JP5702390B2 - タンパク質チロシンキナーゼ2阻害剤としてのピリミジン誘導体 - Google Patents

タンパク質チロシンキナーゼ2阻害剤としてのピリミジン誘導体 Download PDF

Info

Publication number
JP5702390B2
JP5702390B2 JP2012531442A JP2012531442A JP5702390B2 JP 5702390 B2 JP5702390 B2 JP 5702390B2 JP 2012531442 A JP2012531442 A JP 2012531442A JP 2012531442 A JP2012531442 A JP 2012531442A JP 5702390 B2 JP5702390 B2 JP 5702390B2
Authority
JP
Japan
Prior art keywords
membered
alkyl
independently
group
compound 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.)
Active
Application number
JP2012531442A
Other languages
English (en)
Japanese (ja)
Other versions
JP2013506636A (ja
Inventor
ハインツ シュタットミューラー
ハインツ シュタットミューラー
イオアニス サポウンツィス
イオアニス サポウンツィス
Original Assignee
ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング
ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング
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=43048878&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=JP5702390(B2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング, ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング filed Critical ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング
Publication of JP2013506636A publication Critical patent/JP2013506636A/ja
Application granted granted Critical
Publication of JP5702390B2 publication Critical patent/JP5702390B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72Quinazolines; Hydrogenated quinazolines
    • C07D239/78Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
    • C07D239/84Nitrogen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/47One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
    • 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
    • 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
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • 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
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Oncology (AREA)
  • Rheumatology (AREA)
  • Communicable Diseases (AREA)
  • Pain & Pain Management (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
JP2012531442A 2009-10-02 2010-10-01 タンパク質チロシンキナーゼ2阻害剤としてのピリミジン誘導体 Active JP5702390B2 (ja)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
EP09172026 2009-10-02
EP09172026.8 2009-10-02
EP10172460.7 2010-08-11
EP10172460 2010-08-11
PCT/EP2010/064628 WO2011039344A1 (en) 2009-10-02 2010-10-01 Pyrimidine derivatives as protein tyrosine kinase 2 inhibitors

Publications (2)

Publication Number Publication Date
JP2013506636A JP2013506636A (ja) 2013-02-28
JP5702390B2 true JP5702390B2 (ja) 2015-04-15

Family

ID=43048878

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2012531442A Active JP5702390B2 (ja) 2009-10-02 2010-10-01 タンパク質チロシンキナーゼ2阻害剤としてのピリミジン誘導体

Country Status (25)

