BR112013004351A2 - célula hospedeira microbiana recombinante e método para a produção de um óleo microbiano compreendendo ácido eicosapentaenócio. - Google Patents
célula hospedeira microbiana recombinante e método para a produção de um óleo microbiano compreendendo ácido eicosapentaenócio.Info
- Publication number
- BR112013004351A2 BR112013004351A2 BR112013004351A BR112013004351A BR112013004351A2 BR 112013004351 A2 BR112013004351 A2 BR 112013004351A2 BR 112013004351 A BR112013004351 A BR 112013004351A BR 112013004351 A BR112013004351 A BR 112013004351A BR 112013004351 A2 BR112013004351 A2 BR 112013004351A2
- Authority
- BR
- Brazil
- Prior art keywords
- producing
- acid
- microbial
- eicosapentaenate
- host cell
- Prior art date
Links
- 230000000813 microbial effect Effects 0.000 title abstract 5
- 238000004519 manufacturing process Methods 0.000 title abstract 2
- 239000002253 acid Substances 0.000 title 1
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 abstract 2
- 235000020673 eicosapentaenoic acid Nutrition 0.000 abstract 2
- 229960005135 eicosapentaenoic acid Drugs 0.000 abstract 2
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 abstract 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 abstract 1
- 241000235015 Yarrowia lipolytica Species 0.000 abstract 1
- 235000020660 omega-3 fatty acid Nutrition 0.000 abstract 1
Classifications
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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
- C12N9/10—Transferases (2.)
- C12N9/1025—Acyltransferases (2.3)
- C12N9/1029—Acyltransferases (2.3) transferring groups other than amino-acyl groups (2.3.1)
-
- 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
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
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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
- 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
-
- 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
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
- C12N15/81—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
- C12N15/815—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts for yeasts other than Saccharomyces
-
- 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
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0071—Oxidoreductases (1.) acting on paired donors with incorporation of molecular oxygen (1.14)
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/64—Fats; Fatty oils; Ester-type waxes; Higher fatty acids, i.e. having at least seven carbon atoms in an unbroken chain bound to a carboxyl group; Oxidised oils or fats
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/64—Fats; Fatty oils; Ester-type waxes; Higher fatty acids, i.e. having at least seven carbon atoms in an unbroken chain bound to a carboxyl group; Oxidised oils or fats
- C12P7/6436—Fatty acid esters
- C12P7/6445—Glycerides
- C12P7/6458—Glycerides by transesterification, e.g. interesterification, ester interchange, alcoholysis or acidolysis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/64—Fats; Fatty oils; Ester-type waxes; Higher fatty acids, i.e. having at least seven carbon atoms in an unbroken chain bound to a carboxyl group; Oxidised oils or fats
- C12P7/6436—Fatty acid esters
- C12P7/6445—Glycerides
- C12P7/6472—Glycerides containing polyunsaturated fatty acid [PUFA] residues, i.e. having two or more double bonds in their backbone
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Mycology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
célula hospedeiramicrfobiana recombinante e método para a produção de um óleo microbiano compreendendo ácido eicosapentaenóico. são divulgadas na presente invenção cepas geneticamente manipuladas da levedura oleaginosa yarrowia lipolytica que são capazes de produzir óleo microbiano compreendendo mais do que 25 por cento em peso de ácido eicosapentaenóico ["epa'], um ácido graxo poli-insaturado ômega-3,mensurado como uma percentagem em peso celular seco.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US37724810P | 2010-08-26 | 2010-08-26 | |
