CO2019011688A2 - Receptores de linfocitos t e inmunoterapias basadas en el uso de los mismos contra cánceres positivos para prame - Google Patents
Receptores de linfocitos t e inmunoterapias basadas en el uso de los mismos contra cánceres positivos para prameInfo
- Publication number
- CO2019011688A2 CO2019011688A2 CONC2019/0011688A CO2019011688A CO2019011688A2 CO 2019011688 A2 CO2019011688 A2 CO 2019011688A2 CO 2019011688 A CO2019011688 A CO 2019011688A CO 2019011688 A2 CO2019011688 A2 CO 2019011688A2
- Authority
- CO
- Colombia
- Prior art keywords
- antigen
- taa
- recognizing constructs
- tcr
- nucleic acids
- Prior art date
Links
- 206010028980 Neoplasm Diseases 0.000 title abstract 4
- 108091008874 T cell receptors Proteins 0.000 title 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 title 1
- 238000009169 immunotherapy Methods 0.000 title 1
- 239000000427 antigen Substances 0.000 abstract 3
- 102000036639 antigens Human genes 0.000 abstract 3
- 108091007433 antigens Proteins 0.000 abstract 3
- 150000007523 nucleic acids Chemical class 0.000 abstract 2
- 102000039446 nucleic acids Human genes 0.000 abstract 2
- 108020004707 nucleic acids Proteins 0.000 abstract 2
- 210000001744 T-lymphocyte Anatomy 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 238000003745 diagnosis Methods 0.000 abstract 1
- 239000012634 fragment Substances 0.000 abstract 1
- 201000001441 melanoma Diseases 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 239000013598 vector Substances 0.000 abstract 1
Classifications
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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
-
- 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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/463—Cellular immunotherapy characterised by recombinant expression
- A61K39/4632—T-cell receptors [TCR]; antibody T-cell receptor constructs
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464484—Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE
- A61K39/464489—PRAME
-
- 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
- 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 [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3053—Skin, nerves, brain
-
- 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
- C12N5/0638—Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]
-
- 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
- C12N5/10—Cells modified by introduction of foreign genetic material
-
- 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
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- 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
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Cell Biology (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Mycology (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- General Engineering & Computer Science (AREA)
- Hematology (AREA)
- Developmental Biology & Embryology (AREA)
- Virology (AREA)
- Neurology (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
La presente invención atañe a constructos reconocedores de antígeno dirigidos contra antígenos asociados a tumores (TAA), en particular contra el antígeno expresado preferencialmente en el melanoma (PRAME, por sus siglas en inglés). La invención proporciona en concreto moléculas basadas en un nuevo receptor de linfocitos T (TCR) que son selectivas y específicas hacia el antígeno de la invención que es expresado por tumores. El TCR de la invención, así como los fragmentos de unión con el TAA que derivan del mismo, están destinados al uso en el diagnóstico, el tratamiento y la prevención de enfermedades tumorales que expresan el TAA. Además, se proporcionan ácidos nucleicos que codifican los constructos reconocedores del antígeno de la invención, los vectores que comprenden esos ácidos nucleicos, las células recombinantes que expresan los constructos reconocedores del antígeno y las composiciones farmacéuticas que comprenden los compuestos de la invención.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762475329P | 2017-03-23 | 2017-03-23 | |
| DE102017106305.6A DE102017106305A1 (de) | 2017-03-23 | 2017-03-23 | Neue T-Zellrezeptoren und deren Verwendung in Immuntherapien gegen prame-positive Krebsarten |
