ES2563091T3 - Polipéptidos modificados genéticamente que tienen duración de acción potenciada - Google Patents
Polipéptidos modificados genéticamente que tienen duración de acción potenciada Download PDFInfo
- Publication number
- ES2563091T3 ES2563091T3 ES11767876.3T ES11767876T ES2563091T3 ES 2563091 T3 ES2563091 T3 ES 2563091T3 ES 11767876 T ES11767876 T ES 11767876T ES 2563091 T3 ES2563091 T3 ES 2563091T3
- Authority
- ES
- Spain
- Prior art keywords
- genetically modified
- sequence
- action
- modified polypeptides
- enhanced duration
- 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.)
- Active
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title abstract description 7
- 229920001184 polypeptide Polymers 0.000 title abstract description 6
- 102000004196 processed proteins & peptides Human genes 0.000 title abstract description 6
- 102000009027 Albumins Human genes 0.000 abstract 1
- 108010088751 Albumins Proteins 0.000 abstract 1
- 125000003275 alpha amino acid group Chemical group 0.000 abstract 1
- 150000001413 amino acids Chemical class 0.000 abstract 1
- 239000000813 peptide hormone Substances 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 3
- 229930182817 methionine Natural products 0.000 description 3
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 241000235648 Pichia Species 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
Classifications
-
- 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
-
- 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
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/643—Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C07K14/57563—Vasoactive intestinal peptide [VIP]; Related peptides
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
- C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Diabetes (AREA)
- Vascular Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Epidemiology (AREA)
- Child & Adolescent Psychology (AREA)
- Psychiatry (AREA)
- Urology & Nephrology (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38739110P | 2010-09-28 | 2010-09-28 | |
| US387391P | 2010-09-28 | ||
| US42208510P | 2010-12-10 | 2010-12-10 | |
| US422085P | 2010-12-10 | ||
| PCT/US2011/053770 WO2012050923A2 (en) | 2010-09-28 | 2011-09-28 | Engineered polypeptides having enhanced duration of action |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2563091T3 true ES2563091T3 (es) | 2016-03-10 |
Family
ID=44786115
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES11767876.3T Active ES2563091T3 (es) | 2010-09-28 | 2011-09-28 | Polipéptidos modificados genéticamente que tienen duración de acción potenciada |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US9593154B2 (enExample) |
| EP (2) | EP3028720A1 (enExample) |
| JP (1) | JP6121330B2 (enExample) |
| CN (2) | CN103370083B (enExample) |
| BR (1) | BR112013007442A2 (enExample) |
| CA (1) | CA2812951A1 (enExample) |
| EA (1) | EA201390450A1 (enExample) |
| ES (1) | ES2563091T3 (enExample) |
| HK (1) | HK1225307A1 (enExample) |
| MX (1) | MX345245B (enExample) |
| WO (1) | WO2012050923A2 (enExample) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX351128B (es) | 2010-09-28 | 2017-10-03 | Aegerion Pharmaceuticals Inc | Polipeptidos manipulados que tienen duracion de accion incrementada. |
| JP6121330B2 (ja) | 2010-09-28 | 2017-04-26 | アミリン・ファーマシューティカルズ, リミテッド・ライアビリティ・カンパニーAmylin Pharmaceuticals, Llc | 作用持続時間が増した改変ポリペプチド |
