CL2021002491A1 - Receptores de células t mage a4 - Google Patents

Receptores de células t mage a4

Info

Publication number
CL2021002491A1
CL2021002491A1 CL2021002491A CL2021002491A CL2021002491A1 CL 2021002491 A1 CL2021002491 A1 CL 2021002491A1 CL 2021002491 A CL2021002491 A CL 2021002491A CL 2021002491 A CL2021002491 A CL 2021002491A CL 2021002491 A1 CL2021002491 A1 CL 2021002491A1
Authority
CL
Chile
Prior art keywords
tcr
mage
cell receptors
relates
cell
Prior art date
Application number
CL2021002491A
Other languages
English (en)
Inventor
Christian Ellinger
Daniel Sommermeyer
Parsons Geoffrey Blackburn
Jasdeep Mann
Original Assignee
Medigene Immunotherapies Gmbh
2Seventy Bio Inc
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 Medigene Immunotherapies Gmbh, 2Seventy Bio Inc filed Critical Medigene Immunotherapies Gmbh
Publication of CL2021002491A1 publication Critical patent/CL2021002491A1/es

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    • 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
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/7051—T-cell receptor (TcR)-CD3 complex
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A61K40/15—Natural-killer [NK] cells; Natural-killer T [NKT] cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
    • A61K40/32—T-cell receptors [TCR]
    • 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
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4748—Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
    • 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
    • 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
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins
    • 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
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • 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
    • 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
    • C12N5/0646—Natural killers cells [NK], NKT cells
    • 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
    • A61K2121/00—Preparations for use in therapy
    • 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
    • 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
    • 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
    • C12N2510/00—Genetically modified cells
    • 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
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
    • C12N2740/15041—Use of virus, viral particle or viral elements as a vector
    • C12N2740/15043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • 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
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/10—Plasmid DNA
    • C12N2800/106—Plasmid DNA for vertebrates
    • C12N2800/107—Plasmid DNA for vertebrates for mammalian

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Cell Biology (AREA)
  • Wood Science & Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • General Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Hematology (AREA)
  • Microbiology (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Oncology (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La presente invención se refiere a un receptor de células T aislado (TCR) específico para MAGE-A4 y un polipéptido que comprende una porción funcional del TCR. También están implicados un complejo de TCR multivalente, un ácido nucleico que codifica un TCR, una célula que expresa el TCR y una composición farmacéutica que comprende el TCR. La invención también se refiere al TCR para su uso como medicamento, en particular al TCR para su uso en el tratamiento del cáncer.
CL2021002491A 2019-03-27 2021-09-24 Receptores de células t mage a4 CL2021002491A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP19165387.2A EP3714941A1 (en) 2019-03-27 2019-03-27 Mage-a4 tcrs

Publications (1)

Publication Number Publication Date
CL2021002491A1 true CL2021002491A1 (es) 2022-06-10

Family

ID=66000958

Family Applications (1)

Application Number Title Priority Date Filing Date
CL2021002491A CL2021002491A1 (es) 2019-03-27 2021-09-24 Receptores de células t mage a4

Country Status (25)

Country Link
US (2) US12344654B2 (es)
EP (3) EP3714941A1 (es)
JP (2) JP7590982B2 (es)
CN (2) CN114126716B (es)
AU (1) AU2020249598A1 (es)
BR (1) BR112021019066A2 (es)
CA (1) CA3134076A1 (es)
CL (1) CL2021002491A1 (es)
CO (1) CO2021012587A2 (es)
DK (1) DK3946621T3 (es)
EA (1) EA202192327A1 (es)
ES (1) ES3037919T3 (es)
FI (1) FI3946621T3 (es)
HR (1) HRP20250993T1 (es)
HU (1) HUE073008T2 (es)
IL (1) IL286569A (es)
LT (1) LT3946621T (es)
MX (1) MX2021011613A (es)
PL (1) PL3946621T3 (es)
PT (1) PT3946621T (es)
RS (1) RS67109B1 (es)
SG (1) SG11202110171QA (es)
SI (1) SI3946621T1 (es)
SM (1) SMT202500298T1 (es)
WO (1) WO2020193767A1 (es)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MA46862A (fr) 2016-11-17 2019-09-25 Bluebird Bio Inc Convertisseur de signaux tgf béta
KR20210104772A (ko) 2018-12-14 2021-08-25 블루버드 바이오, 인코포레이티드. 이량체화제로 조절된 면역수용체 복합체
EP3714941A1 (en) 2019-03-27 2020-09-30 Medigene Immunotherapies GmbH Mage-a4 tcrs
CA3139011A1 (en) * 2019-05-08 2020-11-12 Medigene Immunotherapies Gmbh Engineered t cells
CA3177181A1 (en) * 2020-03-27 2021-09-30 2Seventy Bio, Inc. T cell receptors
CN111647069B (zh) * 2020-06-17 2022-06-21 深圳豪石生物科技有限公司 一种改进的tcr及其应用
MX2023010541A (es) * 2021-03-09 2023-11-24 Cdr Life Ag Proteinas de union al antigeno del peptido del mhc mage-a4.
US12435444B2 (en) 2021-03-09 2025-10-07 Cdr-Life Ag Rabbit-derived antigen binding protein nucleic acid libraries and methods of making the same
CN115975003B (zh) * 2021-03-09 2024-01-26 科士华(南京)生物技术有限公司 Tcr、多肽、表达载体、宿主细胞、药物组合物和tcr获得方法
EP4091627A1 (en) 2021-05-21 2022-11-23 Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft Tcr constructs specific for magea4-derived epitopes
JP2024525727A (ja) 2021-07-14 2024-07-12 ２セブンティ バイオ インコーポレイテッド 抗体由来の結合ドメインに融合した操作されたｔ細胞受容体
CN116836261A (zh) * 2022-03-24 2023-10-03 香雪生命科学技术（广东）有限公司 一种识别mage-a4抗原的高亲和力tcr及其序列和应用
CA3255500A1 (en) 2022-04-08 2023-10-12 Regeneron Pharmaceuticals, Inc. MULTI-PART RECEIVERS AND SIGNALING COMPLEXES
JP2025520227A (ja) 2022-05-26 2025-07-02 リジェネロン・ファーマシューティカルズ・インコーポレイテッド レンチウイルスベクターを維持するための組成物及びその使用
CA3264474A1 (en) 2022-09-14 2024-03-21 Cdr-Life Ag MAGE-A4 DOUBLE T LYMPHOCYTE ENGAGEMENT
CN119569851A (zh) * 2023-09-05 2025-03-07 香雪生命科学技术（广东）有限公司 针对magea4的高亲和力tcr
EP4635976A1 (en) * 2024-04-19 2025-10-22 Medigene Immunotherapies GmbH Constant uni-tabs
WO2025219541A1 (en) * 2024-04-19 2025-10-23 Medigene Immunotherapies Gmbh Constant uni-tabs
CN121342955B (zh) * 2025-12-18 2026-03-06 中山大学孙逸仙纪念医院 T细胞受体、融合蛋白、慢病毒、tcr-t细胞及其应用

