CN115362252A - 增殖细胞和细胞生产物的生产法、间充质干细胞群和干细胞培养上清及其生产法、治疗剂 - Google Patents

增殖细胞和细胞生产物的生产法、间充质干细胞群和干细胞培养上清及其生产法、治疗剂 Download PDF

Info

Publication number
CN115362252A
CN115362252A CN202180024893.1A CN202180024893A CN115362252A CN 115362252 A CN115362252 A CN 115362252A CN 202180024893 A CN202180024893 A CN 202180024893A CN 115362252 A CN115362252 A CN 115362252A
Authority
CN
China
Prior art keywords
cells
culture
medium
stem cells
mesenchymal stem
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.)
Pending
Application number
CN202180024893.1A
Other languages
English (en)
Chinese (zh)
Inventor
柳田康友
李家中豪
石田尾武文
南一成
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.)
Exocrine Therapy Co ltd
Original Assignee
Exocrine Therapy Co ltd
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
Application filed by Exocrine Therapy Co ltd filed Critical Exocrine Therapy Co ltd
Priority to CN202310081275.1A priority Critical patent/CN116179480A/zh
Publication of CN115362252A publication Critical patent/CN115362252A/zh
Pending legal-status Critical Current

Links

Images

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0652Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0662Stem cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/28Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0652Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0662Stem cells
    • C12N5/0665Blood-borne mesenchymal stem cells, e.g. from umbilical cord blood
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0652Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0662Stem cells
    • C12N5/0668Mesenchymal stem cells from other natural sources
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10Growth factors
    • C12N2501/12Hepatocyte growth factor [HGF]
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10Growth factors
    • C12N2501/15Transforming growth factor beta (TGF-β)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20Cytokines; Chemokines
    • C12N2501/21Chemokines, e.g. MIP-1, MIP-2, RANTES, MCP, PF-4
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20Cytokines; Chemokines
    • C12N2501/23Interleukins [IL]
    • C12N2501/2301Interleukin-1 (IL-1)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20Cytokines; Chemokines
    • C12N2501/23Interleukins [IL]
    • C12N2501/2304Interleukin-4 (IL-4)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20Cytokines; Chemokines
    • C12N2501/23Interleukins [IL]
    • C12N2501/231Interleukin-10 (IL-10)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20Cytokines; Chemokines
    • C12N2501/25Tumour necrosing factors [TNF]
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00Active agents used in cell culture processes, e.g. differentation
    • C12N2501/50Cell markers; Cell surface determinants
    • C12N2501/599Cell markers; Cell surface determinants with CD designations not provided for elsewhere
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2533/00Supports or coatings for cell culture, characterised by material
    • C12N2533/50Proteins
    • C12N2533/52Fibronectin; Laminin

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • General Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Microbiology (AREA)
  • Rheumatology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biochemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
CN202180024893.1A 2020-03-31 2021-03-26 增殖细胞和细胞生产物的生产法、间充质干细胞群和干细胞培养上清及其生产法、治疗剂 Pending CN115362252A (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202310081275.1A CN116179480A (zh) 2020-03-31 2021-03-26 增殖细胞和细胞生产物的生产法、间充质干细胞群和干细胞培养上清及其生产法、治疗剂

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP2020063408 2020-03-31
JP2020-063408 2020-03-31
PCT/JP2021/013099 WO2021200744A1 (ja) 2020-03-31 2021-03-26 増殖細胞の生産方法、細胞生産物の生産方法、間葉系幹細胞集団およびその生産方法、幹細胞の培養上清およびその生産方法、並びに治療剤

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CN202310081275.1A Division CN116179480A (zh) 2020-03-31 2021-03-26 增殖细胞和细胞生产物的生产法、间充质干细胞群和干细胞培养上清及其生产法、治疗剂

Publications (1)

Publication Number Publication Date
CN115362252A true CN115362252A (zh) 2022-11-18

Family

ID=77930052

Family Applications (2)

Application Number Title Priority Date Filing Date
CN202180024893.1A Pending CN115362252A (zh) 2020-03-31 2021-03-26 增殖细胞和细胞生产物的生产法、间充质干细胞群和干细胞培养上清及其生产法、治疗剂
CN202310081275.1A Withdrawn CN116179480A (zh) 2020-03-31 2021-03-26 增殖细胞和细胞生产物的生产法、间充质干细胞群和干细胞培养上清及其生产法、治疗剂

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN202310081275.1A Withdrawn CN116179480A (zh) 2020-03-31 2021-03-26 增殖细胞和细胞生产物的生产法、间充质干细胞群和干细胞培养上清及其生产法、治疗剂

