DK3463435T3 - Alpha-synuklein-antistoffer og anvendelser deraf - Google Patents
Alpha-synuklein-antistoffer og anvendelser deraf Download PDFInfo
- Publication number
- DK3463435T3 DK3463435T3 DK17728525.1T DK17728525T DK3463435T3 DK 3463435 T3 DK3463435 T3 DK 3463435T3 DK 17728525 T DK17728525 T DK 17728525T DK 3463435 T3 DK3463435 T3 DK 3463435T3
- Authority
- DK
- Denmark
- Prior art keywords
- alpha
- synuclein antibodies
- synuclein
- antibodies
- Prior art date
Links
- 102000003802 alpha-Synuclein Human genes 0.000 title 1
- 108090000185 alpha-Synuclein Proteins 0.000 title 1
Classifications
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- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/536—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase
- G01N33/537—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with separation of immune complex from unbound antigen or antibody
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/577—Immunoassay; Biospecific binding assay; Materials therefor involving monoclonal antibodies binding reaction mechanisms characterised by the use of monoclonal antibodies; monoclonal antibodies per se are classified with their corresponding antigens
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
-
- 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
-
- 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
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
-
- 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
- C07K2317/524—CH2 domain
-
- 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
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- 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
- C07K2317/71—Decreased effector function due to an Fc-modification
-
- 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)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Pathology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662344746P | 2016-06-02 | 2016-06-02 | |
| PCT/EP2017/063406 WO2017207739A1 (en) | 2016-06-02 | 2017-06-01 | Antibodies to alpha-synuclein and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK3463435T3 true DK3463435T3 (da) | 2021-11-22 |
Family
ID=59021492
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK17728525.1T DK3463435T3 (da) | 2016-06-02 | 2017-06-01 | Alpha-synuklein-antistoffer og anvendelser deraf |
Country Status (38)
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201512203D0 (en) | 2015-07-13 | 2015-08-19 | Lundbeck & Co As H | Agents,uses and methods |
| RU2019114679A (ru) | 2016-11-15 | 2020-12-17 | Х. Лундбекк А/С | Средства, пути применения и способы лечения синуклеопатии |
| CN110072888B (zh) | 2016-12-16 | 2023-07-18 | H.隆德贝克有限公司 | 药剂、用途和方法 |
| US10364286B2 (en) | 2016-12-22 | 2019-07-30 | H. Lundbeck A/S | Monoclonal anti-alpha-synuclein antibodies for preventing tau aggregation |
| EP3583124A1 (en) | 2017-02-17 | 2019-12-25 | Bristol-Myers Squibb Company | Antibodies to alpha-synuclein and uses thereof |
| GB201720970D0 (en) | 2017-12-15 | 2018-01-31 | Ucb Biopharma Sprl | Antibodies |
| GB201720975D0 (en) | 2017-12-15 | 2018-01-31 | Ucb Biopharma Sprl | Anti-alpha synuclein antibodies |
| BR112021006123A2 (pt) * | 2018-10-19 | 2021-07-20 | Janssen Vaccines & Prevention B.V. | anticorpos anti-sinucleína |
| TWI734279B (zh) | 2018-12-14 | 2021-07-21 | 美商美國禮來大藥廠 | 抗α-突觸核蛋白抗體及其用途 |
| KR20210154179A (ko) | 2019-04-18 | 2021-12-20 | 에이씨 이뮨 에스.에이. | 치료 및 진단용 신규한 분자 |
| CN110172098B (zh) * | 2019-05-27 | 2023-03-10 | 长春工业大学 | 抗α-突触核蛋白的单克隆抗体及其应用 |
| AU2020350769A1 (en) | 2019-09-20 | 2022-03-31 | Denali Therapeutics Inc. | Anti-alpha-synuclein antibodies and methods of use thereof |
| KR102239512B1 (ko) * | 2020-09-10 | 2021-04-12 | 서울대학교산학협력단 | 다중기능성 마이크로캡슐 조성물 및 그 제조방법 |
