SG11201708339QA - Proteins specific for cd137 - Google Patents
Proteins specific for cd137Info
- Publication number
- SG11201708339QA SG11201708339QA SG11201708339QA SG11201708339QA SG11201708339QA SG 11201708339Q A SG11201708339Q A SG 11201708339QA SG 11201708339Q A SG11201708339Q A SG 11201708339QA SG 11201708339Q A SG11201708339Q A SG 11201708339QA SG 11201708339Q A SG11201708339Q A SG 11201708339QA
- Authority
- SG
- Singapore
- Prior art keywords
- proteins specific
- proteins
- specific
- 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
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/775—Apolipopeptides
-
- 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- 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
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
-
- 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
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/998—Proteins not provided for elsewhere
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Biophysics (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Transplantation (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Hematology (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15166184 | 2015-05-04 | ||
| PCT/EP2016/059959 WO2016177762A1 (en) | 2015-05-04 | 2016-05-04 | Proteins specific for cd137 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SG11201708339QA true SG11201708339QA (en) | 2017-11-29 |
Family
ID=53054879
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SG11201708339QA SG11201708339QA (en) | 2015-05-04 | 2016-05-04 | Proteins specific for cd137 |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US11261221B2 (ru) |
| EP (2) | EP4177262A1 (ru) |
| JP (3) | JP6884708B2 (ru) |
| KR (1) | KR20170142200A (ru) |
| CN (2) | CN114573680A (ru) |
| AU (1) | AU2016258952C1 (ru) |
| BR (1) | BR112017020426A2 (ru) |
| CA (1) | CA2980839A1 (ru) |
| CL (1) | CL2017002767A1 (ru) |
| DK (1) | DK3292137T3 (ru) |
| ES (1) | ES2932425T3 (ru) |
| HK (1) | HK1249527A1 (ru) |
| IL (1) | IL254516B (ru) |
| MX (1) | MX2017014082A (ru) |
| NZ (1) | NZ736560A (ru) |
| PH (1) | PH12017501583A1 (ru) |
| RU (1) | RU2736312C2 (ru) |
| SG (1) | SG11201708339QA (ru) |
| WO (1) | WO2016177762A1 (ru) |
| ZA (1) | ZA201705960B (ru) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK2990798T3 (da) | 2009-12-07 | 2019-12-02 | Pieris Pharmaceuticals Gmbh | Muteiner af human lipocalin 2 (lcn2, hngal) med affinitet for et specifikt mål |
| EP2920202B1 (en) | 2012-11-19 | 2018-08-29 | Pieris Pharmaceuticals GmbH | Novel specific-binding polypeptides and uses thereof |
| EP3789397B1 (en) | 2014-05-22 | 2023-12-06 | Pieris Pharmaceuticals GmbH | Novel specific-binding polypeptides and uses thereof |
| WO2016120307A1 (en) | 2015-01-28 | 2016-08-04 | Pieris Ag | Novel proteins specific for angiogenesis |
| AU2016258977C1 (en) | 2015-05-04 | 2022-07-14 | Pieris Pharmaceuticals Gmbh | Anti-cancer fusion polypeptide |
| KR20170142200A (ko) | 2015-05-04 | 2017-12-27 | 피어이스 파마슈티컬즈 게엠베하 | Cd137에 특이적인 신규한 단백질 |
| MX2017014716A (es) | 2015-05-18 | 2018-06-28 | Pieris Pharmaceuticals Gmbh | Polipeptido de fusion anti-cancer. |
