JP5579715B2 - cdk阻害剤および抗悪性腫瘍剤を含む治療用組合せ - Google Patents
cdk阻害剤および抗悪性腫瘍剤を含む治療用組合せ Download PDFInfo
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- JP5579715B2 JP5579715B2 JP2011520505A JP2011520505A JP5579715B2 JP 5579715 B2 JP5579715 B2 JP 5579715B2 JP 2011520505 A JP2011520505 A JP 2011520505A JP 2011520505 A JP2011520505 A JP 2011520505A JP 5579715 B2 JP5579715 B2 JP 5579715B2
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- RXZMYLDMFYNEIM-UHFFFAOYSA-N CC(C)(Cc1cnc(Nc(cc2)ccc2N2CCN(C)CC2)nc1-1)c2c-1[n](C)nc2C(NC)=O Chemical compound CC(C)(Cc1cnc(Nc(cc2)ccc2N2CCN(C)CC2)nc1-1)c2c-1[n](C)nc2C(NC)=O RXZMYLDMFYNEIM-UHFFFAOYSA-N 0.000 description 1
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- 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
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- 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
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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- 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
-
- 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
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with 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
- A61K31/555—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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- General Health & Medical Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
指数関数的に増殖するA2780ヒト卵巣癌細胞を播種し、加湿5%CO2雰囲気中で37℃において温置した。24時間後、式(I)の化合物のスカラー量を培地に24時間添加し、細胞を洗浄し、ゲムシタビンを1時間添加した。次いで、細胞を洗浄し、最初の処理から72時間後に計数した。細胞アデノシン三リン酸モニタリングシステムにより細胞増殖を求めた。細胞増殖を対照細胞と比較した。細胞増殖を50%阻害する濃度(IC50)を算出した。
指数関数的に増殖するA2780ヒト卵巣癌細胞を播種し、加湿5%CO2雰囲気中で37℃において温置した。24時間後、オキサリプラチンのスカラー量を培地に1時間添加し、細胞を洗浄し、式(I)の化合物を24時間添加した。次いで、細胞を洗浄し、最初の処理から72時間後に計数した。細胞アデノシン三リン酸モニタリングシステムにより細胞増殖を求めた。細胞増殖を対照細胞と比較した。細胞増殖を50%阻害する濃度(IC50)を算出した。
SN38は、イリノテカンの活性代謝産物であり、イリノテカンから加水分解により得られる。指数関数的に増殖するA2780ヒト卵巣癌細胞を播種し、加湿5%CO2雰囲気中で37℃において温置した。24時間後、SN−38のスカラー量を培地に1時間添加し、細胞を洗浄し、式(I)の化合物を24時間添加した。次いで、細胞を洗浄し、最初の処理から72時間後に計数した。細胞アデノシン三リン酸モニタリングシステムにより細胞増殖を求めた。細胞増殖を対照細胞と比較した。細胞増殖を50%阻害する濃度(IC50)を算出した。
Harlan(伊国)からのBalb Nu/Nu雄性マウスを、ろ紙カバー、飼料および滅菌した床敷、ならびに酸性化した水とともにケージ内で維持した。U87−MGヒト神経膠芽腫の断片を無胸腺マウスに皮下移植した。この腫瘍モデルは、このモデルがテモゾロミドに感受性であることが以前に実証されており、さらにテモゾロミドが神経膠腫の標準的治療であるので選択した。腫瘍が触診可能であるとき、テモゾロミドによる処置を開始した。化合物は、処置直前に調製した。
Harlan(伊国)からのBalb Nu/Nu雄性マウスを、ろ紙カバー、飼料および滅菌した床敷、ならびに酸性化した水とともにケージ内で維持した。N−592ヒト小細胞肺癌腫瘍の断片を無胸腺マウスに皮下移植した。この腫瘍モデルは、このモデルがトポテカンに感受性であるため、さらにNSCL癌におけるこの薬物の使用に基づき選択した。
Harlan(伊国)からのBalb Nu/Nu雄性マウスを、ろ紙カバー、飼料および滅菌した床敷、ならびに酸性化した水とともにケージ内で維持した。HCT−116ヒト結腸癌の断片を無胸腺マウスに皮下移植した。この腫瘍モデルは、このモデルが5−FUに感受性であるため、さらに結腸癌におけるこの薬物の使用に基づき選択した。
