CN106795561B - 用于对ezh2抑制剂的应答的生物标志物 - Google Patents

用于对ezh2抑制剂的应答的生物标志物 Download PDF

Info

Publication number
CN106795561B
CN106795561B CN201580044280.9A CN201580044280A CN106795561B CN 106795561 B CN106795561 B CN 106795561B CN 201580044280 A CN201580044280 A CN 201580044280A CN 106795561 B CN106795561 B CN 106795561B
Authority
CN
China
Prior art keywords
bap1
cancer
ezh2
biomarker
expression
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.)
Expired - Fee Related
Application number
CN201580044280.9A
Other languages
English (en)
Chinese (zh)
Other versions
CN106795561A (zh
Inventor
R·莱维纳
L·拉费
O·阿卜杜勒-瓦哈卜
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.)
Memorial Sloan Kettering Cancer Center
Original Assignee
Memorial Sloan Kettering Cancer Center
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 Memorial Sloan Kettering Cancer Center filed Critical Memorial Sloan Kettering Cancer Center
Publication of CN106795561A publication Critical patent/CN106795561A/zh
Application granted granted Critical
Publication of CN106795561B publication Critical patent/CN106795561B/zh
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/5748—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving oncogenic proteins
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5011—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/91—Transferases (2.)
    • G01N2333/91005—Transferases (2.) transferring one-carbon groups (2.1)
    • G01N2333/91011—Methyltransferases (general) (2.1.1.)
    • G01N2333/91017—Methyltransferases (general) (2.1.1.) with definite EC number (2.1.1.-)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/914—Hydrolases (3)
    • G01N2333/948—Hydrolases (3) acting on peptide bonds (3.4)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/70—Mechanisms involved in disease identification
    • G01N2800/7023—(Hyper)proliferation
    • G01N2800/7028—Cancer

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Analytical Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Pathology (AREA)
  • General Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Wood Science & Technology (AREA)
  • Hematology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Urology & Nephrology (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Oncology (AREA)
  • Hospice & Palliative Care (AREA)
  • Cell Biology (AREA)
  • General Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biophysics (AREA)
  • Toxicology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
CN201580044280.9A 2014-06-19 2015-06-19 用于对ezh2抑制剂的应答的生物标志物 Expired - Fee Related CN106795561B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201462014594P 2014-06-19 2014-06-19
US62/014,594 2014-06-19
PCT/US2015/036677 WO2015196064A1 (en) 2014-06-19 2015-06-19 Biomarkers for response to ezh2 inhibitors

Publications (2)

Publication Number Publication Date
CN106795561A CN106795561A (zh) 2017-05-31
CN106795561B true CN106795561B (zh) 2021-04-16

Family

ID=54936135

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201580044280.9A Expired - Fee Related CN106795561B (zh) 2014-06-19 2015-06-19 用于对ezh2抑制剂的应答的生物标志物

Country Status (15)

Country Link
US (1) US20170138946A1 (enExample)
EP (1) EP3158086B1 (enExample)
JP (1) JP6684230B2 (enExample)
KR (1) KR20170020463A (enExample)
CN (1) CN106795561B (enExample)
AU (1) AU2015276899B2 (enExample)
BR (1) BR112016029911A2 (enExample)
CA (1) CA2952285A1 (enExample)
EA (1) EA036889B1 (enExample)
ES (1) ES2870096T3 (enExample)
IL (1) IL249443B (enExample)
MX (1) MX384423B (enExample)
SG (2) SG10202007972SA (enExample)
WO (1) WO2015196064A1 (enExample)
ZA (1) ZA201608555B (enExample)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX376008B (es) 2012-10-15 2025-03-07 Epizyme Inc Inhibidor de ezh2 para usarse en el tratamiento de sarcoma epiteloide.
MX2018002344A (es) 2015-08-24 2018-07-06 Epizyme Inc Metodo para tratar el cancer.
TW201718598A (zh) 2015-08-27 2017-06-01 美國禮來大藥廠 Ｅｚｈ２抑制劑
US12442042B2 (en) 2016-02-16 2025-10-14 Agency For Science, Technology And Research Epigenomic profiling reveals the somatic promoter landscape of primary gastric adenocarcinoma
GB201615842D0 (en) * 2016-09-16 2016-11-02 Ucl Business Plc Cell death biomarker
CN106963765B (zh) * 2017-03-28 2020-04-07 上海交通大学医学院附属第九人民医院 Ezh2抑制剂化合物在制备治疗眼部黑色素瘤的药物中的应用
WO2020247130A1 (en) * 2019-06-03 2020-12-10 Icahn School Of Medicine At Mount Sinai Compounds and methods for inhibiting cancers via rest inhibition
GB201919219D0 (en) 2019-12-23 2020-02-05 Otsuka Pharma Co Ltd Cancer biomarkers
CN118161615B (zh) * 2024-03-19 2025-08-12 山东大学齐鲁医院 Phf20抑制剂在制备抗皮肤癌药物中的应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012144220A1 (en) * 2011-04-22 2012-10-26 Oncotherapy Science, Inc. Ezh2 as target gene for cancer therapy and diagnosis
WO2013049770A2 (en) * 2011-09-30 2013-04-04 Glaxosmithkline Llc Methods of treating cancer

