CA2989269C - Hydrophilic linkers for conjugation of a cytotoxic agent or chromophore molecule to a cell-binding molecule - Google Patents

Hydrophilic linkers for conjugation of a cytotoxic agent or chromophore molecule to a cell-binding molecule Download PDF

Info

Publication number
CA2989269C
CA2989269C CA2989269A CA2989269A CA2989269C CA 2989269 C CA2989269 C CA 2989269C CA 2989269 A CA2989269 A CA 2989269A CA 2989269 A CA2989269 A CA 2989269A CA 2989269 C CA2989269 C CA 2989269C
Authority
CA
Canada
Prior art keywords
cell
formula
compound
receptor
drug
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
CA2989269A
Other languages
English (en)
French (fr)
Other versions
CA2989269A1 (en
Inventor
Robert Yongxin Zhao
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.)
Hangzhou Dac Biotech Co Ltd
Original Assignee
Hangzhou Dac Biotech 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 Hangzhou Dac Biotech Co Ltd filed Critical Hangzhou Dac Biotech Co Ltd
Publication of CA2989269A1 publication Critical patent/CA2989269A1/en
Application granted granted Critical
Publication of CA2989269C publication Critical patent/CA2989269C/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/547Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65583Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6801Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6801Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/68031Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being an auristatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6801Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/68033Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a maytansine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6801Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/68035Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a pyrrolobenzodiazepine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6835Medicinal 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
    • A61K47/6851Medicinal 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
    • A61K47/6855Medicinal 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6889Conjugates 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic 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
    • C07D207/30Heterocyclic 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 two double bonds between ring members or between ring members and non-ring members
    • C07D207/34Heterocyclic 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 two double bonds between ring members or between ring members and non-ring members with hetero atoms or with 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
    • C07D207/36Oxygen or sulfur atoms
    • C07D207/402,5-Pyrrolidine-diones
    • C07D207/4042,5-Pyrrolidine-diones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. succinimide
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/46Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with 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
    • C07D213/62Oxygen or sulfur atoms
    • C07D213/70Sulfur atoms
    • C07D213/71Sulfur atoms to which a second hetero atom is attached
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/547Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/572Five-membered rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/547Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576Six-membered rings
    • C07F9/58Pyridine rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/0205Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oncology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (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)
CA2989269A 2015-06-15 2015-06-15 Hydrophilic linkers for conjugation of a cytotoxic agent or chromophore molecule to a cell-binding molecule Active CA2989269C (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IB2015/054521 WO2015151078A2 (en) 2015-06-15 2015-06-15 Hydrophilic linkers for conjugation

Publications (2)

Publication Number Publication Date
CA2989269A1 CA2989269A1 (en) 2015-10-08
CA2989269C true CA2989269C (en) 2020-09-22

Family

ID=54241395

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2989269A Active CA2989269C (en) 2015-06-15 2015-06-15 Hydrophilic linkers for conjugation of a cytotoxic agent or chromophore molecule to a cell-binding molecule

Country Status (6)

Country Link
EP (1) EP3307749A4 (zh)
CN (2) CN108026123B (zh)
AU (3) AU2015242210A1 (zh)
CA (1) CA2989269C (zh)
NZ (1) NZ737471A (zh)
WO (1) WO2015151078A2 (zh)

