JP4791960B2 - ルックスルー突然変異誘発 - Google Patents

ルックスルー突然変異誘発 Download PDF

Info

Publication number
JP4791960B2
JP4791960B2 JP2006517625A JP2006517625A JP4791960B2 JP 4791960 B2 JP4791960 B2 JP 4791960B2 JP 2006517625 A JP2006517625 A JP 2006517625A JP 2006517625 A JP2006517625 A JP 2006517625A JP 4791960 B2 JP4791960 B2 JP 4791960B2
Authority
JP
Japan
Prior art keywords
amino acid
polypeptide
mutagenesis
antibody
region
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.)
Expired - Lifetime
Application number
JP2006517625A
Other languages
English (en)
Japanese (ja)
Other versions
JP2007524390A (ja
Inventor
クレア,ロベルト
Original Assignee
バイオレン,インク.
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 バイオレン,インク. filed Critical バイオレン,インク.
Publication of JP2007524390A publication Critical patent/JP2007524390A/ja
Application granted granted Critical
Publication of JP4791960B2 publication Critical patent/JP4791960B2/ja
Anticipated expiration legal-status Critical
Expired - Lifetime 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
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1034Isolating an individual clone by screening libraries
    • C12N15/1093General methods of preparing gene libraries, not provided for in other subgroups
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/005Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies constructed by phage libraries
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/12Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1267Gram-positive bacteria
    • C07K16/1282Clostridium (G)
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/241Tumor Necrosis Factors
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/44Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
    • 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
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/102Mutagenizing nucleic acids
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55Fab or Fab'
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565Complementarity determining region [CDR]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/60Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622Single chain antibody (scFv)
    • YGENERAL 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
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02PCLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00Technologies relating to chemical industry
    • Y02P20/50Improvements relating to the production of bulk chemicals
    • Y02P20/582Recycling of unreacted starting or intermediate materials

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Virology (AREA)
  • Bioinformatics & Computational Biology (AREA)
  • Peptides Or Proteins (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Enzymes And Modification Thereof (AREA)
JP2006517625A 2003-06-27 2004-06-25 ルックスルー突然変異誘発 Expired - Lifetime JP4791960B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US48328203P 2003-06-27 2003-06-27
US60/483,282 2003-06-27
PCT/US2004/020306 WO2005003345A2 (en) 2003-06-27 2004-06-25 Look-through mutagenesis

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2011062697A Division JP5358604B2 (ja) 2003-06-27 2011-03-22 ルックスルー突然変異誘発

Publications (2)

Publication Number Publication Date
JP2007524390A JP2007524390A (ja) 2007-08-30
JP4791960B2 true JP4791960B2 (ja) 2011-10-12

Family

ID=33563915

Family Applications (2)

Application Number Title Priority Date Filing Date
JP2006517625A Expired - Lifetime JP4791960B2 (ja) 2003-06-27 2004-06-25 ルックスルー突然変異誘発
JP2011062697A Expired - Lifetime JP5358604B2 (ja) 2003-06-27 2011-03-22 ルックスルー突然変異誘発

Family Applications After (1)

Application Number Title Priority Date Filing Date
JP2011062697A Expired - Lifetime JP5358604B2 (ja) 2003-06-27 2011-03-22 ルックスルー突然変異誘発

Country Status (14)

Country Link
US (1) US20050136428A1 (https=)
EP (1) EP1660655B1 (https=)
JP (2) JP4791960B2 (https=)
KR (1) KR20060034650A (https=)
CN (1) CN1836041A (https=)
AU (1) AU2004254352A1 (https=)
BR (1) BRPI0412007A (https=)
CA (1) CA2542192C (https=)
ES (1) ES2609102T3 (https=)
IL (1) IL172736A0 (https=)
NO (1) NO20060108L (https=)
RU (1) RU2005140664A (https=)
WO (1) WO2005003345A2 (https=)
ZA (1) ZA200510460B (https=)

