BR112022005173A2 - Imunocitocina compreendendo complexo de proteína heterodimérica baseado em il-15/il-15ra, ácidos nucleicos, vetor, método célula hospedeira, composições e usos associados - Google Patents
Imunocitocina compreendendo complexo de proteína heterodimérica baseado em il-15/il-15ra, ácidos nucleicos, vetor, método célula hospedeira, composições e usos associadosInfo
- Publication number
- BR112022005173A2 BR112022005173A2 BR112022005173A BR112022005173A BR112022005173A2 BR 112022005173 A2 BR112022005173 A2 BR 112022005173A2 BR 112022005173 A BR112022005173 A BR 112022005173A BR 112022005173 A BR112022005173 A BR 112022005173A BR 112022005173 A2 BR112022005173 A2 BR 112022005173A2
- Authority
- BR
- Brazil
- Prior art keywords
- protein complex
- heterodimeric protein
- vector
- compositions
- nucleic acids
- Prior art date
Links
Classifications
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- 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
- A61K38/19—Cytokines; Lymphokines; Interferons
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- 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/5443—IL-15
-
- 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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
-
- 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
- A61K38/1793—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
-
- 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
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
- A61K38/2086—IL-13 to IL-16
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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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
- C07K14/7155—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons for interleukins [IL]
-
- 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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2827—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
-
- 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
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/515—Complete light chain, i.e. VL + CL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/522—CH1 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/524—CH2 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/526—CH3 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/53—Hinge
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- 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
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- 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
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Toxicology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cell Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
IMUNOCITOCINA COMPREENDENDO COMPLEXO DE PROTEÍNA HETERODIMÉRICA BASEADO EM IL-15/IL-15R?, ÁCIDOS NUCLEICOS, VETOR, MÉTODO CÉLULA HOSPEDEIRA, COMPOSIÇÕES E USOS ASSOCIADOS. A presente invenção refere-se a uma imunocitocina compreendendo um complexo proteico heterodimérico baseado em IL-15/IL-15Ra, e à sua utilização como agente terapêutico, em particular como agente para o tratamento de câncer e uma doença autoimune. A presente invenção refere-se ainda a uma imunocitocina compreendendo um complexo proteico heterodimérico baseado em uma IL-15/IL-15Ra e um anticorpo imunomodulador, e ao seu uso como agente terapêutico, em particular como agente para o tratamento de câncer e uma doença autoimune.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
RU2019129569A RU2753282C2 (ru) | 2019-09-19 | 2019-09-19 | ИММУНОЦИТОКИН, ВКЛЮЧАЮЩИЙ ГЕТЕРОДИМЕРНЫЙ БЕЛКОВЫЙ КОМПЛЕКС НА ОСНОВЕ IL-15/IL-15Rα, И ЕГО ПРИМЕНЕНИЕ |
PCT/RU2020/050233 WO2021054867A1 (ru) | 2019-09-19 | 2020-09-20 | Иммуноцитокин, включающий гетеро димерный белковый комплекс на основе il-15 и il-15rα |
