MX347229B - Antagonistas de péptido de la familia cgrp de calcitonina de hormonas de péptido y su uso. - Google Patents
Antagonistas de péptido de la familia cgrp de calcitonina de hormonas de péptido y su uso.Info
- Publication number
- MX347229B MX347229B MX2014008960A MX2014008960A MX347229B MX 347229 B MX347229 B MX 347229B MX 2014008960 A MX2014008960 A MX 2014008960A MX 2014008960 A MX2014008960 A MX 2014008960A MX 347229 B MX347229 B MX 347229B
- Authority
- MX
- Mexico
- Prior art keywords
- peptide
- terminal fragment
- calcitonin gene
- modified calcitonin
- amino acid
- Prior art date
Links
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 title abstract 4
- 108090000765 processed proteins & peptides Proteins 0.000 title abstract 3
- 102000055006 Calcitonin Human genes 0.000 title 1
- 108060001064 Calcitonin Proteins 0.000 title 1
- 239000005557 antagonist Substances 0.000 title 1
- 229960004015 calcitonin Drugs 0.000 title 1
- 239000000813 peptide hormone Substances 0.000 title 1
- 238000000034 method Methods 0.000 abstract 3
- 108090000932 Calcitonin Gene-Related Peptide Proteins 0.000 abstract 2
- 102000004414 Calcitonin Gene-Related Peptide Human genes 0.000 abstract 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 abstract 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 abstract 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 abstract 2
- 239000004473 Threonine Substances 0.000 abstract 2
- 235000001014 amino acid Nutrition 0.000 abstract 2
- 150000001413 amino acids Chemical class 0.000 abstract 2
- 210000004900 c-terminal fragment Anatomy 0.000 abstract 2
- 239000000203 mixture Substances 0.000 abstract 2
- 210000004898 n-terminal fragment Anatomy 0.000 abstract 2
- 235000018102 proteins Nutrition 0.000 abstract 2
- 108090000623 proteins and genes Proteins 0.000 abstract 2
- 102000004169 proteins and genes Human genes 0.000 abstract 2
- 208000019695 Migraine disease Diseases 0.000 abstract 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 abstract 1
- 150000001408 amides Chemical group 0.000 abstract 1
- 210000004899 c-terminal region Anatomy 0.000 abstract 1
- 239000003735 calcitonin gene related peptide receptor antagonist Substances 0.000 abstract 1
- 235000018417 cysteine Nutrition 0.000 abstract 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 abstract 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 abstract 1
- 229960002591 hydroxyproline Drugs 0.000 abstract 1
- 206010027599 migraine Diseases 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 abstract 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 238000006467 substitution reaction Methods 0.000 abstract 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 abstract 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 abstract 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 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
- A61K38/22—Hormones
- A61K38/225—Calcitonin gene related peptide
-
- 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
- C07K14/57527—Calcitonin gene related peptide
-
- 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
- A61K38/22—Hormones
- A61K38/23—Calcitonins
-
- 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
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
