CN104640572B - 药物偶联物，偶联方法，及其用途 - Google Patents

药物偶联物，偶联方法，及其用途 Download PDF

Info

Publication number
CN104640572B
CN104640572B CN201380025785.1A CN201380025785A CN104640572B CN 104640572 B CN104640572 B CN 104640572B CN 201380025785 A CN201380025785 A CN 201380025785A CN 104640572 B CN104640572 B CN 104640572B
Authority
CN
China
Prior art keywords
compound
alkyl
optionally substituted
group
hydrogen
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
CN201380025785.1A
Other languages
English (en)
Chinese (zh)
Other versions
CN104640572A (zh
Inventor
苗振伟
洪予丰
朱同
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Lian Ning (suzhou) Biopharmaceutical Co Ltd
Original Assignee
Sorento Medical Treatment 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 Sorento Medical Treatment Co Ltd filed Critical Sorento Medical Treatment Co Ltd
Publication of CN104640572A publication Critical patent/CN104640572A/zh
Application granted granted Critical
Publication of CN104640572B publication Critical patent/CN104640572B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

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
    • A61K47/68—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
    • A61K47/6855—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 the tumour determinant being from breast cancer cell
    • 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
    • A61K38/07—Tetrapeptides
    • 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
    • A61K47/6801—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
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • 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
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C07D207/04—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 no double bonds between ring members or between ring members and non-ring members
    • C07D207/08—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
    • 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
    • C07D207/04—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 no double bonds between ring members or between ring members and non-ring members
    • C07D207/08—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
    • C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/587—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with aliphatic hydrocarbon radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms, said aliphatic radicals being substituted in the alpha-position to the ring by a hetero atom, e.g. with m >= 0, Z being a singly or a doubly bound hetero atom
    • C07D277/593—Z being doubly bound oxygen or doubly bound nitrogen, which nitrogen is part of a possibly substituted oximino radical
    • 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
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07F5/02—Boron compounds
    • C07F5/025—Boronic and borinic acid compounds
    • 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
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • 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
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • 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
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C07K5/06052—Val-amino acid
    • 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
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
    • C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Cell Biology (AREA)
  • Diabetes (AREA)
  • Oncology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Endocrinology (AREA)
  • Communicable Diseases (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
CN201380025785.1A 2012-05-15 2013-05-14 药物偶联物，偶联方法，及其用途 Active CN104640572B (zh)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US201261647300P 2012-05-15 2012-05-15
US61/647,300 2012-05-15
US201261648406P 2012-05-17 2012-05-17
US201261648532P 2012-05-17 2012-05-17
US61/648,406 2012-05-17
US61/648,532 2012-05-17
US201261652512P 2012-05-29 2012-05-29
US61/652,512 2012-05-29
PCT/US2013/041028 WO2013173393A1 (en) 2012-05-15 2013-05-14 Drug-conjugates, conjugation methods, and uses thereof

Publications (2)

Publication Number Publication Date
CN104640572A CN104640572A (zh) 2015-05-20
CN104640572B true CN104640572B (zh) 2018-04-27

Family

ID=49584226

Family Applications (4)

Application Number Title Priority Date Filing Date
CN201380025785.1A Active CN104640572B (zh) 2012-05-15 2013-05-14 药物偶联物，偶联方法，及其用途
CN201380025774.3A Active CN104379168B (zh) 2012-05-15 2013-05-14 药物偶联物，偶联方法，及其用途
CN201380025775.8A Active CN104662000B (zh) 2012-05-15 2013-05-14 药物偶联物及其偶联方法和用途
CN201710584374.6A Active CN107982545B (zh) 2012-05-15 2013-05-14 药物偶联物，偶联方法，及其用途

Family Applications After (3)

Application Number Title Priority Date Filing Date
CN201380025774.3A Active CN104379168B (zh) 2012-05-15 2013-05-14 药物偶联物，偶联方法，及其用途
CN201380025775.8A Active CN104662000B (zh) 2012-05-15 2013-05-14 药物偶联物及其偶联方法和用途
CN201710584374.6A Active CN107982545B (zh) 2012-05-15 2013-05-14 药物偶联物，偶联方法，及其用途

Country Status (7)

Country Link
US (7) US9981046B2 (https=)
EP (6) EP3590541B1 (https=)
JP (5) JP6280103B2 (https=)
CN (4) CN104640572B (https=)
ES (2) ES2734259T3 (https=)
HK (1) HK1208216A1 (https=)
WO (3) WO2013173392A1 (https=)

