MX2017012654A - Variantes de protoxina-ii y metodos de uso. - Google Patents
Variantes de protoxina-ii y metodos de uso.Info
- Publication number
- MX2017012654A MX2017012654A MX2017012654A MX2017012654A MX2017012654A MX 2017012654 A MX2017012654 A MX 2017012654A MX 2017012654 A MX2017012654 A MX 2017012654A MX 2017012654 A MX2017012654 A MX 2017012654A MX 2017012654 A MX2017012654 A MX 2017012654A
- Authority
- MX
- Mexico
- Prior art keywords
- protoxin
- variants
- methods
- foregoing
- making
- Prior art date
Links
- 101000844259 Thrixopelma pruriens Beta/omega-theraphotoxin-Tp2a Proteins 0.000 abstract 1
- 102000040430 polynucleotide Human genes 0.000 abstract 1
- 108091033319 polynucleotide Proteins 0.000 abstract 1
- 239000002157 polynucleotide Substances 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1767—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
-
- 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
- A61K47/56—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- 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
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- 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
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
- C07K14/43513—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from arachnidae
- C07K14/43518—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from arachnidae from spiders
-
- 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
- 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
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/31—Fusion polypeptide fusions, other than Fc, for prolonged plasma life, e.g. albumin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/50—Fusion polypeptide containing protease site
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (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)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Insects & Arthropods (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Neurology (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Toxicology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pain & Pain Management (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Biomedical Technology (AREA)
- Rheumatology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562142069P | 2015-04-02 | 2015-04-02 | |
| PCT/US2016/025247 WO2016161100A1 (en) | 2015-04-02 | 2016-03-31 | Protoxin-ii variants and methods of use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2017012654A true MX2017012654A (es) | 2018-01-09 |
Family
ID=57006450
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2017012654A MX2017012654A (es) | 2015-04-02 | 2016-03-31 | Variantes de protoxina-ii y metodos de uso. |
Country Status (16)
| Country | Link |
|---|---|
| US (3) | US10463714B2 (enExample) |
| EP (2) | EP3960757A1 (enExample) |
| JP (2) | JP6985151B2 (enExample) |
| KR (1) | KR20170134542A (enExample) |
| CN (1) | CN107921089A (enExample) |
| AR (1) | AR104173A1 (enExample) |
| AU (2) | AU2016242905B2 (enExample) |
| BR (1) | BR112017020896A2 (enExample) |
| CA (1) | CA2981336A1 (enExample) |
| ES (1) | ES2888799T3 (enExample) |
| IL (2) | IL254599B (enExample) |
| MA (1) | MA41864A (enExample) |
| MX (1) | MX2017012654A (enExample) |
| TW (1) | TW201708249A (enExample) |
| UY (1) | UY36602A (enExample) |
| WO (1) | WO2016161100A1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10414808B2 (en) | 2012-05-18 | 2019-09-17 | Janssen Biotech, Inc. | Huwentoxin-IV variants and methods of use |
