CA3132578A1 - Method for producing influenza ha split vaccine - Google Patents
Method for producing influenza ha split vaccine Download PDFInfo
- Publication number
- CA3132578A1 CA3132578A1 CA3132578A CA3132578A CA3132578A1 CA 3132578 A1 CA3132578 A1 CA 3132578A1 CA 3132578 A CA3132578 A CA 3132578A CA 3132578 A CA3132578 A CA 3132578A CA 3132578 A1 CA3132578 A1 CA 3132578A1
- Authority
- CA
- Canada
- Prior art keywords
- influenza
- split vaccine
- vaccine
- split
- antibody
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229960005486 vaccine Drugs 0.000 title claims abstract description 271
- 206010022000 influenza Diseases 0.000 title claims abstract description 139
- 238000004519 manufacturing process Methods 0.000 title claims description 54
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- 238000000034 method Methods 0.000 claims abstract description 35
- 241000712461 unidentified influenza virus Species 0.000 claims abstract description 29
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- 208000015181 infectious disease Diseases 0.000 abstract description 11
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- 230000000890 antigenic effect Effects 0.000 abstract description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
- 239000012528 membrane Substances 0.000 description 53
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- 239000002953 phosphate buffered saline Substances 0.000 description 33
- 241000699670 Mus sp. Species 0.000 description 20
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- 238000011081 inoculation Methods 0.000 description 14
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- 238000011725 BALB/c mouse Methods 0.000 description 9
- 238000005119 centrifugation Methods 0.000 description 9
- 238000005259 measurement Methods 0.000 description 9
- 229920001213 Polysorbate 20 Polymers 0.000 description 8
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 8
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 8
- 239000007983 Tris buffer Substances 0.000 description 7
- 239000002671 adjuvant Substances 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 7
- 238000011740 C57BL/6 mouse Methods 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 238000002156 mixing Methods 0.000 description 6
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 6
- 229920000053 polysorbate 80 Polymers 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 206010069767 H1N1 influenza Diseases 0.000 description 5
- 241000712431 Influenza A virus Species 0.000 description 5
- 229940098773 bovine serum albumin Drugs 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 201000010740 swine influenza Diseases 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 229960003971 influenza vaccine Drugs 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000011161 development Methods 0.000 description 3
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- 239000000126 substance Substances 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 229940046168 CpG oligodeoxynucleotide Drugs 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 241000713196 Influenza B virus Species 0.000 description 2
- 231100000111 LD50 Toxicity 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 101710198474 Spike protein Proteins 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
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- 231100000518 lethal Toxicity 0.000 description 2
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- 150000002632 lipids Chemical class 0.000 description 2
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- 102000013415 peroxidase activity proteins Human genes 0.000 description 2
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- 239000007793 ph indicator Substances 0.000 description 2
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- 230000008569 process Effects 0.000 description 2
- 239000002510 pyrogen Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- YYGNTYWPHWGJRM-AAJYLUCBSA-N squalene Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C=C(/C)CC\C=C(/C)CCC=C(C)C YYGNTYWPHWGJRM-AAJYLUCBSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000739160 Homo sapiens Secretoglobin family 3A member 1 Proteins 0.000 description 1
- 102000005348 Neuraminidase Human genes 0.000 description 1
- 108010006232 Neuraminidase Proteins 0.000 description 1
- 241000845082 Panama Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 229940096437 Protein S Drugs 0.000 description 1
- 102100037268 Secretoglobin family 3A member 1 Human genes 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000034217 membrane fusion Effects 0.000 description 1
- CEQFOVLGLXCDCX-WUKNDPDISA-N methyl red Chemical compound C1=CC(N(C)C)=CC=C1\N=N\C1=CC=CC=C1C(O)=O CEQFOVLGLXCDCX-WUKNDPDISA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61K39/12—Viral antigens
-
- 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
- A61K39/12—Viral antigens
- A61K39/145—Orthomyxoviridae, e.g. influenza virus
-
- 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
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- 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
- A61K2039/525—Virus
- A61K2039/5252—Virus inactivated (killed)
-
- 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
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
- A61K2039/541—Mucosal route
- A61K2039/543—Mucosal route intranasal
-
- 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
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—Inorganic adjuvants