Families Citing this family (147)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101098854B (zh) 2004-07-23 2012-12-05 恩多塞特公司 二价连接体及其轭合物
AU2008224988A1 (en) 2007-03-14 2008-09-18 Endocyte, Inc. Binding ligand linked drug delivery conjugates of tubulysins
CN101784565B (zh) 2007-06-25 2014-12-10 恩多塞特公司 含有亲水性间隔区接头的共轭物
US9877965B2 (en) 2007-06-25 2018-01-30 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
US10080805B2 (en) 2012-02-24 2018-09-25 Purdue Research Foundation Cholecystokinin B receptor targeting for imaging and therapy
US20140080175A1 (en) 2012-03-29 2014-03-20 Endocyte, Inc. Processes for preparing tubulysin derivatives and conjugates thereof
US20140079636A1 (en) 2012-04-16 2014-03-20 Dinesh U. Chimmanamada Targeted therapeutics
CN104640572B (zh) 2012-05-15 2018-04-27 索伦托医疗有限公司 药物偶联物，偶联方法，及其用途
BR112015008365A2 (pt) 2012-10-16 2017-07-04 Endocyte Inc composto da fórmula b-l(d)x, ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, uso de um composto, composição de forma de dosagem unitária ou dose unitária, composição para tratar um câncer em um paciente, e método para tratar um câncer em um paciente
US9089614B2 (en) 2012-12-21 2015-07-28 Bioalliance C.V. Hydrophilic self-immolative linkers and conjugates thereof
HK1220626A1 (zh) 2013-03-15 2017-05-12 The Centre For Drug Research And Development 具细胞毒性和抗有丝分裂的化合物以及其使用方法
WO2014197991A1 (en) 2013-06-12 2014-12-18 Muhammad Yousaf Compounds for promoting liposomal and cellular adhesion and compositions and methods of use thereof
EP3738594A1 (en) 2013-09-10 2020-11-18 Madrigal Pharmaceuticals, Inc. Targeted therapeutics having an hsp90 ligand as binding moiety
AU2014337317A1 (en) 2013-10-15 2016-09-15 Sorrento Therapeutics Inc. Drug-conjugates with a targeting molecule and two different drugs
NZ758049A (en) 2013-10-15 2024-03-22 Seagen Inc Pegylated drug-linkers for improved ligand-drug conjugate pharmacokinetics
WO2015066053A2 (en) 2013-10-28 2015-05-07 Synta Pharmaceuticals Corp. Targeted therapeutics
BR112016015105A8 (pt) * 2013-12-27 2018-04-24 Var2 Pharmaceuticals Aps conjugados var2csa-droga
WO2015095953A1 (en) 2013-12-27 2015-07-02 The Centre For Drug Research And Development Sulfonamide-containing linkage systems for drug conjugates
WO2015113760A1 (en) * 2014-01-28 2015-08-06 Tube Pharmaceuticals Gmbh Cytotoxic tubulysin compounds for conjugation
EP3099332A4 (en) 2014-01-29 2017-06-21 Madrigal Pharmaceuticals, Inc. Targeted therapeutics
GB201402006D0 (en) 2014-02-06 2014-03-26 Oncomatryx Biopharma S L Antibody-drug conjugates and immunotoxins
JP6576942B6 (ja) 2014-03-03 2019-11-27 マドリガル ファーマシューティカルズ インコーポレイテッド 標的治療薬
MA39483A (fr) 2014-03-18 2015-09-24 Synta Pharmaceuticals Corp Agents thérapeutiques cibles
WO2015183978A1 (en) * 2014-05-28 2015-12-03 Agensys, Inc. Derivatives of dolaproine-dolaisoleuine peptides
US9950077B2 (en) 2014-06-20 2018-04-24 Bioalliance C.V. Anti-folate receptor alpha (FRA) antibody-drug conjugates and methods of using thereof
SMT202000265T1 (it) 2014-07-11 2020-07-08 Genmab As Anticorpi che legano axl
FI3900742T3 (fi) * 2014-09-11 2024-08-16 Seagen Inc Tertiääristä amiinia sisältävien lääkeaineiden kohdennettu antaminen
