RU2011123739A - Протеазы, содержащие одну или несколько комбинируемых мутаций - Google Patents
Протеазы, содержащие одну или несколько комбинируемых мутаций Download PDFInfo
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- RU2011123739A RU2011123739A RU2011123739/10A RU2011123739A RU2011123739A RU 2011123739 A RU2011123739 A RU 2011123739A RU 2011123739/10 A RU2011123739/10 A RU 2011123739/10A RU 2011123739 A RU2011123739 A RU 2011123739A RU 2011123739 A RU2011123739 A RU 2011123739A
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- subtilisin
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- 108091005804 Peptidases Proteins 0.000 title claims 2
- 102000035195 Peptidases Human genes 0.000 title claims 2
- 239000004365 Protease Substances 0.000 title claims 2
- 230000035772 mutation Effects 0.000 title 1
- 108090000787 Subtilisin Proteins 0.000 claims abstract 21
- 239000003599 detergent Substances 0.000 claims abstract 10
- 238000004140 cleaning Methods 0.000 claims abstract 7
- 238000006467 substitution reaction Methods 0.000 claims abstract 6
- 239000013604 expression vector Substances 0.000 claims abstract 4
- 102000039446 nucleic acids Human genes 0.000 claims abstract 4
- 108020004707 nucleic acids Proteins 0.000 claims abstract 4
- 150000007523 nucleic acids Chemical class 0.000 claims abstract 4
- 238000005406 washing Methods 0.000 claims abstract 3
- 102220465972 Cilium assembly protein DZIP1_S24R_mutation Human genes 0.000 claims abstract 2
- 102220545278 Desmoglein-1_S24E_mutation Human genes 0.000 claims abstract 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 2
- 230000000694 effects Effects 0.000 claims abstract 2
- 239000007788 liquid Substances 0.000 claims abstract 2
- 102000004169 proteins and genes Human genes 0.000 claims abstract 2
- 108090000623 proteins and genes Proteins 0.000 claims abstract 2
- 230000002797 proteolythic effect Effects 0.000 claims abstract 2
- 102200143804 rs121434229 Human genes 0.000 claims abstract 2
- 102220270302 rs1416460262 Human genes 0.000 claims abstract 2
- 102220059026 rs786201684 Human genes 0.000 claims abstract 2
- 241000193830 Bacillus <bacterium> Species 0.000 claims 3
- 102000004190 Enzymes Human genes 0.000 claims 2
- 108090000790 Enzymes Proteins 0.000 claims 2
- 108090000854 Oxidoreductases Proteins 0.000 claims 2
- 102000004316 Oxidoreductases Human genes 0.000 claims 2
- 108010056079 Subtilisins Proteins 0.000 claims 2
- 102000005158 Subtilisins Human genes 0.000 claims 2
- 229940088598 enzyme Drugs 0.000 claims 2
- 108010065511 Amylases Proteins 0.000 claims 1
- 102000013142 Amylases Human genes 0.000 claims 1
- 108700038091 Beta-glucanases Proteins 0.000 claims 1
- 102100032487 Beta-mannosidase Human genes 0.000 claims 1
- 102000005575 Cellulases Human genes 0.000 claims 1
- 108010084185 Cellulases Proteins 0.000 claims 1
- 108010023736 Chondroitinases and Chondroitin Lyases Proteins 0.000 claims 1
- 102000011413 Chondroitinases and Chondroitin Lyases Human genes 0.000 claims 1
- 101710121765 Endo-1,4-beta-xylanase Proteins 0.000 claims 1
- 108090000371 Esterases Proteins 0.000 claims 1
- 108050009363 Hyaluronidases Proteins 0.000 claims 1
- 102000001974 Hyaluronidases Human genes 0.000 claims 1
- 108090001060 Lipase Proteins 0.000 claims 1
- 102000004882 Lipase Human genes 0.000 claims 1
- 239000004367 Lipase Substances 0.000 claims 1
- 108090000128 Lipoxygenases Proteins 0.000 claims 1
- 102000003820 Lipoxygenases Human genes 0.000 claims 1
- 108010006035 Metalloproteases Proteins 0.000 claims 1
- 102000005741 Metalloproteases Human genes 0.000 claims 1
- 108700020962 Peroxidase Proteins 0.000 claims 1
- 102000003992 Peroxidases Human genes 0.000 claims 1
- 108010064785 Phospholipases Proteins 0.000 claims 1
- 102000015439 Phospholipases Human genes 0.000 claims 1
- 108010059820 Polygalacturonase Proteins 0.000 claims 1
- 108091007187 Reductases Proteins 0.000 claims 1
- 102000003425 Tyrosinase Human genes 0.000 claims 1
- 108060008724 Tyrosinase Proteins 0.000 claims 1
- 108090000637 alpha-Amylases Proteins 0.000 claims 1
- 108010084650 alpha-N-arabinofuranosidase Proteins 0.000 claims 1
- 235000019418 amylase Nutrition 0.000 claims 1
- 229940025131 amylases Drugs 0.000 claims 1
- 108010055059 beta-Mannosidase Proteins 0.000 claims 1
- 108010005400 cutinase Proteins 0.000 claims 1
- 238000004851 dishwashing Methods 0.000 claims 1
- 108010093305 exopolygalacturonase Proteins 0.000 claims 1
- 239000004744 fabric Substances 0.000 claims 1
- 108010002430 hemicellulase Proteins 0.000 claims 1
- 239000004615 ingredient Substances 0.000 claims 1
- 108010059345 keratinase Proteins 0.000 claims 1
- 108010062085 ligninase Proteins 0.000 claims 1
- 235000019421 lipase Nutrition 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 108010087558 pectate lyase Proteins 0.000 claims 1
- -1 perhydrolases Proteins 0.000 claims 1
- 239000003381 stabilizer Substances 0.000 claims 1
- 108010038851 tannase Proteins 0.000 claims 1
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/52—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea
