JP6514103B2 - 三重変異を有する二量体タンパク質 - Google Patents

三重変異を有する二量体タンパク質 Download PDF

Info

Publication number
JP6514103B2
JP6514103B2 JP2015519244A JP2015519244A JP6514103B2 JP 6514103 B2 JP6514103 B2 JP 6514103B2 JP 2015519244 A JP2015519244 A JP 2015519244A JP 2015519244 A JP2015519244 A JP 2015519244A JP 6514103 B2 JP6514103 B2 JP 6514103B2
Authority
JP
Japan
Prior art keywords
dimeric protein
amino acid
antibody
polypeptide
dimeric
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
JP2015519244A
Other languages
English (en)
Japanese (ja)
Other versions
JP2015524387A5 (enExample
JP2015524387A (ja
Inventor
ヨング ロブ エヌ． デ
ヨング ロブ エヌ． デ
フランク ビュースケンス
フランク ビュースケンス
パウル パルレン
パウル パルレン
アラン フランク ラブレイン
アラン フランク ラブレイン
ジャニーヌ スフールマン
ジャニーヌ スフールマン
アリエン ブルグ
アリエン ブルグ
サンドラ ベルプローゲン
サンドラ ベルプローゲン
Original Assignee
ゲンマブ ビー．ブイ．
ゲンマブ ビー．ブイ．
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=49881390&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=JP6514103(B2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from PCT/EP2012/063339 external-priority patent/WO2013004842A2/en
Application filed by ゲンマブ ビー．ブイ．, ゲンマブ ビー．ブイ． filed Critical ゲンマブ ビー．ブイ．
Publication of JP2015524387A publication Critical patent/JP2015524387A/ja
Publication of JP2015524387A5 publication Critical patent/JP2015524387A5/ja
Application granted granted Critical
Publication of JP6514103B2 publication Critical patent/JP6514103B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/10—RNA viruses
    • C07K16/112—Retroviridae (F), e.g. leukemia viruses
    • C07K16/114—Lentivirus (G), e.g. human immunodeficiency virus [HIV], feline immunodeficiency virus [FIV] or simian immunodeficiency virus [SIV]
    • C07K16/1145—Env proteins, e.g. gp41, gp110/120, gp160, V3, principal neutralising domain [PND] or CD4-binding site
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1267—Gram-positive bacteria
    • C07K16/1271—Micrococcaceae (F); Staphylococcaceae (F), e.g. Staphylococcus (G)
    • 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
    • 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
    • C07K16/2863—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • 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
    • C07K16/2887—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
    • 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
    • C07K16/2896—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
    • 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
    • C07K16/32—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
    • 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
    • C07K16/36—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against blood coagulation factors
    • 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
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • 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
    • C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
    • C07K2317/41—Glycosylation, sialylation, or fucosylation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515—Complete light chain, i.e. VL + CL
    • 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
    • C07K2317/524—CH2 domain
    • 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
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/53—Hinge
    • 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
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
    • 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
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C07K2317/734—Complement-dependent cytotoxicity [CDC]
    • 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
    • C07K2317/74—Inducing cell proliferation
    • 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
    • C07K2317/75—Agonist effect on antigen
    • 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
    • C07K2317/77—Internalization into the cell
    • 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
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Virology (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Communicable Diseases (AREA)
  • Diabetes (AREA)
  • Transplantation (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
JP2015519244A 2012-07-06 2013-07-05 三重変異を有する二量体タンパク質 Active JP6514103B2 (ja)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
PCT/EP2012/063339 WO2013004842A2 (en) 2011-07-06 2012-07-06 Antibody variants and uses thereof
EPPCT/EP2012/063339 2012-07-06
US201361751045P 2013-01-10 2013-01-10
US61/751,045 2013-01-10
DKPA201300019 2013-01-10
DKPA201300019 2013-01-10
PCT/EP2013/064330 WO2014006217A1 (en) 2012-07-06 2013-07-05 Dimeric protein with triple mutations

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2019075809A Division JP2019163262A (ja) 2012-07-06 2019-04-11 三重変異を有する二量体タンパク質

Publications (3)

Publication Number Publication Date
JP2015524387A JP2015524387A (ja) 2015-08-24
JP2015524387A5 JP2015524387A5 (enExample) 2016-08-25
JP6514103B2 true JP6514103B2 (ja) 2019-05-15

Family

ID=49881390

Family Applications (3)

Application Number Title Priority Date Filing Date
JP2015519244A Active JP6514103B2 (ja) 2012-07-06 2013-07-05 三重変異を有する二量体タンパク質
JP2015552050A Active JP6604851B2 (ja) 2013-01-10 2014-01-09 不活性フォーマット
JP2022075888A Pending JP2022115955A (ja) 2012-07-06 2022-05-02 三重変異を有する二量体タンパク質

Family Applications After (2)

Application Number Title Priority Date Filing Date
JP2015552050A Active JP6604851B2 (ja) 2013-01-10 2014-01-09 不活性フォーマット
JP2022075888A Pending JP2022115955A (ja) 2012-07-06 2022-05-02 三重変異を有する二量体タンパク質

Country Status (10)

Country Link
US (4) US11180572B2 (enExample)
EP (3) EP2869845B1 (enExample)
JP (3) JP6514103B2 (enExample)
CN (1) CN104736174B (enExample)
AU (4) AU2013285355A1 (enExample)
BR (1) BR112015000167B1 (enExample)
PL (1) PL2943507T3 (enExample)
SG (2) SG11201408646VA (enExample)
SI (1) SI2943507T1 (enExample)
WO (2) WO2014006217A1 (enExample)

