IL199051A - Marked nucleotides and nucleosides that can be cleaved by light, and methods of using them in DNA sequencing - Google Patents
Marked nucleotides and nucleosides that can be cleaved by light, and methods of using them in DNA sequencingInfo
- Publication number
- IL199051A IL199051A IL199051A IL19905109A IL199051A IL 199051 A IL199051 A IL 199051A IL 199051 A IL199051 A IL 199051A IL 19905109 A IL19905109 A IL 19905109A IL 199051 A IL199051 A IL 199051A
- Authority
- IL
- Israel
- Prior art keywords
- mmol
- compound
- nucleic acid
- triphosphate
- group
- Prior art date
Links
- 125000003729 nucleotide group Chemical group 0.000 title claims abstract description 94
- 239000002773 nucleotide Substances 0.000 title claims abstract description 92
- 239000002777 nucleoside Substances 0.000 title claims abstract description 88
- 238000000034 method Methods 0.000 title claims description 84
- 238000001712 DNA sequencing Methods 0.000 title abstract description 28
- 125000003835 nucleoside group Chemical group 0.000 title description 6
- 150000003833 nucleoside derivatives Chemical class 0.000 claims abstract description 25
- 230000006820 DNA synthesis Effects 0.000 claims abstract description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 569
- 150000001875 compounds Chemical class 0.000 claims description 222
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 181
- 239000001226 triphosphate Substances 0.000 claims description 129
- -1 or NH Inorganic materials 0.000 claims description 116
- 235000011178 triphosphate Nutrition 0.000 claims description 94
- 238000003786 synthesis reaction Methods 0.000 claims description 91
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 claims description 80
- 238000006243 chemical reaction Methods 0.000 claims description 76
- 108020004707 nucleic acids Proteins 0.000 claims description 62
- 102000039446 nucleic acids Human genes 0.000 claims description 62
- 150000007523 nucleic acids Chemical class 0.000 claims description 62
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 59
- 238000012163 sequencing technique Methods 0.000 claims description 55
- 238000010348 incorporation Methods 0.000 claims description 53
- 239000007787 solid Substances 0.000 claims description 51
- 230000005284 excitation Effects 0.000 claims description 40
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 claims description 27
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 claims description 27
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 24
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical group NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 24
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 24
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 24
- 235000011180 diphosphates Nutrition 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 229930024421 Adenine Natural products 0.000 claims description 12
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 12
- 229960000643 adenine Drugs 0.000 claims description 12
- 229940104302 cytosine Drugs 0.000 claims description 12
- 229940113082 thymine Drugs 0.000 claims description 12
- 229940035893 uracil Drugs 0.000 claims description 12
- 102000004190 Enzymes Human genes 0.000 claims description 10
- 108090000790 Enzymes Proteins 0.000 claims description 10
- 239000001177 diphosphate Substances 0.000 claims description 10
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 8
- 150000004712 monophosphates Chemical class 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- 239000000758 substrate Substances 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- 238000003384 imaging method Methods 0.000 claims description 5
- 125000003367 polycyclic group Chemical group 0.000 claims description 5
- 238000007480 sanger sequencing Methods 0.000 claims description 5
