JOP20220294A1 - علاجات سرطان البروستاتا مع توليفات من أسيتات أبيراتيرون ونيراباريب - Google Patents

علاجات سرطان البروستاتا مع توليفات من أسيتات أبيراتيرون ونيراباريب

Info

Publication number
JOP20220294A1
JOP20220294A1 JOJO/P/2022/0294A JOP20220294A JOP20220294A1 JO P20220294 A1 JOP20220294 A1 JO P20220294A1 JO P20220294 A JOP20220294 A JO P20220294A JO P20220294 A1 JOP20220294 A1 JO P20220294A1
Authority
JO
Jordan
Prior art keywords
abiraterone acetate
prostate cancer
combinations
niraparib
treatments
Prior art date
Application number
JOJO/P/2022/0294A
Other languages
Arabic (ar)
English (en)
Inventor
Johny Bertels
Kaustubh Ramesh Tambwekar
Urbain Alfons C Delaet
Thomas Ronald A Quinten
Angela Lopez-Gitlitz
Katrien Luyten
Tatiana Marcozzi
Kok Paul J A Hartman
Philip Erna H Heyns
Original Assignee
Janssen Pharmaceutica Nv
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv
Publication of JOP20220294A1 publication Critical patent/JOP20220294A1/ar

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • 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
    • A61K38/25—Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1682—Processes
    • A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2009—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Endocrinology (AREA)
  • Oncology (AREA)
  • Urology & Nephrology (AREA)
  • Inorganic Chemistry (AREA)
  • Reproductive Health (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Epoxy Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
JOJO/P/2022/0294A 2020-05-08 2022-11-01 علاجات سرطان البروستاتا مع توليفات من أسيتات أبيراتيرون ونيراباريب JOP20220294A1 (ar)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP20173749 2020-05-08
US202163142919P 2021-01-28 2021-01-28
US202163174282P 2021-04-13 2021-04-13
PCT/EP2021/062186 WO2021224469A1 (en) 2020-05-08 2021-05-07 Treatments of prostate cancer with combinations of abiraterone acetate and niraparib

Publications (1)

Publication Number Publication Date
JOP20220294A1 true JOP20220294A1 (ar) 2022-11-01

Family

ID=75888052

Family Applications (3)

Application Number Title Priority Date Filing Date
JOJO/P/2022/0294A JOP20220294A1 (ar) 2020-05-08 2022-11-01 علاجات سرطان البروستاتا مع توليفات من أسيتات أبيراتيرون ونيراباريب
JOJO/P/2022/0288A JOP20220288A1 (ar) 2020-05-08 2022-11-01 علاج سرطان البروستات بتوليفة من أبيراتيرون أسيتات ونيراباريب
JOJO/P/2022/0292A JOP20220292A1 (ar) 2020-05-08 2022-11-01 صياغات صيدلانية من أسيتات أبيراتيرون ونيراباريب

Family Applications After (2)

Application Number Title Priority Date Filing Date
JOJO/P/2022/0288A JOP20220288A1 (ar) 2020-05-08 2022-11-01 علاج سرطان البروستات بتوليفة من أبيراتيرون أسيتات ونيراباريب
JOJO/P/2022/0292A JOP20220292A1 (ar) 2020-05-08 2022-11-01 صياغات صيدلانية من أسيتات أبيراتيرون ونيراباريب

Country Status (19)

Country Link
US (4) US20230226080A1 (https=)
EP (3) EP4146210A1 (https=)
JP (3) JP2023524808A (https=)
KR (3) KR20230008780A (https=)
CN (3) CN115515584A (https=)
AU (5) AU2021267146B2 (https=)
BR (3) BR112022021732A2 (https=)
CA (3) CA3177123A1 (https=)
CR (1) CR20220588A (https=)
EC (1) ECSP22085983A (https=)
IL (3) IL297984B2 (https=)
JO (3) JOP20220294A1 (https=)
MX (3) MX2022014003A (https=)
PE (1) PE20230830A1 (https=)
PH (3) PH12022553029A1 (https=)
TW (3) TWI905184B (https=)
UA (1) UA130040C2 (https=)
UY (3) UY39204A (https=)
WO (3) WO2021224467A1 (https=)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA3243120A1 (en) * 2022-02-04 2023-08-10 Janssen Pharmaceutica Nv Niraparib and abiraterone acetate plus prednisone to improve clinical outcomes in patients with metastatic castration-resistant prostate cancer and changes in hormone receptor function (HRF)
WO2025027138A1 (en) * 2023-08-02 2025-02-06 Janssen Pharmaceutica Nv Combination of niraparib and abiraterone for use in the treatment of metastatic castration-resistant prostate cancer