Families Citing this family (161)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104761637B (zh) 2006-03-31 2021-10-15 中外制药株式会社 调控抗体血液动力学的方法
ES2595638T3 (es) 2007-09-26 2017-01-02 Chugai Seiyaku Kabushiki Kaisha Método para modificar el punto isoeléctrico de un anticuerpo mediante la sustitución de aminoácidos en una CDR
EP3043181B1 (en) 2008-01-15 2020-04-08 The Board of Trustees of the Leland Stanford Junior University Markers of acute myeloid leukemia stem cells
ES2582340T3 (es) 2008-01-15 2016-09-12 The Board Of Trustees Of The Leland Stanford Junior University Métodos para manipular fagocitosis mediada por CD47
KR102057826B1 (ko) 2008-04-11 2019-12-20 추가이 세이야쿠 가부시키가이샤 복수 분자의 항원에 반복 결합하는 항원 결합 분자
HRP20241208T1 (hr) 2010-04-20 2024-11-22 Genmab A/S Heterodimerni proteini koji sadrže fc fragment protutijela i postupci za njihovu proizvodnju
EP2647706B1 (en) 2010-11-30 2023-05-17 Chugai Seiyaku Kabushiki Kaisha Antigen-binding molecule capable of binding to plurality of antigen molecules repeatedly
PT3434767T (pt) 2010-11-30 2026-01-23 Chugai Pharmaceutical Co Ltd Agente terapêutico indutor de citotoxicidade
EP2699596A4 (en) 2011-04-22 2015-01-14 Emergent Product Dev Seattle PROSTATE-SPECIFIC MEMBRANE-BINDING PROTEINS AND COMPOSITIONS AND METHOD THEREFOR
UA117901C2 (uk) 2011-07-06 2018-10-25 Ґенмаб Б.В. Спосіб посилення ефекторної функції вихідного поліпептиду, його варіанти та їх застосування
ES2758979T3 (es) * 2012-07-06 2020-05-07 Genmab Bv Proteína dimérica con mutaciones triples
CN104736174B (zh) 2012-07-06 2019-06-14 根马布私人有限公司 具有三重突变的二聚体蛋白质
WO2014030750A1 (ja) 2012-08-24 2014-02-27 中外製薬株式会社 マウスFcγRII特異的Fc抗体
SG10201709559PA (en) 2012-08-24 2017-12-28 Chugai Pharmaceutical Co Ltd Fcγriib-specific fc region variant
CN112245586A (zh) 2013-03-15 2021-01-22 小利兰·斯坦福大学托管委员会 用于实现治疗有效剂量的抗cd47剂的方法
WO2014145159A2 (en) * 2013-03-15 2014-09-18 Permeon Biologics, Inc. Charge-engineered antibodies or compositions of penetration-enhanced targeting proteins and methods of use
CN105246914B (zh) 2013-04-02 2021-08-27 中外制药株式会社 Fc区变体
WO2014177459A2 (en) 2013-04-29 2014-11-06 F. Hoffmann-La Roche Ag Fc-receptor binding modified asymmetric antibodies and methods of use
UA118029C2 (uk) 2013-04-29 2018-11-12 Ф. Хоффманн-Ля Рош Аг Модифіковане антитіло, що зв'язується з людським fcrn, й способи його застосування
ME03675B (me) 2013-07-05 2020-10-20 Genmab As Humanizovana ili himerna anтi-cd3 antiтela
IL263466B2 (en) 2013-12-17 2023-10-01 Genentech Inc Anti-CD3 antibodies and methods of using them
RU2727639C2 (ru) 2014-01-15 2020-07-22 Ф.Хоффманн-Ля Рош Аг Варианты fc-области с модифицированной способностью связываться с fcrn и с сохраненной способностью связываться с белком а
MX380658B (es) * 2014-01-15 2025-03-11 Hoffmann La Roche Variantes de region fc con union mejorada de la proteina a.
CN113248613B (zh) * 2014-01-15 2024-08-23 豪夫迈·罗氏有限公司 具有修饰的FCRN结合性质的Fc区变体
MX2016010951A (es) 2014-03-05 2016-11-29 Ucb Biopharma Sprl Proteinas de fc multimericas.
AU2015244814B2 (en) 2014-04-07 2020-12-24 Chugai Seiyaku Kabushiki Kaisha Immunoactivating antigen-binding molecule
MX2016014434A (es) 2014-05-13 2017-02-23 Chugai Pharmaceutical Co Ltd Molecula de union a antigeno redirigida a celulas t para celulas que tienen funcion de inmunosupresion.
EA035419B9 (ru) 2014-05-29 2020-08-07 Мэкроудженикс, Инк. Триспецифичные связывающие молекулы и способы их применения
DK3215528T3 (da) 2014-11-06 2019-10-07 Hoffmann La Roche Fc-regionvarianter med modificeret FcRn-binding og anvendelsesfremgangsmåder
CA2960569A1 (en) * 2014-11-06 2016-05-12 F. Hoffmann-Laroche Ag Fc-region variants with modified fcrn- and protein a-binding properties
KR101860280B1 (ko) 2014-12-19 2018-05-21 추가이 세이야쿠 가부시키가이샤 항-마이오스타틴 항체, 변이체 Fc 영역을 함유하는 폴리펩타이드, 및 사용 방법
US10544220B2 (en) * 2015-01-08 2020-01-28 Genmab A/S Bispecific antibodies against CD3 and CD20
KR102605798B1 (ko) 2015-02-05 2023-11-23 추가이 세이야쿠 가부시키가이샤 이온 농도 의존적 항원 결합 도메인을 포함하는 항체, Fc 영역 개변체, IL-8에 결합하는 항체, 및 그들의 사용
KR20180002653A (ko) 2015-04-07 2018-01-08 제넨테크, 인크. 효능작용 활성을 갖는 항원 결합 복합체 및 사용 방법
SG11201708804WA (en) 2015-05-07 2017-11-29 Agenus Inc Anti-ox40 antibodies and methods of use thereof
WO2016194992A1 (ja) * 2015-06-05 2016-12-08 中外製薬株式会社 免疫活性化剤の併用
EP3916018A1 (en) 2015-06-16 2021-12-01 Genentech, Inc. Anti-cd3 antibodies and methods of use
IL256562B2 (en) 2015-07-15 2024-07-01 Genmab As Human CD3 antibodies or chimeras
KR20250053203A (ko) 2015-07-24 2025-04-21 글리크닉 인코포레이티드 향상된 상보체 결합을 갖는 규칙적으로 다형체화된 면역글로불린 fc 조성물을 생성하기 위한 인간 단백질 단편의 융합 단백질
