CN114846007B - 可用作t细胞激活剂的经取代的喹唑啉基化合物 - Google Patents

可用作t细胞激活剂的经取代的喹唑啉基化合物 Download PDF

Info

Publication number
CN114846007B
CN114846007B CN202080089197.4A CN202080089197A CN114846007B CN 114846007 B CN114846007 B CN 114846007B CN 202080089197 A CN202080089197 A CN 202080089197A CN 114846007 B CN114846007 B CN 114846007B
Authority
CN
China
Prior art keywords
cys
gly
ala
thr
leu
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
CN202080089197.4A
Other languages
English (en)
Chinese (zh)
Other versions
CN114846007A (zh
Inventor
U·维拉帕蒂
R·E·奥尔森
J·S·瓦瑞尔
H·拉哈曼
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bristol Myers Squibb Co
Original Assignee
Bristol Myers Squibb Co
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 Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of CN114846007A publication Critical patent/CN114846007A/zh
Application granted granted Critical
Publication of CN114846007B publication Critical patent/CN114846007B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic 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
    • C07D403/04—Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
    • C07D239/80—Oxygen atoms
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Dispersion Chemistry (AREA)
  • Virology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
CN202080089197.4A 2019-12-23 2020-12-22 可用作t细胞激活剂的经取代的喹唑啉基化合物 Active CN114846007B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
IN201911053553 2019-12-23
IN201911053553 2019-12-23
PCT/US2020/066508 WO2021133751A1 (en) 2019-12-23 2020-12-22 Substituted quinazolinyl compounds useful as t cell activators

Publications (2)

Publication Number Publication Date
CN114846007A CN114846007A (zh) 2022-08-02
CN114846007B true CN114846007B (zh) 2024-11-22

Family

ID=74195154

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202080089197.4A Active CN114846007B (zh) 2019-12-23 2020-12-22 可用作t细胞激活剂的经取代的喹唑啉基化合物

Country Status (12)

Country Link
US (1) US12492172B2 (https=)
EP (1) EP4081516B1 (https=)
JP (1) JP2023507847A (https=)
KR (1) KR20220119454A (https=)
CN (1) CN114846007B (https=)
AU (1) AU2020415377A1 (https=)
BR (1) BR112022012179A2 (https=)
CA (1) CA3162985A1 (https=)
ES (1) ES3038401T3 (https=)
IL (1) IL294148A (https=)
MX (1) MX2022006958A (https=)
WO (1) WO2021133751A1 (https=)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL294032A (en) 2019-12-24 2022-08-01 Carna Biosciences Inc Compounds that regulate diacylglycerol kinase
MX2023014762A (es) * 2021-06-23 2024-01-15 Gilead Sciences Inc Compuestos moduladores de diacilglicerol quinasa.
JP7686091B2 (ja) 2021-06-23 2025-05-30 ギリアード サイエンシーズ， インコーポレイテッド ジアシルグリセロールキナーゼ調節化合物
JP7651018B2 (ja) 2021-06-23 2025-03-25 ギリアード サイエンシーズ， インコーポレイテッド ジアシルグリセロールキナーゼ調節化合物
AU2022299051B2 (en) 2021-06-23 2025-03-13 Gilead Sciences, Inc. Diacylglyercol kinase modulating compounds
WO2023122777A1 (en) * 2021-12-22 2023-06-29 Gossamer Bio Services, Inc. Oxime derivatives useful as t cell activators
WO2023122772A1 (en) * 2021-12-22 2023-06-29 Gossamer Bio Services, Inc. Oxime derivatives useful as t cell activators
JP2025507915A (ja) * 2022-03-01 2025-03-21 インシリコ メディスン アイピー リミティド ジアシルグリセロールキナーゼ（ＤＧＫ）α阻害剤及びその使用
EP4486741A4 (en) 2022-03-01 2026-04-08 Insilico Medicine Ip Ltd Diacylglycerol Kinase (DGK) Alpha Inhibitors and Their Uses
WO2023175185A1 (en) 2022-03-17 2023-09-21 Forx Therapeutics Ag 2,4-dioxo-1,4-dihydroquinazoline derivatives as parg inhibitors for the treatment of cancer
WO2023175184A1 (en) 2022-03-17 2023-09-21 Forx Therapeutics Ag 2,4-dioxo-1,4-dihydroquinazoline derivatives as parg inhibitors for the treatment of cancer
US20250215014A1 (en) * 2022-03-31 2025-07-03 InventisBio Co., Ltd. Kinase inhibitors, preparation methods and uses thereof
US12600723B2 (en) 2022-07-18 2026-04-14 Incyte Corporation Tetracyclic compounds as DGK inhibitors
US12600722B2 (en) 2022-07-18 2026-04-14 Incyte Corporation Tetracyclic compounds as DGK inhibitors
EP4661869A1 (en) 2023-02-06 2025-12-17 Bayer Aktiengesellschaft Combinations of dgk (diacylglycerol kinase) inhibitors and immune checkpoint inhibitors and modulators