Country Link
US (1) US8466155B2 (cg-RX-API-DMAC7.html)
EP (1) EP2483249B1 (cg-RX-API-DMAC7.html)
JP (1) JP5702390B2 (cg-RX-API-DMAC7.html)
KR (1) KR20120092617A (cg-RX-API-DMAC7.html)
CN (1) CN102695700A (cg-RX-API-DMAC7.html)
AP (1) AP2012006166A0 (cg-RX-API-DMAC7.html)
AR (1) AR078513A1 (cg-RX-API-DMAC7.html)
AU (1) AU2010302648A1 (cg-RX-API-DMAC7.html)
BR (1) BR112012007300A2 (cg-RX-API-DMAC7.html)
CA (1) CA2775418A1 (cg-RX-API-DMAC7.html)
CL (1) CL2012000825A1 (cg-RX-API-DMAC7.html)
EA (1) EA201200552A1 (cg-RX-API-DMAC7.html)
EC (1) ECSP12011830A (cg-RX-API-DMAC7.html)
IL (1) IL218543A0 (cg-RX-API-DMAC7.html)
IN (1) IN2012DN02714A (cg-RX-API-DMAC7.html)
MA (1) MA33606B1 (cg-RX-API-DMAC7.html)
MX (1) MX2012003101A (cg-RX-API-DMAC7.html)
NZ (1) NZ598614A (cg-RX-API-DMAC7.html)
PE (1) PE20121431A1 (cg-RX-API-DMAC7.html)
PH (1) PH12012500527A1 (cg-RX-API-DMAC7.html)
TN (1) TN2012000142A1 (cg-RX-API-DMAC7.html)
TW (1) TW201124386A (cg-RX-API-DMAC7.html)
UY (1) UY32916A (cg-RX-API-DMAC7.html)
WO (1) WO2011039344A1 (cg-RX-API-DMAC7.html)
ZA (1) ZA201201703B (cg-RX-API-DMAC7.html)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120244141A1 (en) 2010-09-28 2012-09-27 Boehringer Ingelheim International Gmbh Stratification of cancer patients for susceptibility to therapy with PTK2 inhibitors
US8754114B2 (en) 2010-12-22 2014-06-17 Incyte Corporation Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3
WO2012110773A1 (en) 2011-02-17 2012-08-23 Cancer Therapeutics Crc Pty Limited Fak inhibitors
JP5937112B2 (ja) 2011-02-17 2016-06-22 カンサー・セラピューティクス・シーアールシー・プロプライエタリー・リミテッドCancer Therapeutics Crc Pty Limited 選択的fak阻害剤
EP2788378A4 (en) * 2011-12-09 2015-09-09 Oncomed Pharm Inc ASSOCIATION THERAPY FOR THE TREATMENT OF CANCER
EP2832734A4 (en) * 2012-03-28 2015-08-26 Takeda Pharmaceutical HETEROCYCLIC COMPOUND
EP3495367B1 (en) 2012-06-13 2020-09-30 Incyte Holdings Corporation Substituted tricyclic compounds as fgfr inhibitors
WO2014026125A1 (en) 2012-08-10 2014-02-13 Incyte Corporation Pyrazine derivatives as fgfr inhibitors
US9266892B2 (en) 2012-12-19 2016-02-23 Incyte Holdings Corporation Fused pyrazoles as FGFR inhibitors
DK2986610T5 (en) 2013-04-19 2018-12-10 Incyte Holdings Corp BICYCLIC HETEROCYCLES AS FGFR INHIBITORS
WO2014190207A1 (en) * 2013-05-22 2014-11-27 The Regents Of The University Of California Aurora kinase inhibitors
US10851105B2 (en) 2014-10-22 2020-12-01 Incyte Corporation Bicyclic heterocycles as FGFR4 inhibitors
WO2016134294A1 (en) 2015-02-20 2016-08-25 Incyte Corporation Bicyclic heterocycles as fgfr4 inhibitors
CR20170390A (es) 2015-02-20 2017-10-23 Incyte Holdings Corp Heterociclos biciclicos como inhibidores de fgfr
MA41551A (fr) 2015-02-20 2017-12-26 Incyte Corp Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4
AR111960A1 (es) 2017-05-26 2019-09-04 Incyte Corp Formas cristalinas de un inhibidor de fgfr y procesos para su preparación
US11466004B2 (en) 2018-05-04 2022-10-11 Incyte Corporation Solid forms of an FGFR inhibitor and processes for preparing the same
CN112566912A (zh) 2018-05-04 2021-03-26 因赛特公司 Fgfr抑制剂的盐
WO2020185532A1 (en) 2019-03-08 2020-09-17 Incyte Corporation Methods of treating cancer with an fgfr inhibitor
US11591329B2 (en) 2019-07-09 2023-02-28 Incyte Corporation Bicyclic heterocycles as FGFR inhibitors
US12122767B2 (en) 2019-10-01 2024-10-22 Incyte Corporation Bicyclic heterocycles as FGFR inhibitors
GEAP202415945A (en) 2019-10-14 2024-04-25 Incyte Corp Bicyclic heterocycles as fgfr inhibitors
WO2021076728A1 (en) 2019-10-16 2021-04-22 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
BR112022010664A2 (pt) 2019-12-04 2022-08-16 Incyte Corp Derivados de um inibidor de fgfr
EP4069696A1 (en) 2019-12-04 2022-10-12 Incyte Corporation Tricyclic heterocycles as fgfr inhibitors
US12012409B2 (en) 2020-01-15 2024-06-18 Incyte Corporation Bicyclic heterocycles as FGFR inhibitors
TW202304459A (zh) 2021-04-12 2023-02-01 美商英塞特公司 包含fgfr抑制劑及nectin-4靶向劑之組合療法
WO2022261159A1 (en) 2021-06-09 2022-12-15 Incyte Corporation Tricyclic heterocycles as fgfr inhibitors
JP2024522189A (ja) 2021-06-09 2024-06-11 インサイト・コーポレイション Fgfr阻害剤としての三環式ヘテロ環
WO2023107705A1 (en) 2021-12-10 2023-06-15 Incyte Corporation Bicyclic amines as cdk12 inhibitors

