ATE317897T1 - System und methode zur herstellung von rekombinanten, glykosylierten protein in prokaryontischen wirtszellen - Google Patents
System und methode zur herstellung von rekombinanten, glykosylierten protein in prokaryontischen wirtszellenInfo
- Publication number
- ATE317897T1 ATE317897T1 AT03702276T AT03702276T ATE317897T1 AT E317897 T1 ATE317897 T1 AT E317897T1 AT 03702276 T AT03702276 T AT 03702276T AT 03702276 T AT03702276 T AT 03702276T AT E317897 T1 ATE317897 T1 AT E317897T1
- Authority
- AT
- Austria
- Prior art keywords
- prokaryontic
- host cells
- producing recombinant
- glycosylated protein
- recombinant glycosylated
- Prior art date
Links
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
-
- 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
- C12P21/005—Glycopeptides, glycoproteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/12—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from bacteria
- C07K16/1203—Gram-negative bacteria
- C07K16/121—Helicobacter (G); Campylobacter (G)
-
- 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
- C12N15/70—Vectors or expression systems specially adapted for E. coli
-
- 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.)
-
- 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.)
- C12N9/1048—Glycosyltransferases (2.4)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Mycology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH3942002 | 2002-03-07 | ||
| US36465502P | 2002-03-14 | 2002-03-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ATE317897T1 true ATE317897T1 (de) | 2006-03-15 |
Family
ID=27789602
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT03702276T ATE317897T1 (de) | 2002-03-07 | 2003-03-05 | System und methode zur herstellung von rekombinanten, glykosylierten protein in prokaryontischen wirtszellen |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US20050287628A1 (de) |
| EP (1) | EP1481057B1 (de) |
| KR (1) | KR20090110951A (de) |
| AT (1) | ATE317897T1 (de) |
| AU (1) | AU2003205502C1 (de) |
| CA (1) | CA2477794C (de) |
| DE (1) | DE60303591T2 (de) |
| DK (1) | DK1481057T3 (de) |
| ES (1) | ES2258214T3 (de) |
| IL (3) | IL163806A0 (de) |
| PT (1) | PT1481057E (de) |
| WO (1) | WO2003074687A1 (de) |
Families Citing this family (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT1481057E (pt) * | 2002-03-07 | 2006-05-31 | Eidgenoess Tech Hochschule | Sistema e metodo para a producao de proteinas glicosiladas recombinantes num hospedeiro procariota |
| AU2011218682B2 (en) * | 2005-05-11 | 2013-11-21 | Eth Zurich | Recombinant N-glycosylated proteins from procaryotic cells |
| DE602006017207D1 (de) * | 2005-05-11 | 2010-11-11 | Eth Zuerich | Rekombinante n-glykosylierte proteine aus prokaryontischen zellen |
| DK2240595T4 (da) * | 2008-01-03 | 2019-10-07 | Cornell Res Foundation Inc | Glykosyleret proteinekspression i prokaryoter |
| AU2009215341B2 (en) | 2008-02-20 | 2015-03-26 | Glaxosmithkline Biologicals S.A. | Bioconjugates made from recombinant N-glycosylated proteins from procaryotic cells |
| TR201803015T4 (tr) | 2009-11-19 | 2018-03-21 | Glaxosmithkline Biologicals Sa | Prokaryotik hücrelerde immünojenik polisakaridler üreten biyosentetik sistem. |
| HRP20180064T1 (hr) | 2010-05-06 | 2018-02-23 | Glaxosmithkline Biologicals Sa | Cjepiva s kapsularnim biokonjugatima iz gram-pozitivnih bakterija |
| CA2844831A1 (en) | 2011-08-12 | 2013-02-21 | The Governors Of The University Of Alberta | Method of diagnosing bacterial infections using bacterial glycoproteins |
