IL287611B1 - Compounds and methods targeting human tau - Google Patents
Compounds and methods targeting human tauInfo
- Publication number
- IL287611B1 IL287611B1 IL287611A IL28761121A IL287611B1 IL 287611 B1 IL287611 B1 IL 287611B1 IL 287611 A IL287611 A IL 287611A IL 28761121 A IL28761121 A IL 28761121A IL 287611 B1 IL287611 B1 IL 287611B1
- Authority
- IL
- Israel
- Prior art keywords
- amino acid
- acid sequence
- antibody
- seq
- htau
- Prior art date
Links
Classifications
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- 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
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- 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
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- 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
-
- 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
- C07K2317/24—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
- C07K2317/50—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
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- 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
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
- G01N2333/4701—Details
- G01N2333/4709—Amyloid plaque core protein
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/28—Neurological disorders
- G01N2800/2814—Dementia; Cognitive disorders
- G01N2800/2821—Alzheimer
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/56—Staging of a disease; Further complications associated with the disease
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Food Science & Technology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Description
287611/ QASLAVYNNNYLA SEQ ID NO: 14 (exemplified LCDR2) LASSLSS SEQ ID NO: 15 (exemplified LCDR3) QGSYDCTIADCVA SEQ ID NO: 16 (HC of exemplified CNS-only expressed human tau binding antibody) QVQLQQWGAGLLKPSETLSLTCAVYGGSFSPYYWSWIRQPPDKGLEWIGEINWSGDTNYNPSLKSRVTISLDTSKNQFSLNLSSVTAADTAVYYCARSFDRWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVEPRGPTIKPCPPCKCPAPNLLGGPSVFIFPPKIKDVLMISLSPIVTCVVVDVSEDDPDVQISWFVNN VEVHTAQTQTHREDYNSTLRVVSALPIQHQDWMSGKEFKCKVNNKDLPAPIERTISKPKGSVRAPQVYVLPPPEEEMTKKQVTLTCMVTDFMPEDIYVEWTNNGKTELNYKNTEPVLDSDGSYFMYSKLRVEKKNWVERNSYSCSVVHEGLHNHHTTKSFSRTPGK SEQ ID NO: 17 (HCVR of exemplified CNS-only expressed human tau binding antibody) QVQLQQWGAGLLKPSETLSLTCAVYGGSFSPYYWSWIRQPPDKGLEWIGEINWSGDTNYNPSLKSRVTISLDTSKNQFSLNLSSVTAADTAVYYCARSFDRWGQGTLVTVSS SEQ ID NO: 18 (LC of exemplified CNS-only expressed human tau binding antibody) EIVLTQSPGTLSLSPGERATLSCRASQSVRSNYFAWYQQKPGQAPRLLIYGVSRRAFGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGASLITFGQGTRLEIKRTVA APSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC SEQ ID NO: 19 (LCVR of exemplified CNS-only expressed human tau binding antibody) EIVLTQSPGTLSLSPGERATLSCRASQSVRSNYFAWYQQKPGQAPRLLIYGVSRRAFGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGASLITFGQGTRLEIK
Claims (18)
1. Claims to be Filed at National Stage1. A method of detecting hTau-pT217 in a patient sample comprising the steps of: contacting the patient sample with an antibody which specifically binds human tau phosphorylated at threonine at residue 217 of SEQ ID NO. 1 (“hTau-pT217”);contacting the patient sample with a second antibody, said second antibody binding an epitope region of hTau-pT217 that does not overlap with the antibody; anddetecting binding of the antibody with hTau-pT217,wherein the second antibody specifically binds CNS-expressed isoforms of human tau and wherein the second antibody binds an epitope region of human tau comprising glutamine at residue 124 and alanine at residue 125 of SEQ ID NO. 1.
2. The method of claim 1, further comprising the step of quantifying hTau-pT217 in the patient sample.
3. A method of diagnosing a patient as one or more of: (i) having a neurodegenerative disease; (ii) at risk for having a neurodegenerative disease; (iii) in need of treatment for a neurodegenerative disease; or (iv) in need of neurological imaging comprising the steps of:contacting a patient sample with an antibody which specifically binds hTau-p217;contacting the patient sample with a second antibody, said second antibody binding anepitope region of hTau-pT217 that does not overlap with the antibody; anddetecting binding between the antibody and hTau-pT217 in the patient sample, wherein the second antibody specifically binds CNS-expressed isoforms of human tau and wherein the second antibody binds an epitope region of human tau comprising glutamine at residue 124 and alanine at residue 125 of SEQ ID NO. 1.