- A61P5/22—Drugs for disorders of the endocrine system of the parathyroid hormones for decreasing, blocking or antagonising the activity of calcitonin
-
- 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
- C07K14/585—Calcitonins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Endocrinology (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261591236P | 2012-01-26 | 2012-01-26 | |
| PCT/US2013/023260 WO2013112912A1 (en) | 2012-01-26 | 2013-01-25 | Peptide antagonists of the calcitonin cgrp family of peptide hormones and their use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| MX2014008960A MX2014008960A (es) | 2015-01-16 |
| MX347229B true MX347229B (es) | 2017-04-19 |
Family
ID=47682066
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2014008960A MX347229B (es) | 2012-01-26 | 2013-01-25 | Antagonistas de péptido de la familia cgrp de calcitonina de hormonas de péptido y su uso. |
Country Status (14)
| Country | Link |
|---|---|
| US (3) | US9193776B2 (enExample) |
| EP (2) | EP2807187B1 (enExample) |
| JP (3) | JP6025871B2 (enExample) |
| KR (2) | KR101855242B1 (enExample) |
| CN (2) | CN104271596B (enExample) |
| AU (2) | AU2013211929B2 (enExample) |
| CA (1) | CA2861392C (enExample) |
| DK (1) | DK2807187T3 (enExample) |
| ES (2) | ES2819825T3 (enExample) |
| IL (2) | IL233655A (enExample) |
| MX (1) | MX347229B (enExample) |
| NO (1) | NO2864579T3 (enExample) |
| RU (2) | RU2624016C2 (enExample) |
| WO (1) | WO2013112912A1 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2807187B1 (en) * | 2012-01-26 | 2017-07-26 | Christopher J. Soares | Peptide antagonists of the calcitonin cgrp family of peptide hormones and their use |
| EP3027644B1 (en) | 2013-07-30 | 2019-08-21 | Christopher J. Soares | Cgrp agonist peptides |
| JO3669B1 (ar) * | 2015-01-06 | 2020-08-27 | Ferring Bv | بيبتيدات مضَادَّة لببتيد المرتبط بجين الكالسيتونين |
| US11034745B2 (en) * | 2016-01-04 | 2021-06-15 | Adepthera Llc | Superagonist polypeptide analogs of adrenomedullin and intermedin peptide hormones |
| JP7123932B2 (ja) * | 2016-09-02 | 2022-08-23 | クリストファー ジェイ． ソアレス | 神経保護及び神経疾患におけるｃｇｒｐ受容体アンタゴニストの使用 |
| CA2967616A1 (en) * | 2016-09-19 | 2018-03-19 | The Governors Of The University Of Alberta | Brain penetrant amylin receptor based peptides for alzheimer's disease |
| US20200353088A1 (en) * | 2017-11-06 | 2020-11-12 | Auckland Uniservices Limited | Peptide conjugate cgrp receptor antagonists and methods of preparation and uses thereof |
| JP7214104B2 (ja) * | 2019-01-18 | 2023-01-30 | 株式会社大一商会 | 遊技機 |
| JP7214102B2 (ja) * | 2019-01-18 | 2023-01-30 | 株式会社大一商会 | 遊技機 |
| JP7214100B2 (ja) * | 2019-01-18 | 2023-01-30 | 株式会社大一商会 | 遊技機 |
| CN116456981A (zh) * | 2020-11-19 | 2023-07-18 | 辉瑞爱尔兰制药公司 | 用于改善的grp抑制剂递送的组合物 |
Family Cites Families (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2031216A1 (de) | 1969-06-19 | 1971-01-14 | Citizen Watch Co Ltd , Tokio | Tag und Datum Stellvorrichtung fur Uhren mit Kalender |
| US3940475A (en) | 1970-06-11 | 1976-02-24 | Biological Developments, Inc. | Radioimmune method of assaying quantitatively for a hapten |
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| JPS6023084B2 (ja) | 1979-07-11 | 1985-06-05 | 味の素株式会社 | 代用血液 |