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6461468A (en) * 1987-09-01 1989-03-08 Otsuka Pharma Co Ltd Benzohetero ring derivative

Family Cites Families (68)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4324893A (en) 1979-04-18 1982-04-13 American Home Products Corporation 4-Amino-3-carboxy or cyano-1,2-dihydro-2-oxo-1,8-naphthyridine derivatives
UY27304A1 (es) 2001-05-24 2002-12-31 Avanir Pharmaceuticals Inhibidores del factor inhibidor de la migración de los macrófagos y métodos para su identificación
BR0312204A (pt) 2002-06-27 2005-04-26 Schering Ag Antagonista de receptor ccr5 de quinolina substituìda
GB0230018D0 (en) 2002-12-23 2003-01-29 Syngenta Ltd Fungicides
TW200418829A (en) 2003-02-14 2004-10-01 Avanir Pharmaceutics Inhibitors of macrophage migration inhibitory factor and methods for identifying the same
WO2004087880A2 (en) 2003-03-26 2004-10-14 Bayer Pharmaceuticals Corporation Compounds and their use to treat diabetes and related disorders
GB0316915D0 (en) 2003-07-18 2003-08-20 Glaxo Group Ltd Compounds
EP1660087A2 (en) 2003-07-22 2006-05-31 Janssen Pharmaceutica N.V. Quinolinone derivatives as inhibitors of c-fms kinase
CN1839133A (zh) 2003-08-22 2006-09-27 阿文尼尔药品公司 作为巨噬细胞移动抑制因子的抑制剂的取代的二氮杂萘衍生物及其在治疗人类疾病中的应用
US7381401B2 (en) 2004-01-08 2008-06-03 The University Of Chicago T cell anergy is reversed by active Ras and regulated by diacylglycerol kinase
TWI380996B (zh) 2004-09-17 2013-01-01 Hoffmann La Roche 抗ｏｘ４０ｌ抗體
PT2343320T (pt) 2005-03-25 2018-01-23 Gitr Inc Anticorpos anti-gitr e as suas utilizações
PL1879573T3 (pl) 2005-05-10 2013-05-31 Incyte Holdings Corp Modulatory 2,3-dioksygenazy indoloaminy i sposoby ich zastosowania
PT1907424E (pt) 2005-07-01 2015-10-09 Squibb & Sons Llc Anticorpos monoclonais humanos para o ligando 1 de morte programada (pd-l1)
US8450351B2 (en) 2005-12-20 2013-05-28 Incyte Corporation N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase
GB0605689D0 (en) 2006-03-21 2006-05-03 Novartis Ag Organic compounds
JP2007308402A (ja) 2006-05-17 2007-11-29 Sumitomo Chemical Co Ltd シンナモイル化合物及びその用途
JP2007308441A (ja) 2006-05-22 2007-11-29 Sumitomo Chemical Co Ltd 含複素環化合物及びその用途
WO2008036642A2 (en) 2006-09-19 2008-03-27 Incyte Corporation N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase
CL2007002650A1 (es) 2006-09-19 2008-02-08 Incyte Corp Compuestos derivados de heterociclo n-hidroxiamino; composicion farmaceutica, util para tratar cancer, infecciones virales y desordenes neurodegenerativos entre otras.
EP1987839A1 (en) 2007-04-30 2008-11-05 I.N.S.E.R.M. Institut National de la Sante et de la Recherche Medicale Cytotoxic anti-LAG-3 monoclonal antibody and its use in the treatment or prevention of organ transplant rejection and autoimmune disease
US8591886B2 (en) 2007-07-12 2013-11-26 Gitr, Inc. Combination therapies employing GITR binding molecules
EP2044949A1 (en) 2007-10-05 2009-04-08 Immutep Use of recombinant lag-3 or the derivatives thereof for eliciting monocyte immune response
US10047066B2 (en) 2007-11-30 2018-08-14 Newlink Genetics Corporation IDO inhibitors
WO2009156652A1 (fr) 2008-05-29 2009-12-30 Saint-Gobain Centre De Recherches Et D'etudes Europeen Structure en nid d'abeille a base de titanate d'aluminium
AR072999A1 (es) 2008-08-11 2010-10-06 Medarex Inc Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos
WO2010042489A2 (en) 2008-10-06 2010-04-15 Emory University Aminoquinoline derived heat shock protein 90 inhibitors, methods of preparing same, and methods for their use
EP3255060A1 (en) 2008-12-09 2017-12-13 F. Hoffmann-La Roche AG Anti-pd-l1 antibodies and their use to enhance t-cell function
US20110319416A1 (en) 2009-01-28 2011-12-29 Emory University Subunit Selective NMDA Receptor Antagonists For The Treatment Of Neurological Conditions
KR101790802B1 (ko) 2009-09-03 2017-10-27 머크 샤프 앤드 돔 코포레이션 항-ｇｉｔｒ 항체
EP2493862B1 (en) 2009-10-28 2016-10-05 Newlink Genetics Corporation Imidazole derivatives as ido inhibitors
ES2722300T3 (es) 2009-12-10 2019-08-09 Hoffmann La Roche Anticuerpos que se unen preferentemente al dominio extracelular 4 de CSF1R y su uso
