HRP20140692T1 - Postupci i nukleinske kiseline za analizu poremeä†aja proliferacije stanica - Google Patents
Postupci i nukleinske kiseline za analizu poremeä†aja proliferacije stanica Download PDFInfo
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- HRP20140692T1 HRP20140692T1 HRP20140692AT HRP20140692T HRP20140692T1 HR P20140692 T1 HRP20140692 T1 HR P20140692T1 HR P20140692A T HRP20140692A T HR P20140692AT HR P20140692 T HRP20140692 T HR P20140692T HR P20140692 T1 HRP20140692 T1 HR P20140692T1
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- genomic dna
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- 238000000034 method Methods 0.000 title claims abstract 9
- 108020004707 nucleic acids Proteins 0.000 title claims abstract 4
- 150000007523 nucleic acids Chemical class 0.000 title claims abstract 4
- 102000039446 nucleic acids Human genes 0.000 title claims abstract 4
- 230000002062 proliferating effect Effects 0.000 title abstract 2
- 238000004458 analytical method Methods 0.000 title 1
- 230000011987 methylation Effects 0.000 claims abstract 6
- 238000007069 methylation reaction Methods 0.000 claims abstract 6
- 238000001514 detection method Methods 0.000 claims abstract 2
- 108020004414 DNA Proteins 0.000 claims 9
- 239000012472 biological sample Substances 0.000 claims 6
- 206010005003 Bladder cancer Diseases 0.000 claims 5
- 206010006187 Breast cancer Diseases 0.000 claims 5
- 208000026310 Breast neoplasm Diseases 0.000 claims 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 5
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 5
- 210000000481 breast Anatomy 0.000 claims 5
- 239000003153 chemical reaction reagent Substances 0.000 claims 5
- 210000004072 lung Anatomy 0.000 claims 5
- 201000005202 lung cancer Diseases 0.000 claims 5
- 208000020816 lung neoplasm Diseases 0.000 claims 5
- 239000002773 nucleotide Substances 0.000 claims 5
- 125000003729 nucleotide group Chemical group 0.000 claims 5
- 201000005112 urinary bladder cancer Diseases 0.000 claims 5
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims 4
- 239000012634 fragment Substances 0.000 claims 4
- 108091029430 CpG site Proteins 0.000 claims 3
- 230000000295 complement effect Effects 0.000 claims 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims 2
- 108090000790 Enzymes Proteins 0.000 claims 2
- 102000004190 Enzymes Human genes 0.000 claims 2
- 108091034117 Oligonucleotide Proteins 0.000 claims 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims 2
- 230000003321 amplification Effects 0.000 claims 2
- 210000004027 cell Anatomy 0.000 claims 2
- 229940104302 cytosine Drugs 0.000 claims 2
- 238000000605 extraction Methods 0.000 claims 2
- 238000002955 isolation Methods 0.000 claims 2
- 238000003199 nucleic acid amplification method Methods 0.000 claims 2
- 108091008146 restriction endonucleases Proteins 0.000 claims 2
- 101000703741 Homo sapiens Short stature homeobox protein 2 Proteins 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 1
- 206010036790 Productive cough Diseases 0.000 claims 1
- 238000005299 abrasion Methods 0.000 claims 1
- 239000012620 biological material Substances 0.000 claims 1
- 238000001574 biopsy Methods 0.000 claims 1
- 210000004369 blood Anatomy 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 210000000601 blood cell Anatomy 0.000 claims 1
- 210000001124 body fluid Anatomy 0.000 claims 1
- 239000010839 body fluid Substances 0.000 claims 1
- 238000013276 bronchoscopy Methods 0.000 claims 1
- 230000001680 brushing effect Effects 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 230000015556 catabolic process Effects 0.000 claims 1
- 239000007857 degradation product Substances 0.000 claims 1
- 238000006731 degradation reaction Methods 0.000 claims 1
- 238000009396 hybridization Methods 0.000 claims 1
- 230000006607 hypermethylation Effects 0.000 claims 1
- 210000002381 plasma Anatomy 0.000 claims 1
- 230000010076 replication Effects 0.000 claims 1
- 210000002966 serum Anatomy 0.000 claims 1
- 210000003802 sputum Anatomy 0.000 claims 1
- 208000024794 sputum Diseases 0.000 claims 1
- 210000001519 tissue Anatomy 0.000 claims 1
- 229940035893 uracil Drugs 0.000 claims 1
- 210000002700 urine Anatomy 0.000 claims 1
- 238000003745 diagnosis Methods 0.000 abstract 1
Classifications
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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
-
- 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
- C12Q2600/156—Polymorphic or mutational markers
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- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Analytical Chemistry (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Hospice & Palliative Care (AREA)
- Biophysics (AREA)
- Oncology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Claims (8)
1. Postupak otkrivanja raka pluća, dojke ili mjehura u ispitanika, obuhvaća utvrđivanje razine metilacije gena SHOX2 u biološkom uzorku izoliranom iz tog ispitanika pri čemu hiper-metilacija upućuje na prisutnost takvog raka.