Claims (8)
- 同時、別個または連続使用のための、請求項1に記載の組合せ製剤。
- 請求項1に記載の組合せ製剤を医薬的に許容される担体、希釈剤または賦形剤と混合して含む医薬組成物。
- 増殖性障害の進行を治療または遅延させるための医薬品の調製のための、請求項1または2に記載の組合せ製剤の使用。
- 増殖性障害の治療のための医薬品の調製における請求項1に記載の式(I)の化合物の使用であって、前記治療が、上記定義の式(I)の化合物、ならびにゲムシタビン、オキサリプラチン、SN−38、テモゾロミド、トポテカンおよび5−フルオロウラシル(5−FU)からなる群から選択される1種以上の抗悪性腫瘍剤を同時に、連続的に、または別個に対象に投与することを含む使用。
- 増殖性障害を治療するための医薬品の調製における、請求項1に記載の式(I)の化合物、ならびにゲムシタビン、オキサリプラチン、SN−38、テモゾロミド、トポテカンおよび5−フルオロウラシル(5−FU)からなる群から選択される1種以上の抗悪性腫瘍剤の使用。
- 抗悪性腫瘍剤を用いる抗悪性腫瘍療法により引き起こされる副作用の低下を必要とする、ヒトを含む哺乳動物において、抗悪性腫瘍剤を用いる抗悪性腫瘍療法により引き起こされる副作用を低下させるための医薬品の調製における、請求項1に記載の式(I)の化合物、ならびにゲムシタビン、オキサリプラチン、SN−38、テモゾロミド、トポテカンおよび5−フルオロウラシル(5−FU)からなる群から選択される1種以上の抗悪性腫瘍剤を含む組合せ製剤の使用。
- 好適な容器手段中に(a)請求項1に記載の式(I)の化合物、ならびに(b)ゲムシタビン、オキサリプラチン、SN−38、テモゾロミド、トポテカンおよび5−フルオロウラシル(5−FU)からなる群から選択される1種以上の抗悪性腫瘍剤を含み、遊離形態または医薬的に許容されるその塩もしくはその任意の水和物の形態で活性成分がそれぞれに存在し、その同時、別個または連続使用のための取扱説明書を一緒に含む、悪性腫瘍の治療用の市販用包装品。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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EP08161320 | 2008-07-29 | ||
EP08161320.0 | 2008-07-29 | ||
PCT/EP2009/059815 WO2010012777A1 (en) | 2008-07-29 | 2009-07-29 | THERAPEUTIC COMBINATION COMPRISING A CDKs INHIBITOR AND AN ANTINEOPLASTIC AGENT |
Publications (2)
Publication Number | Publication Date |
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JP2011529474A JP2011529474A (ja) | 2011-12-08 |
JP5579715B2 true JP5579715B2 (ja) | 2014-08-27 |
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Application Number | Title | Priority Date | Filing Date |
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JP2011520505A Active JP5579715B2 (ja) | 2008-07-29 | 2009-07-29 | cdk阻害剤および抗悪性腫瘍剤を含む治療用組合せ |
Country Status (7)
Country | Link |
---|---|
US (1) | US8518930B2 (ja) |
EP (2) | EP3173100B1 (ja) |
JP (1) | JP5579715B2 (ja) |
CN (1) | CN102105152B (ja) |
ES (2) | ES2964764T3 (ja) |
HK (1) | HK1154343A1 (ja) |
WO (1) | WO2010012777A1 (ja) |
Families Citing this family (27)
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JP5677296B2 (ja) * | 2008-07-29 | 2015-02-25 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | グリオーマの治療のためのcdk阻害剤の使用 |
WO2010058006A1 (en) * | 2008-11-24 | 2010-05-27 | Nerviano Medical Sciences S.R.L. | Cdk inhibitor for the treatment of mesothelioma |
EP2424868B1 (en) * | 2009-04-29 | 2018-01-10 | Nerviano Medical Sciences S.r.l. | Cdk inhibitor salts |
US8691830B2 (en) | 2010-10-25 | 2014-04-08 | G1 Therapeutics, Inc. | CDK inhibitors |
TWI386203B (zh) | 2011-01-07 | 2013-02-21 | Univ China Medical | 治療腦癌或用以降低腦癌細胞對替莫唑胺之抗藥性之醫藥組合物及其應用 |