Family Cites Families (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US548257A (en) 1895-10-22 Hay rake and loader
US5322770A (en) 1989-12-22 1994-06-21 Hoffman-Laroche Inc. Reverse transcription with thermostable DNA polymerases - high temperature reverse transcription
DE69132905T2 (de) 1990-12-06 2002-08-01 Affymetrix, Inc. (N.D.Ges.D.Staates Delaware) Detektion von Nukleinsäuresequenzen
US6379897B1 (en) 2000-11-09 2002-04-30 Nanogen, Inc. Methods for gene expression monitoring on electronic microarrays
US6465611B1 (en) 1997-02-25 2002-10-15 Corixa Corporation Compounds for immunotherapy of prostate cancer and methods for their use
US5932422A (en) * 1997-11-14 1999-08-03 Millennium Pharmaceuticals, Inc. Modulation of drug resistance via ubiquitin carboxy-terminal hydrolase
US6218114B1 (en) 1998-03-27 2001-04-17 Academia Sinica Methods for detecting differentially expressed genes
US6004755A (en) 1998-04-07 1999-12-21 Incyte Pharmaceuticals, Inc. Quantitative microarray hybridizaton assays
US6218122B1 (en) 1998-06-19 2001-04-17 Rosetta Inpharmatics, Inc. Methods of monitoring disease states and therapies using gene expression profiles
US6406921B1 (en) 1998-07-14 2002-06-18 Zyomyx, Incorporated Protein arrays for high-throughput screening
US6271002B1 (en) 1999-10-04 2001-08-07 Rosetta Inpharmatics, Inc. RNA amplification method
US7429466B2 (en) 2000-01-24 2008-09-30 Hypromatrix, Inc Methods and arrays for detecting biological molecules
WO2001055454A1 (en) 2000-01-28 2001-08-02 Althea Technologies, Inc. Methods for analysis of gene expression
EP1385998A1 (en) 2001-04-19 2004-02-04 Ciphergen Biosystems, Inc. Biomolecule characterization using mass spectrometry and affinity tags
AU2001286171B2 (en) 2001-05-25 2008-01-10 Serono Genetics Institute S.A. Human CDNAs and proteins and uses thereof
US7112408B2 (en) 2001-06-08 2006-09-26 The Brigham And Women's Hospital, Inc. Detection of ovarian cancer based upon alpha-haptoglobin levels
US20030013208A1 (en) 2001-07-13 2003-01-16 Milagen, Inc. Information enhanced antibody arrays
EP1425695A2 (en) 2001-08-13 2004-06-09 Beyong Genomics, Inc. Method and system for profiling biological systems
AU2003213054A1 (en) 2002-02-20 2003-09-09 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF POLYCOMB GROUP PROTEIN EZH2 GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US20030215858A1 (en) 2002-04-08 2003-11-20 Baylor College Of Medicine Enhanced gene expression system
WO2003091735A1 (en) 2002-04-23 2003-11-06 Millipore Corporation Sample preparation of biological fluids for proteomic applications
WO2007001986A2 (en) 2005-06-20 2007-01-04 Yuling Luo Methods of detecting nucleic acids in individual cells and of identifying rare cells from large heterogeneous cell populations
US20110251216A1 (en) 2010-02-19 2011-10-13 The Regents Of The University Of Michigan Compositions and methods for inhibiting ezh2
PL2614369T3 (pl) 2010-09-10 2016-08-31 Epizyme Inc Sposób określania przydatności inhibitorów ludzkiego ezh2 w leczeniu
US9175331B2 (en) 2010-09-10 2015-11-03 Epizyme, Inc. Inhibitors of human EZH2, and methods of use thereof
US20140011696A1 (en) * 2011-02-16 2014-01-09 Thomas Wiesner Bap1 mutational analysis in determining susceptibility to, prognosis of, and treatment of melanocytic neoplasia
EP2825161B1 (en) 2012-03-12 2019-01-02 Epizyme, Inc. Inhibitors of human ezh2, and methods of use thereof
MX376008B (es) 2012-10-15 2025-03-07 Epizyme Inc Inhibidor de ezh2 para usarse en el tratamiento de sarcoma epiteloide.

