MX2023004377A - Acido nucleico que codifica una entidad anti-vegf y un regulador del complemento negativo y sus usos para el tratamiento de la degeneracion macular relacionada con la edad. - Google Patents
Acido nucleico que codifica una entidad anti-vegf y un regulador del complemento negativo y sus usos para el tratamiento de la degeneracion macular relacionada con la edad.Info
- Publication number
- MX2023004377A MX2023004377A MX2023004377A MX2023004377A MX2023004377A MX 2023004377 A MX2023004377 A MX 2023004377A MX 2023004377 A MX2023004377 A MX 2023004377A MX 2023004377 A MX2023004377 A MX 2023004377A MX 2023004377 A MX2023004377 A MX 2023004377A
- Authority
- MX
- Mexico
- Prior art keywords
- vegf
- entity
- treatment
- macular degeneration
- related macular
- Prior art date
Links
- 206010064930 age-related macular degeneration Diseases 0.000 title abstract 3
- 230000000295 complement effect Effects 0.000 title abstract 3
- 208000002780 macular degeneration Diseases 0.000 title abstract 3
- 150000007523 nucleic acids Chemical class 0.000 title 1
- 102000039446 nucleic acids Human genes 0.000 title 1
- 108020004707 nucleic acids Proteins 0.000 title 1
- 102000003689 Complement Factor I Human genes 0.000 abstract 2
- 108090000044 Complement Factor I Proteins 0.000 abstract 2
- 102000016550 Complement Factor H Human genes 0.000 abstract 1
- 108010053085 Complement Factor H Proteins 0.000 abstract 1
- 108091028043 Nucleic acid sequence Proteins 0.000 abstract 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 abstract 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 abstract 1
- 229960002833 aflibercept Drugs 0.000 abstract 1
- 108010081667 aflibercept Proteins 0.000 abstract 1
- 208000030533 eye disease Diseases 0.000 abstract 1
- 102000004169 proteins and genes Human genes 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/472—Complement proteins, e.g. anaphylatoxin, C3a, C5a
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- A61K38/1725—Complement proteins, e.g. anaphylatoxin, C3a or C5a
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
- A61K38/179—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- 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
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
-
- 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
- A61K48/0075—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the delivery route, e.g. oral, subcutaneous
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
- C07K14/4703—Inhibitors; Suppressors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- 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
- C12N15/1136—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 against growth factors, growth regulators, cytokines, lymphokines or hormones
-
- 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
- C12N15/86—Viral vectors
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/32—Fusion polypeptide fusions with soluble part of a cell surface receptor, "decoy receptors"
-
- 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
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14141—Use of virus, viral particle or viral elements as a vector
- C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- 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
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/48—Vector systems having a special element relevant for transcription regulating transport or export of RNA, e.g. RRE, PRE, WPRE, CTE
-
- 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
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/50—Vector systems having a special element relevant for transcription regulating RNA stability, not being an intron, e.g. poly A signal
-
- 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
- C12N2840/00—Vectors comprising a special translation-regulating system
- C12N2840/20—Vectors comprising a special translation-regulating system translation of more than one cistron
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)
- Molecular Biology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Gastroenterology & Hepatology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Toxicology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Virology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Ophthalmology & Optometry (AREA)
- Cell Biology (AREA)
- Marine Sciences & Fisheries (AREA)
- Endocrinology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
La presente invención se refiere a un producto que comprende (i) una entidad anti-VEGF; y (ii) un regulador del complemento negativo, o secuencias de nucleótidos que los codifican, como una preparación combinada para el uso simultáneo, separado o secuencial en terapia. En particular, la entidad anti-VEGF es un anticuerpo anti-VEGF, preferentemente, aflibercept, y el regulador del complemento negativo es Factor I del Complemento (CFI) o proteína 1 de tipo Factor H del Complemento (FHL1). Los principales usos son para el tratamiento de enfermedades oculares, en particular, degeneración macular relacionada con la edad (AMD).
