TWI456197B - 作為早發性大腸直腸癌之生物標記的(line-1低甲基化作用) - Google Patents
作為早發性大腸直腸癌之生物標記的(line-1低甲基化作用) Download PDFInfo
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- TWI456197B TWI456197B TW101109222A TW101109222A TWI456197B TW I456197 B TWI456197 B TW I456197B TW 101109222 A TW101109222 A TW 101109222A TW 101109222 A TW101109222 A TW 101109222A TW I456197 B TWI456197 B TW I456197B
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- 206010009944 Colon cancer Diseases 0.000 title claims 20
- 208000001333 Colorectal Neoplasms Diseases 0.000 title claims 20
- 239000000090 biomarker Substances 0.000 title claims 6
- 230000011987 methylation Effects 0.000 claims 72
- 238000007069 methylation reaction Methods 0.000 claims 72
- 238000000034 method Methods 0.000 claims 18
- 239000000523 sample Substances 0.000 claims 14
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims 12
- 239000012472 biological sample Substances 0.000 claims 11
- 108091029523 CpG island Proteins 0.000 claims 9
- 230000003321 amplification Effects 0.000 claims 9
- 238000004458 analytical method Methods 0.000 claims 9
- 238000001369 bisulfite sequencing Methods 0.000 claims 9
- 238000003199 nucleic acid amplification method Methods 0.000 claims 9
- 239000003814 drug Substances 0.000 claims 7
- 229940079593 drug Drugs 0.000 claims 7
- 238000009396 hybridization Methods 0.000 claims 6
- 238000001114 immunoprecipitation Methods 0.000 claims 6
- CEKFEALYZYCWPG-UHFFFAOYSA-N phosphono dihydrogen phosphate sulfurous acid Chemical group OS(O)=O.OP(O)(=O)OP(O)(O)=O CEKFEALYZYCWPG-UHFFFAOYSA-N 0.000 claims 6
- 206010028980 Neoplasm Diseases 0.000 claims 4
- 201000011510 cancer Diseases 0.000 claims 4
- 238000012163 sequencing technique Methods 0.000 claims 4
- 108020004414 DNA Proteins 0.000 claims 3
- 239000013060 biological fluid Substances 0.000 claims 3
- 239000008280 blood Substances 0.000 claims 3
- 210000004369 blood Anatomy 0.000 claims 3
- 238000006243 chemical reaction Methods 0.000 claims 3
- 238000001514 detection method Methods 0.000 claims 3
- 239000012634 fragment Substances 0.000 claims 3
- 239000003550 marker Substances 0.000 claims 3
- 238000007855 methylation-specific PCR Methods 0.000 claims 3
- 238000002493 microarray Methods 0.000 claims 3
- 238000012544 monitoring process Methods 0.000 claims 3
- 108020004707 nucleic acids Proteins 0.000 claims 3
- 150000007523 nucleic acids Chemical class 0.000 claims 3
- 102000039446 nucleic acids Human genes 0.000 claims 3
- 239000002773 nucleotide Substances 0.000 claims 3
- 125000003729 nucleotide group Chemical group 0.000 claims 3
- 238000011084 recovery Methods 0.000 claims 3
- 239000003153 chemical reaction reagent Substances 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 238000000338 in vitro Methods 0.000 claims 2
- 238000007481 next generation sequencing Methods 0.000 claims 2
- 238000011275 oncology therapy Methods 0.000 claims 2
- 230000003285 pharmacodynamic effect Effects 0.000 claims 2
