JP7600140B2 - Kit及びpdgfra媒介性疾患を治療するための組成物及び方法 - Google Patents

Kit及びpdgfra媒介性疾患を治療するための組成物及び方法 Download PDF

Info

Publication number
JP7600140B2
JP7600140B2 JP2021560255A JP2021560255A JP7600140B2 JP 7600140 B2 JP7600140 B2 JP 7600140B2 JP 2021560255 A JP2021560255 A JP 2021560255A JP 2021560255 A JP2021560255 A JP 2021560255A JP 7600140 B2 JP7600140 B2 JP 7600140B2
Authority
JP
Japan
Prior art keywords
compound
mmol
pharma
foregoing
hydrogen
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.)
Active
Application number
JP2021560255A
Other languages
English (en)
Japanese (ja)
Other versions
JP2022526850A5 (https=
JP2022526850A (ja
Inventor
キム,ジョセフ・エル
ディニーン,トーマス・エイ
グジ,ティモシー
Original Assignee
ブループリント メディシンズ コーポレイション
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=70416596&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=JP7600140(B2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by ブループリント メディシンズ コーポレイション filed Critical ブループリント メディシンズ コーポレイション
Publication of JP2022526850A publication Critical patent/JP2022526850A/ja
Publication of JP2022526850A5 publication Critical patent/JP2022526850A5/ja
Priority to JP2024210028A priority Critical patent/JP2025029094A/ja
Application granted granted Critical
Publication of JP7600140B2 publication Critical patent/JP7600140B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/53Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/04Anorexiants; Antiobesity agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Child & Adolescent Psychology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
JP2021560255A 2019-04-12 2020-04-08 Kit及びpdgfra媒介性疾患を治療するための組成物及び方法 Active JP7600140B2 (ja)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2024210028A JP2025029094A (ja) 2019-04-12 2024-12-03 Kit及びpdgfra媒介性疾患を治療するための組成物及び方法

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US201962833529P 2019-04-12 2019-04-12
US62/833,529 2019-04-12
US201962911016P 2019-10-04 2019-10-04
US62/911,016 2019-10-04
US201962930240P 2019-11-04 2019-11-04
US62/930,240 2019-11-04
PCT/US2020/027177 WO2020210293A1 (en) 2019-04-12 2020-04-08 Pyrrolotriazine derivatives for treating kit- and pdgfra-mediated diseases

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2024210028A Division JP2025029094A (ja) 2019-04-12 2024-12-03 Kit及びpdgfra媒介性疾患を治療するための組成物及び方法

Publications (3)

Publication Number Publication Date
JP2022526850A JP2022526850A (ja) 2022-05-26
JP2022526850A5 JP2022526850A5 (https=) 2023-04-17
JP7600140B2 true JP7600140B2 (ja) 2024-12-16

Family

ID=70416596

Family Applications (2)

Application Number Title Priority Date Filing Date
JP2021560255A Active JP7600140B2 (ja) 2019-04-12 2020-04-08 Kit及びpdgfra媒介性疾患を治療するための組成物及び方法
JP2024210028A Pending JP2025029094A (ja) 2019-04-12 2024-12-03 Kit及びpdgfra媒介性疾患を治療するための組成物及び方法

Family Applications After (1)

Application Number Title Priority Date Filing Date
JP2024210028A Pending JP2025029094A (ja) 2019-04-12 2024-12-03 Kit及びpdgfra媒介性疾患を治療するための組成物及び方法

Country Status (33)

Country Link
US (2) US12552795B2 (https=)
EP (2) EP4424312A3 (https=)
JP (2) JP7600140B2 (https=)
KR (1) KR102875260B1 (https=)
CN (1) CN113939515B (https=)
AU (1) AU2020272743B2 (https=)
BR (1) BR112021020441A2 (https=)
CA (1) CA3136802A1 (https=)
CL (1) CL2021002656A1 (https=)
CO (1) CO2021015113A2 (https=)
DK (1) DK3953357T3 (https=)
EC (1) ECSP21080096A (https=)
ES (1) ES2980811T3 (https=)
FI (1) FI3953357T3 (https=)
HR (1) HRP20240702T1 (https=)
HU (1) HUE067299T2 (https=)
IL (1) IL287168B2 (https=)
LT (1) LT3953357T (https=)
MA (1) MA55604B1 (https=)
MD (1) MD3953357T2 (https=)
MX (1) MX2021012469A (https=)
MY (1) MY209048A (https=)
PE (1) PE20212331A1 (https=)
PH (1) PH12021552568A1 (https=)
PL (1) PL3953357T3 (https=)
PT (1) PT3953357T (https=)
RS (1) RS65644B1 (https=)
SG (1) SG11202111244XA (https=)
SI (1) SI3953357T1 (https=)
SM (1) SMT202400229T1 (https=)
TW (1) TWI857043B (https=)
WO (1) WO2020210293A1 (https=)
ZA (1) ZA202108104B (https=)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2025029094A (ja) * 2019-04-12 2025-03-05 ブループリント メディシンズ コーポレイション Kit及びpdgfra媒介性疾患を治療するための組成物及び方法