| EP4229082A1 (en) | 2020-10-16 | 2023-08-23 | AC Immune SA | Antibodies binding to alpha-synuclein for therapy and diagnosis |
| CN112920274A (zh) * | 2021-03-17 | 2021-06-08 | 江苏贝格尔生物医药有限公司 | 一种检测alpha-synuclein蛋白的鼠单克隆抗体及其应用 |
| CN113912716B (zh) * | 2021-12-15 | 2022-03-01 | 北京凯祥弘康生物科技有限公司 | 针对α-突触核蛋白抗原的抗体及其应用 |
| WO2024141576A1 (en) | 2022-12-29 | 2024-07-04 | Astrazeneca Ab | Compositions and methods for treating alpha-synucleinopathies |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE414151T1 (de) | 2000-03-03 | 2008-11-15 | Cambridge Antibody Tech | Antikörper gegen eotaxin und deren verwendung |
| WO2002057445A1 (en) | 2000-05-26 | 2002-07-25 | National Research Council Of Canada | Single-domain brain-targeting antibody fragments derived from llama antibodies |
| EP1309341A2 (en) | 2000-07-07 | 2003-05-14 | Lars Lannfelt | Prevention and treatment of alzheimer's disease |
| TW200509968A (en) | 2002-11-01 | 2005-03-16 | Elan Pharm Inc | Prevention and treatment of synucleinopathic disease |
| US20080014194A1 (en) | 2003-10-31 | 2008-01-17 | Elan Pharmaceuticals, Inc. | Prevention and Treatment of Synucleinopathic and Amyloidogenic Disease |
| US9034337B2 (en) | 2003-10-31 | 2015-05-19 | Prothena Biosciences Limited | Treatment and delay of outset of synucleinopathic and amyloidogenic disease |
| US8506959B2 (en) | 2002-11-01 | 2013-08-13 | Neotope Biosciences Limited | Prevention and treatment of synucleinopathic and amyloidogenic disease |
| US7358331B2 (en) | 2003-05-19 | 2008-04-15 | Elan Pharmaceuticals, Inc. | Truncated fragments of alpha-synuclein in Lewy body disease |
| HUE035044T2 (en) | 2003-05-19 | 2018-05-02 | Prothena Biosciences Ltd | Truncated fragments of alpha-synuclein in Lewy-body disease |
| US7674599B2 (en) | 2003-11-08 | 2010-03-09 | Elan Pharmaceuticals, Inc. | Methods of using antibodies to detect alpha-synuclein in fluid samples |
| MX2007001679A (es) | 2004-08-09 | 2007-05-23 | Elan Pharm Inc | Prevencion y tratamiento de la enfermedad sinucleinopatica y amiloidogenica. |
| US20090233357A1 (en) | 2005-09-27 | 2009-09-17 | Abedelnasser Abulrob | Targeted Delivery of Compounds Using Multimerization Technology |
| JP5558834B2 (ja) | 2007-02-23 | 2014-07-23 | ヤンセン アルツハイマー イミュノセラピー | シヌクレイノパチーおよびアミロイド形成疾患（ａｍｙｌｏｉｄｏｇｅｎｉｃｄｉｓｅａｓｅ）の予防および処置 |
| US8147833B2 (en) | 2007-02-23 | 2012-04-03 | Neotope Biosciences Limited | Prevention and treatment of synucleinopathic and amyloidogenic disease |
| JP4934074B2 (ja) | 2007-03-07 | 2012-05-16 | 株式会社アルファ | スイッチ固定構造 |
| LT2282758T (lt) | 2008-04-29 | 2019-03-12 | Bioarctic Ab | Antikūnai ir vakcinos, skirti su alfa sinukleinu susijusių sutrikimų gydymo ir diagnostiniams metodams |
| CA2746778C (en) | 2008-12-19 | 2019-04-23 | University Of Zurich | Human anti-alpha-synuclein autoantibodies |
| JP4654348B1 (ja) | 2010-02-23 | 2011-03-16 | 多摩川精機株式会社 | 検出装置用巻線の正弦波巻線方法 |
| CN102869680B (zh) | 2010-02-26 | 2016-10-05 | 生命北极神经科学公司 | 原细纤维结合抗体及其在帕金森氏症、路易体痴呆和其他α-共核蛋白病的治疗和诊断方法中的应用 |
| SI2723379T1 (sl) | 2011-06-23 | 2019-03-29 | Biogen International Neuroscience Gmbh | Molekule, ki se vežejo ma anti alfa-sinuklein |
| BR112014010198B1 (pt) | 2011-10-28 | 2022-12-06 | Prothena Biosciences Limited | Anticorpos humanizados que reconhecem alfa-sinucleína |
| UA118441C2 (uk) | 2012-10-08 | 2019-01-25 | Протена Біосаєнсиз Лімітед | Антитіло, що розпізнає альфа-синуклеїн |
| US9534044B2 (en) * | 2013-02-28 | 2017-01-03 | United Arab Emirates University | Alpha-synuclein antibodies and uses thereof |
| SI3071597T1 (sl) * | 2013-11-21 | 2020-11-30 | F. Hoffmann-La Roche Ag | Anti alfa-sinukleinska protitelesa in postopki uporabe |