ES2905569T3 (es) * 2014-09-17 2022-04-11 Zymeworks Inc Compuestos citotóxicos y antimitóticos y métodos para utilizarlos
EP3218009B1 (en) 2014-10-14 2021-04-07 Polytherics Limited Process for the conjugation of a peptide or protein with a reagent comprising a leaving group including a portion of peg
US10077287B2 (en) 2014-11-10 2018-09-18 Bristol-Myers Squibb Company Tubulysin analogs and methods of making and use
BR112017012042A2 (pt) * 2014-12-08 2018-01-16 Sorrento Therapeutics Inc composição de conjugado anticorpo-droga e método para tratar câncer de mama
US9968683B2 (en) 2014-12-17 2018-05-15 Organolinx Corp. Method for conjugating molecules
EP3250238B1 (en) * 2015-01-28 2022-06-01 Sorrento Therapeutics, Inc. Antibody drug conjugates
US20170224835A1 (en) * 2015-02-06 2017-08-10 Sorrento Therapeutics, Inc. Antibody Drug Conjugates
WO2016127790A1 (zh) * 2015-02-15 2016-08-18 江苏恒瑞医药股份有限公司 配体-细胞毒性药物偶联物、其制备方法及其应用
CN106279352B (zh) * 2015-05-29 2020-05-22 上海新理念生物医药科技有限公司 海兔毒素10的衍生物及其应用
CN106243127B (zh) 2015-06-09 2021-01-26 凯惠科技发展(上海)有限公司 抗体药物偶联物、中间体、制备方法、药物组合物及应用
PL3319993T3 (pl) 2015-07-10 2020-07-27 Genmab A/S Specyficzne wobec AXL koniugaty przeciwciało-lek do leczenia raka
NZ739830A (en) 2015-07-12 2021-12-24 Hangzhou Dac Biotech Co Ltd Bridge linkers for conjugation of cell-binding molecules
US9839687B2 (en) 2015-07-15 2017-12-12 Suzhou M-Conj Biotech Co., Ltd. Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule
WO2017054080A1 (en) * 2015-09-29 2017-04-06 Zymeworks Inc. Cytotoxic and anti-mitotic compounds, and methods of using the same
WO2017058808A1 (en) * 2015-10-02 2017-04-06 Sirenas Llc Anti-cancer compounds and conjugates thereof
CN107029242A (zh) 2015-11-03 2017-08-11 财团法人工业技术研究院 抗体药物复合物及其制造方法
CN106729743B (zh) * 2015-11-23 2021-09-21 四川科伦博泰生物医药股份有限公司 抗ErbB2抗体-药物偶联物及其组合物、制备方法和应用
KR20180090290A (ko) 2015-12-04 2018-08-10 시애틀 지네틱스, 인크. 사차화 튜불리신 화합물들의 컨쥬게이트들
US11793880B2 (en) 2015-12-04 2023-10-24 Seagen Inc. Conjugates of quaternized tubulysin compounds
IL260289B (en) 2016-01-08 2022-08-01 Bioalliance Cv Tetravalent anti-psgl-1 antibodies and uses thereof
CN107029244B (zh) 2016-02-04 2021-04-27 浙江昭华生物医药有限公司 抗her2抗体-药物偶联物及其应用
PE20231050A1 (es) 2016-03-02 2023-07-11 Eisai Randd Man Co Ltd Conjugados de anticuerpo y farmaco basados en eribulina y metodos para su uso
CN109843919A (zh) 2016-03-25 2019-06-04 西雅图基因公司 用于制备聚乙二醇化的药物-接头及其中间体的方法
WO2017172907A1 (en) * 2016-03-29 2017-10-05 Sorrento Therapeutics, Inc. Calicheamicin antibody drug conjugates linking an amidoacetyl group to a sugar moiety on calicheamicin
CN108779146B (zh) * 2016-03-29 2022-03-18 东丽株式会社 肽衍生物及其用途
JP2019513371A (ja) 2016-04-01 2019-05-30 アビディティー バイオサイエンシーズ エルエルシー 核酸ポリペプチド組成物とその使用
WO2017210288A1 (en) * 2016-05-31 2017-12-07 Sorrento Therapeutics, Inc. Antibody drug conjugates having derivatives of amatoxin as the drug
IL263744B2 (en) 2016-06-17 2023-11-01 Magenta Therapeutics Inc Compositions and methods for the depletion of cd117 plus cells
WO2018036438A1 (zh) * 2016-08-23 2018-03-01 四川科伦博泰生物医药股份有限公司 一种抗体-药物偶联物及其制备方法和应用
US10517958B2 (en) 2016-10-04 2019-12-31 Zymeworks Inc. Compositions and methods for the treatment of platinum-drug resistant cancer