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11873281B2 (en) 2012-07-12 2024-01-16 Hangzhou Dac Biotech Co., Ltd. Conjugates of cell binding molecules with cytotoxic agents
PL2872157T3 (pl) 2012-07-12 2020-07-13 Hangzhou Dac Biotech Co., Ltd Koniugaty wiążących komórkę cząsteczek ze środkami cytotoksycznymi
US10441654B2 (en) 2014-01-24 2019-10-15 Children's Hospital Of Eastern Ontario Research Institute Inc. SMC combination therapy for the treatment of cancer
AU2016363013B2 (en) * 2015-12-04 2022-03-10 Seagen Inc. Conjugates of quaternized tubulysin compounds
US11793880B2 (en) 2015-12-04 2023-10-24 Seagen Inc. Conjugates of quaternized tubulysin compounds
US10961311B2 (en) 2016-04-15 2021-03-30 Macrogenics, Inc. B7-H3 binding molecules, antibody drug conjugates thereof and methods of use thereof
TWI794171B (zh) 2016-05-11 2023-03-01 美商滬亞生物國際有限公司 Hdac抑制劑與pd-l1抑制劑之組合治療
TWI808055B (zh) 2016-05-11 2023-07-11 美商滬亞生物國際有限公司 Hdac 抑制劑與 pd-1 抑制劑之組合治療
WO2018009916A1 (en) 2016-07-07 2018-01-11 The Board Of Trustees Of The Leland Stanford Junior University Antibody adjuvant conjugates
ES2928773T3 (es) 2017-01-17 2022-11-22 Heparegenix Gmbh Inhibidores de proteína cinasas para fomentar la regeneración hepática o reducir o prevenir la muerte de hepatocitos
EA201992081A1 (ru) * 2017-04-06 2020-01-21 Ханчжоу Дэк Биотек Ко., Лтд Конъюгирование цитотоксических лекарственных средств посредством бис-связывания
JP7320455B2 (ja) * 2017-06-21 2023-08-03 グリコス・フィンランド・オーワイ 親水性リンカーおよびそのコンジュゲート
US10772970B2 (en) 2017-12-01 2020-09-15 Abbvie Inc. Glucocorticoid receptor agonist and immunoconjugates thereof
WO2019109415A1 (zh) * 2017-12-04 2019-06-13 清华大学 一种靶向降解hmgcr的化合物及其应用
EP3621652A4 (en) * 2017-12-31 2021-01-13 Hangzhou DAC Biotech Co, Ltd CONJUGATE OF ANALOGUE OF TUBULYSIN WITH BRANCHED LINKS
CN110152014B (zh) * 2018-02-13 2022-09-27 烟台市和元艾迪斯生物医药科技有限公司 抗trailr2抗体-毒素-偶联物及其在抗肿瘤治疗中的药物用途
WO2019157772A1 (zh) * 2018-02-13 2019-08-22 和元生物技术(上海)股份有限公司 抗trailr2抗体-毒素-偶联物及其在抗肿瘤治疗中的药物用途
CN108727376B (zh) * 2018-05-21 2020-09-11 中国计量大学 9-氮杂双环[3.3.1]壬烷偶联富碘类化合物及其制备方法与用途
CN108676002B (zh) * 2018-06-04 2020-09-15 中国计量大学 9-氮(6’-氨基)己基杂双环[3.3.1]壬烷偶联罗丹明b类化合物及用途
CN108864251B (zh) * 2018-06-30 2022-06-14 大连理工大学 一类氨肽酶n激活的药物前体化合物及其制备方法和应用
KR20210065991A (ko) * 2018-09-27 2021-06-04 피에르 파브르 메디카먼트 설포말레이미드계 링커 및 상응하는 컨쥬게이트
JP2022525594A (ja) 2019-03-15 2022-05-18 ボルト バイオセラピューティクス、インコーポレーテッド Her2を標的とする免疫結合体
CA3138197A1 (en) 2019-05-14 2020-11-19 Nuvation Bio Inc. Anti-cancer nuclear hormone receptor-targeting compounds
CN112386707B (zh) * 2019-08-19 2023-08-11 辽宁医学诊疗科技研发中心有限公司 一种肿瘤靶向多肽药物偶联物及其制备方法
CN110938035B (zh) * 2019-10-28 2022-07-01 广西师范大学 9-苯磺酸-10-咪蒽腙及其合成方法和应用
EP4058464A1 (en) 2019-11-13 2022-09-21 Nuvation Bio Inc. Anti-cancer nuclear hormone receptor-targeting compounds
CN113135990A (zh) * 2020-01-20 2021-07-20 宁波鲲鹏生物科技有限公司 利拉鲁肽衍生物及其制备方法
CA3108168A1 (en) * 2020-02-05 2021-08-05 Yue Zhang Conjugates of cell-binding molecules with cytotoxic agents
CN113816990B (zh) * 2021-03-22 2023-08-22 联宁(苏州)生物制药有限公司 修饰的氨基酸及其在adc中的应用
US11834458B2 (en) 2021-03-23 2023-12-05 Nuvation Bio Inc. Anti-cancer nuclear hormone receptor-targeting compounds
CN114200126A (zh) * 2021-12-09 2022-03-18 牟奕 N型青霉素类与头孢菌素类抗生素抗体检测的固相矩阵及其制备方法
US11981694B2 (en) 2022-01-03 2024-05-14 Lilac Therapeutics, Inc. Acyclic thiol prodrugs
CN115286669A (zh) * 2022-07-15 2022-11-04 北京大学 抗体-高分子-药物偶联物的制备方法及应用
CN116773826B (zh) * 2023-08-21 2023-11-17 迪亚莱博(张家港)生物科技有限公司 一种用于检测抗蛋白酶3抗体的胶乳比浊生化试剂盒