| BR112016007062A2 (pt) | 2013-10-03 | 2017-09-12 | Janssen Biotech Inc | variantes de protoxina-ii e métodos de uso |
| MA41642A (fr) | 2015-03-03 | 2018-01-09 | Janssen Biotech Inc | Variants de protoxine ii et méthodes d'utilisation |
| WO2016161100A1 (en) | 2015-04-02 | 2016-10-06 | Janssen Biotech, Inc. | Protoxin-ii variants and methods of use |
| TWI724392B (zh) | 2018-04-06 | 2021-04-11 | 美商美國禮來大藥廠 | 生長分化因子15促效劑化合物及其使用方法 |
| CN109369784B (zh) * | 2018-11-14 | 2019-08-30 | 青海芬陀利华生物科技有限公司 | PaTx-1毒素及其应用 |
| US20230241259A1 (en) * | 2020-06-10 | 2023-08-03 | Memorial Sloan Kettering Cancer Center | IMAGING COMPOUNDS SELECTIVE FOR NaV1.7 |
| EP4547264A4 (en) * | 2022-07-01 | 2026-07-15 | Univ Miami | Cannabinoid conopeptide gene therapies for pain relief |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4309989A (en) | 1976-02-09 | 1982-01-12 | The Curators Of The University Of Missouri | Topical application of medication by ultrasound with coupling agent |
| US4767402A (en) | 1986-07-08 | 1988-08-30 | Massachusetts Institute Of Technology | Ultrasound enhancement of transdermal drug delivery |
| AU742270B2 (en) | 1997-04-16 | 2001-12-20 | Enteris Biopharma, Inc. | Direct expression of peptides into culture media |
| IL120943A (en) | 1997-05-29 | 2004-03-28 | Univ Ben Gurion | A system for administering drugs through the skin |
| US6670127B2 (en) | 1997-09-16 | 2003-12-30 | Egea Biosciences, Inc. | Method for assembly of a polynucleotide encoding a target polypeptide |
| ES2243007T3 (es) | 1997-09-16 | 2005-11-16 | Egea Biosciences Llc | Sintesis quimica completa y sintesis de genes de genomas. |
| US20030148273A1 (en) * | 2000-08-26 | 2003-08-07 | Shoulian Dong | Target enrichment and amplification |
| EP1348466A3 (en) | 2002-02-01 | 2003-10-29 | Inspire Pharmaceuticals, Inc. | Method for treating pain with adenosine-tetraphosphates |
| US7659082B2 (en) | 2002-02-19 | 2010-02-09 | Xenon Pharmaceuticals Inc. | Methods for identifying analgesic agents |
| US7833979B2 (en) | 2005-04-22 | 2010-11-16 | Amgen Inc. | Toxin peptide therapeutic agents |
| AU2006311725B2 (en) | 2005-11-04 | 2011-11-24 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of NAV1.8 gene |
| WO2007109324A2 (en) | 2006-03-21 | 2007-09-27 | Xenon Pharmaceuticals, Inc. | Potent and selective nav 1.7 sodium channel blockers |
| JP2010502231A (ja) | 2006-09-08 | 2010-01-28 | メイヨ・ファウンデーション・フォー・メディカル・エデュケーション・アンド・リサーチ | 血管拡張作用を欠く水利尿およびナトリウム利尿ポリペプチド |
| WO2008033564A1 (en) | 2006-09-15 | 2008-03-20 | Hydra Biosciences Inc. | Compounds for modulating trpv3 function |
| PE20081140A1 (es) | 2006-10-25 | 2008-09-22 | Amgen Inc | Agentes terapeuticos a base de peptidos derivados de toxinas |
| JP5801197B2 (ja) | 2008-09-03 | 2015-10-28 | ノノ インコーポレイテッド | 痛みの治療に関する薬剤及び方法 |
| WO2010104115A1 (ja) | 2009-03-10 | 2010-09-16 | 独立行政法人産業技術総合研究所 | 膜タンパク質を特異的に認識するポリペプチドの調製方法 |
| CA2774350A1 (en) | 2009-09-15 | 2011-03-24 | Alomone Preclinical Ltd. | Novel peptides isolated from spider venom, and uses thereof |
| KR101550489B1 (ko) * | 2010-03-08 | 2015-09-07 | 다나-파버 캔서 인스티튜트 인크. | 기준 차단 서열을 이용한 완전 ｃｏｌｄ－ｐｃｒ 풍부화 |
| WO2012004664A2 (en) | 2010-07-07 | 2012-01-12 | Purdue Pharma L.P. | Analogs of sodium channel peptide toxin |
| CN101979411A (zh) | 2010-10-21 | 2011-02-23 | 湖南师范大学 | 虎纹捕鸟蛛蛋白酶抑制剂 |
| WO2012099983A1 (en) | 2011-01-18 | 2012-07-26 | Amgen Inc. | Nav1.7 knockout mice and uses thereof |
| KR20210056458A (ko) | 2011-05-04 | 2021-05-18 | 바이오셉트 인코포레이티드 | 핵산 서열 변이체를 검출하는 방법 |
| CA2873860A1 (en) | 2012-05-18 | 2013-11-21 | Janssen Biotech, Inc. | Huwentoxin-iv variants and methods of use |