IL319047A (en) 2015-08-28 2025-04-01 Amunix Operating Inc Chimeric polypeptide composition and methods for its preparation and use
AU2016317915B2 (en) 2015-09-01 2021-02-18 Agenus Inc. Anti-PD-1 antibodies and methods of use thereof
WO2017053469A2 (en) 2015-09-21 2017-03-30 Aptevo Research And Development Llc Cd3 binding polypeptides
WO2017086419A1 (ja) 2015-11-18 2017-05-26 中外製薬株式会社 液性免疫応答の増強方法
WO2017086367A1 (ja) 2015-11-18 2017-05-26 中外製薬株式会社 免疫抑制機能を有する細胞に対するｔ細胞リダイレクト抗原結合分子を用いた併用療法
CN109476737A (zh) * 2015-12-01 2019-03-15 根马布有限公司 抗dr5抗体及其使用方法
WO2017110981A1 (en) 2015-12-25 2017-06-29 Chugai Seiyaku Kabushiki Kaisha Anti-myostatin antibodies and methods of use
KR20250071286A (ko) 2016-01-10 2025-05-21 네오티엑스 테라퓨틱스 엘티디. 면역강화제에 의해 증진되는 초항원 매개된 암 면역요법
AU2017213117A1 (en) * 2016-01-27 2018-07-19 CSL Behring Lengnau AG Recombinant IgG Fc multimers
WO2017165464A1 (en) 2016-03-21 2017-09-28 Elstar Therapeutics, Inc. Multispecific and multifunctional molecules and uses thereof
GEP20227398B (en) 2016-04-15 2022-07-25 Macrogenics Inc Novel b7-h3 binding molecules, antibody drug conjugates thereof and usage thereof
EP3464360B1 (en) 2016-05-27 2025-11-12 Agenus Inc. Anti-tim-3 antibodies and methods of use thereof
AU2017279538A1 (en) 2016-06-07 2019-01-03 Gliknik Inc. Cysteine-optimized stradomers
WO2018011421A1 (en) 2016-07-14 2018-01-18 Genmab A/S Multispecific antibodies against cd40 and cd137
AU2017300794A1 (en) * 2016-07-22 2019-01-24 Gliknik Inc. Fusion proteins of human protein fragments to create orderly multimerized immunoglobulin fc compositions with enhanced fc receptor binding
HRP20260151T1 (hr) 2016-08-02 2026-03-27 Visterra, Inc. Modificirani polipeptidi i njihova uporaba
EP3494991A4 (en) 2016-08-05 2020-07-29 Chugai Seiyaku Kabushiki Kaisha COMPOSITION FOR THE PROPHYLAXIS OR TREATMENT OF IL-8 RELATED DISEASES
WO2018031400A1 (en) * 2016-08-12 2018-02-15 Janssen Biotech, Inc. Fc engineered anti-tnfr superfamily member antibodies having enhanced agonistic activity and methods of using them
KR102480965B1 (ko) 2016-09-13 2022-12-26 알레간 인코포레이티드 안정화된 비단백질 클로스트리듐 독소 조성물
SG10201607778XA (en) 2016-09-16 2018-04-27 Chugai Pharmaceutical Co Ltd Anti-Dengue Virus Antibodies, Polypeptides Containing Variant Fc Regions, And Methods Of Use
JP7066696B2 (ja) 2016-10-11 2022-05-13 アジェナス インコーポレイテッド 抗ｌａｇ－３抗体及びその使用方法
US20190276549A1 (en) 2016-11-01 2019-09-12 Genmab B.V. Polypeptide variants and uses thereof
JP7784795B2 (ja) 2016-11-15 2025-12-12 ジェネンテック， インコーポレイテッド 抗ｃｄ２０／抗ｃｄ３二重特異性抗体による処置のための投与
DK3551660T5 (da) 2016-12-07 2024-09-02 Agenus Inc Anti-ctla-4-antistoffer og fremgangsmåder til anvendelse deraf
EP3576793A4 (en) * 2017-02-06 2021-03-31 Dana Farber Cancer Institute, Inc. COMPOSITIONS AND PROCEDURES FOR ENHANCING ANTIBODY-MEDIATED RECEPTOR SIGNALING
EP3580233A1 (en) * 2017-02-10 2019-12-18 Genmab B.V. Polypeptide variants and uses thereof
WO2018151820A1 (en) 2017-02-16 2018-08-23 Elstar Therapeutics, Inc. Multifunctional molecules comprising a trimeric ligand and uses thereof
JP7330942B2 (ja) 2017-03-31 2023-08-22 ジェンマブ ホールディング ビー．ブイ． 二重特異性抗ｃｄ３７抗体、モノクローナル抗ｃｄ３７抗体、およびそれらの使用方法
KR20240017409A (ko) 2017-04-13 2024-02-07 아게누스 인코포레이티드 항-cd137 항체 및 이의 사용 방법
LT3618863T (lt) 2017-05-01 2023-10-10 Agenus Inc. Anti-tigit antikūnai ir jų panaudojimo būdai
US11220550B2 (en) 2017-05-25 2022-01-11 Bristol-Myers Squibb Company Antagonistic anti-CD40 antibodies and methods of antagonizing CD40 activity
EP3630836A1 (en) 2017-05-31 2020-04-08 Elstar Therapeutics, Inc. Multispecific molecules that bind to myeloproliferative leukemia (mpl) protein and uses thereof
EP3635005A1 (en) * 2017-06-07 2020-04-15 Genmab B.V. Therapeutic antibodies based on mutated igg hexamers
SG11202000198QA (en) 2017-08-04 2020-02-27 Genmab As Binding agents binding to pd-l1 and cd137 and use thereof
HUE065510T2 (hu) * 2017-08-10 2024-05-28 Grifols Diagnostic Solutions Inc Immunglobulin Fc-régiót és poli-His domént tartalmazó oligomerizációs címke
WO2019035938A1 (en) 2017-08-16 2019-02-21 Elstar Therapeutics, Inc. MULTISPECIFIC MOLECULES BINDING TO BCMA AND USES THEREOF
CN111051350B (zh) * 2017-09-07 2022-11-01 苏州丁孚靶点生物技术有限公司 包含信号调节蛋白α的免疫缀合物
EP3684818A2 (en) 2017-09-21 2020-07-29 UMC Utrecht Holding B.V. Anti-gd2 antibody for the treatment of neuroblastoma
US20190153096A1 (en) 2017-10-02 2019-05-23 Covagen Ag Cd3/cd33 bispecific binding molecules
US20190100587A1 (en) * 2017-10-02 2019-04-04 Covagen Ag IgG1 Fc MUTANTS WITH ABLATED EFFECTOR FUNCTIONS