Country Status (8)

Country Link
US (1) US20230172992A1 (https=)
EP (2) EP4130240A4 (https=)
JP (3) JPWO2021200744A1 (https=)
CN (2) CN115362252A (https=)
AU (2) AU2021247879B2 (https=)
CA (2) CA3177567A1 (https=)
TW (2) TW202204605A (https=)
WO (1) WO2021200744A1 (https=)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPWO2021200744A1 (https=) * 2020-03-31 2021-10-07
EP4324914B1 (en) * 2021-06-11 2026-03-18 Fullstem Co., Ltd. Exosome production promoting agent and exosome production promoting method
JP7763475B2 (ja) * 2021-12-24 2025-11-04 株式会社日本バイオセラピー研究所 培養上清を生産する方法
WO2024019080A1 (ja) * 2022-07-19 2024-01-25 国立大学法人 長崎大学 血管内皮増殖因子を高発現する臍帯由来間葉系細胞の製造方法、および肺疾患治療用医薬組成物
JP7851648B2 (ja) * 2022-12-23 2026-04-27 Cell Exosome Therapeutics株式会社 間葉系幹細胞又はその培養上清の利用
WO2025151805A1 (en) * 2024-01-10 2025-07-17 Biotech Therapeutics, LLC Mesenchymal stromal cell-derived extracellular vesicle-exosomes

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160137965A1 (en) * 2013-06-12 2016-05-19 Osaka University Cell culture equipment coated with laminin fragments in dry state
CN106559994A (zh) * 2014-07-16 2017-04-05 国立大学法人大阪大学 层粘连蛋白片段的细胞培养基质活性增强方法
US20180334656A1 (en) * 2015-11-10 2018-11-22 Kyoto University Cell culture method using laminin fragment-containing medium
CN109312303A (zh) * 2016-03-09 2019-02-05 阿威他国际有限公司 表达间充质和神经元标志物的干细胞、其组合物及其制备方法

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5378612A (en) * 1990-05-11 1995-01-03 Juridical Foundation The Chemo-Sero-Therapeutic Research Institute Culture medium for production of recombinant protein
JPH05207875A (ja) * 1992-01-28 1993-08-20 Mitsui Toatsu Chem Inc 無血清培地
AU680909B2 (en) * 1994-04-06 1997-08-14 Immunex Corporation Interleukin-15
JPH10179147A (ja) * 1996-12-27 1998-07-07 Ishikawajima Harima Heavy Ind Co Ltd 植物細胞培養方法および二次代謝物高生産性植物細胞
EP1930413B1 (en) * 2005-08-23 2011-01-12 Oriental Yeast Co., Ltd. Technique for culture of mesenchymal stem cell utilizing laminin-5
AU2007294731B2 (en) * 2006-09-13 2014-04-17 Abbvie Inc. Cell culture improvements
WO2010040262A1 (zh) * 2008-10-10 2010-04-15 深圳市嘉天源生物科技有限公司 分离动物胚胎间质性干细胞并提取其分泌物的方法
WO2012137970A1 (ja) 2011-04-08 2012-10-11 国立大学法人大阪大学 改変ラミニンおよびその利用
WO2012145682A1 (en) * 2011-04-21 2012-10-26 Amgen Inc. A method for culturing mammalian cells to improve recombinant protein production
CN104884468B (zh) 2012-12-28 2018-08-31 国立大学法人大阪大学 附加有胶原结合性分子的改造层粘连蛋白及其利用
CN104651305A (zh) * 2015-02-13 2015-05-27 沈阳澔源生物科技有限公司 一种利用脐带间充质干细胞获取生物活性蛋白的方法
AU2018228352B2 (en) * 2017-02-28 2024-08-01 Centre Hospitalier Régional Universitaire De Nancy Mesenchymal stem cells obtained from Wharton's jelly for the treatment of sepsis
JP6469287B1 (ja) * 2018-06-22 2019-02-13 株式会社 バイオミメティクスシンパシーズ 中空糸細胞培養装置,細胞培養方法,培養上清の製造方法
JPWO2021200744A1 (https=) * 2020-03-31 2021-10-07

