BR112022004863A2 - Composição conjugado de ligante fármaco, compostos conjugado de ligante-fármaco e conector de fármaco, e, formulação farmaceuticamente aceitável - Google Patents
Composição conjugado de ligante fármaco, compostos conjugado de ligante-fármaco e conector de fármaco, e, formulação farmaceuticamente aceitávelInfo
- Publication number
- BR112022004863A2 BR112022004863A2 BR112022004863A BR112022004863A BR112022004863A2 BR 112022004863 A2 BR112022004863 A2 BR 112022004863A2 BR 112022004863 A BR112022004863 A BR 112022004863A BR 112022004863 A BR112022004863 A BR 112022004863A BR 112022004863 A2 BR112022004863 A2 BR 112022004863A2
- Authority
- BR
- Brazil
- Prior art keywords
- drug
- linker
- conjugate
- pharmaceutically acceptable
- acceptable formulation
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/545—Heterocyclic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/6807—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug or compound being a sugar, nucleoside, nucleotide, nucleic acid, e.g. RNA antisense
- A61K47/6809—Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
- A61K47/6817—Toxins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Organic Chemistry (AREA)
- Cell Biology (AREA)
- Toxicology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (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
composição conjugado de ligante fármaco, compostos conjugado de ligante-fármaco e conector de fármaco, e, formulação farmaceuticamente aceitável. a invenção refere-se a conjugados de compostos biologicamente ativos, em que tal conjugado é composto por uma sequência de aminoácidos contendo um tripeptídeo que confere clivagem seletiva por homogenato de tecido tumoral para liberação de fármaco livre e/ou melhora a biodistribuição no tecido tumoral em comparação com homogeneizado de tecido normal da mesma espécie, em que o tecido normal é o sítio de um evento adverso associado à administração a um indivíduo humano que necessite do mesmo de uma quantidade terapeuticamente eficaz de um conjugado comparador cuja sequência de aminoácidos é um dipeptídeo conhecido por ser seletivamente clivável por catepsina b.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201962902888P | 2019-09-19 | 2019-09-19 | |
PCT/US2020/051648 WO2021055865A1 (en) | 2019-09-19 | 2020-09-18 | Selective drug release from internalized conjugates of biologically active compounds |
Publications (1)
Publication Number | Publication Date |
---|---|
BR112022004863A2 true BR112022004863A2 (pt) | 2022-06-07 |
Family
ID=72744895
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
BR112022004863A BR112022004863A2 (pt) | 2019-09-19 | 2020-09-18 | Composição conjugado de ligante fármaco, compostos conjugado de ligante-fármaco e conector de fármaco, e, formulação farmaceuticamente aceitável |
Country Status (13)
Country | Link |
---|---|
US (1) | US20210138077A1 (pt) |
EP (1) | EP4031186A1 (pt) |
JP (1) | JP2022548306A (pt) |
KR (1) | KR20220084056A (pt) |
CN (1) | CN114728073A (pt) |
AR (1) | AR120079A1 (pt) |
AU (1) | AU2020348876A1 (pt) |
BR (1) | BR112022004863A2 (pt) |
CA (1) | CA3155093A1 (pt) |
IL (1) | IL291422A (pt) |
MX (1) | MX2022003268A (pt) |
TW (1) | TW202126334A (pt) |
WO (1) | WO2021055865A1 (pt) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA3200974A1 (en) | 2020-11-08 | 2022-05-12 | Seagen Inc. | Combination therapy |
US11571481B2 (en) | 2020-12-21 | 2023-02-07 | Cornell University | Peptide-linked drug delivery system |
JP2024511360A (ja) * | 2021-03-18 | 2024-03-13 | シージェン インコーポレイテッド | 生体活性化合物の内部移行複合体からの選択的薬物放出 |
MX2023010902A (es) * | 2021-03-18 | 2023-09-27 | Seagen Inc | Liberacion selectiva de farmacos a partir de conjugados internalizados de compuestos biologicamente activos. |
EP4321522A1 (en) | 2022-08-12 | 2024-02-14 | Seagen Inc. | Cytotoxic compounds and conjugates thereof |
Family Cites Families (27)
Publication number | Priority date | Publication date | Assignee | Title |
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GB2036891B (en) | 1978-12-05 | 1983-05-05 | Windsor Smith C | Change speed gear |
GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