| MX2017014730A (es) | 2015-05-18 | 2018-06-28 | Pieris Pharmaceuticals Gmbh | Muteinas de lipocalina 2 humana con afinidad por glipicano-3 (gpc3). |
| MX2018006559A (es) | 2015-11-30 | 2019-06-12 | Pieris Australia Pty Ltd | Nuevos polipeptidos de fusion anti-angiogenicos. |
| TW201725212A (zh) | 2015-12-10 | 2017-07-16 | 第一三共股份有限公司 | 特異性於降鈣素基因相關胜肽的新穎蛋白 |
| WO2018087108A1 (en) * | 2016-11-09 | 2018-05-17 | Pieris Pharmaceuticals Gmbh | Proteins specific for cd137 |
| JP2021519292A (ja) | 2018-03-26 | 2021-08-10 | ４エスツェー アクチェンゲゼルシャフト | 癌療法のためのｈｄａｃ阻害薬とｃｄ１３７作動薬とを含む併用 |
| SI3830120T1 (sl) * | 2018-07-31 | 2023-10-30 | Pieris Pharmaceuticals GbmH | Novi fuzijski protein, specifičen za CD137 in PD-L1 |
| JP7453219B2 (ja) | 2018-10-11 | 2024-03-19 | インヒブリックス， インコーポレイテッド | Ｐｄ－１単一ドメイン抗体およびその治療用組成物 |
| JP7476219B2 (ja) | 2019-02-26 | 2024-04-30 | ピエリス ファーマシューティカルズ ゲーエムベーハー | Ｃｄ１３７およびｇｐｃ３に特異的な新規融合タンパク質 |
| AU2020253034A1 (en) | 2019-03-29 | 2021-08-19 | Pieris Pharmaceuticals Gmbh | Inhaled administration of lipocalin muteins |
| CN113677403A (zh) | 2019-04-12 | 2021-11-19 | 豪夫迈·罗氏有限公司 | 包含脂质运载蛋白突变蛋白的双特异性抗原结合分子 |
| US20240166763A1 (en) | 2019-11-04 | 2024-05-23 | Pieris Pharmaceuticals Gmbh | Her2/4-1bb bispecific fusion proteins for the treatment of cancer |
| EP4161957A1 (en) | 2020-06-05 | 2023-04-12 | Pieris Pharmaceuticals GmbH | Multimeric immunomodulator targeting 4-1bb |
| WO2022058505A1 (en) | 2020-09-18 | 2022-03-24 | Pieris Pharmaceuticals Gmbh | Biomarker methods and uses |
| US20240166764A1 (en) | 2021-03-23 | 2024-05-23 | Pieris Pharmaceuticals Gmbh | Her2/4-1bb bispecific fusion proteins for the treatment of cancer |
| WO2022200478A1 (en) | 2021-03-24 | 2022-09-29 | Pieris Pharmaceuticals Gmbh | Tumor treatment with a 4-1bb/her2-bispecific agent and a her2-targeted tyrosine kinase inhibitor |
| WO2023118497A1 (en) | 2021-12-22 | 2023-06-29 | Pieris Pharmaceuticals Gmbh | Novel il-18 variants |
| WO2023180523A1 (en) | 2022-03-24 | 2023-09-28 | Pieris Pharmaceuticals Gmbh | Process for purifying fusion proteins |
| WO2024064713A1 (en) | 2022-09-21 | 2024-03-28 | Seagen Inc. | Novel fusion protein specific for cd137 and cd228 |
Family Cites Families (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE76311T1 (de) | 1986-08-19 | 1992-06-15 | Genentech Inc | Einrichtung und dispersion zum intrapulmonalen eingeben von polypeptidwuchsstoffen und zytokinen. |
| JPH01215289A (ja) | 1988-02-22 | 1989-08-29 | Toa Nenryo Kogyo Kk | 遺伝子組換えによる正常ヒト血清アルブミンａの製造方法 |
| FR2649991B2 (fr) | 1988-08-05 | 1994-03-04 | Rhone Poulenc Sante | Utilisation de derives stables du plasmide pkd1 pour l'expression et la secretion de proteines heterologues dans les levures du genre kluyveromyces |
| US5728553A (en) | 1992-09-23 | 1998-03-17 | Delta Biotechnology Limited | High purity albumin and method of producing |
| KR100384353B1 (ko) | 1994-05-18 | 2003-10-04 | 네크타르 테라퓨틱스 | 인터페론의건조분말제형을제조하기위한방법및조성물 |
| DE4417598A1 (de) | 1994-05-19 | 1995-12-14 | Max Planck Gesellschaft | Verwendung des Tetracyclinpromotors zur stringent regulierten Produktion von rekombinanten Proteinen in prokaryontischen Zellen |