US201061428277P | 2010-12-30 | 2010-12-30 | |
US201161479921P | 2011-04-28 | 2011-04-28 | |
PCT/US2011/049384 WO2012027689A1 (en) | 2010-08-26 | 2011-08-26 | Recombinant microbial host cells for high eicosapentaenoic acid production |
Publications (1)
Publication Number | Publication Date |
---|---|
BR112013004351A2 true BR112013004351A2 (pt) | 2016-05-31 |
Family
ID=45697764
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
BR112013004351A BR112013004351A2 (pt) | 2010-08-26 | 2011-08-26 | célula hospedeira microbiana recombinante e método para a produção de um óleo microbiano compreendendo ácido eicosapentaenócio. |
Country Status (11)
Country | Link |
---|---|
US (1) | US8703473B2 (pt) |
EP (1) | EP2609203B1 (pt) |
JP (1) | JP2013535987A (pt) |
KR (1) | KR20130138760A (pt) |
CN (1) | CN103249834B (pt) |
AU (1) | AU2011293180B2 (pt) |
BR (1) | BR112013004351A2 (pt) |
CA (1) | CA2807834C (pt) |
CL (1) | CL2013000533A1 (pt) |
DK (1) | DK2609203T3 (pt) |
WO (1) | WO2012027689A1 (pt) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2609202A1 (en) * | 2010-08-26 | 2013-07-03 | E.I. Du Pont De Nemours And Company | Mutant hpgg motif and hdash motif delta-5 desaturases and their use in making polyunsaturated fatty acids |
WO2012135773A1 (en) * | 2011-03-31 | 2012-10-04 | E. I. Du Pont De Nemours And Company | Yarrowia diacylglycerol acyltransferase promoter regions for gene expression in yeast |
US8735094B2 (en) | 2011-04-05 | 2014-05-27 | E I Du Pont De Nemours And Company | Yarrowia n-alkane-hydroxylating cytochrome P450 promoter regions for gene expression in yeast |
JP2014516537A (ja) | 2011-05-26 | 2014-07-17 | イー・アイ・デュポン・ドウ・ヌムール・アンド・カンパニー | 組換え油性微生物における、その中のオイル含量を増加させるためのカレオシンの発現 |
JP6351582B2 (ja) | 2012-06-19 | 2018-07-04 | イー・アイ・デュポン・ドウ・ヌムール・アンド・カンパニーE.I.Du Pont De Nemours And Company | アシルCoA:リゾホスファチジルコリンアシルトランスフェラーゼおよびリン脂質:ジアシルグリセロールアシルトランスフェラーゼの同時発現による多価不飽和脂肪酸の産生の改善 |
DK2935601T3 (en) | 2012-12-21 | 2018-06-18 | Du Pont | RECOMBINANT MICROBELL CELLS PRODUCING AT LEAST 28% EICOSAPENTAIC ACID AS DRY WEIGHT |
JP2016502851A (ja) | 2012-12-21 | 2016-02-01 | イー・アイ・デュポン・ドウ・ヌムール・アンド・カンパニーE.I.Du Pont De Nemours And Company | 微生物細胞中における脂質生成を改変するためのsou2ソルビトール利用タンパク質をコードするポリヌクレオチドの下方制御 |
US9074160B2 (en) * | 2013-03-07 | 2015-07-07 | Algisys, Llc | Production of omega-3 fatty acids from pythium species |
US10513711B2 (en) | 2014-08-13 | 2019-12-24 | Dupont Us Holding, Llc | Genetic targeting in non-conventional yeast using an RNA-guided endonuclease |
ES2590220B1 (es) * | 2015-05-18 | 2017-12-18 | Neol Biosolutions, S.A. | Producción de aceites microbianos con alto contenido en acido oleico |
WO2017066175A1 (en) | 2015-10-12 | 2017-04-20 | E. I. Du Pont De Nemours And Company | Protected dna templates for gene modification and increased homologous recombination in cells and methods of use |
CN108330114B (zh) * | 2018-03-21 | 2020-11-03 | 北京大学 | 一种利用epa的甘油二酯酰基转移酶及其应用 |
WO2019209241A1 (en) | 2018-04-23 | 2019-10-31 | Dupont Nutrition Biosciences Aps | Increasing export of 2' fucosyllactose from microbial cells through the expression of a heterologous nucleic acid |
WO2020082221A1 (zh) * | 2018-10-23 | 2020-04-30 | 利时雨 | 重组磷酸胆碱胞苷转移酶的粘红酵母携带外源多肽的活细胞脂质体及其应用 |
CN116555054B (zh) * | 2023-06-09 | 2024-05-14 | 陕西海斯夫生物工程有限公司 | 一株高产dha的重组裂殖壶菌、其构建方法及应用 |
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US4880741A (en) | 1983-10-06 | 1989-11-14 | Pfizer Inc. | Process for transformation of Yarrowia lipolytica |
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US5246841A (en) | 1986-12-26 | 1993-09-21 | Sagami Chemical Research Center | Microbial process for production of eicosapentaenoic acid |
US5366860A (en) | 1989-09-29 | 1994-11-22 | Applied Biosystems, Inc. | Spectrally resolvable rhodamine dyes for nucleic acid sequence determination |