4. The method of claim 3 further comprising the step of diagnosing the patient as one of: (i) having a neurodegenerative disease; (ii) at risk for having a neurodegenerative disease; (iii) in need of treatment for a neurodegenerative disease; or (iv) in need of neurological imaging if the level of hTau-pT217 detected in the patient sample exceeds a reference level.
5. The method of claim 3 further comprising the step of diagnosing the patient as having a neurodegenerative disease, wherein the neurodegenerative disease is a tauopathy.
6. The method of claim 5, wherein the tauopathy is selected from the group consisting of Alzheimer’s disease (AD), Progressive Supranuclear Palsy (PSP) and Frontal Temporal Dementia (FTD).
7. The method of any of claims 1-6, wherein the patient sample is one of blood, plasma, serum or CSF.
8. The method of any of claims 1-7, wherein one of the antibody or the second antibody comprises a detectable label and said step of detecting comprises detecting a signal provided by the detectable label upon formation of a complex comprising the antibody, the second antibody and hTau-pT217.
9. The method of any of claims 1-8, wherein the antibody which specifically binds hTau-pT2comprises a light chain variable region (LCVR) and a heavy chain variable region (HCVR), wherein the LCVR comprises complementarity determining regions (CDRs) LCDR1, LCDR2, and LCDR3 and the HCVR comprises CDRs HCDR1, HCDR2 and HCDR3, wherein the amino acid sequences of the CDRs is selected from:(a) LCDR1 has the amino acid sequence of SEQ ID NO: 13; LCDR2 has the amino acid sequence of SEQ ID NO: 14, LCDR3 has the amino acid sequence of SEQ ID NO: 15, HCDR1 has the amino acid sequence of SEQ ID NO: 10, HCDR2 has the amino acid sequence of SEQ ID NO: 11, and HCDR3 has the amino acid sequence of SEQ ID NO: 12; or(b) LCDR1 has an amino acid sequence with at least 95% homology to the amino acid sequence of SEQ ID NO: 13; LCDR2 has an amino acid sequence with at least 95% homology to the amino acid sequence of SEQ ID NO: 14, LCDR3 has an amino acid sequence with at least 95% homology to the amino acid sequence of SEQ ID NO: 15, HCDR1 has an amino acid sequence with at least 95% homology to the amino acid sequence of SEQ ID NO: 10, HCDR2 has an amino acid sequence with at least 95% homology to the amino acid sequence of SEQ ID NO: 11, and HCDR3 has an amino acid sequence with at least 95% homology to the amino acid sequence of SEQ ID NO: 12.
10. The method of claim 9, wherein the LCVR and HCVR of the antibody is selected from:a. the LCVR having the amino acid sequence of SEQ ID NO: 5 and the HCVR having the amino acid sequence of SEQ ID NO: 3;b. the LCVR having the amino acid sequence of SEQ ID NO: 8 and the HCVR having the amino acid sequence of SEQ ID NO: 6;c. the LCVR having an amino acid sequence with at least 95% homology to the amino acid sequence of SEQ ID NO: 5 and the HCVR having an amino acid sequence with at least 95% homology to the amino acid sequence of SEQ ID NO: 3; andd. the LCVR having an amino acid sequence with at least 95% homology to the amino acid sequence of SEQ ID NO: 8 and the HCVR having an amino acid sequence with at least 95% homology to the amino acid sequence of SEQ ID NO: 6.
11. The method of claim 6, wherein the tauopathy is Alzheimer’s disease (AD).
12. The method of claim 7, wherein the patient sample is CSF.
13. The method of claim 7, wherein the patient sample is plasma.
14. The method of any of claims 1-13, wherein one of the antibody and the second antibody are immobilized on a substrate.
15. The method of claim 14, wherein the substrate is selected from one of a micro-well plate or bead.
16. The method of any of claims 1-13, wherein said steps of contacting the patient sample with the antibody and contacting the patient sample with the second antibody occur simultaneously.