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109970745B (zh) 2018-04-16 2020-12-08 深圳市塔吉瑞生物医药有限公司 取代的吡咯并三嗪类化合物及其药物组合物及其用途
US20230391780A1 (en) * 2020-10-14 2023-12-07 Blueprint Medicines Corporation Compositions and methods for treating kit- and pdgfra-mediated diseases
US20240010652A1 (en) * 2020-10-14 2024-01-11 Blueprint Medicines Corporation Compositions and methods for treating kit- and pdgfra-mediated diseases
HU231413B1 (hu) 2021-02-26 2023-08-28 Egis Gyógyszergyár Zrt. Eljárás avapritinib és intermedierek előállítására
AU2022231009A1 (en) * 2021-03-03 2023-09-21 Blueprint Medicines Corporation Synthetic methods and intermediates for producing compounds for treating kit- and pdgfra-mediated diseases
CN117794935A (zh) * 2021-03-10 2024-03-29 缆图药品公司 激酶抑制剂的盐和固体形式
JP2024509276A (ja) * 2021-03-10 2024-02-29 ブループリント メディシンズ コーポレイション キナーゼ阻害剤の塩及び固体形態
CN113278023B (zh) * 2021-07-22 2021-10-15 上海睿跃生物科技有限公司 含氮杂环化合物及其制备方法和应用
AU2022379973A1 (en) * 2021-11-08 2024-06-27 Progentos Therapeutics, Inc. Platelet-derived growth factor receptor (pdgfr) alpha inhibitors and uses thereof
WO2024171143A1 (en) 2023-02-17 2024-08-22 Assia Chemical Industries Ltd. Salts and solid forms of elenestinib

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016538257A (ja) 2013-10-17 2016-12-08 ブループリント メディシンズ コーポレイション Kitに関連する疾患を治療するために有用な組成物
WO2018183712A1 (en) 2017-03-31 2018-10-04 Blueprint Medicines Corporation Pyrrolo[1,2-b]pyridazine compounds and compositions useful for treating disorders related to kit and pdgfr