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4003862A (en) * 1975-10-23 1977-01-18 Michigan Chemical Corporation N-substituted tetrahalophthalimides as flame retardants
WO2008034019A2 (en) * 2006-09-13 2008-03-20 Polymerix Corporation Active agents and their oligomers and polymers
WO2008070291A2 (en) * 2006-10-24 2008-06-12 Kereos, Inc. Improved linkers for anchoring targeting ligands
EP3569251A1 (en) * 2007-06-25 2019-11-20 Endocyte, Inc. Conjugates containing hydrophilic spacer linkers
CA2891280C (en) * 2012-11-24 2018-03-20 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and their uses for conjugation of drugs to cell binding molecules
CN104688740A (zh) * 2012-12-21 2015-06-10 百奥泰生物科技(广州)有限公司 类美登素衍生物及其制备方法和用途
NZ717003A (en) * 2013-09-02 2019-05-31 Hangzhou Dac Biotech Co Ltd Novel cytotoxic agents for conjugation of drugs to cell binding molecule
US10550190B2 (en) * 2014-04-04 2020-02-04 Merck Sharp & Dohme Corp. Phosphate based linkers for intracellular delivery of drug conjugates
EP3733209A1 (en) 2014-10-03 2020-11-04 Synaffix B.V. Sulfamide linker, conjugates thereof, and methods of preparation

Also Published As

Publication number Publication date
CA2989269A1 (en) 2015-10-08
AU2023200925A1 (en) 2023-03-23
AU2021201765B2 (en) 2022-12-08
AU2015242210A1 (en) 2017-12-07
CN112125929A (zh) 2020-12-25
NZ737471A (en) 2022-02-25
EP3307749A2 (en) 2018-04-18
CN108026123A (zh) 2018-05-11
EP3307749A4 (en) 2019-06-19
CN108026123B (zh) 2021-02-05
WO2015151078A2 (en) 2015-10-08
AU2021201765A1 (en) 2021-04-15
WO2015151078A3 (en) 2016-03-10
WO2015151078A4 (en) 2016-07-14

Similar Documents

Publication Publication Date Title
AU2021201765B2 (en) Hydrophilic Linkers for Conjugate
AU2021202467B2 (en) Bridge Linkers for Conjugation of Cell-Binding Molecules
US10975112B2 (en) Linkers for conjugation of cell-binding molecules
US10328157B2 (en) Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule
US10265291B2 (en) Disulfur bridge linkers for conjugation of a cell-binding molecule
US10696700B2 (en) Charged linkers and their uses for conjugation
CA2991384C (en) Bridge linkers for conjugation of a cell-binding molecule
CA2891280C (en) Hydrophilic linkers and their uses for conjugation of drugs to cell binding molecules
WO2015155753A2 (en) Novel linkers and their uses in specific conjugation of drugs to a biological molecule

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20171212

EEER Examination request

Effective date: 20171212