EP2668190B1 (en) * | 2011-01-26 | 2016-08-17 | Nerviano Medical Sciences S.r.l. | Tricyclic pyrrolo derivatives, process for their preparation and their use as kinase inhibitors |
JP5925808B2 (ja) * | 2011-01-26 | 2016-05-25 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | 三環式誘導体、これらの調製方法およびこれらのキナーゼ阻害剤としての使用 |
CN103857395A (zh) | 2011-04-01 | 2014-06-11 | 基因泰克公司 | Akt抑制剂化合物和阿比特龙的组合及使用方法 |
US9271952B2 (en) | 2011-10-11 | 2016-03-01 | Complexa, Inc. | Compositions and methods for treating nephropathy |
WO2014063087A1 (en) * | 2012-10-19 | 2014-04-24 | The Regents Of The University Of California | Treating tumors of the central nervous system |
ME03557B (me) | 2013-03-15 | 2020-07-20 | G1 Therapeutics Inc | Privremena zaštiтa normalnih ćelija током hemoterapije |
JP6435315B2 (ja) | 2013-03-15 | 2018-12-05 | ジー1、セラピューティクス、インコーポレイテッドG1 Therapeutics, Inc. | 高活性抗新生物薬及び抗増殖剤 |
US9717735B2 (en) | 2014-04-17 | 2017-08-01 | G1 Therapeutics, Inc. | Tricyclic lactams for use in HSPC-sparing treatments for RB-positive abnormal cellular proliferation |
EP3191098A4 (en) | 2014-09-12 | 2018-04-25 | G1 Therapeutics, Inc. | Combinations and dosing regimes to treat rb-positive tumors |
WO2016040848A1 (en) | 2014-09-12 | 2016-03-17 | G1 Therapeutics, Inc. | Treatment of rb-negative tumors using topoisomerase inhibitors in combination with cyclin dependent kinase 4/6 inhibitors |
US20160220569A1 (en) * | 2015-02-03 | 2016-08-04 | G1 Therapeutics, Inc. | CDK4/6 Inhibitor Dosage Formulations For The Protection Of Hematopoietic Stem And Progenitor Cells During Chemotherapy |
DK3303339T3 (da) | 2015-07-07 | 2021-04-12 | H Lundbeck As | Pde9-inhibitorer med imidazotriazinonskelet og imidazopyrazinonskelet til behandling af perifere sygdomme |
EP3355879A4 (en) | 2015-10-02 | 2019-05-22 | Complexa, Inc. | PREVENTION, TREATMENT AND INVERSION OF DISEASE USING THERAPEUTICALLY EFFECTIVE AMOUNTS OF ACTIVATED FATTY ACIDS |
WO2018005863A1 (en) | 2016-07-01 | 2018-01-04 | G1 Therapeutics, Inc. | Pyrimidine-based compounds for the treatment of cancer |
KR20190092478A (ko) | 2016-12-05 | 2019-08-07 | 쥐원 쎄라퓨틱스, 인크. | 화학요법 레지멘 동안의 면역 반응의 보존 |
BR112019013814A2 (pt) | 2017-01-06 | 2020-01-21 | G1 Therapeutics Inc | método para tratamento de câncer ou de um tumor em um indivíduo, composição farmacêutica, combinação, e, kit. |
KR102659211B1 (ko) | 2017-06-29 | 2024-04-18 | 쥐원 쎄라퓨틱스, 인크. | G1t38의 형체 형태 및 그의 제조 방법 |
WO2019090332A1 (en) * | 2017-11-06 | 2019-05-09 | Tiziana Life Sciences Plc | Formulations of milciclib and therapeutic combinations of the same for use in the treatment of cancer |
JP2021509680A (ja) | 2018-01-08 | 2021-04-01 | ジー1、セラピューティクス、インコーポレイテッドG1 Therapeutics, Inc. | G1t38の優れた投与レジメン |
