JP5726515B2 - Ｐｉ３ｋ−アルファのキナゾリン阻害剤を用いた阻害による治療方法 - Google Patents

Ｐｉ３ｋ−アルファのキナゾリン阻害剤を用いた阻害による治療方法 Download PDF

Info

Publication number
JP5726515B2
JP5726515B2 JP2010503043A JP2010503043A JP5726515B2 JP 5726515 B2 JP5726515 B2 JP 5726515B2 JP 2010503043 A JP2010503043 A JP 2010503043A JP 2010503043 A JP2010503043 A JP 2010503043A JP 5726515 B2 JP5726515 B2 JP 5726515B2
Authority
JP
Japan
Prior art keywords
nhc
cancer
alkyl
formula
compound
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
JP2010503043A
Other languages
English (en)
Japanese (ja)
Other versions
JP2010523669A (ja
JP2010523669A5 (enExample
Inventor
ピーター ラム，
ピーター ラム，
デイヴィッド マシューズ，
デイヴィッド マシューズ，
Original Assignee
エクセリクシス， インク．
エクセリクシス， インク．
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 エクセリクシス， インク．, エクセリクシス， インク． filed Critical エクセリクシス， インク．
Publication of JP2010523669A publication Critical patent/JP2010523669A/ja
Publication of JP2010523669A5 publication Critical patent/JP2010523669A5/ja
Application granted granted Critical
Publication of JP5726515B2 publication Critical patent/JP5726515B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/436—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
    • 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
    • A61K31/495—Heterocyclic 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
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic 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
    • A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • 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
    • A61K31/495—Heterocyclic 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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • A61K31/495—Heterocyclic 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • 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
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • 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
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
JP2010503043A 2007-04-11 2008-04-08 Ｐｉ３ｋ−アルファのキナゾリン阻害剤を用いた阻害による治療方法 Active JP5726515B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US92316407P 2007-04-11 2007-04-11
US60/923,164 2007-04-11
PCT/US2008/004570 WO2008127594A2 (en) 2007-04-11 2008-04-08 Combination therapies comprising quinoxaline inhibitors of pi3k-alpha for use in the treatment of cancer

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2013228684A Division JP2014074031A (ja) 2007-04-11 2013-11-01 Ｐｉ３ｋ−アルファのキナゾリン阻害剤を用いた阻害による治療方法

Publications (3)

Publication Number Publication Date
JP2010523669A JP2010523669A (ja) 2010-07-15
JP2010523669A5 JP2010523669A5 (enExample) 2013-05-16
JP5726515B2 true JP5726515B2 (ja) 2015-06-03

Family

ID=39864581

Family Applications (2)

Application Number Title Priority Date Filing Date
JP2010503043A Active JP5726515B2 (ja) 2007-04-11 2008-04-08 Ｐｉ３ｋ−アルファのキナゾリン阻害剤を用いた阻害による治療方法
JP2013228684A Pending JP2014074031A (ja) 2007-04-11 2013-11-01 Ｐｉ３ｋ−アルファのキナゾリン阻害剤を用いた阻害による治療方法

Family Applications After (1)

Application Number Title Priority Date Filing Date
JP2013228684A Pending JP2014074031A (ja) 2007-04-11 2013-11-01 Ｐｉ３ｋ−アルファのキナゾリン阻害剤を用いた阻害による治療方法

Country Status (33)

Country Link
US (1) US8481001B2 (enExample)
EP (1) EP2139483B9 (enExample)
JP (2) JP5726515B2 (enExample)
KR (1) KR101586774B1 (enExample)
CN (2) CN103202842A (enExample)
AU (1) AU2008239668B2 (enExample)
BR (1) BRPI0810208A2 (enExample)
CA (1) CA2684056A1 (enExample)
CO (1) CO6140024A2 (enExample)
CR (1) CR11099A (enExample)
CY (1) CY1114608T1 (enExample)
DK (1) DK2139483T3 (enExample)
EA (1) EA019064B1 (enExample)
EC (1) ECSP099723A (enExample)
ES (1) ES2438998T3 (enExample)
GT (1) GT200900263A (enExample)
HR (1) HRP20131081T1 (enExample)
IL (1) IL201211A (enExample)
MA (1) MA31335B1 (enExample)
ME (1) ME00937B (enExample)
MX (1) MX2009010929A (enExample)
MY (1) MY150797A (enExample)
NI (1) NI200900184A (enExample)
NZ (1) NZ580009A (enExample)
PL (1) PL2139483T3 (enExample)
PT (1) PT2139483E (enExample)
RS (1) RS53020B (enExample)
SI (1) SI2139483T1 (enExample)
SV (1) SV2009003390A (enExample)
TN (1) TN2009000399A1 (enExample)
UA (1) UA98141C2 (enExample)
WO (1) WO2008127594A2 (enExample)
ZA (1) ZA200906765B (enExample)