- C12N9/54—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea bacteria being Bacillus
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/38—Products with no well-defined composition, e.g. natural products
- C11D3/386—Preparations containing enzymes, e.g. protease or amylase
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/38—Products with no well-defined composition, e.g. natural products
- C11D3/386—Preparations containing enzymes, e.g. protease or amylase
- C11D3/38609—Protease or amylase in solid compositions only
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/38—Products with no well-defined composition, e.g. natural products
- C11D3/386—Preparations containing enzymes, e.g. protease or amylase
- C11D3/38618—Protease or amylase in liquid compositions only
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/38—Products with no well-defined composition, e.g. natural products
- C11D3/386—Preparations containing enzymes, e.g. protease or amylase
- C11D3/38627—Preparations containing enzymes, e.g. protease or amylase containing lipase
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/38—Products with no well-defined composition, e.g. natural products
- C11D3/386—Preparations containing enzymes, e.g. protease or amylase
- C11D3/38636—Preparations containing enzymes, e.g. protease or amylase containing enzymes other than protease, amylase, lipase, cellulase, oxidase or reductase
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/38—Products with no well-defined composition, e.g. natural products
- C11D3/386—Preparations containing enzymes, e.g. protease or amylase
- C11D3/38645—Preparations containing enzymes, e.g. protease or amylase containing cellulase
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/38—Products with no well-defined composition, e.g. natural products
- C11D3/386—Preparations containing enzymes, e.g. protease or amylase
- C11D3/38654—Preparations containing enzymes, e.g. protease or amylase containing oxidase or reductase
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/38—Products with no well-defined composition, e.g. natural products
- C11D3/386—Preparations containing enzymes, e.g. protease or amylase
- C11D3/38663—Stabilised liquid enzyme compositions
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- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/38—Products with no well-defined composition, e.g. natural products
- C11D3/386—Preparations containing enzymes, e.g. protease or amylase
- C11D3/38681—Chemically modified or immobilised enzymes
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21062—Subtilisin (3.4.21.62)
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/52—Genes encoding for enzymes or proenzymes
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- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Plant Pathology (AREA)
- Enzymes And Modification Thereof (AREA)
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Abstract
1. Выделенный вариант субтилизина, который является зрелой формой, обладающей протеолитической активностью и включающей замену в двух или более положениях, выбираемых из положений 24, 45, 101, 109, 118, 213 и 217, нумерация которых соответствует аминокислотной последовательности субтилизина BPN' B. amyloliquefaciens, представленной как SEQ ID NO:1.2. Выделенный вариант субтилизина по п.1, который имеет относительный индекс продуктивности уровня экспрессии белка (ТСА PI) и/или индекс продуктивности активности по удалению пятен (BMI PI), больший или равный 0,5.3. Выделенный вариант субтилизина по п.1 или 2, где указанный субтилизинпредставляет собой GG36 и где указанная замена в двух или более положениях выбрана из S24Q, S24E, S24L, S24R, R45Q, R45E, R45L, S101Q, S101E, S101L, S101R, Q109E, Q109L, Q109R, G118Q, G118E, G118L, G118R, T213Q, T213L, T213R, T213E, L217Q и L217E, соответствующих положениям субтилизина BPN' SEQ ID NO:1.4. Выделенный вариант субтилизина по любому из п.1 или 2, где указанный субтилизинпредставляет собой GG36 и где указанная замена в двух или более положениях представляет собой S24Q-R45Q-S101Q-G118Q-T213Q, соответствующую положениям субтилизина BPN' SEQ ID NO:1.5. Выделенная нуклеиновая кислота, кодирующая вариант субтилизина по любому из пп.1-4.6. Экспрессирующий вектор, содержащий нуклеиновую кислоту по п.5.7. Клетка-хозяин, содержащая экспрессирующий вектор по п.6.8. Очищающая композиция, содержащая по меньшей мере один вариант субтилизина по любому из пп.1-4.9. Очищающая композиция по п.8, которая является детергентом.10. Очищающая композиция по п.9, в которой указанный детергент является сверхсильным жидким или сухим стиральным детергентом.11. Очищающая композиция по п.9, в которой указанный детергент является детергентом для мыть�
Claims (15)
1. Выделенный вариант субтилизина Bacillus, который является зрелой формой, обладающей протеолитической активностью и включающей замену в двух или более положениях, выбираемых из положений 24, 45, 101, 109, 118, 213 и 217, нумерация которых соответствует аминокислотной последовательности субтилизина BPN' B. amyloliquefaciens, представленной как SEQ ID NO:1.
