MA44207B1 - Immunoglobulines conjuguées cys80 - Google Patents

Immunoglobulines conjuguées cys80

Info

Publication number
MA44207B1
MA44207B1 MA44207A MA44207A MA44207B1 MA 44207 B1 MA44207 B1 MA 44207B1 MA 44207 A MA44207 A MA 44207A MA 44207 A MA44207 A MA 44207A MA 44207 B1 MA44207 B1 MA 44207B1
Authority
MA
Morocco
Prior art keywords
immunoglobulins
chain variable
cys80
conjugated
immunoglobulin
Prior art date
Application number
MA44207A
Other languages
English (en)
Other versions
MA44207A (fr
Inventor
Jared Spidel
Earl Albone
Luigi Grasso
James Kline
Original Assignee
Eisai R&D Man Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Eisai R&D Man Co Ltd filed Critical Eisai R&D Man Co Ltd
Publication of MA44207A publication Critical patent/MA44207A/fr
Publication of MA44207B1 publication Critical patent/MA44207B1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
    • 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
    • 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
    • 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
    • A61K47/6891—Pre-targeting systems involving an antibody for targeting specific cells
    • A61K47/6897—Pre-targeting systems with two or three steps using antibody conjugates; Ligand-antiligand therapies
    • A61K47/6898—Pre-targeting systems with two or three steps using antibody conjugates; Ligand-antiligand therapies using avidin- or biotin-conjugated antibodies
    • 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
    • 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
    • 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
    • C07K16/2851—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 lectin superfamily, e.g. CD23, CD72
    • 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
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/531—Production of immunochemical test materials
    • G01N33/532—Production of labelled immunochemicals
    • G01N33/533—Production of labelled immunochemicals with fluorescent label
    • 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
    • A61K2039/507—Comprising a combination of two or more separate antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • 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
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/567—Framework region [FR]
    • 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
    • C07K2317/90—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

Abstract

La présente invention concerne des procédés de génération d'immunoglobulines conjuguées, le procédé comprenant : le décoiffage d'une cystéine à la position d'acide aminé 80 ("cys80") dans une région variable de chaîne légère d'une immunoglobuline, l'immunoglobuline comprenant une région variable de chaîne lourde et la région variable de chaîne légère ; et la conjugaison d'un composé réactif avec thiol avec cys80, le composé réactif avec thiol comprenant un groupe réactif avec thiol. L'invention concerne en outre des molécules de liaison d'antigène et des procédés de génération de celles-ci, des immunoglobulines ainsi que des molécules d'acide nucléique codant pour les immunoglobulines et des cellules hôtes comprenant les molécules d'acide nucléique, des immunoglobulines conjuguées, et des régions variables de chaîne légère pour utilisation dans une immunoglobuline conjuguée.
MA44207A 2015-06-19 2016-06-17 Immunoglobulines conjuguées cys80 MA44207B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201562182020P 2015-06-19 2015-06-19
PCT/US2016/038041 WO2016205618A1 (fr) 2015-06-19 2016-06-17 Immunoglobulines conjuguées cys80

Publications (2)

Publication Number Publication Date
MA44207A MA44207A (fr) 2018-12-26
MA44207B1 true MA44207B1 (fr) 2020-11-30

Family

ID=56404289

Family Applications (1)

Application Number Title Priority Date Filing Date
MA44207A MA44207B1 (fr) 2015-06-19 2016-06-17 Immunoglobulines conjuguées cys80

Country Status (33)

Country Link
US (3) US10273310B2 (fr)
EP (2) EP3795591B1 (fr)
JP (2) JP6823606B2 (fr)
KR (1) KR20180021807A (fr)
CN (1) CN107949575B (fr)
AU (1) AU2016280190B9 (fr)
BR (1) BR112017027252A2 (fr)
CA (1) CA2989637C (fr)
CL (1) CL2017003273A1 (fr)
CO (1) CO2017013303A2 (fr)
CY (1) CY1123481T1 (fr)
DK (2) DK3310816T3 (fr)
ES (2) ES2829251T3 (fr)
HK (1) HK1252625A1 (fr)
HR (1) HRP20201489T1 (fr)
HU (2) HUE064407T2 (fr)
IL (1) IL256263B (fr)
LT (1) LT3310816T (fr)
MA (1) MA44207B1 (fr)
MD (1) MD3310816T2 (fr)
MX (1) MX2017016674A (fr)
MY (1) MY189024A (fr)
PE (1) PE20180498A1 (fr)
PH (1) PH12017502352A1 (fr)
PL (1) PL3310816T3 (fr)
PT (1) PT3310816T (fr)
RS (1) RS60943B1 (fr)
RU (1) RU2756101C2 (fr)
SG (1) SG10201913935RA (fr)
SI (1) SI3310816T1 (fr)
UA (1) UA124830C2 (fr)
WO (1) WO2016205618A1 (fr)
ZA (2) ZA201708619B (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4055053A1 (fr) 2019-11-07 2022-09-14 Eisai R&D Management Co., Ltd. Conjugués anticorps-médicament d'éribuline dirigés contre la mésothéline et procédés d'utilisation
JP7399305B2 (ja) * 2020-02-12 2023-12-15 イーライ リリー アンド カンパニー 抗体または抗原結合フラグメントの結晶化
CA3184645A1 (fr) 2020-06-05 2021-12-09 Eisai R&D Management Co., Ltd. Conjugues anticorps anti-bcma-medicament et procedes d'utilisation
CN112694521B (zh) * 2020-12-02 2023-01-17 杭州百凌生物科技有限公司 一种人工多肽lh、其抗体及在病理检测中的应用

