EP3775257A4 - Procédé et système pour caractériser des affections liées à une allergie et associées à des micro-organismes - Google Patents

Procédé et système pour caractériser des affections liées à une allergie et associées à des micro-organismes Download PDF

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Publication number
EP3775257A4
EP3775257A4 EP17881032.1A EP17881032A EP3775257A4 EP 3775257 A4 EP3775257 A4 EP 3775257A4 EP 17881032 A EP17881032 A EP 17881032A EP 3775257 A4 EP3775257 A4 EP 3775257A4
Authority
EP
European Patent Office
Prior art keywords
allergy
characterizing
microorganisms
conditions associated
related conditions
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.)
Withdrawn
Application number
EP17881032.1A
Other languages
German (de)
English (en)
Other versions
EP3775257A1 (fr
Inventor
Zachary APTE
Jessica RICHMAN
Daniel Almonacid
Catalina Valdivia
Rodrigo Ortiz
Inti PEDROSA
Victoria Dumas
Paz Tapia
Eduardo Morales
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.)
Psomagen Inc
Original Assignee
Psomagen Inc
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 US15/606,743 external-priority patent/US10803991B2/en
Application filed by Psomagen Inc filed Critical Psomagen Inc
Publication of EP3775257A1 publication Critical patent/EP3775257A1/fr
Publication of EP3775257A4 publication Critical patent/EP3775257A4/fr
Withdrawn legal-status Critical Current

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    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B30/00—ICT specially adapted for sequence analysis involving nucleotides or amino acids
    • G16B30/10—Sequence alignment; Homology search
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B20/00—ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B20/00—ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
    • G16B20/40—Population genetics; Linkage disequilibrium
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B40/00—ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
    • G16B40/20—Supervised data analysis
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B40/00—ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
    • G16B40/30—Unsupervised data analysis
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B50/00—ICT programming tools or database systems specially adapted for bioinformatics
    • G16B50/30—Data warehousing; Computing architectures
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H10/00—ICT specially adapted for the handling or processing of patient-related medical or healthcare data
    • G16H10/40—ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H20/00—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
    • G16H20/10—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H20/00—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
    • G16H20/30—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to physical therapies or activities, e.g. physiotherapy, acupressure or exercising
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H20/00—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
    • G16H20/60—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to nutrition control, e.g. diets
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H20/00—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
    • G16H20/70—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to mental therapies, e.g. psychological therapy or autogenous training
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H40/00—ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices
    • G16H40/60—ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices
    • G16H40/63—ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for local operation
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H50/00—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
    • G16H50/20—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H50/00—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
    • G16H50/50—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for simulation or modelling of medical disorders
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A90/00—Technologies having an indirect contribution to adaptation to climate change
    • Y02A90/10—Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Microbiology (AREA)
  • Immunology (AREA)
  • Bioinformatics & Computational Biology (AREA)
  • Theoretical Computer Science (AREA)
  • Medical Informatics (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Evolutionary Biology (AREA)
  • Pathology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
EP17881032.1A 2016-12-15 2017-12-15 Procédé et système pour caractériser des affections liées à une allergie et associées à des micro-organismes Withdrawn EP3775257A4 (fr)

Applications Claiming Priority (16)

Application Number Priority Date Filing Date Title
US201662434881P 2016-12-15 2016-12-15
US201662434917P 2016-12-15 2016-12-15
US201662434902P 2016-12-15 2016-12-15
US201662434912P 2016-12-15 2016-12-15
US201662434923P 2016-12-15 2016-12-15
US201662434894P 2016-12-15 2016-12-15
US15/606,743 US10803991B2 (en) 2014-10-21 2017-05-26 Method and system for microbiome-derived diagnostics and therapeutics
US201762522293P 2017-06-20 2017-06-20
US201762555782P 2017-09-08 2017-09-08
US201762557423P 2017-09-12 2017-09-12
US201762558489P 2017-09-14 2017-09-14
US201762564777P 2017-09-28 2017-09-28
US201762582172P 2017-11-06 2017-11-06
US201762582191P 2017-11-06 2017-11-06
US201762582162P 2017-11-06 2017-11-06
PCT/US2017/066866 WO2018112437A1 (fr) 2016-12-15 2017-12-15 Procédé et système pour caractériser des affections liées à une allergie et associées à des micro-organismes

Publications (2)

Publication Number Publication Date
EP3775257A1 EP3775257A1 (fr) 2021-02-17
EP3775257A4 true EP3775257A4 (fr) 2022-03-09

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ID=62559438

Family Applications (1)

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EP17881032.1A Withdrawn EP3775257A4 (fr) 2016-12-15 2017-12-15 Procédé et système pour caractériser des affections liées à une allergie et associées à des micro-organismes

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EP (1) EP3775257A4 (fr)
WO (1) WO2018112437A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110343637B (zh) * 2019-06-28 2021-06-08 浙江工业大学 肠杆菌hy1及在降解对苯二甲酸双羟乙酯中的应用
CN114686557A (zh) * 2022-03-07 2022-07-01 中国农业大学 用于评估食物过敏的肠道菌群生物标志物及其用途和试剂盒