| US10414808B2 (en) | 2012-05-18 | 2019-09-17 | Janssen Biotech, Inc. | Huwentoxin-IV variants and methods of use |
| US9102751B2 (en) | 2012-05-18 | 2015-08-11 | Janssen Biotech, Inc. | Huwentoxin-IV variants and methods of use |
| US9718865B2 (en) | 2012-07-27 | 2017-08-01 | Purdue Pharma L.P. | Sodium channel blocking peptides and the use thereof |
| WO2014165277A2 (en) | 2013-03-12 | 2014-10-09 | Amgen Inc. | POTENT AND SELECTIVE INHIBITORS OF Nav1.7 |
| CN104065367B (zh) | 2013-03-20 | 2017-11-07 | 江苏多维科技有限公司 | 一种低功耗磁电阻开关传感器 |
| BR112016007062A2 (pt) * | 2013-10-03 | 2017-09-12 | Janssen Biotech Inc | variantes de protoxina-ii e métodos de uso |
| MA41642A (fr) * | 2015-03-03 | 2018-01-09 | Janssen Biotech Inc | Variants de protoxine ii et méthodes d'utilisation |
| WO2016161100A1 (en) | 2015-04-02 | 2016-10-06 | Janssen Biotech, Inc. | Protoxin-ii variants and methods of use |
-
2016
- 2016-03-31 WO PCT/US2016/025247 patent/WO2016161100A1/en not_active Ceased
- 2016-03-31 MA MA041864A patent/MA41864A/fr unknown
- 2016-03-31 TW TW105110361A patent/TW201708249A/zh unknown
- 2016-03-31 CA CA2981336A patent/CA2981336A1/en not_active Abandoned
- 2016-03-31 MX MX2017012654A patent/MX2017012654A/es unknown
- 2016-03-31 EP EP21189427.4A patent/EP3960757A1/en not_active Withdrawn
- 2016-03-31 JP JP2017551164A patent/JP6985151B2/ja not_active Expired - Fee Related
- 2016-03-31 BR BR112017020896A patent/BR112017020896A2/pt not_active Application Discontinuation
- 2016-03-31 CN CN201680020883.XA patent/CN107921089A/zh active Pending
- 2016-03-31 EP EP16774187.5A patent/EP3277304B1/en active Active
- 2016-03-31 KR KR1020177031290A patent/KR20170134542A/ko not_active Withdrawn
- 2016-03-31 AU AU2016242905A patent/AU2016242905B2/en not_active Ceased
- 2016-03-31 ES ES16774187T patent/ES2888799T3/es active Active
- 2016-04-01 AR ARP160100893A patent/AR104173A1/es not_active Application Discontinuation
- 2016-04-04 US US15/090,328 patent/US10463714B2/en not_active Expired - Fee Related
- 2016-04-04 UY UY0001036602A patent/UY36602A/es unknown
-
2017
- 2017-09-19 IL IL254599A patent/IL254599B/en active IP Right Grant
-
2019
- 2019-11-04 US US16/673,750 patent/US11083776B2/en not_active Expired - Fee Related
-
2021
- 2021-04-21 IL IL282508A patent/IL282508A/en unknown
- 2021-08-09 US US17/397,586 patent/US20220054590A1/en not_active Abandoned
- 2021-09-21 JP JP2021153626A patent/JP2022008474A/ja not_active Withdrawn
- 2021-11-12 AU AU2021266345A patent/AU2021266345A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20220054590A1 (en) | 2022-02-24 |
| IL254599A0 (en) | 2017-11-30 |
| EP3277304B1 (en) | 2021-08-04 |
| UY36602A (es) | 2016-09-30 |
| JP2022008474A (ja) | 2022-01-13 |
| US20160287666A1 (en) | 2016-10-06 |
| CN107921089A (zh) | 2018-04-17 |
| CA2981336A1 (en) | 2016-10-06 |
| HK1250476A1 (en) | 2018-12-21 |
| AR104173A1 (es) | 2017-07-05 |
| TW201708249A (zh) | 2017-03-01 |
| US11083776B2 (en) | 2021-08-10 |
| ES2888799T3 (es) | 2022-01-07 |
| KR20170134542A (ko) | 2017-12-06 |
| IL254599B (en) | 2021-05-31 |
| JP6985151B2 (ja) | 2021-12-22 |
| IL282508A (en) | 2021-06-30 |
| AU2021266345A1 (en) | 2021-12-09 |
| US10463714B2 (en) | 2019-11-05 |
| BR112017020896A2 (pt) | 2018-07-10 |
| US20200054712A1 (en) | 2020-02-20 |
| EP3277304A1 (en) | 2018-02-07 |
| WO2016161100A1 (en) | 2016-10-06 |
| AU2016242905A1 (en) | 2017-10-12 |
| JP2018511326A (ja) | 2018-04-26 |
| MA41864A (fr) | 2021-03-24 |
| EP3960757A1 (en) | 2022-03-02 |
| AU2016242905B2 (en) | 2021-08-12 |
| EP3277304A4 (en) | 2018-12-19 |
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