| US20140256621A1 (en) | 2011-07-08 | 2014-09-11 | Astrazeneca Pharmaceuticals Lp | Engineered poypeptides having enhanced duration of action and reduced immunogenicity |
| HK1208155A1 (en) * | 2012-03-28 | 2016-02-26 | Amylin Pharmaceuticals, Llc | Transmucosal delivery of engineered polypeptides |
| EP2830665A1 (en) * | 2012-03-28 | 2015-02-04 | Affibody AB | Oral administration |
| UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
| MX362190B (es) | 2012-12-21 | 2019-01-08 | Sanofi Sa | Agonistas duales de glp1/gip o trigonales de glp1/gip/glucagon. |
| HK1215681A1 (zh) | 2013-04-18 | 2016-09-09 | Armo Biosciences, Inc. | 使用白细胞介素-10治疗疾病和病症的方法 |
| US9823255B2 (en) | 2013-06-17 | 2017-11-21 | Armo Biosciences, Inc. | Method for assessing protein identity and stability |
| AU2014311432A1 (en) | 2013-08-30 | 2016-03-03 | Armo Biosciences, Inc. | Methods of using interleukin-10 for treating diseases and disorders |
| CA2928710A1 (en) | 2013-11-11 | 2015-05-14 | Armo Biosciences, Inc. | Methods of using interleukin-10 for treating diseases and disorders |
| WO2015086728A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Exendin-4 peptide analogues as dual glp-1/gip receptor agonists |
| TW201609796A (zh) | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | 非醯化之艾塞那肽－４（ｅｘｅｎｄｉｎ－４）胜肽類似物 |
| WO2015086733A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Dual glp-1/glucagon receptor agonists |
| WO2015086729A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Dual glp-1/gip receptor agonists |
| TW201625668A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 作為胜肽性雙重ｇｌｐ－１／昇糖素受體激動劑之艾塞那肽－４衍生物 |
| TW201625670A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自ｅｘｅｎｄｉｎ－４之雙重ｇｌｐ－１／升糖素受體促效劑 |
| TW201625669A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自艾塞那肽－４（Ｅｘｅｎｄｉｎ－４）之肽類雙重ＧＬＰ－１／升糖素受體促效劑 |
| WO2015187295A2 (en) | 2014-06-02 | 2015-12-10 | Armo Biosciences, Inc. | Methods of lowering serum cholesterol |
| US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
| WO2016060996A2 (en) | 2014-10-14 | 2016-04-21 | Armo Biosciences, Inc. | Interleukin-15 compositions and uses thereof |
| CA2963995A1 (en) | 2014-10-22 | 2016-04-28 | Armo Biosciences, Inc. | Methods of using interleukin-10 for treating diseases and disorders |
| WO2016126615A1 (en) | 2015-02-03 | 2016-08-11 | Armo Biosciences, Inc. | Methods of using interleukin-10 for treating diseases and disorders |
| HK1246201A1 (zh) | 2015-05-28 | 2018-09-07 | Armo Biosciences, Inc. | 用於治疗癌症的聚乙二醇化白细胞介素-10 |
| AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
| TW201706291A (zh) | 2015-07-10 | 2017-02-16 | 賽諾菲公司 | 作為選擇性肽雙重ｇｌｐ－１／升糖素受體促效劑之新毒蜥外泌肽（ｅｘｅｎｄｉｎ－４）衍生物 |
| ES3039640T3 (en) | 2015-08-25 | 2025-10-23 | Armo Biosciences Inc | Methods of using interleukin-10 for treating diseases and disorders |
| KR20180045001A (ko) | 2015-09-22 | 2018-05-03 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | 개질된 세포독소 및 이의 치료 용도 |
| US10286079B2 (en) | 2015-09-22 | 2019-05-14 | The Regents Of The University Of California | Modified cytotoxins and their therapeutic use |
| WO2017081082A2 (en) * | 2015-11-09 | 2017-05-18 | Curevac Ag | Optimized nucleic acid molecules |
| KR102508651B1 (ko) | 2015-12-23 | 2023-03-13 | 더 존스 홉킨스 유니버시티 | 신경계 및 신경변성 상태의 요법으로서 장기간 작용하는 glf-1r 작용제 |
| KR102460198B1 (ko) * | 2016-03-10 | 2022-10-31 | 메디뮨 리미티드 | 비만 치료를 위한 글루카곤 및 glp-1 공동-작용제 |
| KR20200135618A (ko) * | 2019-05-23 | 2020-12-03 | ㈜ 디앤디파마텍 | 폴리펩티드를 포함하는 비알코올성 지방간 질환의 예방 또는 치료용 약학 조성물 |
