JP2019515880A - 炭酸無水酵素ix阻害剤抱合体およびその使用 - Google Patents

炭酸無水酵素ix阻害剤抱合体およびその使用 Download PDF

Info

Publication number
JP2019515880A
JP2019515880A JP2018549266A JP2018549266A JP2019515880A JP 2019515880 A JP2019515880 A JP 2019515880A JP 2018549266 A JP2018549266 A JP 2018549266A JP 2018549266 A JP2018549266 A JP 2018549266A JP 2019515880 A JP2019515880 A JP 2019515880A
Authority
JP
Japan
Prior art keywords
alkyl
alkenyl
alkynyl
conjugate
pharmaceutically acceptable
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
JP2018549266A
Other languages
English (en)
Japanese (ja)
Other versions
JP2019515880A5 (enExample
Inventor
クリストファー・ピー・リーモン
イオンチョ・アール・ヴラホフ
ジョナサン・エム・シリングフォード
ポール・ジェイ・クラインドル
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.)
Endocyte Inc
Original Assignee
Endocyte 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
Application filed by Endocyte Inc filed Critical Endocyte Inc
Publication of JP2019515880A publication Critical patent/JP2019515880A/ja
Publication of JP2019515880A5 publication Critical patent/JP2019515880A5/ja
Pending legal-status Critical Current

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/54Medicinal 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 compound
    • A61K47/545Heterocyclic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/07Tetrapeptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/54Medicinal 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 compound
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/62Medicinal 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 a protein, peptide or polyamino acid
    • A61K47/65Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING 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
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/527Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving lyase
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5091Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing the pathological state of an organism
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/582Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06Dipeptides
    • C07K5/06008Dipeptides with the first amino acid being neutral
    • C07K5/06017Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C07K5/06043Leu-amino acid
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06Dipeptides
    • C07K5/06104Dipeptides with the first amino acid being acidic
    • C07K5/06113Asp- or Asn-amino acid
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06Dipeptides
    • C07K5/06139Dipeptides with the first amino acid being heterocyclic
    • C07K5/06165Dipeptides with the first amino acid being heterocyclic and Pro-amino acid; Derivatives thereof
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08Tripeptides
    • C07K5/0819Tripeptides with the first amino acid being acidic
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10Tetrapeptides
    • C07K5/1021Tetrapeptides with the first amino acid being acidic
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/70Mechanisms involved in disease identification
    • G01N2800/7023(Hyper)proliferation
    • G01N2800/7028Cancer

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Analytical Chemistry (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Pathology (AREA)
  • Cell Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Oncology (AREA)
  • Hospice & Palliative Care (AREA)
  • Physiology (AREA)
JP2018549266A 2016-03-16 2017-03-16 炭酸無水酵素ix阻害剤抱合体およびその使用 Pending JP2019515880A (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662309271P 2016-03-16 2016-03-16
US62/309,271 2016-03-16
PCT/US2017/022755 WO2017161144A1 (en) 2016-03-16 2017-03-16 Carbonic anhydrase ix inhibitor conjugates and uses thereof

Publications (2)

Publication Number Publication Date
JP2019515880A true JP2019515880A (ja) 2019-06-13
JP2019515880A5 JP2019515880A5 (enExample) 2020-04-23

Family

ID=59852036

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2018549266A Pending JP2019515880A (ja) 2016-03-16 2017-03-16 炭酸無水酵素ix阻害剤抱合体およびその使用

Country Status (5)

Country Link
US (1) US10857234B2 (enExample)
EP (1) EP3429637A4 (enExample)
JP (1) JP2019515880A (enExample)
CA (1) CA3017211A1 (enExample)
WO (1) WO2017161144A1 (enExample)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2019512511A (ja) * 2016-03-16 2019-05-16 パーデュー・リサーチ・ファウンデイションPurdue Research Foundation 炭酸無水酵素ixを標的とする薬剤および方法