| JP2014526449A (ja) | 2011-09-06 | 2014-10-06 | グリコヴァキシン アーゲー | 原核細胞において製造されるバイオコンジュゲートワクチン |
| HK1202896A1 (en) | 2011-11-04 | 2015-10-09 | 康奈尔大学 | A prokaryote-based cell-free system for the synthesis of glycoproteins |
| EP3444352B1 (de) | 2012-11-07 | 2020-12-16 | GlaxoSmithKline Biologicals SA | Herstellung von rekombinantem impfstoff in e. coli durch enzymatische konjugation |
| PT2945651T (pt) | 2013-01-17 | 2018-06-12 | Arsanis Biosciences Gmbh | Anticorpo específico para mdr e. coli |
| ES2753369T3 (es) * | 2013-04-05 | 2020-04-08 | Univ Alberta | Vacuna de Campylobacter |
| AU2015220723C1 (en) | 2014-02-24 | 2018-04-05 | Glaxosmithkline Biologicals Sa | Novel polysaccharide and uses thereof |
| HRP20201021T1 (hr) | 2014-04-17 | 2020-10-16 | Glaxosmithkline Biologicals S.A. | Modificirane stanice domaćini i njihova upotreba |
| EP3177325B1 (de) | 2014-08-08 | 2020-04-01 | GlaxoSmithKline Biologicals S.A. | Modifizierte wirtszellen und oligosaccharid-hybride zur verwendung in der herstellung von biokonjugaten |
| US9616114B1 (en) | 2014-09-18 | 2017-04-11 | David Gordon Bermudes | Modified bacteria having improved pharmacokinetics and tumor colonization enhancing antitumor activity |
| US10676723B2 (en) | 2015-05-11 | 2020-06-09 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| TWI715617B (zh) | 2015-08-24 | 2021-01-11 | 比利時商葛蘭素史密斯克藍生物品公司 | 對抗腸道外病原性大腸桿菌之免疫保護之方法及組合物 |
| WO2017117539A1 (en) | 2015-12-30 | 2017-07-06 | Northwestern University | Cell-free glycoprotein synthesis (cfgps) in prokaryotic cell lysates enriched with components for glycosylation |
| GB201610599D0 (en) | 2016-06-17 | 2016-08-03 | Glaxosmithkline Biologicals Sa | Immunogenic Composition |
| US10829795B2 (en) | 2016-07-14 | 2020-11-10 | Northwestern University | Method for rapid in vitro synthesis of glycoproteins via recombinant production of N-glycosylated proteins in prokaryotic cell lysates |
| AR109621A1 (es) | 2016-10-24 | 2018-12-26 | Janssen Pharmaceuticals Inc | Formulaciones de vacunas contra glucoconjugados de expec |
| US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| US11180535B1 (en) | 2016-12-07 | 2021-11-23 | David Gordon Bermudes | Saccharide binding, tumor penetration, and cytotoxic antitumor chimeric peptides from therapeutic bacteria |
| GB201704117D0 (en) * | 2017-03-15 | 2017-04-26 | London School Hygiene & Tropical Medicine | Oligosaccharyl Transferase polypeptide |
| GB201711635D0 (en) | 2017-07-19 | 2017-08-30 | Glaxosmithkline Biologicals Sa | Immunogenic composition |
| WO2019035916A1 (en) | 2017-08-15 | 2019-02-21 | Northwestern University | DESIGN OF PROTEIN GLYCOSYLATION SITES BY RAPID EXPRESSION AND CHARACTERIZATION OF N-GLYCOSYLTRANSFERASES |
| GB201721582D0 (en) | 2017-12-21 | 2018-02-07 | Glaxosmithkline Biologicals Sa | S aureus antigens and immunogenic compositions |
| GB201721576D0 (en) | 2017-12-21 | 2018-02-07 | Glaxosmithkline Biologicals Sa | Hla antigens and glycoconjugates thereof |
| US11530432B2 (en) | 2018-03-19 | 2022-12-20 | Northwestern University | Compositions and methods for rapid in vitro synthesis of bioconjugate vaccines in vitro via production and N-glycosylation of protein carriers in detoxified prokaryotic cell lysates |
| US11725224B2 (en) | 2018-04-16 | 2023-08-15 | Northwestern University | Methods for co-activating in vitro non-standard amino acid (nsAA) incorporation and glycosylation in crude cell lysates |
| WO2020072127A2 (en) | 2018-08-03 | 2020-04-09 | Northwestern University | On demand, portable, cell-free molecular sensing platform |