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB2016463.8A GB202016463D0 (en) | 2020-10-16 | 2020-10-16 | Product |
GBGB2104148.8A GB202104148D0 (en) | 2021-03-24 | 2021-03-24 | Product |
PCT/GB2021/052689 WO2022079453A1 (en) | 2020-10-16 | 2021-10-18 | Nucleic acid encoding an anti-vegf entity and a negative complement regulator and uses thereof for the treatment of age-related macular degeneration |
Publications (1)
Publication Number | Publication Date |
---|---|
MX2023004377A true MX2023004377A (es) | 2023-06-28 |
Family
ID=78463555
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
MX2023004377A MX2023004377A (es) | 2020-10-16 | 2021-10-18 | Acido nucleico que codifica una entidad anti-vegf y un regulador del complemento negativo y sus usos para el tratamiento de la degeneracion macular relacionada con la edad. |
Country Status (14)
Country | Link |
---|---|
US (1) | US20230212275A1 (es) |
EP (1) | EP4229076A1 (es) |
JP (1) | JP2023545229A (es) |
KR (1) | KR20230088630A (es) |
AU (1) | AU2021362770A1 (es) |
CA (1) | CA3182337A1 (es) |
CL (1) | CL2023001072A1 (es) |
CO (1) | CO2023005981A2 (es) |
CR (1) | CR20230202A (es) |
DO (1) | DOP2023000076A (es) |
EC (1) | ECSP23034907A (es) |
IL (1) | IL298527A (es) |
MX (1) | MX2023004377A (es) |
WO (1) | WO2022079453A1 (es) |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8445267B2 (en) | 2007-04-09 | 2013-05-21 | University Of Florida Research Foundation, Inc. | Tyrosine-modified recombinant rAAV vector compositions and methods for use |
SG11201808426XA (en) * | 2016-04-15 | 2018-10-30 | Univ Pennsylvania | Compositions for treatment of wet age-related macular degeneration |
CN111788311A (zh) * | 2017-10-20 | 2020-10-16 | 双子治疗公司 | 用于治疗年龄相关性黄斑变性的组合物和方法 |
US20210093734A1 (en) | 2018-02-20 | 2021-04-01 | The Trustees Of The University Of Pennsylvania | Compositions for treatment of wet age-realted macular degeneration |
GB201821082D0 (en) * | 2018-12-21 | 2019-02-06 | Gyroscope Therapeutics Ltd | Combination of complement factors i and h, and vector encoding thereof |
MX2022004939A (es) * | 2019-10-23 | 2022-08-10 | Gemini Therapeutics Sub Inc | Metodos para tratar pacientes que tienen mutaciones de cfh con proteinas de cfh recombinantes. |
-
2021
- 2021-10-18 MX MX2023004377A patent/MX2023004377A/es unknown
- 2021-10-18 KR KR1020227041935A patent/KR20230088630A/ko unknown
- 2021-10-18 AU AU2021362770A patent/AU2021362770A1/en active Pending
- 2021-10-18 JP JP2022573176A patent/JP2023545229A/ja active Pending
- 2021-10-18 EP EP21801205.2A patent/EP4229076A1/en active Pending
- 2021-10-18 US US17/928,803 patent/US20230212275A1/en active Pending
- 2021-10-18 IL IL298527A patent/IL298527A/en unknown
- 2021-10-18 CR CR20230202A patent/CR20230202A/es unknown
- 2021-10-18 CA CA3182337A patent/CA3182337A1/en active Pending
- 2021-10-18 WO PCT/GB2021/052689 patent/WO2022079453A1/en active Application Filing
-
2023
- 2023-04-14 CL CL2023001072A patent/CL2023001072A1/es unknown
- 2023-04-14 DO DO2023000076A patent/DOP2023000076A/es unknown
- 2023-05-10 CO CONC2023/0005981A patent/CO2023005981A2/es unknown
- 2023-05-11 EC ECSENADI202334907A patent/ECSP23034907A/es unknown
Also Published As
Publication number | Publication date |
---|---|
WO2022079453A1 (en) | 2022-04-21 |
ECSP23034907A (es) | 2023-06-30 |
JP2023545229A (ja) | 2023-10-27 |
AU2021362770A1 (en) | 2022-12-08 |
CL2023001072A1 (es) | 2023-12-01 |
DOP2023000076A (es) | 2023-06-15 |
CR20230202A (es) | 2023-06-13 |
EP4229076A1 (en) | 2023-08-23 |
IL298527A (en) | 2023-01-01 |
CO2023005981A2 (es) | 2023-05-29 |
KR20230088630A (ko) | 2023-06-20 |
CA3182337A1 (en) | 2022-04-21 |
US20230212275A1 (en) | 2023-07-06 |
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