CA3044898C (en) * 2016-11-25 2022-04-05 Mabwell (shanghai) Bioscience Co., Ltd. Di-substituted maleic amide linker for antibody-drug conjugating and preparation method and use thereof
CN108101825B (zh) * 2016-11-25 2022-02-22 迈威(上海)生物科技股份有限公司 用于抗体-药物偶联的双取代马来酰胺类连接子及其制备方法和用途
CN109810039B (zh) * 2017-11-22 2021-11-12 迈威(上海)生物科技股份有限公司 一种用于抗体-药物偶联的双取代马来酰胺类连接子及其制备方法和用途
US10864279B2 (en) 2016-12-16 2020-12-15 Industrial Technology Research Institute Linker-drug and antibody-drug conjugate (ADC) employing the same
MX2019008199A (es) 2017-01-06 2019-11-25 Avidity Biosciences Llc Composiciones de acido nucleico polipeptido y metodos de induccion de la omision de exon.
EP3571230A4 (en) 2017-01-20 2020-12-16 Magenta Therapeutics, Inc. COMPOSITIONS AND METHODS FOR DELETION OF CD137 + CELLS
KR102648564B1 (ko) 2017-03-24 2024-03-19 씨젠 인크. 글루쿠로니드 약물-링커의 제조 공정 및 그 중간물
KR20210122319A (ko) * 2017-04-06 2021-10-08 항저우 디에이씨 바이오테크 씨오, 엘티디 비스-링키지를 사용한 세포독성 약물의 접합
WO2018192407A1 (zh) 2017-04-19 2018-10-25 四川科伦博泰生物医药股份有限公司 细胞毒素和偶联物、其用途和制备方法
CA3067572A1 (en) 2017-06-20 2018-12-27 Madrigal Pharmaceuticals, Inc. Targeted therapeutics
KR20200016874A (ko) 2017-06-20 2020-02-17 마드리갈 파마슈티칼스 인코포레이티드 표적화 치료제를 포함하는 병용 요법
EP3641831B1 (en) * 2017-06-20 2024-11-06 Sorrento Therapeutics, Inc. Cd38 antibody drug conjugate
GB201711809D0 (en) 2017-07-21 2017-09-06 Governors Of The Univ Of Alberta Antisense oligonucleotide
CN111201030B (zh) 2017-07-25 2024-11-01 真和制药有限公司 通过阻断tim-3和其配体的相互作用治疗癌症
US10799598B2 (en) 2017-08-01 2020-10-13 Sorrento Therapeutics, Inc. Disulfide bridging conjugates
EP4321523A3 (en) 2017-08-10 2024-04-24 Sumitomo Pharma Co., Ltd. Hemiasterlin derivatives and antibody-drug conjugates including same
KR20200051733A (ko) 2017-09-08 2020-05-13 시애틀 지네틱스, 인크. 튜불리신 및 그 중간물의 제조 공정
EP3691657A4 (en) 2017-10-04 2021-07-21 Avidity Biosciences, Inc. NUCLEIC ACID POLYPEPTIDE COMPOSITIONS AND USES THEREOF
KR102762352B1 (ko) * 2017-11-30 2025-02-05 씨젠 인크. 약물 링커 화합물의 제조방법
AU2018378812B2 (en) 2017-12-06 2025-05-22 Avidity Biosciences, Inc. Compositions and methods of treating muscle atrophy and myotonic dystrophy
CN119241554A (zh) 2017-12-15 2025-01-03 四川科伦博泰生物医药股份有限公司 生物活性物偶联物及其制备方法和用途
WO2019149116A1 (zh) * 2018-01-30 2019-08-08 四川科伦博泰生物医药股份有限公司 制备偶联物的方法
SG11202007540SA (en) * 2018-02-20 2020-09-29 Seattle Genetics Inc Hydrophobic auristatin f compounds and conjugates thereof
CN119405832A (zh) 2018-06-01 2025-02-11 卫材R&D管理有限公司 剪接调节抗体-药物缀合物及其使用方法
EP3801523B1 (en) 2018-06-01 2024-09-11 Eisai R&D Management Co., Ltd. Splicing modulators
US20210276971A1 (en) 2018-06-20 2021-09-09 The Research Foundation For The State University Of New York Triazamacrocycle-derived chelator compositions for coordination of imaging and therapy metal ions and methods of using same
IL282182B2 (en) * 2018-10-12 2025-09-01 Hangzhou Dac Biotech Co Ltd Cytotoxic drug conjugates with a bis linkage
WO2020081493A1 (en) 2018-10-16 2020-04-23 Molecular Templates, Inc. Pd-l1 binding proteins
US12583932B2 (en) 2018-11-16 2026-03-24 Virtuoso Binco, Inc. CD38 and ICAM1 antibodies and uses thereof