EP2542256B1 (en) 2010-03-04 2019-05-22 MacroGenics, Inc. Antibodies reactive with b7-h3, immunologically active fragments thereof and uses thereof
US9169323B2 (en) 2010-03-05 2015-10-27 Hoffmann-La Roche Inc. Antibodies against human CSF-1R
JP5989547B2 (ja) 2010-03-05 2016-09-07 エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト ヒトｃｓｆ−１ｒに対する抗体及びその使用
HRP20190047T1 (hr) 2010-05-04 2019-02-22 Five Prime Therapeutics, Inc. Protutijela koja se vežu na csf1r
US9050334B2 (en) 2010-07-16 2015-06-09 Innov88 Llc MIF inhibitors and their uses
MX337040B (es) 2010-09-09 2016-02-09 Pfizer Moleculas de union a 4-1bb.
WO2012142498A2 (en) 2011-04-13 2012-10-18 Innovimmune Biotherapeutics, Inc. Mif inhibitors and their uses
NO2694640T3 (https=) 2011-04-15 2018-03-17
JP6072771B2 (ja) 2011-04-20 2017-02-01 メディミューン，エルエルシー Ｂ７−ｈ１およびｐｄ−１に結合する抗体およびその他の分子
KR101764096B1 (ko) 2011-11-28 2017-08-02 메르크 파텐트 게엠베하 항-ｐｄ-ｌ1 항체 및 그의 용도
RU2658603C2 (ru) 2011-12-15 2018-06-21 Ф.Хоффманн-Ля Рош Аг Антитела против человеческого csf-1r и их применения
KR20140127855A (ko) 2012-02-06 2014-11-04 제넨테크, 인크. Csf1r 억제제를 사용하는 조성물 및 방법
AR089939A1 (es) 2012-02-09 2014-10-01 Glenmark Pharmaceuticals Sa COMPUESTOS BICICLICOS COMO INHIBIDORES DE mPGES-1
AR090263A1 (es) 2012-03-08 2014-10-29 Hoffmann La Roche Terapia combinada de anticuerpos contra el csf-1r humano y las utilizaciones de la misma
RU2670743C9 (ru) 2012-05-11 2018-12-19 Файв Прайм Терапьютикс, Инк. Способы лечения состояний антителами, которые связывают рецептор колониестимулирующего фактора 1 (csf1r)
UY34887A (es) 2012-07-02 2013-12-31 Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware Optimización de anticuerpos que se fijan al gen de activación de linfocitos 3 (lag-3) y sus usos
CN107759690A (zh) 2012-08-31 2018-03-06 戊瑞治疗有限公司 用结合群落刺激因子1受体(csf1r)的抗体治疗病状的方法
WO2014039513A2 (en) 2012-09-04 2014-03-13 The Trustees Of The University Of Pennsylvania Inhibition of diacylglycerol kinase to augment adoptive t cell transfer
JP6461468B2 (ja) 2013-11-22 2019-01-30 Ntn株式会社 Ｖベルト式無段変速機
MA41168A (fr) 2014-12-17 2017-10-24 Acraf Nouveaux composés antibactériens
ES2898765T3 (es) 2015-04-10 2022-03-08 Araxes Pharma Llc Compuestos de quinazolina sustituidos y métodos de uso de los mismos
PT3889145T (pt) 2015-12-17 2024-04-02 Merck Patent Gmbh 8-ciano-5-piperidino-quinolinas como antagonistas de tlr7/8 e suas utilizações para tratamento de distúrbios imunitários
US10946020B2 (en) 2016-04-06 2021-03-16 University Of Virginia Patent Foundation Compositions and methods for treating cancer
CN110366550A (zh) 2016-12-22 2019-10-22 美国安进公司 作为用于治疗肺癌、胰腺癌或结直肠癌的KRAS G12C抑制剂的苯并异噻唑、异噻唑并[3,4-b]吡啶、喹唑啉、酞嗪、吡啶并[2,3-d]哒嗪和吡啶并[2,3-d]嘧啶衍生物
GB201700814D0 (en) 2017-01-17 2017-03-01 Liverpool School Tropical Medicine Compounds
AU2018273356B2 (en) 2017-05-22 2021-09-16 Amgen Inc. KRAS G12C inhibitors and methods of using the same
US12187687B2 (en) 2017-06-26 2025-01-07 University Of Virginia Patent Foundation Compositions and uses thereof
AU2018340475B2 (en) 2017-09-28 2023-01-19 Transthera Sciences (Nanjing), Inc. PDE9 inhibitor and use thereof
CA3098574A1 (en) 2018-05-04 2019-11-07 Amgen Inc. Kras g12c inhibitors and methods of using the same
CN112585139B (zh) 2018-06-27 2023-12-01 百时美施贵宝公司 用作t细胞激活剂的萘啶酮化合物
KR102767739B1 (ko) 2018-06-27 2025-02-12 브리스톨-마이어스 스큅 컴퍼니 T 세포 활성화제로서 유용한 치환된 나프티리디논 화합물
WO2020071550A1 (ja) 2018-10-04 2020-04-09 京都薬品工業株式会社 Ｃｄｋ８阻害剤およびその用途
AR119821A1 (es) 2019-08-28 2022-01-12 Bristol Myers Squibb Co Compuestos de piridopirimidinonilo sustituidos útiles como activadores de células t
US20230064809A1 (en) 2019-11-28 2023-03-02 Bayer Aktiengesellschaft Substituted aminoquinolones as dgkalpha inhibitors for immune activation
CR20220236A (es) 2019-11-28 2022-10-03 Bayer Pharma AG Aminoquinolonas sustituidas como inhibidores de dgk alfa para la activación inmune
US20230062100A1 (en) 2019-11-28 2023-03-02 Bayer Aktiengesellschaft Substituted aminoquinolones as dgkalpha inhibitors for immune activation

