CR20190249A - Constructos de vacuna y sus usos contrainfecciones causadas por staphylococcus - Google Patents
Constructos de vacuna y sus usos contrainfecciones causadas por staphylococcusInfo
- Publication number
- CR20190249A CR20190249A CR20190249A CR20190249A CR20190249A CR 20190249 A CR20190249 A CR 20190249A CR 20190249 A CR20190249 A CR 20190249A CR 20190249 A CR20190249 A CR 20190249A CR 20190249 A CR20190249 A CR 20190249A
- Authority
- CR
- Costa Rica
- Prior art keywords
- polypeptide
- seq
- amino acid
- set forth
- nos
- Prior art date
Links
- 241000191940 Staphylococcus Species 0.000 title 1
- 208000015181 infectious disease Diseases 0.000 title 1
- 229960005486 vaccine Drugs 0.000 title 1
- 229920001184 polypeptide Polymers 0.000 abstract 44
- 108090000765 processed proteins & peptides Proteins 0.000 abstract 44
- 102000004196 processed proteins & peptides Human genes 0.000 abstract 44
- 150000001413 amino acids Chemical class 0.000 abstract 10
- 125000003275 alpha amino acid group Chemical group 0.000 abstract 8
- 230000004927 fusion Effects 0.000 abstract 6
- 108090000623 proteins and genes Proteins 0.000 abstract 5
- 241000344863 Staphylococcus aureus subsp. aureus COL Species 0.000 abstract 4
- 230000002163 immunogen Effects 0.000 abstract 4
- 239000000203 mixture Substances 0.000 abstract 4
- 101100211536 Staphylococcus aureus (strain COL) SACOL2365 gene Proteins 0.000 abstract 2
- 101100227953 Staphylococcus aureus (strain COL) fur gene Proteins 0.000 abstract 2
- 101100404789 Staphylococcus aureus (strain COL) nikC gene Proteins 0.000 abstract 2
- 101100422138 Staphylococcus aureus (strain COL) splC gene Proteins 0.000 abstract 2
- 239000012634 fragment Substances 0.000 abstract 2
- 239000011230 binding agent Substances 0.000 abstract 1
- 230000002068 genetic effect Effects 0.000 abstract 1
Classifications
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- 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
- A61K39/02—Bacterial antigens
- A61K39/085—Staphylococcus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- 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
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/305—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Micrococcaceae (F)
- C07K14/31—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Micrococcaceae (F) from Staphylococcus (G)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- 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
-
- 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
- C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
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- 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
-
- 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
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/52—Bacterial cells; Fungal cells; Protozoal cells
- A61K2039/522—Bacterial cells; Fungal cells; Protozoal cells avirulent or attenuated
-
- 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
- A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
- A61K2039/552—Veterinary vaccine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
- C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Mycology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Abstract
