CN112079922B - 抗人p40蛋白域抗体及其用途 - Google Patents
抗人p40蛋白域抗体及其用途 Download PDFInfo
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- CN112079922B CN112079922B CN202010740669.XA CN202010740669A CN112079922B CN 112079922 B CN112079922 B CN 112079922B CN 202010740669 A CN202010740669 A CN 202010740669A CN 112079922 B CN112079922 B CN 112079922B
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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
- C07K16/24—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/244—Interleukins [IL]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6845—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a cytokine, e.g. growth factors, VEGF, TNF, a lymphokine or an interferon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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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
- G01N33/6854—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
- G01N33/68—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
-
- 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
- C07K2317/30—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
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- 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
- C07K2317/50—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
- C07K2317/567—Framework region [FR]
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- 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
- G01N2333/52—Assays involving cytokines
- G01N2333/54—Interleukins [IL]
- G01N2333/5434—IL-12
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/06—Gastro-intestinal diseases
- G01N2800/065—Bowel diseases, e.g. Crohn, ulcerative colitis, IBS
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/10—Musculoskeletal or connective tissue disorders
- G01N2800/101—Diffuse connective tissue disease, e.g. Sjögren, Wegener's granulomatosis
- G01N2800/104—Lupus erythematosus [SLE]
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/20—Dermatological disorders
- G01N2800/205—Scaling palpular diseases, e.g. psoriasis, pytiriasis
-
- 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
- G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
- G01N33/6869—Interleukin
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Cell Biology (AREA)
- Dermatology (AREA)
- Food Science & Technology (AREA)
- Pathology (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Microbiology (AREA)
- General Physics & Mathematics (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Nutrition Science (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)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2019107061371 | 2019-07-30 | ||
| CN201910706137 | 2019-07-30 | ||
| CN201911040745X | 2019-10-29 | ||
| CN201911040745 | 2019-10-29 | ||
| CN2019111717542 | 2019-11-25 | ||
| CN201911171754 | 2019-11-25 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112079922A CN112079922A (zh) | 2020-12-15 |
| CN112079922B true CN112079922B (zh) | 2022-08-12 |
Family
ID=73735954
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010740669.XA Active CN112079922B (zh) | 2019-07-30 | 2020-07-28 | 抗人p40蛋白域抗体及其用途 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US12595300B2 (https=) |
| EP (1) | EP4008727A4 (https=) |
| JP (2) | JP7638955B2 (https=) |
| KR (1) | KR20220038775A (https=) |
| CN (1) | CN112079922B (https=) |
| AU (1) | AU2020320910A1 (https=) |
| BR (1) | BR112022001632A2 (https=) |
| CA (1) | CA3145909A1 (https=) |
| IL (1) | IL290167A (https=) |
| MX (1) | MX2022001305A (https=) |
| PH (1) | PH12022550223A1 (https=) |
| WO (1) | WO2021018114A1 (https=) |
| ZA (1) | ZA202202380B (https=) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112022001632A2 (pt) | 2019-07-30 | 2022-04-19 | Akeso Biopharma Inc | Anticorpos, polipeptídeo, polinucleotídeo, vetor, célula hospedeira, conjugado de anticorpo, proteína de fusão, kit, usos do anticorpo, composição farmacêutica, métodos in vivo ou in vitro, para preparar o anticorpo e para prevenção, tratamento, tratamento adjuvante e/ou de diagnóstico de doenças autoimunes |
| CN118620077B (zh) * | 2024-08-13 | 2024-11-12 | 苏州百道医疗科技有限公司 | 一种抗p40重组兔单克隆抗体及其应用 |
| WO2026062296A1 (en) * | 2024-09-23 | 2026-03-26 | Ose Immunotherapeutics | Therapy by antagonizing il-7 or cd127, and il-12, il-23, il-12r or il-23r |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102177178A (zh) * | 2008-08-14 | 2011-09-07 | 赛福伦澳大利亚私人有限公司 | 抗il-12/il-23抗体 |