- 230000001588 bifunctional effect Effects 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 238000001668 nucleic acid synthesis Methods 0.000 claims description 4
- 125000003456 2,6-dinitrophenyl group Chemical group [H]C1=C([H])C(=C(*)C(=C1[H])[N+]([O-])=O)[N+]([O-])=O 0.000 claims description 3
- 150000004820 halides Chemical class 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 229910052727 yttrium Inorganic materials 0.000 claims description 3
- 230000000295 complement effect Effects 0.000 claims description 2
- 238000003752 polymerase chain reaction Methods 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 claims 2
- 102100029764 DNA-directed DNA/RNA polymerase mu Human genes 0.000 claims 2
- 102100034343 Integrase Human genes 0.000 claims 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 claims 2
- 239000007850 fluorescent dye Substances 0.000 abstract description 23
- 238000005516 engineering process Methods 0.000 abstract description 22
- 238000004458 analytical method Methods 0.000 abstract description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 235
- 239000000243 solution Substances 0.000 description 204
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- 230000015572 biosynthetic process Effects 0.000 description 88
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- 238000010898 silica gel chromatography Methods 0.000 description 72
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 60
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 42
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- 125000006239 protecting group Chemical group 0.000 description 29
- 238000001269 time-of-flight mass spectrometry Methods 0.000 description 29
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 28
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- 238000007792 addition Methods 0.000 description 24
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- 239000012299 nitrogen atmosphere Substances 0.000 description 23
- 238000004007 reversed phase HPLC Methods 0.000 description 23
- 238000003756 stirring Methods 0.000 description 23
- WQZIDRAQTRIQDX-UHFFFAOYSA-N 6-carboxy-x-rhodamine Chemical compound OC(=O)C1=CC=C(C([O-])=O)C=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 WQZIDRAQTRIQDX-UHFFFAOYSA-N 0.000 description 21
- 238000005481 NMR spectroscopy Methods 0.000 description 21
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 21
- 238000000746 purification Methods 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 20
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- 238000003556 assay Methods 0.000 description 17
- 238000010511 deprotection reaction Methods 0.000 description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 16
- NCGWKCHAJOUDHQ-UHFFFAOYSA-N n,n-diethylethanamine;formic acid Chemical compound OC=O.OC=O.CCN(CC)CC NCGWKCHAJOUDHQ-UHFFFAOYSA-N 0.000 description 16
- 229920006395 saturated elastomer Polymers 0.000 description 16
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- 229960000549 4-dimethylaminophenol Drugs 0.000 description 14
- OIRDTQYFTABQOQ-KQYNXXCUSA-N Adenosine Natural products C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 14
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- WVLBCYQITXONBZ-UHFFFAOYSA-N trimethyl phosphate Chemical compound COP(=O)(OC)OC WVLBCYQITXONBZ-UHFFFAOYSA-N 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 13
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- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- MWEQTWJABOLLOS-UHFFFAOYSA-L disodium;[[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-oxidophosphoryl] hydrogen phosphate;trihydrate Chemical compound O.O.O.[Na+].[Na+].C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP([O-])(=O)OP(O)([O-])=O)C(O)C1O MWEQTWJABOLLOS-UHFFFAOYSA-L 0.000 description 1