2. Выделенный вариант субтилизина по п.1, который имеет относительный индекс продуктивности уровня экспрессии белка (ТСА PI) и/или индекс продуктивности активности по удалению пятен (BMI PI), больший или равный 0,5.
3. Выделенный вариант субтилизина по п.1 или 2, где указанный субтилизин Bacillus представляет собой GG36 и где указанная замена в двух или более положениях выбрана из S24Q, S24E, S24L, S24R, R45Q, R45E, R45L, S101Q, S101E, S101L, S101R, Q109E, Q109L, Q109R, G118Q, G118E, G118L, G118R, T213Q, T213L, T213R, T213E, L217Q и L217E, соответствующих положениям субтилизина BPN' SEQ ID NO:1.
4. Выделенный вариант субтилизина по любому из п.1 или 2, где указанный субтилизин Bacillus представляет собой GG36 и где указанная замена в двух или более положениях представляет собой S24Q-R45Q-S101Q-G118Q-T213Q, соответствующую положениям субтилизина BPN' SEQ ID NO:1.
5. Выделенная нуклеиновая кислота, кодирующая вариант субтилизина по любому из пп.1-4.
6. Экспрессирующий вектор, содержащий нуклеиновую кислоту по п.5.
7. Клетка-хозяин, содержащая экспрессирующий вектор по п.6.
8. Очищающая композиция, содержащая по меньшей мере один вариант субтилизина по любому из пп.1-4.
9. Очищающая композиция по п.8, которая является детергентом.
10. Очищающая композиция по п.9, в которой указанный детергент является сверхсильным жидким или сухим стиральным детергентом.
11. Очищающая композиция по п.9, в которой указанный детергент является детергентом для мытья посуды.
12. Очищающая композиция по любому из пп.8-11, дополнительно содержащая один или несколько дополнительных ферментов или производных ферментов, выбираемых из гемицеллюлаз, целлюлаз, пероксидаз, протеаз, металлопротеаз, ксиланаз, липаз, фосфолипаз, эстераз, пергидролаз, кутиназ, пектиназ, пектат-лиаз, маннаназ, кератиназ, редуктаз, оксидаз, фенолоксидаз, липоксигеназ, лигниназ, пуллуланаз, танназ, пентозаназ, маланаз, β-глюканаз, арабинозидаз, гиалуронидаз, хондроитиназ, лакказ и амилаз или их смесей.
13. Очищающая композиция по любому из пп.8-11, дополнительно содержащая по меньшей мере один стабилизатор.
14. Очищающая композиция, содержащая по меньшей мере 0,0001 мас.% по меньшей мере одного варианта субтилизина по любому из пп.1-4 и необязательно по меньшей мере один приемлемый дополнительный ингредиент.
