CA2551131A1 - Novel recombinant proteins with n-terminal free thiol - Google Patents
Novel recombinant proteins with n-terminal free thiol Download PDFInfo
- Publication number
- CA2551131A1 CA2551131A1 CA002551131A CA2551131A CA2551131A1 CA 2551131 A1 CA2551131 A1 CA 2551131A1 CA 002551131 A CA002551131 A CA 002551131A CA 2551131 A CA2551131 A CA 2551131A CA 2551131 A1 CA2551131 A1 CA 2551131A1
- Authority
- CA
- Canada
- Prior art keywords
- epo
- moiety
- conjugate
- erythropoietin
- erythropoietic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
- C07K1/1075—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of amino acids or peptide residues
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
- C07K1/1077—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/505—Erythropoietin [EPO]
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Analytical Chemistry (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US53361703P | 2003-12-31 | 2003-12-31 | |
| US60/533,617 | 2003-12-31 | ||
| PCT/US2004/043081 WO2005065239A2 (en) | 2003-12-31 | 2004-12-23 | Novel recombinant proteins with n-terminal free thiol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2551131A1 true CA2551131A1 (en) | 2005-07-21 |
Family
ID=34748926
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002551131A Abandoned CA2551131A1 (en) | 2003-12-31 | 2004-12-23 | Novel recombinant proteins with n-terminal free thiol |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US20050170457A1 (https=) |
| EP (1) | EP1699920A4 (https=) |
| JP (1) | JP2008500275A (https=) |
| CN (1) | CN1902311A (https=) |
| AU (1) | AU2004311796A1 (https=) |
| CA (1) | CA2551131A1 (https=) |
| WO (1) | WO2005065239A2 (https=) |
Families Citing this family (98)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101678079B (zh) | 2006-11-28 | 2013-12-25 | 韩诺生物制约株式会社 | 修饰的促红细胞生成素多肽及其治疗用途 |
| TW201307390A (zh) | 2007-02-02 | 2013-02-16 | Amgen Inc | 海帕西啶（ｈｅｐｃｉｄｉｎ）、海帕西啶拮抗劑及使用方法 |
| EP2205280B1 (en) * | 2007-09-27 | 2019-09-04 | Amgen Inc. | Pharmaceutical formulations |
| EP2219602A1 (en) | 2007-11-15 | 2010-08-25 | Amgen, Inc | Aqueous formulation of erythropoiesis stimulating protein stablised by antioxidants for parenteral administration |
| ES2500066T3 (es) | 2008-01-25 | 2014-09-30 | Amgen, Inc | Anticuerpos frente a ferroportina y métodos de uso |
| CA2722600C (en) | 2008-05-01 | 2014-01-21 | Amgen Inc. | Anti-hepcidin antibodies and methods of use |
| JP6018753B2 (ja) | 2008-11-13 | 2016-11-02 | ザ・ジェネラル・ホスピタル・コーポレイションＴｈｅ Ｇｅｎｅｒａｌ Ｈｏｓｐｉｔａｌ Ｃｏｒｐｏｒａｔｉｏｎ | Ｂｍｐ−６の調節によって鉄の恒常性を制御するための方法および組成物 |
| MX344382B (es) | 2009-10-23 | 2016-12-14 | Amgen Inc * | Adaptador de vial y sistema. |
| WO2011156373A1 (en) | 2010-06-07 | 2011-12-15 | Amgen Inc. | Drug delivery device |
| CA2831100C (en) | 2011-03-31 | 2020-02-18 | Mark Dominis Holt | Vial adapter and system |
| EP2699293B8 (en) | 2011-04-20 | 2022-07-20 | Amgen Inc. | Autoinjector apparatus |
| EA018116B1 (ru) * | 2011-06-06 | 2013-05-30 | Общество С Ограниченной Ответственностью "Форт" (Ооо "Форт") | Способ получения ковалентного конъюгата полиэтиленгликоля с эритропоэтином |
| ES2675035T3 (es) | 2011-10-14 | 2018-07-05 | Amgen, Inc | Inyector y método de ensamblaje |
