CN113543812A - 具有巯基多重接头的adc - Google Patents

具有巯基多重接头的adc Download PDF

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Publication number
CN113543812A
CN113543812A CN201980085333.XA CN201980085333A CN113543812A CN 113543812 A CN113543812 A CN 113543812A CN 201980085333 A CN201980085333 A CN 201980085333A CN 113543812 A CN113543812 A CN 113543812A
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CN
China
Prior art keywords
group
antibody
drug
mla
adc
Prior art date
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Pending
Application number
CN201980085333.XA
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English (en)
Chinese (zh)
Inventor
S·杰弗瑞
王坤鹏
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Xijin Co
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Xijin Co
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Filing date
Publication date
Application filed by Xijin Co filed Critical Xijin Co
Publication of CN113543812A publication Critical patent/CN113543812A/zh
Pending legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2878—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • 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
    • 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
    • A61K47/68031—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being an auristatin
    • 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
    • A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
    • 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
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/44—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members
    • C07D207/444—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5
    • C07D207/448—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. maleimide
    • C07D207/452—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. maleimide with hydrocarbon radicals, substituted by hetero atoms, directly attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/36—Seven-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • 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
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515—Complete light chain, i.e. VL + CL

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Cell Biology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Plural Heterocyclic Compounds (AREA)
CN201980085333.XA 2018-12-21 2019-12-20 具有巯基多重接头的adc Pending CN113543812A (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201862783582P 2018-12-21 2018-12-21
US201862783707P 2018-12-21 2018-12-21
US62/783,582 2018-12-21
US62/783,707 2018-12-21
PCT/US2019/068178 WO2020132655A1 (en) 2018-12-21 2019-12-20 Adcs with thiol multiplex linkers

Publications (1)

Publication Number Publication Date
CN113543812A true CN113543812A (zh) 2021-10-22

Family

ID=71101991

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201980085333.XA Pending CN113543812A (zh) 2018-12-21 2019-12-20 具有巯基多重接头的adc

Country Status (12)

Country Link
US (1) US20220040320A1 (https=)
EP (1) EP3897734A4 (https=)
JP (2) JP2022514348A (https=)
KR (1) KR20210141918A (https=)
CN (1) CN113543812A (https=)
AU (1) AU2019403552A1 (https=)
CA (1) CA3122316A1 (https=)
IL (1) IL284147A (https=)
MX (1) MX2021007548A (https=)
SG (1) SG11202106122QA (https=)
TW (1) TW202039008A (https=)
WO (1) WO2020132655A1 (https=)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021207701A1 (en) * 2020-04-10 2021-10-14 Seagen Inc. Charge variant linkers
CA3254333A1 (en) * 2022-05-18 2025-07-04 Systimmune, Inc. Ligand-drug conjugate and use thereof
AR132368A1 (es) 2023-04-18 2025-06-18 Astrazeneca Ab Conjugados que comprenden enlazadores escindibles

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160176964A1 (en) * 2013-08-28 2016-06-23 Stemcentrx, Inc. Site-specific antibody conjugation methods and compositions
CN105764503A (zh) * 2013-10-15 2016-07-13 西雅图基因公司 用于改善配体-药物偶联物药代动力学的peg化的药物-接头
WO2018098269A2 (en) * 2016-11-23 2018-05-31 Mersana Therapeutics, Inc. Peptide-containing linkers for antibody-drug conjugates

Family Cites Families (14)

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ATE234635T1 (de) * 1995-12-22 2003-04-15 Bristol Myers Squibb Co Verzweigte hydrazongruppen enthaltende kuppler
JP2001505194A (ja) * 1996-11-05 2001-04-17 ブリストル―マイヤーズ・スクイブ・カンパニー 分枝ペプチド・リンカー
DE10048417A1 (de) * 2000-09-29 2002-04-11 Roche Diagnostics Gmbh Verbindungen mit verzweigtem Linker
US6821529B2 (en) * 2001-09-05 2004-11-23 Deanna Jean Nelson Oligo(ethylene glycoll)-terminated 1,2-dithiolanes and their conjugates useful for preparing self-assembled monolayers
KR100889587B1 (ko) * 2006-05-12 2009-03-19 한국생명공학연구원 기질표면 처리 및 특이적 단백질 고정용 링커분자, 및 그제조방법
US9056129B2 (en) * 2007-02-09 2015-06-16 Northeastern University Precision-guided nanoparticle systems for drug delivery
US20130195799A1 (en) * 2010-08-19 2013-08-01 Peg Biosciences, Inc. Synergistic biomolecule-polymer conjugates
EP3842074A1 (en) * 2010-09-29 2021-06-30 Philogen S.p.A. Protein-drug conjugates
US9981046B2 (en) * 2012-05-15 2018-05-29 Concortis Biosystems, Corp., a wholly owned Subsidiary of Sorrento Therapeutics, Inc. Drug-conjugates, conjugation methods, and uses thereof
KR102557309B1 (ko) * 2012-05-15 2023-07-20 씨젠 인크. 자가-안정화 링커 접합체
PL2872157T3 (pl) * 2012-07-12 2020-07-13 Hangzhou Dac Biotech Co., Ltd Koniugaty wiążących komórkę cząsteczek ze środkami cytotoksycznymi
TW201511774A (zh) * 2013-09-18 2015-04-01 Iner Aec Executive Yuan 放射性標誌之主動標靶性醫藥組合物及其用途
WO2016025752A1 (en) * 2014-08-14 2016-02-18 Prolynx Llc Reagents for thiol conjugation and conjugates formed therefrom
WO2021207701A1 (en) * 2020-04-10 2021-10-14 Seagen Inc. Charge variant linkers

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160176964A1 (en) * 2013-08-28 2016-06-23 Stemcentrx, Inc. Site-specific antibody conjugation methods and compositions
CN105764503A (zh) * 2013-10-15 2016-07-13 西雅图基因公司 用于改善配体-药物偶联物药代动力学的peg化的药物-接头
WO2018098269A2 (en) * 2016-11-23 2018-05-31 Mersana Therapeutics, Inc. Peptide-containing linkers for antibody-drug conjugates

Also Published As

Publication number Publication date
EP3897734A1 (en) 2021-10-27
JP2022514348A (ja) 2022-02-10
JP2024178320A (ja) 2024-12-24
US20220040320A1 (en) 2022-02-10
AU2019403552A1 (en) 2021-06-17
MX2021007548A (es) 2021-12-10
SG11202106122QA (en) 2021-07-29
EP3897734A4 (en) 2022-12-07
TW202039008A (zh) 2020-11-01
WO2020132655A1 (en) 2020-06-25
IL284147A (en) 2021-08-31
CA3122316A1 (en) 2020-06-25
KR20210141918A (ko) 2021-11-23

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