JP6568060B2 - 黒色腫の治療のための組合せ医薬 - Google Patents

黒色腫の治療のための組合せ医薬 Download PDF

Info

Publication number
JP6568060B2
JP6568060B2 JP2016524936A JP2016524936A JP6568060B2 JP 6568060 B2 JP6568060 B2 JP 6568060B2 JP 2016524936 A JP2016524936 A JP 2016524936A JP 2016524936 A JP2016524936 A JP 2016524936A JP 6568060 B2 JP6568060 B2 JP 6568060B2
Authority
JP
Japan
Prior art keywords
melanoma
braf
compound
inhibitor
effective amount
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
JP2016524936A
Other languages
English (en)
Japanese (ja)
Other versions
JP2016525097A5 (enExample
JP2016525097A (ja
Inventor
アガーワル,ヴィーナ
ペリヤサミ,ギリドハラン
ラトス,マギー
シュリーヴァスタヴァ,アンキタ
シュリニヴァーサ,スリーシャ
Original Assignee
ピラマル エンタープライズイズ リミテッド
ピラマル エンタープライズイズ リミテッド
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 ピラマル エンタープライズイズ リミテッド, ピラマル エンタープライズイズ リミテッド filed Critical ピラマル エンタープライズイズ リミテッド
Publication of JP2016525097A publication Critical patent/JP2016525097A/ja
Publication of JP2016525097A5 publication Critical patent/JP2016525097A5/ja
Application granted granted Critical
Publication of JP6568060B2 publication Critical patent/JP6568060B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4025Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
    • 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
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/04Antineoplastic agents specific for metastasis
    • 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)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oncology (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
JP2016524936A 2013-07-12 2014-07-11 黒色腫の治療のための組合せ医薬 Active JP6568060B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361845749P 2013-07-12 2013-07-12
US61/845,749 2013-07-12
PCT/IB2014/063022 WO2015004636A1 (en) 2013-07-12 2014-07-11 A pharmaceutical combination for the treatment of melanoma

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2019141995A Division JP2019206565A (ja) 2013-07-12 2019-08-01 黒色腫の治療のための組合せ医薬

Publications (3)

Publication Number Publication Date
JP2016525097A JP2016525097A (ja) 2016-08-22
JP2016525097A5 JP2016525097A5 (enExample) 2017-08-10
JP6568060B2 true JP6568060B2 (ja) 2019-08-28

Family

ID=52279411

Family Applications (5)

Application Number Title Priority Date Filing Date
JP2016524936A Active JP6568060B2 (ja) 2013-07-12 2014-07-11 黒色腫の治療のための組合せ医薬
JP2019141995A Pending JP2019206565A (ja) 2013-07-12 2019-08-01 黒色腫の治療のための組合せ医薬
JP2020152028A Pending JP2021001186A (ja) 2013-07-12 2020-09-10 黒色腫の治療のための組合せ医薬
JP2022026851A Pending JP2022068335A (ja) 2013-07-12 2022-02-24 黒色腫の治療のための組合せ医薬
JP2023210858A Pending JP2024037891A (ja) 2013-07-12 2023-12-14 黒色腫の治療のための組合せ医薬

Family Applications After (4)

Application Number Title Priority Date Filing Date
JP2019141995A Pending JP2019206565A (ja) 2013-07-12 2019-08-01 黒色腫の治療のための組合せ医薬
JP2020152028A Pending JP2021001186A (ja) 2013-07-12 2020-09-10 黒色腫の治療のための組合せ医薬
JP2022026851A Pending JP2022068335A (ja) 2013-07-12 2022-02-24 黒色腫の治療のための組合せ医薬
JP2023210858A Pending JP2024037891A (ja) 2013-07-12 2023-12-14 黒色腫の治療のための組合せ医薬

Country Status (12)

