RU2003128977A - Способы секреторной продукции белков - Google Patents
Способы секреторной продукции белков Download PDFInfo
- Publication number
- RU2003128977A RU2003128977A RU2003128977/13A RU2003128977A RU2003128977A RU 2003128977 A RU2003128977 A RU 2003128977A RU 2003128977/13 A RU2003128977/13 A RU 2003128977/13A RU 2003128977 A RU2003128977 A RU 2003128977A RU 2003128977 A RU2003128977 A RU 2003128977A
- Authority
- RU
- Russia
- Prior art keywords
- signal peptide
- coryneform bacterium
- mutant
- heterologous protein
- seq
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract 12
- 230000014616 translation Effects 0.000 title 1
- 241000186254 coryneform bacterium Species 0.000 claims abstract 13
- 108010076504 Protein Sorting Signals Proteins 0.000 claims abstract 12
- 108090000623 proteins and genes Proteins 0.000 claims abstract 12
- 102000004169 proteins and genes Human genes 0.000 claims abstract 10
- 241000186226 Corynebacterium glutamicum Species 0.000 claims abstract 5
- 238000004519 manufacturing process Methods 0.000 claims abstract 3
- 102000018697 Membrane Proteins Human genes 0.000 claims 4
- 108010052285 Membrane Proteins Proteins 0.000 claims 4
- 125000003275 alpha amino acid group Chemical group 0.000 claims 3
- 241000186031 Corynebacteriaceae Species 0.000 claims 2
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 150000007523 nucleic acids Chemical group 0.000 claims 2
- 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 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims 1
- 241000186145 Corynebacterium ammoniagenes Species 0.000 claims 1
- 238000007792 addition Methods 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 229910001424 calcium ion Inorganic materials 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 238000012217 deletion Methods 0.000 claims 1
- 230000037430 deletion Effects 0.000 claims 1
- 230000014509 gene expression Effects 0.000 claims 1
- 238000003780 insertion Methods 0.000 claims 1
- 230000037431 insertion Effects 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- 230000002068 genetic effect Effects 0.000 abstract 1
- 230000003248 secreting effect Effects 0.000 abstract 1
Classifications
-
- 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
- C12P21/00—Preparation of peptides or proteins
- C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/36—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Actinomyces; from Streptomyces (G)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/34—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Corynebacterium (G)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- 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
- C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
- C12N15/77—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora for Corynebacterium; for Brevibacterium
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
- Peptides Or Proteins (AREA)
Claims (11)
1. Способ получения гетерологичного белка, предусматривающий культивирование коринеформной бактерии, содержащей генную экспрессирующую конструкцию, в которой последовательность нуклеиновой кислоты, кодирующая область сигнального пептида, полученная из коринеформной бактерии, соединена в прямом направлении с последовательностью промотора, который функционирует в коринеформной бактерии, и последовательность нуклеиновой кислоты, кодирующая гетерологичный белок, связана в прямом направлении с указанной последовательностью нуклеиновой кислоты, кодирующей указанную область сигнального пептида, где указанная коринеформная бактерия представляет собой мутантную коринеформную бактерию, обладающую, по меньшей мере, в 2 раза более высокой способностью секретировать гетерологичный белок по сравнению с Corynebacterium glutamicum ATCC13869 дикого типа, что обеспечивает продукцию указанной коринеформной бактерией указанного гетерологичного белка и выделение указанного продуцированного гетерологичного белка.
2. Способ по п.1, в котором мутантная коринеформная бактерия представляет собой Corynebacterium glutamicum AJ12036 (FERM BP-734) или ее мутант.
3. Способ по п.1, в котором мутантная коринеформная бактерия представляет собой мутантный штамм, который не продуцирует белок клеточной поверхности и который получен из Corynebacterium glutamicum AJ12036 (FERM BP-734).
4. Способ по любому из пп.1-3, в котором сигнальный пептид представляет собой сигнальный пептид клеточного поверхностного белка из коринеформной бактерии.
5. Способ по любому из пп.1-3, в котором сигнальный пептид представляет собой сигнальный пептид клеточного поверхностного белка из Corynebacterium glutamicum.
6. Способ по п.5, в котором сигнальный пептид имеет аминокислотную последовательность SEQ ID NO:1 или SEQ ID NO:2.
7. Способ по любому из пп.1-3, в котором сигнальный пептид представляет собой сигнальный пептид клеточного поверхностного белка, полученного из Corynebacterium ammoniagenes.
8. Способ по п.7, в котором сигнальный пептид имеет аминокислотную последовательность SEQ ID NO:7.