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- KDSNLYIMUZNERS-UHFFFAOYSA-N isobutyl amine Natural products CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 1
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- SWFDTFBWXCNRGN-UHFFFAOYSA-N phosphonato phosphate;tributylazanium Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O.CCCC[NH+](CCCC)CCCC.CCCC[NH+](CCCC)CCCC.CCCC[NH+](CCCC)CCCC.CCCC[NH+](CCCC)CCCC SWFDTFBWXCNRGN-UHFFFAOYSA-N 0.000 description 1
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- 238000012545 processing Methods 0.000 description 1
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 102000004169 proteins and genes Human genes 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/567,193 US7893227B2 (en) | 2006-12-05 | 2006-12-05 | 3′-OH unblocked nucleotides and nucleosides base modified with non-cleavable, terminating groups and methods for their use in DNA sequencing |
| US11/567,189 US7897737B2 (en) | 2006-12-05 | 2006-12-05 | 3′-OH unblocked, nucleotides and nucleosides, base modified with photocleavable, terminating groups and methods for their use in DNA sequencing |
| PCT/US2007/086559 WO2008070749A2 (en) | 2006-12-05 | 2007-12-05 | Photocleavable labeled nucleotides and nucleosides and labeled nucleotides and nucleosides and methods for their use in dna sequencing |
Publications (1)
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|---|---|
| IL199051A true IL199051A (en) | 2013-11-28 |
Family
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| IL199051A IL199051A (en) | 2006-12-05 | 2009-06-01 | Marked nucleotides and nucleosides that can be cleaved by light, and methods of using them in DNA sequencing |
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| KR (1) | KR101504640B1 (https=) |
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| IL (1) | IL199051A (https=) |
| MX (2) | MX338089B (https=) |
| NZ (1) | NZ577303A (https=) |
| RU (1) | RU2009121089A (https=) |
| WO (1) | WO2008070749A2 (https=) |
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| US7897737B2 (en) | 2006-12-05 | 2011-03-01 | Lasergen, Inc. | 3′-OH unblocked, nucleotides and nucleosides, base modified with photocleavable, terminating groups and methods for their use in DNA sequencing |
| NZ590265A (en) | 2008-06-11 | 2012-11-30 | Lasergen Inc | Nucleotides and nucleosides and methods for their use in dna sequencing |
| EP2321429B1 (en) | 2008-09-03 | 2016-08-17 | Quantumdx Group Limited | Methods and kits for nucleic acid sequencing |
| US10759824B2 (en) | 2008-09-03 | 2020-09-01 | Quantumdx Group Limited | Design, synthesis and use of synthetic nucleotides comprising charge mass tags |
| WO2013040257A1 (en) | 2011-09-13 | 2013-03-21 | Lasergen, Inc. | 5-methoxy. 3'-oh unblocked, fast photocleavable terminating nucleotides and methods for nucleic acid sequencing |
| WO2013105025A1 (en) * | 2012-01-13 | 2013-07-18 | Koninklijke Philips N.V. | Dna sequencing with reagent recycling on wiregrid |
| CN103602719B (zh) * | 2013-04-07 | 2016-06-08 | 北京迈基诺基因科技有限责任公司 | 一种基因测序方法 |
| WO2015015913A1 (ja) * | 2013-07-31 | 2015-02-05 | 株式会社 日立ハイテクノロジーズ | 核酸分析用フローセル、及び核酸分析装置 |
| GB201414098D0 (en) | 2014-08-08 | 2014-09-24 | Illumina Cambridge Ltd | Modified nucleotide linkers |
| RU2582198C1 (ru) * | 2014-11-20 | 2016-04-20 | Федеральное государственное бюджетное учреждение науки Лимнологический институт Сибирского отделения Российской академии наук (ЛИН СО РАН) | Аналоги природных дезоксирибонуклеозидтрифосфатов и рибонуклеозидтрифосфатов, содержащие репортёрные флуоресцентные группы, для использования в аналитической биоорганической химии |
| CN105001292A (zh) * | 2015-07-14 | 2015-10-28 | 深圳市瀚海基因生物科技有限公司 | 一种光可断裂的荧光标记可逆终端化合物及其在dna或rna测序中的用途 |
| EP3400444A4 (en) | 2016-01-04 | 2019-10-16 | QuantuMDx Group Limited | DESIGN, SYNTHESIS AND USE OF SYNTHETIC NUCLEOTIDES WITH LOADING MASS MARKINGS |
| GB201711219D0 (en) | 2017-07-12 | 2017-08-23 | Illumina Cambridge Ltd | Short pendant arm linkers for nucleotides in sequencing applications |