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX2020011991A (es) 2018-05-10 2021-04-12 Univ Louisville Res Found Inc Inhibidores de la oncoproteina ras, metodos de produccion y metodos de uso de los mismos.
KR20240069480A (ko) * 2022-11-11 2024-05-20 울산과학기술원 자가조립 가능한 펩타이드 분자를 포함하는 양친매성 접합체 및 이의 용도
JP2025537882A (ja) * 2022-11-17 2025-11-20 ハンス-ゲオルク レルケン 腫瘍微小環境において切断可能な小分子-薬物コンジュゲート
WO2025044924A1 (zh) * 2023-08-25 2025-03-06 无锡诺宇医药科技有限公司 靶向碳酸酐酶放射性药物

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008101231A2 (en) * 2007-02-16 2008-08-21 Endocyte, Inc. Methods and compositions for treating and diagnosing kidney disease
JP2014520076A (ja) * 2011-05-09 2014-08-21 ビセン メディカル, インコーポレイテッド 炭酸脱水酵素標的化剤およびそれの使用方法
WO2014134543A1 (en) * 2013-03-01 2014-09-04 Endocyte, Inc. Processes for preparing tubulysins

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101648028B (zh) 2002-05-06 2012-11-21 恩多塞特公司 维生素-定向的显象剂
BRPI0615354A2 (pt) * 2005-08-19 2011-05-17 Endocyte Inc conjugado de liberação de fármaco de ligação de receptor, composição farmacêutica que o compreende, bem como seu uso
US20090043099A1 (en) 2006-03-17 2009-02-12 The Burnham Institute Methods and compositions for derepression of IAP-inhibited caspase
EP3569251A1 (en) 2007-06-25 2019-11-20 Endocyte, Inc. Conjugates containing hydrophilic spacer linkers
CA2696627C (en) 2007-08-17 2016-09-27 Purdue Research Foundation Psma binding ligand-linker conjugates and methods for using
EP2823826A3 (en) * 2008-01-09 2015-03-25 Molecular Insight Pharmaceuticals, Inc. Inhibitors of carbonic anhydrase IX
US8940501B2 (en) 2009-01-30 2015-01-27 Whitehead Institute For Biomedical Research Methods for ligation and uses thereof
CN101596433B (zh) 2009-07-15 2011-07-06 中国科学院工程热物理研究所 U形返料器的冷却式隔板
FR2951449B1 (fr) 2009-10-15 2011-11-25 Commissariat Energie Atomique Procede de fonctionnalisation de molecules biologiques
WO2011090710A2 (en) 2009-12-28 2011-07-28 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Composite probes and use thereof in super resolution methods
EP2533775A1 (en) 2010-02-12 2012-12-19 Universita' Degli Studi di Firenze Carbonic anhydrase inhibitors
JP5544239B2 (ja) 2010-07-29 2014-07-09 富士フイルム株式会社 重合性組成物
PL2766364T3 (pl) * 2011-08-17 2024-12-16 Merck & Cie Kmg Koniugaty folianowe jednostek wiążących albuminę
US10183970B2 (en) 2014-01-28 2019-01-22 Tube Pharmaceuticals Gmbh Cytotoxic tubulysin compounds for conjugation
US9771380B2 (en) 2014-06-09 2017-09-26 University Of Oregon Gold nanoparticles and methods of making and using gold nanoparticles
JP7027325B2 (ja) * 2016-03-16 2022-03-01 パーデュー・リサーチ・ファウンデイション 炭酸無水酵素ixを標的とする薬剤および方法
JP7282521B2 (ja) * 2016-04-08 2023-05-29 パーデュー・リサーチ・ファウンデイション Car t細胞療法のための方法および組成物

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008101231A2 (en) * 2007-02-16 2008-08-21 Endocyte, Inc. Methods and compositions for treating and diagnosing kidney disease
JP2014520076A (ja) * 2011-05-09 2014-08-21 ビセン メディカル, インコーポレイテッド 炭酸脱水酵素標的化剤およびそれの使用方法
WO2014134543A1 (en) * 2013-03-01 2014-09-04 Endocyte, Inc. Processes for preparing tubulysins