| EP3656426B1 (en) | 2012-11-21 | 2023-05-17 | Amgen Inc. | Drug delivery device |
| US9657098B2 (en) | 2013-03-15 | 2017-05-23 | Intrinsic Lifesciences, Llc | Anti-hepcidin antibodies and uses thereof |
| SG11201507417RA (en) | 2013-03-15 | 2015-10-29 | Amgen Inc | Body contour adaptable autoinjector device |
| EP2968760B1 (en) | 2013-03-15 | 2024-01-03 | Amgen Inc. | Drug cassette, autoinjector, and autoinjector system |
| CA2904661C (en) | 2013-03-15 | 2022-03-15 | Amgen Inc. | Drug cassette, autoinjector, and autoinjector system |
| IL292270B2 (en) | 2013-03-22 | 2024-04-01 | Amgen Inc | Injector and method of assembly |
| WO2015032981A1 (en) * | 2013-09-09 | 2015-03-12 | Lek Pharmaceuticals D.D. | Erythropoietin conjugates having oral bioavailability |
| ES3062706T3 (en) | 2013-10-24 | 2026-04-13 | Amgen Inc | Drug delivery system with temperature-sensitive control |
| MX373358B (es) | 2013-10-24 | 2020-07-06 | Amgen Inc | Inyector y método de montaje. |
| WO2015119906A1 (en) | 2014-02-05 | 2015-08-13 | Amgen Inc. | Drug delivery system with electromagnetic field generator |
| KR102496507B1 (ko) | 2014-05-07 | 2023-02-03 | 암겐 인코포레이티드 | 충격 감소 요소들을 가진 자동 주사기 |
| US20170103186A1 (en) | 2014-06-03 | 2017-04-13 | Amgen Inc. | Systems and methods for supporting patient use of a drug delivery device |
| AU2015321462B2 (en) | 2014-09-22 | 2020-04-30 | Intrinsic Lifesciences Llc | Humanized anti-hepcidin antibodies and uses thereof |
| EP3206739B1 (en) | 2014-10-14 | 2021-12-01 | Amgen Inc. | Drug injection device with visual and audio indicators |
| US10046058B2 (en) | 2014-12-02 | 2018-08-14 | Rezolute, Inc. | Use of hydrophobic organic acids to increase hydrophobicity of proteins and protein conjugates |
| WO2016100781A1 (en) | 2014-12-19 | 2016-06-23 | Amgen Inc. | Drug delivery device with proximity sensor |
| US11357916B2 (en) | 2014-12-19 | 2022-06-14 | Amgen Inc. | Drug delivery device with live button or user interface field |
| CA2976935C (en) | 2015-02-17 | 2020-03-10 | Amgen Inc. | Drug delivery device with vacuum assisted securement and/or feedback |
| EP3261690B1 (en) | 2015-02-27 | 2021-12-15 | Amgen Inc. | Drug delivery device having a needle guard mechanism with a tunable threshold of resistance to needle guard movement |
| WO2016196017A1 (en) | 2015-06-04 | 2016-12-08 | Antriabio, Inc. | Amine pegylation methods for the preparation of site-specific protein conjugates |
| WO2017039786A1 (en) | 2015-09-02 | 2017-03-09 | Amgen Inc. | Syringe assembly adapter for a syringe |
| CN105367629B (zh) * | 2015-11-09 | 2019-01-08 | 天津药物研究院有限公司 | 一种促红细胞生成素模拟肽以及其制备方法和用途 |
| US11351308B2 (en) | 2015-12-09 | 2022-06-07 | Amgen Inc. | Auto-injector with signaling cap |
| US11154661B2 (en) | 2016-01-06 | 2021-10-26 | Amgen Inc. | Auto-injector with signaling electronics |
| ES2814287T3 (es) | 2016-03-15 | 2021-03-26 | Amgen Inc | Reducir la probabilidad de rotura de cristal en dispositivos de administración de fármaco |
| US11541168B2 (en) | 2016-04-29 | 2023-01-03 | Amgen Inc. | Drug delivery device with messaging label |
| GB2549798A (en) * | 2016-04-29 | 2017-11-01 | Univ Bradford | Peptides and nanoparticle formulations thereof |
| WO2017192287A1 (en) | 2016-05-02 | 2017-11-09 | Amgen Inc. | Syringe adapter and guide for filling an on-body injector |