Families Citing this family (54)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7329725B1 (en) * 2003-10-29 2008-02-12 Nastech Pharmaceutical Company Inc. Phage displayed Trp cage ligands
CA2572961C (en) 2004-07-06 2016-08-16 Bioren, Inc. Universal antibody libraries
CA2573259A1 (en) * 2004-07-06 2006-02-09 Bioren Inc. High affinity anti-tnf-alpha antibodies and method
JP4939410B2 (ja) 2004-07-06 2012-05-23 バイオレン,インク. 強化された特性を持つ変性ポリペプチドを発生させるためのルックスルー変異誘発
WO2006094234A1 (en) * 2005-03-03 2006-09-08 Xencor, Inc. Methods for the design of libraries of protein variants
US20080207467A1 (en) * 2005-03-03 2008-08-28 Xencor, Inc. Methods for the design of libraries of protein variants
CA2605697A1 (en) * 2005-04-26 2006-11-02 Bioren, Inc. Method of producing human igg antibodies with enhanced effector functions
KR20080068004A (ko) * 2005-08-15 2008-07-22 아라나 테라퓨틱스 리미티드 뉴 월드 영장류 구조형성영역을 가진 조작 항체
JP2009515516A (ja) * 2005-11-14 2009-04-16 バイオレン・インク 推定成熟cdrのブラスティングならびにコホートライブラリの作製およびスクリーニングによる抗体の超ヒト化
WO2007086994A1 (en) * 2005-11-15 2007-08-02 Balyasnikova Irina V Single chain fragment of monoclonal antibody 9b9 and uses thereof
CA2634080A1 (en) 2005-12-20 2007-06-28 Arana Therapeutics Limited Anti-inflammatory dab
CN101400703B (zh) 2006-02-01 2013-05-08 赛法隆澳大利亚控股有限公司 结构域抗体构建体
US7704953B2 (en) * 2006-02-17 2010-04-27 Mdrna, Inc. Phage displayed cell binding peptides
WO2007112054A2 (en) * 2006-03-23 2007-10-04 Sea Lane Biotechnologies, Llc Facilitation of translocation of molecules through the gastrointestinal tract
EP2024393A2 (en) 2006-05-15 2009-02-18 Sea Lane Biotechnologies,llc. Neutralizing antibodies to influenza viruses
WO2007136840A2 (en) * 2006-05-20 2007-11-29 Codon Devices, Inc. Nucleic acid library design and assembly
EP2057191A1 (en) 2006-08-18 2009-05-13 Ablynx N.V. Amino acid sequences directed against il-6r and polypeptides comprising the same for the treatment of deseases and disorders associated with il-6-mediated signalling
EP2069558B1 (en) * 2006-10-02 2013-05-01 Sea Lane Biotechnologies,llc. Design and construction of diverse synthetic peptide and polypeptide libraries
US20080287320A1 (en) * 2006-10-04 2008-11-20 Codon Devices Libraries and their design and assembly
KR20100028031A (ko) * 2007-06-06 2010-03-11 다니스코 유에스 인크. 단백질 특성의 개선 방법
WO2009009045A2 (en) * 2007-07-10 2009-01-15 The Scripps Research Institute Escape libraries of target polypeptides
US8680019B2 (en) * 2007-08-10 2014-03-25 Protelica, Inc. Universal fibronectin Type III binding-domain libraries
US8470966B2 (en) 2007-08-10 2013-06-25 Protelica, Inc. Universal fibronectin type III binding-domain libraries
US20090176654A1 (en) * 2007-08-10 2009-07-09 Protelix, Inc. Universal fibronectin type III binding-domain libraries
EP2220120A2 (en) 2007-11-27 2010-08-25 Ablynx N.V. Amino acid sequences directed against heterodimeric cytokines and/or their receptors and polypeptides comprising the same
WO2009121004A2 (en) 2008-03-28 2009-10-01 Sea Lane Biotechnologies, Llc Neutralizing molecules to viral antigens
EP2131245A3 (en) * 2008-06-02 2012-08-01 ASML Netherlands BV Lithographic apparatus and its focus determination method
WO2010115995A2 (en) 2009-04-10 2010-10-14 Ablynx Nv Improved amino acid sequences directed against il-6r and polypeptides comprising the same for the treatment of il-6r related diseases and disorders