JPS6147500A (ja) | 1984-08-15 | 1986-03-07 | Res Dev Corp Of Japan | キメラモノクロ−ナル抗体及びその製造法 |
EP0173494A3 (en) | 1984-08-27 | 1987-11-25 | The Board Of Trustees Of The Leland Stanford Junior University | Chimeric receptors by dna splicing and expression |
GB8422238D0 (en) | 1984-09-03 | 1984-10-10 | Neuberger M S | Chimeric proteins |
JPS61134325A (ja) | 1984-12-04 | 1986-06-21 | Teijin Ltd | ハイブリツド抗体遺伝子の発現方法 |
AU606320B2 (en) | 1985-11-01 | 1991-02-07 | International Genetic Engineering, Inc. | Modular assembly of antibody genes, antibodies prepared thereby and use |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
AU728657B2 (en) | 1996-03-18 | 2001-01-18 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
NZ520458A (en) * | 2000-02-24 | 2005-02-25 | Genentech Inc | Caspase activated prodrugs therapy |
US20030083263A1 (en) | 2001-04-30 | 2003-05-01 | Svetlana Doronina | Pentapeptide compounds and uses related thereto |
US6884869B2 (en) | 2001-04-30 | 2005-04-26 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
DK2357006T3 (en) | 2002-07-31 | 2015-12-21 | Seattle Genetics Inc | Drug conjugates and their use for treating cancer, an autoimmune disease or an infectious disease |
CN1938046B (zh) | 2003-11-06 | 2014-03-19 | 西雅图基因公司 | 能够与配体偶联的单甲基缬氨酸化合物 |
WO2005082023A2 (en) | 2004-02-23 | 2005-09-09 | Genentech, Inc. | Heterocyclic self-immolative linkers and conjugates |
WO2007008848A2 (en) | 2005-07-07 | 2007-01-18 | Seattle Genetics, Inc. | Monomethylvaline compounds having phenylalanine carboxy modifications at the c-terminus |
EP3498289A1 (en) | 2005-07-07 | 2019-06-19 | Seattle Genetics, Inc. | Monomethylvaline compounds having phenylalanine side-chain modifications at the c-terminus |
DK3248613T3 (da) | 2005-07-18 | 2022-03-14 | Seagen Inc | Beta-glucuronid-lægemiddel-linkerkonjugater |
EP2265283B1 (en) | 2008-03-18 | 2014-09-03 | Seattle Genetics, Inc. | Auristatin drug linker conjugates |
AU2014337555C1 (en) | 2013-10-15 | 2021-01-28 | Seagen Inc. | PEGylated drug-linkers for improved Ligand-Drug Conjugate pharmacokinetics |
WO2016080626A2 (en) * | 2014-11-20 | 2016-05-26 | Pharosgen | Prodrugs activated by caspase |
EP3620471A4 (en) * | 2017-05-02 | 2021-01-06 | National Cancer Center Japan | ANTIBODY-ANTI-FIBRIN DRUG CONJUGATE INSOLUBLE, POSSIBLE TO BE CLIVID BY PLASMINE |
WO2018218004A1 (en) * | 2017-05-24 | 2018-11-29 | The Board Of Regents Of The University Of Texas System | Linkers for antibody drug conjugates |
US20230158141A1 (en) * | 2017-11-08 | 2023-05-25 | Yafei Shanghai Biolog Medicine Science & Technolog Co., Ltd | Conjugates of Biomolecule and Use Thereof |
EP3719032A4 (en) * | 2017-12-01 | 2021-09-01 | Good T Cells, Inc. | COMPOSITION FOR THE PREVENTION OR TREATMENT OF HAIR LOSS |
-
2020
- 2020-09-18 AU AU2020348876A patent/AU2020348876A1/en active Pending
- 2020-09-18 MX MX2022003268A patent/MX2022003268A/es unknown
- 2020-09-18 JP JP2022517783A patent/JP2022548306A/ja active Pending
- 2020-09-18 EP EP20786166.7A patent/EP4031186A1/en active Pending
- 2020-09-18 KR KR1020227012938A patent/KR20220084056A/ko unknown
- 2020-09-18 WO PCT/US2020/051648 patent/WO2021055865A1/en unknown
- 2020-09-18 US US17/026,048 patent/US20210138077A1/en active Pending
- 2020-09-18 CN CN202080079500.2A patent/CN114728073A/zh active Pending
- 2020-09-18 CA CA3155093A patent/CA3155093A1/en active Pending
- 2020-09-18 BR BR112022004863A patent/BR112022004863A2/pt unknown
- 2020-09-18 TW TW109132465A patent/TW202126334A/zh unknown
- 2020-09-18 AR ARP200102602A patent/AR120079A1/es unknown
-
2022
- 2022-03-16 IL IL291422A patent/IL291422A/en unknown
Also Published As
Publication number | Publication date |
---|---|
IL291422A (en) | 2022-05-01 |
US20210138077A1 (en) | 2021-05-13 |
AU2020348876A1 (en) | 2022-04-07 |
CN114728073A (zh) | 2022-07-08 |
JP2022548306A (ja) | 2022-11-17 |
KR20220084056A (ko) | 2022-06-21 |
TW202126334A (zh) | 2021-07-16 |
CA3155093A1 (en) | 2021-03-25 |
MX2022003268A (es) | 2022-06-02 |
EP4031186A1 (en) | 2022-07-27 |
AR120079A1 (es) | 2022-02-02 |
WO2021055865A1 (en) | 2021-03-25 |
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