| CN103275222A (zh) * | 2013-05-15 | 2013-09-04 | 中山康方生物医药有限公司 | 一种阻断白介素12 p40功能的单克隆抗体及其编码基因和应用 |
| CN103813804A (zh) * | 2010-10-06 | 2014-05-21 | Abbvie公司 | 用于治疗银屑病的方法 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| EP0281604B1 (en) | 1986-09-02 | 1993-03-31 | Enzon Labs Inc. | Single polypeptide chain binding molecules |
| US5260203A (en) | 1986-09-02 | 1993-11-09 | Enzon, Inc. | Single polypeptide chain binding molecules |
| US6902734B2 (en) | 2000-08-07 | 2005-06-07 | Centocor, Inc. | Anti-IL-12 antibodies and compositions thereof |
| CN103145842A (zh) * | 2005-06-30 | 2013-06-12 | Abbvie公司 | Il-12/p40结合蛋白 |
| WO2009114040A2 (en) * | 2007-09-28 | 2009-09-17 | Centocor Ortho Biotech Inc. | Anti-il-12/23p40 antibodies, epitopes, formulations, compositions, methods and uses |
| TW201242976A (en) | 2011-01-07 | 2012-11-01 | Abbott Lab | Anti-IL-12/IL-23 antibodies and uses thereof |
| PT2692865E (pt) * | 2012-07-30 | 2015-02-06 | Nbe Therapeutics Llc | Identificação mediada por transposição de proteínas funcionais ou de ligação específicas |
| BR112015013431A2 (pt) * | 2012-12-12 | 2017-11-14 | Vasculox Inc | anticorpos monoclonais ou respectivos fragmentos ligantes de antígenos, composição farmacêutica, e usos de anticorpo monoclonal ou respectivo fragmento ligante de antígenos |
| CN109293777A (zh) * | 2015-11-13 | 2019-02-01 | 叶才果 | 双功能抗体及其用途 |
| TW201922780A (zh) | 2017-09-25 | 2019-06-16 | 美商健生生物科技公司 | 以抗il12/il23抗體治療狼瘡之安全且有效之方法 |
| GB201720351D0 (en) * | 2017-12-06 | 2018-01-17 | Iontas Ltd | Selecting for developability in drug discovery |
| BR112022001632A2 (pt) | 2019-07-30 | 2022-04-19 | Akeso Biopharma Inc | Anticorpos, polipeptídeo, polinucleotídeo, vetor, célula hospedeira, conjugado de anticorpo, proteína de fusão, kit, usos do anticorpo, composição farmacêutica, métodos in vivo ou in vitro, para preparar o anticorpo e para prevenção, tratamento, tratamento adjuvante e/ou de diagnóstico de doenças autoimunes |
-
2020
- 2020-07-28 BR BR112022001632A patent/BR112022001632A2/pt unknown
- 2020-07-28 PH PH1/2022/550223A patent/PH12022550223A1/en unknown
- 2020-07-28 AU AU2020320910A patent/AU2020320910A1/en active Pending
- 2020-07-28 WO PCT/CN2020/105039 patent/WO2021018114A1/zh not_active Ceased
- 2020-07-28 JP JP2022505553A patent/JP7638955B2/ja active Active
- 2020-07-28 EP EP20847243.1A patent/EP4008727A4/en active Pending
- 2020-07-28 CN CN202010740669.XA patent/CN112079922B/zh active Active
- 2020-07-28 CA CA3145909A patent/CA3145909A1/en active Pending
- 2020-07-28 KR KR1020227006902A patent/KR20220038775A/ko not_active Ceased
- 2020-07-28 US US17/631,797 patent/US12595300B2/en active Active
- 2020-07-28 MX MX2022001305A patent/MX2022001305A/es unknown
-
2022
- 2022-01-27 IL IL290167A patent/IL290167A/en unknown
- 2022-02-24 ZA ZA2022/02380A patent/ZA202202380B/en unknown
-
2025
- 2025-02-19 JP JP2025024929A patent/JP2025081517A/ja active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102177178A (zh) * | 2008-08-14 | 2011-09-07 | 赛福伦澳大利亚私人有限公司 | 抗il-12/il-23抗体 |
| CN103813804A (zh) * | 2010-10-06 | 2014-05-21 | Abbvie公司 | 用于治疗银屑病的方法 |
| CN103275222A (zh) * | 2013-05-15 | 2013-09-04 | 中山康方生物医药有限公司 | 一种阻断白介素12 p40功能的单克隆抗体及其编码基因和应用 |
Non-Patent Citations (3)
| Title |
|---|
| P40家族成员及其在自身免疫性疾病中的作用;郭薇等;《药物生物技术》;20110215;第18卷(第01期);81-84 * |
| Structural basis for the dual recognition of IL-12 and IL-23 by ustekinumab;Luo J等;《Journal of Molecular Biology》;20100804;第402卷(第05期);797-812 * |
| 阻断白介素12p40功能的新型治疗性单克隆抗体的开发;李百勇等;《中国医药生物技术》;20140810;第09卷(第04期);283-287 * |
Also Published As
| Publication number | Publication date |
|---|---|
| ZA202202380B (en) | 2025-06-25 |
| PH12022550223A1 (en) | 2022-12-19 |
| WO2021018114A1 (zh) | 2021-02-04 |
| MX2022001305A (es) | 2022-05-06 |
| JP2022544050A (ja) | 2022-10-17 |
| BR112022001632A2 (pt) | 2022-04-19 |
| IL290167A (en) | 2022-03-01 |
| CN112079922A (zh) | 2020-12-15 |
| EP4008727A4 (en) | 2024-01-17 |
| JP2025081517A (ja) | 2025-05-27 |
| AU2020320910A1 (en) | 2022-03-10 |
| CA3145909A1 (en) | 2021-02-04 |
| KR20220038775A (ko) | 2022-03-29 |
| US20220298235A1 (en) | 2022-09-22 |
| EP4008727A1 (en) | 2022-06-08 |
| JP7638955B2 (ja) | 2025-03-04 |
| US12595300B2 (en) | 2026-04-07 |
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