NZ595461A (en) 2009-04-10 2013-01-25 Ablynx Nv Improved amino acid sequences directed against il-6r and polypeptides comprising the same for the treatment of il-6r related diseases and disorders
ES2643034T3 (es) 2009-06-05 2017-11-21 Ablynx N.V. Construcciones de Nanobody contra el virus respiratorio sincicial humano (VRSH) trivalentes para la prevención y/o el tratamiento de infecciones de las vías respiratorias
ES2652340T3 (es) * 2009-07-17 2018-02-01 Bioatla Llc Selección y evolución simultáneas e integradas de rendimiento y expresión de proteínas humanas en huéspedes de producción
GB0914691D0 (en) * 2009-08-21 2009-09-30 Lonza Biologics Plc Immunoglobulin variants
EP2494046B1 (en) 2009-10-30 2018-09-12 Novartis AG Universal fibronectin type iii bottom-side binding domain libraries
WO2011064382A1 (en) 2009-11-30 2011-06-03 Ablynx N.V. Improved amino acid sequences directed against human respiratory syncytial virus (hrsv) and polypeptides comprising the same for the prevention and/or treatment of respiratory tract infections
CN107903321A (zh) 2010-07-30 2018-04-13 诺华有限公司 纤连蛋白摇篮分子和其库
EP2647704B1 (en) 2010-12-01 2017-11-01 Mitsubishi Tanabe Pharma Corporation Polynucleotide construct capable of presenting fab in acellular translation system, and method for manufacturing and screening fab using same
US10138302B2 (en) 2011-09-23 2018-11-27 Ablynx N.V. Methods for treating rheumatoid arthritis by administering interleukin-6 receptor antibodies
SG11201404532XA (en) 2012-03-02 2014-08-28 Ablynx Nv Pseudomonas aeruginosa pcrv binding single variable domain antibodies
US9777055B2 (en) * 2012-04-20 2017-10-03 Thomas Jefferson University Engineered antibody for inhibition of fibrosis
NZ725398A (en) * 2012-05-25 2018-05-25 Chr Hansen As Variants of chymosin with improved milk-clotting properties
WO2014087010A1 (en) 2012-12-07 2014-06-12 Ablynx N.V. IMPROVED POLYPEPTIDES DIRECTED AGAINST IgE
KR101600899B1 (ko) * 2012-12-11 2016-03-09 주식회사 셀레믹스 초병렬적 핵산 합성법을 통한 dna 라이브러리의 동시 합성 방법
US20140314741A1 (en) * 2013-04-18 2014-10-23 Developmen Center For Biotechnology Human Antibody against Interleukin-20 and Treatment for Inflammatory Diseases
US9416197B2 (en) 2013-11-01 2016-08-16 Ibc Pharmaceuticals, Inc. Bispecific antibodies that neutralize both TNF-α and IL-6: novel therapeutic agent for autoimmune disease
CN104805507B (zh) * 2014-01-29 2019-01-22 杭州康万达医药科技有限公司 噬菌体展示文库及其应用和制备方法
RU2739004C1 (ru) 2014-02-26 2020-12-21 Кхр. Хансен А/С Варианты химозина с улучшенными молокосвертывающими свойствами
CA2963712A1 (en) 2014-10-21 2016-04-28 Ablynx Nv Treatment of il-6r related diseases
WO2016207214A1 (en) 2015-06-22 2016-12-29 Chr. Hansen A/S Variants of chymosin with improved properties
MX2018002366A (es) 2015-08-31 2018-04-11 Chr Hansen As Variantes de quimosina con propiedades mejoradas.
IL260185B (en) * 2016-01-08 2022-09-01 Momotaro Gene Inc A combination therapy using reic/dkk-3 gene and a checkpoint inhibitor
CA3024211A1 (en) 2016-05-19 2017-11-23 Chr. Hansen A/S Variants of chymosin with improved milk-clotting properties
JP7395251B2 (ja) 2016-05-19 2023-12-11 セーホーエル.ハンセン アクティーゼルスカブ 改善された凝乳特性を有するキモシン変異体
EP4282969A3 (en) 2016-09-02 2024-01-31 Lentigen Technology, Inc. Compositions and methods for treating cancer with duocars
MX2020006297A (es) 2017-12-15 2020-12-07 Aleta Biotherapeutics Inc Variantes de cd19.