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012144220A1 (en) * 2011-04-22 2012-10-26 Oncotherapy Science, Inc. Ezh2 as target gene for cancer therapy and diagnosis
WO2013049770A2 (en) * 2011-09-30 2013-04-04 Glaxosmithkline Llc Methods of treating cancer

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Interplay between the Cancer Genome and Epigenome;Hui Shen等;《CELL》;20130301;第153卷(第1期);38-55 *
Reply to "Uveal melanoma cells are resistant to EZH2 inhibition regardless of BAP1 status;LAFAVE等;《NATURE MEDICINE》;20160601;第22卷(第6期);578-579 *
Uveal melanoma cells are resistant to EZH2 inhibition regardless of BAP1 status;MARIE SCHOUMACHER等;《NATURE MEDICINE》;20160601;第22卷(第6期);577-578 *

Also Published As

Publication number Publication date
AU2015276899A1 (en) 2017-01-05
JP2017525337A (ja) 2017-09-07
CN106795561A (zh) 2017-05-31
EP3158086A4 (en) 2018-01-10
KR20170020463A (ko) 2017-02-22
ZA201608555B (en) 2022-05-25
WO2015196064A1 (en) 2015-12-23
CA2952285A1 (en) 2015-12-23
BR112016029911A2 (pt) 2017-10-24
JP6684230B2 (ja) 2020-04-22
AU2015276899B2 (en) 2021-08-12
EA201692497A1 (ru) 2017-06-30
EA036889B1 (ru) 2021-01-12
IL249443B (en) 2022-05-01
SG11201610610YA (en) 2017-01-27
US20170138946A1 (en) 2017-05-18
ES2870096T3 (es) 2021-10-26
IL249443A0 (en) 2017-02-28
MX384423B (es) 2025-03-14
MX2016017097A (es) 2017-05-01
EP3158086B1 (en) 2021-03-24
SG10202007972SA (en) 2020-10-29
EP3158086A1 (en) 2017-04-26

Similar Documents

Publication Publication Date Title
CN106795561B (zh) 用于对ezh2抑制剂的应答的生物标志物
Fan et al. CircNR3C2 promotes HRD1-mediated tumor-suppressive effect via sponging miR-513a-3p in triple-negative breast cancer
Zhang et al. Blocking immunosuppressive neutrophils deters pY696-EZH2–driven brain metastases
Zhang et al. CircPLEKHM3 acts as a tumor suppressor through regulation of the miR-9/BRCA1/DNAJB6/KLF4/AKT1 axis in ovarian cancer
Yu et al. CXCL12/CXCR4 promotes inflammation-driven colorectal cancer progression through activation of RhoA signaling by sponging miR-133a-3p
Song et al. Targeting FOXA1-mediated repression of TGF-β signaling suppresses castration-resistant prostate cancer progression
Choi et al. YAP/TAZ initiates gastric tumorigenesis via upregulation of MYC
LaFave et al. Loss of BAP1 function leads to EZH2-dependent transformation
McNee et al. Citrullination of histone H3 drives IL-6 production by bone marrow mesenchymal stem cells in MGUS and multiple myeloma
Ye et al. Overexpression of CDCA7 predicts poor prognosis and induces EZH2‐mediated progression of triple‐negative breast cancer
Cheng et al. The m6A methyltransferase METTL3 is functionally implicated in DLBCL development by regulating m6A modification in PEDF
Liu et al. C/EBPB-dependent adaptation to palmitic acid promotes tumor formation in hormone receptor negative breast cancer
Athie et al. Analysis of copy number alterations reveals the lncRNA ALAL-1 as a regulator of lung cancer immune evasion
Che et al. Opposing transcriptional programs of KLF5 and AR emerge during therapy for advanced prostate cancer
Chu et al. Induction of senescence-associated secretory phenotype underlies the therapeutic efficacy of PRC2 inhibition in cancer
Li et al. UHRF2 promotes intestinal tumorigenesis through stabilization of TCF4 mediated Wnt/β‐catenin signaling
Huang et al. DDB2 is a novel regulator of Wnt signaling in colon cancer
Lu et al. CircETFA upregulates CCL5 by sponging miR-612 and recruiting EIF4A3 to promote hepatocellular carcinoma
Chen et al. hsa_circ_0121582 inhibits leukemia growth by dampening Wnt/β-catenin signaling
Song et al. Overexpression of RACGAP1 by E2F1 promotes neuroendocrine differentiation of prostate cancer by stabilizing EZH2 expression
Bai et al. Exo-miR-1290-induced by COX-2 overexpression promotes cancer-associated fibroblasts activation and tumor progression by CUL3-Nrf2 pathway in lung adenocarcinoma
Shen et al. ALKBH4 functions as a suppressor of colorectal cancer metastasis via competitively binding to WDR5
Chen et al. CD146 promotes malignant progression of breast phyllodes tumor through suppressing DCBLD2 degradation and activating the AKT pathway
Nayak et al. Nuclear Vav3 is required for polycomb repression complex-1 activity in B-cell lymphoblastic leukemogenesis
Wu et al. B-cell lymphoma/leukemia 10 promotes oral cancer progression through STAT1/ATF4/S100P signaling pathway

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20210416

CF01 Termination of patent right due to non-payment of annual fee