HRP20191108T1 - Postupak dijagnosticiranja kolorektalnog raka iz uzorka ljudskog izmeta kvantitivnim pcr-om - Google Patents
Postupak dijagnosticiranja kolorektalnog raka iz uzorka ljudskog izmeta kvantitivnim pcr-om Download PDFInfo
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- HRP20191108T1 HRP20191108T1 HRP20191108TT HRP20191108T HRP20191108T1 HR P20191108 T1 HRP20191108 T1 HR P20191108T1 HR P20191108T T HRP20191108T T HR P20191108TT HR P20191108 T HRP20191108 T HR P20191108T HR P20191108 T1 HRP20191108 T1 HR P20191108T1
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- 238000000034 method Methods 0.000 title claims 17
- 206010009944 Colon cancer Diseases 0.000 title claims 11
- 208000001333 Colorectal Neoplasms Diseases 0.000 title claims 11
- 210000003608 fece Anatomy 0.000 title claims 5
- 238000011002 quantification Methods 0.000 claims 14
- 239000000523 sample Substances 0.000 claims 11
- 230000001580 bacterial effect Effects 0.000 claims 7
- 239000013068 control sample Substances 0.000 claims 6
- 108020004465 16S ribosomal RNA Proteins 0.000 claims 5
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 3
- 108020004711 Nucleic Acid Probes Proteins 0.000 claims 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims 2
- 238000002052 colonoscopy Methods 0.000 claims 2
- 239000002853 nucleic acid probe Substances 0.000 claims 2
- 108020004707 nucleic acids Proteins 0.000 claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 2
- 102000039446 nucleic acids Human genes 0.000 claims 2
- 238000003753 real-time PCR Methods 0.000 claims 2
- 239000000090 biomarker Substances 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 238000001514 detection method Methods 0.000 claims 1
- 239000012528 membrane Substances 0.000 claims 1
- 238000012216 screening Methods 0.000 claims 1
- 235000012239 silicon dioxide Nutrition 0.000 claims 1
- 239000000377 silicon dioxide Substances 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
- C12Q1/6806—Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
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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
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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
- C12Q1/6888—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
- C12Q1/689—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
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- 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
- C12Q2600/118—Prognosis of disease development
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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
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
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- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Immunology (AREA)
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- Bioinformatics & Cheminformatics (AREA)
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- Hospice & Palliative Care (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
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Claims (13)
1. Postupak određivanja rizika od razvoja kolorektalnog raka (CRC) kod ljudskog subjekta, naznačen time što se sastoji u:
i. kvantificiranju najmanje jednog bakterijskog 16S rDNA slijeda, kojeg se bira iz spiska kojeg čine SEQ ID NO:1, SEQ ID NO:7 i SEQ ID NO:10, iz uzorka izmeta iz navedenog subjekta;
ii. uspoređivanju razina kvantificiranja u uzorku iz subjekta u (i) s razinama kvantificiranja u kontrolnom uzorku; i
iii. određivanju rizika od razvoja CRC u navedenom ljudskom subjektu, kada dolazi do odstupanja vrijednosti iz uzorka iz subjekta od vrijednosti u navedenom kontrolnom uzorku.
2. Postupak probiranja na kolorektalni rak (CRC) kod ljudskog subjekta, naznačen time što se sastoji u:
i. kvantificiranju najmanje jednog bakterijskog 16S rDNA slijeda, kojeg se bira iz spiska kojeg čine SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:7 i SEQ ID NO:10 iz uzorka izmeta iz navedenog subjekta;
ii. uspoređivanju razina kvantificiranja u uzorku iz subjekta u (i) s razinama kvantificiranja u kontrolnom uzorku; i
iii. dijagnosticiranju, ranom detektiranju, ili određivanju povrata CRC u navedenom ljudskom subjektu, ili određivanju da treba provesti kolonoskopiju kod navedenog ljudskog subjekta, kada dolazi do odstupanja vrijednosti iz uzorka iz subjekta od vrijednosti u navedenom kontrolnom uzorku.
3. Postupak u skladu s bilo kojim od patentnih zahtjeva 1 ili 2, naznačen time što se navedeni postupak sastoji u koraku (i) u kvantificiranju 2, 3 ili svih navedenih bakterijskih sljedova, po mogućnosti svih navedenih bakterijskih sljedova.
4. Postupak u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačen time što se najmanje dva navedena bakterijska slijeda kvantificira u koraku i), te se određuje najmanje jedan od omjera između razina kvantificiranja navedenih sljedova, što dodatno uključuje uspoređivanje najmanje jednog od navedenih omjera u navedenom subjektu s omjerom u kontrolnom uzorku, gdje odstupanje omjera od navedenog kontrolnog uzorka ukazuje na CRC.