17. The method of claim 8, wherein the detectable label is a chemiluminescent or enzymatic label.
18. The method of claim 3 further comprising the step of diagnosing the patient as in need of neurological imaging, wherein the neurological imaging is Amyvid™ or flortaucipir.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962855331P | 2019-05-31 | 2019-05-31 | |
| PCT/US2020/034274 WO2020242963A1 (en) | 2019-05-31 | 2020-05-22 | Compounds and methods targeting human tau |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| IL287611A IL287611A (en) | 2021-12-01 |
| IL287611B1 true IL287611B1 (en) | 2025-12-01 |
| IL287611B2 IL287611B2 (en) | 2026-04-01 |
Family
ID=71083730
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL322784A IL322784B1 (en) | 2019-05-31 | 2020-05-22 | Compounds and methods targeting human tau |
| IL287611A IL287611B2 (en) | 2019-05-31 | 2020-05-22 | Compounds and methods targeting human tau |
| IL326001A IL326001A (en) | 2019-05-31 | 2020-05-22 | Compounds and methods targeting human tau |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL322784A IL322784B1 (en) | 2019-05-31 | 2020-05-22 | Compounds and methods targeting human tau |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL326001A IL326001A (en) | 2019-05-31 | 2020-05-22 | Compounds and methods targeting human tau |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US20220146535A1 (en) |
| EP (1) | EP3977135A1 (en) |
| JP (3) | JP7291250B2 (en) |
| KR (3) | KR102905634B1 (en) |
| CN (2) | CN120559249A (en) |
| AU (2) | AU2020283534B2 (en) |
| BR (1) | BR112021021062A2 (en) |
| CA (3) | CA3297188A1 (en) |
| EA (1) | EA202192888A1 (en) |
| IL (3) | IL322784B1 (en) |
| MX (2) | MX2021014473A (en) |
| WO (1) | WO2020242963A1 (en) |
| ZA (1) | ZA202502606B (en) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI843040B (en) | 2021-01-11 | 2024-05-21 | 美商美國禮來大藥廠 | ANTI-N3pGlu AMYLOID BETA ANTIBODIES AND USES THEREOF |
| TW202300517A (en) | 2021-03-12 | 2023-01-01 | 美商美國禮來大藥廠 | Anti-amyloid beta antibodies and uses thereof |
| TW202300518A (en) | 2021-03-12 | 2023-01-01 | 美商美國禮來大藥廠 | Anti-n3pglu amyloid beta antibodies and uses thereof |
| WO2022251048A1 (en) | 2021-05-24 | 2022-12-01 | Eli Lilly And Company | Anti-amyloid beta antibodies and uses thereof |
| CA3231228A1 (en) | 2021-09-09 | 2023-03-16 | Andreas Jeromin | Phospho-tau antibodies and methods of use |
| MX2024004514A (en) | 2021-10-22 | 2024-05-07 | Lilly Co Eli | O-glcnacase (oga) inhibitor combination therapy. |
| US20260125460A1 (en) | 2021-10-29 | 2026-05-07 | Eli Lilly And Company | Compounds and methods targeting interleukin-34 |
| MX2024005144A (en) | 2021-10-29 | 2024-05-13 | Lilly Co Eli | Compounds and methods targeting interleukin-34. |
| CA3236560A1 (en) | 2021-10-29 | 2023-05-04 | Marcio Chedid | Compounds and methods targeting interleukin-34 |
| IL312380A (en) | 2021-10-29 | 2024-06-01 | Lilly Co Eli | Compounds and methods targeting interleukin-34 |
| CN117003863A (en) * | 2022-04-28 | 2023-11-07 | 厦门大学 | Antibodies against p-tau 217 and their uses |
| JP2025535203A (en) | 2022-09-15 | 2025-10-23 | ボイジャー セラピューティクス インコーポレイテッド | Tau-binding compounds |
| US20260079168A1 (en) * | 2024-09-19 | 2026-03-19 | BioLegend, Inc. | Tau phospho (thr217) binding antibodies and antigen binding fragments thereof |