| PT3218406T (pt) | 2014-11-10 | 2021-06-17 | Medimmune Ltd | Moléculas de ligação específicas para cd73 e seus usos |
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2017
- 2017-06-01 TW TW111117603A patent/TW202309093A/zh unknown
- 2017-06-01 WO PCT/EP2017/063406 patent/WO2017207739A1/en not_active Ceased
- 2017-06-01 SG SG11201810420YA patent/SG11201810420YA/en unknown
- 2017-06-01 NZ NZ748616A patent/NZ748616A/en unknown
- 2017-06-01 EP EP21202106.7A patent/EP4000632A1/en active Pending
- 2017-06-01 HU HUE17728525A patent/HUE057214T2/hu unknown
- 2017-06-01 UA UAA201811679A patent/UA124733C2/uk unknown
- 2017-06-01 JP JP2018563050A patent/JP7078552B2/ja active Active
- 2017-06-01 KR KR1020187037675A patent/KR102499438B1/ko active Active
- 2017-06-01 AU AU2017272804A patent/AU2017272804B2/en active Active
- 2017-06-01 SM SM20220008T patent/SMT202200008T1/it unknown
- 2017-06-01 PT PT177285251T patent/PT3463435T/pt unknown
- 2017-06-01 TW TW106118078A patent/TWI765890B/zh active
- 2017-06-01 MX MX2018014456A patent/MX393740B/es unknown
- 2017-06-01 SI SI201731025T patent/SI3463435T1/sl unknown
- 2017-06-01 MD MDE20190406T patent/MD3463435T2/ro unknown
- 2017-06-01 LT LTEPPCT/EP2017/063406T patent/LT3463435T/lt unknown
- 2017-06-01 MA MA45125A patent/MA45125B1/fr unknown
- 2017-06-01 RS RS20211502A patent/RS62682B1/sr unknown
- 2017-06-01 CN CN201780045951.2A patent/CN109475616B/zh active Active
- 2017-06-01 ES ES17728525T patent/ES2903402T3/es active Active
- 2017-06-01 MY MYPI2018002168A patent/MY188183A/en unknown
- 2017-06-01 DK DK17728525.1T patent/DK3463435T3/da active
- 2017-06-01 PE PE2023002924A patent/PE20250392A1/es unknown
- 2017-06-01 AR ARP170101504A patent/AR108663A1/es unknown
- 2017-06-01 CA CA3025987A patent/CA3025987A1/en active Pending
- 2017-06-01 EA EA202191380A patent/EA202191380A1/ru unknown
- 2017-06-01 EP EP17728525.1A patent/EP3463435B1/en active Active
- 2017-06-01 EA EA201892548A patent/EA038358B1/ru unknown
- 2017-06-01 CN CN202211223767.1A patent/CN116120445A/zh active Pending
- 2017-06-01 HR HRP20211935TT patent/HRP20211935T1/hr unknown
- 2017-06-01 PL PL17728525T patent/PL3463435T3/pl unknown
- 2017-06-01 GE GEAP201714964A patent/GEP20217253B/en unknown
- 2017-06-01 PE PE2018003155A patent/PE20190440A1/es unknown
- 2017-06-01 BR BR112018074978-8A patent/BR112018074978A2/pt unknown
- 2017-06-01 US US15/611,416 patent/US10160800B2/en active Active
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2018
- 2018-10-25 US US16/170,468 patent/US10889639B2/en active Active
- 2018-11-22 IL IL263243A patent/IL263243A/en unknown
- 2018-11-29 PH PH12018502538A patent/PH12018502538A1/en unknown
- 2018-11-30 CL CL2018003438A patent/CL2018003438A1/es unknown
- 2018-12-19 ZA ZA2018/08582A patent/ZA201808582B/en unknown
- 2018-12-21 CO CONC2018/0014010A patent/CO2018014010A2/es unknown
- 2018-12-28 EC ECSENADI201896095A patent/ECSP18096095A/es unknown
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2020
- 2020-12-03 US US17/111,159 patent/US11560424B2/en active Active
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2022
- 2022-01-05 CY CY20221100010T patent/CY1124896T1/el unknown
- 2022-05-19 JP JP2022082099A patent/JP2022110117A/ja active Pending
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2023
- 2023-01-20 US US18/099,671 patent/US20230331830A1/en active Pending
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2024
- 2024-01-31 AU AU2024200601A patent/AU2024200601A1/en active Pending
- 2024-06-27 JP JP2024103562A patent/JP2024123247A/ja active Pending
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2025
- 2025-01-16 US US19/025,554 patent/US20250263477A1/en active Pending
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