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CN1187094C (zh) * 1998-04-28 2005-02-02 应用研究系统Ars股份公司 多元醇干扰素β偶联物
US6904369B1 (en) * 2000-06-29 2005-06-07 The Trustees Of Columbia University In The City Of New York Conjugated ligands for the stimulation of blood cell proliferation by effecting dimerization of the receptor for stem cell factor
US7402409B2 (en) 2003-01-23 2008-07-22 Epitomics, Inc. Cell fusion method
AU2003259718A1 (en) 2003-08-07 2005-03-07 Epitomics, Inc. Methods for humanizing rabbit monoclonal antibodies
WO2006017759A2 (fr) * 2004-08-05 2006-02-16 Kirin Brewery Co., Ltd. Anticorps fixant le marqueur specifique des cellules endotheliales (tem1) et leurs utilisations
NZ580115A (en) 2004-09-23 2010-10-29 Genentech Inc Cysteine engineered antibody light chains and conjugates
GB0428012D0 (en) * 2004-12-22 2005-01-26 Hammersmith Imanet Ltd Radiolabelling methods
JP5791895B2 (ja) * 2007-05-04 2015-10-07 テクノファージ， インベスティガサン エ デセンボルビメント エム ビオテクノロジア，エスエー 遺伝子操作されたウサギ抗体可変ドメイン及びその使用
EP2162469A4 (fr) * 2007-05-21 2012-08-01 Alderbio Holdings Llc Nouveaux procedes d'humanisation d'anticorps de lapin et anticorps de lapin humanises
US20110033378A1 (en) * 2008-01-18 2011-02-10 Medlmmune, Llc. Cysteine Engineered Antibodies For Site-Specific Conjugation
EP2842575B1 (fr) 2008-03-18 2017-09-27 Seattle Genetics, Inc. Conjugués lieurs de médicament auristatin
WO2010118203A2 (fr) 2009-04-09 2010-10-14 Morphotek, Inc. Molécules de liaison à l'endosialine
CN114246952A (zh) * 2010-06-08 2022-03-29 基因泰克公司 半胱氨酸改造的抗体和偶联物
AR082205A1 (es) * 2010-07-12 2012-11-21 Covx Technologies Ireland Ltd Conjugados de anticuerpos multifuncionales
CN102008732B (zh) * 2010-11-08 2012-10-24 武汉华耀生物医药有限公司 一种叶酸偶联抗体药物及其制备方法与应用
CA2882753C (fr) 2012-08-21 2021-08-24 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anticorps monoclonaux specifiques au domaine de la mesotheline et utilisation de ces derniers
RS58928B1 (sr) * 2012-08-29 2019-08-30 Hoffmann La Roche Transporter za krvno-moždanu barijeru
EP3892294A1 (fr) 2013-08-28 2021-10-13 AbbVie Stemcentrx LLC Procédés et compositions de conjugaison d'anticorps spécifique à un site

Also Published As

Publication number Publication date
IL256263B (en) 2022-06-01
PH12017502352A1 (en) 2018-06-25
PE20180498A1 (es) 2018-03-09
MX2017016674A (es) 2018-08-01
AU2016280190B9 (en) 2022-05-19
JP6823606B2 (ja) 2021-02-03
AU2016280190B2 (en) 2022-04-28
CN107949575A (zh) 2018-04-20
DK3310816T3 (da) 2020-10-12
HUE051315T2 (hu) 2021-03-01
ZA201708619B (en) 2022-11-30
ES2967613T3 (es) 2024-05-03
KR20180021807A (ko) 2018-03-05
RU2017146220A (ru) 2019-07-19
LT3310816T (lt) 2020-11-25
US20190202933A1 (en) 2019-07-04
HK1252625A1 (zh) 2019-05-31
CY1123481T1 (el) 2022-03-24
IL256263A (en) 2018-02-28
HRP20201489T1 (hr) 2020-12-11
NZ738496A (en) 2023-08-25
RU2756101C2 (ru) 2021-09-28
CO2017013303A2 (es) 2018-03-20
US11129904B2 (en) 2021-09-28
MY189024A (en) 2022-01-20
SG10201913935RA (en) 2020-03-30
ZA202102093B (en) 2023-03-29
PT3310816T (pt) 2020-10-19
US20230001004A1 (en) 2023-01-05
EP3310816A1 (fr) 2018-04-25
BR112017027252A2 (pt) 2018-08-28
JP7042876B2 (ja) 2022-03-28
EP3310816B1 (fr) 2020-09-09
RS60943B1 (sr) 2020-11-30
MD3310816T2 (ro) 2021-01-31
UA124830C2 (uk) 2021-12-01
MA44207A (fr) 2018-12-26
HUE064407T2 (hu) 2024-03-28
US10273310B2 (en) 2019-04-30
SI3310816T1 (sl) 2020-12-31
CA2989637A1 (fr) 2016-12-22
CN107949575B (zh) 2022-03-08
US20160369011A1 (en) 2016-12-22
EP3795591B1 (fr) 2023-09-27
CA2989637C (fr) 2023-01-10
CL2017003273A1 (es) 2018-12-21
ES2829251T3 (es) 2021-05-31
JP2020178717A (ja) 2020-11-05
WO2016205618A1 (fr) 2016-12-22
RU2017146220A3 (fr) 2019-11-07
PL3310816T3 (pl) 2020-12-14
AU2016280190A1 (en) 2018-01-18
EP3795591A1 (fr) 2021-03-24
DK3795591T3 (da) 2024-01-02
JP2018526975A (ja) 2018-09-20

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