| PCT/EP2018/057482 WO2018172533A2 (en) | 2017-03-23 | 2018-03-23 | T cell receptors and immune therapy using the same against prame positive cancers |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CO2019011688A2 true CO2019011688A2 (es) | 2020-02-28 |
Family
ID=61899213
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CONC2019/0011688A CO2019011688A2 (es) | 2017-03-23 | 2019-10-22 | Receptores de linfocitos t e inmunoterapias basadas en el uso de los mismos contra cánceres positivos para prame |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US11236145B2 (es) |
| EP (1) | EP3600409A2 (es) |
| JP (2) | JP2020511152A (es) |
| KR (1) | KR20190132655A (es) |
| CN (1) | CN110494160A (es) |
| AU (1) | AU2018240501A1 (es) |
| BR (1) | BR112019019523A2 (es) |
| CA (1) | CA3056493A1 (es) |
| CL (1) | CL2019002645A1 (es) |
| CO (1) | CO2019011688A2 (es) |
| CR (1) | CR20190482A (es) |
| IL (2) | IL269578B1 (es) |
| MX (2) | MX2019011260A (es) |
| PE (1) | PE20191493A1 (es) |
| PH (1) | PH12019502151A1 (es) |
| SG (1) | SG11201908023YA (es) |
| TW (1) | TWI799922B (es) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3670530A1 (en) * | 2018-12-18 | 2020-06-24 | Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft | Cd22-specific t cell receptors and adoptive t cell therapy for treatment of b cell malignancies |
| GB2596461B (en) | 2019-02-20 | 2023-09-27 | Fred Hutchinson Cancer Center | Binding proteins specific for RAS neoantigens and uses thereof |
| US20200297768A1 (en) | 2019-03-19 | 2020-09-24 | Immatics US, Inc. | Cd28 t cell cultures, compositions, and methods of using thereof |
| DE102019108125B4 (de) | 2019-03-28 | 2022-02-03 | Immatics US, Inc. | Cd28 t-zellkulturen, zusammensetzungen und verfahren zu deren verwendung |
| TW202108618A (zh) * | 2019-05-08 | 2021-03-01 | 美商健生生物科技公司 | 用於調節t細胞介導之免疫的材料及方法 |
| US11975025B2 (en) | 2019-05-27 | 2024-05-07 | Immatics US, Inc. | Viral vectors and use thereof in adoptive cellular therapy |
| KR20230012465A (ko) | 2020-02-24 | 2023-01-26 | 이매틱스 유에스 인코포레이티드 | 암 및 관련 악성 종양을 치료하기 위해 t 세포를 확장하는 방법 |
| DE102020111571A1 (de) | 2020-03-11 | 2021-09-16 | Immatics US, Inc. | Wpre-mutantenkonstrukte, zusammensetzungen und zugehörige verfahren |
| WO2022017435A1 (zh) * | 2020-07-22 | 2022-01-27 | 信达生物制药(苏州)有限公司 | 一系列TCR-β链的CDR3序列中共有序列的生物标志物及其应用 |
| WO2022040631A1 (en) | 2020-08-21 | 2022-02-24 | Immatics US, Inc. | Methods for isolating cd8+ selected t cells |
| JP2024502034A (ja) | 2020-12-31 | 2024-01-17 | イマティクス ユーエス，アイエヌシー． | Ｃｄ８ポリペプチド、組成物、及びそれらの使用方法 |
| TW202309071A (zh) | 2021-05-05 | 2023-03-01 | 德商英麥提克生物技術股份有限公司 | 特異性結合ｐｒａｍｅ之抗原結合蛋白 |
| AU2022310862A1 (en) | 2021-07-14 | 2024-02-01 | Regeneron Pharmaceuticals, Inc. | Engineered t cell receptors fused to binding domains from antibodies |
| TW202332765A (zh) | 2021-09-20 | 2023-08-16 | 美商英麥提克斯股份有限公司 | 用於ｔ細胞療法之ｔ細胞群體的單核球耗盡 |
| US20230190807A1 (en) | 2021-10-06 | 2023-06-22 | Immatics Biotechnologies Gmbh | Tcr compounds, compositions, and methods of treating |
| CN113789304B (zh) * | 2021-10-14 | 2023-03-31 | 深圳大学总医院 | 高亲和力tcr及其应用 |
| CN113817044B (zh) * | 2021-10-14 | 2023-10-13 | 深圳大学总医院 | T细胞受体、相关工程化细胞及其应用 |
| WO2023081925A1 (en) | 2021-11-08 | 2023-05-11 | Immatics Biotechnologies Gmbh | Adoptive cell therapy combination treatment and compositions thereof |
| WO2023081461A1 (en) | 2021-11-08 | 2023-05-11 | Immatics US, Inc. | Methods for generating cell spheroids |
| WO2023196996A2 (en) | 2022-04-08 | 2023-10-12 | 2Seventy Bio, Inc. | Multipartite receptor and signaling complexes |
| WO2023212655A1 (en) | 2022-04-28 | 2023-11-02 | Immatics US, Inc. | Il-12 polypeptides, il-15 polypeptides, il-18 polypeptides, cd8 polypeptides, compositions, and methods of using thereof |
| WO2023212691A1 (en) | 2022-04-28 | 2023-11-02 | Immatics US, Inc. | DOMINANT NEGATIVE TGFβ RECEPTOR POLYPEPTIDES, CD8 POLYPEPTIDES, CELLS, COMPOSITIONS, AND METHODS OF USING THEREOF |
| WO2023212697A1 (en) | 2022-04-28 | 2023-11-02 | Immatics US, Inc. | Membrane-bound il-15, cd8 polypeptides, cells, compositions, and methods of using thereof |