EP3694885A1 (en) 2017-10-14 2020-08-19 CytomX Therapeutics, Inc. Antibodies, activatable antibodies, bispecific antibodies, and bispecific activatable antibodies and methods of use thereof
US12247060B2 (en) 2018-01-09 2025-03-11 Marengo Therapeutics, Inc. Calreticulin binding constructs and engineered T cells for the treatment of diseases
IL325995A (en) 2018-02-08 2026-03-01 Genentech Inc Bispecific antigen binding molecules and methods of use
SG11202008399QA (en) 2018-03-12 2020-09-29 Genmab As Antibodies
EP3765517A1 (en) 2018-03-14 2021-01-20 Elstar Therapeutics, Inc. Multifunctional molecules that bind to calreticulin and uses thereof
BR112020018492A2 (pt) 2018-03-14 2020-12-29 Affimed Gmbh Proteína de ligação ao antígeno egfr/cd16 biespecífica
EP3765516A2 (en) 2018-03-14 2021-01-20 Elstar Therapeutics, Inc. Multifunctional molecules and uses thereof
CN112119090B (zh) 2018-03-15 2023-01-13 中外制药株式会社 对寨卡病毒具有交叉反应性的抗登革热病毒抗体及使用方法
US20210070860A1 (en) * 2018-03-21 2021-03-11 Dana-Farber Cancer Institute, Inc. Fc variant compositions and methods of use thereof
CA3095373A1 (en) * 2018-04-13 2019-10-17 Affimed Gmbh Nk cell engaging antibody fusion constructs
MX2020011552A (es) * 2018-05-03 2020-11-24 Genmab Bv Combinaciones de variantes de anticuerpos y usos de las mismas.
TW202016144A (zh) * 2018-06-21 2020-05-01 日商第一三共股份有限公司 包括cd3抗原結合片段之組成物及其用途
WO2019243636A1 (en) * 2018-06-22 2019-12-26 Genmab Holding B.V. Anti-cd37 antibodies and anti-cd20 antibodies, compositions and methods of use thereof
CA3105448A1 (en) 2018-07-03 2020-01-09 Elstar Therapeutics, Inc. Anti-tcr antibody molecules and uses thereof
US20200017600A1 (en) * 2018-07-13 2020-01-16 Genmab A/S Variants of cd38 antibody and uses thereof
US20240254252A1 (en) * 2018-07-13 2024-08-01 Genmab A/S Trogocytosis-mediated therapy using cd38 antibodies
US12331320B2 (en) 2018-10-10 2025-06-17 The Research Foundation For The State University Of New York Genome edited cancer cell vaccines
AU2019366960A1 (en) * 2018-10-23 2021-05-27 Regeneron Pharmaceuticals, Inc. Fc silenced antibody drug conjugates (ADCs) and uses thereof
AR117091A1 (es) 2018-11-19 2021-07-07 Bristol Myers Squibb Co Anticuerpos monoclonales antagonistas contra cd40 y sus usos
TWI874341B (zh) 2018-12-18 2025-03-01 美商健生生物科技公司 產生異二聚體抗體之方法
CN119039441A (zh) 2019-02-21 2024-11-29 马伦戈治疗公司 与nkp30结合的抗体分子及其用途
EP3927746A1 (en) 2019-02-21 2021-12-29 Marengo Therapeutics, Inc. Multifunctional molecules that bind to calreticulin and uses thereof
JP7737306B2 (ja) 2019-02-21 2025-09-10 マレンゴ・セラピューティクス，インコーポレーテッド Ｔ細胞に結合する多機能性分子および自己免疫障害を処置するためのその使用
EP3927431A1 (en) 2019-02-21 2021-12-29 Marengo Therapeutics, Inc. Anti-tcr antibody molecules and uses thereof
GB2599228B (en) 2019-02-21 2024-02-07 Marengo Therapeutics Inc Multifunctional molecules that bind to T cell related cancer cells and uses thereof
WO2020168554A1 (zh) * 2019-02-22 2020-08-27 武汉友芝友生物制药有限公司 改造的Fc片段，包含其的抗体及其应用
WO2020223148A1 (en) * 2019-04-27 2020-11-05 Figene, Llc Enhancement of fibroblast therapeutic activity by t cell modulation
GB201910900D0 (en) 2019-07-31 2019-09-11 Scancell Ltd Modified fc-regions to enhance functional affinity of antibodies and antigen binding fragments thereof
TW202122420A (zh) 2019-08-30 2021-06-16 美商艾吉納斯公司 抗ｃｄ９６抗體及其使用方法
WO2021048423A1 (en) 2019-09-12 2021-03-18 Genmab A/S Bispecific antibodies binding to 5t4 and cd3 for use in treatment of cancer
CN112646041B (zh) * 2019-10-12 2023-11-10 上海睿智化学研究有限公司 包含抗体ch3域的异源二聚体及含其的抗体、融合蛋白
JP2023500701A (ja) * 2019-11-06 2023-01-10 ジェンマブ ビー．ブイ． 抗体変種の組み合わせおよびその使用
WO2021119505A1 (en) 2019-12-13 2021-06-17 Genentech, Inc. Anti-ly6g6d antibodies and methods of use
EP4084821A4 (en) 2020-01-03 2024-04-24 Marengo Therapeutics, Inc. Multifunctional molecules that bind to cd33 and uses thereof
AU2020416273A1 (en) 2020-01-03 2022-07-28 Marengo Therapeutics, Inc. Anti-TCR antibody molecules and uses thereof
TWI869528B (zh) 2020-01-13 2025-01-11 美商威特拉公司 C5ar1抗體分子及其用途
US20230272105A1 (en) * 2020-01-16 2023-08-31 Genmab A/S Formulations of cd38 antibodies and uses thereof
WO2021165417A1 (en) * 2020-02-19 2021-08-26 Adivo Gmbh Modified fc regions
CN115485302A (zh) 2020-03-09 2022-12-16 百时美施贵宝公司 具有增强的激动剂活性的针对cd40的抗体
MX2022009936A (es) * 2020-03-18 2022-09-12 Genmab As Anticuerpos que se unen al dominio v-set que contiene el inhibidor de activacion de celulas t 1 (b7h4).
CN115843312A (zh) 2020-04-24 2023-03-24 马伦戈治疗公司 结合至t细胞相关癌细胞的多功能性分子及其用途
MX2022013797A (es) 2020-05-08 2022-11-30 Genmab As Anticuerpos biespecificos contra cd3 y cd20.