Publications (1)
Publication Number | Publication Date |
---|---|
BR112022005173A2 true BR112022005173A2 (pt) | 2022-08-16 |
Family
ID=74873995
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
BR112022005173A BR112022005173A2 (pt) | 2019-09-19 | 2020-09-20 | Imunocitocina compreendendo complexo de proteína heterodimérica baseado em il-15/il-15ra, ácidos nucleicos, vetor, método célula hospedeira, composições e usos associados |
Country Status (18)
Country | Link |
---|---|
US (1) | US20230011234A1 (pt) |
EP (1) | EP4032539A4 (pt) |
JP (1) | JP2022549276A (pt) |
KR (1) | KR20220145323A (pt) |
CN (1) | CN115297885A (pt) |
AR (1) | AR120011A1 (pt) |
AU (1) | AU2020351560A1 (pt) |
BR (1) | BR112022005173A2 (pt) |
CA (1) | CA3151780A1 (pt) |
CO (1) | CO2022003156A2 (pt) |
JO (1) | JOP20220071A1 (pt) |
MA (1) | MA56286B1 (pt) |
MX (1) | MX2022003306A (pt) |
PE (1) | PE20220603A1 (pt) |
RU (1) | RU2753282C2 (pt) |
TW (1) | TW202124420A (pt) |
UY (1) | UY38889A (pt) |
WO (1) | WO2021054867A1 (pt) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113286812A (zh) | 2018-09-27 | 2021-08-20 | 西里欧发展公司 | 掩蔽型细胞因子多肽 |
WO2023133595A2 (en) | 2022-01-10 | 2023-07-13 | Sana Biotechnology, Inc. | Methods of ex vivo dosing and administration of lipid particles or viral vectors and related systems and uses |
CN115141283A (zh) * | 2022-03-10 | 2022-10-04 | 厦门柏慈生物科技有限公司 | 一种融合蛋白、制备方法及其应用 |
WO2023193015A1 (en) | 2022-04-01 | 2023-10-05 | Sana Biotechnology, Inc. | Cytokine receptor agonist and viral vector combination therapies |
CN116854821A (zh) * | 2022-08-15 | 2023-10-10 | 海徕科(北京)生物技术有限公司 | IL-15突变体-Fc/IL-15Rα亚基-Fc异源二聚体及其用途 |
Family Cites Families (30)
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US4634665A (en) | 1980-02-25 | 1987-01-06 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
US5179017A (en) | 1980-02-25 | 1993-01-12 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
US4510245A (en) | 1982-11-18 | 1985-04-09 | Chiron Corporation | Adenovirus promoter system |
US4740461A (en) | 1983-12-27 | 1988-04-26 | Genetics Institute, Inc. | Vectors and methods for transformation of eucaryotic cells |
US5168062A (en) | 1985-01-30 | 1992-12-01 | University Of Iowa Research Foundation | Transfer vectors and microorganisms containing human cytomegalovirus immediate-early promoter-regulatory DNA sequence |
GB2183662B (en) | 1985-04-01 | 1989-01-25 | Celltech Ltd | Transformed myeloma cell-line and a process for the expression of a gene coding for a eukaryotic polypeptide employing same |
US4968615A (en) | 1985-12-18 | 1990-11-06 | Ciba-Geigy Corporation | Deoxyribonucleic acid segment from a virus |
GB8601597D0 (en) | 1986-01-23 | 1986-02-26 | Wilson R H | Nucleotide sequences |
US4959455A (en) | 1986-07-14 | 1990-09-25 | Genetics Institute, Inc. | Primate hematopoietic growth factors IL-3 and pharmaceutical compositions |
US4912040A (en) | 1986-11-14 | 1990-03-27 | Genetics Institute, Inc. | Eucaryotic expression system |
IL85035A0 (en) | 1987-01-08 | 1988-06-30 | Int Genetic Eng | Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same |
GB8717430D0 (en) | 1987-07-23 | 1987-08-26 | Celltech Ltd | Recombinant dna product |
GB8809129D0 (en) | 1988-04-18 | 1988-05-18 | Celltech Ltd | Recombinant dna methods vectors and host cells |
EP1400536A1 (en) | 1991-06-14 | 2004-03-24 | Genentech Inc. | Method for making humanized antibodies |
US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
EP1777294A1 (en) | 2005-10-20 | 2007-04-25 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | IL-15Ralpha sushi domain as a selective and potent enhancer of IL-15 action through IL-15Rbeta/gamma, and hyperagonist (IL15Ralpha sushi -IL15) fusion proteins |
