DK2190863T3 - New albumin binding compositions, methods and uses - Google Patents
New albumin binding compositions, methods and uses Download PDFInfo
- Publication number
- DK2190863T3 DK2190863T3 DK08786222.3T DK08786222T DK2190863T3 DK 2190863 T3 DK2190863 T3 DK 2190863T3 DK 08786222 T DK08786222 T DK 08786222T DK 2190863 T3 DK2190863 T3 DK 2190863T3
- Authority
- DK
- Denmark
- Prior art keywords
- seq
- albumin
- polypeptide
- binding
- protein
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- 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
- C07K14/315—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Streptococcus (G), e.g. Enterococci
-
- 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
- C07K14/305—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Micrococcaceae (F)
- C07K14/31—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Micrococcaceae (F) from Staphylococcus (G)
-
- 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/53—Colony-stimulating factor [CSF]
- C07K14/535—Granulocyte CSF; Granulocyte-macrophage CSF
-
- 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
- C07K14/575—Hormones
- C07K14/605—Glucagons
-
- 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
- C07K14/575—Hormones
- C07K14/61—Growth hormone [GH], i.e. somatotropin
-
- 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
- C07K14/745—Blood coagulation or fibrinolysis factors
- C07K14/755—Factors VIII, e.g. factor VIII C (AHF), factor VIII Ag (VWF)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- A61K47/62—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 a protein, peptide or polyamino acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US96261807P | 2007-07-31 | 2007-07-31 | |
| EP07113533 | 2007-07-31 | ||
| PCT/EP2008/059389 WO2009016043A2 (en) | 2007-07-31 | 2008-07-17 | New albumin binding compositions, methods and uses |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2190863T3 true DK2190863T3 (en) | 2015-11-30 |
Family
ID=40057660
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK08786222.3T DK2190863T3 (en) | 2007-07-31 | 2008-07-17 | New albumin binding compositions, methods and uses |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US8937153B2 (enExample) |
| EP (2) | EP2190863B1 (enExample) |
| JP (1) | JP5718638B2 (enExample) |
| CN (2) | CN104710518A (enExample) |
| AU (1) | AU2008281913B2 (enExample) |
| CA (1) | CA2694139C (enExample) |
| DE (1) | DE08786222T1 (enExample) |
| DK (1) | DK2190863T3 (enExample) |
| ES (1) | ES2346178T3 (enExample) |
| HK (1) | HK1211040A1 (enExample) |
| WO (1) | WO2009016043A2 (enExample) |
Families Citing this family (83)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2008281913B2 (en) * | 2007-07-31 | 2013-11-07 | Affibody Ab | New albumin binding compositions, methods and uses |
| US20120134984A1 (en) * | 2009-06-01 | 2012-05-31 | Olga Lubman | Molecules with extended half-lives and uses thereof |
| DK2544785T3 (en) * | 2010-03-08 | 2016-01-18 | Ge Healthcare Bio Sciences Ab | Immunoglobulin G Fc region binding polypeptide |
| JP5827218B2 (ja) * | 2010-04-30 | 2015-12-02 | 株式会社三和化学研究所 | 生理活性物質等の生体内安定性向上のためのペプチド及び生体内安定性が向上した生理活性物質 |
| WO2012004384A2 (en) * | 2010-07-09 | 2012-01-12 | Affibody Ab | Polypeptides |
| CA2807127C (en) * | 2010-08-02 | 2019-02-12 | Leslie S. Johnson | Covalent diabodies and uses thereof |
| EA201390450A1 (ru) * | 2010-09-28 | 2013-07-30 | Амилин Фармасьютикалс, Ллк. | Полипептиды с увеличенной продолжительностью действия |
| PT2621515T (pt) * | 2010-09-28 | 2017-07-12 | Aegerion Pharmaceuticals Inc | Polipéptido quimérico de leptina de foca-ser humano com solubilidade aumentada |