- 208000015634 Rectal Neoplasms Diseases 0.000 claims 1
- 238000003745 diagnosis Methods 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 229940000406 drug candidate Drugs 0.000 claims 1
- 229940079826 hydrogen sulfite Drugs 0.000 claims 1
- 210000002429 large intestine Anatomy 0.000 claims 1
- 238000007854 ligation-mediated PCR Methods 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 230000001613 neoplastic effect Effects 0.000 claims 1
- 230000000144 pharmacologic effect Effects 0.000 claims 1
- 206010038038 rectal cancer Diseases 0.000 claims 1
- 201000001275 rectum cancer Diseases 0.000 claims 1
- 239000013643 reference control Substances 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
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- 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
-
- 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
- C12Q2600/154—Methylation markers
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- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
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- Biotechnology (AREA)
- Microbiology (AREA)
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- Oncology (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Claims (21)
- 一種預測、偵測、診斷或監控人類個體之初癌或癌症之方法,其包含步驟:確定一或多個自該人類個體獲得之生物樣品之LINE-1甲基化作用程度;及將該LINE-1甲基化作用程度與LINE-1甲基化作用對照程度比較,其中較低LINE-1甲基化作用程度表示早發性大腸直腸癌。
- 如請求項1之方法,其中該等生物樣品係選自由以下組成之群:組織樣品、糞便樣品、細胞均質物、血液樣品、一或多種生物流體或其任何組合。
- 如請求項1之方法,其中該LINE-1甲基化作用程度係藉由以下方法確定:甲基化間位點之擴增;亞硫酸氫鹽轉化,接著捕捉及定序;亞硫酸氫鹽甲基化作用概況分析;亞硫酸氫鹽定序;亞硫酸氫鹽掛鎖探針;相對甲基化作用之高通量陣列;亞硫酸氫鹽限制分析;差異甲基化雜交;藉由連接介導PCR之HpaII小型片段富集;甲基化CpG島擴增;利用微陣列雜交之甲基化CpG島擴增;甲基化DNA免疫沉澱;甲基化CpG免疫沉澱;甲基化CpG島回收分析;基於微陣列之甲基化作用評估;甲基化作用敏感任意引物PCR;甲基化作用敏感切除計數;甲基化作用特異PCR;甲基化作用敏感單核苷酸引子延伸;次世代定序;限制標記基因組掃描;簡化表示亞硫酸氫鹽定序;或全基因組霰彈槍亞硫酸氫鹽定序。
- 如請求項1之方法,其中該LINE-1甲基化作用程度係藉由定量亞硫酸氫鹽焦磷酸定序確定。
- 如請求項1之方法,其中該LINE-1甲基化作用程度係藉由定量亞硫酸氫鹽焦磷酸定序,使用核酸SEQ ID NO:13至16確定。
- 一種預測、偵測、診斷或監控人類個體之早發性大腸直腸癌之生物標記,其包含:確定LINE-1甲基化作用程度之生物標記,其中較低之LINE-1甲基化作用程度表示該人類個體存在早發性大腸直腸癌。
- 一種確定人類個體之早發性大腸直腸癌之套組,其包含:用於測量樣品之LINE-1甲基化作用程度之生物標記偵測試劑;及關於將該生物標記偵測試劑用於診斷早發性大腸直腸癌之存在之操作指南,其中該等操作指南包含將該樣品之LINE-1甲基化作用程度與LINE-1甲基化作用對照程度比較之逐步指示。
- 如請求項7之套組,其中該樣品係選自由以下組成之群:組織樣品、糞便樣品、細胞均質物、血液樣品、一或多種生物流體或其任何組合。
- 如請求項7之套組,其中該LINE-1甲基化作用對照程度係獲自健康個體之樣品,其中該健康個體係不罹患早發性大腸直腸癌之人類個體。
- 如請求項7之套組,其中該LINE-1甲基化作用程度係藉由以下方法確定:甲基化間位點之擴增;亞硫酸氫鹽轉化,接著捕捉及定序;亞硫酸氫鹽甲基化作用概況分析;亞硫酸氫鹽定序;亞硫酸氫鹽掛鎖探針;相對甲基化作用之高通量陣列;亞硫酸氫鹽限制分析;差異甲基化雜交;藉由連接介導PCR之HpaII小型片段富集;甲基化CpG島擴增;利用微陣列雜交之甲基化CpG島擴增;甲基化DNA免疫沉澱;甲基化CpG免疫沉澱;甲基化CpG島回收分析;基於微陣列之甲基化作用評估;甲基化作用敏感任意引物PCR;甲基化作用敏感切除計數;甲基化作用特異PCR;甲基化作用敏感單核苷酸引子延伸;次世代定序;限制標記基因組掃描;簡化表示亞硫酸氫鹽定序;或全基因組霰彈槍亞硫酸氫鹽定序。
- 如請求項7之套組,其中該偵測係藉由定量亞硫酸氫鹽焦磷酸定序實施。
- 如請求項7之套組,其中該偵測係藉由定量亞硫酸氫鹽焦磷酸定序,使用核酸SEQ ID NO:13至16實施。
- 一種對診斷罹患早發性大腸直腸癌之病患選擇癌症療法之方法,該方法包含步驟:確定個體之生物樣品之LINE-1甲基化作用程度,其中該LINE-1甲基化作用程度指示早發性大腸直腸癌;及基於早發性大腸直腸癌確定存在於該個體中選擇癌症療法。
- 一種體外實施臨床試驗以評估據信可用於治療早發性大 腸直腸癌之候選藥物之方法,該方法包含:a)藉由包含以下步驟之方法確定早發性大腸直腸癌之存在:確定獲自個體之生物樣品之一或多個細胞之整體LINE-1甲基化作用程度,其中相較於參考對照較低之整體LINE-1甲基化作用程度表示存在早發性大腸直腸癌;b)在將候選藥物投與第一病患子集或將安慰劑、可相比藥物或該候選藥物與另一活性劑之藥物組合投與第二病患子集之後,重複步驟a);及c)監控整體LINE-1甲基化作用程度相較於在該第二病患子集中發生之任何下降之變化,其中第二病患子集中整體LINE-1甲基化作用之統計學顯著下降表示該候選藥物可用於治療該疾病狀態。