US5244921A (en) | 1990-03-21 | 1993-09-14 | Martek Corporation | Eicosapentaenoic acids and methods for their production |
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DE60227525D1 (de) | 2002-10-18 | 2008-08-21 | Sloning Biotechnology Gmbh | Verfahren zur Herstellung von Nukleinsäuremolekülen |
EP1576166B1 (en) | 2002-12-19 | 2014-10-15 | University Of Bristol | Novel method for the production of polyunsaturated fatty acids |
EP1599582B1 (de) | 2003-02-27 | 2011-07-27 | BASF Plant Science GmbH | Verfahren zur herstellung mehrfach ungesättigter fettsäuren |
AU2004225838B2 (en) | 2003-03-31 | 2009-11-05 | University Of Bristol | Novel plant acyltransferases specific for long-chained, multiply unsaturated fatty acids |
US7125672B2 (en) | 2003-05-07 | 2006-10-24 | E. I. Du Pont De Nemours And Company | Codon-optimized genes for the production of polyunsaturated fatty acids in oleaginous yeasts |
US8313911B2 (en) | 2003-05-07 | 2012-11-20 | E I Du Pont De Nemours And Company | Production of polyunsaturated fatty acids in oleaginous yeasts |
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US20110059496A1 (en) | 2003-06-25 | 2011-03-10 | E. I. Du Pont De Nemours And Company | Glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate mutase promoters for gene expression in oleaginous yeast |
US7259255B2 (en) | 2003-06-25 | 2007-08-21 | E. I. Du Pont De Nemours And Company | Glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate mutase promoters for gene expression in oleaginous yeast |
US7267976B2 (en) | 2003-07-02 | 2007-09-11 | E.I. Du Pont De Nemours And Company | Acyltransferases for alteration of polyunsaturated fatty acids and oil content in oleaginous yeasts |
EP2166090B1 (de) | 2003-08-01 | 2015-07-01 | BASF Plant Science GmbH | Verfahren zur Herstellung mehrfach ungesättigter Fettsäuren in transgenen Organismen |
CA2542574C (en) | 2003-11-12 | 2014-03-18 | E. I. Du Pont De Nemours And Company | Delta-15 desaturases suitable for altering levels of polyunsaturated fatty acids in oleaginous plants and yeast |
US7504259B2 (en) | 2003-11-12 | 2009-03-17 | E. I. Du Pont De Nemours And Company | Δ12 desaturases suitable for altering levels of polyunsaturated fatty acids in oleaginous yeast |
EP1723220B1 (de) | 2004-02-27 | 2013-04-10 | BASF Plant Science GmbH | Verfahren zur herstellung mehrfach ungesättigter fettsäuren in transgenen pflanzen |
WO2006012325A1 (en) | 2004-06-25 | 2006-02-02 | E.I. Dupont De Nemours And Company | Delta-8 desaturase and its use in making polyunsaturated fatty acids |
US20060094102A1 (en) | 2004-11-04 | 2006-05-04 | Zhixiong Xue | Ammonium transporter promoter for gene expression in oleaginous yeast |
US7879591B2 (en) * | 2004-11-04 | 2011-02-01 | E.I. Du Pont De Nemours And Company | High eicosapentaenoic acid producing strains of Yarrowia lipolytica |
US7550286B2 (en) * | 2004-11-04 | 2009-06-23 | E. I. Du Pont De Nemours And Company | Docosahexaenoic acid producing strains of Yarrowia lipolytica |
DE102004062294A1 (de) | 2004-12-23 | 2006-07-06 | Basf Plant Science Gmbh | Verfahren zur Herstellung von mehrfach ungesättigten langkettigen Fettsäuren in transgenen Organismen |
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US7470532B2 (en) | 2005-10-19 | 2008-12-30 | E.I. Du Pont De Nemours And Company | Mortierella alpina C16/18 fatty acid elongase |
BRPI0620552A2 (pt) * | 2005-11-23 | 2011-11-22 | Du Pont | polinucleotìdeo isolado, polipeptìdeo delta-9 elongase, construção recombinante, célula vegetal, método para transformar uma célula, método para produção de uma planta transgênica, sementes transgênicas, método para fabricar ácidos graxos poliinsaturados de cadeia longa, óleos, método para produzir pelo menos um ácido graxo poliinsaturado, plantas de semente oleaginosa, sementes, alimentos, fragmento de ácido nucléico isolado e progênies de plantas |