| WO1996023879A1 (en) | 1995-01-30 | 1996-08-08 | Terrapin Technologies, Inc. | Glubodies - multiplicities of proteins capable of binding a variety of small molecules |
| US5908621A (en) | 1995-11-02 | 1999-06-01 | Schering Corporation | Polyethylene glycol modified interferon therapy |
| US6620413B1 (en) | 1995-12-27 | 2003-09-16 | Genentech, Inc. | OB protein-polymer chimeras |
| DE19641876B4 (de) | 1996-10-10 | 2011-09-29 | Iba Gmbh | Streptavidinmuteine |
| WO1998016873A1 (fr) | 1996-10-14 | 1998-04-23 | Firm Forsat Ltd. | Procede de preparation de dispersions a base de composants chromogenes |
| DE19742706B4 (de) | 1997-09-26 | 2013-07-25 | Pieris Proteolab Ag | Lipocalinmuteine |
| GB9722131D0 (en) | 1997-10-20 | 1997-12-17 | Medical Res Council | Method |
| CA2233725A1 (en) | 1998-03-31 | 1999-09-30 | Hemosol Inc. | Hemoglobin-hydroxyethyl starch complexes |
| IL139786A0 (en) | 1998-06-08 | 2002-02-10 | Hoffmann La Roche | Use of peg-ifn-alpha and ribavirin for the treatment of chronic hepatitis c |
| US6403564B1 (en) | 1998-10-16 | 2002-06-11 | Schering Corporation | Ribavirin-interferon alfa combination therapy for eradicating detectable HCV-RNA in patients having chronic hepatitis C infection |
| DE19926068C1 (de) | 1999-06-08 | 2001-01-11 | Arne Skerra | Muteine des Bilin-Bindungsproteins |
| US7211395B2 (en) | 2001-03-09 | 2007-05-01 | Dyax Corp. | Serum albumin binding moieties |
| CA2464690A1 (en) | 2001-09-27 | 2003-04-10 | Pieris Proteolab Ag | Muteins of apolipoprotein d |
| WO2003029462A1 (en) | 2001-09-27 | 2003-04-10 | Pieris Proteolab Ag | Muteins of human neutrophil gelatinase-associated lipocalin and related proteins |
| EP1658308A1 (en) | 2003-08-25 | 2006-05-24 | Pieris ProteoLab AG | Muteins of a bilin-binding protein with affinity for a given target |
| AU2003275958A1 (en) * | 2003-08-25 | 2005-03-10 | Pieris Proteolab Ag | Muteins of tear lipocalin |
| US7288638B2 (en) | 2003-10-10 | 2007-10-30 | Bristol-Myers Squibb Company | Fully human antibodies against human 4-1BB |
| JP2007284351A (ja) | 2004-07-27 | 2007-11-01 | Osaka Bioscience Institute | アミロイド蛋白質の凝集を抑制する物質とその作用 |
| WO2006056464A2 (en) | 2004-11-26 | 2006-06-01 | Pieris Ag | Compound with affinity for the cytotoxic t lymphocyte-associated antigen (ctla-4) |
| AU2006294644A1 (en) | 2005-09-27 | 2007-04-05 | Amunix, Inc. | Proteinaceous pharmaceuticals and uses thereof |
| ES2354653T3 (es) * | 2006-08-01 | 2011-03-16 | Pieris Ag | Muteínas de lipocalina lacrimal y procedimientos para obtener las mismas. |
| CN105112477A (zh) | 2006-08-01 | 2015-12-02 | 皮里斯股份公司 | 泪液脂质运载蛋白的突变蛋白及其获得方法 |
| JP5848006B2 (ja) | 2007-10-19 | 2016-01-27 | アボット・ラボラトリーズＡｂｂｏｔｔ Ｌａｂｏｒａｔｏｒｉｅｓ | Ｎｇａｌの検出用イムノアッセイ及びキット |
| US8420051B2 (en) * | 2008-06-24 | 2013-04-16 | Technische Universitaet Meunchen | Muteins of hNGAL and related proteins with affinity for a given target |
| DK2990798T3 (da) | 2009-12-07 | 2019-12-02 | Pieris Pharmaceuticals Gmbh | Muteiner af human lipocalin 2 (lcn2, hngal) med affinitet for et specifikt mål |
