CO2023014681A2 - Composiciones y métodos para inhibir la expresión del componente 3 del complemento - Google Patents
Composiciones y métodos para inhibir la expresión del componente 3 del complementoInfo
- Publication number
- CO2023014681A2 CO2023014681A2 CONC2023/0014681A CO2023014681A CO2023014681A2 CO 2023014681 A2 CO2023014681 A2 CO 2023014681A2 CO 2023014681 A CO2023014681 A CO 2023014681A CO 2023014681 A2 CO2023014681 A2 CO 2023014681A2
- Authority
- CO
- Colombia
- Prior art keywords
- expression
- methods
- complement component
- inhibiting
- compositions
- Prior art date
Links
- 102000016918 Complement C3 Human genes 0.000 title abstract 2
- 108010028780 Complement C3 Proteins 0.000 title abstract 2
- 238000000034 method Methods 0.000 title abstract 2
- 230000002401 inhibitory effect Effects 0.000 title 1
- 239000000203 mixture Substances 0.000 title 1
- 108091034117 Oligonucleotide Proteins 0.000 abstract 5
- 108091030071 RNAI Proteins 0.000 abstract 3
- 230000009368 gene silencing by RNA Effects 0.000 abstract 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 2
- 230000004913 activation Effects 0.000 abstract 1
- 230000000692 anti-sense effect Effects 0.000 abstract 1
- 230000024203 complement activation Effects 0.000 abstract 1
- 230000003831 deregulation Effects 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000035475 disorder Diseases 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 230000001404 mediated effect Effects 0.000 abstract 1
- 108020004999 messenger RNA Proteins 0.000 abstract 1
- 238000011321 prophylaxis Methods 0.000 abstract 1
- 238000011282 treatment Methods 0.000 abstract 1
Classifications
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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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/321—2'-O-R Modification
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/322—2'-R Modification
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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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/344—Position-specific modifications, e.g. on every purine, at the 3'-end
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/352—Nature of the modification linked to the nucleic acid via a carbon atom
- C12N2310/3521—Methyl
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/353—Nature of the modification linked to the nucleic acid via an atom other than carbon
- C12N2310/3533—Halogen
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/50—Physical structure
- C12N2310/53—Physical structure partially self-complementary or closed
- C12N2310/531—Stem-loop; Hairpin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Psychiatry (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Transplantation (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202163177254P | 2021-04-20 | 2021-04-20 | |
| PCT/US2022/025648 WO2022226127A1 (en) | 2021-04-20 | 2022-04-20 | Compositions and methods for inhibiting complement component 3 expression |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CO2023014681A2 true CO2023014681A2 (es) | 2024-01-25 |
Family
ID=83723122
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CONC2023/0014681A CO2023014681A2 (es) | 2021-04-20 | 2023-10-30 | Composiciones y métodos para inhibir la expresión del componente 3 del complemento |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20250002908A1 (https=) |
| EP (1) | EP4326876A4 (https=) |
| JP (2) | JP2024515344A (https=) |
| KR (1) | KR20230173116A (https=) |
| CN (1) | CN117295819A (https=) |
| AU (1) | AU2022261922A1 (https=) |
| BR (1) | BR112023021703A2 (https=) |
| CA (1) | CA3177629A1 (https=) |
