) 1997-10-02 2000-04-25 Ribozyme Pharmaceuticals, Inc. Deprotection of RNA
US6482932B1 (en) 1997-11-05 2002-11-19 Ribozyme Pharmaceuticals, Incorporated Nucleoside triphosphates and their incorporation into oligonucleotides
US6127535A (en) 1997-11-05 2000-10-03 Ribozyme Pharmaceuticals, Inc. Nucleoside triphosphates and their incorporation into oligonucleotides
US6528640B1 (en) 1997-11-05 2003-03-04 Ribozyme Pharmaceuticals, Incorporated Synthetic ribonucleic acids with RNAse activity
US6617438B1 (en) 1997-11-05 2003-09-09 Sirna Therapeutics, Inc. Oligoribonucleotides with enzymatic activity
CN1192102C (zh) 1998-01-23 2005-03-09 新生物生物公司 酶催化的治疗剂
US6030957A (en) 1998-06-29 2000-02-29 Wayne Hughes Institute Aryl phosphate derivatives of d4T having anti-HIV activity
MY164523A (en) 2000-05-23 2017-12-29 Univ Degli Studi Cagliari Methods and compositions for treating hepatitis c virus
CZ301182B6 (cs) 2000-05-26 2009-12-02 Idenix (Cayman) Limited Použití nukleosidových derivátu pro výrobu farmaceutických prostredku pro lécení infekcí vyvolaných flaviviry a pestiviry
US20030008841A1 (en) 2000-08-30 2003-01-09 Rene Devos Anti-HCV nucleoside derivatives
DK2251015T3 (da) 2000-10-18 2013-05-13 Gilead Pharmasset Llc Modificerede nukleotider til behandling af virusinfektioner og abnorm celleproliferation
US7105499B2 (en) 2001-01-22 2006-09-12 Merck & Co., Inc. Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase
SK286630B6 (sk) 2001-01-22 2009-02-05 Merck & Co., Inc. Nukleozidové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie
US8481712B2 (en) 2001-01-22 2013-07-09 Merck Sharp & Dohme Corp. Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase
AU2002316118A1 (en) 2001-05-16 2002-11-25 Micrologix Biotech, Inc. Nucleic acid-based compounds and methods of use thereof
GB0114286D0 (en) 2001-06-12 2001-08-01 Hoffmann La Roche Nucleoside Derivatives
WO2003062256A1 (en) 2002-01-17 2003-07-31 Ribapharm Inc. 2'-beta-modified-6-substituted adenosine analogs and their use as antiviral agents
US20040002476A1 (en) 2002-02-14 2004-01-01 Stuyver Lieven J. Modified fluorinated nucleoside analogues
CA2484921A1 (en) 2002-05-06 2003-11-13 Genelabs Technologies, Inc. Nucleoside derivatives for treating hepatitis c virus infection
WO2003099840A1 (en) 2002-05-24 2003-12-04 Isis Pharmaceuticals, Inc. Oligonucleotides having modified nucleoside units
MXPA04012802A (es) 2002-06-28 2005-04-19 Idenix Cayman Ltd Ester 2'-c-metil-3'-o-l-valina de ribofuranosil-citidina para el tratamiento de infecciones por flaviviridae.
US7608600B2 (en) 2002-06-28 2009-10-27 Idenix Pharmaceuticals, Inc. Modified 2′ and 3′-nucleoside prodrugs for treating Flaviviridae infections
CN104193791A (zh) 2002-06-28 2014-12-10 埃迪尼克斯医药公司 用于治疗黄病毒感染的修饰的2’和3’-核苷前药
NZ537662A (en) 2002-06-28 2007-10-26 Idenix Cayman Ltd 2'-C-methyl-3'-O-L-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections
EP1545558A4 (en) 2002-09-24 2010-02-17 Koronis Pharmaceuticals Inc 1, 3, 5-TRIAZINES FOR THE TREATMENT OF VIRAL DISEASES
US7598373B2 (en) 2002-12-12 2009-10-06 Idenix Pharmaceuticals, Inc. Process for the production of 2-C-methyl-D-ribonolactone
AR043006A1 (es) 2003-02-12 2005-07-13 Merck & Co Inc Proceso para preparar ribonucleosidos ramificados
US20040229839A1 (en) 2003-05-14 2004-11-18 Biocryst Pharmaceuticals, Inc. Substituted nucleosides, preparation thereof and use as inhibitors of RNA viral polymerases