SG11202102419VA (en) 2018-12-13 2021-04-29 Eisai R&D Man Co Ltd Herboxidiene splicing modulator antibody-drug conjugates and methods of use
IL312067B2 (en) 2018-12-21 2025-08-01 Avidity Biosciences Inc Anti-transferrin receptor antibodies and uses thereof
AU2019403552A1 (en) * 2018-12-21 2021-06-17 Seagen Inc. ADCs with thiol multiplex linkers
WO2020160156A2 (en) 2019-01-30 2020-08-06 Immutics, Inc. Anti-gal3 antibodies and uses thereof
WO2020166592A1 (ja) 2019-02-13 2020-08-20 大日本住友製薬株式会社 ヘミアスタリン誘導体とその抗体薬物複合体
JP7432531B2 (ja) 2019-02-13 2024-02-16 住友ファーマ株式会社 システイン残基を有するヘミアスタリン誘導体
CN109824759A (zh) * 2019-03-08 2019-05-31 联宁（苏州）生物制药有限公司 一种用于抗体药物偶联物的药物-连接子mc-mmaf的制备方法及其中间体
WO2020219820A1 (en) 2019-04-25 2020-10-29 Avidity Biosciences, Inc. Nucleic acid compositions and methods of multi-exon skipping
US12006499B2 (en) 2019-06-06 2024-06-11 Avidity Biosciences, Inc. Una amidites and uses thereof
CN114375296A (zh) 2019-06-06 2022-04-19 艾维迪提生物科学公司 核酸多肽组合物及其用途
WO2021055816A1 (en) 2019-09-18 2021-03-25 Molecular Templates, Inc. Pd-l1 binding molecules comprising shiga toxin a subunit scaffolds
JP7835441B2 (ja) 2019-12-06 2026-03-25 トゥルーバインディング，インコーポレイテッド Ｇａｌ３とインスリン受容体又はインテグリンとの相互作用を妨害する抗体及びそれらの使用方法
CN115666656A (zh) 2020-01-13 2023-01-31 西纳福克斯股份有限公司 通过环加成双侧功能化抗体
JP7807375B2 (ja) 2020-01-13 2026-01-27 シンアフィックス ビー．ブイ． 付加環化を介して両側官能化された抗体
WO2021144315A1 (en) 2020-01-13 2021-07-22 Synaffix B.V. Conjugates of antibodies an immune cell engagers
CA3168986A1 (en) 2020-02-26 2021-09-02 Sorrento Therapeutics, Inc. Activatable antigen binding proteins with universal masking moieties
FR3107648B1 (fr) * 2020-02-27 2022-03-18 Mc Saf conjugués anticorps-médicament anti-CD56 et leur utilisation en thérapie
KR20220151166A (ko) * 2020-03-09 2022-11-14 시그마-알드리치 컴퍼니., 엘엘씨 중간체 공통 중간체를 통한 돌라스타틴 및 아우리스타틴 유사체의 효율적인 제조
WO2021188390A1 (en) 2020-03-19 2021-09-23 Avidity Biosciences, Inc. Compositions and methods of treating facioscapulohumeral muscular dystrophy
SI4126066T1 (sl) 2020-03-27 2026-04-30 Avidity Biosciences, Inc. Sestavki in postopki zdravljenja mišične distrofije
US10987487B1 (en) 2020-04-29 2021-04-27 Cure Medical Llc Gripper sleeve for urinary catheter
EP4157338A4 (en) 2020-05-26 2024-11-13 TrueBinding, Inc. METHOD FOR TREATING INFLAMMATORY DISEASES BY GALECTIN-3 BLOCKING
AU2021284401A1 (en) 2020-06-05 2023-01-05 Eisai R&D Management Co., Ltd. Anti-BCMA antibody-drug conjugates and methods of use
EP4172141A1 (en) 2020-06-26 2023-05-03 Synaffix B.V. Methods for the preparation of linker payload constructs
NL2026400B1 (en) 2020-09-02 2022-05-04 Synaffix Bv Methods for the preparation of bioconjugates
EP4208259A2 (en) 2020-09-04 2023-07-12 NovaRock Biotherapeutics, Ltd. Nectin-4 antibodies and uses thereof
JP2023541637A (ja) 2020-09-15 2023-10-03 シンアフィックス ビー．ブイ． 抗体－エクサテカンコンジュゲート
NL2026947B1 (en) 2020-11-20 2022-07-01 Synaffix Bv Tyrosine-based antibody conjugates
UY39587A (es) 2020-12-23 2022-07-29 Univ Muenchen Ludwig Maximilians Conjugados anticuerpo-droga mejorados dirigidos contra cd30 y usos de los mismos
CA3198230A1 (en) * 2021-01-28 2022-08-04 Jian Chen Conjugate and use thereof
JP2024506022A (ja) 2021-02-08 2024-02-08 シンアフィックス ビー．ブイ． 多機能性抗体