Country Link
US (4) US11007174B2 (enExample)
EP (1) EP3019166B1 (enExample)
JP (5) JP6568060B2 (enExample)
CN (3) CN117731786A (enExample)
AR (1) AR096892A1 (enExample)
AU (1) AU2014288857B2 (enExample)
CA (1) CA2917742C (enExample)
DK (1) DK3019166T3 (enExample)
ES (1) ES2733929T3 (enExample)
IL (1) IL243572B (enExample)
TW (4) TWI839690B (enExample)
WO (1) WO2015004636A1 (enExample)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI839690B (zh) 2013-07-12 2024-04-21 印度商皮拉馬爾企業有限公司 治療黑色素瘤的藥物組合的用途
WO2016197129A1 (en) 2015-06-05 2016-12-08 The Board Of Trustees Of The University Of Illinois Pac-1 combination therapy
CN108135854B (zh) * 2015-06-30 2022-03-11 基因泰克公司 含有药物的立即释放片剂和用于形成片剂的方法
JP6987084B2 (ja) * 2016-03-16 2021-12-22 ディセルナ ファーマシューティカルズ インコーポレイテッド β−カテニン関連疾患又は障害の治療のための組成物及び方法
AU2018209164B2 (en) 2017-01-17 2021-11-04 Heparegenix Gmbh Protein kinase inhibitors for promoting liver regeneration or reducing or preventing hepatocyte death
CN110799245B (zh) * 2017-05-16 2022-08-09 生物医学谷探索股份有限公司 用于治疗具有非典型braf突变的癌症的组合物和方法
AU2018368453B2 (en) 2017-11-17 2024-05-30 The Board Of Trustees Of The University Of Illinois Cancer therapy by degrading dual MEK signaling
CN107827726B (zh) * 2017-11-28 2020-09-15 辽宁中医药大学 马齿苋中化合物Oleracone E及其提取分离方法
CN108591464B (zh) * 2018-06-28 2020-06-23 宁波奥克斯高科技有限公司 一种气体绝缘开关柜用密封结构
KR20210084442A (ko) 2018-10-05 2021-07-07 더 보오드 오브 트러스티스 오브 더 유니버시티 오브 일리노이즈 포도막 흑색종 치료를 위한 병용 요법
EP3952861A4 (en) 2019-04-11 2023-01-11 MEI Pharma, Inc. VORUCICLIB POLYMORPHS AND PROCESSES FOR THEIR PRODUCTION AND USE
US20240000789A1 (en) * 2020-05-12 2024-01-04 Novartis Ag Therapeutic combinations comprising a craf inhibitor
CN112168821B (zh) * 2020-11-09 2022-10-14 中南大学湘雅医院 一种治疗维罗非尼耐药的黑色素瘤的联合用药物及其应用
CN117043159A (zh) * 2020-11-19 2023-11-10 梅制药公司 Kras突变型癌症的治疗
JP2024500288A (ja) * 2020-11-19 2024-01-09 メイ ファーマ,インク. Kras変異癌の治療