| SG10201505785QA (en) | 2010-08-16 | 2015-09-29 | Pieris Ag | Binding proteins for hepcidin |
| US9260492B2 (en) | 2010-11-15 | 2016-02-16 | Pieris Ag | Muteins of human lipocalin 2 with affinity for glypican-3 (GPC-3) |
| EP2920202B1 (en) * | 2012-11-19 | 2018-08-29 | Pieris Pharmaceuticals GmbH | Novel specific-binding polypeptides and uses thereof |
| CN105246503A (zh) | 2013-03-14 | 2016-01-13 | 第一三共株式会社 | Pcsk9的新颖结合蛋白 |
| AU2015205530B8 (en) * | 2014-01-13 | 2019-09-19 | Pieris Pharmaceuticals Gmbh | Multi-specific polypeptide useful for localized tumor immunomodulation |
| WO2016120307A1 (en) | 2015-01-28 | 2016-08-04 | Pieris Ag | Novel proteins specific for angiogenesis |
| WO2016131804A1 (en) | 2015-02-18 | 2016-08-25 | Sanofi | Novel proteins specific for pyoverdine and pyochelin |
| KR20170142200A (ko) | 2015-05-04 | 2017-12-27 | 피어이스 파마슈티컬즈 게엠베하 | Cd137에 특이적인 신규한 단백질 |
| AU2016258977C1 (en) | 2015-05-04 | 2022-07-14 | Pieris Pharmaceuticals Gmbh | Anti-cancer fusion polypeptide |
| MX2017014730A (es) | 2015-05-18 | 2018-06-28 | Pieris Pharmaceuticals Gmbh | Muteinas de lipocalina 2 humana con afinidad por glipicano-3 (gpc3). |
| MX2017014716A (es) * | 2015-05-18 | 2018-06-28 | Pieris Pharmaceuticals Gmbh | Polipeptido de fusion anti-cancer. |
| WO2018087108A1 (en) | 2016-11-09 | 2018-05-17 | Pieris Pharmaceuticals Gmbh | Proteins specific for cd137 |
-
2016
- 2016-05-04 KR KR1020177034948A patent/KR20170142200A/ko not_active Application Discontinuation
- 2016-05-04 RU RU2017135599A patent/RU2736312C2/ru active
- 2016-05-04 AU AU2016258952A patent/AU2016258952C1/en active Active
- 2016-05-04 CA CA2980839A patent/CA2980839A1/en active Pending
- 2016-05-04 DK DK16721149.9T patent/DK3292137T3/da active
- 2016-05-04 JP JP2017557299A patent/JP6884708B2/ja active Active
- 2016-05-04 ES ES16721149T patent/ES2932425T3/es active Active
- 2016-05-04 WO PCT/EP2016/059959 patent/WO2016177762A1/en active Application Filing
- 2016-05-04 EP EP22193830.1A patent/EP4177262A1/en active Pending
- 2016-05-04 US US15/571,611 patent/US11261221B2/en active Active
- 2016-05-04 EP EP16721149.9A patent/EP3292137B1/en active Active
- 2016-05-04 MX MX2017014082A patent/MX2017014082A/es unknown
- 2016-05-04 BR BR112017020426A patent/BR112017020426A2/pt active Search and Examination
- 2016-05-04 SG SG11201708339QA patent/SG11201708339QA/en unknown
- 2016-05-04 CN CN202210118268.XA patent/CN114573680A/zh active Pending
- 2016-05-04 NZ NZ736560A patent/NZ736560A/en unknown
- 2016-05-04 CN CN201680025274.3A patent/CN107820500B/zh active Active
-
2017
- 2017-09-01 ZA ZA2017/05960A patent/ZA201705960B/en unknown
- 2017-09-04 PH PH12017501583A patent/PH12017501583A1/en unknown
- 2017-09-14 IL IL254516A patent/IL254516B/en unknown
- 2017-11-02 CL CL2017002767A patent/CL2017002767A1/es unknown
-
2018
- 2018-06-22 HK HK18107993.2A patent/HK1249527A1/zh unknown
-
2021
- 2021-03-09 JP JP2021036823A patent/JP7149363B2/ja active Active
-
2022
- 2022-01-19 US US17/579,392 patent/US20220144901A1/en active Pending
- 2022-09-26 JP JP2022152103A patent/JP7477905B2/ja active Active
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