| NO812612L (no) | 1980-08-06 | 1982-02-08 | Ferring Pharma Ltd | Enzym-inhibitorer. |
| US4640835A (en) | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
| CH657779A5 (de) | 1982-10-05 | 1986-09-30 | Sandoz Ag | Galenische zusammensetzungen enthaltend calcitonin. |
| IT1164225B (it) | 1983-05-13 | 1987-04-08 | Anic Spa | Analoghi retro-invertiti del pentapeptide potenziante la bradichina bpp5a e metodi per la loro preparazione |
| US4530838A (en) | 1983-07-08 | 1985-07-23 | The Salk Institute For Biological Studies | Synthetic calcitonin-gene-related peptides for lowering blood pressure or gastric acid secretion in mammals |
| US4496689A (en) | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
| EP0206448B1 (en) | 1985-06-19 | 1990-11-14 | Ajinomoto Co., Inc. | Hemoglobin combined with a poly(alkylene oxide) |
| JPS62129297A (ja) * | 1985-08-09 | 1987-06-11 | Toyo Jozo Co Ltd | カルシトニン遺伝子関連ペプチド誘導体 |
| JPS62231168A (ja) | 1986-03-21 | 1987-10-09 | ハイブリテツク・インコ−ポレイテツド | アナライト−レセプタ−分析用内部標準を設けるための改良法 |
| US4791192A (en) | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
| US6552170B1 (en) | 1990-04-06 | 2003-04-22 | Amgen Inc. | PEGylation reagents and compounds formed therewith |
| US5206161A (en) | 1991-02-01 | 1993-04-27 | Genentech, Inc. | Human plasma carboxypeptidase B |
| AU680422B2 (en) | 1992-06-11 | 1997-07-31 | Alkermes Controlled Therapeutics, Inc. | Erythropoietin drug delivery system |
| US5354934A (en) | 1993-02-04 | 1994-10-11 | Amgen Inc. | Pulmonary administration of erythropoietin |
| WO1994021665A1 (en) | 1993-03-24 | 1994-09-29 | Amylin Pharmaceuticals, Inc. | Cloned receptors and methods for screening |
| US5698401A (en) | 1995-11-14 | 1997-12-16 | Abbott Laboratories | Use of nuclear magnetic resonance to identify ligands to target biomolecules |
| US5910482A (en) * | 1996-03-19 | 1999-06-08 | Board Of Regents, The University Of Texas System | Treatment or prevention of preeclampsia, eclampsia with calcitonin gene related peptide, CGRP analog, progestational agent, nitric oxide source, and cyclooxygenase inhibitor |
| WO1997041223A1 (en) | 1996-04-15 | 1997-11-06 | The University Of Miami | Molecular clone of cgrp receptor component protein and uses thereof |
| US20050054557A1 (en) | 2002-05-09 | 2005-03-10 | Goldberg Michael M. | Compositions for delivering parathyroid hormone and calcitonin |
| US7812120B2 (en) | 2003-03-21 | 2010-10-12 | Par Pharmaceutical, Inc. | Nasal calcitonin formulations containing chlorobutanol |
| US20060286129A1 (en) | 2003-12-19 | 2006-12-21 | Emisphere Technologies, Inc. | Oral GLP-1 formulations |
| RU2385878C2 (ru) | 2004-02-11 | 2010-04-10 | Амилин Фармасьютикалз, Инк. | Пептид, обладающий свойствами амилина (варианты), и его применение (варианты) |
| DK1814590T4 (da) | 2004-11-01 | 2014-02-24 | Amylin Pharmaceuticals Llc | Behandling af obesitet og beslægtede sygdomme. |
| US8263545B2 (en) * | 2005-02-11 | 2012-09-11 | Amylin Pharmaceuticals, Inc. | GIP analog and hybrid polypeptides with selectable properties |
| CA2597649A1 (en) * | 2005-02-11 | 2006-08-17 | Amylin Pharmaceuticals, Inc. | Gip analog and hybrid polypeptides with selectable properties |
| CN101208098A (zh) * | 2005-03-31 | 2008-06-25 | 安米林药品公司 | 用于治疗精神病和精神障碍的胰淀素和胰淀素激动剂 |