| CA3184544A1 (en) * | 2020-07-02 | 2022-01-06 | Sanofi | Glp-1r agonistic peptides with reduced activity |
| CN115925951B (zh) * | 2022-11-30 | 2024-05-24 | 上海交通大学医学院附属仁济医院 | Cd70特异性诊疗一体化分子影像探针的制备方法及应用 |
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| JP5608368B2 (ja) * | 2006-08-01 | 2014-10-15 | ピエリス アーゲー | 涙リポカリンの突然変異タンパク質およびそれを得るための方法 |
| JP2008169195A (ja) | 2007-01-05 | 2008-07-24 | Hanmi Pharmaceutical Co Ltd | キャリア物質を用いたインスリン分泌ペプチド薬物結合体 |
| JP2009003340A (ja) | 2007-06-25 | 2009-01-08 | Oki Data Corp | 画像形成装置 |
| JP2009019027A (ja) | 2007-07-16 | 2009-01-29 | Hanmi Pharmaceutical Co Ltd | アミノ末端のアミノ酸が変異したインスリン分泌ペプチド誘導体 |
| EP2190863B1 (en) * | 2007-07-31 | 2015-09-02 | Affibody AB | New albumin binding compositions, methods and uses |
| EP2259802A1 (en) * | 2008-03-31 | 2010-12-15 | Glaxo Group Limited | Drug fusions and conjugates |
| US8329419B2 (en) | 2008-05-23 | 2012-12-11 | Amylin Pharmaceuticals, Llc | GLP-1 receptor agonist bioassays |
| WO2010054699A1 (en) * | 2008-11-17 | 2010-05-20 | Affibody Ab | Conjugates of albumin binding domain |
| CN105061593B (zh) * | 2009-02-19 | 2018-08-03 | 葛兰素集团有限公司 | 改良的抗血清清蛋白结合变体 |
| US8642544B2 (en) | 2009-04-01 | 2014-02-04 | Amylin Pharmaceuticals, Llc | N-terminus conformationally constrained GLP-1 receptor agonist compounds |
| JP6121330B2 (ja) * | 2010-09-28 | 2017-04-26 | アミリン・ファーマシューティカルズ, リミテッド・ライアビリティ・カンパニーAmylin Pharmaceuticals, Llc | 作用持続時間が増した改変ポリペプチド |
| HK1208155A1 (en) * | 2012-03-28 | 2016-02-26 | Amylin Pharmaceuticals, Llc | Transmucosal delivery of engineered polypeptides |
-
2011
- 2011-09-28 JP JP2013531784A patent/JP6121330B2/ja not_active Expired - Fee Related
- 2011-09-28 ES ES11767876.3T patent/ES2563091T3/es active Active
- 2011-09-28 WO PCT/US2011/053770 patent/WO2012050923A2/en not_active Ceased
- 2011-09-28 BR BR112013007442A patent/BR112013007442A2/pt not_active IP Right Cessation
- 2011-09-28 CN CN201180057092.1A patent/CN103370083B/zh not_active Expired - Fee Related
- 2011-09-28 MX MX2013003481A patent/MX345245B/es active IP Right Grant
- 2011-09-28 EP EP15200093.1A patent/EP3028720A1/en not_active Withdrawn
- 2011-09-28 CN CN201610892824.3A patent/CN106986940A/zh active Pending
- 2011-09-28 EP EP11767876.3A patent/EP2621538B1/en not_active Revoked
- 2011-09-28 CA CA2812951A patent/CA2812951A1/en not_active Abandoned
- 2011-09-28 EA EA201390450A patent/EA201390450A1/ru unknown
-
2013
- 2013-03-28 US US13/852,899 patent/US9593154B2/en not_active Expired - Fee Related
-
2016
- 2016-12-01 HK HK16113722.0A patent/HK1225307A1/en unknown
-
2017
- 2017-01-04 US US15/398,627 patent/US20170114114A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| HK1225307A1 (en) | 2017-09-08 |
| CN103370083A (zh) | 2013-10-23 |
| EA201390450A1 (ru) | 2013-07-30 |
| EP3028720A1 (en) | 2016-06-08 |
| JP2013545724A (ja) | 2013-12-26 |
| CN103370083B (zh) | 2016-11-16 |
| WO2012050923A2 (en) | 2012-04-19 |
| MX2013003481A (es) | 2013-10-25 |
| BR112013007442A2 (pt) | 2019-09-24 |
| US9593154B2 (en) | 2017-03-14 |
| CN106986940A (zh) | 2017-07-28 |
| US20170114114A1 (en) | 2017-04-27 |
| HK1188710A1 (zh) | 2014-05-16 |
| CA2812951A1 (en) | 2012-04-19 |
| WO2012050923A3 (en) | 2012-07-19 |
| EP2621538A2 (en) | 2013-08-07 |
| MX345245B (es) | 2017-01-23 |
| JP6121330B2 (ja) | 2017-04-26 |
| EP2621538B1 (en) | 2015-12-16 |
| US20140107019A1 (en) | 2014-04-17 |
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