Se proporciona un constructo de fusión de fórmula (I): X-A-ligante-B-Z (I) donde : (1) A y B son idénticos o diferentes y son independientemente: (a) un polipéptido que comprende un polipéptido SACOL0029 según lo expuesto en cualquiera de las secuencias descritas en FIG. 24 (SEC ID NOs: 5 y 121 a 131), un polipéptido SACOL0264 (SEC ID NO : 185), un polipéptido SACOL0442 según lo expuesto en cualquiera de las secuencias descritas en FIG. 22D (SEC ID NOs: 29 y 82 a 92), un polipéptido SACOL0718 (SEC ID NO : 186), un polipéptido SACOL0720 según lo expuesto en cualquiera de las secuencias descritas en FIGs. 23I-J (SEC ID NOs: 11 y 109 a 120), un polipéptido SACOL1353 (SEC ID NO : 187), un polipéptido SACOL1416 (SEC ID NO : 188), un polipéptido SACOL1611 (SEC ID NO : 189), un polipéptido SACOL1867 según lo expuesto en cualquiera de las secuencias descritas en FIG. 25D (SEC ID NOs: 152 a 164), un polipéptido SACOL1912 (SEC ID NO : 43), un polipéptido SACOL1944 (SEC ID NO : 190), un polipéptido SACOL2144 (SEC ID NO : 191), un polipéptido SACOL2365 (SEC ID NO : 192), un polipéptido SACOL2385 (SEC ID NO : 50) o un polipéptido SACOL2599 (SEC ID NO : 193), sobre la base de la nomenclatura genética del genoma COL (SACOL) de Staphylococcus aureus expuesto en la Secuencia de Referencia en el NCBI NC_002951.2; (b) un polipéptido codificado por un gen de un mismo operón que un gen que codifica al polipéptido de (a); (c) un polipéptido que comprende un fragmento inmunogénico de por lo menos 13 aminoácidos consecutivos de (a) o (b); (d) un polipéptido que comprende una secuencia de aminoácidos por lo menos 60% idéntica en su totalidad a la secuencia del polipéptido de cualquiera de (a) a (c); o (e) un polipéptido que comprende una variante inmunogénica que comprende por lo menos 13 aminoácidos consecutivos de cualquiera de (a) a (c); (2) el ligante es una secuencia de aminoácidos de por lo menos un aminoácido o está ausente; (3) X está ausente o es una secuencia de aminoácidos de por lo menos un aminoácido; y (4) Z está ausente o es una secuencia de aminoácidos de por lo menos un aminoácido. Se proporcionan además composiciones y kits que comprenden la fusión y usos de estas fusiones, composiciones y kits.There is provided a fusion construct of formula (I): X-A-linker-B-Z (I) wherein : (1) A and B are identical or different and are independently: (a) a polypeptide comprising a SACOL0029 polypeptide as set forth in any one of the sequences depicted in FIG. 24 (SEQ ID NOs: 5 and 121 to 131), a SACOL0264 polypeptide (SEQ ID NO : 185), a SACOL0442 polypeptide as set forth in any one of the sequences depicted in FIG. 22D (SEQ ID NOs: 29 and 82 to 92), a SACOL0718 polypeptide (SEQ ID NO : 186), a SACOL0720 polypeptide as set forth in any one of the sequences depicted in FIGs. 23I-J (SEQ ID NOs: 11 and 109 to 120), a SACOL1353 polypeptide (SEQ ID NO : 187), a SACOL1416 polypeptide (SEQ ID NO : 188), a SACOL1611 polypeptide (SEQ ID NO : 189), a SACOL1867 polypeptide as set forth in any one of the sequences depicted in FIG. 25D (SEQ ID NOs: 152 to 164), a SACOL1912 polypeptide (SEQ ID NO : 43), a SACOL1944 polypeptide (SEQ ID NO : 190), a SACOL2144 polypeptide (SEQ ID NO : 191), a SACOL2365 polypeptide (SEQ ID NO : 192), a SACOL2385 polypeptide (SEQ ID NO : 50) or a SACOL2599 polypeptide (SEQ ID NO : 193), based on the gene nomenclature from the Staphylococcus aureus COL (SACOL) genome set forth in NCBI Reference Sequence NC_002951.2; (b) a polypeptide encoded by a gene from a same operon as a gene encoding the polypeptide of (a); (c) a polypeptide comprising an immunogenic fragment of at least 13 consecutive amino acids of (a) or (b); (d) a polypeptide comprising an amino acid sequence at least 