- 一種偵測人類個體之大腸直腸癌初癌或早發性大腸直腸癌之方法,其包含步驟:識別疑罹患大腸直腸癌之人類個體;確定一或多個自該人類個體獲得之生物樣品之LINE-1甲基化作用程度;及將該LINE-1甲基化作用程度與LINE-1甲基化作用對照程度比較,其中較低之該LINE-1甲基化作用程度表示存在早發性大腸直腸癌。
- 如請求項15之方法,其中該等生物樣品係選自由以下組成之群:組織樣品、糞便樣品、細胞均質物、血液樣品、一或多種生物流體或其任何組合。
- 如請求項15之方法,其中該LINE-1甲基化作用程度係藉 由以下方法確定:甲基化間位點之擴增;亞硫酸氫鹽轉化,接著捕捉及定序;亞硫酸氫鹽甲基化作用概況分析;亞硫酸氫鹽定序;亞硫酸氫鹽掛鎖探針;相對甲基化作用之高通量陣列;亞硫酸氫鹽限制分析;差異甲基化雜交;藉由連接介導PCR之HpaII小型片段富集;甲基化CpG島擴增;利用微陣列雜交之甲基化CpG島擴增;甲基化DNA免疫沉澱;甲基化CpG免疫沉澱;甲基化CpG島回收分析;基於微陣列之甲基化作用評估;甲基化作用敏感任意引物PCR;甲基化作用敏感切除計數;甲基化作用特異PCR;甲基化作用敏感單核苷酸引子延伸;次世代定序;限制標記基因組掃描;簡化表示亞硫酸氫鹽定序;或全基因組霰彈槍亞硫酸氫鹽定序。
- 如請求項15之方法,其中該LINE-1甲基化作用程度係藉由定量亞硫酸氫鹽焦磷酸定序確定。
- 如請求項15之方法,其中該LINE-1甲基化作用程度係藉由定量亞硫酸氫鹽焦磷酸定序,使用核酸SEQ ID NO:13至16確定。
- 一種偵測人類個體之初癌或癌症之方法,其包含步驟:處理一或多個自該人類個體獲得之生物樣品以確定該一或多個生物樣品之LINE-1甲基化作用程度;及將來自該一或多個生物樣品之該LINE-1甲基化作用程度與來自正常大腸直腸組織之LINE-1甲基化作用程度比較,其中較低之該LINE-1甲基化作用程度表示存在早發性大腸直腸癌。
- 一種體外使用藥效學(PD)生物標記以確定對早發性大腸直腸癌之治療之藥理學反應之方法,該方法包含:第一次確定獲自個體之第一生物樣品之一或多個細胞之整體LINE-1甲基化作用程度,其中若該整體LINE-1甲基化作用程度相較於不疑具有癌症之個體之正常樣品較低,則表示存在早發性大腸直腸癌;在投與藥物之後,重複步驟:第二次確定獲自該個體之第二生物樣品之一或多個細胞之整體LINE-1甲基化作用程度;及比較該第一與第二次之整體LINE-1甲基化作用,其中第一次之LINE-1甲基化作用發生統計學顯著下降表示該藥物可用於治療早發性大腸直腸癌。
Applications Claiming Priority (1)
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US201161454130P | 2011-03-18 | 2011-03-18 |
Publications (2)
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TW201243331A TW201243331A (en) | 2012-11-01 |
TWI456197B true TWI456197B (zh) | 2014-10-11 |
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TW101109222A TWI456197B (zh) | 2011-03-18 | 2012-03-16 | 作為早發性大腸直腸癌之生物標記的(line-1低甲基化作用) |
Country Status (6)
Country | Link |
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US (1) | US20120238463A1 (zh) |
EP (1) | EP2686451A4 (zh) |
AR (1) | AR085818A1 (zh) |
CA (1) | CA2830329A1 (zh) |
TW (1) | TWI456197B (zh) |
WO (1) | WO2012129008A1 (zh) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2014093825A1 (en) * | 2012-12-14 | 2014-06-19 | Chronix Biomedical | Personalized biomarkers for cancer |
WO2014153327A1 (en) * | 2013-03-18 | 2014-09-25 | Barbeau James M | Methods to determine carcinogenesis, identify markers for early cancer diagnosis and identify targets of therapy |
CN103710452B (zh) * | 2013-12-27 | 2015-05-27 | 朱运峰 | 检测外周血游离dna的试剂盒及寡核苷酸 |
TWI637172B (zh) * | 2016-02-25 | 2018-10-01 | 國立清華大學 | 心血管疾病的檢測方法 |
US11142801B2 (en) * | 2015-10-07 | 2021-10-12 | Japanese Foundation For Cancer Research | Tumor determination method |
IL290309B2 (en) | 2015-11-06 | 2024-04-01 | Ventana Med Syst Inc | Representative diagnoses |
ES2619116B1 (es) * | 2015-12-23 | 2018-04-12 | Fundación Para La Investigación Biomédica Del Hospital Universitario 12 De Octubre | Biomarcador para el diagnóstico, pronóstico y seguimiento de cáncer colorrectal de aparición precoz |
WO2018009696A1 (en) * | 2016-07-06 | 2018-01-11 | Youhealth Biotech, Limited | Colon cancer methylation markers and uses thereof |