WO2004106356A1 (en) 2003-05-27 2004-12-09 Syddansk Universitet Functionalized nucleotide derivatives
EP2345659A1 (en) 2003-05-30 2011-07-20 Pharmasset, Inc. Modified fluorinated nucleoside analogues
GB0317009D0 (en) 2003-07-21 2003-08-27 Univ Cardiff Chemical compounds
EP1680436A1 (en) 2003-10-27 2006-07-19 Genelabs Technologies, Inc. Nucleoside compounds for treating viral infections
KR100570697B1 (ko) 2004-09-24 2006-04-12 삼성에스디아이 주식회사 연료 전지 시스템 및 이에 사용되는 개질기
WO2006121820A1 (en) 2005-05-05 2006-11-16 Valeant Research & Development Phosphoramidate prodrugs for treatment of viral infection
WO2007027248A2 (en) 2005-05-16 2007-03-08 Valeant Research & Development 3', 5' - cyclic nucleoside analogues for treatment of hcv
WO2006133353A2 (en) 2005-06-08 2006-12-14 The University Of North Carolina At Chapel Hill Methods of facilitating neural cell survival using non-peptide and peptide bdnf neurotrophin mimetics
JP2009504704A (ja) 2005-08-15 2009-02-05 エフ．ホフマン−ラ ロシュ アーゲー 抗ウイルス４′−置換プロヌクレオチドホスホルアミダート
US7888330B2 (en) 2005-11-09 2011-02-15 Wayne State University Phosphoramidate derivatives of FAU
US8236904B2 (en) 2005-12-28 2012-08-07 Ethicon, Inc. Bioabsorbable polymer compositions exhibiting enhanced crystallization and hydrolysis rates
EP1987050A2 (en) 2006-02-14 2008-11-05 Merck & Co., Inc. Nucleoside aryl phosphoramidates for the treatment of rna-dependent rna viral infection
US7842672B2 (en) 2006-07-07 2010-11-30 Gilead Sciences, Inc. Phosphonate inhibitors of HCV
EP2041156B1 (en) 2006-07-13 2013-11-20 Achillion Pharmaceuticals, Inc. 4-amino-4-oxobutanoyl peptides as inhibitors of viral replication
GB0623493D0 (en) 2006-11-24 2007-01-03 Univ Cardiff Chemical compounds
WO2008079206A1 (en) 2006-12-20 2008-07-03 Merck & Co., Inc. Nucleoside cyclic phosphoramidates for the treatment of rna-dependent rna viral infection
CA2672944A1 (en) 2006-12-22 2008-07-03 Ablynx N.V. Amino acid sequences directed against chemokines and polypeptides comprising the same for the treatment of chemokine-related diseases and disorders
US7951789B2 (en) 2006-12-28 2011-05-31 Idenix Pharmaceuticals, Inc. Compounds and pharmaceutical compositions for the treatment of viral infections
JP2010515680A (ja) 2007-01-05 2010-05-13 メルク・シャープ・エンド・ドーム・コーポレイション Ｒｎａ依存性ｒｎａウイルス感染症の治療用としてのヌクレオシドアリールホスホロアミデート
MX2009008139A (es) 2007-01-31 2009-08-12 Alios Biopharma Inc Derivdos de 2-5a y su uso como agentes anti-cancer, antivirales y anti-parasitos.
US8324179B2 (en) 2007-02-09 2012-12-04 Gilead Sciences, Inc. Nucleoside analogs for antiviral treatment
US7964580B2 (en) 2007-03-30 2011-06-21 Pharmasset, Inc. Nucleoside phosphoramidate prodrugs
EP1980568A1 (de) 2007-04-13 2008-10-15 Eberhard Karls Universität Tübingen Ethinylierte Heterodinucleosidphosphatanaloga, Verfahren zu deren Herstellung und deren Verwendung
GB0709791D0 (en) 2007-05-22 2007-06-27 Angeletti P Ist Richerche Bio Antiviral agents
WO2009058800A2 (en) 2007-10-29 2009-05-07 President And Fellows Of Harvard College Synthesis of nucleosides
US20090318380A1 (en) 2007-11-20 2009-12-24 Pharmasset, Inc. 2',4'-substituted nucleosides as antiviral agents
WO2009086192A1 (en) 2007-12-21 2009-07-09 Alios Biopharma, Inc. Biodegradable phosphate protected nucleotide derivatives and their use as cancer, anti viral and anti parasitic agents
US20090181921A1 (en) 2007-12-21 2009-07-16 Alios Biopharma Inc. 2-5a analogs and their methods of use