| AU2017263558B2 (en) | 2016-05-13 | 2022-12-22 | Amgen Inc. | Vial sleeve assembly |
| US11238150B2 (en) | 2016-05-16 | 2022-02-01 | Amgen Inc. | Data encryption in medical devices with limited computational capability |
| US11541176B2 (en) | 2016-06-03 | 2023-01-03 | Amgen Inc. | Impact testing apparatuses and methods for drug delivery devices |
| WO2018004842A1 (en) | 2016-07-01 | 2018-01-04 | Amgen Inc. | Drug delivery device having minimized risk of component fracture upon impact events |
| WO2018034784A1 (en) | 2016-08-17 | 2018-02-22 | Amgen Inc. | Drug delivery device with placement detection |
| WO2018081234A1 (en) | 2016-10-25 | 2018-05-03 | Amgen Inc. | On-body injector |
| US20190358411A1 (en) | 2017-01-17 | 2019-11-28 | Amgen Inc. | Injection devices and related methods of use and assembly |
| US11752258B2 (en) | 2017-02-17 | 2023-09-12 | Amgen Inc. | Drug delivery device with sterile fluid flowpath and related method of assembly |
| MX2019009755A (es) | 2017-02-17 | 2019-10-07 | Amgen Inc | Mecanismo de insercion para dispositivo de suministro de farmacos. |
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| WO2018164829A1 (en) | 2017-03-07 | 2018-09-13 | Amgen Inc. | Needle insertion by overpressure |
| MX2019010671A (es) | 2017-03-09 | 2019-10-21 | Amgen Inc | Mecanismo de insercion para dispositivo de administracion de farmacos. |
| JP2020511499A (ja) | 2017-03-20 | 2020-04-16 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | 赤血球生成刺激タンパク質のインビトロでの糖鎖改変のための方法 |
| SG11201907676PA (en) | 2017-03-28 | 2019-09-27 | Amgen Inc | Plunger rod and syringe assembly system and method |
| EP3634539A1 (en) | 2017-06-08 | 2020-04-15 | Amgen Inc. | Syringe assembly for a drug delivery device and method of assembly |
| MX2019014615A (es) | 2017-06-08 | 2020-02-07 | Amgen Inc | Dispositivo de administracion de farmacos accionado por par de torsion. |
| MX2019015472A (es) | 2017-06-22 | 2020-02-19 | Amgen Inc | Reduccion del impacto/choque de la activacion del mecanismo. |
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| EP3651832B1 (en) | 2017-07-14 | 2023-12-13 | Amgen Inc. | Needle insertion-retraction system having dual torsion spring system |
| US11672733B2 (en) | 2017-07-21 | 2023-06-13 | Amgen Inc. | Gas permeable sealing member for drug container and methods of assembly |
| WO2019022950A1 (en) | 2017-07-25 | 2019-01-31 | Amgen Inc. | DRUG DELIVERY DEVICE WITH CONTAINER ACCESS SYSTEM AND ASSEMBLY METHOD THEREOF |
| US11617837B2 (en) | 2017-07-25 | 2023-04-04 | Amgen Inc. | Drug delivery device with gear module and related method of assembly |
| MA49838A (fr) | 2017-08-09 | 2020-06-17 | Amgen Inc | Systèm de administration de médicaments avec pression hydraulique-pneumatique de chambre |
| US11077246B2 (en) | 2017-08-18 | 2021-08-03 | Amgen Inc. | Wearable injector with sterile adhesive patch |
| US11103636B2 (en) | 2017-08-22 | 2021-08-31 | Amgen Inc. | Needle insertion mechanism for drug delivery device |
| EP3691717B1 (en) | 2017-10-04 | 2023-02-08 | Amgen Inc. | Flow adapter for drug delivery device |
| CN111132711B (zh) | 2017-10-06 | 2022-07-01 | 安进公司 | 带有联锁组件的药物递送装置及相关组装方法 |
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| MA50527A (fr) | 2017-11-03 | 2020-09-09 | Amgen Inc | Système et approches pour stériliser un dispositif d'administration de médicament |