US7678560B2 (en) | 2006-05-17 | 2010-03-16 | E.I. Du Pont De Nemours And Company | Δ 5 desaturase and its use in making polyunsaturated fatty acids |
AU2007314481B2 (en) | 2006-10-30 | 2012-11-29 | E. I. Du Pont De Nemours And Company | Delta17 desaturase and its use in making polyunsaturated fatty acids |
US7709239B2 (en) | 2006-12-07 | 2010-05-04 | E.I. Du Pont De Nemours And Company | Mutant Δ8 desaturase genes engineered by targeted mutagenesis and their use in making polyunsaturated fatty acids |
US8846374B2 (en) | 2006-12-12 | 2014-09-30 | E I Du Pont De Nemours And Company | Carotenoid production in a recombinant oleaginous yeast |
ES2559312T3 (es) * | 2007-04-03 | 2016-02-11 | E. I. Du Pont De Nemours And Company | Multienzimas y su uso en la fabricación de ácidos grasos poliinsaturados |
US8188338B2 (en) | 2007-04-10 | 2012-05-29 | E. I. Du Pont De Nemours And Company | Delta-8 desaturases and their use in making polyunsaturated fatty acids |
US7794701B2 (en) | 2007-04-16 | 2010-09-14 | E.I. Du Pont De Nemours And Company | Δ-9 elongases and their use in making polyunsaturated fatty acids |
US7943365B2 (en) | 2007-05-03 | 2011-05-17 | E.I. Du Pont De Nemours And Company | Δ-5 desaturases and their use in making polyunsaturated fatty acids |
WO2009001315A2 (en) | 2007-06-26 | 2008-12-31 | Staahl Ulf | Use of a class of genes encoding lysophospholipid acyl transferases for application in agriculture, biotechnology, and medicine |
CA2707372C (en) | 2007-07-23 | 2015-11-24 | Suntory Holdings Limited | Fatty acid compositions having novel fatty acid rate |
EP2195415A1 (en) | 2007-10-03 | 2010-06-16 | E. I. du Pont de Nemours and Company | Optimized strains of yarrowia lipolytica for high eicosapentaenoic acid production |
BRPI0913714A2 (pt) | 2008-09-19 | 2020-10-13 | E. I. Du Pont De Nemours And Company | polipeptídeo mutante que possui atividade de a5 dessaturase, molécula de ácido nucleico isolada, célula hospedeira microbiana e métodos de produção de ácido araquidônico e de ácido eicosapentaenoico |
WO2010080388A1 (en) | 2008-12-18 | 2010-07-15 | E. I. Du Pont De Nemours And Company | Reducing byproduction of malonates in a fermentation process |
US8524485B2 (en) | 2009-06-16 | 2013-09-03 | E I Du Pont De Nemours And Company | Long chain omega-3 and omega-6 polyunsaturated fatty acid biosynthesis by expression of acyl-CoA lysophospholipid acyltransferases |
-
2011
- 2011-08-26 BR BR112013004351A patent/BR112013004351A2/pt not_active IP Right Cessation
- 2011-08-26 WO PCT/US2011/049384 patent/WO2012027689A1/en active Application Filing
- 2011-08-26 US US13/218,708 patent/US8703473B2/en active Active
- 2011-08-26 KR KR1020137007481A patent/KR20130138760A/ko not_active Application Discontinuation
- 2011-08-26 AU AU2011293180A patent/AU2011293180B2/en not_active Ceased
- 2011-08-26 DK DK11752426.4T patent/DK2609203T3/da active
- 2011-08-26 CN CN201180041064.0A patent/CN103249834B/zh not_active Expired - Fee Related
- 2011-08-26 EP EP11752426.4A patent/EP2609203B1/en not_active Not-in-force
- 2011-08-26 JP JP2013526178A patent/JP2013535987A/ja active Pending
- 2011-08-26 CA CA2807834A patent/CA2807834C/en not_active Expired - Fee Related
-
2013
- 2013-02-25 CL CL2013000533A patent/CL2013000533A1/es unknown
Also Published As
Publication number | Publication date |
---|---|
US8703473B2 (en) | 2014-04-22 |
DK2609203T3 (da) | 2018-10-01 |
AU2011293180A1 (en) | 2013-01-24 |
CL2013000533A1 (es) | 2013-10-18 |
CN103249834A (zh) | 2013-08-14 |
CA2807834C (en) | 2019-06-25 |
JP2013535987A (ja) | 2013-09-19 |
CA2807834A1 (en) | 2012-03-01 |
EP2609203A1 (en) | 2013-07-03 |
EP2609203B1 (en) | 2018-06-20 |
KR20130138760A (ko) | 2013-12-19 |
WO2012027689A1 (en) | 2012-03-01 |
CN103249834B (zh) | 2016-10-26 |
AU2011293180B2 (en) | 2017-03-02 |
US20120052537A1 (en) | 2012-03-01 |
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