| EP2643349B1 (en) | 2010-11-26 | 2019-09-04 | Molecular Partners AG | Designed repeat proteins binding to serum albumin |
| WO2012162068A2 (en) * | 2011-05-21 | 2012-11-29 | Macrogenics, Inc. | Deimmunized serum-binding domains and their use for extending serum half-life |
| US20140256621A1 (en) | 2011-07-08 | 2014-09-11 | Astrazeneca Pharmaceuticals Lp | Engineered poypeptides having enhanced duration of action and reduced immunogenicity |
| CN104271588B (zh) * | 2011-07-08 | 2017-10-10 | 安米林药品有限责任公司 | 具有增强的作用持续时间和降低的免疫原性的工程改造的多肽 |
| EP3511339B1 (en) | 2012-02-20 | 2025-04-09 | IPC Research, LLC | Polypeptides binding to human complement c5 |
| JP2020033372A (ja) * | 2012-03-28 | 2020-03-05 | アフィボディ・アーベー | 経口投与 |
| KR20140142298A (ko) * | 2012-03-28 | 2014-12-11 | 애피바디 에이비 | 경구투여 |
| US20150133373A1 (en) * | 2012-03-28 | 2015-05-14 | Amylin Pharmaceuticals, Llc | Transmucosal delivery of engineered polypeptides |
| US9156887B2 (en) | 2012-05-25 | 2015-10-13 | Janssen Biotech, Inc. | Non-natural consensus albumin binding domains |
| WO2014048977A1 (en) * | 2012-09-25 | 2014-04-03 | Affibody Ab | Albumin binding polzpeptide |
| WO2014053586A1 (en) | 2012-10-05 | 2014-04-10 | Affibody Ab | Her3 binding polypeptides |
| ES2639099T3 (es) * | 2012-10-25 | 2017-10-25 | Affibody Ab | Polipéptido de unión a albúmina |
| PL2912051T3 (pl) | 2012-10-25 | 2018-08-31 | Affibody Ab | Sposób rozdzielania białek zawierających domenę wiążącą albuminę |
| WO2014076179A1 (en) | 2012-11-14 | 2014-05-22 | Affibody Ab | New polypeptide |
| US9255262B2 (en) * | 2013-03-06 | 2016-02-09 | Vision Global Holdings Ltd. | Albumin-binding arginine deminase and the use thereof |
| USRE48805E1 (en) | 2013-03-06 | 2021-11-02 | Vision Global Holdings Ltd. | Method for cancer targeting treatment and detection of arginine using albumin-binding arginine deiminase fusion protein |
| HK1218534A1 (zh) | 2013-03-14 | 2017-02-24 | 多伦多大学管理委员会 | 支架化肽文库以及其制备和筛选方法 |
| EP2968490A1 (en) | 2013-03-14 | 2016-01-20 | Daiichi Sankyo Co., Ltd. | Novel binding proteins for pcsk9 |
| KR102191654B1 (ko) | 2013-03-15 | 2020-12-16 | 애피바디 에이비 | 신규 폴리펩티드 |
| AU2014254019B2 (en) | 2013-04-18 | 2018-09-27 | Armo Biosciences, Inc. | Methods of using interleukin-10 for treating diseases and disorders |
| CA2914837A1 (en) | 2013-06-17 | 2014-12-24 | Armo Biosciences, Inc. | Method for assessing protein identity and stability |
| AU2014314214C1 (en) | 2013-08-28 | 2019-01-24 | Affibody Ab | Binding polypeptides having a mutated scaffold |
| JP6767865B2 (ja) | 2013-08-28 | 2020-10-14 | スウェディッシュ・オーファン・バイオヴィトラム・アーベー(ペーウーベーエル) | ヒト補体c5に結合する安定なポリペプチド |
| US10010588B2 (en) | 2013-08-30 | 2018-07-03 | Armo Biosciences, Inc. | Methods of using pegylated interleukin-10 for treating hyperlipidemia |
| MX2016005915A (es) | 2013-11-11 | 2016-12-16 | Armo Biosciences Inc | Metodos de uso de interleucina-10 para tratar enfermedades y trastornos. |
| US10167322B2 (en) | 2013-12-20 | 2019-01-01 | Affibody Ab | Engineered albumin binding polypeptide |
| US10293043B2 (en) | 2014-06-02 | 2019-05-21 | Armo Biosciences, Inc. | Methods of lowering serum cholesterol |
| UA123432C2 (uk) | 2014-07-30 | 2021-04-07 | Нджм Біофармасьютікалз, Інк. | Димер та спосіб його застосування для лікування метаболічних розладів |
| EP3193930B1 (en) | 2014-09-17 | 2019-06-19 | Affibody AB | New polypeptides |
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| ES2941234T3 (es) | 2014-10-22 | 2023-05-19 | Armo Biosciences Inc | Métodos de uso de la interleucina-10 para el tratamiento de enfermedades y trastornos |