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GEP20115304B (en) * 2005-10-07 2011-10-10 Exelixis Inc PYRIDOPYRIMIDINONE INHIBITORS OF PI3Kα
WO2007044729A2 (en) * 2005-10-07 2007-04-19 Exelixis, Inc. N- (3-amino-quinoxalin-2-yl) -sulfonamide derivatives and their use as phosphatidylinositol 3-kinase inhibitors
ATE539752T1 (de) 2006-08-16 2012-01-15 Exelixis Inc Verwendung von pi3k- und mek-modulatoren bei der krebsbehandlung
JP2010523670A (ja) * 2007-04-10 2010-07-15 エクセリクシス， インク． Ｐｉ３ｋアルファのピリドピリミジノン阻害剤を使用した治療方法
US8673908B2 (en) 2008-11-10 2014-03-18 Kyowa Hakko Kirin Co., Ltd. Kynurenine production inhibitor
DE102009049679A1 (de) 2009-10-19 2011-04-21 Merck Patent Gmbh Pyrazolopyrimidinderivate
WO2011100319A1 (en) 2010-02-09 2011-08-18 Exelixis, Inc. Methods of treating cancer using pyridopyrimidinone inhibitors of pi3k and mtor in combination with autophagy inhibitors
AR084469A1 (es) 2010-07-09 2013-05-22 Exelixis Inc Combinaciones de inhibidores de quinasas para el tratamiento del cancer
AU2011302196B2 (en) 2010-09-14 2016-04-28 Exelixis, Inc. Inhibitors of PI3K-delta and methods of their use and manufacture
DE102010048800A1 (de) * 2010-10-20 2012-05-10 Merck Patent Gmbh Chinoxalinderivate
AU2011317675A1 (en) 2010-10-20 2013-05-02 Merck Serono S.A. Geneva Method for preparing substituted N-(3-amino-quinoxalin-2-yl)-sulfonamides and their intermediates N-(3-chloro-quinoxalin-2-yl)sulfonamides
DE102010049595A1 (de) 2010-10-26 2012-04-26 Merck Patent Gmbh Chinazolinderivate
WO2012065057A2 (en) 2010-11-12 2012-05-18 Exelixis, Inc. Phosphatidylinositol 3-kinase inhibitors and methods of their use
AU2012308414A1 (en) * 2011-09-14 2014-05-01 Exelixis, Inc. Phosphatidylinositol 3-kinase inhibitors for the treatment of cancer
CA2850763A1 (en) * 2011-10-04 2013-04-11 Gilead Calistoga Llc Novel quinoxaline inhibitors of pi3k
WO2013056067A1 (en) 2011-10-13 2013-04-18 Exelixis, Inc. Compounds for use in the treatment of basal cell carcinoma
CA2853095A1 (en) * 2011-10-28 2013-05-02 Novartis Ag Method of treating gastrointestinal stromal tumors
SG11201401961UA (en) * 2011-11-01 2014-05-29 Exelixis Inc N- (3- { [ (3- { [2-chloro-5- (methoxy) phenyl] amino} quinoxalin- 2 -yl) amino] sulfonyl} phe nyl) - 2 -methylalaninamide as phosphatidylinositol 3 - kinase inhibitor for the treatment of lymphoproliferative malignancies
WO2013067306A1 (en) * 2011-11-02 2013-05-10 Exelixis, Inc. Phosphatidylinositol 3-kinase inhibitors for the treatment of childhood cancers
CA2860051A1 (en) 2011-12-27 2013-07-04 Kadmon Corporation, Llc Methods for treatment of breast cancer nonresponsive to trastuzumab
EP2860181B1 (en) 2012-04-10 2019-02-13 Shanghai Yingli Pharmaceutical Co. Ltd. Fused pyrimidine compound, and preparation method, intermediate, composition and uses thereof
JP6193374B2 (ja) 2012-08-13 2017-09-06 武田薬品工業株式会社 Ｇｐｒ６モジュレーターとしてのキノキサリン誘導体
CN104513254B (zh) 2013-09-30 2019-07-26 上海璎黎药业有限公司 稠合嘧啶类化合物、中间体、其制备方法、组合物和应用
RU2663999C2 (ru) 2013-10-16 2018-08-14 Шанхай Инли Фармасьютикал Ко., Лтд Конденсированное гетероциклическое соединение, способ его получения, его фармацевтическая композиция и применения
JP6526034B2 (ja) 2014-02-14 2019-06-05 武田薬品工業株式会社 Ｇｐｒ６のピリドピラジンモジュレーター
US9950194B2 (en) 2014-09-09 2018-04-24 Mevion Medical Systems, Inc. Patient positioning system
WO2019119206A1 (en) 2017-12-18 2019-06-27 Merck Sharp & Dohme Corp. Purine inhibitors of human phosphatidylinositol 3-kinase delta