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6461468A (en) * 1987-09-01 1989-03-08 Otsuka Pharma Co Ltd Benzohetero ring derivative

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Jiang, Y. 等.Selectivity of the diacylglycerol kinase inhibitor 3-{2-(4-[bis-(4-fluorophenyl)methylene]-1-pip eridinyl)ethyl}-2,3-dihydro-2-thioxo-4(1H)quinazolinone (R59949) among diacylglycerol kinase subtypes.Biochemical Pharmacology.2000,第59卷(第7期),763-772. *

Also Published As

Publication number Publication date
US20230094758A1 (en) 2023-03-30
US12492172B2 (en) 2025-12-09
IL294148A (en) 2022-08-01
JP2023507847A (ja) 2023-02-27
ES3038401T3 (en) 2025-10-13
KR20220119454A (ko) 2022-08-29
MX2022006958A (es) 2022-07-12
AU2020415377A1 (en) 2022-08-18
CN114846007A (zh) 2022-08-02
EP4081516A1 (en) 2022-11-02
BR112022012179A2 (pt) 2022-09-06
CA3162985A1 (en) 2021-07-01
EP4081516B1 (en) 2025-07-30
WO2021133751A1 (en) 2021-07-01

Similar Documents

Publication Publication Date Title
CN114846007B (zh) 可用作t细胞激活剂的经取代的喹唑啉基化合物
CN114846015B (zh) 用作t细胞激活剂的经取代的杂芳基化合物
CN115103841B (zh) 可用作t细胞激活剂的经取代的喹啉酮基哌嗪化合物
CN114728950B (zh) 可作为helios蛋白质抑制剂的化合物
KR20220120624A (ko) T 세포 활성화제로서 유용한 치환된 피페라진 유도체
JP7789280B1 (ja) 置換フェニルオキソオキサゾリルピペリジンジオン化合物
CN121646585A (zh) 作为抗癌剂的经取代的氧代异吲哚啉基哌啶-2,6-二酮化合物
CN121487946A (zh) 螺环取代的氧代异吲哚啉基哌啶-2,6-二酮化合物
CN119654312A (zh) 用作t细胞活化剂的取代的四唑基化合物
CN119677740A (zh) 用作t细胞活化剂的叔胺取代的双环化合物
EA047609B1 (ru) Замещенные гетероарильные соединения, полезные в качестве активаторов т-клеток

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant