RU2017132185A - Конъюгаты аматоксин - антитело - Google Patents

Конъюгаты аматоксин - антитело Download PDF

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RU2017132185A
RU2017132185A RU2017132185A RU2017132185A RU2017132185A RU 2017132185 A RU2017132185 A RU 2017132185A RU 2017132185 A RU2017132185 A RU 2017132185A RU 2017132185 A RU2017132185 A RU 2017132185A RU 2017132185 A RU2017132185 A RU 2017132185A
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heavy chain
antibody
group
thiol
118cys
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RU2017132185A
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RU2724328C2 (ru
RU2017132185A3 (ru
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Ян АНДЕРЛЬ
Торстен ХЕХЛЕР
Кристоф МЮЛЛЕР
Андреас Паль
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Хайдельберг Фарма Гмбх
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    • 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
    • A61K47/6817—Toxins
    • A61K47/6831—Fungal toxins, e.g. alpha sarcine, mitogillin, zinniol or restrictocin
    • 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
    • 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
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—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
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/64—Cyclic peptides containing only normal peptide links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/55—Fusion polypeptide containing a fusion with a toxin, e.g. diphteria toxin

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Toxicology (AREA)
  • Oncology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Plant Substances (AREA)

Claims (14)

1. Конъюгат общей формулы:
Ama-L-X-S-Ab,
в котором Ama - аматоксин, L - линкер, X - фрагмент, полученный в результате связывания тиольной группы с тиол-реагирующей группой, S - атом серы аминокислотного остатка цистеина и Ab - последовательность антитела, или функциональный фрагмент антитела, содержащая(ий) указанный остаток цистеина, причем этот остаток цистеина выбран из перечня: 118Cys с тяжелой цепью, 239Cys с тяжелой цепью и 265Cys с тяжелой цепью, особенно 118Cys с тяжелой цепью и 265Cys с тяжелой цепью.
2. Конъюгат по п. 1, в котором линкер выбран из стабильного линкера и расщепляемого линкера.
3. Конъюгат по п. 1 или 2, в котором тиол-реагирующая группа выбрана из бромацетамида, йодацетамида, 4,6-дихлор-1,3,5-триазин-2-иламино, 4-[5-(метилсульфонил)-1Н-тетразол-1-ил]фенил, 2-(метилсульфонил)-бензо[d]тиазол-5-ил, 4-[5-(метилсульфонил)-1,3,4-оксадиазол-2-ил]-фенил, 2-пиридилдитио-, 2-(5-нитропиридил)дитио-, метилтиосульфонил и малеимид, особенно малеимид.
4. Способ синтеза конъюгата общей формулы:
Ama-L-X-S-Ab
реакцией соединения Ama-L-X', в котором X' - тиол-реагирующая группа, с антителом или функциональным фрагментом антитела, Ab-SH, в котором группа -SH - тиол аминокислотного остатка цистеина и Ab - последовательность антитела, или последовательность функционального фрагмента антитела, содержащая указанный остаток цистеина, причем этот остаток цистеина выбран из перечня: 118Cys с тяжелой цепью, 239Cys с тяжелой цепью и 265Cys с тяжелой цепью, особенно 118Cys с тяжелой цепью и 265Cys с тяжелой цепью.
5. Набор, содержащий (i) соединение Ama-L-X', где X'- тиол-реагирующая группа, и (ii) антитело, или функциональный фрагмент антитела, Ab-SH, в котором группа -SH - тиол аминокислотного остатка цистеина, и Ab - последовательность антитела, или последовательность функционального фрагмента антитела, содержащая указанный остаток цистеина, причем этот остаток цистеина выбран из перечня: 118Cys с тяжелой цепью, 239Cys с тяжелой цепью и 265Cys с тяжелой цепью, особенно 118Cys с тяжелой цепью и 265Cys с тяжелой цепью.
6. Способ синтеза соединения Ama-L-X', в котором X' - малеимидная группа, включающий этап (а), на котором осуществляют реакцию аматоксина, содержащего нуклеофильную группу, с соединением Y-L-X'', в котором
Y - уходящая группа и
X'' - защищенная малеимидная группа.
7. Фармацевтическая композиция, содержащая конъюгат по любому из пп. 1-3.
8. Способ лечения заболевания, ассоциированного с клетками, представляющими собой мишень, включающий этап, на котором осуществляют контакт указанных клеток с конъюгатом по любому из пп. 1-3, в котором указанное антитело, или указанный функциональный фрагмент антитела, является специфичным для указанной мишени.
RU2017132185A 2015-03-09 2016-03-07 Конъюгаты аматоксин - антитело RU2724328C2 (ru)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP15000681 2015-03-09
EP15000681.5 2015-03-09
PCT/EP2016/000397 WO2016142049A1 (en) 2015-03-09 2016-03-07 Amatoxin-antibody conjugates

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RU2017132185A true RU2017132185A (ru) 2019-04-09
RU2017132185A3 RU2017132185A3 (ru) 2019-05-23
RU2724328C2 RU2724328C2 (ru) 2020-06-23

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EP (2) EP4115910A1 (ru)
JP (2) JP6863900B2 (ru)
KR (1) KR20180003537A (ru)
CN (2) CN114395050A (ru)
AU (1) AU2016228415B2 (ru)
BR (1) BR112017019300B1 (ru)
CA (1) CA2978064A1 (ru)
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ES (1) ES2968012T3 (ru)
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HR (1) HRP20240075T1 (ru)
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MX (1) MX2017011281A (ru)
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Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9938323B2 (en) 2014-11-06 2018-04-10 Novartis Ag Amatoxin derivatives and conjugates thereof as inhibitors of RNA polymerase
AU2016228415B2 (en) * 2015-03-09 2021-04-01 Heidelberg Pharma Gmbh Amatoxin-antibody conjugates
EP3222292A1 (en) * 2016-03-03 2017-09-27 Heidelberg Pharma GmbH Amanitin conjugates
MX2018015684A (es) 2016-06-17 2019-08-29 Magenta Therapeutics Inc Composiciones y metodos para el agotamiento de celulas cd117.
BR112018076263A2 (pt) 2016-06-17 2019-03-26 Magenta Therapeutics, Inc. composições e métodos para a depleção de células
KR102455175B1 (ko) * 2016-12-23 2022-10-17 하이델베르크 파마 리서치 게엠베하 아마니틴 접합체
EP3571230A4 (en) 2017-01-20 2020-12-16 Magenta Therapeutics, Inc. COMPOSITIONS AND METHODS FOR DELETION OF CD137 + CELLS
AU2018314668B2 (en) * 2017-08-07 2022-06-02 Heidelberg Pharma Research Gmbh Novel method for synthesizing amanitins
EP3738608A4 (en) * 2017-08-18 2021-12-08 Sichuan Baili Pharm Co. Ltd NON-NATURAL AMATOXIN TYPE ANTIBODY CONJUGATE
WO2019047941A1 (zh) * 2017-09-08 2019-03-14 四川百利药业有限责任公司 鹅膏毒肽类抗体偶联物
JP7389022B2 (ja) * 2017-09-22 2023-11-29 ハイデルベルク ファルマ リサーチ ゲゼルシャフト ミット ベシュレンクテル ハフツング Ｐｓｍａ標的化アマニチンコンジュゲート
CA3079897A1 (en) * 2017-10-24 2019-05-02 Magenta Therapeutics, Inc. Compositions and methods for the depletion of cd117+ cells
AU2018354189A1 (en) 2017-10-24 2020-04-23 Crispr Therapeutics Ag Compositions and methods for the depletion of CD117+ cells
SG11202004294XA (en) * 2017-11-29 2020-06-29 Magenta Therapeutics Inc Compositions and methods for the depletion of cd5+ cells
CA3080236A1 (en) 2017-12-15 2019-06-20 Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. Bioactive molecule conjugate, preparation method and use thereof
US20210077571A1 (en) * 2018-04-13 2021-03-18 Heidelberg Pharma Research Gmbh Targeted amatoxin conjugate for the treatment of solid tumors
WO2020023556A1 (en) * 2018-07-23 2020-01-30 Magenta Therapeutics, Inc. Use of anti-cd137 antibody drug conjugate (adc) in allogeneic cell therapy
MX2021004231A (es) * 2018-10-23 2021-06-15 Magenta Therapeutics Inc Conjugados de anticuerpos y fármacos (caf) con silenciamiento de fc y usos de los mismos.
WO2020176794A1 (en) * 2019-02-27 2020-09-03 Angiex, Inc. Antibody-drug conjugates comprising anti-tm4sf1 antibodies and methods of using the same
SG11202110287QA (en) * 2019-04-24 2021-10-28 Heidelberg Pharma Res Gmbh Amatoxin antibody-drug conjugates and uses thereof
WO2020234461A1 (en) 2019-05-23 2020-11-26 Heidelberg Pharma Research Gmbh Antibody drug conjugates with cleavable linkers
AR120218A1 (es) * 2019-10-15 2022-02-02 Heidelberg Pharma Res Gmbh Conjugados de amatoxina y anticuerpo específico de linfocitos b
CN111308100B (zh) * 2020-04-13 2023-04-21 北京维德维康生物技术有限公司 一种检测β-鹅膏毒肽的酶联免疫试剂盒及其制备和应用
JP2023529455A (ja) 2020-06-09 2023-07-10 ハイデルベルク ファルマ リサーチ ゲゼルシャフト ミット ベシュレンクテル ハフツング チオエーテル含有ペプチドの合成方法
WO2021255217A1 (en) 2020-06-19 2021-12-23 Heidelberg Pharma Research Gmbh Amatoxin and amatoxin conjugates for use in inhibition of rna virus replication
MX2023005192A (es) 2020-11-04 2023-05-15 Heidelberg Pharma Res Gmbh Composicion que comprende una combinacion de inhibidor de punto de control inmunitario y conjugado de anticuerpo-amatoxina para uso en la terapia del cancer.
IL304966A (en) 2021-03-19 2023-10-01 Heidelberg Pharma Res B-lymphocyte specific Amatoxin conjugated antibodies
TW202304929A (zh) * 2021-04-29 2023-02-01 美商艾伯維有限公司 抗c-Met抗體藥物結合物
WO2022233718A2 (en) 2021-05-03 2022-11-10 Merck Patent Gmbh Her2 targeting fc antigen binding fragment-drug conjugates
CN113980909B (zh) * 2021-11-16 2022-06-14 江南大学 一种α-鹅膏蕈碱人工抗原、单克隆抗体、杂交瘤细胞株及应用
WO2023194539A1 (en) 2022-04-07 2023-10-12 Heidelberg Pharma Research Gmbh Methods of improving the therapeutic index of amatoxin-antibody conjugates
WO2024094688A1 (en) 2022-11-01 2024-05-10 Heidelberg Pharma Research Gmbh Anti-gucy2c antibody and uses thereof
WO2024189048A1 (en) 2023-03-13 2024-09-19 Heidelberg Pharma Research Gmbh Subcutaneously administered antibody-drug conjugates for use in cancer treatment
WO2024194851A1 (en) 2023-03-23 2024-09-26 Beigene Switzerland Gmbh Bioactive conjugate, preparation method therefor and use thereof

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE69120146T2 (de) 1990-01-12 1996-12-12 Cell Genesys Inc Erzeugung xenogener antikörper
US6214345B1 (en) 1993-05-14 2001-04-10 Bristol-Myers Squibb Co. Lysosomal enzyme-cleavable antitumor drug conjugates
US7115390B1 (en) * 1998-12-14 2006-10-03 Fibrogen, Inc. Connective tissue growth factor fragments and methods and uses thereof
NZ553500A (en) 2004-09-23 2009-11-27 Genentech Inc Genentech Inc Cysteine engineered antibodies and conjugates withCysteine engineered antibodies and conjugates with a free cysteine amino acid in the heavy chain a free cysteine amino acid in the heavy chain
ES2371085T3 (es) 2006-05-27 2011-12-27 Faulstich, Heinz, Dr. Utilización de conjugados de amatoxinas o falotoxinas con macromoléculas para la terapia tumoral y de la inflamación.
ES2523915T5 (es) * 2006-12-01 2022-05-26 Seagen Inc Agentes de unión a la diana variantes y usos de los mismos
EP3192529B1 (en) 2009-04-08 2020-03-25 Faulstich, Heinz, Dr. Amatoxin-armed therapeutic cell surface binding components designed for tumour therapy
WO2010115630A1 (en) 2009-04-08 2010-10-14 Deutsches Krebsforschungszentrum Amatoxin-armed target-binding moieties for the treatment of cancer
MX2012000121A (es) 2009-06-22 2012-03-07 Medimmune Llc Regiones fc modificadas para la conjugacion especifica del sitio.
JP5972864B2 (ja) 2010-04-15 2016-08-17 メディミューン リミテッド ピロロベンゾジアゼピン及びそれらのコンジュゲート
ES2402254T3 (es) * 2010-09-30 2013-04-30 Heidelberg Pharma Ag Conjugados de amatoxinas con ligadores mejorados
WO2014043403A1 (en) * 2012-09-12 2014-03-20 Agensys, Inc. Amatoxin derivatives and cell-permeable conjugates thereof as inhibitors of rna polymerase
EP2774624A1 (en) * 2013-03-04 2014-09-10 Heidelberg Pharma GmbH Amatoxin derivatives
NZ710745A (en) 2013-03-13 2019-03-29 Genentech Inc Pyrrolobenzodiazepines and conjugates thereof
WO2015023355A1 (en) * 2013-08-12 2015-02-19 Genentech, Inc. 1-(chloromethyl)-2,3-dihydro-1h-benzo[e]indole dimer antibody-drug conjugate compounds, and methods of use and treatment
CA2938450C (en) * 2014-02-11 2023-10-17 Seattle Genetics, Inc. Selective reduction of proteins
US9938323B2 (en) * 2014-11-06 2018-04-10 Novartis Ag Amatoxin derivatives and conjugates thereof as inhibitors of RNA polymerase
AU2016228415B2 (en) * 2015-03-09 2021-04-01 Heidelberg Pharma Gmbh Amatoxin-antibody conjugates
US20230057350A1 (en) * 2019-01-31 2023-02-23 Hangzhou Dac Biotech Co., Ltd. A conjugate of an amanita toxin with branched linkers
SG11202110287QA (en) * 2019-04-24 2021-10-28 Heidelberg Pharma Res Gmbh Amatoxin antibody-drug conjugates and uses thereof

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