RU2017132185A - Конъюгаты аматоксин - антитело - Google Patents
Конъюгаты аматоксин - антитело Download PDFInfo
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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
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- thiol
- 118cys
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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
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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
-
- 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
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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
- A61K47/6835—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
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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
- A61K47/6835—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
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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
- A61K47/6889—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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
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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
- 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
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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
- 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
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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
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
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- 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
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- 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
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- 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
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- 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
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.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP15000681.5 | 2015-03-09 | ||
EP15000681 | 2015-03-09 | ||
PCT/EP2016/000397 WO2016142049A1 (en) | 2015-03-09 | 2016-03-07 | Amatoxin-antibody conjugates |
Publications (3)
Publication Number | Publication Date |
---|---|
RU2017132185A true RU2017132185A (ru) | 2019-04-09 |
RU2017132185A3 RU2017132185A3 (ru) | 2019-05-23 |
RU2724328C2 RU2724328C2 (ru) | 2020-06-23 |
Family
ID=52648788
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
RU2017132185A RU2724328C2 (ru) | 2015-03-09 | 2016-03-07 | Конъюгаты аматоксин - антитело |
Country Status (25)
Country | Link |
---|---|
US (1) | US10842882B2 (ru) |
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) |
DK (1) | DK3268047T3 (ru) |
ES (1) | ES2968012T3 (ru) |
FI (1) | FI3268047T3 (ru) |
HR (1) | HRP20240075T1 (ru) |
HU (1) | HUE064698T2 (ru) |
IL (2) | IL254108B (ru) |
LT (1) | LT3268047T (ru) |
MX (1) | MX2017011281A (ru) |
NZ (1) | NZ734892A (ru) |
PL (1) | PL3268047T3 (ru) |
PT (1) | PT3268047T (ru) |
RS (1) | RS64955B1 (ru) |
RU (1) | RU2724328C2 (ru) |
SG (2) | SG11201707054PA (ru) |
SI (1) | SI3268047T1 (ru) |
WO (1) | WO2016142049A1 (ru) |
ZA (1) | ZA201705770B (ru) |
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IL263744B2 (en) | 2016-06-17 | 2023-11-01 | Magenta Therapeutics Inc | Compositions and methods for depleting CD117 plus cells |
BR112019012937A2 (pt) | 2016-12-23 | 2019-12-10 | Heidelberg Pharma Res Gmbh | novo conjugado de amanitina |
BR112019014991A2 (pt) | 2017-01-20 | 2020-04-07 | Magenta Therapeutics Inc | composições e métodos para a supressão de células cd137+ |
AU2018314668B2 (en) * | 2017-08-07 | 2022-06-02 | Heidelberg Pharma Research Gmbh | Novel method for synthesizing amanitins |
WO2019034175A1 (zh) * | 2017-08-18 | 2019-02-21 | 四川百利药业有限责任公司 | 一种非天然鹅膏毒肽类抗体偶联物 |
JP7296396B2 (ja) * | 2017-09-08 | 2023-06-22 | バイリ-バイオ(チェンドゥ)ファーマスーティカル シーオー.,エルティーディー. | アマニチン類抗体複合物 |
EP3684416B1 (en) * | 2017-09-22 | 2023-03-15 | Heidelberg Pharma Research GmbH | Psma-targeting amanitin conjugates |
CA3079897A1 (en) | 2017-10-24 | 2019-05-02 | Magenta Therapeutics, Inc. | Compositions and methods for the depletion of cd117+ cells |
WO2019084057A2 (en) | 2017-10-24 | 2019-05-02 | Magenta Therapeutics, Inc. | COMPOSITIONS AND METHODS FOR DEPLOYING CD117 + CELLS |
CN113683622A (zh) | 2017-12-15 | 2021-11-23 | 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 |
CN111989122A (zh) * | 2018-04-13 | 2020-11-24 | 海德堡医药研究有限责任公司 | 用于治疗实体瘤的靶向鹅膏毒素缀合物 |
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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 |
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WO2021255217A1 (en) | 2020-06-19 | 2021-12-23 | Heidelberg Pharma Research Gmbh | Amatoxin and amatoxin conjugates for use in inhibition of rna virus replication |
KR20230104653A (ko) | 2020-11-04 | 2023-07-10 | 하이델베르크 파마 리서치 게엠베하 | 암 요법에 사용하기 위한 면역 체크포인트 억제제 및 항체-아마톡신 접합체의 조합물을 포함하는 조성물 |
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