JP6856183B1 - 二重特異性抗体 - Google Patents

二重特異性抗体 Download PDF

Info

Publication number
JP6856183B1
JP6856183B1 JP2020570992A JP2020570992A JP6856183B1 JP 6856183 B1 JP6856183 B1 JP 6856183B1 JP 2020570992 A JP2020570992 A JP 2020570992A JP 2020570992 A JP2020570992 A JP 2020570992A JP 6856183 B1 JP6856183 B1 JP 6856183B1
Authority
JP
Japan
Prior art keywords
amino acid
antibody
seq
acid sequence
arm
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.)
Active
Application number
JP2020570992A
Other languages
English (en)
Japanese (ja)
Other versions
JPWO2021020416A1 (ja
Inventor
史朗 柴山
史朗 柴山
拓也 新坊
拓也 新坊
智也 手塚
智也 手塚
マーク スロスビー
マーク スロスビー
クルイフ コルネリス アドリアン デ
クルイフ コルネリス アドリアン デ
ロー ピーテル フォッコ ヴァン
ロー ピーテル フォッコ ヴァン
リンス クロースター
リンス クロースター
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.)
Ono Pharmaceutical Co Ltd
Original Assignee
Ono Pharmaceutical 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 Ono Pharmaceutical Co Ltd filed Critical Ono Pharmaceutical Co Ltd
Priority to JP2021025286A priority Critical patent/JP7574692B2/ja
Application granted granted Critical
Publication of JP6856183B1 publication Critical patent/JP6856183B1/ja
Publication of JPWO2021020416A1 publication Critical patent/JPWO2021020416A1/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2809—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2818—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • 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
    • 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
    • C07K2317/526—CH3 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/71—Decreased effector function due to an Fc-modification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance

Landscapes

  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Transplantation (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
JP2020570992A 2019-07-30 2020-07-29 二重特異性抗体 Active JP6856183B1 (ja)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2021025286A JP7574692B2 (ja) 2019-07-30 2021-02-19 二重特異性抗体

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP2019139751 2019-07-30
JP2019139751 2019-07-30
PCT/JP2020/028972 WO2021020416A1 (ja) 2019-07-30 2020-07-29 二重特異性抗体

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2021025286A Division JP7574692B2 (ja) 2019-07-30 2021-02-19 二重特異性抗体

Publications (2)

Publication Number Publication Date
JP6856183B1 true JP6856183B1 (ja) 2021-04-07
JPWO2021020416A1 JPWO2021020416A1 (ja) 2021-09-13

Family

ID=74229916

Family Applications (2)

Application Number Title Priority Date Filing Date
JP2020570992A Active JP6856183B1 (ja) 2019-07-30 2020-07-29 二重特異性抗体
JP2021025286A Active JP7574692B2 (ja) 2019-07-30 2021-02-19 二重特異性抗体

Family Applications After (1)

Application Number Title Priority Date Filing Date
JP2021025286A Active JP7574692B2 (ja) 2019-07-30 2021-02-19 二重特異性抗体

Country Status (14)

Country Link
US (1) US20220281977A1 (https=)
EP (1) EP4008348A4 (https=)
JP (2) JP6856183B1 (https=)
KR (1) KR20220039720A (https=)
CN (1) CN114174343A (https=)
AU (1) AU2020322765A1 (https=)
BR (1) BR112022001473A2 (https=)
CA (1) CA3149309A1 (https=)
IL (1) IL290050A (https=)
MX (1) MX2022000971A (https=)
PH (1) PH12022550190A1 (https=)
TW (1) TW202118790A (https=)
WO (1) WO2021020416A1 (https=)
ZA (1) ZA202201247B (https=)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI890481B (zh) * 2018-02-09 2025-07-11 日商小野藥品工業股份有限公司 雙特異性抗體
KR20250156121A (ko) 2023-03-16 2025-10-31 오노 야꾸힝 고교 가부시키가이샤 항체 제제
WO2024190892A1 (ja) 2023-03-16 2024-09-19 小野薬品工業株式会社 抗体製剤