9. Способ по п.5 или 7, в котором сигнальный пептид имеет последовательность, содержащую, по меньшей мере, одну замену, делецию, добавление, вставку аминокислоты или их комбинацию в аминокислотной последовательности SEQ ID NO:1 - SEQ ID NO:3.
10. Способ по любому из пп.1-9, в котором культивирование мутантной коринеформной бактерии проводят в среде, содержащей 0,25 г/л (2,25 мМ) или несколько ионов кальция.
11. Способ по любому из пп.1-9, в котором культивирование мутантной коринеформной бактерии проводят, поддерживая концентрацию растворенного кислорода на уровне 3% или ниже.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001-98808 | 2001-03-30 | ||
| JP2001098808 | 2001-03-30 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2003128977A true RU2003128977A (ru) | 2005-02-27 |
| RU2264463C2 RU2264463C2 (ru) | 2005-11-20 |
Family
ID=18952423
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2003128977/13A RU2264463C2 (ru) | 2001-03-30 | 2002-03-27 | Способ секреторной продукции белка |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US7252972B2 (ru) |
| EP (1) | EP1375664B1 (ru) |
| JP (1) | JP4362651B2 (ru) |
| KR (1) | KR100602807B1 (ru) |
| CN (1) | CN1250722C (ru) |
| AT (1) | ATE447615T1 (ru) |
| AU (1) | AU2002242986A1 (ru) |
| BR (1) | BR0208136B1 (ru) |
| CA (1) | CA2442679C (ru) |
| DE (1) | DE60234247D1 (ru) |
| DK (1) | DK1375664T3 (ru) |
| ES (1) | ES2335750T3 (ru) |
| RU (1) | RU2264463C2 (ru) |
| WO (1) | WO2002081694A1 (ru) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7723081B1 (en) | 2000-01-21 | 2010-05-25 | Ajinomoto Co., Inc. | Bacteria containing aspartate-semialdehyde dehydrogenase, phosphoenolpyruvate carboxylase, and transhydrogenase to produce L-lysine in escherichia, and methods of using same |
| CA2518049C (en) * | 2003-03-07 | 2013-05-07 | Ajinomoto Co., Inc. | Method of producing microbial transglutaminase |
| DE10359660A1 (de) * | 2003-12-18 | 2005-07-28 | Basf Ag | Psod-Expressionseinheiten |
| DE10359594A1 (de) * | 2003-12-18 | 2005-07-28 | Basf Ag | PEF-TU-Expressionseinheiten |
| JP4730302B2 (ja) * | 2004-04-20 | 2011-07-20 | 味の素株式会社 | タンパク質の製造法 |
| WO2005121333A1 (en) * | 2004-06-14 | 2005-12-22 | Novozymes A/S | Signal peptide for producing a polypeptide |
| US7527947B2 (en) | 2004-06-14 | 2009-05-05 | Novozymes A/S | Signal peptide for producing a polypeptide |
| DE102004035065A1 (de) | 2004-07-20 | 2006-02-16 | Basf Ag | P-ET-TS-Expressionseinheiten |
| KR100620092B1 (ko) * | 2004-12-16 | 2006-09-08 | 씨제이 주식회사 | 코리네박테리움 속 세포로부터 유래된 신규한 프로모터서열, 그를 포함하는 발현 카세트 및 벡터, 상기 벡터를포함하는 숙주 세포 및 그를 이용하여 유전자를 발현하는방법 |
| EP1902126A1 (en) * | 2005-07-12 | 2008-03-26 | Codon Devices, Inc | Compositions and methods for biocatalytic engineering |
| RU2338784C2 (ru) * | 2006-03-24 | 2008-11-20 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" (ЗАО АГРИ) | Новая альдолаза, днк, кодирующая альдолазу, клетки, трансформированные днк, способ получения альдолазы и способ получения 4-гидрокси-l-изолейцина (варианты) |
| EP2082045B1 (en) * | 2006-10-24 | 2015-03-18 | Basf Se | Method of reducing gene expression using modified codon usage |
| JPWO2008099898A1 (ja) * | 2007-02-15 | 2010-05-27 | 味の素株式会社 | ジスルフィド結合導入トランスグルタミナーゼ |