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
AHLSKOG, JULIA K. J. ET AL.: "In vivo targeting of tumor-associated carbonic anhydrases using acetazolamide derivatives", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 19(16),, JPN6021006782, 2009, pages 4851 - 4856, ISSN: 0004454107 *
CECCHI, ALESSANDRO ET AL.: "Carbonic Anhydrase Inhibitors. Design of Fluorescent Sulfonamides as Probes of Tumor-Associated Carb", JOURNAL OF MEDICINAL CHEMISTRY, vol. 48(15),, JPN6021006781, 2005, pages 4834 - 4841, ISSN: 0004454106 *
CECCHI, ALESSANDRO ET AL.: "Carbonic anhydrase inhibitors: synthesis and inhibition ofcytosolic/tumor-associated carbonic anhydr", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 14(23),, JPN6021006784, 2004, pages 5775 - 5780, ISSN: 0004454108 *
KRALL, NIKOLAUS ET AL.: "A small-molecule drug conjugate for the treatment of carbonic anhydrase IX expressing tumors", ANGEWANDTE CHEMIE, INTERNATIONAL EDITION, vol. 53(16),, JPN6021006777, 2014, pages 4231 - 4235, ISSN: 0004607945 *
RAMI, MAROUAN ET AL.: "Carbonic anhydrase inhibitors: Copper(II) complexes ofpolyamino-polycarboxylamido aromatic/heterocyc", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 18(2),, JPN6021006779, 2008, pages 836 - 841, ISSN: 0004607946 *
WICHERT, MORENO ET AL.: "Dual-display of small molecules enables the discovery of ligand pairs and facilitates affinity matur", NATURE CHEMISTRY, vol. 7(3),, JPN6021006780, 2015, pages 241 - 249, ISSN: 0004607947 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2019512511A (ja) * 2016-03-16 2019-05-16 パーデュー・リサーチ・ファウンデイションPurdue Research Foundation 炭酸無水酵素ixを標的とする薬剤および方法
JP7027325B2 (ja) 2016-03-16 2022-03-01 パーデュー・リサーチ・ファウンデイション 炭酸無水酵素ixを標的とする薬剤および方法

Also Published As

Publication number Publication date
CA3017211A1 (en) 2017-09-21
WO2017161144A1 (en) 2017-09-21
US10857234B2 (en) 2020-12-08
EP3429637A4 (en) 2020-03-11
US20190083631A1 (en) 2019-03-21
EP3429637A1 (en) 2019-01-23

Similar Documents

Publication Publication Date Title
US11872291B2 (en) Fibroblast activation protein (FAP)-targeted imaging and therapy
US11883498B2 (en) Luteinizing hormone-releasing hormone receptor (LHRH-R) conjugates and uses thereof
US20240316224A1 (en) Carbonic anhydrase ix targeting agents and methods
JP2019515880A (ja) 炭酸無水酵素ix阻害剤抱合体およびその使用
JP2023099047A (ja) 炭酸脱水酵素陽性がんを標的とするfbsa系治療および放射性造影複合体
JP2018525399A (ja) Cck2r−薬物コンジュゲート
HK40016572A (en) Luteinizing hormone-releasing hormone receptor (lhrh-r) conjugates and uses thereof
HK40016572B (en) Luteinizing hormone-releasing hormone receptor (lhrh-r) conjugates and uses thereof
HK40031566A (en) Fbsa-based therapeutic and radioimaging conjugates targeting carbonic anhydrase positive cancers
HK40016594B (en) Fibroblast activation protein (fap)-targeted imaging and therapy
HK40016594A (en) Fibroblast activation protein (fap)-targeted imaging and therapy

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20200311

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20200311

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20210218

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20210302

A02 Decision of refusal

Free format text: JAPANESE INTERMEDIATE CODE: A02

Effective date: 20211005