60% identical overall to the sequence of the polypeptide of any one of (a) to (c); or (e) a polypeptide comprising an immunogenic variant comprising at least 13 consecutive amino acids of any one of (a) to (c); (2) the linker is an amino acid sequence of at least one amino acid or is absent; (3) X is absent or is an amino acid sequence of at least one amino acid; and (4) Z is absent or is an amino acid sequence of at least one amino acid. Also provided are compositions and kits comprising the fusion and uses of these fusions, compositions and kits.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662411120P | 2016-10-21 | 2016-10-21 | |
| PCT/CA2017/051253 WO2018072031A1 (en) | 2016-10-21 | 2017-10-20 | Vaccine constructs and uses thereof against staphylococcus infections |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CR20190249A true CR20190249A (es) | 2019-10-16 |
Family
ID=62018642
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CR20190249A CR20190249A (es) | 2016-10-21 | 2017-10-20 | Constructos de vacuna y sus usos contrainfecciones causadas por staphylococcus |
Country Status (24)
| Country | Link |
|---|---|
| US (2) | US11324815B2 (es) |
| EP (1) | EP3529260A4 (es) |
| JP (2) | JP7181208B2 (es) |
| KR (1) | KR20190082229A (es) |
| CN (1) | CN109843910A (es) |
| AR (1) | AR109847A1 (es) |
| AU (2) | AU2017346974B2 (es) |
| BR (1) | BR112019007796A2 (es) |
| CA (1) | CA3037070A1 (es) |
| CL (1) | CL2019001048A1 (es) |
| CO (1) | CO2019005169A2 (es) |
| CR (1) | CR20190249A (es) |
| DO (1) | DOP2019000102A (es) |
| IL (1) | IL265869A (es) |
| MX (2) | MX2019004539A (es) |
| MY (1) | MY195369A (es) |
| NZ (1) | NZ751880A (es) |
| PE (1) | PE20191320A1 (es) |
| PH (1) | PH12019500843A1 (es) |
| RU (2) | RU2766354C2 (es) |
| SG (2) | SG10201912431XA (es) |
| TW (1) | TW201819402A (es) |
| UY (1) | UY37448A (es) |
| WO (1) | WO2018072031A1 (es) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113777317A (zh) * | 2020-06-09 | 2021-12-10 | 首都医科大学附属北京世纪坛医院 | 尿液主穹隆蛋白及其多肽片段在烧伤中的应用 |
| WO2022125928A1 (en) * | 2020-12-11 | 2022-06-16 | Bayer Animal Health Gmbh | Methods and compositions for improved production of an antigen for use in an s. aureus vaccine |
| US12161970B1 (en) | 2024-08-09 | 2024-12-10 | Jiaxing Research Institute, Zhejiang University | CO2 desorption system suitable for limited space in complex sailing region and flexible control method |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3669503D1 (de) | 1985-01-07 | 1990-04-19 | Syntex Inc | Oberflaechenaktive n-(omega, omega-1-dialkoxy)- und n-(omega, omega-1-dialkenoxy)-alk-1-yl-n,n,n-trisubstituierte ammoniumverbindungen, deren herstellung und sie enthaltende pharmazeutische formulierungen. |
| US6228844B1 (en) | 1991-11-12 | 2001-05-08 | Vical Incorporated | Stimulating vascular growth by administration of DNA sequences encoding VEGF |
| US7060458B1 (en) | 1997-08-14 | 2006-06-13 | Wyeth | Nucleic acid and amino acid sequences relating to Staphylococcus epidermidis for diagnostics and therapeutics |
| US6380370B1 (en) * | 1997-08-14 | 2002-04-30 | Genome Therapeutics Corporation | Nucleic acid and amino acid sequences relating to Staphylococcus epidermidis for diagnostics and therapeutics |
| US6833134B2 (en) | 2000-06-12 | 2004-12-21 | University Of Saskacthewan | Immunization of dairy cattle with GapC protein against Streptococcus infection |
| GB0107661D0 (en) | 2001-03-27 | 2001-05-16 | Chiron Spa | Staphylococcus aureus |