GB2595299B (en) 2020-05-21 2022-08-03 Mabsolve Ltd Modified immunoglobulin FC regions
GB2616128A (en) 2020-08-26 2023-08-30 Marengo Therapeutics Inc Antibody molecules that bind to NKp30 and uses thereof
AU2021331075A1 (en) 2020-08-26 2023-04-06 Marengo Therapeutics, Inc. Multifunctional molecules that bind to calreticulin and uses thereof
GB2616354A (en) 2020-08-26 2023-09-06 Marengo Therapeutics Inc Methods of detecting TRBC1 or TRBC2
IL300835A (en) * 2020-09-02 2023-04-01 Genmab As Antibody therapy
US20240034812A1 (en) 2020-09-10 2024-02-01 Genmab A/S Bispecific antibody against cd3 and cd20 in combination therapy for treating diffuse large b-cell lymphoma
CA3190376A1 (en) 2020-09-10 2022-03-17 Brian Elliott Bispecific antibody against cd3 and cd20 in combination therapy for treating follicular lymphoma
KR20230066040A (ko) 2020-09-10 2023-05-12 젠맵 에이/에스 만성 림프구성 백혈병을 치료하기 위한 cd3 및 cd20에 대한 이중특이적 항체
CN116782933A (zh) 2020-09-10 2023-09-19 健玛保 用于治疗弥漫性大b细胞淋巴瘤的联合疗法中的针对cd3和cd20的双特异性抗体
CA3189883A1 (en) 2020-09-10 2022-03-17 Brian Elliott Bispecific antibody against cd3 and cd20 in combination therapy for treating follicular lymphoma
JP2023547329A (ja) 2020-10-02 2023-11-10 ジェンマブ エー／エス Ｒｏｒ２へと結合することができる抗体ならびにｒｏｒ２およびｃｄ３に結合する二重特異性抗体
TWI874719B (zh) 2020-11-04 2025-03-01 美商建南德克公司 用抗cd20/抗cd3雙特異性抗體進行治療之給藥
AU2021374594B2 (en) 2020-11-04 2026-03-05 Genentech, Inc. Dosing for treatment with anti-cd20/anti-cd3 bispecific antibodies and anti-cd79b antibody drug conjugates
JP7716473B2 (ja) 2020-11-04 2025-07-31 ジェネンテック， インコーポレイテッド 抗ｃｄ２０／抗ｃｄ３二重特異性抗体の皮下投薬
CA3173944A1 (en) 2021-01-13 2022-07-21 Visterra, Inc. Humanized complement 5a receptor 1 antibodies and methods of use thereof
MX2023010567A (es) * 2021-03-12 2023-09-21 Genmab As Variantes de anticuerpos no activadoras.
WO2022216993A2 (en) 2021-04-08 2022-10-13 Marengo Therapeutics, Inc. Multifuntional molecules binding to tcr and uses thereof
EP4330277A4 (en) * 2021-04-28 2025-03-26 NGM Biopharmaceuticals, Inc. Multimerization of binding molecules with a variant of the constant region of an antibody
WO2022234146A1 (en) 2021-05-07 2022-11-10 Genmab A/S PHARMACEUTICAL COMPOSITIONS COMPRISING BISPECIFIC ANTIBODIES BINDING TO B7H4 and CD3
EP4337330A1 (en) 2021-05-14 2024-03-20 Genentech, Inc. Methods for treatment of cd20-positive proliferative disorder with mosunetuzumab and polatuzumab vedotin
WO2022263357A1 (en) 2021-06-14 2022-12-22 Argenx Iip Bv Anti-il-9 antibodies and methods of use thereof
IL311141A (en) 2021-09-06 2024-04-01 Genmab As Antibodies capable of binding to CD27, their variants and uses thereof
EP4413039A1 (en) * 2021-10-08 2024-08-14 Genmab A/S Antibodies binding to cd30 and cd3
WO2023174521A1 (en) 2022-03-15 2023-09-21 Genmab A/S Binding agents binding to epcam and cd137
US11958906B2 (en) 2022-04-13 2024-04-16 Genentech, Inc. Pharmaceutical compositions of mosunetuzumab and methods of use
WO2023218051A1 (en) 2022-05-12 2023-11-16 Genmab A/S Binding agents capable of binding to cd27 in combination therapy
EP4522657A1 (en) 2022-05-12 2025-03-19 Genmab A/S Binding agents capable of binding to cd27 in combination therapy
CN119698429A (zh) 2022-06-15 2025-03-25 阿根思有限公司 Fcrn结合分子及使用方法
KR20250054799A (ko) * 2022-08-29 2025-04-23 다이이찌 산쿄 가부시키가이샤 변이 Fc 영역을 포함하는 항체 약물 콘쥬게이트
KR20250173600A (ko) 2023-03-17 2025-12-10 옥시토프 파마 비.브이. 항-포스포콜린 항체 및 그 사용 방법
WO2024194685A2 (en) 2023-03-17 2024-09-26 Oxitope Pharma B.V. Anti-phosphocholine antibodies and methods of use thereof
AR132290A1 (es) 2023-04-05 2025-06-11 Genmab As Composiciones farmacéuticas que comprenden anticuerpos que se unen a cd30 y cd3
TW202509077A (zh) 2023-06-30 2025-03-01 丹麥商珍美寶股份有限公司 與纖維母細胞活化蛋白α及死亡受體４結合之抗體
WO2025056180A1 (en) 2023-09-15 2025-03-20 BioNTech SE Methods of treatment using agents binding to epcam and cd137 in combination with pd-1 axis binding antagonists
WO2025133707A1 (en) 2023-12-19 2025-06-26 Vectory Therapeutics B.V. Anti-tdp-43 antibodies and uses thereof
WO2025133694A1 (en) 2023-12-20 2025-06-26 argenx BV Fcrn/hsa-binding molecules and methods of use
EP4644413A1 (en) 2024-05-03 2025-11-05 Genmab B.V. Binding agents having altered fc-mediated effector functions
WO2025228542A1 (en) 2024-05-03 2025-11-06 Genmab B.V. Method for co-expression of a plurality of antibodies
WO2026011013A1 (en) 2024-07-02 2026-01-08 Epibiologics, Inc. Binding agents and uses thereof
WO2026050572A2 (en) 2024-08-29 2026-03-05 Marengo Therapeutics, Inc. Multifunctional molecules binding to tcr and uses thereof