US20240181073A1 (en) 2021-03-03 2024-06-06 Sorrento Therapeutics, Inc. Antibody-Drug Conjugates Comprising an Anti-BCMA Antibody
WO2022197945A1 (en) 2021-03-17 2022-09-22 Molecular Templates, Inc. Pd-l1 binding proteins comprising shiga toxin a subunit scaffolds and cd8+ t cell antigens
CN116897149A (zh) * 2021-03-30 2023-10-17 上海复旦张江生物医药股份有限公司 一种连接基药物偶联物的制备方法及其中间体
JP2024526764A (ja) 2021-07-13 2024-07-19 トゥルーバインディング，インコーポレイテッド タンパク質凝集を防止する方法
CN118265544A (zh) 2021-09-16 2024-06-28 艾维迪提生物科学公司 治疗面肩肱型肌营养不良的组合物和方法
CN118524852A (zh) 2021-11-09 2024-08-20 真和制药有限公司 治疗或抑制心血管疾病的方法
AU2022422149A1 (en) 2021-12-23 2024-08-01 Mirecule, Inc. Compositions for delivery of polynucleotides
EP4489790A1 (en) 2022-03-10 2025-01-15 Vivasor, Inc. Antibody-drug conjugates and uses thereof
US12071621B2 (en) 2022-04-05 2024-08-27 Avidity Biosciences, Inc. Anti-transferrin receptor antibody-PMO conjugates for inducing DMD exon 44 skipping
CN120659627A (zh) 2022-07-29 2025-09-16 瑞泽恩制药公司 用于转铁蛋白受体（tfr）介导的脑和肌肉递送的组合物和方法
CN119997985A (zh) 2022-08-15 2025-05-13 西纳福克斯股份有限公司 蒽环类药物及其缀合物
WO2024067841A1 (zh) 2022-09-30 2024-04-04 上海迪诺医药科技有限公司 苯并氮杂卓衍生物、含其的偶联物及其应用
KR20250116795A (ko) 2022-11-14 2025-08-01 리제너론 파마슈티칼스 인코포레이티드 별아교세포로의 섬유아세포 성장 인자 수용체 3-매개된 전달을 위한 조성물 및 방법
EP4389152A1 (en) 2022-12-23 2024-06-26 Synaffix B.V. Conjugates of pbd prodrugs
CN116621927B (zh) * 2023-01-09 2024-03-26 联宁（苏州）生物制药有限公司 带有伊喜替康和C-lock定点偶联基团的抗体偶联中间体、偶联方法及抗体偶联药物
EP4410313A1 (en) 2023-01-31 2024-08-07 Synaffix B.V. Homogeneous antibody-conjugates with high payload loading
AU2024229817A1 (en) 2023-02-28 2025-08-14 Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. Chemical coupling linker and use thereof
CN121969397A (zh) 2023-04-05 2026-05-01 维硕公司 抗体偶联药物及其用途
WO2024211235A1 (en) 2023-04-05 2024-10-10 Sorrento Therapeutics, Inc. Antibody-drug conjugates and uses thereof
CN121969398A (zh) 2023-04-05 2026-05-01 维硕公司 抗体偶联药物及其用途
WO2024218164A1 (en) 2023-04-17 2024-10-24 Synaffix B.V. Stable 4-isoxazoline conjugates
EP4450093A1 (en) 2023-04-17 2024-10-23 Synaffix B.V. Cleavable immune cell engagers
EP4735602A2 (en) 2023-06-27 2026-05-06 Atrium Therapeutics, Inc. Compositions and methods of using prkag2-targeting antibody-oligonucleotide conjugates abstract
AU2024308906A1 (en) 2023-06-30 2026-02-05 Atrium Therapeutics, Inc. Compositions and methods of using pln-targeting antibody-oligonucleotide conjugates
WO2025027529A1 (en) 2023-07-31 2025-02-06 Advesya Anti-il-1rap antibody drug conjugates and methods of use thereof
TW202530255A (zh) 2023-12-15 2025-08-01 法商亞維西亞有限公司 抗ｉｌ－１ｒａｐ結合結構域及其抗體－藥物偶聯物
CN117964682A (zh) * 2024-01-12 2024-05-03 杭州爱科瑞思生物医药有限公司 Dolastatin衍生物及其制备方法和应用
WO2025238253A1 (en) 2024-05-16 2025-11-20 Synaffix B.V. Antibody-oligonucleotide conjugates
WO2026008881A1 (en) 2024-07-05 2026-01-08 Synaffix B.V. Extracellular vesicles comprising biomolecule-conjugates
US20260078179A1 (en) 2024-07-18 2026-03-19 Novarock Biotherapeutics, Ltd. Cdh17 antibodies and uses thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1938046A (zh) * 2003-11-06 2007-03-28 西雅图基因公司 能够与配体偶联的单甲基缬氨酸化合物
CN101678124A (zh) * 2007-03-14 2010-03-24 恩多塞特公司 结合配体连接的微管溶素递药缀合物
CN102215844A (zh) * 2008-09-17 2011-10-12 恩多塞特公司 抗叶酸剂的叶酸受体结合轭合物