Family Cites Families (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS61238784A (ja) 1985-04-17 1986-10-24 Sumitomo Seiyaku Kk コハク酸イミド誘導体及びその酸付加塩
US6982265B1 (en) 1999-05-21 2006-01-03 Bristol Myers Squibb Company Pyrrolotriazine inhibitors of kinases
JP4649046B2 (ja) 1999-05-21 2011-03-09 ブリストル−マイヤーズ スクイブ カンパニー キナーゼのピロロトリアジン阻害剤
MXPA02003436A (es) 1999-10-07 2002-08-20 Amgen Inc Inhibidores de triazina cinasa.
SE0102616D0 (sv) 2001-07-25 2001-07-25 Astrazeneca Ab Novel compounds
PT1497019E (pt) 2002-04-23 2015-09-10 Bristol Myers Squibb Co Compostos de pirrolotriazina anilina úteis como inibidores de quinase
TW200508224A (en) 2003-02-12 2005-03-01 Bristol Myers Squibb Co Cyclic derivatives as modulators of chemokine receptor activity
US7468376B2 (en) 2003-02-27 2008-12-23 Palau Pharma, S.A. Pyrazolopyridine derivates
MY145634A (en) 2003-12-29 2012-03-15 Bristol Myers Squibb Co Pyrrolotriazine compounds as kinase inhibitors
WO2005117909A2 (en) 2004-04-23 2005-12-15 Exelixis, Inc. Kinase modulators and methods of use
WO2006028524A2 (en) 2004-04-29 2006-03-16 Pharmix Corporation Compositions and treatments for inhibiting kinase and/or hmg-coa reductase
UY28931A1 (es) 2004-06-03 2005-12-30 Bayer Pharmaceuticals Corp Derivados de pirrolotriazina utiles para tratar trastornos hiper-proliferativos y enfermedades asociadas con angiogenesis
US7173031B2 (en) 2004-06-28 2007-02-06 Bristol-Myers Squibb Company Pyrrolotriazine kinase inhibitors
JP5116687B2 (ja) 2005-11-02 2013-01-09 バイエル・ファルマ・アクチェンゲゼルシャフト がんおよび他の過剰増殖性疾患の処置のためのピロロ[2,1−f][1,2,4]トリアジン−4−イルアミンIGF−1Rキナーゼ阻害剤
US7348325B2 (en) 2005-11-30 2008-03-25 Bristol-Myers Squibb Company Pyrrolotriazine kinase inhibitors
DK1973910T3 (da) 2006-01-27 2013-08-12 Shanghai Hengrui Pharm Co Ltd Pyrrolo[3,2-c]pyridin-4-on-2-indolinon-proteinkinaseinhibitorer
HRP20140688T1 (hr) 2006-07-07 2014-10-24 Bristol-Myers Squibb Company Inhibitori piroltriazin kinaze
US8415340B2 (en) 2007-07-25 2013-04-09 Bristol-Myers Squibb Company Triazine kinase inhibitors
CA2716856C (en) 2008-03-20 2013-02-19 Amgen Inc. Aurora kinase modulators and method of use
WO2010022055A2 (en) 2008-08-20 2010-02-25 Amgen Inc. Inhibitors of voltage-gated sodium channels
JP2012529512A (ja) 2009-06-08 2012-11-22 アブラクシス バイオサイエンス リミテッド ライアビリティー カンパニー トリアジン誘導体類及びそれらの治療応用
CA2767008C (en) 2009-07-07 2018-01-30 Pathway Therapeutics, Inc. Pyrimidinyl and 1,3,5-triazinyl benzimidazoles and their use in cancer therapy
WO2011103196A1 (en) 2010-02-17 2011-08-25 Amgen Inc. Aryl carboxamide derivatives as sodium channel inhibitors for treatment of pain
US8609672B2 (en) 2010-08-27 2013-12-17 University Of The Pacific Piperazinylpyrimidine analogues as protein kinase inhibitors
CN102040494A (zh) 2010-11-12 2011-05-04 西北师范大学 对氟苯甲醛的制备方法
SG195100A1 (en) 2011-07-01 2013-12-30 Bayer Ip Gmbh Hydroxymethylaryl-substituted pyrrolotriazines as alk1 inhibitors
UY34484A (es) 2011-12-15 2013-07-31 Bayer Ip Gmbh Benzotienilo-pirrolotriazinas disustituidas y sus usos
EP2892534B8 (en) 2012-09-06 2021-09-15 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
MX365640B (es) 2012-12-21 2019-06-10 Plexxikon Inc Compuestos y metodos para la modulacion de quinasas y sus indicaciones.
WO2014160521A1 (en) 2013-03-15 2014-10-02 Blueprint Medicines Corporation Piperazine derivatives and their use as kit modulators
WO2015058129A1 (en) 2013-10-17 2015-04-23 Blueprint Medicines Corporation Compositions useful for treating disorders related to kit
US9688680B2 (en) 2014-08-04 2017-06-27 Blueprint Medicines Corporation Compositions useful for treating disorders related to kit
CN108026102A (zh) 2015-07-24 2018-05-11 蓝印药品公司 可用于治疗与kit和pdgfr相关的病症的化合物
SI3371171T1 (sl) 2015-11-02 2024-03-29 Blueprint Medicines Corporation Inhibitorji ret
AR110963A1 (es) 2017-02-07 2019-05-22 Dae Woong Pharma Compuestos heterocíclicos, su método de preparación y composición farmacéutica que los comprende
KR102398659B1 (ko) 2017-03-17 2022-05-16 주식회사 대웅제약 카이네이즈 저해제로서의 피롤로트리아진 유도체
CN109400610A (zh) 2017-08-18 2019-03-01 浙江海正药业股份有限公司 吡咯并三嗪类衍生物、其制备方法及其在医药上的用途
CN108191874B (zh) 2018-01-16 2019-11-29 成都施贝康生物医药科技有限公司 一种C-Kit抑制剂及其应用
CN109970745B (zh) 2018-04-16 2020-12-08 深圳市塔吉瑞生物医药有限公司 取代的吡咯并三嗪类化合物及其药物组合物及其用途
CR20200588A (es) 2018-05-04 2021-06-24 Inflazome Ltd Compuestos novedosos
US20220010382A1 (en) 2018-11-12 2022-01-13 Blueprint Medicines Corporation Avapritinib resistance of kit mutants
MA54526A (fr) 2018-12-20 2022-03-30 Pfizer NOUVELLES FORMES POLYMORPHES D'UN INHIBITEUR DE TGFBeta
BR112021020441A2 (pt) * 2019-04-12 2021-12-14 Blueprint Medicines Corp Derivados de pirrolotriazina para tratar doenças mediadas por kit e pdgfra
TWI771766B (zh) 2019-10-04 2022-07-21 美商輝瑞股份有限公司 二醯基甘油醯基轉移酶2 抑制劑
CN110938077B (zh) 2019-12-25 2021-04-27 武汉九州钰民医药科技有限公司 合成Avapritinib的方法
CN110950872A (zh) 2019-12-25 2020-04-03 武汉九州钰民医药科技有限公司 制备靶向抗癌药avapritinib的方法
US20230391780A1 (en) 2020-10-14 2023-12-07 Blueprint Medicines Corporation Compositions and methods for treating kit- and pdgfra-mediated diseases