5. Postupak u skladu s bilo kojim od patentnih zahtjeva 1 do 4, naznačen time što se, prije kvantificiranja navedenih bakterijskih sljedova, DNA ekstrahira iz uzorka izmeta, što implicira fizičko narušavanje uzorka na bilo koji način, a DNA se pročišćuje na stupcima od membrana silicijevog dioksida.
6. Postupak u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačen time što se kvantificiranje navedenih bakterijskih sljedova provodi kvantitativnim PCR-om.
7. Postupak u skladu s patentnim zahtjevom 6, naznačen time što se razine kvantificiranja sljedova izražava kao graničnu vrijednost ciklusa (Ct).
8. Postupak u skladu s bilo kojim od patentnih zahtjeva 1 do 7, naznačen time što se najmanje jednu navedenu razinu kvantificiranja 16S rDNA određuje kvantitativnim PCR-om iz navedenog uzorka ljudskog izmeta, te što se kvantificiranje razina SEQ ID NO: 1 određuje upotrebom početnica s najmanje 90 % istovjetnosti sa SEQ ID NO: 2 odnosno 13; kvantificiranje razina SEQ ID NO: 4 se određuje upotrebom početnica s najmanje 90 % istovjetnosti sa SEQ ID NO: 5 odnosno 6; kvantificiranje razina SEQ ID NO: 7 se određuje upotrebom početnica s najmanje 90 % istovjetnosti sa SEQ ID NO: 8 odnosno 9; i kvantificiranje razina SEQ ID NO: 10 se određuje upotrebom početnica s najmanje 90 % istovjetnosti sa SEQ ID NO: 11 odnosno 12.
9. Postupak u skladu s bilo kojim od patentnih zahtjeva 1 do 8, naznačen time što se razine SEQ ID NO: 1 određuje upotrebom početnica sa slijedom SEQ ID NO: 2 i 13, razine SEQ ID NO: 4 se određuje upotrebom početnica sa slijedom SEQ ID NO: 5 i 6; razine SEQ ID NO: 7 se određuje upotrebom početnica sa slijedom SEQ ID NO: 8 i 9; i razine SEQ ID NO: 10 se određuje upotrebom početnica sa slijedom SEQ ID NO: 11 i 12.
10. Postupak u skladu s bilo kojim od patentnih zahtjeva 1 do 9, naznačen time što navedeni postupak dodatno uključuje detektiranje i/ili kvantificiranje jednog ili više molekulskih bioloških biljega za koje se zna da ukazuju na CRC.
11. Postupak u skladu s bilo kojim od patentnih zahtjeva 1 do 10, naznačen time što navedeni postupak dodatno uključuje spremanje rezultata postupka u računalno čitljivom mediju.
12. Upotreba kompleta za dijagnosticiranje, rano detektiranje ili određivanje povrata CRC, određivanje rizika od razvoja CRC ili određivanje treba li provesti kolonoskopiju, iz uzorka izmeta iz ljudskog subjekta, postupkom u skladu s bilo kojim od patentnih zahtjeva 1 do 11, naznačena time što navedeni komplet sadrži:
a. reagens kojeg se bira iz skupine koju čine:
i. nukleinskokiselinske sonde koje mogu specifično hibridizirati s najmanje jednim 16S rDNA slijedom kojeg se bira iz spiska kojeg čine SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:7 i SEQ ID NO: 10; ili
ii. par nukleinskokiselinskih početnica koje mogu specifično amplificirati najmanje jedan 16S rDNA slijed kojeg se bira iz spiska kojeg čine SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:7 i SEQ ID NO:10; i
b. upute o kvantificiranju razina jednog ili više navedenih sljedova iz uzorka ljudskog izmeta.