CA2722308C (en) 2008-04-15 2024-02-27 Rfs Pharma, Llc. Nucleoside derivatives for treatment of caliciviridae infections, including norovirus infections
WO2010014134A1 (en) 2008-07-02 2010-02-04 Idenix Pharamaceuticals, Inc. Compounds and pharmaceutical compositions for the treatment of viral infections
ES2487525T3 (es) 2008-08-08 2014-08-21 Scinopharm Taiwan Ltd. Procedimiento para preparar nucleósidos de 5-azacitosina y sus derivados
GB0815968D0 (en) 2008-09-03 2008-10-08 Angeletti P Ist Richerche Bio Antiviral agents
WO2010030858A1 (en) 2008-09-15 2010-03-18 Enanta Pharmaceuticals, Inc. 4'-allene-substituted nucleoside derivatives
PA8852101A1 (es) 2008-12-08 2010-07-27 Medivir Ab Nucleótidos uracil ciclopropílicos
AU2009324643B2 (en) 2008-12-10 2014-08-28 Achillion Pharmaceuticals, Inc. New 4-amino-4-oxobutanoyl peptides as inhibitors of viral replication
CN102245598B (zh) 2008-12-10 2014-01-29 艾其林医药公司 病毒复制抑制剂4-氨基-4-氧代丁酰基肽环状类似物
JP2012514657A (ja) 2009-01-09 2012-06-28 ユニバーシテイ・カレツジ・オブ・カーデイフ・コンサルタンツ・リミテツド ウィルス感染を治療するためのグアノシンヌクレオシド化合物のホスホルアミダート誘導体
US8609627B2 (en) 2009-02-06 2013-12-17 Rfs Pharma, Llc Purine nucleoside monophosphate prodrugs for treatment of cancer and viral infections
US20100240604A1 (en) 2009-03-20 2010-09-23 Alios Biopharma, Inc. Protected nucleotide analogs
US20100249068A1 (en) 2009-03-20 2010-09-30 Alios Biopharma, Inc. Substituted nucleoside and nucleotide analogs
JO3027B1 (ar) 2009-05-14 2016-09-05 Janssen Products Lp نيوكليوسيدات يوراسيل سبيرواوكسيتان
US8618076B2 (en) * 2009-05-20 2013-12-31 Gilead Pharmasset Llc Nucleoside phosphoramidates
WO2010135520A1 (en) 2009-05-20 2010-11-25 Chimerix, Inc. Compounds, compositions and methods for treating viral infection
WO2011097607A1 (en) 2010-02-08 2011-08-11 Southern Research Institute Anti-viral treatment and assay to screen for anti-viral agent
SMT201700412T1 (it) 2010-03-31 2017-11-15 Gilead Pharmasset Llc Procedimento per la cristallizzazione di (s)-isopropil 2-(((s)-(perfluorofenossi)(fenossi)fosforil)ammino)propanoato
US8563530B2 (en) 2010-03-31 2013-10-22 Gilead Pharmassel LLC Purine nucleoside phosphoramidate
BR112012024661A2 (pt) 2010-04-01 2015-09-15 Centre Nat Rech Scient composto, composição farmacêutica e método de tratamento de um hospedeiro infectado com vírus de hepatite c
KR101995598B1 (ko) * 2010-07-19 2019-07-02 길리애드 사이언시즈, 인코포레이티드 부분입체 이성질성으로 순수한 포스포라미데이트 전구약물의 제조 방법
ES2514670T3 (es) 2010-08-04 2014-10-28 Herbert Schott Fármacos dobles de bisfosfonato dirigidos al hueso
CA2812962C (en) 2010-09-22 2020-03-31 Alios Biopharma, Inc. Azido nucleosides and nucleotide analogs
WO2012040126A1 (en) 2010-09-22 2012-03-29 Alios Biopharma, Inc. Substituted nucleotide analogs
WO2012041965A1 (en) 2010-09-29 2012-04-05 Universidad Nacional De Quilmes Process for producing dialkylphosphotriesters of nucleosides by enzymatic transesterification and deprotection thereof for producing nucleoside monophosphates
WO2012062869A1 (en) 2010-11-10 2012-05-18 Janssen Products, Lp Uracyl spirooxetane nucleoside phosphoramidates
PT3042910T (pt) 2010-11-30 2019-04-16 Gilead Pharmasset Llc 2'-espiro-nucleósidos para utilização na terapia da hepatite c
AU2011349278C1 (en) 2010-12-22 2017-01-19 Alios Biopharma, Inc. Cyclic nucleotide analogs
EP2658857B1 (en) 2010-12-29 2016-11-02 Inhibitex, Inc. Substituted purine nucleosides, phosphoroamidate and phosphorodiamidate derivatives for treatment of viral infections