| CN113272443B (zh) | 2019-01-07 | 2025-01-10 | 安捷伦科技有限公司 | 用于单细胞中的基因组dna和基因表达分析的组合物和方法 |
| CN110568039B (zh) * | 2019-09-06 | 2021-05-04 | 中国科学院生物物理研究所 | 使用新型电化学传感器的氨基酸特异实时检测方法 |
| WO2021194640A1 (en) * | 2020-03-26 | 2021-09-30 | Agilent Technologies, Inc. | Methods and compositions for multistage primer extension reactions |
| GB2605404A (en) * | 2021-03-30 | 2022-10-05 | Sumitomo Chemical Co | Sequencing method |
| WO2022263489A1 (en) * | 2021-06-17 | 2022-12-22 | F. Hoffmann-La Roche Ag | Nucleoside-5 -oligophosphates having a cationically-modified nucleobase |
| IL309368A (en) * | 2021-06-29 | 2024-02-01 | Agilent Technologies Inc | polymerase mutants and use with 3'-OH UNBLOCKED REVERSIBLE TERMINATORS |
| CN114250283B (zh) * | 2021-10-15 | 2022-10-04 | 深圳铭毅智造科技有限公司 | 基于环境敏感染料的单色荧光mrt基因测序试剂及方法 |
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| US5302509A (en) * | 1989-08-14 | 1994-04-12 | Beckman Instruments, Inc. | Method for sequencing polynucleotides |
| YU187991A (sh) * | 1990-12-11 | 1994-09-09 | Hoechst Aktiengesellschaft | 3-(2)-amino-ali tiol-modifikovani, s fluorescentnom bojom vezani nukleozidi, nukleotidi i oligonukleotidi, postupak za njihovo dobijanje i njihova upotreba |
| US6211165B1 (en) * | 1997-05-09 | 2001-04-03 | The Trustees Of The University Of Pennsylvania | Methods and compositions for reducing ischemic injury of the heart by administering adenosine receptor agonists and antagonists |
| US6586413B2 (en) * | 1999-11-05 | 2003-07-01 | The United States Of America As Represented By The Department Of Health And Human Services | Methods and compositions for reducing ischemic injury of the heart by administering adenosine receptor agonists and antagonists |
| AU2001296645A1 (en) | 2000-10-06 | 2002-04-15 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding dna and rna |
| DE60212642T2 (de) * | 2001-04-10 | 2007-06-14 | ECOLE POLYTECHNIQUE FéDéRALE DE LAUSANNE | Verfahren zur verwendung von o6-alkylguanin-dna-alkyltransferasen |
| GB0128526D0 (en) * | 2001-11-29 | 2002-01-23 | Amersham Pharm Biotech Uk Ltd | Nucleotide analogues |
| US7057026B2 (en) * | 2001-12-04 | 2006-06-06 | Solexa Limited | Labelled nucleotides |
| PT3438116T (pt) | 2002-08-23 | 2021-03-23 | Illumina Cambridge Ltd | Nucleótidos identificados |
| CZ294538B6 (cs) * | 2002-12-30 | 2005-01-12 | Ústav Experimentální Botaniky Akademie Vědčeské Re | Substituční deriváty N6-benzyladenosinu, způsob jejich přípravy, jejich použití pro přípravu léčiv, kosmetických přípravků a růstových regulátorů, farmaceutické přípravky, kosmetické přípravky a růstové regulátory tyto sloučeniny obsahující |
| EP2436778A3 (en) * | 2004-03-03 | 2012-07-11 | The Trustees of Columbia University in the City of New York | Photocleavable fluorescent nucleotides for DNA sequencing on chip constructed by site-specific coupling chemistry |
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Also Published As
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|---|---|
| AU2007329361A1 (en) | 2008-06-12 |
| JP5513122B2 (ja) | 2014-06-04 |
| CA2670937C (en) | 2016-07-26 |
| RU2009121089A (ru) | 2011-01-20 |
| MX338089B (es) | 2016-04-01 |
| CN102443030A (zh) | 2012-05-09 |
| BRPI0719923A2 (pt) | 2014-03-04 |
| EP2125856A2 (en) | 2009-12-02 |
| CN102443030B (zh) | 2015-12-16 |
| AU2007329361B2 (en) | 2013-07-18 |
| CA2670937A1 (en) | 2008-06-12 |
| KR101504640B1 (ko) | 2015-03-20 |
| BRPI0719923B1 (pt) | 2021-08-17 |
| MX2009005936A (es) | 2010-01-15 |
| WO2008070749A2 (en) | 2008-06-12 |
| JP2011506265A (ja) | 2011-03-03 |
| HK1169413A1 (zh) | 2013-01-25 |
| EP2125856B1 (en) | 2016-09-14 |
| NZ577303A (en) | 2011-12-22 |
| WO2008070749A3 (en) | 2008-11-27 |
| KR20090101451A (ko) | 2009-09-28 |
| EP2125856A4 (en) | 2013-12-25 |
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