| PT1565478T (pt) | 2002-11-12 | 2017-11-14 | The Brigham And Women`S Hospital Inc | Vacina de polissacáridos para infeções estafilocócicas |
| CN1569893A (zh) | 2003-07-21 | 2005-01-26 | 中国人民解放军军事医学科学院基础医学研究所 | 金葡菌毒力因子调控蛋白的抗原表位及其模拟表位和用途 |
| RU2419628C2 (ru) * | 2004-09-22 | 2011-05-27 | ГлаксоСмитКлайн Байолоджикалз с.а. | Иммуногенная композиция для применения в вакцинации против стафилококков |
| JP2008517918A (ja) * | 2004-10-21 | 2008-05-29 | ワイス | Ｓｔａｐｈｙｌｏｃｏｃｃｕｓｅｐｉｄｅｒｍｉｄｉｓポリペプチド抗原の免疫原性組成物 |
| WO2006059846A1 (en) | 2004-12-01 | 2006-06-08 | Lg Life Sciences, Ltd. | Formulation of sec1 mutated protein and method for formulation of the same |
| WO2008152447A2 (en) | 2006-10-30 | 2008-12-18 | The University Of Western Ontario | Staphylococcus aureus specific anti-infectives |
| WO2010111273A1 (en) | 2009-03-23 | 2010-09-30 | Epitopix, Llc | Polypeptides and immunizing compositions containing gram positive polypeptides and methods of use |
| EP2419129A2 (en) * | 2009-04-14 | 2012-02-22 | Novartis AG | Compositions for immunising against staphylococcus aerus |
| HUE052610T2 (hu) | 2010-03-17 | 2021-05-28 | Socpra Sciences Et Genie Sec | Bakteriális vakcina komponensek Staphylococcus aureusból és alkalmazásaik |
| BR112013032774B1 (pt) | 2011-06-19 | 2020-05-05 | Univ New York | composições compreendendo proteína luke isolada ou polipeptídeo da mesma, uma proteína lukd isolada ou polipeptídeo da mesma ou sua combinação, bem como seu uso |
-
2017
- 2017-10-20 PE PE2019000844A patent/PE20191320A1/es unknown
- 2017-10-20 EP EP17863203.0A patent/EP3529260A4/en active Pending
- 2017-10-20 UY UY0001037448A patent/UY37448A/es unknown
- 2017-10-20 SG SG10201912431XA patent/SG10201912431XA/en unknown
- 2017-10-20 AU AU2017346974A patent/AU2017346974B2/en not_active Ceased
- 2017-10-20 MY MYPI2019002159A patent/MY195369A/en unknown
- 2017-10-20 CN CN201780064991.1A patent/CN109843910A/zh active Pending
- 2017-10-20 MX MX2019004539A patent/MX2019004539A/es unknown
- 2017-10-20 US US16/337,457 patent/US11324815B2/en active Active
- 2017-10-20 NZ NZ751880A patent/NZ751880A/en unknown
- 2017-10-20 TW TW106136089A patent/TW201819402A/zh unknown
- 2017-10-20 SG SG11201901483QA patent/SG11201901483QA/en unknown
- 2017-10-20 RU RU2019115303A patent/RU2766354C2/ru active
- 2017-10-20 WO PCT/CA2017/051253 patent/WO2018072031A1/en active Application Filing
- 2017-10-20 BR BR112019007796A patent/BR112019007796A2/pt not_active IP Right Cessation
- 2017-10-20 CA CA3037070A patent/CA3037070A1/en active Pending
- 2017-10-20 RU RU2022100889A patent/RU2022100889A/ru unknown
- 2017-10-20 AR ARP170102922A patent/AR109847A1/es not_active Application Discontinuation
- 2017-10-20 KR KR1020197014191A patent/KR20190082229A/ko active Pending
- 2017-10-20 CR CR20190249A patent/CR20190249A/es unknown
- 2017-10-20 JP JP2019542759A patent/JP7181208B2/ja active Active
-
2019
- 2019-04-07 IL IL265869A patent/IL265869A/en unknown
- 2019-04-16 PH PH12019500843A patent/PH12019500843A1/en unknown
- 2019-04-17 MX MX2023001219A patent/MX2023001219A/es unknown
- 2019-04-17 DO DO2019000102A patent/DOP2019000102A/es unknown
- 2019-04-17 CL CL2019001048A patent/CL2019001048A1/es unknown
- 2019-05-21 CO CONC2019/0005169A patent/CO2019005169A2/es unknown
-
2022
- 2022-04-05 US US17/713,683 patent/US20220288183A1/en active Pending
- 2022-06-28 AU AU2022204585A patent/AU2022204585A1/en not_active Abandoned
- 2022-11-16 JP JP2022183528A patent/JP2023025066A/ja not_active Withdrawn
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