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016538257A (ja) 2013-10-17 2016-12-08 ブループリント メディシンズ コーポレイション Kitに関連する疾患を治療するために有用な組成物
WO2018183712A1 (en) 2017-03-31 2018-10-04 Blueprint Medicines Corporation Pyrrolo[1,2-b]pyridazine compounds and compositions useful for treating disorders related to kit and pdgfr

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2025029094A (ja) * 2019-04-12 2025-03-05 ブループリント メディシンズ コーポレイション Kit及びpdgfra媒介性疾患を治療するための組成物及び方法

Also Published As

Publication number Publication date
US20220153748A1 (en) 2022-05-19
ZA202108104B (en) 2024-02-28
US12552795B2 (en) 2026-02-17
US20200325141A1 (en) 2020-10-15
JP2025029094A (ja) 2025-03-05
IL287168A (en) 2021-12-01
WO2020210293A1 (en) 2020-10-15
CL2021002656A1 (es) 2022-08-26
CN113939515A (zh) 2022-01-14
PL3953357T3 (pl) 2024-09-02
CA3136802A1 (en) 2020-10-15
EP4424312A3 (en) 2025-01-08
FI3953357T3 (fi) 2024-07-15
EP3953357A1 (en) 2022-02-16
BR112021020441A2 (pt) 2021-12-14
CO2021015113A2 (es) 2022-02-28
EP3953357B1 (en) 2024-04-17
TWI857043B (zh) 2024-10-01
MY209048A (en) 2025-06-18
KR20220025704A (ko) 2022-03-03
SI3953357T1 (sl) 2024-08-30
ECSP21080096A (es) 2022-02-25
US10829493B2 (en) 2020-11-10
TW202104231A (zh) 2021-02-01
AU2020272743B2 (en) 2025-10-16
HRP20240702T1 (hr) 2024-08-16
DK3953357T3 (en) 2024-06-10
PH12021552568A1 (en) 2022-07-04
JP2022526850A (ja) 2022-05-26
PT3953357T (pt) 2024-07-24
MA55604A (fr) 2022-02-16
IL287168B1 (en) 2025-06-01
SMT202400229T1 (it) 2024-07-09
PE20212331A1 (es) 2021-12-14
RS65644B1 (sr) 2024-07-31
AU2020272743A1 (en) 2021-11-11
HUE067299T2 (hu) 2024-10-28
ES2980811T3 (es) 2024-10-03
MD3953357T2 (ro) 2024-09-30
SG11202111244XA (en) 2021-11-29
KR102875260B1 (ko) 2025-10-23
MA55604B1 (fr) 2024-08-30
CN113939515B (zh) 2024-06-18
EP4424312A2 (en) 2024-09-04
IL287168B2 (en) 2025-10-01
LT3953357T (lt) 2024-07-25
MX2021012469A (es) 2022-01-18

Similar Documents

Publication Publication Date Title
JP7600140B2 (ja) Kit及びpdgfra媒介性疾患を治療するための組成物及び方法
TWI418554B (zh) 結晶形(r)-(e)-2-(4-(2-(5-(1-(3,5-二氯吡啶-4-基)乙氧基)-1h-吲唑-3-基)乙烯基)-1h-吡唑-1-基)乙醇
TW201940472A (zh) Erbb/btk抑制劑
WO2016022569A1 (en) Compositions useful for treating disorders related to kit
CN116600808A (zh) 一类作为kras突变体g12c抑制剂的四氢萘啶类衍生物、其制备方法及其应用
CN117098760B (zh) 用于治疗kit和pdgfra介导的疾病的组合物和方法
WO2022081626A1 (en) Compositions and methods for treating kit-and pdgfra-mediated diseases
RU2817354C2 (ru) Композиции и способы лечения kit- и pdgfra-опосредованных заболеваний
HK40071629B (en) Pyrrolotriazine derivatives for treating kit- and pdgfra-mediated diseases
HK40071629A (en) Pyrrolotriazine derivatives for treating kit- and pdgfra-mediated diseases
CN116217561A (zh) 一类具有二甲基异吲哚酮结构的新型激酶抑制剂及其制备方法和用途
CN117715642A (zh) 杂环化合物和使用方法
CN122003414A (zh) 作为kras降解剂的取代三环化合物
WO2024254490A1 (en) Pyrazolo-pyrimidinone compounds for use in methods of inhibiting wee1 a kinase
HK1207374B (en) Imidazo[1,2-b]pyridazine derivatives as kinase inhibitors
HK1207374A1 (en) Imidazo[1,2-b]pyridazine derivatives as kinase inhibitors

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20230407

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20230407

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20240502

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20240802

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20241105

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20241204

R150 Certificate of patent or registration of utility model

Ref document number: 7600140

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150