Family Cites Families (148)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4179337A (en) 1973-07-20 1979-12-18 Davis Frank F Non-immunogenic polypeptides
JPS5896026A (ja) 1981-10-30 1983-06-07 Nippon Chemiphar Co Ltd 新規ウロキナ−ゼ誘導体およびその製造法ならびにそれを含有する血栓溶解剤
DE3380726D1 (en) 1982-06-24 1989-11-23 Japan Chem Res Long-acting composition
GB8308235D0 (en) 1983-03-25 1983-05-05 Celltech Ltd Polypeptides
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US4681581A (en) 1983-12-05 1987-07-21 Coates Fredrica V Adjustable size diaper and folding method therefor
US4766106A (en) 1985-06-26 1988-08-23 Cetus Corporation Solubilization of proteins for pharmaceutical compositions using polymer conjugation
US4735210A (en) 1985-07-05 1988-04-05 Immunomedics, Inc. Lymphographic and organ imaging method and kit
US5776093A (en) 1985-07-05 1998-07-07 Immunomedics, Inc. Method for imaging and treating organs and tissues
US5101827A (en) 1985-07-05 1992-04-07 Immunomedics, Inc. Lymphographic and organ imaging method and kit
US5057313A (en) 1986-02-25 1991-10-15 The Center For Molecular Medicine And Immunology Diagnostic and therapeutic antibody conjugates
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.
US5648471A (en) 1987-12-03 1997-07-15 Centocor, Inc. One vial method for labeling antibodies with Technetium-99m
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
US5703055A (en) 1989-03-21 1997-12-30 Wisconsin Alumni Research Foundation Generation of antibodies through lipid mediated DNA delivery
DK0486622T3 (da) 1989-08-09 1999-07-19 Rhomed Inc Direkte radiomærkning af antistoffer og andre proteiner med technetium eller rhenium
US5151504A (en) 1989-11-17 1992-09-29 E. R. Squibb & Sons, Inc. Method for purification of monoclonal antibodies
ATE158021T1 (de) 1990-08-29 1997-09-15 Genpharm Int Produktion und nützung nicht-menschliche transgentiere zur produktion heterologe antikörper
US5814318A (en) 1990-08-29 1998-09-29 Genpharm International Inc. Transgenic non-human animals for producing heterologous antibodies
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
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
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic 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
US5874299A (en) 1990-08-29 1999-02-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5625126A (en) 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US5789650A (en) 1990-08-29 1998-08-04 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US6300129B1 (en) 1990-08-29 2001-10-09 Genpharm International Transgenic non-human animals for producing heterologous antibodies
GB9022543D0 (en) 1990-10-17 1990-11-28 Wellcome Found Antibody production
WO1992022645A1 (en) 1991-06-14 1992-12-23 Genpharm International, Inc. Transgenic immunodeficient non-human animals
CA2113113A1 (en) 1991-07-08 1993-01-21 Simon W. Kantor Thermotropic liquid crystal segmented block copolymer
EP0523949B1 (en) 1991-07-15 2003-06-25 The Wellcome Foundation Limited Production of antibodies
GB9203459D0 (en) 1992-02-19 1992-04-08 Scotgen Ltd Antibodies with germ-line variable regions
US5733743A (en) 1992-03-24 1998-03-31 Cambridge Antibody Technology Limited Methods for producing members of specific binding pairs
AU687010B2 (en) 1992-07-17 1998-02-19 Dana-Farber Cancer Institute Method of intracellular binding of target molecules
US5635483A (en) 1992-12-03 1997-06-03 Arizona Board Of Regents Acting On Behalf Of Arizona State University Tumor inhibiting tetrapeptide bearing modified phenethyl amides
US5780588A (en) 1993-01-26 1998-07-14 Arizona Board Of Regents Elucidation and synthesis of selected pentapeptides
JPH08509612A (ja) 1993-04-26 1996-10-15 ジェンファーム インターナショナル インコーポレイテッド 異種抗体を産生することができるトランスジェニック非ヒト動物
US6214345B1 (en) 1993-05-14 2001-04-10 Bristol-Myers Squibb Co. Lysosomal enzyme-cleavable antitumor drug conjugates
FR2717187B1 (fr) 1994-03-10 1996-05-31 Transgene Sa Usage combiné de deux cassettes d'expression pour la production d'une protéine d'intérêt.
US6077835A (en) 1994-03-23 2000-06-20 Case Western Reserve University Delivery of compacted nucleic acid to cells
US5663149A (en) 1994-12-13 1997-09-02 Arizona Board Of Regents Acting On Behalf Of Arizona State University Human cancer inhibitory pentapeptide heterocyclic and halophenyl amides
US5731168A (en) 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
KR970029803A (ko) 1995-11-03 1997-06-26 김광호 반도체 메모리장치의 프리차지 회로