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016168354A1 (fr) * 2015-04-13 2016-10-20 uBiome, Inc. Procédé et système de diagnostic et de traitement dérivés du microbiome pour des pathologies associées aux caractéristiques fonctionnelles du microbiome
WO2016168344A1 (fr) * 2015-04-13 2016-10-20 uBiome, Inc. Procédé et système pour la caractérisation, le diagnostic et le traitement dérivés du microbiome d'affections associées à des caractéristiques fonctionnelles

Family Cites Families (3)

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Publication number Priority date Publication date Assignee Title
CN105407728A (zh) * 2013-07-21 2016-03-16 霍勒拜欧姆公司 用于微生物组表征、监测和治疗的方法和系统
US9760676B2 (en) * 2014-10-21 2017-09-12 uBiome, Inc. Method and system for microbiome-derived diagnostics and therapeutics for endocrine system conditions
MA41020A (fr) * 2014-11-25 2017-10-03 Evelo Biosciences Inc Compositions probiotiques et prébiotiques, et leurs procédés d'utilisation pour la modulation du microbiome

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016168354A1 (fr) * 2015-04-13 2016-10-20 uBiome, Inc. Procédé et système de diagnostic et de traitement dérivés du microbiome pour des pathologies associées aux caractéristiques fonctionnelles du microbiome
WO2016168344A1 (fr) * 2015-04-13 2016-10-20 uBiome, Inc. Procédé et système pour la caractérisation, le diagnostic et le traitement dérivés du microbiome d'affections associées à des caractéristiques fonctionnelles

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
ALMONACID DANIEL E. ET AL: "16S rRNA gene sequencing as a clinical diagnostic aid for gastroitestinal related conditions", BIORXIV, 31 October 2016 (2016-10-31), XP055820608, Retrieved from the Internet <URL:https://www.biorxiv.org/content/10.1101/084657v1.> [retrieved on 20210702], DOI: 10.1101/084657 *
BLÁZQUEZ ANA B ET AL: "Microbiome and food allergy", TRANSLATIONAL RESEARCH, ELSEVIER, AMSTERDAM, NL, vol. 179, 13 September 2016 (2016-09-13), pages 199 - 203, XP029850269, ISSN: 1931-5244, DOI: 10.1016/J.TRSL.2016.09.003 *
COPE E K ET AL: "Novel Microbiome-Based Therapeutics for Chronic Rhinosinusitis", CURRENT ALLERGY AND ASTHMA REPORTS, SPRINGER US, NEW YORK, vol. 15, no. 3, 17 March 2015 (2015-03-17), pages 1 - 10, XP035510395, ISSN: 1529-7322, [retrieved on 20150317], DOI: 10.1007/S11882-014-0504-Y *
DIESNER SUSANNE C ET AL: "A distinct microbiota composition is associated with protection from food allergy in an oral mouse immunization model", CLINICAL IMMUNOLOGY, ELSEVIER, AMSTERDAM, NL, vol. 173, 24 October 2016 (2016-10-24), pages 10 - 18, XP029842626, ISSN: 1521-6616, DOI: 10.1016/J.CLIM.2016.10.009 *
FUJIMURA KEI E ET AL: "Microbiota in Allergy and Asthma and the Emerging Relationship with the Gut Microbiome", CELL HOST & MICROBE, ELSEVIER, NL, vol. 17, no. 5, 13 May 2015 (2015-05-13), pages 592 - 602, XP029169452, ISSN: 1931-3128, DOI: 10.1016/J.CHOM.2015.04.007 *
JOHN MOLLOY ET AL: "The Potential Link between Gut Microbiota and IgE-Mediated Food Allergy in Early Life", INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH, vol. 10, no. 12, 16 December 2013 (2013-12-16), pages 7235 - 7256, XP055730645, DOI: 10.3390/ijerph10127235 *
NADJA B. KRISTENSEN ET AL: "Alterations in fecal microbiota composition by probiotic supplementation in healthy adults: a systematic review of randomized controlled trials", GENOME MEDICINE, vol. 8, no. 1, 10 May 2016 (2016-05-10), XP055439213, DOI: 10.1186/s13073-016-0300-5 *
See also references of WO2018112437A1 *
SHEN NAN ET AL: "Engineering the Microbiome: a Novel Approach to Immunotherapy for Allergic and Immune Diseases", CURRENT ALLERGY AND ASTHMA REPORTS, SPRINGER US, NEW YORK, vol. 15, no. 7, 5 July 2015 (2015-07-05), pages 1 - 10, XP035511567, ISSN: 1529-7322, [retrieved on 20150705], DOI: 10.1007/S11882-015-0538-9 *

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EP3775257A1 (fr) 2021-02-17
WO2018112437A1 (fr) 2018-06-21

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