MX347298B - In vivo polynucleotide delivery conjugates having enzyme sensitive linkages. - Google Patents

In vivo polynucleotide delivery conjugates having enzyme sensitive linkages.

Info

Publication number
MX347298B
MX347298B MX2016006733A MX2016006733A MX347298B MX 347298 B MX347298 B MX 347298B MX 2016006733 A MX2016006733 A MX 2016006733A MX 2016006733 A MX2016006733 A MX 2016006733A MX 347298 B MX347298 B MX 347298B
Authority
MX
Mexico
Prior art keywords
rnai
polynucleotide delivery
vivo
delivery conjugates
enzyme sensitive
Prior art date
Application number
MX2016006733A
Other languages
Spanish (es)
Inventor
Mohr Peter
H Wakefield Darren
B Rozema David
L Lewis David
Hadwiger Philipp
V Blokhin Andrei
C Carlson Jeffrey
A Kitas Eric
A Wolff Jon
Roehl Ingo
Hoffmann Torsten
Jahn-Hofmann Kerstin
Martin Mueller Hans
Ott Guenther
D Benson Jonathan
Original Assignee
Arrowhead Res Corp
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
Priority claimed from US13/336,028 external-priority patent/US8426554B2/en
Application filed by Arrowhead Res Corp filed Critical Arrowhead Res Corp
Publication of MX347298B publication Critical patent/MX347298B/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C07C233/04—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C233/05—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • 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
    • A61K47/56—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/58—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
    • 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
    • A61K47/56—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/96—Esters of carbonic or haloformic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06104—Dipeptides with the first amino acid being acidic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06104—Dipeptides with the first amino acid being acidic
    • C07K5/06113—Asp- or Asn-amino acid
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
    • C08G63/91—Polymers modified by chemical after-treatment
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/111—General methods applicable to biologically active non-coding nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering N.A.
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3513—Protein; Peptide
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/32—Special delivery means, e.g. tissue-specific
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/95—Protection of vectors from inactivation by agents such as antibodies or enzymes, e.g. using polymers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2810/00—Vectors comprising a targeting moiety
    • C12N2810/10—Vectors comprising a non-peptidic targeting moiety

Abstract

The present invention is directed compositions for delivery of RNA interference (RNAi) polynucleotides to cells in vivo. The compositions comprise amphipathic membrane active poiyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines (dynamic polyconjugate or DPC) are further covalentiy linked to an RNAi polynucleotide or co-administered with a targeted RNAi polynucleotide-targeting molecule conjugate.
MX2016006733A 2010-12-29 2011-12-28 In vivo polynucleotide delivery conjugates having enzyme sensitive linkages. MX347298B (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201061427936P 2010-12-29 2010-12-29
US13/336,028 US8426554B2 (en) 2010-12-29 2011-12-23 In vivo polynucleotide delivery conjugates having enzyme sensitive linkages
PCT/US2011/067588 WO2012092373A2 (en) 2010-12-29 2011-12-28 In vivo polynucleotide delivery conjugates having enzyme sensitive linkages

Publications (1)

Publication Number Publication Date
MX347298B true MX347298B (en) 2017-04-21

Family

ID=46383848

Family Applications (2)

Application Number Title Priority Date Filing Date
MX2013007316A MX341118B (en) 2010-12-29 2011-12-28 In vivo polynucleotide delivery conjugates having enzyme sensitive linkages.
MX2016006733A MX347298B (en) 2010-12-29 2011-12-28 In vivo polynucleotide delivery conjugates having enzyme sensitive linkages.

Family Applications Before (1)

Application Number Title Priority Date Filing Date
MX2013007316A MX341118B (en) 2010-12-29 2011-12-28 In vivo polynucleotide delivery conjugates having enzyme sensitive linkages.

Country Status (15)

Country Link
EP (1) EP2658579A4 (en)
JP (1) JP5941926B2 (en)
KR (1) KR20130136494A (en)
CN (1) CN103491982B (en)
AU (1) AU2011352204B2 (en)
BR (1) BR112013014115A2 (en)
CA (1) CA2816041C (en)
CL (2) CL2013001876A1 (en)
MX (2) MX341118B (en)
NZ (1) NZ611656A (en)
PE (1) PE20140198A1 (en)
RU (1) RU2619453C2 (en)
SG (1) SG189942A1 (en)
WO (1) WO2012092373A2 (en)
ZA (1) ZA201302896B (en)