Family Cites Families (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4783443A (en) 1986-03-03 1988-11-08 The University Of Chicago Amino acyl cephalosporin derivatives
US6569834B1 (en) 1992-12-03 2003-05-27 George R. Pettit Elucidation and synthesis of antineoplastic tetrapeptide w-aminoalkyl-amides
US5780588A (en) 1993-01-26 1998-07-14 Arizona Board Of Regents Elucidation and synthesis of selected pentapeptides
US6214345B1 (en) 1993-05-14 2001-04-10 Bristol-Myers Squibb Co. Lysosomal enzyme-cleavable antitumor drug conjugates
EP0731106B1 (en) 1993-10-01 2004-11-17 Teikoku Hormone Mfg. Co., Ltd. Dolastatin derivatives
US5525474A (en) * 1994-01-31 1996-06-11 Boehringer Mannheim Corporation Piperidine analogs and conjugates of procainamide and NAPA
CA2427146A1 (en) 2000-10-25 2002-07-18 Mayo Foundation For Medical Education And Research Transcobalamin binding conjugates useful for treating abnormal cellular proliferation
US7771727B2 (en) * 2002-03-01 2010-08-10 The Administrators Of The Tulane Educational Fund Conjugates of therapeutic or cytotoxic agents and biologically active peptides
US20090068178A1 (en) 2002-05-08 2009-03-12 Genentech, Inc. Compositions and Methods for the Treatment of Tumor of Hematopoietic Origin
DK1523493T3 (da) 2002-07-09 2013-12-02 Alexander Doemling Nye tubulysinanaloge
DK1545613T3 (da) 2002-07-31 2011-11-14 Seattle Genetics Inc Auristatinkonjugater og deres anvendelse til behandling af cancer, en autoimmun sygdom eller en infektiøs sygdom
DE10254439A1 (de) 2002-11-21 2004-06-03 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Tubulysine, Herstellungsverfahren und Tubulysin-Mittel
US8088387B2 (en) 2003-10-10 2012-01-03 Immunogen Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates
US7276497B2 (en) 2003-05-20 2007-10-02 Immunogen Inc. Cytotoxic agents comprising new maytansinoids
CN101087611B (zh) * 2003-10-10 2019-04-23 伊缪诺金公司 用经不可切割接头连接的细胞结合剂美登木素生物碱偶联物靶向特定细胞群的方法、所述偶联物和制备所述偶联物的方法
DK1791565T3 (en) 2004-09-23 2016-08-01 Genentech Inc Cysteingensplejsede antibodies and conjugates
JP4993645B2 (ja) * 2004-12-01 2012-08-08 ジェネンテック， インコーポレイテッド 抗体薬剤結合体および方法
US20070134243A1 (en) 2004-12-01 2007-06-14 Gazzard Lewis J Antibody drug conjugates and methods
JP2008537673A (ja) * 2005-01-31 2008-09-25 ジェネンテック・インコーポレーテッド 抗ｅｐｈｂ２抗体とその使用方法
DK3248613T3 (da) * 2005-07-18 2022-03-14 Seagen Inc Beta-glucuronid-lægemiddel-linkerkonjugater
EP2354163A3 (en) * 2005-09-26 2013-04-24 Medarex, Inc. Conjugates of duocarmycin and anti-CD70 or anti-PSMA antibodies
AR059900A1 (es) 2006-03-17 2008-05-07 Genentech Inc Anticuerpos anti-tat226 e inmunoconjugados
AR063942A1 (es) 2006-06-06 2009-03-04 Enanta Pharm Inc Compuestos de oximilo aciclico inhibidores de proteasa del virus de hepatitis c
EP2056709A4 (en) * 2006-08-11 2013-05-01 Univ New Jersey Med DOUBLE-SENSITIZER WITH LUMINESCENCE COMPOUNDS, CONJUGATES AND USE
CN101500548A (zh) * 2006-08-18 2009-08-05 弗·哈夫曼-拉罗切有限公司 用于体内递送多核苷酸的多缀合物
WO2008128164A1 (en) 2007-04-12 2008-10-23 The Penn State Research Foundation Accumulation field effect microelectronic device and process for the formation thereof
CN101784565B (zh) * 2007-06-25 2014-12-10 恩多塞特公司 含有亲水性间隔区接头的共轭物
EP2181101A2 (en) * 2007-07-20 2010-05-05 Helmholtz-Zentrum für Infektionsforschung GmbH Tubulysin d analogues
AU2009270988A1 (en) 2008-07-15 2010-01-21 Genentech, Inc. Anthracycline derivative conjugates, process for their preparation and their use as antitumor compounds
EP2174947A1 (en) 2008-09-25 2010-04-14 Universität des Saarlandes Bioactive pre-tubulysins and use thereof
WO2010081004A1 (en) * 2009-01-09 2010-07-15 Seattle Genetics, Inc. Weekly dosing regimens for anti-cd30 vc-pab-mmae antibody drug-conjugates
EP2403538B1 (en) 2009-03-04 2017-10-04 Polytherics Limited Conjugated proteins and peptides
US8394922B2 (en) * 2009-08-03 2013-03-12 Medarex, Inc. Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof
CN102844045A (zh) * 2010-02-08 2012-12-26 艾更斯司股份有限公司 结合于161p2f10b蛋白的抗体药物偶联物(adc)
NZ701208A (en) * 2010-06-03 2016-05-27 Genentech Inc Immuno-pet imaging of antibodies and immunoconjugates and uses thereof
CA2799540A1 (en) 2010-06-08 2011-12-15 Genentech, Inc. Cysteine engineered antibodies and conjugates
EP2409983A1 (en) 2010-07-19 2012-01-25 Leibniz-Institut für Pflanzenbiochemie (IPB) Tubulysin analogues
JP5933562B2 (ja) 2010-09-29 2016-06-15 シアトル ジェネティックス， インコーポレイテッド Ｎ−カルボキシアルキル−アウリスタチンおよびその使用
KR101897307B1 (ko) 2010-12-02 2018-09-10 네르비아노 메디칼 사이언시스 에스.알.엘. 모르폴리닐 안트라사이클린 유도체의 제조 방법
CN110078789A (zh) 2011-05-27 2019-08-02 Ambrx 公司 含有非天然氨基酸连接的海兔毒素衍生物的组合物、涉及该海兔毒素衍生物的方法及其用途
KR102356286B1 (ko) 2011-05-27 2022-02-08 암브룩스, 인코포레이티드 비-천연 아미노산 연결된 돌라스타틴 유도체를 함유하는 조성물, 이를 수반하는 방법, 및 용도
US8815226B2 (en) 2011-06-10 2014-08-26 Mersana Therapeutics, Inc. Protein-polymer-drug conjugates
JP6209159B2 (ja) 2011-06-21 2017-10-04 イミュノジェン・インコーポレーテッド ペプチドリンカーを有する新規メイタンシノイド誘導体およびその結合体
RU2014124984A (ru) 2011-12-05 2016-01-27 Идженика Биотерапьютикс, Инк. Конъюгаты антитело-лекарственное средство и родственные соединения, композиции и способы
CN104640572B (zh) 2012-05-15 2018-04-27 索伦托医疗有限公司 药物偶联物，偶联方法，及其用途
CN108727466B (zh) 2012-06-07 2023-04-28 Ambrx公司 前列腺特异性膜抗原抗体药物结合物
KR102190832B1 (ko) 2012-06-19 2020-12-15 암브룩스, 인코포레이티드 항cd70 항체 약물 컨쥬게이트
CN104411337A (zh) 2012-07-09 2015-03-11 基因泰克公司 包含抗cd79b抗体的免疫偶联物
AU2014337317A1 (en) * 2013-10-15 2016-09-15 Sorrento Therapeutics Inc. Drug-conjugates with a targeting molecule and two different drugs
EP3250238B1 (en) 2015-01-28 2022-06-01 Sorrento Therapeutics, Inc. Antibody drug conjugates
US20170224835A1 (en) 2015-02-06 2017-08-10 Sorrento Therapeutics, Inc. Antibody Drug Conjugates