US9156874B2 (en) 2011-01-03 2015-10-13 Nanjing Molecular Research, Inc. Double-liver-targeting phosphoramidate and phosphonoamidate prodrugs
WO2012094248A1 (en) 2011-01-03 2012-07-12 Nanjing Molecular Research, Inc. O-(substituted benzyl) phosphoramidate compounds and therapeutic use
US9085599B2 (en) 2011-03-16 2015-07-21 Enanta Pharmaceuticals, Inc. 2′allene-substituted nucleoside derivatives
US9243025B2 (en) 2011-03-31 2016-01-26 Idenix Pharmaceuticals, Llc Compounds and pharmaceutical compositions for the treatment of viral infections
WO2012142075A1 (en) 2011-04-13 2012-10-18 Merck Sharp & Dohme Corp. 2'-azido substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases
EA201391519A1 (ru) 2011-04-13 2014-03-31 Мерк Шарп И Доум Корп. 2'-замещенные нуклеозидные производные и способы их применения для лечения вирусных заболеваний
US20140212382A1 (en) 2011-05-19 2014-07-31 Emory University Purine monophosphate prodrugs for treatment of viral infections
EP3059241B1 (en) 2011-05-27 2017-11-01 Achillion Pharmaceuticals, Inc. Intermediates in the preparation of a bis(benzimidazole)cyclophane derivative
JP2014520772A (ja) 2011-06-30 2014-08-25 ステラ・アンパルトセルスカブ Ｈｃｖ併用療法
WO2013009737A1 (en) 2011-07-13 2013-01-17 Merck Sharp & Dohme Corp. 5'-substituted nucleoside analogs and methods of use thereof for the treatment of viral diseases
EP2731434A4 (en) 2011-07-13 2014-12-31 Merck Sharp & Dohme 5'-SUBSTITUTED NUCLEOSIDE DERIVATIVES AND METHOD FOR THEIR USE FOR THE TREATMENT OF VIRUS DISEASES
WO2013024155A1 (en) 2011-08-17 2013-02-21 Inserm (Institut National De La Sante Et De La Recherche Medicale) Combinations of anti-hcv-entry factor antibodies and direct acting antivirals for the treatment and the prevention of hcv infection
PH12014500386A1 (en) 2011-08-24 2019-10-07 Glaxosmithkline Llc Combination treatment for hepatitis c
AR088441A1 (es) 2011-09-12 2014-06-11 Idenix Pharmaceuticals Inc Compuestos de carboniloximetilfosforamidato sustituido y composiciones farmaceuticas para el tratamiento de infecciones virales
AU2012308900A1 (en) 2011-09-12 2013-05-09 Idenix Pharmaceuticals, Inc. Compounds and pharmaceutical compositions for the treatment of viral infections
EP2755689A1 (en) 2011-09-16 2014-07-23 AbbVie Inc. Methods for treating hcv
US8575119B2 (en) 2011-09-23 2013-11-05 Enanta Pharmaceuticals, Inc. 2′-chloroacetylenyl substituted nucleoside derivatives
WO2013056046A1 (en) 2011-10-14 2013-04-18 Idenix Pharmaceuticals, Inc. Substituted 3',5'-cyclic phosphates of purine nucleotide compounds and pharmaceutical compositions for the treatment of viral infections
WO2013066991A1 (en) 2011-10-31 2013-05-10 Inhibitex, Inc. Crystalline solvates of nucleoside phosphoroamidates, their stereoselective preparation, novel intermediates thereof, and their use in the treatment of viral disease
WO2013090420A2 (en) 2011-12-12 2013-06-20 Catabasis Pharmaceuticals, Inc. Fatty acid antiviral conjugates and their uses
US20130172240A1 (en) 2011-12-28 2013-07-04 Abbvie Inc. Methods for treating hcv
US20130172239A1 (en) 2011-12-29 2013-07-04 Abbvie Inc. Solid compositions
WO2013133927A1 (en) 2012-02-13 2013-09-12 Idenix Pharmaceuticals, Inc. Pharmaceutical compositions of 2'-c-methyl-guanosine, 5'-[2-[(3-hydroxy-2,2-dimethyl-1-oxopropyl)thio]ethyl n-(phenylmethyl)phosphoramidate]

