AR121008A1 - Quelatos macrocíclicos y sus usos - Google Patents

Quelatos macrocíclicos y sus usos

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Publication number
AR121008A1
AR121008A1 ARP210100041A ARP210100041A AR121008A1 AR 121008 A1 AR121008 A1 AR 121008A1 AR P210100041 A ARP210100041 A AR P210100041A AR P210100041 A ARP210100041 A AR P210100041A AR 121008 A1 AR121008 A1 AR 121008A1
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AR
Argentina
Prior art keywords
optionally substituted
alkylene
alkyl
heteroalkylene
independently
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ARP210100041A
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English (en)
Inventor
Stuart J Mahoney
Michael B Johansen
Matthew D Moran
Melissa Chass
Ryan W Simms
Eric S Burak
John F Valliant
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Fusion Pharmaceuticals Inc
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Publication of AR121008A1 publication Critical patent/AR121008A1/es

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    • 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
    • A61K47/6849—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 receptor, a cell surface antigen or a cell surface determinant
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A61K51/1027—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against receptors, cell-surface antigens or cell-surface determinants
    • A61K51/103—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against receptors, cell-surface antigens or cell-surface determinants against receptors for growth factors or receptors for growth regulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/0474—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group
    • A61K51/0482—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group chelates from cyclic ligands, e.g. DOTA
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A61K51/1045—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants
    • A61K51/1063—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants the tumor cell being from stomach or intestines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A61K51/1093—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody conjugates with carriers being antibodies
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/003—Compounds containing elements of Groups 3 or 13 of the Periodic Table without C-Metal linkages
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/003—Compounds containing elements of Groups 4 or 14 of the Periodic Table without C-Metal linkages
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Cell Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Oncology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicinal Preparation (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Reivindicación 1: Un compuesto que tiene la estructura de la fórmula (1) a continuación o un complejo metálico de esta o una sal farmacéuticamente aceptable de esta, caracterizado por que R¹, R² y R³ cada uno son, independientemente, -L-U, R⁴ es -X-W y R⁵ es H, -L-U o -X-W; o R¹, R², R³ y R⁴ cada uno son, independientemente, -L-U y R⁵ es -X-W; y n es un número entero de 0 - 3, cuando n es 0 y R⁵ es H, R¹, R³ y R⁴ no son todos iguales a el resto de fórmula (3), donde L es C=O o -CH(R)-, en el que R es H, alquilo opcionalmente sustituido, heteroalquilo opcionalmente sustituido o -L¹-Z¹-L²-Z²-B; U es arilo opcionalmente sustituido, heteroarilo opcionalmente sustituido, ácido carboxílico opcionalmente sustituido o ácido fosfónico opcionalmente sustituido; o -L-U es -L¹-Z¹-L²-Z²-B; al menos uno de R¹ - R³ tiene U como heteroarilo opcionalmente sustituido; X es C=O o alquileno C₁₋₃ opcionalmente sustituido; y W es una porción de donación capaz de coordinarse a un radiometal, donde la porción de donación es una hidroxipiridinona opcionalmente sustituida que tiene la estructura seleccionada del grupo que consiste en los compuestos del grupo de fórmulas (4) en el que V¹ es arilo o heteroarilo eliminado o