Family Cites Families (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IN164232B (enExample) 1986-04-11 1989-02-04 Hoechst India
US5116954A (en) 1988-04-06 1992-05-26 Lipha, Lyonnaise Industrielle Pharmaceutique Pharmaceutically useful flavonoic compounds containing at least one substituent on the benzopyranone ring moiety
USH1427H (en) 1988-04-06 1995-04-04 Briet; Phillipe Substituted flavonoid compounds, their salts, their manufacture and their use in combination with interleukin-2
US5284856A (en) 1988-10-28 1994-02-08 Hoechst Aktiengesellschaft Oncogene-encoded kinases inhibition using 4-H-1-benzopyran-4-one derivatives
US5723313A (en) 1995-09-27 1998-03-03 St. Jude Children's Research Hospital ARF-p19, a novel regulator of the mammalian cell cycle
US5733920A (en) 1995-10-31 1998-03-31 Mitotix, Inc. Inhibitors of cyclin dependent kinases
US5849733A (en) 1996-05-10 1998-12-15 Bristol-Myers Squibb Co. 2-thio or 2-oxo flavopiridol analogs
US6281223B1 (en) 1999-04-13 2001-08-28 Supergen, Inc. Radioenhanced camptothecin derivative cancer treatments
HUP0300382A3 (en) 2000-03-29 2006-11-28 Cyclacel Ltd 2-substituted 4-heteroaryl-pyrimidines and their use in the treatmetn of proliferative disorders and pharmaceutical compositions containing the compounds
EP1280789A1 (en) 2000-05-03 2003-02-05 LG Life Sciences Ltd. Cdk inhibitors having 3-hydroxychromen-4-one structure
IL153688A0 (en) 2000-06-28 2003-07-06 Teva Pharma Carvedilol
US7884127B2 (en) 2002-07-08 2011-02-08 Pirimal Life Sciences Ltd. Inhibitors of cyclin dependent kinases and their use
TWI331034B (en) 2002-07-08 2010-10-01 Piramal Life Sciences Ltd Inhibitors of cyclin-dependent kinases and their use
US7915301B2 (en) 2002-07-08 2011-03-29 Piramal Life Science Limited Inhibitors of cyclin dependent kinases and their use
US7271193B2 (en) * 2002-07-08 2007-09-18 Nicholas Piramal India, Ltd. Inhibitors of cyclin-dependent kinases and their use
CA2502979A1 (en) 2002-11-06 2004-05-21 Cyclacel Limited Pharmaceutical composition comprising a cdk inhibitor and gemcitabine
GB0328180D0 (en) 2003-12-04 2004-01-07 Cyclacel Ltd Combination
WO2005055952A2 (en) 2003-12-08 2005-06-23 The Arizona Board Of Regents On Behalf Of The University Of Arizona Synergistic anti-cancer compositions
CA2600797A1 (en) 2005-03-11 2006-09-21 The Regents Of The University Of Michigan Chromen-4-one inhibitors of anti-apoptotic bcl-2 family members and the uses thereof
DK2395004T3 (en) * 2005-06-22 2016-03-21 Plexxikon Inc Pyrrolo [2,3-b] pyridine derivatives as protein kinase inhibitors
EP2046738B1 (en) * 2006-06-21 2014-06-11 Piramal Enterprises Limited Enantiomerically pure flavone derivatives for the treatment of proliferative disorders and processes for their preparation
CA2658215C (en) 2006-07-07 2013-08-27 Piramal Life Sciences Limited An enantioselective synthesis of pyrrolidines-substituted flavones
GB0706633D0 (en) 2007-04-04 2007-05-16 Cyclacel Ltd Combination
US8822526B2 (en) * 2007-05-15 2014-09-02 Piramal Enterprises Limited Synergistic pharmaceutical combination for the treatment of cancer
US20100152129A1 (en) * 2008-03-31 2010-06-17 Periyasamy Giridharan Novel synergistic combination of gemcitabine with P276-00 or P1446A in treatment of cancer
TWI461194B (zh) 2009-05-05 2014-11-21 Piramal Entpr Ltd 吡咯啶取代黃酮作為輻射致敏劑
EP2538941A1 (en) 2010-02-26 2013-01-02 Piramal Enterprises Limited Pyrrolidine substituted flavones for the treatment of inflammatory disorders
CN101841463B (zh) * 2010-03-05 2012-05-16 清华大学 基于sctp的多路径并发传输方法
US20130165456A1 (en) * 2010-08-26 2013-06-27 Tona M. Gilmer Combination
CA2818544A1 (en) * 2010-11-19 2012-05-24 Glaxosmithkline Intellectual Property (No.2) Limited Method of treatment with braf inhibitor
MX2013005661A (es) 2010-11-19 2013-09-13 Piramal Entpr Ltd Combinacion farmaceutica de paclitaxel y un inhibidor cdk (quinasa dependiente de ciclina).
WO2012123889A1 (en) * 2011-03-14 2012-09-20 Piramal Healthcare Limited A synergistic pharmaceutical combination for the treatment of pancreatic cancer
TW201300105A (zh) 2011-05-31 2013-01-01 Piramal Life Sciences Ltd 治療頭頸鱗狀細胞癌之相乘藥物組合物
US20120321637A1 (en) * 2011-06-20 2012-12-20 The Board Of Regents Of The University Of Texas System Combination cancer therapy with herv inhibition
CA2840017A1 (en) 2011-06-24 2012-12-27 Piramal Enterprises Limited Compounds for the treatment of cancers associated with human papillomavirus
TW201338774A (zh) 2012-01-13 2013-10-01 Piramal Entpr Ltd 口腔粘膜炎預防或治療化合物
WO2014049515A1 (en) 2012-09-25 2014-04-03 Piramal Enterprises Limited Pyrrolidine substituted flavones for treatment of renal cystic diseases
WO2014128523A1 (en) 2013-02-19 2014-08-28 Piramal Enterprises Limited A process for preparation of an intermediate of the pyrrolidine substituted flavones
TWI839690B (zh) 2013-07-12 2024-04-21 印度商皮拉馬爾企業有限公司 治療黑色素瘤的藥物組合的用途
WO2015181737A1 (en) 2014-05-28 2015-12-03 Piramal Enterprises Limited Pharmaceutical combination for the treatment of cancer