| WO2008120798A1 (ja) | 2007-03-29 | 2008-10-09 | Ajinomoto Co., Inc. | 接着用酵素製剤及び接着成形食品の製造方法 |
| EP2213785A4 (en) | 2007-11-19 | 2013-01-09 | Ajinomoto Kk | TREATED FIBER AND METHOD FOR MANUFACTURING THE SAME |
| EP2302066A4 (en) * | 2008-07-09 | 2012-02-08 | Ajinomoto Kk | METHOD FOR PRODUCING AMINOHYDROXYBENZOIC ACID |
| TWI444146B (zh) | 2008-09-25 | 2014-07-11 | Ajinomoto Kk | 黏著成型食品用酵素製劑及黏著成型食品之製造方法 |
| CN102341497B (zh) | 2009-03-06 | 2013-11-06 | 味之素株式会社 | 放线菌来源的耐热性转谷氨酰胺酶 |
| MY160554A (en) | 2010-02-23 | 2017-03-15 | Toray Industries | Process for production of cadaverine |
| CN103917656B (zh) | 2011-10-25 | 2016-09-28 | 味之素株式会社 | 蛋白质的分泌产生方法 |
| AU2012333451B2 (en) | 2011-11-02 | 2015-05-21 | Ajinomoto Co., Inc. | Method for secretory production of protein |
| AU2012333515B2 (en) | 2011-11-02 | 2015-07-16 | Ajinomoto Co., Inc. | Method for secreting and producing proteins |
| AU2013240184B2 (en) | 2012-03-26 | 2017-05-25 | Axcella Health Inc. | Nutritive fragments, proteins and methods |
| EP2831100A4 (en) | 2012-03-26 | 2016-02-10 | Pronutria Inc | NUTRIENT PROTEINS AND METHOD |
| SG10201604464SA (en) | 2012-03-26 | 2016-07-28 | Axcella Health Inc | Charged nutritive proteins and methods |
| CA2868469A1 (en) | 2012-03-26 | 2013-10-03 | Pronutria, Inc. | Nutritive fragments, proteins and methods |
| AU2014324901A1 (en) | 2013-09-25 | 2016-05-19 | Axcella Health Inc. | Compositions and formulations for prevention and treatment of diabetes and obesity, and methods of production and use thereof in glucose and caloric control |
| EP3287523B1 (en) | 2015-04-24 | 2022-06-29 | Ajinomoto Co., Inc. | Method for secretory production of protein |
| EP3375883B1 (en) | 2015-11-12 | 2021-02-03 | Ajinomoto Co., Inc. | Method for producing n epsilon -acyl-l-lysine |
| JP7020403B2 (ja) | 2016-05-02 | 2022-02-16 | 味の素株式会社 | アジド基含有Ｆｃタンパク質 |
| US11242545B2 (en) | 2016-09-01 | 2022-02-08 | Ningxia Eppen Biotech Co., Ltd | Corynebacterium for producing L-lysine by fermentation |
| JP7021639B2 (ja) | 2016-10-21 | 2022-02-17 | 味の素株式会社 | タンパク質の分泌生産法 |
| EP3530747A4 (en) | 2016-10-21 | 2020-07-22 | Ajinomoto Co., Inc. | SECRETORY PROTEIN PRODUCTION PROCESS |
| EP3572522A4 (en) | 2017-01-19 | 2020-10-28 | Ajinomoto Co., Inc. | PROCESS FOR THE PRODUCTION OF A HEPAROSANE COMPOUND CONTAINING A RESIDUE OF ISOMERIZED HEXULONIC ACID |
| EP3415622A1 (en) | 2017-06-14 | 2018-12-19 | Evonik Degussa GmbH | Method for production of fine chemicals using a corynebacterium secreting modified alpha-1,6-glucosidases |
| JP7200948B2 (ja) | 2017-09-05 | 2023-01-10 | 味の素株式会社 | ２－ｏ－硫酸化酵素変異体、および３－ｏ－硫酸化酵素変異体、ならびにそれらを用いる方法 |
| JP7439749B2 (ja) | 2018-04-20 | 2024-02-28 | 味の素株式会社 | タンパク質の分泌生産法 |
| WO2020085511A1 (ja) | 2018-10-25 | 2020-04-30 | 味の素株式会社 | タンパク質の分泌生産法 |
| JPWO2020090979A1 (ja) | 2018-10-31 | 2021-09-24 | 味の素株式会社 | 抗体に対する親和性物質、切断性部分および反応性基を有する化合物またはその塩 |
| EP4115740A4 (en) | 2020-03-04 | 2024-04-03 | Ajinomoto Co., Inc. | MUTANT TRANSGLUTAMINASE |
| WO2022071061A1 (ja) | 2020-09-29 | 2022-04-07 | 味の素株式会社 | 変異型トランスグルタミナーゼ |
| KR20240032941A (ko) | 2021-07-07 | 2024-03-12 | 아지노모토 가부시키가이샤 | 비천연 아미노산 함유 단백질의 분비 생산법 |
| JPWO2023200008A1 (ru) | 2022-04-15 | 2023-10-19 | ||