fusionado, carbociclo o heterociclo fusionado, alquilo, éter, alcohol, ácido, éster, amida, fosfonato o sulfonato; y V² es H, alquilo o acilo, donde L¹ es enlace, alquileno C₁₋₆ opcionalmente sustituido o heteroalquileno C₁₋₆ opcionalmente sustituido; Z¹ es enlace, C=O(NR⁴), C=S(NR⁴), OC=O(NR⁴), NR⁴C=O(O), NR⁴C=O(NR⁴), -CH₂PhC=O(NR⁴), -CH₂Ph(NR⁴)C=O o -CH₂Ph(NH)C=S(NR⁴), cada R⁴ que es, independientemente, H, alquilo C₁₋₆ opcionalmente sustituido, heteroalquilo C₁₋₆ opcionalmente sustituido, o arilo o heteroarilo opcionalmente sustituido; L² es alquileno C₁₋₅₀ opcionalmente sustituido o heteroalquileno C₁₋₅₀ opcionalmente sustituido o polietilenglicol C₅₋₂₀; Z² es C=O, -NR’-(C=O)- o -NR’-(C=O)-R’’, R’ que es H o alquilo C₁₋₆ y R’’ que es alquileno C₁₋₂₀, heteroalquileno o arileno C₂₋₂₀; y B es una porción terapéutica, una porción dirigida o grupo de reticulación. Reivindicación 29: Un compuesto que tiene la estructura de la fórmula (1) a continuación o un complejo metálico de esta o una sal farmacéuticamente aceptable de esta, caracterizado por que R¹, R² y R³ cada uno son, independientemente, -L-U, R⁴ es -X-W y R⁵ es H, -L-U o -X-W; o R¹, R², R³ y R⁴ cada uno son, independientemente, -L-U y R⁵ es -X-W; y n es un número entero de 0 - 3, donde L es alquileno C₁₋₃ opcionalmente sustituido; U es ácido carboxílico opcionalmente sustituido o ácido fosfónico opcionalmente sustituido; W es una porción de donación capaz de coordinarse a un radiometal, en el que la porción de donación es una hidroxipiridinona opcionalmente sustituida o una porción seleccionada del grupo que consiste en los compuestos del grupo de fórmulas (5); m es un número entero de 1 - 3; y X es -L¹-Z¹-L²-N(R)-(C=O)-, en el que R es H, alquilo opcionalmente sustituido, heteroalquilo opcionalmente sustituido o -L³-Z²-B, donde L¹ y L² cada uno son, independientemente, enlace, alquileno C₁₋₆ opcionalmente sustituido o heteroalquileno C₁₋₆ opcionalmente sustituido; L³ es alquileno C₁₋₅₀ opcionalmente sustituido o heteroalquileno C₁₋₅₀ opcionalmente sustituido o polietilenglicol C₅₋₂₀; Z¹ es enlace, C=O(NR⁴), C=S(NR⁴), OC=O(NR⁴), NR⁴C=O(O), NR⁴C=O(NR⁴), -CH₂PhC=O(NR⁴), -CH₂Ph(NR⁴)C=O o -CH₂Ph(NH)C=S(NR⁴), cada R⁴ que es, independientemente, H, alquilo C₁₋₆ opcionalmente sustituido, heteroalquilo C₁₋₆ opcionalmente sustituido, o arilo o heteroarilo opcionalmente sustituido; Z² es C=O, -NR’-(C=O)- o -NR’-(C=O)-R’’, R’ que es H o alquilo C₁₋₆ y R’’ que es alquileno C₁₋₂₀, heteroalquileno o arileno C₂₋₂₀; y B es una porción terapéutica, una porción dirigida o grupo de reticulación. Reivindicación 58: Un compuesto que tiene la estructura de la fórmula (2) a continuación o un complejo metálico de esta o una sal farmacéuticamente aceptable de esta, caracterizado por que R¹, R² y R³ cada uno son, independientemente, -L-U y W es H o -L¹-Z¹-L²-Z²-B, donde L es C=O o -CH(R)-, en el que R es H, alquilo opcionalmente sustituido, heteroalquilo opcionalmente sustituido o -L¹-Z¹-L²-Z²-B; U es arilo opcionalmente sustituido, heteroarilo opcionalmente sustituido, ácido carboxílico opcionalmente sustituido o ácido fosfónico opcionalmente sustituido; o -L-U es -L¹-Z¹-L²-Z²-B; al menos uno de R¹ - R³ tiene U como heteroarilo opcionalmente sustituido; donde L¹ es enlace, alquileno C₁₋₆ opcionalmente sustituido o heteroalquileno C₁₋₆ opcionalmente sustituido; Z¹ es enlace, C=O(NR⁴), C=S(NR⁴), OC=O(NR⁴), NR⁴C=O(O), NR⁴C=O(NR⁴), -CH₂PhC=O(NR⁴), -CH₂Ph(NR⁴)C=O o -CH₂Ph(NH)C=S(NR⁴), cada R⁴ que es, independientemente, H, alquilo C₁₋₆ opcionalmente sustituido, heteroalquilo C₁₋₆ opcionalmente sustituido, o arilo o heteroarilo opcionalmente sustituido; L² es alquileno C₁₋₅₀ opcionalmente sustituido o heteroalquileno C₁₋₅₀ opcionalmente sustituido o polietilenglicol C₅₋₂₀; Z² es C=O, -NR’-(C=O)- o -NR’-(C=O)-R’’, R’ que es H o alquilo C₁₋₆ y R’’ que es alquileno C₁₋₂₀, heteroalquileno o arileno C₂₋₂₀; y B es una porción terapéutica, una porción dirigida o grupo de reticulación.
ARP210100041A 2020-01-10 2021-01-08 Quelatos macrocíclicos y sus usos AR121008A1 (es)