13. Upotreba kompleta u skladu s patentnim zahtjevom 12, naznačena time što se navedene nukleinskokiselinske sonde u (i) ili par nukleinskokiselinskih početnica u (ii) bira iz skupine koju čine SEQ ID NO: 2, SEQ ID NO: 13, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 11, te SEQ ID NO:12; ili s najmanje 90 % istovjetnosti prema njima.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14382074.4A EP2915884B1 (en) | 2014-03-03 | 2014-03-03 | Method for diagnosing colorectal cancer from a human feces sample by quantitive PCR |
| EP15708187.8A EP3114234B1 (en) | 2014-03-03 | 2015-03-03 | Method for diagnosing colorectal cancer from a human feces sample by quantitive pcr |
| PCT/EP2015/054451 WO2015132273A1 (en) | 2014-03-03 | 2015-03-03 | Method for diagnosing colorectal cancer from a human feces sample by quantitive pcr, primers and kit |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20191108T1 true HRP20191108T1 (hr) | 2019-09-20 |
Family
ID=50241352
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20191108TT HRP20191108T1 (hr) | 2014-03-03 | 2019-06-18 | Postupak dijagnosticiranja kolorektalnog raka iz uzorka ljudskog izmeta kvantitivnim pcr-om |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US10927416B2 (hr) |
| EP (2) | EP2915884B1 (hr) |
| JP (2) | JP7053146B2 (hr) |
| KR (1) | KR102354660B1 (hr) |
| CN (1) | CN106574294A (hr) |
| AU (1) | AU2015226203B2 (hr) |
| CA (1) | CA2941502C (hr) |
| DK (1) | DK3114234T3 (hr) |
| ES (2) | ES2661684T3 (hr) |
| HR (1) | HRP20191108T1 (hr) |
| IL (1) | IL247370B (hr) |
| MX (1) | MX2016011377A (hr) |
| PT (1) | PT3114234T (hr) |
| RU (1) | RU2692555C2 (hr) |
| SI (1) | SI3114234T1 (hr) |
| TR (1) | TR201909533T4 (hr) |
| WO (1) | WO2015132273A1 (hr) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3130680A1 (en) | 2015-08-11 | 2017-02-15 | Universitat de Girona | Method for the detection, follow up and/or classification of intestinal diseases |
| CN105543354B (zh) * | 2015-12-31 | 2019-07-26 | 广州市康立明生物科技有限责任公司 | 一种肿瘤分子检测/诊断试剂 |
| WO2017172894A2 (en) * | 2016-03-30 | 2017-10-05 | The Trustees Of Columbia University In The City Of New York | Methods of preventing, treating and detecting colorectal cancer using butyrate producing bacteria |
| CN108690864A (zh) * | 2017-10-31 | 2018-10-23 | 中山大学 | 一种粪便样本中菌群稳态评价方法及在结直肠癌筛查中的应用 |
| KR102282490B1 (ko) | 2018-01-12 | 2021-07-28 | 주식회사 엠디헬스케어 | 패칼리박테리움 프라우스니찌 유래 나노소포 및 이의 용도 |
| WO2019226035A1 (ko) * | 2018-05-25 | 2019-11-28 | 주식회사 엠디헬스케어 | Qpcr 분석을 통한 대장암 진단방법 |
| CN110857450B (zh) * | 2018-08-22 | 2023-04-07 | 深圳华大生命科学研究院 | 结直肠癌标志物及其应用 |
| CA3118304A1 (en) * | 2018-11-02 | 2020-05-07 | The Regents Of The University Of California | Methods to diagnose and treat cancer using non-human nucleic acids |
| US20220145400A1 (en) | 2019-03-13 | 2022-05-12 | Goodgut S.L. | Improved method for the screening, diagnosis and/or monitoring of colorectal advanced neoplasia, advanced adenoma and/or colorectal cancer |
| JP2022528749A (ja) * | 2019-03-28 | 2022-06-15 | シージェイ バイオサイエンス， インク． | フィーカリバクテリウム属微生物およびそれを含む抗癌組成物 |
| KR102308931B1 (ko) * | 2019-05-24 | 2021-10-06 | 주식회사 엠디헬스케어 | qPCR 분석을 통한 대장염 진단방법 |
| CN111500732A (zh) * | 2020-05-25 | 2020-08-07 | 福建医科大学 | 微生物在作为子宫内膜癌的诊断标志物中的应用和试剂盒 |
| CN117305487A (zh) | 2020-05-27 | 2023-12-29 | 微度(苏州)生物科技有限公司 | 一种用于结直肠癌早期诊断的生物标志物组合物及应用 |
| CN112048564A (zh) * | 2020-08-11 | 2020-12-08 | 康美华大基因技术有限公司 | 一种快速检测瘤胃球菌的荧光定量pcr引物组、试剂盒及其应用 |
| CN114107527A (zh) * | 2021-12-10 | 2022-03-01 | 中国药科大学 | 用于检测丁酰辅酶a脱氢酶基因的引物对及试剂盒 |
| CN115261271B (zh) * | 2022-08-01 | 2023-12-12 | 厦门承葛生物科技有限公司 | 一种肠道菌群的高通量分离培养与筛选方法 |
| CN115963268B (zh) * | 2023-02-14 | 2023-09-19 | 浙江大学 | 一种用于结直肠癌早期诊断的血浆分泌蛋白组合及应用 |
| CN117051113B (zh) * | 2023-10-12 | 2023-12-29 | 上海爱谱蒂康生物科技有限公司 | 生物标志物组合在制备预测结直肠癌的试剂盒中的应用 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6054278A (en) * | 1997-05-05 | 2000-04-25 | The Perkin-Elmer Corporation | Ribosomal RNA gene polymorphism based microorganism identification |