DK3327040T3 (da) * | 2010-09-21 | 2021-09-20 | Altor Bioscience Corp | Multimeriske opløselige il-15-fusionsmolekyler og fremgangsmåder til at fremstille og anvende samme |
EP2537933A1 (en) * | 2011-06-24 | 2012-12-26 | Institut National de la Santé et de la Recherche Médicale (INSERM) | An IL-15 and IL-15Ralpha sushi domain based immunocytokines |
SI3030575T1 (sl) | 2013-08-08 | 2018-11-30 | Cytune Pharma | Modulokini na osnovi IL-15 in IL-15R-alfa sushi domene |
RU2689717C2 (ru) * | 2014-01-08 | 2019-05-28 | Шанхай Хэнжуй Фармасьютикал Ко., Лтд. | Гетеродимерный белок il-15 и его применения |
EP3673915A1 (en) * | 2014-06-30 | 2020-07-01 | Altor BioScience Corporation | Il-15-based molecules and methods of use thereof |
PL3235830T3 (pl) | 2014-12-19 | 2020-12-14 | Jiangsu Hengrui Medicine Co., Ltd. | Kompleks białkowy interleukiny 15 i jego zastosowanie |
RU2656181C1 (ru) | 2016-07-13 | 2018-05-31 | Закрытое Акционерное Общество "Биокад" | Анти-pd-1-антитела, способ их получения и способ применения |
PE20191034A1 (es) | 2016-10-14 | 2019-08-05 | Xencor Inc | Proteinas de fusion heterodimericas biespecificas que contienen proteinas de fusion fc il-15/il-15r y fragmentos de anticuerpo pd-1 |
SG11201903306SA (en) * | 2016-10-21 | 2019-05-30 | Altor Bioscience Corp | Multimeric il-15-based molecules |
WO2018165208A1 (en) * | 2017-03-06 | 2018-09-13 | Altor Bioscience Corporation | Il-15-based fusions to il-12 and il-18 |
RU2665790C1 (ru) | 2017-04-17 | 2018-09-04 | Закрытое Акционерное Общество "Биокад" | Моноклональное антитело к pd-l1 |
CN111132733A (zh) | 2017-06-30 | 2020-05-08 | Xencor股份有限公司 | 含有IL-15/IL-15Rα和抗原结合结构域的靶向异源二聚体Fc融合蛋白 |
GB2580228B (en) * | 2017-07-03 | 2022-11-02 | Torque Therapeutics Inc | Immunostimulatory fusion molecules and uses thereof |
-
2019
- 2019-09-19 RU RU2019129569A patent/RU2753282C2/ru active
-
2020
- 2020-09-18 AR ARP200102607A patent/AR120011A1/es unknown
- 2020-09-20 JP JP2022518285A patent/JP2022549276A/ja active Pending
- 2020-09-20 WO PCT/RU2020/050233 patent/WO2021054867A1/ru active Application Filing
- 2020-09-20 KR KR1020227013100A patent/KR20220145323A/ko unknown
- 2020-09-20 JO JOP/2022/0071A patent/JOP20220071A1/ar unknown
- 2020-09-20 AU AU2020351560A patent/AU2020351560A1/en active Pending
- 2020-09-20 US US17/761,838 patent/US20230011234A1/en active Pending
- 2020-09-20 MX MX2022003306A patent/MX2022003306A/es unknown
- 2020-09-20 MA MA56286A patent/MA56286B1/fr unknown
- 2020-09-20 PE PE2022000447A patent/PE20220603A1/es unknown
- 2020-09-20 BR BR112022005173A patent/BR112022005173A2/pt unknown
- 2020-09-20 CN CN202080080165.8A patent/CN115297885A/zh active Pending
- 2020-09-20 CA CA3151780A patent/CA3151780A1/en active Pending
- 2020-09-20 EP EP20865705.6A patent/EP4032539A4/en active Pending
- 2020-09-21 TW TW109132634A patent/TW202124420A/zh unknown
- 2020-09-22 UY UY0001038889A patent/UY38889A/es unknown
-
2022
- 2022-03-18 CO CONC2022/0003156A patent/CO2022003156A2/es unknown
Also Published As
Publication number | Publication date |
---|---|
JP2022549276A (ja) | 2022-11-24 |
MA56286B1 (fr) | 2023-09-27 |
UY38889A (es) | 2021-04-30 |
US20230011234A1 (en) | 2023-01-12 |
RU2019129569A3 (pt) | 2021-03-19 |
RU2753282C2 (ru) | 2021-08-12 |
MA56286A1 (fr) | 2023-05-31 |
MX2022003306A (es) | 2022-04-26 |
PE20220603A1 (es) | 2022-04-25 |
KR20220145323A (ko) | 2022-10-28 |
CN115297885A (zh) | 2022-11-04 |
AU2020351560A1 (en) | 2022-11-24 |
CO2022003156A2 (es) | 2022-04-19 |
EP4032539A1 (en) | 2022-07-27 |
WO2021054867A1 (ru) | 2021-03-25 |
RU2019129569A (ru) | 2021-03-19 |
JOP20220071A1 (ar) | 2023-01-30 |
CA3151780A1 (en) | 2021-03-25 |
TW202124420A (zh) | 2021-07-01 |
AR120011A1 (es) | 2022-01-26 |
EP4032539A4 (en) | 2023-09-13 |
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