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EP (1) EP4087621A4 (es)
JP (1) JP2023510306A (es)
KR (1) KR20220139883A (es)
CN (1) CN115243729A (es)
AR (1) AR121008A1 (es)
AU (1) AU2021206242A1 (es)
BR (1) BR112022013678A2 (es)
CA (1) CA3167409A1 (es)
CL (1) CL2022001868A1 (es)
IL (1) IL294602A (es)
MX (1) MX2022008605A (es)
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EP4234540A1 (en) * 2020-10-22 2023-08-30 Nihon Medi-Physics Co., Ltd Method for producing radioactive zirconium complex
WO2023240135A2 (en) 2022-06-07 2023-12-14 Actinium Pharmaceuticals, Inc. Bifunctional chelators and conjugates
WO2024044552A1 (en) * 2022-08-22 2024-02-29 Abdera Therapeutics Inc. Vhh antibody dota conjugates
TW202421115A (zh) * 2022-08-22 2024-06-01 美商雅博得樂醫療公司 Vhh抗體結合物

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US6846915B2 (en) * 2001-08-13 2005-01-25 The Regents Of The University Of California Hydroxypyridonate and hydroxypyrimidinone chelating agents
US8926945B2 (en) * 2005-10-07 2015-01-06 Guerbet Compounds comprising a biological target recognizing part, coupled to a signal part capable of complexing gallium
FR2942227B1 (fr) * 2009-02-13 2011-04-15 Guerbet Sa Utilisation de tampons pour la complexation de radionucleides
GB201208309D0 (en) * 2012-05-11 2012-06-27 Algeta As Complexes
GB201417067D0 (en) * 2014-09-26 2014-11-12 South African Nuclear Energy Radiopharmaceutical conjugate
JP2020518673A (ja) * 2017-05-05 2020-06-25 フュージョン・ファーマシューティカルズ・インコーポレイテッド 二官能性キレートの薬物動態増強及びその使用
IL313115A (en) * 2017-05-05 2024-07-01 Centre For Probe Dev And Commercialization R1–IGF monoclonal antibodies and their use
US10093741B1 (en) * 2017-05-05 2018-10-09 Fusion Pharmaceuticals Inc. IGF-1R monoclonal antibodies and uses thereof

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WO2021142258A8 (en) 2022-08-18
JP2023510306A (ja) 2023-03-13
KR20220139883A (ko) 2022-10-17
EP4087621A1 (en) 2022-11-16
IL294602A (en) 2022-09-01
WO2021142258A1 (en) 2021-07-15
BR112022013678A2 (pt) 2022-11-16
CL2022001868A1 (es) 2023-04-14
AU2021206242A1 (en) 2022-08-25
US20210395281A1 (en) 2021-12-23
EP4087621A4 (en) 2024-01-17
CA3167409A1 (en) 2021-07-15
TW202140432A (zh) 2021-11-01
MX2022008605A (es) 2022-08-11

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