BR112023003688A2 - Métodos, terapias e usos para tratar câncer - Google Patents
Métodos, terapias e usos para tratar câncerInfo
- Publication number
- BR112023003688A2 BR112023003688A2 BR112023003688A BR112023003688A BR112023003688A2 BR 112023003688 A2 BR112023003688 A2 BR 112023003688A2 BR 112023003688 A BR112023003688 A BR 112023003688A BR 112023003688 A BR112023003688 A BR 112023003688A BR 112023003688 A2 BR112023003688 A2 BR 112023003688A2
- Authority
- BR
- Brazil
- Prior art keywords
- therapies
- methods
- treat cancer
- cancer
- agent
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2809—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- 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
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2827—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2878—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2896—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- A61K2039/507—Comprising a combination of two or more separate antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/53—Hinge
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202063078211P | 2020-09-14 | 2020-09-14 | |
| US202063106302P | 2020-10-27 | 2020-10-27 | |
| US202163185357P | 2021-05-06 | 2021-05-06 | |
| PCT/IB2021/058229 WO2022053990A1 (en) | 2020-09-14 | 2021-09-10 | Methods, therapies and uses for treating cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BR112023003688A2 true BR112023003688A2 (pt) | 2023-03-28 |
Family
ID=77989848
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112023003688A BR112023003688A2 (pt) | 2020-09-14 | 2021-09-10 | Métodos, terapias e usos para tratar câncer |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20230340137A1 (https=) |
| EP (1) | EP4211167A1 (https=) |
| JP (1) | JP2023540795A (https=) |
| KR (1) | KR20230069181A (https=) |
| CN (1) | CN116194105A (https=) |
| AU (2) | AU2021339096B2 (https=) |
| BR (1) | BR112023003688A2 (https=) |
| CA (1) | CA3194925A1 (https=) |
| IL (1) | IL300884A (https=) |
| MX (1) | MX2023003034A (https=) |
| WO (1) | WO2022053990A1 (https=) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20250116736A (ko) * | 2022-12-09 | 2025-08-01 | 화이자 인코포레이티드 | Cd47 차단제 및 항-bcma/항-cd3 이중특이성 항체 병용 요법 |
| EP4731255A1 (en) * | 2023-06-22 | 2026-04-29 | Genentech, Inc. | Treatment of multiple myeloma |
| TW202523350A (zh) | 2023-08-10 | 2025-06-16 | 美商輝瑞股份有限公司 | 治療癌症之方法,療法及用途 |
| WO2025096717A1 (en) * | 2023-11-01 | 2025-05-08 | Janssen Biotech, Inc. | Methods for treating multiple myeloma |
| WO2025122813A1 (en) * | 2023-12-08 | 2025-06-12 | Board Of Regents, The University Of Texas System | Protecting cell therapies from tgf-beta induced immunosuppression |
| TW202532072A (zh) * | 2023-12-08 | 2025-08-16 | 美商西建公司 | 治療多發性骨髓瘤之療法 |
| WO2026059920A1 (en) * | 2024-09-10 | 2026-03-19 | Regeneron Pharmaceuticals, Inc. | Methods of treating multiple myeloma with bcma inhibitors in combination with pd1/pd-l1 inhibitors |
| WO2026072671A1 (en) | 2024-09-24 | 2026-04-02 | City Of Hope | Methods comprising oncolytic viruses expressing bcmat and bcma-targeted therapies |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| HK1044159A1 (zh) | 1998-12-01 | 2002-10-11 | 蛋白质设计实验室股份有限公司 | 抗γ-干扰素的人化抗体 |
| AR045563A1 (es) | 2003-09-10 | 2005-11-02 | Warner Lambert Co | Anticuerpos dirigidos a m-csf |
| DK1730119T3 (da) | 2004-03-23 | 2008-08-11 | Pfizer Prod Inc | Imidazolforbindelser til behandling af neurodegenerative forstyrrelser |