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1938046A (zh) * 2003-11-06 2007-03-28 西雅图基因公司 能够与配体偶联的单甲基缬氨酸化合物
CN101678124A (zh) * 2007-03-14 2010-03-24 恩多塞特公司 结合配体连接的微管溶素递药缀合物
CN102215844A (zh) * 2008-09-17 2011-10-12 恩多塞特公司 抗叶酸剂的叶酸受体结合轭合物

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Antineoplastic Agents. 592. Highly Effective Cancer Cell Growth Inhibitory Structural Modifications of Dolastatin 10;George R. Pettit et al;《J. Nat. Prod.》;20110502;第74卷;第962页-968页，尤其是第962页左栏 *

Also Published As

Publication number Publication date
JP6239598B2 (ja) 2017-11-29
US12115228B2 (en) 2024-10-15
EP3590541A1 (en) 2020-01-08
JP2015518831A (ja) 2015-07-06
US10967071B2 (en) 2021-04-06
EP2849790B1 (en) 2019-04-10
WO2013173391A1 (en) 2013-11-21
US20150105539A1 (en) 2015-04-16
US20150141646A1 (en) 2015-05-21
EP2849797A1 (en) 2015-03-25
EP3925627A1 (en) 2021-12-22
US9884127B2 (en) 2018-02-06
CN104662000A (zh) 2015-05-27
HK1208163A1 (en) 2016-02-26
CN107982545A (zh) 2018-05-04
CN104662000B (zh) 2018-08-17
CN104640572A (zh) 2015-05-20
CN104379168B (zh) 2017-08-15
EP2850059A4 (en) 2016-06-29
ES2887208T3 (es) 2021-12-22
US20180243438A1 (en) 2018-08-30
WO2013173392A1 (en) 2013-11-21
US20160067350A1 (en) 2016-03-10
US20250135024A1 (en) 2025-05-01
US9801951B2 (en) 2017-10-31
CN107982545B (zh) 2021-04-09
EP3590541B1 (en) 2021-08-11
EP2849797B1 (en) 2019-12-18
EP2849790A4 (en) 2016-04-13
ES2734259T3 (es) 2019-12-05
EP3520817A1 (en) 2019-08-07
EP2850059A1 (en) 2015-03-25
JP2015518832A (ja) 2015-07-06
EP2849790A1 (en) 2015-03-25
HK1208165A1 (en) 2016-04-01
US9981046B2 (en) 2018-05-29
JP6239597B2 (ja) 2017-11-29
JP2018052951A (ja) 2018-04-05
US20180085471A1 (en) 2018-03-29
JP2018058851A (ja) 2018-04-12
EP2849797A4 (en) 2016-04-27
HK1208216A1 (en) 2016-02-26
JP6280103B2 (ja) 2018-02-14
JP2015518833A (ja) 2015-07-06
US20210187119A1 (en) 2021-06-24
CN104379168A (zh) 2015-02-25
WO2013173393A1 (en) 2013-11-21

Similar Documents

Publication Publication Date Title
CN104640572B (zh) 药物偶联物，偶联方法，及其用途
DK2575467T3 (en) Macrocyclic compounds useful as inhibitors of histone deacetylases
CN106132431A (zh) 具有靶向分子和两种不同药物的药物偶联物
US8247372B2 (en) Depsipeptides and their therapeutic use
WO2015187540A1 (en) Peptide-drug conjugates
US20200316214A1 (en) Anti-cancer compounds and conjugates thereof
HK1208163B (en) Drug-conjugates, conjugation methods, and uses thereof
CN113633780B (zh) 一种小分子偶联物及其用途
HK40012657A (en) Drug-conjugates, conjugation methods, and uses thereof
HK40064991A (en) Drug-conjugates and uses thereof
Bodero Padilla Synthesis of novel conjugates based on a functionalized cyclo [DKP-isoDGR] integrin ligand and potent cytotoxic agents

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
TR01 Transfer of patent right
TR01 Transfer of patent right

Effective date of registration: 20180905

Address after: B8-301, 218 Xing Hu Street, Suzhou Industrial Park, Jiangsu.

Patentee after: Lian Ning (Suzhou) biopharmaceutical Co., Ltd.

Address before: American California

Patentee before: Sorento medical treatment company limited