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012527477A (ja) * 2009-05-20 2012-11-08 ギリアド ファーマセット エルエルシー Ｎ−［（２’ｒ）−２’−デオキシ−２’−フルオロ−２’−メチル−ｐ−フェニル−５’−ウリジリル］−ｌ−アラニン１−メチルエチルエステルおよびその製造のためのプロセス
WO2012040127A1 (en) * 2010-09-22 2012-03-29 Alios Biopharma, Inc. Substituted nucleotide analogs
WO2012142523A2 (en) * 2011-04-13 2012-10-18 Gilead Sciences, Inc. 1'-substituted pyrimidine n-nucleoside analogs for antiviral treatment

Also Published As

Publication number Publication date
AU2014250762A1 (en) 2015-10-29
EP2984097B1 (en) 2017-03-29
KR20160002896A (ko) 2016-01-08
RU2015148010A (ru) 2017-05-15
WO2014169278A1 (en) 2014-10-16
RU2015148006A3 (OSRAM) 2018-08-01
RU2015148006A (ru) 2017-05-18
JP2016518359A (ja) 2016-06-23
US20140309189A1 (en) 2014-10-16
BR112015025716A2 (pt) 2017-07-18
CN105705511A (zh) 2016-06-22
US9447132B2 (en) 2016-09-20
BR112015025766A2 (pt) 2017-10-17
WO2014169280A3 (en) 2014-12-18
KR20160003700A (ko) 2016-01-11
AU2014250764A1 (en) 2015-10-29
EP2984098A2 (en) 2016-02-17
CA2909270A1 (en) 2014-10-16
WO2014169280A2 (en) 2014-10-16
CA2909273A1 (en) 2014-10-16
CN105377868A (zh) 2016-03-02
RU2015148010A3 (OSRAM) 2018-04-28
EP2984097A1 (en) 2016-02-17
US20140309164A1 (en) 2014-10-16
ES2623287T3 (es) 2017-07-10

Similar Documents

Publication Publication Date Title
JP2016522172A (ja) Ｈｃｖを治療するのに有用な重水素化されたヌクレオシドプロドラッグ
EP3980400B1 (en) Peptidomimetics for the treatment of coronavirus and picornavirus infections
RU2519947C2 (ru) Соединения и фармацевтические композиции для лечения вирусных инфекций
JP6198721B2 (ja) Ｈｃｖ感染症を治療するのに有用な置換されたアリファン、シクロファン、ヘテラファン、ヘテロファン、ヘテロ−ヘテラファンおよびメタロセン
US20170233428A1 (en) Nucleoside analogs for treatment of the flaviviridae family of viruses and cancer
CA2818853A1 (en) 2'-spirocyclo-nucleosides for use in therapy of hcv or dengue virus
KR20200140865A (ko) 간경변증을 갖는 hcv 감염 환자의 치료
EP2953462B1 (en) Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis c
JP2017502975A (ja) ウラシルヌクレオチド類縁体、それらの製造方法、およびそれらの用途
WO2016044243A1 (en) Pyrimidine nucleoside phosphoramidate
BR112019017843A2 (pt) pró-fármaco de um inibidor de polimerase ns5b de hcv e método de produção e utilização do mesmo
RU2650610C1 (ru) Противовирусная композиция и способ ее применения
HK1156038B (en) Compounds and pharmaceutical compositions for the treatment of viral infections

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20170413

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20170413

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20180119

A02 Decision of refusal

Free format text: JAPANESE INTERMEDIATE CODE: A02

Effective date: 20180807