| IL273664B1 (en) | 2017-11-06 | 2026-02-01 | Amgen Inc | Full-fledged assemblies and related methods |
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| CA3079665A1 (en) | 2017-11-10 | 2019-05-16 | Amgen Inc. | Plungers for drug delivery devices |
| EP3710089A1 (en) | 2017-11-16 | 2020-09-23 | Amgen Inc. | Autoinjector with stall and end point detection |
| MX2020004996A (es) | 2017-11-16 | 2020-08-27 | Amgen Inc | Un mecanismo de pestillo de puerta para un dispositivo de administracion de farmacos. |
| BR112020017645A2 (pt) * | 2018-03-02 | 2020-12-29 | Elicio Therapeutics Inc. | Compostos que incluem uma sequência kras mutante e um lipídio e usos dos mesmos |
| US10835685B2 (en) | 2018-05-30 | 2020-11-17 | Amgen Inc. | Thermal spring release mechanism for a drug delivery device |
| US11083840B2 (en) | 2018-06-01 | 2021-08-10 | Amgen Inc. | Modular fluid path assemblies for drug delivery devices |
| EP3826699A1 (en) | 2018-07-24 | 2021-06-02 | Amgen Inc. | Delivery devices for administering drugs |
| WO2020023336A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Hybrid drug delivery devices with grip portion |
| US12303677B2 (en) | 2018-07-24 | 2025-05-20 | Amgen Inc. | Hybrid drug delivery devices with optional grip portion and related method of preparation |
| MA53379A (fr) | 2018-07-24 | 2021-06-02 | Amgen Inc | Dispositifs d'administration pour l'administration de médicaments |
| CA3103105A1 (en) | 2018-07-31 | 2020-02-06 | Amgen Inc. | Fluid path assembly for a drug delivery device |
| MA53724A (fr) | 2018-09-24 | 2021-12-29 | Amgen Inc | Systèmes et procédés de dosage interventionnel |
| MA53718A (fr) | 2018-09-28 | 2022-01-05 | Amgen Inc | Ensemble d'activation d'échappement de fil de muscle pour un dispositif d'administration de médicament |
| TWI857975B (zh) | 2018-10-02 | 2024-10-11 | 美商安進公司 | 具有內部力傳遞的用於藥物遞送之注射系統 |
| TW202529830A (zh) | 2018-10-05 | 2025-08-01 | 美商安進公司 | 具有劑量指示器之藥物遞送裝置 |
| MA53912A (fr) | 2018-10-15 | 2022-01-19 | Amgen Inc | Dispositif d'administration de médicament comprenant un mécanisme d'amortissement |
| EA202191038A1 (ru) | 2018-10-15 | 2021-07-06 | Эмджен Инк. | Способ платформенной сборки для устройства доставки лекарственного средства |
| AU2019370159B2 (en) | 2018-11-01 | 2025-05-29 | Amgen Inc. | Drug delivery devices with partial drug delivery member retraction |
| EP3873566B1 (en) | 2018-11-01 | 2024-11-27 | Amgen Inc. | Drug delivery devices with partial drug delivery member retraction |
| TWI831847B (zh) | 2018-11-01 | 2024-02-11 | 美商安進公司 | 部分針頭縮回之藥物遞送裝置及其操作方法 |
| WO2020219482A1 (en) | 2019-04-24 | 2020-10-29 | Amgen Inc. | Syringe sterilization verification assemblies and methods |
| JP7608439B2 (ja) | 2019-08-23 | 2025-01-06 | アムジエン・インコーポレーテツド | 構成可能な針シールド係合構成要素を備えた薬物送達デバイス及び関連方法 |
| WO2022159414A1 (en) | 2021-01-22 | 2022-07-28 | University Of Rochester | Erythropoietin for gastroinfestinal dysfunction |
| KR20240011135A (ko) | 2021-05-21 | 2024-01-25 | 암젠 인크 | 약물 용기를 위한 충전 레시피를 최적화하는 방법 |
| WO2024094457A1 (en) | 2022-11-02 | 2024-05-10 | F. Hoffmann-La Roche Ag | Method for producing glycoprotein compositions |