| WO2020044371A1 (en) * | 2018-08-29 | 2020-03-05 | Council Of Scientific And Industrial Research | Recombinant microbial system for directed evolution of glycocins and a method of preparation thereof |
| US20220054632A1 (en) | 2018-12-12 | 2022-02-24 | Glaxosmithkline Biologicals Sa | Modified carrier proteins for o-linked glycosylation |
| WO2020146814A1 (en) * | 2019-01-11 | 2020-07-16 | Northwestern University | Bioconjugate vaccines' synthesis in prokaryotic cell lysates |
| WO2020185451A2 (en) | 2019-03-04 | 2020-09-17 | Northwestern University | Riboswitch-based fluoride sensing in cell-free extract |
| EP3941516A1 (de) | 2019-03-18 | 2022-01-26 | Janssen Pharmaceuticals, Inc. | Biokonjugate von e. coli, o-antigen-polysacchariden verfahren zur herstellung davon und verfahren zur verwendung davon |
| IL286467B2 (en) | 2019-03-18 | 2026-02-01 | Janssen Pharmaceuticals Inc | Methods for producing bioconjugates of polysaccharides E. coli o-antigen, preparations thereof and methods for using them |
| EP3757217A1 (de) | 2019-06-27 | 2020-12-30 | GlaxoSmithKline Biologicals S.A. | Verfahren zur proteinaufreinigung |
| EP3770269A1 (de) | 2019-07-23 | 2021-01-27 | GlaxoSmithKline Biologicals S.A. | Quantifizierung von biokonjugatglykosylierung |
| EP3777884A1 (de) | 2019-08-15 | 2021-02-17 | GlaxoSmithKline Biologicals S.A. | Immunogene zusammensetzung |
| US12226410B2 (en) | 2019-10-18 | 2025-02-18 | Northwestern University | Methods for enhancing cellular clearance of pathological molecules via activation of the cellular protein ykt6 |
| AU2020371793A1 (en) | 2019-10-25 | 2022-06-02 | Northwestern University | Cell-free extract preparation protocol for enrichment of membrane vesicles and increased glycoprotein yields |
| JP2023530154A (ja) | 2020-06-18 | 2023-07-13 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | 赤痢菌４価（Ｓｈｉｇｅｌｌａ４Ｖ）バイオコンジュゲート |
| BR112022023234A2 (pt) | 2020-06-25 | 2023-01-03 | Glaxosmithkline Biologicals Sa | Proteínas de exotoxina a modificada |
| AU2021342797B2 (en) | 2020-09-17 | 2024-02-08 | Janssen Pharmaceuticals, Inc. | Multivalent vaccine compositions and uses thereof |
| EP4452308A1 (de) | 2021-12-22 | 2024-10-30 | GlaxoSmithKline Biologicals S.A. | Impfstoff |
| GB202302579D0 (en) | 2023-02-23 | 2023-04-12 | Glaxosmithkline Biologicals Sa | Immunogenic composition |
| KR20260051063A (ko) | 2023-08-09 | 2026-04-15 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 변형된 단백질 |
| WO2025032534A2 (en) | 2023-08-09 | 2025-02-13 | Glaxosmithkline Biologicals Sa | Modified proteins |
| WO2025172892A1 (en) | 2024-02-16 | 2025-08-21 | Glaxosmithkline Biologicals Sa | Modified proteins and methods |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3584198D1 (de) | 1984-08-01 | 1991-10-31 | Boehringer Ingelheim Int | Neue genetische sequenzen, die durch sie codierten interferon-peptide vom typ i und diese sie produzierende organismen. |
| US5643758A (en) * | 1987-03-10 | 1997-07-01 | New England Biolabs, Inc. | Production and purification of a protein fused to a binding protein |
| JPH09501044A (ja) | 1993-05-14 | 1997-02-04 | ジ・アップジョン・カンパニー | ＵＤＰ−ＧＡＬＮＡｃ：ポリペプチド、Ｎ−アセチルガラクトサミニルトランスフェラーゼをコードするクローン化されたＤＮＡ |
| US6503744B1 (en) | 1999-02-01 | 2003-01-07 | National Research Council Of Canada | Campylobacter glycosyltransferases for biosynthesis of gangliosides and ganglioside mimics |
| CA2363297C (en) * | 1999-03-02 | 2011-08-09 | Michael J. Betenbaugh | Engineering intracellular sialylation pathways |