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013022091A1 (ja) * 2011-08-11 2013-02-14 小野薬品工業株式会社 Ｐｄ－１アゴニストからなる自己免疫疾患治療剤
WO2019070047A1 (ja) * 2017-10-06 2019-04-11 小野薬品工業株式会社 二重特異性抗体

Family Cites Families (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4474893A (en) 1981-07-01 1984-10-02 The University of Texas System Cancer Center Recombinant monoclonal antibodies
GB8308235D0 (en) 1983-03-25 1983-05-05 Celltech Ltd Polypeptides
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US5225539A (en) 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
US4801687A (en) 1986-10-27 1989-01-31 Bioprobe International, Inc. Monoclonal antibody purification process using protein A
FI884924L (fi) 1987-10-28 1989-04-29 Oncogen Humanimmuglobulin som producerats med hybrid-dna-teknik.
US5476996A (en) 1988-06-14 1995-12-19 Lidak Pharmaceuticals Human immune system in non-human animal
US5223409A (en) 1988-09-02 1993-06-29 Protein Engineering Corp. Directed evolution of novel binding proteins
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
US5151504A (en) 1989-11-17 1992-09-29 E. R. Squibb & Sons, Inc. Method for purification of monoclonal antibodies
US6075181A (en) 1990-01-12 2000-06-13 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6673986B1 (en) 1990-01-12 2004-01-06 Abgenix, Inc. Generation of xenogeneic antibodies
US6150584A (en) 1990-01-12 2000-11-21 Abgenix, Inc. Human antibodies derived from immunized xenomice
DE69120146T2 (de) 1990-01-12 1996-12-12 Cell Genesys Inc Erzeugung xenogener antikörper
US5427908A (en) 1990-05-01 1995-06-27 Affymax Technologies N.V. Recombinant library screening methods
GB9015198D0 (en) 1990-07-10 1990-08-29 Brien Caroline J O Binding substance
US6172197B1 (en) 1991-07-10 2001-01-09 Medical Research Council Methods for producing members of specific binding pairs
ATE158021T1 (de) 1990-08-29 1997-09-15 Genpharm Int Produktion und nützung nicht-menschliche transgentiere zur produktion heterologe antikörper
US5789650A (en) 1990-08-29 1998-08-04 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US5625126A (en) 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US5661016A (en) 1990-08-29 1997-08-26 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5877397A (en) 1990-08-29 1999-03-02 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5770429A (en) 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5874299A (en) 1990-08-29 1999-02-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5814318A (en) 1990-08-29 1998-09-29 Genpharm International Inc. Transgenic non-human animals for producing heterologous antibodies
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
GB9022543D0 (en) 1990-10-17 1990-11-28 Wellcome Found Antibody production
EP0523949B1 (en) 1991-07-15 2003-06-25 The Wellcome Foundation Limited Production of antibodies
PT1024191E (pt) 1991-12-02 2008-12-22 Medical Res Council Produção de auto-anticorpos a partir de reportórios de segmentos de anticorpo e exibidos em fagos
HK1048138B (zh) 1999-04-15 2009-06-12 荷兰克鲁塞尔公司 用编码腺病毒e1蛋白的序列在人体细胞中生产重组蛋白
CA2430013C (en) 2000-11-30 2011-11-22 Medarex, Inc. Transgenic transchromosomal rodents for making human antibodies
NZ519012A (en) 2001-05-21 2003-10-31 Orgapack Gmbh Manually actuated strapping unit for wrapping a steel strap around a packaged item
US20040241745A1 (en) 2001-07-31 2004-12-02 Tasuku Honjo Substance specific to pd-1
DK2314629T4 (da) 2002-07-18 2023-02-06 Merus Nv Rekombinant produktion af blandinger af antistoffer
JP2004072286A (ja) 2002-08-05 2004-03-04 Nippon Telegr & Teleph Corp <Ntt> 構造変化検出方法および通信網異常状態検出方法、並びに、その装置およびプログラム
US7563869B2 (en) * 2003-01-23 2009-07-21 Ono Pharmaceutical Co., Ltd. Substance specific to human PD-1
WO2005047327A2 (en) * 2003-11-12 2005-05-26 Biogen Idec Ma Inc. NEONATAL Fc RECEPTOR (FcRn)-BINDING POLYPEPTIDE VARIANTS, DIMERIC Fc BINDING PROTEINS AND METHODS RELATED THERETO
CA2569509C (en) 2004-06-03 2014-08-12 Novimmune S.A. Anti-cd3 antibodies and methods of use thereof
AU2005304624B2 (en) * 2004-11-12 2010-10-07 Xencor, Inc. Fc variants with altered binding to FcRn
EP2147594B1 (en) 2008-06-27 2013-11-13 Merus B.V. Antibody producing non-human mammals
US9248181B2 (en) 2012-04-20 2016-02-02 Merus B.V. Methods and means for the production of Ig-like molecules
HUE042040T2 (hu) 2012-09-27 2019-06-28 Merus Nv Bispecifikus IGG antitestek mint T-sejt kapcsolók
US9914777B2 (en) * 2015-07-10 2018-03-13 Merus N.V. Human CD3 binding antibody
PE20181046A1 (es) * 2015-09-25 2018-07-03 Genentech Inc Anticuerpos anti-tigit y metodos de uso
CR20190550A (es) * 2017-06-05 2020-04-05 Janssen Biotech Inc Anticuerpos que se unen específicamente a pd-1 y métodos de uso
TWI890481B (zh) * 2018-02-09 2025-07-11 日商小野藥品工業股份有限公司 雙特異性抗體