| WO2026030152A1 (en) | 2024-07-29 | 2026-02-05 | Amgen Inc. | System and method for assessing transferability of a fill recipe |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4775622A (en) * | 1982-03-08 | 1988-10-04 | Genentech, Inc. | Expression, processing and secretion of heterologous protein by yeast |
| US5206344A (en) * | 1985-06-26 | 1993-04-27 | Cetus Oncology Corporation | Interleukin-2 muteins and polymer conjugation thereof |
| US5766897A (en) * | 1990-06-21 | 1998-06-16 | Incyte Pharmaceuticals, Inc. | Cysteine-pegylated proteins |
| EP0815134B1 (en) * | 1995-03-14 | 2002-06-05 | Praecis Pharmaceuticals Incorporated | Modulators of amyloid aggregation |
| US5939286A (en) * | 1995-05-10 | 1999-08-17 | University Of Florida | Hybrid interferon tau/alpha polypeptides, their recombinant production, and methods using them |
| US6015662A (en) * | 1996-01-23 | 2000-01-18 | Abbott Laboratories | Reagents for use as calibrators and controls |
| US6083725A (en) * | 1996-09-13 | 2000-07-04 | Transkaryotic Therapies, Inc. | Tranfected human cells expressing human α-galactosidase A protein |
| IL129177A0 (en) * | 1996-09-26 | 2000-02-17 | Univ Southern California | Methods and compositions for lipidization of hydrophilic molecules |
| ATE375363T1 (de) * | 1997-07-14 | 2007-10-15 | Bolder Biotechnology Inc | Derivate des wachstumshormons und verwandte proteine |
| US6433145B1 (en) * | 1998-07-21 | 2002-08-13 | Human Genome Sciences, Inc. | Keratinocyte derived interferon |
| BR122013003013B8 (pt) * | 1999-01-14 | 2021-07-06 | Bolder Biotechnology Inc | proteína isolada monopeguilada do hormônio do crescimento e método para sua obtenção |
| IL152804A0 (en) * | 2000-05-16 | 2003-06-24 | Bolder Biotechnology Inc | Methods for refolding proteins containing free cysteine residues |
| US6908963B2 (en) * | 2001-10-09 | 2005-06-21 | Nektar Therapeutics Al, Corporation | Thioester polymer derivatives and method of modifying the N-terminus of a polypeptide therewith |
| WO2003055526A2 (en) * | 2001-12-21 | 2003-07-10 | Maxygen Aps | Erythropoietin conjugates |
| US7074755B2 (en) * | 2003-05-17 | 2006-07-11 | Centocor, Inc. | Erythropoietin conjugate compounds with extended half-lives |
| KR20060032140A (ko) * | 2003-05-30 | 2006-04-14 | 센토코 인코포레이티드 | 트랜스글루타미나아제를 이용한 신규 에리트로포이에틴접합체의 형성 |
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- 2004-12-23 AU AU2004311796A patent/AU2004311796A1/en not_active Abandoned
- 2004-12-23 EP EP04815195A patent/EP1699920A4/en not_active Withdrawn
- 2004-12-23 JP JP2006547297A patent/JP2008500275A/ja active Pending
- 2004-12-23 CA CA002551131A patent/CA2551131A1/en not_active Abandoned
- 2004-12-23 CN CNA2004800396501A patent/CN1902311A/zh active Pending
- 2004-12-23 US US11/021,516 patent/US20050170457A1/en not_active Abandoned
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2009
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| US20090239790A1 (en) | 2009-09-24 |
| WO2005065239A2 (en) | 2005-07-21 |
| WO2005065239A3 (en) | 2005-11-24 |
| EP1699920A2 (en) | 2006-09-13 |
| US20050170457A1 (en) | 2005-08-04 |
| JP2008500275A (ja) | 2008-01-10 |
| WO2005065239A8 (en) | 2006-08-17 |
| EP1699920A4 (en) | 2008-05-28 |
| CN1902311A (zh) | 2007-01-24 |
| AU2004311796A1 (en) | 2005-07-21 |
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