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160137965A1 (en) * 2013-06-12 2016-05-19 Osaka University Cell culture equipment coated with laminin fragments in dry state
CN106559994A (zh) * 2014-07-16 2017-04-05 国立大学法人大阪大学 层粘连蛋白片段的细胞培养基质活性增强方法
US20170159020A1 (en) * 2014-07-16 2017-06-08 Osaka University Method for enhancing activity of laminin fragments as cell culture matrix
US20180334656A1 (en) * 2015-11-10 2018-11-22 Kyoto University Cell culture method using laminin fragment-containing medium
CN109312303A (zh) * 2016-03-09 2019-02-05 阿威他国际有限公司 表达间充质和神经元标志物的干细胞、其组合物及其制备方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
扎拉嘎胡等: "层粘连蛋白促脐带间充质干细胞向成骨细胞分化与黏着斑激酶表达", 中国组织工程研究与临床康复, vol. 15, no. 6, pages 970 *
野向阳等: "人脐带间充质干细胞体外成骨及其免疫学特征", 中国组织工程研究与临床康复, vol. 13, no. 36, pages 7032 *

Also Published As

Publication number Publication date
AU2021247879A1 (en) 2022-11-03
EP4155389A3 (en) 2023-07-12
JPWO2021200744A1 (https=) 2021-10-07
EP4130240A1 (en) 2023-02-08
CA3177567A1 (en) 2021-10-07
EP4130240A4 (en) 2024-05-08
EP4155389A2 (en) 2023-03-29
CN116179480A (zh) 2023-05-30
TW202311526A (zh) 2023-03-16
AU2022259729B2 (en) 2025-05-01
AU2022259729A1 (en) 2022-12-01
AU2021247879B2 (en) 2025-04-24
JP2024015245A (ja) 2024-02-01
US20230172992A1 (en) 2023-06-08
JP2022181218A (ja) 2022-12-07
WO2021200744A1 (ja) 2021-10-07
TW202204605A (zh) 2022-02-01
CA3173721A1 (en) 2021-10-07

Similar Documents

Publication Publication Date Title
CN115362252A (zh) 增殖细胞和细胞生产物的生产法、间充质干细胞群和干细胞培养上清及其生产法、治疗剂
Chen et al. Stromal cell-derived factor-1/CXCR4 signaling modifies the capillary-like organization of human embryonic stem cell-derived endothelium in vitro
Wei et al. JNKi-and DAC-programmed mesenchymal stem/stromal cells from hESCs facilitate hematopoiesis and alleviate hind limb ischemia
Calle et al. Strategies for whole lung tissue engineering
JP4085062B2 (ja) 霊長類の胚性幹細胞から由来した内皮細胞
JP6378321B2 (ja) 筋幹細胞生体外培養方法およびその用途
CN110898078B (zh) 一种间充质干细胞分泌因子的制备及应用
US20210292712A1 (en) Methods for the long-term expansion of granulocyte-macrophage progenitors and applications thereof
KR20100094970A (ko) 중간엽 공급자 세포로부터의 파라크린 시그널 및 이를 이용한 간 전구세포의 확장 및 분화 조절
TW201512399A (zh) Nk細胞的調製方法
WO2003050273A1 (en) Human cell culture medium and culture method
US20240117301A1 (en) Method for producing proliferating cells, method for producing cell product, mesenchymal stem cell population and method for producing same, culture supernatant of stem cells and method for producing same, and therapeutic agent
US20220378845A1 (en) Method of isolation of pure culture of vascular endothelial cells, medium for maintaining characteristics of vascular endothelial cells, and culture method including same
JP6695795B2 (ja) 造血細胞の増殖ペプチドおよびその用途
HK40089499A (zh) 增殖细胞和细胞生产物的生产法、间充质干细胞群和干细胞培养上清及其生产法、治疗剂
HK40084736A (en) Method for producing proliferating cells, method for producing cell product, mesenchymal stem cell population and method for producing same, culture supernatant of stem cells and method for producing same, and therapeutic agent
NZ793106A (en) Method of producing proliferated cells, method of producing cell product, mesenchymal stem cell population and method of producing same, culture supernatant of stem cells and method of producing same, and therapeutic agent
CN116396940A (zh) 造血干祖细胞及其制备方法和用途
CN110468100A (zh) 培养基及骨髓间充质干细胞的成骨诱导方法
KR102257950B1 (ko) 혈관 내피세포 특성 유지 배지 및 이를 포함하는 배양 방법
JP2003235548A (ja) ヒト細胞の培養用培地および培養方法
KR20250142323A (ko) 세포분화도의 조절 방법
CN121100176A (zh) 由生物体组织或器官制造高纯度血管内皮细胞群的方法
CN106635981A (zh) 破骨细胞培养基及其制备方法和培养破骨细胞的方法
TW200533754A (en) Preparation method of cytokine-induced killer cells and the application thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
REG Reference to a national code

Ref country code: HK

Ref legal event code: DE

Ref document number: 40084736

Country of ref document: HK

WD01 Invention patent application deemed withdrawn after publication
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20221118