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013022091A1 (ja) * 2011-08-11 2013-02-14 小野薬品工業株式会社 Ｐｄ－１アゴニストからなる自己免疫疾患治療剤
JP2017088617A (ja) * 2011-08-11 2017-05-25 小野薬品工業株式会社 Ｐｄ−１アゴニストからなる自己免疫疾患治療剤
WO2019070047A1 (ja) * 2017-10-06 2019-04-11 小野薬品工業株式会社 二重特異性抗体

Also Published As

Publication number Publication date
EP4008348A1 (en) 2022-06-08
BR112022001473A2 (pt) 2022-03-22
AU2020322765A1 (en) 2022-02-24
MX2022000971A (es) 2022-02-14
KR20220039720A (ko) 2022-03-29
ZA202201247B (en) 2023-08-30
PH12022550190A1 (en) 2022-11-21
IL290050A (en) 2022-03-01
EP4008348A4 (en) 2023-11-15
CN114174343A (zh) 2022-03-11
JPWO2021020416A1 (ja) 2021-09-13
JP7574692B2 (ja) 2024-10-29
TW202118790A (zh) 2021-05-16
US20220281977A1 (en) 2022-09-08
JP2021075580A (ja) 2021-05-20
CA3149309A1 (en) 2021-02-04
WO2021020416A1 (ja) 2021-02-04

Similar Documents

Publication Publication Date Title
JP6844719B2 (ja) 二重特異性抗体
JP7476997B2 (ja) 二重特異性抗体
JP7688805B2 (ja) 二重特異性抗体
JP6856183B1 (ja) 二重特異性抗体
JP7714992B2 (ja) 二重特異性抗体を有効成分として含む医薬組成物
TWI923111B (zh) 雙特異性抗體
HK40069431A (en) Bispecific antibody
HK40036202A (en) Bispecific antibody
HK40036202B (zh) 双特异性抗体

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20201218

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20201218

A871 Explanation of circumstances concerning accelerated examination

Free format text: JAPANESE INTERMEDIATE CODE: A871

Effective date: 20201218

A975 Report on accelerated examination

Free format text: JAPANESE INTERMEDIATE CODE: A971005

Effective date: 20210126

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20210216

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20210301

R150 Certificate of patent or registration of utility model

Ref document number: 6856183

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250