CA2257861A1 (en) * 1996-06-14 1997-12-18 Smithkline Beecham Corporation Hexameric fusion proteins and uses therefor
ATE299938T1 (de) 1997-05-02 2005-08-15 Genentech Inc Ein verfahren zur herstellung multispezifischer antikörper die heteromultimere und gemeinsame komponenten besitzen
ATE375365T1 (de) 1998-04-02 2007-10-15 Genentech Inc Antikörper varianten und fragmente davon
PL209392B1 (pl) 1999-01-15 2011-08-31 Genentech Inc Przeciwciało, komórka gospodarza, sposób wytwarzania przeciwciała oraz zastosowanie przeciwciała
US6737056B1 (en) 1999-01-15 2004-05-18 Genentech, Inc. Polypeptide variants with altered effector function
WO2000046147A2 (en) 1999-02-03 2000-08-10 Biosante Pharmaceuticals, Inc. Therapeutic calcium phosphate particles and methods of manufacture and use
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
US6281005B1 (en) 1999-05-14 2001-08-28 Copernicus Therapeutics, Inc. Automated nucleic acid compaction device
MXPA02000962A (es) 1999-07-29 2002-07-02 Medarex Inc Anticuerpos monoclonales humanos para her2/neu.
EP1212422B1 (en) 1999-08-24 2007-02-21 Medarex, Inc. Human ctla-4 antibodies and their uses
CA2430013C (en) 2000-11-30 2011-11-22 Medarex, Inc. Transgenic transchromosomal rodents for making human antibodies
US7083784B2 (en) 2000-12-12 2006-08-01 Medimmune, Inc. Molecules with extended half-lives, compositions and uses thereof
EP1243276A1 (en) 2001-03-23 2002-09-25 Franciscus Marinus Hendrikus De Groot Elongated and multiple spacers containing activatible prodrugs
US6989452B2 (en) 2001-05-31 2006-01-24 Medarex, Inc. Disulfide prodrugs and linkers and stabilizers useful therefor
US7595378B2 (en) 2001-06-13 2009-09-29 Genmab A/S Human monoclonal antibodies to epidermal growth factor receptor (EGFR)
PT1600510E (pt) 2001-07-04 2007-06-25 Chromagenics Bv Sequências de adn com actividade anti-repressora.
AU2003217912A1 (en) * 2002-03-01 2003-09-16 Xencor Antibody optimization
WO2003107218A1 (ja) 2002-05-31 2003-12-24 セレスター・レキシコ・サイエンシズ株式会社 相互作用予測装置
DK2314629T4 (da) 2002-07-18 2023-02-06 Merus Nv Rekombinant produktion af blandinger af antistoffer
DK1545613T3 (da) 2002-07-31 2011-11-14 Seattle Genetics Inc Auristatinkonjugater og deres anvendelse til behandling af cancer, en autoimmun sygdom eller en infektiøs sygdom
BRPI0315295C1 (pt) 2002-10-17 2021-05-25 Genmab As anticorpo monoclonal humano isolado, célula hospedeira procariótica, composição farmacêutica, molécula biespecífica, usos de um anticorpo, métodos in vitro de detectar a presença de antígeno de cd20 ou uma célula que expressa cd20 em uma amostra, kit, e, vetor de expressão
WO2004043493A1 (en) 2002-11-14 2004-05-27 Syntarga B.V. Prodrugs built as multiple self-elimination-release spacers
US7438907B2 (en) 2002-11-15 2008-10-21 Genmab A/S Human monoclonal antibodies against CD25
NZ541050A (en) 2002-12-16 2010-06-25 Genmab As Human monoclonal antibodies against interleukin 8 (IL-8)
SI1583830T1 (sl) 2003-01-07 2006-12-31 Symphogen As Postopek za pripravo rekombinantnih poliklonskih proteinov
EP1439234A1 (en) 2003-01-08 2004-07-21 ARTEMIS Pharmaceuticals GmbH Targeted transgenesis using the rosa26 locus
EP2478912B1 (en) 2003-11-06 2016-08-31 Seattle Genetics, Inc. Auristatin conjugates with anti-HER2 or anti-CD22 antibodies and their use in therapy
CN101124245A (zh) * 2003-11-12 2008-02-13 比奥根艾迪克Ma公司 新生儿Fc受体(FcRn)-结合多肽变体、二聚体Fc结合蛋白及其相关方法
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
SI1706424T1 (sl) 2004-01-12 2010-01-29 Applied Molecular Evolution Variante fc regij
PT1737891E (pt) * 2004-04-13 2013-04-16 Hoffmann La Roche Anticorpos anti p-selectina
US7850962B2 (en) 2004-04-20 2010-12-14 Genmab A/S Human monoclonal antibodies against CD20
CA2569509C (en) 2004-06-03 2014-08-12 Novimmune S.A. Anti-cd3 antibodies and methods of use thereof
AU2005274905B2 (en) 2004-08-04 2010-12-23 Mentrik Biotech, Llc Variant Fc regions
JP4487068B2 (ja) 2004-10-12 2010-06-23 国立大学法人 岡山大学 細胞の遺伝子変異機能の制御による変異タンパク質の作製方法
AU2005304624B2 (en) * 2004-11-12 2010-10-07 Xencor, Inc. Fc variants with altered binding to FcRn
US7741568B2 (en) 2005-01-13 2010-06-22 The Wiremold Company Downward facing receptacle assembly for cable raceway
JP5225069B2 (ja) 2005-03-23 2013-07-03 ゲンマブ エー／エス 多発性骨髄腫の治療のためのｃｄ３８に対する抗体
US20110123440A1 (en) 2005-03-29 2011-05-26 Genevieve Hansen Altered Antibody FC Regions and Uses Thereof
AU2006232287B2 (en) 2005-03-31 2011-10-06 Chugai Seiyaku Kabushiki Kaisha Methods for producing polypeptides by regulating polypeptide association