| US20230355678A1 (en) | 2022-05-05 | 2023-11-09 | Immatics US, Inc. | Methods for improving t cell efficacy |
| CN115073584B (zh) * | 2022-05-07 | 2023-10-20 | 溧阳瑅赛生物医药有限公司 | 一种特异性识别prame抗原肽的tcr及其应用 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6066909B2 (ja) | 2011-06-28 | 2017-01-25 | 株式会社癌免疫研究所 | ペプチド癌抗原特異的ｔ細胞のレセプター遺伝子 |
| RU2578009C2 (ru) | 2013-05-08 | 2016-03-20 | Закрытое акционерное общество "ЕВРОГЕН" | Способ идентификации нативных пар фрагментов днк или рнк, присутствующих в одних и тех же живых клетках |
| EP3169773B1 (en) | 2014-07-15 | 2023-07-12 | Juno Therapeutics, Inc. | Engineered cells for adoptive cell therapy |
| CA3214521A1 (en) | 2015-03-10 | 2016-09-15 | ACADEMISCH ZIEKENHUIS LEIDEN (h.o.d.n. LUMC) | T-cell receptors directed against the preferentially expressed antigen of melanoma and uses thereof |
| EP3067366A1 (en) | 2015-03-13 | 2016-09-14 | Max-Delbrück-Centrum Für Molekulare Medizin | Combined T cell receptor gene therapy of cancer against MHC I and MHC II-restricted epitopes of the tumor antigen NY-ESO-1 |
| EP3297673A4 (en) | 2015-05-22 | 2019-05-08 | Memorial Sloan-Kettering Cancer Center | FOR A PRAME-PEPTIDE SPECIFIC T-CELL RECEPTOR-SIMILAR ANTIBODIES |
| CN106084036A (zh) | 2015-11-02 | 2016-11-09 | 广州市香雪制药股份有限公司 | 识别prame抗原短肽的t细胞受体 |
| CN106519019B (zh) | 2015-11-06 | 2018-07-03 | 广东香雪精准医疗技术有限公司 | 识别prame抗原的tcr |
| CN106478809B (zh) | 2015-11-06 | 2018-06-01 | 广东香雪精准医疗技术有限公司 | 识别prame抗原短肽的tcr |
| CN106831978B (zh) | 2015-12-04 | 2020-05-26 | 中国科学院广州生物医药与健康研究院 | 识别prame抗原的t细胞受体 |
| CN106699874B (zh) | 2016-03-29 | 2018-06-05 | 广东香雪精准医疗技术有限公司 | 识别prame抗原短肽的t细胞受体 |
| CA3022129A1 (en) | 2016-06-17 | 2017-12-21 | Medigene Immunotherapies Gmbh | T cell receptors and uses thereof |
| DE102017106305A1 (de) * | 2017-03-23 | 2018-09-27 | Immatics Biotechnologies Gmbh | Neue T-Zellrezeptoren und deren Verwendung in Immuntherapien gegen prame-positive Krebsarten |
-
2018
- 2018-03-22 US US15/928,785 patent/US11236145B2/en active Active
- 2018-03-23 CN CN201880019206.5A patent/CN110494160A/zh active Pending
- 2018-03-23 JP JP2019552175A patent/JP2020511152A/ja active Pending
- 2018-03-23 CA CA3056493A patent/CA3056493A1/en active Pending
- 2018-03-23 PE PE2019001902A patent/PE20191493A1/es unknown
- 2018-03-23 MX MX2019011260A patent/MX2019011260A/es unknown
- 2018-03-23 KR KR1020197030006A patent/KR20190132655A/ko not_active Application Discontinuation
- 2018-03-23 AU AU2018240501A patent/AU2018240501A1/en active Pending
- 2018-03-23 EP EP18715559.3A patent/EP3600409A2/en active Pending
- 2018-03-23 IL IL269578A patent/IL269578B1/en unknown
- 2018-03-23 CR CR20190482A patent/CR20190482A/es unknown
- 2018-03-23 IL IL310552A patent/IL310552A/en unknown
- 2018-03-23 BR BR112019019523A patent/BR112019019523A2/pt unknown
- 2018-03-23 SG SG11201908023Y patent/SG11201908023YA/en unknown
- 2018-03-23 TW TW110126772A patent/TWI799922B/zh active
-
2019
- 2019-09-16 CL CL2019002645A patent/CL2019002645A1/es unknown
- 2019-09-19 PH PH12019502151A patent/PH12019502151A1/en unknown
- 2019-09-20 MX MX2023003463A patent/MX2023003463A/es unknown
- 2019-10-22 CO CONC2019/0011688A patent/CO2019011688A2/es unknown
-
2021
- 2021-12-16 US US17/553,017 patent/US20220098270A1/en active Pending
-
2023
- 2023-03-20 JP JP2023044130A patent/JP2023088973A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US11236145B2 (en) | 2022-02-01 |
| US20220098270A1 (en) | 2022-03-31 |
| TWI799922B (zh) | 2023-04-21 |
| KR20190132655A (ko) | 2019-11-28 |
| MX2019011260A (es) | 2019-12-05 |
| US20180273602A1 (en) | 2018-09-27 |
| IL310552A (en) | 2024-03-01 |
| CN110494160A (zh) | 2019-11-22 |
| PE20191493A1 (es) | 2019-10-21 |
| JP2023088973A (ja) | 2023-06-27 |
| SG11201908023YA (en) | 2019-10-30 |
| TW202208420A (zh) | 2022-03-01 |
| AU2018240501A1 (en) | 2019-10-31 |
| CL2019002645A1 (es) | 2019-12-13 |
| JP2020511152A (ja) | 2020-04-16 |
| EP3600409A2 (en) | 2020-02-05 |
| PH12019502151A1 (en) | 2020-06-29 |
| IL269578A (en) | 2019-11-28 |
| MX2023003463A (es) | 2023-04-19 |
| CR20190482A (es) | 2020-01-07 |
| CA3056493A1 (en) | 2018-09-27 |
| BR112019019523A2 (pt) | 2020-04-22 |
| IL269578B1 (en) | 2024-03-01 |
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