Family Cites Families (19)

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US4851341A (en) 1986-12-19 1989-07-25 Immunex Corporation Immunoaffinity purification system
US7157091B1 (en) 1999-06-18 2007-01-02 Ludwig Institute For Cancer Research MAGE-A1 peptides presented by HLA class II molecules
IL160359A0 (en) 2001-08-31 2004-07-25 Avidex Ltd Soluble t cell receptor
US7311914B2 (en) 2002-08-13 2007-12-25 Ludwig Institute For Cancer Research MAGE-A4 antigenic peptides and uses thereof
EP2006376A1 (en) 2007-06-21 2008-12-24 Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH Fusion protein comprising a caspase domain and a nuclear hormone receptor binding domain and methods and uses thereof
KR102480188B1 (ko) * 2012-09-14 2022-12-21 더 유나이티드 스테이츠 오브 어메리카, 애즈 리프리젠티드 바이 더 세크러테리, 디파트먼트 오브 헬쓰 앤드 휴먼 서비씨즈 Mhc ii형 제한된 mage-a3을 인식하는 t 세포 수용체
GB2508414A (en) 2012-11-30 2014-06-04 Max Delbrueck Centrum Tumour specific T cell receptors (TCRs)
EP2944652A1 (en) 2014-05-13 2015-11-18 Technische Universität München Glypican-3-specific T-cell receptors and their uses for immunotherapy of hepatocellular carcinoma
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DK3440106T3 (da) * 2016-04-08 2021-10-04 Adaptimmune Ltd T-cellereceptorer
SMT202200306T1 (it) * 2016-04-08 2022-09-14 Immunocore Ltd Recettori di cellule t
MX2019003768A (es) 2016-10-03 2019-06-24 Juno Therapeutics Inc Moleculas de enlace especificas de hpv.
MA46862A (fr) 2016-11-17 2019-09-25 Bluebird Bio Inc Convertisseur de signaux tgf béta
US20210147550A1 (en) * 2017-08-18 2021-05-20 Joshua Michael Francis Antigen-binding proteins targeting shared antigens
EP3714941A1 (en) 2019-03-27 2020-09-30 Medigene Immunotherapies GmbH Mage-a4 tcrs
CA3139011A1 (en) 2019-05-08 2020-11-12 Medigene Immunotherapies Gmbh Engineered t cells

Also Published As

Publication number Publication date
CN118580335A (zh) 2024-09-03
SI3946621T1 (sl) 2025-10-30
SG11202110171QA (en) 2021-10-28
AU2020249598A1 (en) 2021-10-28
JP2025024103A (ja) 2025-02-19
EP3946621B1 (en) 2025-05-21
CA3134076A1 (en) 2020-10-01
CN114126716A (zh) 2022-03-01
BR112021019066A2 (pt) 2021-11-30
CN114126716B (zh) 2024-05-24
JP7590982B2 (ja) 2024-11-27
MX2021011613A (es) 2021-12-15
KR20210150440A (ko) 2021-12-10
US20230159612A1 (en) 2023-05-25
LT3946621T (lt) 2025-08-25
FI3946621T3 (fi) 2025-07-31
DK3946621T3 (da) 2025-08-18
PL3946621T3 (pl) 2025-11-03
EP4631516A2 (en) 2025-10-15
HRP20250993T1 (hr) 2025-10-24
RS67109B1 (sr) 2025-09-30
IL286569A (en) 2021-12-01
HUE073008T2 (hu) 2025-12-28
EP3714941A1 (en) 2020-09-30
EA202192327A1 (ru) 2022-01-19
CO2021012587A2 (es) 2022-02-28
JP2022527635A (ja) 2022-06-02
US12344654B2 (en) 2025-07-01
WO2020193767A1 (en) 2020-10-01
EP3946621A1 (en) 2022-02-09
ES3037919T3 (en) 2025-10-08
PT3946621T (pt) 2025-08-14
SMT202500298T1 (it) 2025-09-12
US20250346648A1 (en) 2025-11-13

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