Family Cites Families (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0004887D0 (en) * 2000-03-01 2000-04-19 Astrazeneca Uk Ltd Chemical compounds
WO2002096888A1 (de) * 2001-05-29 2002-12-05 Schering Aktiengesellschaft Cdk inhibitorische pyrimidine, deren herstellung und verwendung als arzneimittel
CA2463989C (en) 2001-10-17 2012-01-31 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pyrimidine derivatives, pharmaceutical compositions containing these compounds, the use thereof and process for the preparation thereof
AU2003212282A1 (en) * 2002-03-11 2003-09-22 Schering Aktiengesellschaft Cdk inhibiting 2-heteroaryl pyrimidine, the production thereof, and use thereof as a medicament
AR042486A1 (es) * 2002-12-18 2005-06-22 Glaxo Group Ltd Compuesto de quinolina y naftiridina halosustituido en la posicion 3, procedimiento para preparar el compuesto, composicion farmaceutica que lo comprende y su uso para preparar dicha composicion .
EP1763514A2 (en) 2004-05-18 2007-03-21 Rigel Pharmaceuticals, Inc. Cycloalkyl substituted pyrimidinediamine compounds and their uses
EP1794134A1 (de) * 2004-09-29 2007-06-13 Bayer Schering Pharma Aktiengesellschaft Substituierte 2-anilinopyrimidine als zellzyklus -kinase oder rezeptortyrosin-kinase inhibitoren, deren herstellung und verwendung als arzneimittel
US20070032514A1 (en) 2005-07-01 2007-02-08 Zahn Stephan K 2,4-diamino-pyrimidines as aurora inhibitors
JP4332590B2 (ja) * 2005-12-21 2009-09-16 ファイザー・プロダクツ・インク 異常細胞増殖を治療するためのピリミジン誘導体
US8623887B2 (en) 2006-05-15 2014-01-07 Boehringer Ingelheim International Gmbh Compounds
TW200808325A (en) * 2006-07-06 2008-02-16 Astrazeneca Ab Novel compounds
GB0619343D0 (en) 2006-09-30 2006-11-08 Vernalis R&D Ltd New chemical compounds
US20100144706A1 (en) * 2006-12-22 2010-06-10 Boehringer Ingelheim International Gmbh Compounds
PL2154967T3 (pl) 2007-04-16 2014-08-29 Hutchison Medipharma Entpr Ltd Pochodne pirymidyny
US8338439B2 (en) 2008-06-27 2012-12-25 Celgene Avilomics Research, Inc. 2,4-disubstituted pyrimidines useful as kinase inhibitors
CA2986640C (en) 2008-06-27 2019-03-26 Celgene Avilomics Research, Inc. Heteroaryl compounds and uses thereof
AR074209A1 (es) 2008-11-24 2010-12-29 Boehringer Ingelheim Int Derivados de pirimidina utiles para el tratamiento del cancer
KR101705158B1 (ko) 2009-05-05 2017-02-09 다나-파버 캔서 인스티튜트 인크. Egfr 억제제 및 질환 치료방법

Also Published As

Publication number Publication date
IL218543A0 (en) 2012-05-31
EA201200552A1 (ru) 2013-03-29
MX2012003101A (es) 2012-04-11
EP2483249A1 (en) 2012-08-08
KR20120092617A (ko) 2012-08-21
CL2012000825A1 (es) 2012-08-24
JP2013506636A (ja) 2013-02-28
WO2011039344A1 (en) 2011-04-07
CN102695700A (zh) 2012-09-26
EP2483249B1 (en) 2015-12-23
NZ598614A (en) 2013-08-30
CA2775418A1 (en) 2011-04-07
AU2010302648A1 (en) 2012-04-05
PH12012500527A1 (en) 2012-10-22
US8466155B2 (en) 2013-06-18
US20110237598A1 (en) 2011-09-29
MA33606B1 (fr) 2012-09-01
UY32916A (es) 2011-04-29
AR078513A1 (es) 2011-11-16
AP2012006166A0 (en) 2012-04-30
PE20121431A1 (es) 2012-11-10
ZA201201703B (en) 2014-05-28
BR112012007300A2 (pt) 2017-11-07
IN2012DN02714A (cg-RX-API-DMAC7.html) 2015-09-11
TN2012000142A1 (en) 2013-09-19
TW201124386A (en) 2011-07-16
ECSP12011830A (es) 2012-06-29

Similar Documents

Publication Publication Date Title
JP5702390B2 (ja) タンパク質チロシンキナーゼ2阻害剤としてのピリミジン誘導体
EP2978757B1 (en) Indolinone analogues as brd4 inhibitors
AU2013346809B2 (en) Triazolopyrazine
EP2978758B1 (en) Dihydroquinazolinone analogues as brd4 inhibitors
EP3066104B1 (en) Triazolopyrazine derivatives as brd4 inhibitors
EP3140304B1 (en) Benzimidazole derivatives
EP2571877A1 (en) 1h - imidazo [4, 5 - c]quinolines
US8466162B2 (en) 5-alkynyl-pyridines
HK1172027A (en) Pyrimidine derivatives as protein tyrosine kinase 2 inhibitors

Legal Events

Date Code Title Description
A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20140213

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20140213

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20140512

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20140825

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20141117

A602 Written permission of extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A602

Effective date: 20141125

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20141222

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: 20150121

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20150219

R150 Certificate of patent or registration of utility model

Ref document number: 5702390

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

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

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250