2. Postupak otkrivanja raka pluća, dojke ili mjehura prema zahtjevu 1, obuhvaća dovođenje genomske DNA, izolirane iz biološkog uzorka dobivenog od ispitanika, u doticaj s barem jednim reagensom, ili serijom reagenasa koji razlikuju metilirane i ne-metilirane CpG dinukleotide unutar barem jedne ciljne regije genomske DNA, pri čemu ciljna regija obuhvaća, ili se hibridizira pod strogim uvjetima u sekvencu od barem 16 dodirnih nukleotida u SEQ ID NO: 5, i gdje ti dodirni nukleotidi obuhvaćaju barem jednu CpG dinukleotidnu sekvencu.
3. Postupak otkrivanja raka pluća, dojke ili mjehura prema zahtjevu 1 ili 2, obuhvaća:
a) ekstrakciju ili drugačiju izolaciju genomske DNA iz biološkog uzorka dobivenog od ispitanika,
b) obradu genomske DNA iz a), ili njezinog fragmenta, s jednim ili više reagenasa radi pretvorbe citozin baza koje nisu metilirane na svom položaju 5 u uracil ili drugu bazu koja za otkrivanje nije slična citozinu u vidu svojstava hibridizacije;
c) dovođenje obrađene genomske DNA, ili njezinog obrađenog fragmenta, u doticaj s enzimom za umnožavanje i barem jednom početnicom koja obuhvaća dodirnu sekvencu od barem 9 nukleotida koja je komplementarna, ili se hibridizira pod umjereno strogim ili strogim uvjetima u sekvencu izabranu iz grupe koja obuhvaća SEQ ID NOs: 21, 22, 45 i 46, i njihove komplemente, pri čemu se ciljna genomska DNA ili njezin fragment umnožava radi dobivanja barem jedne kopije, ili se ne umnožava; i
d) utvrđivanje, na temelju prisutnosti ili odsutnosti, ili svojstva te kopije, stanja ili razine metilacije barem jednog CpG dinukleotida u SEQ ID NO: 5, ili prosjeka, ili vrijednosti koja pokazuje srednje stanje ili razinu metilacije više CpG dinukleotida u SEQ ID NO: 5.
4. Postupak prema bilo kojem od zahtjeva 1 do 3, gdje se biološki uzorak dobiven od ispitanika izabire iz grupe koja obuhvaća stanice ili stanične linije, histološka stakalca, biopsije, tkiva fiksirana parafinom, tjelesne tekućine, ejakulat, urin, krvnu plazmu, krvni serum, punu krv, izolirane krvne stanice, sputum i biološku tvar dobivenu bronhoskopijom (uključujući, ali bez ograničavanja, ispiranje bronhija, ispiranje bronhijalnih alveola, četkanje bronhija, abraziju bronhija i kombinacije).
5. Postupak otkrivanja raka pluća, dojke ili mjehura prema zahtjevu 1, obuhvaća:
a) ekstrakciju ili drugačiju izolaciju genomske DNA iz biološkog uzorka dobivenog od ispitanika,
b) razgradnju genomske DNA iz a), ili njezinog fragmenta, s jednim ili više restriktivnih enzima osjetljivih na metilaciju;
c) dovođenje razgradnog produkta DNA od restrikcijskog enzima iz b) u doticaj s enzimom za umnožavanje i barem dvije početnice prikladne za umnožavanje sekvence koja obuhvaća barem jedan CpG nukleotid u SEQ ID NO: 5,
d) utvrđivanje, na temelju prisutnosti ili odsutnosti kopije, stanja ili razine metilacije barem jednog CpG dinukleotida u SEQ ID NO: 5.