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CA2889044A1 (en) 2012-11-15 2014-05-22 Roche Innovation Center Copenhagen A/S Anti apob antisense conjugate compounds
EP3030244B1 (en) * 2013-08-07 2021-04-21 Arrowhead Pharmaceuticals, Inc. Polyconjugates for delivery of rnai triggers to tumor cells in vivo
JOP20210043A1 (en) 2015-10-01 2017-06-16 Arrowhead Pharmaceuticals Inc Compositions and Methods for Inhibiting Gene Expression of LPA
MA45328A (en) 2016-04-01 2019-02-06 Avidity Biosciences Llc NUCLEIC ACID-POLYPEPTIDE COMPOSITIONS AND USES THEREOF
EP3630742B1 (en) * 2017-05-24 2023-08-16 Ramot at Tel-Aviv University Ltd. Chemiluminescent probes for imaging/detection of proteases
MX2020005860A (en) 2017-12-06 2020-09-09 Avidity Biosciences Inc Compositions and methods of treating muscle atrophy and myotonic dystrophy.
CN115244064A (en) * 2018-12-28 2022-10-25 圣诺制药公司 Targeted delivery of therapeutic molecules
US11525137B2 (en) 2020-03-19 2022-12-13 Avidity Biosciences, Inc. Compositions and methods of treating Facioscapulohumeral muscular dystrophy
CN115209922A (en) * 2021-01-28 2022-10-18 南京桦冠生物技术有限公司 Conjugates and uses thereof
KR20240024104A (en) * 2021-06-24 2024-02-23 가부시키가이샤 토호쿠 테크노 아치 fluorescent probe
KR20230016999A (en) * 2021-07-27 2023-02-03 안동대학교 산학협력단 Pharmaceutical composition comprising the extract from vespa velutina nigrithorax as an effective component for prevention or treatment of thrombosis and health functional food comprising the same
CN113621003B (en) * 2021-09-10 2023-02-03 国科温州研究院(温州生物材料与工程研究所) Method for preparing organic molecule covalent modification functionalized nucleic acid material and application thereof
AU2022345098A1 (en) 2021-09-16 2024-04-04 Avidity Biosciences, Inc. Compositions and methods of treating facioscapulohumeral muscular dystrophy

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US6214345B1 (en) * 1993-05-14 2001-04-10 Bristol-Myers Squibb Co. Lysosomal enzyme-cleavable antitumor drug conjugates
US6180095B1 (en) * 1997-12-17 2001-01-30 Enzon, Inc. Polymeric prodrugs of amino- and hydroxyl-containing bioactive agents
AU3366901A (en) * 1999-12-30 2001-07-16 Novartis Ag Novel colloid synthetic vectors for gene therapy
PL358187A1 (en) * 2000-02-24 2004-08-09 Genentech, Inc. Caspase activated prodrugs therapy
EP1243276A1 (en) * 2001-03-23 2002-09-25 Franciscus Marinus Hendrikus De Groot Elongated and multiple spacers containing activatible prodrugs
US7091186B2 (en) * 2001-09-24 2006-08-15 Seattle Genetics, Inc. p-Amidobenzylethers in drug delivery agents
US7541330B2 (en) * 2004-06-15 2009-06-02 Kosan Biosciences Incorporated Conjugates with reduced adverse systemic effects
CA2627190A1 (en) * 2005-11-10 2007-05-24 Medarex, Inc. Duocarmycin derivatives as novel cytotoxic compounds and conjugates
CA2660842C (en) * 2006-08-18 2012-03-13 F. Hoffmann-La Roche Ag Polyconjugates for in vivo delivery of polynucleotides
RU2430740C2 (en) * 2006-08-18 2011-10-10 Ф.Хоффманн-Ля Рош Аг Polyconjugates for polynucleotide introduction in vivo
WO2008088658A2 (en) * 2007-01-17 2008-07-24 Immunomedics, Inc. Polymeric carriers of therapeutic agents and recognition moieties for antibody-based targeting of disease sites
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US8501930B2 (en) * 2010-12-17 2013-08-06 Arrowhead Madison Inc. Peptide-based in vivo siRNA delivery system

Also Published As

Publication number Publication date
JP5941926B2 (en) 2016-06-29
SG189942A1 (en) 2013-06-28
MX2013007316A (en) 2013-07-29
PE20140198A1 (en) 2014-02-21
JP2014505685A (en) 2014-03-06
KR20130136494A (en) 2013-12-12
MX341118B (en) 2016-08-09
CL2015003580A1 (en) 2016-07-15
EP2658579A2 (en) 2013-11-06
CA2816041C (en) 2019-01-08
CL2013001876A1 (en) 2014-04-11
ZA201302896B (en) 2014-07-25
WO2012092373A2 (en) 2012-07-05
CN103491982B (en) 2017-09-12
BR112013014115A2 (en) 2019-09-24
CN103491982A (en) 2014-01-01
AU2011352204A1 (en) 2013-05-02
WO2012092373A3 (en) 2013-10-24
AU2011352204B2 (en) 2015-05-21
RU2013117286A (en) 2015-03-10
RU2619453C2 (en) 2017-05-16
CA2816041A1 (en) 2012-07-05
EP2658579A4 (en) 2015-07-22
NZ611656A (en) 2014-10-31

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