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2132449C (en) 1992-03-31 2002-09-10 Susan E. Barrie 17 - substituted steroids useful in cancer treatment
JP2003104888A (ja) * 2001-09-28 2003-04-09 Taiyo Yakuhin Kogyo Kk ジヒドロピリジン誘導体の錠剤
BRPI0719236A2 (pt) * 2006-10-13 2014-07-08 Janssen Pharmaceutica Nv Composições de carbamato de fenilalquila
JP4611444B2 (ja) 2007-01-10 2011-01-12 イステイチユート・デイ・リチエルケ・デイ・ビオロジア・モレコラーレ・ピ・アンジエレツテイ・エツセ・ピー・アー ポリ（ａｄｐ−リボース）ポリメラーゼ（ｐａｒｐ）阻害剤としてのアミド置換インダゾール
KR101653548B1 (ko) 2008-01-08 2016-09-02 머크 샤프 앤드 돔 리미티드 2-｛4-［（3ｓ）-피페리딘-3-일］페닐｝-2ｈ-인다졸-7-카복스아미드의 약제학적으로 허용되는 염
CN102026628A (zh) * 2008-02-15 2011-04-20 太阳医药高级研发有限公司 具有降低崩裂效果的口服控释片剂
CA2808501A1 (en) * 2010-08-23 2012-03-01 Vertex Pharmaceuticals Incorporated Pharmaceutical composition of (r)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-n-(1-(2,3-dihydroxy propyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1h-indol-5-yl) cyclopropanecarboxamide and administration therof
CN102743393A (zh) * 2012-07-27 2012-10-24 海南盛科生命科学研究院 一种含有醋酸阿比特龙的药物组合物及制备工艺
HK1213197A1 (zh) * 2013-03-04 2016-06-30 Vtv治疗有限责任公司 包括葡糖激酶活化劑的固體組合物及其製備和使用方法
WO2015032873A1 (en) * 2013-09-06 2015-03-12 Synthon B.V. High-load pharmaceutical compositions comprising abiraterone acetate
EP3160450A1 (en) * 2014-06-30 2017-05-03 Galenicum Health S.L. Stable pharmaceutical compositions in the form of immediate release tablets
SG11201701139YA (en) * 2014-09-18 2017-03-30 Iceutica Inc Abiraterone acetate formulation and methods of use
SG11201811564QA (en) * 2016-06-29 2019-01-30 Tesaro Inc Methods of treating ovarian cancer
CN110944638A (zh) * 2017-03-27 2020-03-31 特沙诺有限公司 尼拉帕尼组合物
HUE060460T2 (hu) * 2017-04-13 2023-03-28 Janssen Pharmaceutica Nv Niraparib, abirateron-acetát és prednizon prosztatarák kezelésére
TWI843707B (zh) * 2017-09-26 2024-06-01 美商提薩羅有限公司 尼拉帕尼（ｎｉｒａｐａｒｉｂ）調配物
JOP20200072A1 (ar) * 2017-10-11 2020-04-29 Janssen Oncology Inc طرق علاج سرطان البروستاتا من خلال إعطاء أسيتات الأبيراتيرون إلى جانب البريدنيزون مع المعالجة بحرمان الأندروجين
CA3098208A1 (en) * 2018-04-26 2019-10-31 Synthon B.V. Tablet compositions comprising abiraterone acetate
CN113166071B (zh) 2018-10-03 2025-03-21 特沙诺有限公司 尼拉帕利盐

Also Published As

Publication number Publication date
IL297990A (en) 2023-01-01
CN115515584A (zh) 2022-12-23
MX2022014003A (es) 2022-11-30
KR20230008783A (ko) 2023-01-16
TW202207926A (zh) 2022-03-01
CN115551506A (zh) 2022-12-30
AU2021269115A1 (en) 2023-01-19
JP2023524808A (ja) 2023-06-13
US20260097048A1 (en) 2026-04-09
WO2021224469A1 (en) 2021-11-11
IL297984A (en) 2023-01-01
CA3177137A1 (en) 2021-11-11
ECSP22085983A (es) 2022-12-30
PH12022553029A1 (en) 2024-05-13
AU2021266409A1 (en) 2023-01-19
UY39201A (es) 2021-11-30
IL297991A (en) 2023-01-01
MX2022014005A (es) 2022-11-30
UY39203A (es) 2021-11-30
CA3177094A1 (en) 2021-11-11
JOP20220292A1 (ar) 2022-11-01
PH12022553013A1 (en) 2024-05-13
US20230218640A1 (en) 2023-07-13
UY39204A (es) 2021-11-30
AU2026202283A1 (en) 2026-04-09
CA3177123A1 (en) 2021-11-11
PE20230830A1 (es) 2023-05-19
EP4146209A1 (en) 2023-03-15
EP4146211A1 (en) 2023-03-15
CR20220588A (es) 2023-01-17
KR20230008780A (ko) 2023-01-16
BR112022021732A2 (pt) 2022-12-06
TW202207925A (zh) 2022-03-01
WO2021224467A1 (en) 2021-11-11
WO2021224471A1 (en) 2021-11-11
AU2021267146B2 (en) 2026-04-23
US20230226081A1 (en) 2023-07-20
CN115515583A (zh) 2022-12-23
AU2026202227A1 (en) 2026-04-09
JP2023524794A (ja) 2023-06-13
PH12022553030A1 (en) 2024-05-13
IL297984B2 (en) 2025-03-01
MX2022014004A (es) 2022-11-30
EP4146210A1 (en) 2023-03-15
TWI905184B (zh) 2025-11-21
JP2023525026A (ja) 2023-06-14
TW202211921A (zh) 2022-04-01
US20230226080A1 (en) 2023-07-20
IL297984B1 (en) 2024-11-01
JOP20220288A1 (ar) 2022-11-01
AU2021267146A1 (en) 2023-01-19
KR20230008782A (ko) 2023-01-16
BR112022022590A2 (pt) 2022-12-13
BR112022022534A2 (pt) 2022-12-13
TWI894266B (zh) 2025-08-21
UA130040C2 (uk) 2025-10-22

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