6. Uporaba nukleinske kiseline koja obuhvaća barem 16 dodirnih nukleotida obrađene genomske DNA sekvence izabrane iz grupe koja obuhvaća SEQ ID NOs: 21, 22, 45, 46, i njima komplementarne sekvence za otkrivanje raka pluća, dojke ili mjehura postupkom prema bilo kojem od zahtjeva 1 do 5.
7. Uporaba prema zahtjevu 6, gdje ta nukleinska kiselina obuhvaća barem 50 dodirnih nukleotida.
8. Uporaba kita za provođenje postupka prema bilo kojem od zahtjeva 1 do 4, kit sadrži (a) bisulfit reagens; (b) spremnik prikladan za držanje tog bisulfit reagensa i biološkog uzorka bolesnika; (c) barem jedan set oligonukleotida koji sadrži dva oligonukleotida čije su sekvence u svakom slučaju identične, komplementarne ili hibridiziraju pod strogim ili iznimno strogim uvjetima u segment dužine 9 ili poželjnije 18 baza sekvence izabrane između SEQ ID NOs: 21, 22, 45 i 46.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP07100829 | 2007-01-19 | ||
EP07110019 | 2007-06-11 | ||
EP07113449 | 2007-07-30 |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20140692T1 true HRP20140692T1 (hr) | 2014-09-26 |
Family
ID=39430717
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HRP20140692AT HRP20140692T1 (hr) | 2007-01-19 | 2014-07-18 | Postupci i nukleinske kiseline za analizu poremeä†aja proliferacije stanica |
Country Status (15)
Country | Link |
---|---|
EP (2) | EP2115165B1 (hr) |
JP (2) | JP5342456B2 (hr) |
AT (1) | ATE549418T1 (hr) |
AU (1) | AU2008207110B2 (hr) |
CA (2) | CA2921557C (hr) |
CY (1) | CY1115439T1 (hr) |
DK (1) | DK2258871T3 (hr) |
EA (1) | EA018010B1 (hr) |
ES (2) | ES2384071T3 (hr) |
HR (1) | HRP20140692T1 (hr) |
IL (2) | IL199894A (hr) |
PL (1) | PL2258871T3 (hr) |
PT (1) | PT2258871E (hr) |
SI (1) | SI2258871T1 (hr) |
WO (1) | WO2008087040A2 (hr) |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008077095A2 (en) * | 2006-12-19 | 2008-06-26 | Cornell Research Foundation, Inc. | Use of lecithin:retinol acyl transferase gene promoter methylation in evaluating the cancer state of a subject |
SI2258871T1 (sl) * | 2007-01-19 | 2014-09-30 | Epigenomics Ag Intellectual Property | Postopki in nukleinske kisline za analize celičnih proliferativnih motenj |
US8399193B2 (en) * | 2007-08-30 | 2013-03-19 | City Of Hope | DNA methylation biomarkers for lung cancer |
WO2009074328A2 (en) * | 2007-12-11 | 2009-06-18 | Epigenomics Ag | Methods and nucleic acids for analyses of lung carcinoma |
GB0823445D0 (en) * | 2008-12-23 | 2009-01-28 | Univ Surrey | Biomarker |
EP2966181B1 (en) * | 2009-06-26 | 2018-02-14 | Epigenomics AG | Methods and nucleic acids for analysis of bladder carcinoma |
JP6017458B2 (ja) | 2011-02-02 | 2016-11-02 | ユニヴァーシティ・オブ・ワシントン・スルー・イッツ・センター・フォー・コマーシャリゼーション | 大量並列連続性マッピング |
JP2013074837A (ja) * | 2011-09-30 | 2013-04-25 | Sumitomo Chemical Co Ltd | 哺乳動物由来の検体の癌化度を評価する方法 |
US9683230B2 (en) | 2013-01-09 | 2017-06-20 | Illumina Cambridge Limited | Sample preparation on a solid support |
DK3553175T3 (da) | 2013-03-13 | 2021-08-23 | Illumina Inc | Fremgangsmåde til fremstilling af et nukleinsyresekvenseringsbibliotek |