| AU2001263149A1 (en) | 2000-05-12 | 2001-11-26 | Neose Technologies, Inc. | In vitro fucosylation recombinant glycopeptides |
| PT1294910E (pt) | 2000-06-30 | 2009-02-16 | Vib Vzw | Modificação da glicosilação de proteínas em pichia pastoris |
| PT1481057E (pt) * | 2002-03-07 | 2006-05-31 | Eidgenoess Tech Hochschule | Sistema e metodo para a producao de proteinas glicosiladas recombinantes num hospedeiro procariota |
| KR20130101592A (ko) * | 2002-03-07 | 2013-09-13 | 아이드게노쉬쉐 테흐니쉐 호흐슐레 쥬리히 | 원핵 숙주에서의 재조합 글리코실화 단백질 생산 방법 및 생산계 |
| BR0312896A (pt) | 2002-08-01 | 2005-06-14 | Ca Nat Research Council | Glicanos e glicopeptìdeos de campylobacter |
| EP2657251B1 (de) | 2004-05-24 | 2018-03-21 | The Government of The United States of America, as represented by The Secretary, Department of Health and Human Services | Lebender, oraler Impfstoff gegen Shigella dysenteriae Serotyp 1 |
| DE602006017207D1 (de) | 2005-05-11 | 2010-11-11 | Eth Zuerich | Rekombinante n-glykosylierte proteine aus prokaryontischen zellen |
| AU2009215341B2 (en) | 2008-02-20 | 2015-03-26 | Glaxosmithkline Biologicals S.A. | Bioconjugates made from recombinant N-glycosylated proteins from procaryotic cells |
| TR201803015T4 (tr) * | 2009-11-19 | 2018-03-21 | Glaxosmithkline Biologicals Sa | Prokaryotik hücrelerde immünojenik polisakaridler üreten biyosentetik sistem. |
| HRP20180064T1 (hr) * | 2010-05-06 | 2018-02-23 | Glaxosmithkline Biologicals Sa | Cjepiva s kapsularnim biokonjugatima iz gram-pozitivnih bakterija |
-
2003
- 2003-03-05 PT PT03702276T patent/PT1481057E/pt unknown
- 2003-03-05 DE DE60303591T patent/DE60303591T2/de not_active Expired - Lifetime
- 2003-03-05 IL IL16380603A patent/IL163806A0/xx unknown
- 2003-03-05 KR KR1020097020064A patent/KR20090110951A/ko not_active Ceased
- 2003-03-05 DK DK03702276T patent/DK1481057T3/da active
- 2003-03-05 US US10/506,917 patent/US20050287628A1/en not_active Abandoned
- 2003-03-05 EP EP03702276A patent/EP1481057B1/de not_active Expired - Lifetime
- 2003-03-05 WO PCT/CH2003/000153 patent/WO2003074687A1/en not_active Ceased
- 2003-03-05 AT AT03702276T patent/ATE317897T1/de active
- 2003-03-05 ES ES03702276T patent/ES2258214T3/es not_active Expired - Lifetime
- 2003-03-05 CA CA2477794A patent/CA2477794C/en not_active Expired - Lifetime
- 2003-03-05 AU AU2003205502A patent/AU2003205502C1/en not_active Expired
-
2004
- 2004-08-30 IL IL163806A patent/IL163806A/en active IP Right Grant
-
2008
- 2008-07-21 US US12/219,383 patent/US8703471B2/en not_active Expired - Lifetime
-
2012
- 2012-06-12 IL IL220322A patent/IL220322A0/en active IP Right Grant
-
2014
- 2014-02-25 US US14/189,673 patent/US20140335127A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1481057B1 (de) | 2006-02-15 |
| EP1481057A1 (de) | 2004-12-01 |
| DE60303591T2 (de) | 2007-03-01 |
| DK1481057T3 (da) | 2006-05-15 |
| US20090074798A1 (en) | 2009-03-19 |
| US20140335127A1 (en) | 2014-11-13 |
| IL220322A0 (en) | 2012-07-31 |
| WO2003074687A1 (en) | 2003-09-12 |
| AU2003205502A1 (en) | 2003-09-16 |
| AU2003205502B2 (en) | 2008-01-31 |
| IL163806A0 (en) | 2005-12-18 |
| ES2258214T3 (es) | 2006-08-16 |
| AU2003205502C1 (en) | 2011-08-25 |
| CA2477794A1 (en) | 2003-09-12 |
| CA2477794C (en) | 2013-08-20 |
| IL163806A (en) | 2012-08-30 |
| US8703471B2 (en) | 2014-04-22 |
| KR20090110951A (ko) | 2009-10-23 |
| DE60303591D1 (de) | 2006-04-20 |
| PT1481057E (pt) | 2006-05-31 |
| US20050287628A1 (en) | 2005-12-29 |
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