-
- 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
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
- A61K2039/575—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 humoral response
-
- 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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/16011—Orthomyxoviridae
- C12N2760/16111—Influenzavirus A, i.e. influenza A virus
- C12N2760/16134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Pulmonology (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Mycology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2019-038662 | 2019-03-04 | ||
| JP2019038662 | 2019-03-04 | ||
| PCT/JP2020/008974 WO2020179797A1 (ja) | 2019-03-04 | 2020-03-03 | インフルエンザｈａスプリットワクチンの製造方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3132578A1 true CA3132578A1 (en) | 2020-09-10 |
Family
ID=72337458
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3132578A Pending CA3132578A1 (en) | 2019-03-04 | 2020-03-03 | Method for producing influenza ha split vaccine |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US20220152191A1 (en, 2012) |
| EP (1) | EP3936147A4 (en, 2012) |
| JP (1) | JP7545955B2 (en, 2012) |
| KR (1) | KR20210135261A (en, 2012) |
| CN (1) | CN114096273A (en, 2012) |
| AU (1) | AU2020233456A1 (en, 2012) |
| BR (1) | BR112021017310A8 (en, 2012) |
| CA (1) | CA3132578A1 (en, 2012) |
| EA (1) | EA202192398A1 (en, 2012) |
| IL (1) | IL285984A (en, 2012) |
| MX (1) | MX2021010685A (en, 2012) |
| PH (1) | PH12021552094A1 (en, 2012) |
| SG (1) | SG11202109566XA (en, 2012) |
| WO (1) | WO2020179797A1 (en, 2012) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PH12021550175A1 (en) | 2018-07-23 | 2022-07-11 | Japan As Represented By Director General Of Nat Institute Of Infectious Diseases | Composition containing influenza vaccine |
| CN114929270A (zh) * | 2019-11-07 | 2022-08-19 | 塞其里斯英国有限公司 | 用于生产具有减小的颗粒大小的病毒疫苗的组合物和方法 |
| WO2024225404A1 (ja) * | 2023-04-26 | 2024-10-31 | 国立感染症研究所長が代表する日本国 | 抗インフルエンザ抗体 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2374894B1 (en) * | 1993-09-13 | 2014-09-17 | Protein Sciences Corporation | A method for producing influenza hemagglutinin multivalent vaccines |
| US20230201329A1 (en) * | 2006-07-17 | 2023-06-29 | Glaxosmithkline Biologicals Sa | Influenza vaccine |
| US20090181078A1 (en) * | 2006-09-26 | 2009-07-16 | Infectious Disease Research Institute | Vaccine composition containing synthetic adjuvant |
| PE20090146A1 (es) * | 2007-04-20 | 2009-03-23 | Glaxosmithkline Biolog Sa | Composicion inmunogenica contra el virus influenza |
| CA2744354C (en) * | 2008-11-25 | 2018-10-02 | Avir Green Hills Biotechnology Research Development Trade Ag | Method for production of ph stable enveloped viruses |
| CN102406931B (zh) * | 2011-11-25 | 2014-02-05 | 成都康华生物制品有限公司 | 大流行流感病毒裂解疫苗 |
| CN104302317B (zh) * | 2012-05-16 | 2016-07-06 | Kj生物科学有限公司 | 新型和改进的流感疫苗 |
| KR20140118682A (ko) | 2013-03-29 | 2014-10-08 | (주)셀트리온 | 2 이상의 인플루엔자 ａ 바이러스 중화 결합 분자를 포함하는 조성물 |
| WO2016178811A1 (en) * | 2015-05-04 | 2016-11-10 | Epivax, Inc. | Modified h7 hemagluttinin glycoprotein of the influenza a/shanghai/2/2013 h7 sequence |
| ES2805724T3 (es) * | 2015-09-29 | 2021-02-15 | Sumitomo Dainippon Pharma Co Ltd | Compuestos de adenina conjugados y su uso como adyuvantes de vacunas |
| CN110650729B (zh) * | 2017-03-29 | 2024-08-20 | 住友制药株式会社 | 疫苗佐剂制剂 |
| JP7403733B2 (ja) * | 2017-09-04 | 2023-12-25 | 国立感染症研究所長 | インフルエンザｈａスプリットワクチンの製造方法 |
| PH12021550175A1 (en) * | 2018-07-23 | 2022-07-11 | Japan As Represented By Director General Of Nat Institute Of Infectious Diseases | Composition containing influenza vaccine |
| CA3121613A1 (en) * | 2018-12-26 | 2020-07-02 | Sumitomo Dainippon Pharma Co., Ltd. | Preparation including vaccine adjuvant |
| BR112021017074A2 (pt) * | 2019-02-28 | 2021-11-09 | Novavax Inc | Métodos para prevenir doença ou distúrbio causado(a) por infecção por rsv |
-
2020
- 2020-03-03 EA EA202192398A patent/EA202192398A1/ru unknown
- 2020-03-03 EP EP20766488.9A patent/EP3936147A4/en active Pending
- 2020-03-03 WO PCT/JP2020/008974 patent/WO2020179797A1/ja active Application Filing
- 2020-03-03 PH PH1/2021/552094A patent/PH12021552094A1/en unknown
- 2020-03-03 CA CA3132578A patent/CA3132578A1/en active Pending
- 2020-03-03 MX MX2021010685A patent/MX2021010685A/es unknown
- 2020-03-03 US US17/435,590 patent/US20220152191A1/en active Pending
- 2020-03-03 JP JP2021504119A patent/JP7545955B2/ja active Active
- 2020-03-03 CN CN202080033434.5A patent/CN114096273A/zh active Pending
- 2020-03-03 KR KR1020217030986A patent/KR20210135261A/ko active Pending
- 2020-03-03 AU AU2020233456A patent/AU2020233456A1/en active Pending
- 2020-03-03 BR BR112021017310A patent/BR112021017310A8/pt unknown
- 2020-03-03 SG SG11202109566X patent/SG11202109566XA/en unknown
-
2021
- 2021-08-31 IL IL285984A patent/IL285984A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BR112021017310A2 (en, 2012) | 2021-11-16 |
| IL285984A (en) | 2021-10-31 |
| PH12021552094A1 (en) | 2022-05-30 |
| AU2020233456A1 (en) | 2021-10-07 |
| EP3936147A4 (en) | 2022-09-28 |
| WO2020179797A1 (ja) | 2020-09-10 |
| MX2021010685A (es) | 2021-12-10 |
| BR112021017310A8 (pt) | 2022-12-06 |
| US20220152191A1 (en) | 2022-05-19 |
| EA202192398A1 (ru) | 2021-11-23 |
| JP7545955B2 (ja) | 2024-09-05 |
| EP3936147A1 (en) | 2022-01-12 |
| JPWO2020179797A1 (en, 2012) | 2020-09-10 |
| CN114096273A (zh) | 2022-02-25 |
| SG11202109566XA (en) | 2021-10-28 |
| KR20210135261A (ko) | 2021-11-12 |
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