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004064734A2 (en) * 2003-01-17 2004-08-05 Threshold Pharmaceuticals, Inc. Combination therapies for the treatment of cancer
EP1917252B1 (en) * 2005-08-26 2014-01-01 Merck Serono SA Pyrazine derivatives and use as pi3k inhibitors
GEP20115304B (en) * 2005-10-07 2011-10-10 Exelixis Inc PYRIDOPYRIMIDINONE INHIBITORS OF PI3Kα
WO2007044729A2 (en) * 2005-10-07 2007-04-19 Exelixis, Inc. N- (3-amino-quinoxalin-2-yl) -sulfonamide derivatives and their use as phosphatidylinositol 3-kinase inhibitors
ATE539752T1 (de) 2006-08-16 2012-01-15 Exelixis Inc Verwendung von pi3k- und mek-modulatoren bei der krebsbehandlung
BRPI0808013A2 (pt) 2007-02-22 2014-06-17 Merck Serono Sa Compostos de quinoxalina e uso dos mesmos
JP2010523670A (ja) * 2007-04-10 2010-07-15 エクセリクシス， インク． Ｐｉ３ｋアルファのピリドピリミジノン阻害剤を使用した治療方法
JP4623164B2 (ja) * 2008-08-21 2011-02-02 セイコーエプソン株式会社 プロジェクタ

Also Published As

Publication number Publication date
PL2139483T3 (pl) 2014-02-28
CA2684056A1 (en) 2008-10-23
RS53020B (sr) 2014-04-30
HK1140141A1 (en) 2010-10-08
GT200900263A (es) 2014-01-15
CR11099A (es) 2010-01-19
JP2010523669A (ja) 2010-07-15
MX2009010929A (es) 2010-01-20
AU2008239668A1 (en) 2008-10-23
IL201211A (en) 2015-09-24
EA019064B1 (ru) 2013-12-30
MY150797A (en) 2014-02-28
NI200900184A (es) 2011-09-08
EP2139483B1 (en) 2013-09-18
CN101959516B (zh) 2013-05-08
SV2009003390A (es) 2010-05-21
EP2139483A2 (en) 2010-01-06
KR101586774B1 (ko) 2016-01-19
MA31335B1 (fr) 2010-04-01
AU2008239668B2 (en) 2013-11-07
CY1114608T1 (el) 2016-10-05
TN2009000399A1 (fr) 2010-12-31
CN101959516A (zh) 2011-01-26
KR20100019436A (ko) 2010-02-18
CN103202842A (zh) 2013-07-17
WO2008127594A2 (en) 2008-10-23
EA200970935A1 (ru) 2010-04-30
UA98141C2 (ru) 2012-04-25
ES2438998T3 (es) 2014-01-21
DK2139483T3 (da) 2014-01-13
CO6140024A2 (es) 2010-03-19
BRPI0810208A2 (pt) 2014-10-21
WO2008127594A3 (en) 2009-04-30
EP2139483B9 (en) 2014-05-21
HRP20131081T1 (hr) 2013-12-20
NZ580009A (en) 2012-06-29
ZA200906765B (en) 2010-05-26
JP2014074031A (ja) 2014-04-24
ECSP099723A (es) 2010-03-31
US8481001B2 (en) 2013-07-09
IL201211A0 (en) 2010-05-31
ME00937B (me) 2012-06-20
PT2139483E (pt) 2013-12-27
US20110123434A1 (en) 2011-05-26
SI2139483T1 (sl) 2013-11-29

Similar Documents

Publication Publication Date Title
JP5726515B2 (ja) Ｐｉ３ｋ−アルファのキナゾリン阻害剤を用いた阻害による治療方法
JP5270353B2 (ja) ホスファチジルイノシトール３−キナーゼインヒビターとその使用方法
EP2056829B9 (en) Using pi3k and mek modulators in treatments of cancer
CN1976906B (zh) 用作parp抑制剂的取代2-烷基喹唑啉酮衍生物
WO2012065057A2 (en) Phosphatidylinositol 3-kinase inhibitors and methods of their use
JP2010523677A (ja) 癌の治療のためのＰＩ３Ｋα阻害剤としてのピリド［２，３−Ｄ］ピリミジン−７−オン
HK1140141B (en) Combination therapies comprising a quinoxaline inhibitors of pi3k-alpha for use in the treatment of cancer
HK1130438B (en) Using pi3k and mek modulators in treatments of cancer
HK1119697B (en) N- (3-amino-quinoxalin-2-yl) -sulfonamide derivatives and their use as phosphatidylinositol 3-kinase inhibitors

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20110407

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20110407

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20130329

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20130604

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20130823

A602 Written permission of extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A602

Effective date: 20130830

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20131001

A602 Written permission of extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A602

Effective date: 20131008

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20131101

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20140415

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20140711

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: 20150303

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20150401

R150 Certificate of patent or registration of utility model

Ref document number: 5726515

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