| PT2594590E (pt) | 2007-12-14 | 2015-01-14 | Bristol Myers Squibb Co | Moléculas de ligação ao recetor humano ox40 |
| MX337040B (es) | 2010-09-09 | 2016-02-09 | Pfizer | Moleculas de union a 4-1bb. |
| SA112330278B1 (ar) | 2011-02-18 | 2015-10-09 | ستيم سينتركس، انك. | مواد ضابطة جديدة وطرق للاستخدام |
| CN104185477B (zh) | 2011-11-17 | 2017-05-24 | 辉瑞公司 | 细胞毒性肽及其抗体‑药物缀合物 |
| WO2016001810A1 (en) | 2014-07-01 | 2016-01-07 | Pfizer Inc. | Bispecific heterodimeric diabodies and uses thereof |
| TWI595006B (zh) | 2014-12-09 | 2017-08-11 | 禮納特神經系統科學公司 | 抗pd-1抗體類和使用彼等之方法 |
| TWI703159B (zh) * | 2015-04-13 | 2020-09-01 | 美商輝瑞股份有限公司 | Bcma特異性治療性抗體及其用途 |
| MX2018002043A (es) * | 2015-08-17 | 2018-07-06 | Janssen Pharmaceutica Nv | ANTICUERPOS ANTI-BCMA, MOLíCULAS DE UNIíN A ANTíGENOS BIESPECíFICAS QUE SE UNEN A BCMA Y CD3, Y USOS DE ESTOS. |
| IL313608A (en) * | 2015-12-09 | 2024-08-01 | Hoffmann La Roche | Antibody against CD20 type II to reduce the formation of antibodies against drugs |
| JP7267914B2 (ja) * | 2016-11-02 | 2023-05-02 | エンクマフ エスアーエールエル | Bcma及びcd3に対する二重特異性抗体、及び多発性骨髄腫を治療するために併用して使用される免疫療法薬 |
| US20200179511A1 (en) * | 2017-04-28 | 2020-06-11 | Novartis Ag | Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor |
| KR20200015602A (ko) | 2017-05-31 | 2020-02-12 | 주식회사 에스티큐브앤컴퍼니 | Btn1a1에 면역특이적으로 결합하는 항체 및 분자 및 이의 치료적 용도 |
| MY201312A (en) | 2017-06-02 | 2024-02-16 | Pfizer | Antibodies specific for flt3 and their uses |
| TWI838389B (zh) * | 2018-07-19 | 2024-04-11 | 美商再生元醫藥公司 | 雙特異性抗-BCMAx抗-CD3抗體及其用途 |
| CA3105729A1 (en) * | 2018-07-31 | 2020-02-06 | Amgen Research (Munich) Gmbh | Dosing regimen for bcma-cd3 bispecific antibodies |
| CA3110513A1 (en) * | 2018-08-31 | 2020-03-05 | Regeneron Pharmaceuticals, Inc. | Dosing strategy that mitigates cytokine release syndrome for cd3/c20 bispecific antibodies |
| US20220003772A1 (en) * | 2018-10-31 | 2022-01-06 | Glaxosmithkline Intellectual Property Development Limited | Methods of treating cancer |
| BR112022021956A2 (pt) * | 2020-05-13 | 2022-12-13 | Pfizer | Métodos, terapias e usos para o tratamento de câncer |
-
2021
- 2021-09-10 WO PCT/IB2021/058229 patent/WO2022053990A1/en not_active Ceased
- 2021-09-10 AU AU2021339096A patent/AU2021339096B2/en active Active
- 2021-09-10 MX MX2023003034A patent/MX2023003034A/es unknown
- 2021-09-10 EP EP21782599.1A patent/EP4211167A1/en active Pending
- 2021-09-10 US US18/025,879 patent/US20230340137A1/en active Pending
- 2021-09-10 IL IL300884A patent/IL300884A/en unknown
- 2021-09-10 CN CN202180062823.5A patent/CN116194105A/zh active Pending
- 2021-09-10 JP JP2023516052A patent/JP2023540795A/ja active Pending
- 2021-09-10 BR BR112023003688A patent/BR112023003688A2/pt unknown
- 2021-09-10 KR KR1020237012640A patent/KR20230069181A/ko active Pending
- 2021-09-10 CA CA3194925A patent/CA3194925A1/en active Pending
-
2026
- 2026-03-11 AU AU2026201847A patent/AU2026201847A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| IL300884A (en) | 2023-04-01 |
| US20230340137A1 (en) | 2023-10-26 |
| TW202224703A (zh) | 2022-07-01 |
| MX2023003034A (es) | 2023-04-10 |
| CN116194105A (zh) | 2023-05-30 |
| AU2026201847A1 (en) | 2026-04-02 |
| JP2023540795A (ja) | 2023-09-26 |
| AU2021339096A1 (en) | 2023-04-06 |
| CA3194925A1 (en) | 2022-03-17 |
| EP4211167A1 (en) | 2023-07-19 |
| AU2021339096B2 (en) | 2025-12-11 |
| KR20230069181A (ko) | 2023-05-18 |
| WO2022053990A1 (en) | 2022-03-17 |
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