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| CN107952080A (zh) * | 2016-10-14 | 2018-04-24 | 中国科学院过程工程研究所 | 一种肿瘤靶向多肽-药物偶联衍生物、其制备方法及应用 |
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| WO2018213320A1 (en) | 2017-05-15 | 2018-11-22 | Duke University | Recombinant production of hybrid lipid-biopolymer materials that self-assemble and encapsulate agents |
| US11680083B2 (en) | 2017-06-30 | 2023-06-20 | Duke University | Order and disorder as a design principle for stimuli-responsive biopolymer networks |
| WO2019032827A1 (en) | 2017-08-09 | 2019-02-14 | Massachusetts Institute Of Technology | PEPTIDE ALBUMIN BINDING CONJUGATES AND METHODS THEREOF |
| US11198722B2 (en) | 2017-10-06 | 2021-12-14 | University Of Utah Research Foundation | Immune tolerant elastin-like peptide tetramer guided nanoparticles and methods of use |
| US20200239575A1 (en) * | 2017-10-06 | 2020-07-30 | University Of Utah Research Foundation | A fusion protein for targeted therapy of autoimmune disease |
| WO2019147954A1 (en) * | 2018-01-26 | 2019-08-01 | Duke University | Albumin binding peptide-drug (aibiped) conjugates and methods of making and using same |
| WO2019175176A1 (en) | 2018-03-13 | 2019-09-19 | Affibody Ab | Polypeptides based on a novel scaffold |
| US12257308B2 (en) | 2018-04-30 | 2025-03-25 | Duke University | Stimuli-responsive PEG-like polymer-based drug delivery platform |
| US11649275B2 (en) | 2018-08-02 | 2023-05-16 | Duke University | Dual agonist fusion proteins |
| US20210316007A1 (en) * | 2018-09-07 | 2021-10-14 | Duke University | Nanoparticulate drug delivery systems |
| WO2020176478A1 (en) | 2019-02-25 | 2020-09-03 | The University Of Chicago | Methods and compositions for treating inflammatory and autoimmune conditions with ecm-affinity peptides linked to anti-inflammatory agents |
| CA3138805A1 (en) | 2019-06-04 | 2020-12-10 | Johannes Schilling | Designed ankyrin repeat domain with improved stability |
| US11512314B2 (en) | 2019-07-12 | 2022-11-29 | Duke University | Amphiphilic polynucleotides |
| EP4017521A1 (en) | 2019-09-02 | 2022-06-29 | Biotest AG | Factor viii protein with increased half-life |
| EP3785726A1 (en) | 2019-09-02 | 2021-03-03 | Biotest AG | Factor viii protein with increased half-life |
| US20220389066A1 (en) | 2019-11-05 | 2022-12-08 | Affibody Ab | Polypeptides |
| EP4106798A1 (en) | 2020-02-17 | 2022-12-28 | Biotest AG | Subcutaneous administration of factor viii |
| EP3878515A1 (en) * | 2020-03-09 | 2021-09-15 | Hober Biotech AB | Therapeutic agent targeting her2 |
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| CA3200702A1 (en) | 2020-12-21 | 2022-06-30 | Affibody Ab | New polypeptide |
| WO2022171892A1 (en) | 2021-02-15 | 2022-08-18 | Affibody Ab | New her2-binding polypeptide |
| CN118632866A (zh) | 2022-02-08 | 2024-09-10 | 阿菲博迪公司 | 结合胸腺基质淋巴细胞生成素的蛋白质z变体及其医疗用途 |
| AR129357A1 (es) | 2022-05-18 | 2024-08-14 | Protomer Tech Inc | Compuestos aromáticos que contienen boro y análogos de insulina relacionados |
| TW202416938A (zh) | 2022-08-10 | 2024-05-01 | 日商興和股份有限公司 | 親和體微胞(affibody micelle)藥物複合體 |
| EP4665755A1 (en) | 2023-02-17 | 2025-12-24 | Ablynx N.V. | Polypeptides binding to the neonatal fc receptor |
| AU2024265436A1 (en) | 2023-05-04 | 2025-11-06 | Affibody Ab | New polypeptide |
| WO2025073871A1 (en) | 2023-10-03 | 2025-04-10 | Bicycletx Limited | Bicyclic peptide ligand complexes specific for tfr1 |
| TW202545983A (zh) | 2024-01-25 | 2025-12-01 | 瑞典商艾菲博迪公司 | 新穎多肽 |
| CN121041473A (zh) * | 2024-05-29 | 2025-12-02 | 烟台蓝纳成生物技术股份有限公司 | 一种双功能性融合蛋白、放射性核素标记物及其应用 |
| CN118666961B (zh) * | 2024-08-23 | 2024-11-26 | 通化安睿特生物制药股份有限公司 | 人白蛋白特异结合多肽及其应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE509359C2 (sv) | 1989-08-01 | 1999-01-18 | Cemu Bioteknik Ab | Användning av stabiliserade protein- eller peptidkonjugat för framställning av ett läkemedel |