| KR20080003849A (ko) * | 2005-03-31 | 2008-01-08 | 아밀린 파마슈티칼스, 인크. | 비만 및 섭식 장애의 조절, 예방 및 치료를 위한 조성물 및방법 |
| WO2007055743A2 (en) * | 2005-11-01 | 2007-05-18 | Amylin Pharmaceuticals, Inc. | Treatment of obesity and related disorders |
| AU2006312307A1 (en) * | 2005-11-01 | 2007-05-18 | Amylin Pharmaceuticals, Inc. | Treatment of obesity and related disorders |
| SI3045182T1 (en) * | 2005-11-14 | 2018-08-31 | Teva Pharmaceuticals International Gmbh | An antibody to a peptide-associated peptide antagonist to calcitonin for treating a headache in aggregates |
| EP2219664A1 (en) | 2007-11-14 | 2010-08-25 | Amylin Pharmaceuticals, Inc. | Methods for treating obesity and obesity related diseases and disorders |
| WO2010107874A2 (en) | 2009-03-17 | 2010-09-23 | Amylin Pharmaceuticals, Inc. | Methods for affecting body composition using amylin agonists |
| WO2013059336A1 (en) | 2011-10-18 | 2013-04-25 | Amylin Pharmaceuticals, Llc | Amylin-calcitonin chimeric peptides conjugated to duration enchancing moieties |
| EP2807187B1 (en) * | 2012-01-26 | 2017-07-26 | Christopher J. Soares | Peptide antagonists of the calcitonin cgrp family of peptide hormones and their use |
| RS56556B1 (sr) | 2012-02-27 | 2018-02-28 | Bristol Myers Squibb Co | N- (5s, 6s, 9r) - 5 -amino- 6 - (2, 3 - difluorofenil) -6, 7, 8, 9 - tetrahidro - 5h - ciklohepta [b]piridin-9 -il- 4 - (2 - okso-2, 3 - dihidro - 1h- imidazo [4, 5 -b]piridin - 1 - il) piperidin - 1 - karboksilat, hemisulfatna so |
-
2013
- 2013-01-25 EP EP13703494.8A patent/EP2807187B1/en active Active
- 2013-01-25 US US13/821,936 patent/US9193776B2/en active Active
- 2013-01-25 KR KR1020147023782A patent/KR101855242B1/ko active Active
- 2013-01-25 JP JP2014554880A patent/JP6025871B2/ja active Active
- 2013-01-25 ES ES17175988T patent/ES2819825T3/es active Active
- 2013-01-25 RU RU2014131605A patent/RU2624016C2/ru active
- 2013-01-25 KR KR1020177016079A patent/KR102052983B1/ko active Active
- 2013-01-25 ES ES13703494.8T patent/ES2641325T3/es active Active
- 2013-01-25 CN CN201380010942.1A patent/CN104271596B/zh not_active Expired - Fee Related
- 2013-01-25 AU AU2013211929A patent/AU2013211929B2/en not_active Ceased
- 2013-01-25 MX MX2014008960A patent/MX347229B/es active IP Right Grant
- 2013-01-25 EP EP17175988.9A patent/EP3272769B1/en active Active
- 2013-01-25 CN CN201810931542.9A patent/CN108997490A/zh active Pending
- 2013-01-25 CA CA2861392A patent/CA2861392C/en active Active
- 2013-01-25 WO PCT/US2013/023260 patent/WO2013112912A1/en not_active Ceased
- 2013-01-25 DK DK13703494.8T patent/DK2807187T3/en active
- 2013-06-18 NO NO13806163A patent/NO2864579T3/no unknown
-
2014
- 2014-07-15 IL IL233655A patent/IL233655A/en active IP Right Grant
-
2015
- 2015-11-20 US US14/948,032 patent/US20160145315A1/en not_active Abandoned
-
2016
- 2016-07-18 AU AU2016205801A patent/AU2016205801A1/en not_active Abandoned
- 2016-10-07 JP JP2016199234A patent/JP6411425B2/ja active Active
-
2017
- 2017-04-03 US US15/478,053 patent/US10370425B2/en active Active
- 2017-05-28 IL IL252555A patent/IL252555B/en active IP Right Grant
- 2017-06-06 RU RU2017119773A patent/RU2742826C2/ru active
-
2018
- 2018-09-21 JP JP2018177504A patent/JP2019006821A/ja active Pending
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