| WO2026164954A1 (en) * | 2025-01-29 | 2026-08-06 | Beckman Coulter, Inc. | Calibrator dipeptide for phosphorylated tau (p-tau) 217 immunoassays |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998022120A1 (en) * | 1996-11-19 | 1998-05-28 | The Wistar Institute Of Anatomy & Biology | Diagnostic and therapeutic reagents for alzheimer's disease |
| BR0107851A (en) * | 2000-01-24 | 2002-10-29 | Innogenetics Nv | Tauopathy diagnosis |
| DE60334460D1 (en) * | 2002-08-14 | 2010-11-18 | Mitsubishi Chem Medience Corp | ANTIBODIES SPECIFIC FOR THE TAU PROTEIN OF THE CENTRAL NERVOUS SYSTEM |
| US20080220449A1 (en) * | 2007-02-08 | 2008-09-11 | Oligomerix, Inc. | Biomarkers and assays for Alzheimer's disease |
| EP3275461A1 (en) * | 2011-09-19 | 2018-01-31 | Axon Neuroscience SE | Protein-based therapy and diagnosis of tau-mediated pathology in alzheimer's disease field |
| WO2014011972A1 (en) * | 2012-07-13 | 2014-01-16 | Bristol-Myers Squibb Company | Tau immunoassay |
| JP6284548B2 (en) * | 2012-12-21 | 2018-02-28 | バイオジェン・エムエイ・インコーポレイテッドＢｉｏｇｅｎ ＭＡ Ｉｎｃ． | Human anti-tau antibody |
| KR101696061B1 (en) * | 2015-03-05 | 2017-01-13 | 재단법인 아산사회복지재단 | Methods and apparatus for acquiring image based biomarkers suitable for diagnosis of neurodegenerative diseases and methods for diagnosing neurodegenerative diseases |
| CA3053379A1 (en) * | 2017-02-17 | 2018-08-23 | Denali Therapeutics Inc. | Anti-tau antibodies and methods of use thereof |
| TWI771389B (en) * | 2017-03-16 | 2022-07-21 | 美商健生生物科技公司 | Anti-phf-tau antibodies and uses thereof |
| WO2019171258A1 (en) * | 2018-03-05 | 2019-09-12 | Janssen Pharmaceutica Nv | Assays to detect neurodegeneration |
| CA3203800A1 (en) * | 2021-02-19 | 2022-08-25 | Eisai R&D Management Co., Ltd. | Anti-pt217 tau antibody |
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2020
- 2020-05-22 KR KR1020247003769A patent/KR102905634B1/en active Active
- 2020-05-22 CN CN202510691426.4A patent/CN120559249A/en active Pending
- 2020-05-22 IL IL322784A patent/IL322784B1/en unknown
- 2020-05-22 CN CN202080039868.6A patent/CN113950625B/en active Active
- 2020-05-22 IL IL287611A patent/IL287611B2/en unknown
- 2020-05-22 KR KR1020217038312A patent/KR102633666B1/en active Active
- 2020-05-22 CA CA3297188A patent/CA3297188A1/en active Pending
- 2020-05-22 CA CA3140201A patent/CA3140201A1/en active Pending
- 2020-05-22 IL IL326001A patent/IL326001A/en unknown
- 2020-05-22 BR BR112021021062A patent/BR112021021062A2/en unknown
- 2020-05-22 CA CA3297280A patent/CA3297280A1/en active Pending
- 2020-05-22 MX MX2021014473A patent/MX2021014473A/en unknown
- 2020-05-22 AU AU2020283534A patent/AU2020283534B2/en active Active
- 2020-05-22 WO PCT/US2020/034274 patent/WO2020242963A1/en not_active Ceased
- 2020-05-22 EP EP20732390.8A patent/EP3977135A1/en active Pending
- 2020-05-22 JP JP2021570981A patent/JP7291250B2/en active Active
- 2020-05-22 EA EA202192888A patent/EA202192888A1/en unknown
- 2020-05-22 KR KR1020257042926A patent/KR20260006702A/en active Pending
-
2021
- 2021-11-24 US US17/535,059 patent/US20220146535A1/en active Pending
- 2021-11-25 MX MX2026001143A patent/MX2026001143A/en unknown
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2023
- 2023-06-02 JP JP2023091572A patent/JP7544911B2/en active Active
-
2024
- 2024-05-08 AU AU2024203048A patent/AU2024203048B2/en active Active
- 2024-07-05 JP JP2024108570A patent/JP7862475B2/en active Active
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2025
- 2025-03-26 ZA ZA2025/02606A patent/ZA202502606B/en unknown
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