| FR2718452B1 (fr) * | 1994-04-06 | 1996-06-28 | Pf Medicament | Elément d'immunogène, agent immunogène, composition pharmaceutique et procédé de préparation. |
| FR2726471B1 (fr) * | 1994-11-07 | 1997-01-31 | Pf Medicament | Procede pour ameliorer l'immunogenicite d'un compose immunogene ou d'un haptene et application a la preparation de vaccins |
| DE19742706B4 (de) * | 1997-09-26 | 2013-07-25 | Pieris Proteolab Ag | Lipocalinmuteine |
| GB9823071D0 (en) * | 1998-10-21 | 1998-12-16 | Affibody Technology Ab | A method |
| GB9911287D0 (en) * | 1999-05-14 | 1999-07-14 | Affibody Technology Sweden Ab | Self-assembling protein structures |
| US20040001827A1 (en) | 2002-06-28 | 2004-01-01 | Dennis Mark S. | Serum albumin binding peptides for tumor targeting |
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| CN1169827C (zh) | 2001-08-07 | 2004-10-06 | 沈阳三生制药股份有限公司 | 一种增强多肽在体内稳定性药物的生产方法及其应用 |
| WO2003029462A1 (en) * | 2001-09-27 | 2003-04-10 | Pieris Proteolab Ag | Muteins of human neutrophil gelatinase-associated lipocalin and related proteins |
| EP1430136A1 (en) * | 2001-09-27 | 2004-06-23 | Pieris ProteoLab AG | Muteins of apolipoprotein d |
| SE0400274D0 (sv) * | 2004-02-09 | 2004-02-09 | Affibody Ab | New polypeptide |
| JP5634008B2 (ja) | 2004-04-06 | 2014-12-03 | アフィボディ・アーベー | 新規の使用および方法 |
| EP2899277A1 (en) | 2004-11-26 | 2015-07-29 | Pieris AG | Compound with affinity for the cytotoxic T lymphocyte-associated antigen (CTLA-4) |
| AU2008281913B2 (en) * | 2007-07-31 | 2013-11-07 | Affibody Ab | New albumin binding compositions, methods and uses |
| JP5960598B2 (ja) * | 2009-11-04 | 2016-08-02 | アフィボディ・アーベー | Her3結合ポリペプチド |
-
2008
- 2008-07-17 AU AU2008281913A patent/AU2008281913B2/en active Active
- 2008-07-17 US US12/452,731 patent/US8937153B2/en active Active
- 2008-07-17 EP EP08786222.3A patent/EP2190863B1/en active Active
- 2008-07-17 DE DE08786222T patent/DE08786222T1/de active Pending
- 2008-07-17 CA CA2694139A patent/CA2694139C/en active Active
- 2008-07-17 EP EP12176805.5A patent/EP2546261A3/en not_active Withdrawn
- 2008-07-17 ES ES08786222.3T patent/ES2346178T3/es active Active
- 2008-07-17 JP JP2010518606A patent/JP5718638B2/ja active Active
- 2008-07-17 CN CN201510071238.8A patent/CN104710518A/zh active Pending
- 2008-07-17 CN CN200880101168.4A patent/CN101765608B/zh active Active
- 2008-07-17 WO PCT/EP2008/059389 patent/WO2009016043A2/en not_active Ceased
- 2008-07-17 DK DK08786222.3T patent/DK2190863T3/da active
-
2014
- 2014-11-24 US US14/551,931 patent/US10118949B2/en active Active
-
2015
- 2015-12-02 HK HK15111838.6A patent/HK1211040A1/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP2546261A3 (en) | 2013-08-14 |
| ES2346178T1 (es) | 2010-10-13 |
| JP5718638B2 (ja) | 2015-05-13 |
| US20150158916A1 (en) | 2015-06-11 |
| CA2694139C (en) | 2018-06-05 |
| JP2010534486A (ja) | 2010-11-11 |
| WO2009016043A3 (en) | 2009-06-04 |
| DE08786222T1 (de) | 2010-11-25 |
| US10118949B2 (en) | 2018-11-06 |
| EP2546261A2 (en) | 2013-01-16 |
| US20100273979A1 (en) | 2010-10-28 |
| AU2008281913A1 (en) | 2009-02-05 |
| US8937153B2 (en) | 2015-01-20 |
| ES2346178T3 (es) | 2015-11-02 |
| CA2694139A1 (en) | 2009-02-05 |
| WO2009016043A2 (en) | 2009-02-05 |
| CN104710518A (zh) | 2015-06-17 |
| EP2190863A2 (en) | 2010-06-02 |
| CN101765608B (zh) | 2015-03-11 |
| HK1211040A1 (en) | 2016-05-13 |
| AU2008281913B2 (en) | 2013-11-07 |
| EP2190863B1 (en) | 2015-09-02 |
| CN101765608A (zh) | 2010-06-30 |
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