DK3083994T3 (da) | 2013-12-20 | 2021-09-13 | Illumina Inc | Bevarelse af genomisk konnektivitetsinformation i fragmenterede genomiske DNA-prøver |
CA2964799A1 (en) * | 2014-10-17 | 2016-04-21 | Illumina Cambridge Limited | Contiguity preserving transposition |
WO2017123996A1 (en) | 2016-01-15 | 2017-07-20 | City Of Hope | Targeting glioblastoma stem cells through the tlx-tet3 axis |
CN106222080A (zh) * | 2016-08-12 | 2016-12-14 | 深圳市天元印科技有限公司 | 肺癌预测系统 |
JPWO2020241816A1 (hr) | 2019-05-31 | 2020-12-03 | ||
JP7469771B1 (ja) | 2023-12-13 | 2024-04-17 | 17Live株式会社 | サーバおよび方法 |
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US5457183A (en) | 1989-03-06 | 1995-10-10 | Board Of Regents, The University Of Texas System | Hydroxylated texaphyrins |
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BRPI0518734A2 (pt) * | 2004-11-30 | 2008-12-02 | Veridex Llc | prognàstico de cÂncer de pulmço |
EP1904649A2 (en) * | 2005-07-18 | 2008-04-02 | Epigenomics AG | Compositions and methods for cancer diagnostics comprising pan-cancer markers |
SI2258871T1 (sl) * | 2007-01-19 | 2014-09-30 | Epigenomics Ag Intellectual Property | Postopki in nukleinske kisline za analize celičnih proliferativnih motenj |
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2008
- 2008-01-18 SI SI200831251T patent/SI2258871T1/sl unknown
- 2008-01-18 PT PT101568467T patent/PT2258871E/pt unknown
- 2008-01-18 EA EA200970695A patent/EA018010B1/ru not_active IP Right Cessation
- 2008-01-18 DK DK10156846.7T patent/DK2258871T3/da active
- 2008-01-18 JP JP2009545876A patent/JP5342456B2/ja not_active Expired - Fee Related
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- 2008-01-18 WO PCT/EP2008/000384 patent/WO2008087040A2/en active Application Filing
- 2008-01-18 ES ES08701160T patent/ES2384071T3/es active Active
- 2008-01-18 PL PL10156846T patent/PL2258871T3/pl unknown
- 2008-01-18 CA CA2921557A patent/CA2921557C/en active Active
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Publication number | Publication date |
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IL199894A (en) | 2014-11-30 |
AU2008207110B2 (en) | 2013-10-17 |
EP2115165A2 (en) | 2009-11-11 |
AU2008207110A1 (en) | 2008-07-24 |
SI2258871T1 (sl) | 2014-09-30 |
JP5342456B2 (ja) | 2013-11-13 |
EA018010B1 (ru) | 2013-04-30 |
CA2921557C (en) | 2022-02-08 |
IL233548A0 (en) | 2014-08-31 |
EP2258871A1 (en) | 2010-12-08 |
CA2921557A1 (en) | 2008-07-24 |
WO2008087040A2 (en) | 2008-07-24 |
CA2675895A1 (en) | 2008-07-24 |
ES2384071T3 (es) | 2012-06-29 |
JP2013150611A (ja) | 2013-08-08 |
ES2486190T3 (es) | 2014-08-18 |
JP5818374B2 (ja) | 2015-11-18 |
IL233548A (en) | 2015-07-30 |
AU2008207110A2 (en) | 2009-09-03 |
EA200970695A1 (ru) | 2010-02-26 |
WO2008087040A3 (en) | 2008-10-16 |
IL199894A0 (en) | 2010-04-15 |
PL2258871T3 (pl) | 2014-10-31 |
JP2010516234A (ja) | 2010-05-20 |
EP2115165B1 (en) | 2012-03-14 |
PT2258871E (pt) | 2014-08-27 |
ATE549418T1 (de) | 2012-03-15 |
CY1115439T1 (el) | 2017-01-04 |
CA2675895C (en) | 2016-03-22 |
EP2258871B1 (en) | 2014-05-14 |
DK2258871T3 (da) | 2014-08-11 |
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