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003516755A (ja) * 1999-12-15 2003-05-20 ジェネンテック・インコーポレーテッド ショットガン走査、すなわち機能性タンパク質エピトープをマッピングするための組み合わせ方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2078518T3 (es) * 1990-04-05 1995-12-16 Roberto Crea Mutagenesis por desplazamiento completo.
EP0748338A4 (en) * 1994-03-04 2001-03-28 Merck & Co Inc IN VITRO MATURATION OF ANTIBODIES BY MEANS OF ALANINE 'SCANNING' MUTAGENESIS

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003516755A (ja) * 1999-12-15 2003-05-20 ジェネンテック・インコーポレーテッド ショットガン走査、すなわち機能性タンパク質エピトープをマッピングするための組み合わせ方法

Also Published As

Publication number Publication date
AU2004254352A1 (en) 2005-01-13
CN1836041A (zh) 2006-09-20
JP5358604B2 (ja) 2013-12-04
EP1660655A2 (en) 2006-05-31
EP1660655B1 (en) 2016-11-02
US20050136428A1 (en) 2005-06-23
WO2005003345A3 (en) 2005-03-24
CA2542192A1 (en) 2005-01-13
ZA200510460B (en) 2006-11-29
ES2609102T3 (es) 2017-04-18
KR20060034650A (ko) 2006-04-24
IL172736A0 (en) 2006-04-10
JP2007524390A (ja) 2007-08-30
BRPI0412007A (pt) 2006-08-15
WO2005003345A2 (en) 2005-01-13
NO20060108L (no) 2006-03-24
JP2011182794A (ja) 2011-09-22
CA2542192C (en) 2013-05-28
RU2005140664A (ru) 2007-08-27

Similar Documents

Publication Publication Date Title
JP4791960B2 (ja) ルックスルー突然変異誘発
JP4939410B2 (ja) 強化された特性を持つ変性ポリペプチドを発生させるためのルックスルー変異誘発
EP2231904B1 (en) Design and generation of human de novo pix phage display libraries via fusion to pix or pvii, vectors, antibodies and methods
US10253313B2 (en) Universal fibronectin type III bottom-side binding domain libraries
US9102711B2 (en) Methods and materials for targeted mutagenesis
JPH06121696A (ja) 抗原結合性タンパク質およびその製造方法
EP1499887B1 (en) Universal libraries for immunoglobulins
JP4433798B2 (ja) ウォークスルー突然変異誘発における「ドーピング」
JP7337850B2 (ja) 抗体ライブラリー及びこれを用いた抗体スクリーニング方法
MXPA06000080A (en) Look-through mutagenesis
Jermutus Probing a protein-protein interaction by in vitro evolution

Legal Events

Date Code Title Description
A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20070614

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20100720

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20101018

A02 Decision of refusal

Free format text: JAPANESE INTERMEDIATE CODE: A02

Effective date: 20101130

RD03 Notification of appointment of power of attorney

Free format text: JAPANESE INTERMEDIATE CODE: A7423

Effective date: 20110228

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20110322

A911 Transfer to examiner for re-examination before appeal (zenchi)

Free format text: JAPANESE INTERMEDIATE CODE: A911

Effective date: 20110510

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: 20110719

A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20110722

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20140729

Year of fee payment: 3

R150 Certificate of patent or registration of utility model

Ref document number: 4791960

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

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

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

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

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

EXPY Cancellation because of completion of term