KR101833023B1 (ko) * | 2016-07-28 | 2018-02-28 | 국립암센터 | 랫트 line-1 글로벌 dna 메틸화 여부 검출 방법 |
WO2018224731A1 (en) * | 2017-06-05 | 2018-12-13 | Ls Cancerdiag Oy | A method for determining whether a subject is at risk to develop cancer and tools related thereto |
WO2020010311A2 (en) * | 2018-07-05 | 2020-01-09 | Active Genomes Expressed Diagnostics, Inc | Viral oncogene influences and gene expression patterns as indicators of early tumorigenesis |
CN108841959B (zh) * | 2018-07-12 | 2022-03-01 | 吉林大学 | 一种口腔及头颈部恶性肿瘤易感性预测试剂盒及系统 |
CN108866189B (zh) * | 2018-07-12 | 2022-03-01 | 吉林大学 | 一种喉鳞状细胞癌易感性预测试剂盒及系统 |
KR102164432B1 (ko) * | 2019-09-18 | 2020-10-13 | 한국과학기술원 | Dna 메틸화 변이를 이용한 면역항암치료 반응성 예측방법 |
WO2023023123A1 (en) * | 2021-08-17 | 2023-02-23 | City Of Hope | Compositions and methods for cell-free dna epigenetic gastrointestinal cancer detection and treatment |
Citations (1)
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CA2685376A1 (en) * | 2007-04-25 | 2008-11-06 | John Wayne Cancer Institute | Use of methylated or unmethylated line-1 dna as a cancer marker |
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JP2008545418A (ja) * | 2005-05-27 | 2008-12-18 | ジョン ウェイン キャンサー インスティチュート | 癌の診断、予後診断、および治療のための遊離循環dnaの使用 |
US20080234223A1 (en) * | 2006-10-30 | 2008-09-25 | University Of Southern California | N4 modifications of pyrimidine analogs and uses thereof |
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2012
- 2012-03-13 CA CA2830329A patent/CA2830329A1/en not_active Abandoned
- 2012-03-13 WO PCT/US2012/028919 patent/WO2012129008A1/en active Application Filing
- 2012-03-13 EP EP12761423.8A patent/EP2686451A4/en not_active Withdrawn
- 2012-03-14 AR ARP120100844A patent/AR085818A1/es unknown
- 2012-03-14 US US13/419,744 patent/US20120238463A1/en not_active Abandoned
- 2012-03-16 TW TW101109222A patent/TWI456197B/zh not_active IP Right Cessation
Patent Citations (1)
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CA2685376A1 (en) * | 2007-04-25 | 2008-11-06 | John Wayne Cancer Institute | Use of methylated or unmethylated line-1 dna as a cancer marker |
Non-Patent Citations (1)
Title |
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S. Ogino et al., "LINE-1 hypomethylation is inversely associated with microsatellite instability and CpG island methylator phenotype in colorectal cancer", Int. J. Cancer, 2008, Vol. 122, No. 12, p. 2767~2763. M. D. Giraldez et al., "MSH6 and MUTYH Deficiency Is a Frequent Event in Early-Onset Colorectal Cancer", Clin. Cancer Res., 2010, Vol. 16, p. 5402~5413. * |
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Publication number | Publication date |
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AR085818A1 (es) | 2013-10-30 |
WO2012129008A1 (en) | 2012-09-27 |
US20120238463A1 (en) | 2012-09-20 |
EP2686451A1 (en) | 2014-01-22 |
TW201243331A (en) | 2012-11-01 |
EP2686451A4 (en) | 2014-12-24 |
CA2830329A1 (en) | 2012-09-27 |
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