| CO (1) | CO2023014681A2 (https=) |
| IL (1) | IL307721A (https=) |
| MX (1) | MX2023012385A (https=) |
| WO (1) | WO2022226127A1 (https=) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI868755B (zh) | 2022-06-24 | 2025-01-01 | 丹麥商諾佛 儂迪克股份有限公司 | 抑制跨膜絲胺酸蛋白酶６（ｔｍｐｒｓｓ６）表現的組成物及方法 |
| WO2024169907A1 (zh) * | 2023-02-17 | 2024-08-22 | 苏州时安生物技术有限公司 | 一种调节补体C3表达的siRNA、其缀合物和药物组合物及用途 |
| CN121488036A (zh) * | 2023-07-21 | 2026-02-06 | 上海舶望制药有限公司 | 用于抑制补体成分3(c3)表达的组合物和方法 |
| WO2025168134A1 (zh) * | 2024-02-08 | 2025-08-14 | 北京安龙生物医药有限公司 | 靶向补体成分c3基因的寡核苷酸及其用途 |
| CN121154665B (zh) * | 2025-11-21 | 2026-02-27 | 天津医科大学第二医院 | 尿苷在防治糖尿病肾病药物开发过程中及药物中的应用 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2305812A3 (en) * | 2002-11-14 | 2012-06-06 | Dharmacon, Inc. | Fuctional and hyperfunctional sirna |
| WO2007064846A2 (en) * | 2005-11-30 | 2007-06-07 | Intradigm Corporation | COMPOSITIONS AND METHODS OF USING siRNA TO KNOCKDOWN GENE EXPRESSION AND TO IMPROVE SOLID ORGAN AND CELL TRANSPLANTATION |
| WO2010042755A2 (en) * | 2008-10-08 | 2010-04-15 | Chimeros Inc. | Chimeric therapeutics, compositions, and methods for using same |
| SG10201804960RA (en) * | 2013-12-12 | 2018-07-30 | Alnylam Pharmaceuticals Inc | Complement component irna compositions and methods of use thereof |
| RU2019113301A (ru) * | 2016-10-17 | 2020-11-17 | Апеллис Фармасьютикалс, Инк. | Комбинированная терапия для ингибирования с3 |
| AU2018360697A1 (en) * | 2017-11-01 | 2020-05-14 | Alnylam Pharmaceuticals, Inc. | Complement component C3 iRNA compositions and methods of use thereof |
| CA3119234A1 (en) * | 2018-11-23 | 2020-05-28 | Silence Therapeutics Gmbh | Nucleic acids for inhibiting expression of c3 in a cell |
| EP4022060A1 (en) * | 2019-08-27 | 2022-07-06 | Silence Therapeutics GmbH | Nucleic acids for inhibiting expression of c3 in a cell |
| TW202134435A (zh) * | 2019-10-22 | 2021-09-16 | 美商阿尼拉製藥公司 | 補體成分ｃ３ ｉｒｎａ組成物及其使用方法 |
| CN115335524A (zh) * | 2020-02-14 | 2022-11-11 | 阿佩利斯制药有限公司 | 用于补体抑制的rna |
| MX2023008469A (es) * | 2021-01-22 | 2023-11-22 | Alnylam Pharmaceuticals Inc | Oligonucleotidos de doble hebra modificados. |
| WO2022251484A1 (en) * | 2021-05-26 | 2022-12-01 | Apellis Pharmaceuticals, Inc. | Treatment of complement-mediated disorders |
-
2022
- 2022-04-20 WO PCT/US2022/025648 patent/WO2022226127A1/en not_active Ceased
- 2022-04-20 CN CN202280034163.4A patent/CN117295819A/zh active Pending
- 2022-04-20 MX MX2023012385A patent/MX2023012385A/es unknown
- 2022-04-20 KR KR1020237036421A patent/KR20230173116A/ko active Pending
- 2022-04-20 AU AU2022261922A patent/AU2022261922A1/en active Pending
- 2022-04-20 CA CA3177629A patent/CA3177629A1/en active Pending
- 2022-04-20 IL IL307721A patent/IL307721A/en unknown
- 2022-04-20 US US18/287,260 patent/US20250002908A1/en active Pending
- 2022-04-20 JP JP2023564255A patent/JP2024515344A/ja active Pending
- 2022-04-20 BR BR112023021703A patent/BR112023021703A2/pt unknown
- 2022-04-20 EP EP22792454.5A patent/EP4326876A4/en active Pending
-
2023
- 2023-10-30 CO CONC2023/0014681A patent/CO2023014681A2/es unknown
-
2025
- 2025-04-15 JP JP2025066627A patent/JP2025100729A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| BR112023021703A2 (pt) | 2024-01-30 |
| WO2022226127A1 (en) | 2022-10-27 |
| EP4326876A1 (en) | 2024-02-28 |
| KR20230173116A (ko) | 2023-12-26 |
| JP2025100729A (ja) | 2025-07-03 |
| US20250002908A1 (en) | 2025-01-02 |
| CN117295819A (zh) | 2023-12-26 |
| IL307721A (en) | 2023-12-01 |
| CA3177629A1 (en) | 2022-10-27 |
| AU2022261922A1 (en) | 2023-10-26 |
| JP2024515344A (ja) | 2024-04-09 |
| EP4326876A4 (en) | 2026-04-08 |
| MX2023012385A (es) | 2024-02-07 |
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