RU2016134258A - Конъюгат лекарственного средства с направляющей молекулой и двумя различными лекарственными средствами - Google Patents

Конъюгат лекарственного средства с направляющей молекулой и двумя различными лекарственными средствами Download PDF

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RU2016134258A
RU2016134258A RU2016134258A RU2016134258A RU2016134258A RU 2016134258 A RU2016134258 A RU 2016134258A RU 2016134258 A RU2016134258 A RU 2016134258A RU 2016134258 A RU2016134258 A RU 2016134258A RU 2016134258 A RU2016134258 A RU 2016134258A
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drug conjugate
conjugate
dual drug
absent
component
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Чжэньвэй Мяо
Ган ЧЭНЬ
Тун Чжу
Алишер Б. КХАСАНОВ
Юйфын Хун
Александр ХУХОЛОВСКИЙ
Хун ЧЖАНЬ
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Сорренто Терапьютикс Инк.
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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    • 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
    • A61K47/54—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 organic compound
    • A61K47/55—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 organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
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    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • 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
    • 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
    • A61K47/68033—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a maytansine

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  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Claims (44)

1. Двойной конъюгат лекарственных средств, включающий структуру Формулы I:
Figure 00000001
(I)
или его фармацевтически приемлемая соль,
где:
A является направляющим белком;
каждый D 1 может быть выбран независимо, где каждый D 1 включает активное вещество;
каждый L 1 независимо является линкером, включающим по меньшей мере один атом N (азота);
каждый D 2 выбран независимо, где каждый D 2 включает активное вещество;
каждый L 2 независимо является линкером;
E-компонент является необязательно замещенным гетероарилом или необязательно замещенным гетероциклилом;
каждый L 3 является необязательно замещенным C1-C6 алкилом, или каждый L 3 отсутствует, когда L 3 отсутствует, сера непосредственно связана с E-компонентом; и
каждый L 4 является необязательно замещенным C1-C6 алкилом, или каждый L 4 отсутствует, когда L 4 отсутствует, сера непосредственно связана с E-компонентом;
m является 1, 2, 3, 4, 5, 6, 7, 8, 9 или 10; и
n является 1, 2, 3, 4, 5, 6, 7, 8, 9 или 10.
2. Двойной конъюгат лекарственных средств по п. 1, где E-компонент включает фрагмент, выбранный из группы, состоящей из:
Figure 00000002
3. Двойной конъюгат лекарственных средств по п. 1, где L 3 представляет собой -(CH2)-; и L 4 представляет собой -(CH2)-.
4. Двойной конъюгат лекарственных средств по п. 1, где L 3 отсутствует; и L 4 отсутствует.
5. Двойной конъюгат лекарственных средств по п. 1, где:
Figure 00000003
является:
Figure 00000004
6. Двойной конъюгат лекарственных средств по п. 1, где L 1 включает
Figure 00000005
, где X 1 представляет собой N (азот) или CH; Y 1 представляет собой N (азот) или CH; и p является 0, 1 или 2.
7. Конъюгат активного вещества по п. 6, где L1 включает:
Figure 00000006
8. Двойной конъюгат лекарственных средств по п. 1, где каждый D 1 независимо выбран из группы, состоящей из тубулин-связывающих средств, ДНК-алкилирующих средств, ДНК-интеркалятора, ингибиторов ферментов, иммуномодуляторов, пептидов и нуклеотидов.
9. Двойной конъюгат лекарственных средств по п. 1, где каждый D 2 независимо выбран из группы, состоящей из тубулин-связывающих средств, ДНК-алкилирующих средств, ДНК-интеркалятора, ингибиторов ферментов, иммуномодуляторов, пептидов и нуклеотидов.
10. Двойной конъюгат лекарственных средств по п. 1, где L 1 или L 2 включает -(CH2)n-, где n является 1, 2, 3, 4, 5, 6, 7, 8, 9 или 10.
11. Двойной конъюгат лекарственных средств по п. 1, где L 1 или L 2 включает -(CH2CH2O)n-, где n является 1, 2, 3, 4, 5, 6, 7, 8, 9 или 10.
12. Двойной конъюгат лекарственных средств по п. 1, где компонент A включает по меньшей мере один модифицированный остаток L-аланина, который связан по меньшей мере с одной серой в L 1 .
13. Двойной конъюгат лекарственных средств по п. 1, где каждый
Figure 00000007
является:
Figure 00000008
Figure 00000009
где G является -NH-.
14. Двойной конъюгат лекарственных средств по п. 1, где каждый
Figure 00000010
является:
Figure 00000011
Figure 00000012
Figure 00000013
15. Двойной конъюгат лекарственных средств по п. 1, где структура выбрана из группы, состоящей из:
Figure 00000014
Figure 00000015
Figure 00000016
Figure 00000017
или их фармацевтически приемлемой соли.
RU2016134258A 2013-10-15 2014-10-15 Конъюгат лекарственного средства с направляющей молекулой и двумя различными лекарственными средствами RU2016134258A (ru)

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US201361891310P 2013-10-15 2013-10-15
US61/891,310 2013-10-15
PCT/US2014/060750 WO2015057876A1 (en) 2013-10-15 2014-10-15 Drug-conjugates with a targeting molecule and two different drugs

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CA (1) CA2934030A1 (ru)
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