15. Способ очистки, который включает стадии:
а) контактирования поверхности и/или изделия, содержащего ткань, с очищающей композицией по любому из пп.7-14; и
b) необязательно промывки и/или прополаскивания указанной поверхности или изделия.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11354508P | 2008-11-11 | 2008-11-11 | |
| US61/113,545 | 2008-11-11 | ||
| US21880209P | 2009-06-19 | 2009-06-19 | |
| US61/218,802 | 2009-06-19 | ||
| PCT/US2009/063837 WO2010056653A2 (en) | 2008-11-11 | 2009-11-10 | Proteases comprising one or more combinable mutations |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2011123739A true RU2011123739A (ru) | 2012-12-20 |
| RU2560978C2 RU2560978C2 (ru) | 2015-08-20 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2011123739/10A RU2560978C2 (ru) | 2008-11-11 | 2009-11-10 | Протеазы, содержащие одну или несколько комбинируемых мутаций |
Country Status (11)
| Country | Link |
|---|---|
| US (4) | US8753861B2 (ru) |
| EP (3) | EP3031894A1 (ru) |
| JP (3) | JP2012508031A (ru) |
| KR (1) | KR20110095260A (ru) |
| CN (4) | CN102209775A (ru) |
| AR (1) | AR074311A1 (ru) |
| BR (2) | BRPI0922083A2 (ru) |
| CA (1) | CA2743302A1 (ru) |
| MX (1) | MX2011004802A (ru) |
| RU (1) | RU2560978C2 (ru) |
| WO (1) | WO2010056653A2 (ru) |
Families Citing this family (117)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE450606T1 (de) * | 2002-01-16 | 2009-12-15 | Genencor Int | Mehrfachsubstituierte proteasevarianten |
| US20090060933A1 (en) * | 2004-06-14 | 2009-03-05 | Estell David A | Proteases producing an altered immunogenic response and methods of making and using the same |
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-
2009
- 2009-11-10 CN CN2009801445264A patent/CN102209775A/zh active Pending
- 2009-11-10 BR BRPI0922083A patent/BRPI0922083A2/pt not_active Application Discontinuation
- 2009-11-10 MX MX2011004802A patent/MX2011004802A/es active IP Right Grant
- 2009-11-10 AR ARP090104342A patent/AR074311A1/es unknown
- 2009-11-10 CN CN201310225070.2A patent/CN103361196B/zh not_active Expired - Fee Related
- 2009-11-10 EP EP15194914.6A patent/EP3031894A1/en not_active Withdrawn
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- 2009-11-10 RU RU2011123739/10A patent/RU2560978C2/ru not_active IP Right Cessation
- 2009-11-10 BR BR122013014157-0A patent/BR122013014157A2/pt not_active Application Discontinuation
- 2009-11-10 US US13/128,854 patent/US8753861B2/en active Active
- 2009-11-10 CN CN201610814735.7A patent/CN106399280B/zh active Active
- 2009-11-10 EP EP20090752658 patent/EP2362896A2/en not_active Withdrawn
- 2009-11-10 WO PCT/US2009/063837 patent/WO2010056653A2/en not_active Ceased
- 2009-11-10 KR KR1020117010706A patent/KR20110095260A/ko not_active Ceased
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- 2014-08-07 JP JP2014161183A patent/JP6120815B2/ja active Active
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Also Published As
| Publication number | Publication date |
|---|---|
| BR122013014157A2 (pt) | 2018-11-13 |
| US20140308736A1 (en) | 2014-10-16 |
| KR20110095260A (ko) | 2011-08-24 |
| US9096838B2 (en) | 2015-08-04 |
| CN102209775A (zh) | 2011-10-05 |
| EP2650354A2 (en) | 2013-10-16 |
| CA2743302A1 (en) | 2010-05-20 |
| CN106399280A (zh) | 2017-02-15 |
| MX2011004802A (es) | 2011-06-16 |
| JP2012508031A (ja) | 2012-04-05 |
| US8753861B2 (en) | 2014-06-17 |
| WO2010056653A3 (en) | 2010-09-16 |
| BRPI0922083A2 (pt) | 2017-05-30 |
| WO2010056653A2 (en) | 2010-05-20 |
| EP3031894A1 (en) | 2016-06-15 |
| EP2362896A2 (en) | 2011-09-07 |
| JP2015015952A (ja) | 2015-01-29 |
| RU2560978C2 (ru) | 2015-08-20 |
| US20160010072A1 (en) | 2016-01-14 |
| AR074311A1 (es) | 2011-01-05 |
| CN106399280B (zh) | 2020-12-22 |
| EP2650354A3 (en) | 2014-02-12 |
| US20120003718A1 (en) | 2012-01-05 |
| CN103361196A (zh) | 2013-10-23 |
| CN103361196B (zh) | 2016-01-27 |
| US20150065412A1 (en) | 2015-03-05 |
| CN103122345A (zh) | 2013-05-29 |
| JP5893584B2 (ja) | 2016-03-23 |
| JP6120815B2 (ja) | 2017-04-26 |
| JP2013236632A (ja) | 2013-11-28 |
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