JP2021526134A (ja) | 2018-05-25 | 2021-09-30 | イマラ インク. | 6−[(3S,4S)−4−メチル−l−(ピリミジン−2−イルメチル)ピロリジン−3−イル]−3−テトラヒドロピラン−4−イル−7H−イミダゾ[l,5−A]ピラジン−8−オンの一水和物および結晶形態 |
CN112839657A (zh) | 2018-08-24 | 2021-05-25 | G1治疗公司 | 1,4-二氮杂螺[5.5]十一烷-3-酮改进的合成 |
US10988479B1 (en) | 2020-06-15 | 2021-04-27 | G1 Therapeutics, Inc. | Morphic forms of trilaciclib and methods of manufacture thereof |
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EP1429764A1 (en) | 2001-08-31 | 2004-06-23 | Bristol-Myers Squibb Company | Compositions and methods for the treatment of cancer |
JP2005526086A (ja) * | 2002-03-15 | 2005-09-02 | サイクラセル・リミテッド | 癌の治療用のcdk阻害剤と5−fuの組合せ |
AU2003276453A1 (en) * | 2002-11-06 | 2004-06-07 | Cyclacel Limited | Pharmaceutical composition comprising a cdk inhibitor and gemcitabine |
RS20050944A (en) | 2003-05-22 | 2008-06-05 | Nerviano Medical Sciences S.R.L., | Pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors |
GB0313511D0 (en) * | 2003-06-11 | 2003-07-16 | Cyclacel Ltd | Combination |
WO2005094830A1 (en) | 2004-03-30 | 2005-10-13 | Pfizer Products Inc. | Combinations of signal transduction inhibitors |
BRPI0707580A2 (pt) | 2006-02-10 | 2011-05-10 | Nerviano Medical Sciences Srl | combinaÇÕes compreendendo um inibidor cdk e um anticorpo do fator de crescimento ou antimitàtico |
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2009
- 2009-07-29 JP JP2011520505A patent/JP5579715B2/ja active Active
- 2009-07-29 WO PCT/EP2009/059815 patent/WO2010012777A1/en active Application Filing
- 2009-07-29 EP EP17151885.5A patent/EP3173100B1/en active Active
- 2009-07-29 ES ES17151885T patent/ES2964764T3/es active Active
- 2009-07-29 CN CN2009801292678A patent/CN102105152B/zh active Active
- 2009-07-29 ES ES09781243.2T patent/ES2622559T3/es active Active
- 2009-07-29 EP EP09781243.2A patent/EP2320903B1/en active Active
- 2009-07-29 US US13/055,541 patent/US8518930B2/en active Active
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- 2011-08-12 HK HK11108482.5A patent/HK1154343A1/en unknown
Also Published As
Publication number | Publication date |
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EP3173100B1 (en) | 2023-09-06 |
WO2010012777A1 (en) | 2010-02-04 |
EP2320903A1 (en) | 2011-05-18 |
US8518930B2 (en) | 2013-08-27 |
ES2622559T3 (es) | 2017-07-06 |
EP3173100A1 (en) | 2017-05-31 |
CN102105152B (zh) | 2012-10-17 |
CN102105152A (zh) | 2011-06-22 |
EP2320903B1 (en) | 2017-01-18 |
JP2011529474A (ja) | 2011-12-08 |
US20110312909A1 (en) | 2011-12-22 |
ES2964764T3 (es) | 2024-04-09 |
HK1154343A1 (en) | 2012-04-20 |
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