Also Published As

Publication number Publication date
CN105530931A (zh) 2016-04-27
US11839591B2 (en) 2023-12-12
US20240165076A1 (en) 2024-05-23
CA2917742C (en) 2020-04-14
TW202502325A (zh) 2025-01-16
CA2917742A1 (en) 2015-01-15
CN105530931B (zh) 2019-11-08
AR096892A1 (es) 2016-02-03
DK3019166T3 (da) 2019-07-29
JP2021001186A (ja) 2021-01-07
CN111053768A (zh) 2020-04-24
JP2019206565A (ja) 2019-12-05
TW202031253A (zh) 2020-09-01
TW201534297A (zh) 2015-09-16
US12383530B2 (en) 2025-08-12
CN117731786A (zh) 2024-03-22
ES2733929T3 (es) 2019-12-03
TWI839690B (zh) 2024-04-21
AU2014288857A1 (en) 2016-02-04
AU2014288857B2 (en) 2019-03-14
TWI680760B (zh) 2020-01-01
US20190282544A1 (en) 2019-09-19
JP2022068335A (ja) 2022-05-09
EP3019166B1 (en) 2019-05-08
EP3019166A1 (en) 2016-05-18
US11007174B2 (en) 2021-05-18
US20160136132A1 (en) 2016-05-19
IL243572A0 (en) 2016-02-29
EP3019166A4 (en) 2017-04-19
TW202233177A (zh) 2022-09-01
WO2015004636A1 (en) 2015-01-15
JP2024037891A (ja) 2024-03-19
JP2016525097A (ja) 2016-08-22
US20210393589A1 (en) 2021-12-23
CN111053768B (zh) 2023-12-12
IL243572B (en) 2019-10-31

Similar Documents

Publication Publication Date Title
JP6568060B2 (ja) 黒色腫の治療のための組合せ医薬
US20240208965A1 (en) Heteroaryl alkylene substituted 2-oxoquinazoline derivatives as methionine adenosyltransferase 2a inhibitors
US20230321042A1 (en) Combination therapy
KR20240051953A (ko) Pi3k 이소형 알파를 억제하는 화합물 및 암 치료 방법
RU2736123C1 (ru) Производные 2-аминохиназолина в качестве ингибиторов p70s6 киназы
HK40026870A (en) A pharmaceutical combination for the treatment of melanoma
HK1224936A1 (en) A pharmaceutical combination for the treatment of melanoma
HK1224936B (en) A pharmaceutical combination for the treatment of melanoma
EA049995B1 (ru) Соединения, ингибирующие изоформу альфа pi3k, и способы лечения онкологического заболевания

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20170703

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20170703

RD04 Notification of resignation of power of attorney

Free format text: JAPANESE INTERMEDIATE CODE: A7424

Effective date: 20170712

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20180227

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20180521

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20180726

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20181218

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20190312

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20190513

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20190617

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: 20190702

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20190801

R150 Certificate of patent or registration of utility model

Ref document number: 6568060

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250