| WO2001023608A2 (en) * | 1999-09-27 | 2001-04-05 | Merck Sharp & Dohme De Espana, S.A.E. | Hybridization probes which specifically detect strains of the genera microbispora, microtetraspora, nonomuria and planobispora |
| US20100255481A1 (en) * | 2007-10-30 | 2010-10-07 | Olympus Corporation | Method for detection of adenoma or cancer by genetic analysis |
| JP2009165401A (ja) * | 2008-01-16 | 2009-07-30 | Olympus Corp | 標的物質の定量方法 |
| WO2010010914A1 (ja) | 2008-07-23 | 2010-01-28 | オリンパス株式会社 | 糞便試料からの核酸回収方法、核酸解析方法及び糞便試料処理装置 |
| WO2012170478A2 (en) * | 2011-06-06 | 2012-12-13 | The University Of North Carolina At Chapel Hill | Methods and kits for detecting adenomas, colorectal cancer, and uses thereof |
| EP2988761A1 (en) * | 2013-03-05 | 2016-03-02 | Rijksuniversiteit Groningen | Use of faecali bacterium prausnitzii htf-f (dsm 26943) to suppress inflammation. |
| US10023918B2 (en) * | 2013-03-14 | 2018-07-17 | University Of Ottawa | Methods for the diagnosis and treatment of inflammatory bowel disease |
| CN105473738B (zh) * | 2013-08-06 | 2018-09-21 | 深圳华大基因科技有限公司 | 结直肠癌生物标志物 |
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2014
- 2014-03-03 EP EP14382074.4A patent/EP2915884B1/en active Active
- 2014-03-03 ES ES14382074.4T patent/ES2661684T3/es active Active
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2015
- 2015-03-03 EP EP15708187.8A patent/EP3114234B1/en active Active
- 2015-03-03 TR TR2019/09533T patent/TR201909533T4/tr unknown
- 2015-03-03 CA CA2941502A patent/CA2941502C/en active Active
- 2015-03-03 ES ES15708187T patent/ES2734143T3/es active Active
- 2015-03-03 WO PCT/EP2015/054451 patent/WO2015132273A1/en active Application Filing
- 2015-03-03 PT PT15708187T patent/PT3114234T/pt unknown
- 2015-03-03 JP JP2016555535A patent/JP7053146B2/ja active Active
- 2015-03-03 RU RU2016138766A patent/RU2692555C2/ru active
- 2015-03-03 MX MX2016011377A patent/MX2016011377A/es active IP Right Grant
- 2015-03-03 SI SI201530802T patent/SI3114234T1/sl unknown
- 2015-03-03 US US15/122,897 patent/US10927416B2/en active Active
- 2015-03-03 DK DK15708187.8T patent/DK3114234T3/da active
- 2015-03-03 CN CN201580022938.6A patent/CN106574294A/zh active Pending
- 2015-03-03 AU AU2015226203A patent/AU2015226203B2/en active Active
- 2015-03-03 KR KR1020167027370A patent/KR102354660B1/ko active IP Right Grant
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2016
- 2016-08-21 IL IL247370A patent/IL247370B/en active IP Right Grant
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2019
- 2019-06-18 HR HRP20191108TT patent/HRP20191108T1/hr unknown
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2020
- 2020-05-27 JP JP2020092167A patent/JP2020146052A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP3114234B1 (en) | 2019-04-24 |
| KR20170028296A (ko) | 2017-03-13 |
| ES2734143T3 (es) | 2019-12-04 |
| EP2915884A1 (en) | 2015-09-09 |
| PT3114234T (pt) | 2019-07-12 |
| EP3114234A1 (en) | 2017-01-11 |
| JP7053146B2 (ja) | 2022-04-12 |
| TR201909533T4 (tr) | 2019-07-22 |
| US10927416B2 (en) | 2021-02-23 |
| KR102354660B1 (ko) | 2022-01-24 |
| WO2015132273A1 (en) | 2015-09-11 |
| IL247370A0 (en) | 2016-11-30 |
| RU2692555C2 (ru) | 2019-06-25 |
| MX2016011377A (es) | 2017-05-04 |
| US20170096709A1 (en) | 2017-04-06 |
| ES2661684T3 (es) | 2018-04-03 |
| RU2016138766A (ru) | 2018-04-03 |
| RU2016138766A3 (hr) | 2018-04-03 |
| CN106574294A (zh) | 2017-04-19 |
| CA2941502A1 (en) | 2015-09-11 |
| AU2015226203A1 (en) | 2016-10-20 |
| AU2015226203B2 (en) | 2020-11-12 |
| CA2941502C (en) | 2023-09-26 |
| JP2017508464A (ja) | 2017-03-30 |
| EP2915884B1 (en) | 2017-12-06 |
| JP2020146052A (ja) | 2020-09-17 |
| DK3114234T3 (da) | 2019-07-15 |
| IL247370B (en) | 2020-07-30 |
| SI3114234T1 (sl) | 2019-09-30 |
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