| EP4534547A1 (en) | 2022-06-02 | 2025-04-09 | Ajinomoto Co., Inc. | Affinity substance, compound, and antibody and their salts |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3584848D1 (de) * | 1984-04-04 | 1992-01-23 | Ajinomoto Kk | Zusammengesetztes transduzierbares plasmid. |
| JPH07112431B2 (ja) * | 1985-09-06 | 1995-12-06 | 味の素株式会社 | 遺伝子発現調節法 |
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| US4965197A (en) * | 1987-06-12 | 1990-10-23 | Massachusetts Institute Of Technology | Coryneform expression and secretion system |
| WO1988009821A1 (en) * | 1987-06-12 | 1988-12-15 | Massachusetts Institute Of Technology | Coryneform expression and secretion system |
| EP0551506A1 (fr) * | 1991-07-30 | 1993-07-21 | Orsan | Systeme d'expression et de secretion de proteines utilisables en particulier chez les corynebacteries |
| KR0164235B1 (ko) * | 1993-01-13 | 1999-01-15 | 도바 다다스 | 신규한 세포 표층 단백질 |
| JP3711658B2 (ja) | 1996-10-07 | 2005-11-02 | 味の素株式会社 | コリネバクテリウム・アンモニアゲネス由来の新規な細胞表層蛋白質 |
| EP0897003B1 (en) * | 1997-07-05 | 2004-05-12 | Societe Des Produits Nestle S.A. | Enhanced expression of proteolytic enzymes in koji mold |
| JPH11169182A (ja) * | 1997-12-10 | 1999-06-29 | Mitsubishi Chemical Corp | コリネ型細菌内で蛋白質を効率よく培地中へ分泌させる変異型分泌装置遺伝子 |
| WO2001023591A1 (fr) * | 1999-09-30 | 2001-04-05 | Ajinomoto Co., Inc. | Procédé de production de transglutaminase |
-
2002
- 2002-03-27 KR KR1020037012833A patent/KR100602807B1/ko not_active Expired - Fee Related
- 2002-03-27 DE DE60234247T patent/DE60234247D1/de not_active Expired - Lifetime
- 2002-03-27 CA CA2442679A patent/CA2442679C/en not_active Expired - Lifetime
- 2002-03-27 CN CNB028076265A patent/CN1250722C/zh not_active Expired - Lifetime
- 2002-03-27 AU AU2002242986A patent/AU2002242986A1/en not_active Abandoned
- 2002-03-27 JP JP2002580057A patent/JP4362651B2/ja not_active Expired - Lifetime
- 2002-03-27 DK DK02708684.2T patent/DK1375664T3/da active
- 2002-03-27 EP EP02708684A patent/EP1375664B1/en not_active Expired - Lifetime
- 2002-03-27 ES ES02708684T patent/ES2335750T3/es not_active Expired - Lifetime
- 2002-03-27 AT AT02708684T patent/ATE447615T1/de not_active IP Right Cessation
- 2002-03-27 RU RU2003128977/13A patent/RU2264463C2/ru active
- 2002-03-27 BR BRPI0208136-9A patent/BR0208136B1/pt active IP Right Grant
- 2002-03-27 WO PCT/JP2002/002978 patent/WO2002081694A1/ja active Application Filing
-
2003
- 2003-09-30 US US10/673,860 patent/US7252972B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| EP1375664B1 (en) | 2009-11-04 |
| US7252972B2 (en) | 2007-08-07 |
| JP4362651B2 (ja) | 2009-11-11 |
| KR20030087042A (ko) | 2003-11-12 |
| KR100602807B1 (ko) | 2006-07-20 |
| CN1500145A (zh) | 2004-05-26 |
| BR0208136A (pt) | 2004-03-02 |
| RU2264463C2 (ru) | 2005-11-20 |
| JPWO2002081694A1 (ja) | 2004-07-29 |
| DE60234247D1 (de) | 2009-12-17 |
| BR0208136B1 (pt) | 2014-10-21 |
| WO2002081694A1 (fr) | 2002-10-17 |
| WO2002081694A8 (fr) | 2002-11-14 |
| ATE447615T1 (de) | 2009-11-15 |
| CN1250722C (zh) | 2006-04-12 |
| CA2442679C (en) | 2010-06-01 |
| EP1375664A1 (en) | 2004-01-02 |
| ES2335750T3 (es) | 2010-04-05 |
| CA2442679A1 (en) | 2002-10-17 |
| AU2002242986A1 (en) | 2002-10-21 |
| EP1375664A4 (en) | 2005-08-17 |
| US20040126847A1 (en) | 2004-07-01 |
| DK1375664T3 (da) | 2010-02-08 |
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