BRPI0611445A2 (pt) 2005-05-09 2010-09-08 Glycart Biotechnology Ag molécula de ligação a antìgeno glicomanipulada, polinucleotìdeo, polipeptìdeo, vetor, célula hospedeira, método para produção, uso e composição farmacêutica
AU2006265936A1 (en) * 2005-07-01 2007-01-11 Medimmune, Llc An integrated approach for generating multidomain protein therapeutics
US8158590B2 (en) 2005-08-05 2012-04-17 Syntarga B.V. Triazole-containing releasable linkers, conjugates thereof, and methods of preparation
US7612181B2 (en) 2005-08-19 2009-11-03 Abbott Laboratories Dual variable domain immunoglobulin and uses thereof
EP1940881B1 (en) 2005-10-11 2016-11-30 Amgen Research (Munich) GmbH Compositions comprising cross-species-specific antibodies and uses thereof
CA2631184A1 (en) 2005-11-28 2007-05-31 Genmab A/S Recombinant monovalent antibodies and methods for production thereof
BRPI0706840A2 (pt) 2006-01-05 2011-04-05 Genentech Inc anticorpos anti- ephb4 isolado polinucleotìdeo, vetor, célula hospedeira, método para produção de um anticorpo anti ephb4, método para produção de um imunoconjugado anti ephb4, método para a detecção de ephb4, método para diagnosticar um distúrbio composição, método para inibir a angiogênese, método para tratar um cáncer, tumor e/ou distúrbio da proliferação celular e uso de um anticorpo
US8940784B2 (en) 2006-02-02 2015-01-27 Syntarga B.V. Water-soluble CC-1065 analogs and their conjugates
EP1999470A4 (en) * 2006-03-10 2009-08-19 Macrogenics Inc IDENTIFICATION AND GENETIC MODIFICATION OF ANTIBODIES WITH HEAVY CHAINS OF VARIANTS AND METHODS OF USE THEREOF
CA2646508A1 (en) 2006-03-17 2007-09-27 Biogen Idec Ma Inc. Stabilized polypeptide compositions
PT1999154E (pt) 2006-03-24 2013-01-24 Merck Patent Gmbh Domínios proteicos heterodiméricos modificados
AT503902B1 (de) 2006-07-05 2008-06-15 F Star Biotech Forsch & Entw Verfahren zur manipulation von immunglobulinen
WO2008090958A1 (ja) 2007-01-24 2008-07-31 Kyowa Hakko Kirin Co., Ltd. ドメイン交換された遺伝子組換え抗体組成物
WO2008114011A2 (en) 2007-03-19 2008-09-25 Medimmune Limited Fc polypeptide variants obtained by ribosome display methodology
EP2155789B1 (en) * 2007-05-01 2013-07-24 Research Development Foundation Immunoglobulin fc libraries
EP2158221B1 (en) 2007-06-21 2018-08-29 MacroGenics, Inc. Covalent diabodies and uses thereof
US20110077383A1 (en) 2007-07-03 2011-03-31 Medimmune, Llc Hinge domain engineering
CA2695297C (en) 2007-08-01 2017-03-21 Syntarga B.V. Substituted cc-1065 analogs and their conjugates
JP5588866B2 (ja) 2007-08-10 2014-09-10 メダレックス エル．エル．シー． Ｈｃｏ３２およびｈｃｏ２７、ならびに関連実施例
JP6157046B2 (ja) 2008-01-07 2017-07-05 アムジェン インコーポレイテッド 静電的ステアリング（ｅｌｅｃｔｒｏｓｔａｔｉｃｓｔｅｅｒｉｎｇ）効果を用いた抗体Ｆｃヘテロ二量体分子を作製するための方法
MX2010008099A (es) * 2008-01-28 2010-08-04 Medimmune Ltd Anticuerpos y angiopoyetina-2 estabilizados y sus usos.
KR20160070165A (ko) 2008-02-08 2016-06-17 메디뮨 엘엘씨 Ｆｃ 리간드 친화성이 감소된 항-ＩＦＮＡＲ１ 항체
EP2147594B1 (en) 2008-06-27 2013-11-13 Merus B.V. Antibody producing non-human mammals
WO2010015792A1 (en) 2008-08-06 2010-02-11 Argenta Discovery Limited Nitrogen containing heterocyclic compounds useful as bifunctional modulators of m3 receptors and beta-2 receptors
DE102008039957A1 (de) 2008-08-27 2010-03-04 Continental Automotive Gmbh Verfahren zur Ermittlung eines Unfallschwerekriteriums mittels eines Beschleunigungssignals und eines Körperschallsignals
JP5397668B2 (ja) 2008-09-02 2014-01-22 ソニー株式会社 記憶素子および記憶装置
JP5913980B2 (ja) 2008-10-14 2016-05-11 ジェネンテック， インコーポレイテッド 免疫グロブリン変異体及びその用途
ES2647317T3 (es) 2008-11-03 2017-12-20 Syntarga B.V. Análogos de CC-1065 y sus conjugados
UA109633C2 (uk) 2008-12-09 2015-09-25 Антитіло людини проти тканинного фактора
DK2786762T3 (da) 2008-12-19 2019-05-06 Macrogenics Inc Kovalente diabodies og anvendelser deraf
EP2233500A1 (en) * 2009-03-20 2010-09-29 LFB Biotechnologies Optimized Fc variants
WO2010129304A2 (en) 2009-04-27 2010-11-11 Oncomed Pharmaceuticals, Inc. Method for making heteromultimeric molecules
WO2010132872A1 (en) 2009-05-15 2010-11-18 Novimmune S.A Combination therapies and methods using anti-cd3 modulating agents and anti-tnf antagonists
MY192182A (en) 2009-06-26 2022-08-04 Regeneron Pharma Readily isolated bispecific antibodies with native immunoglobulin format
WO2011028952A1 (en) 2009-09-02 2011-03-10 Xencor, Inc. Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens
PL2504364T3 (pl) 2009-11-24 2017-12-29 Medimmune Limited Ukierunkowane środki wiążące przeciwko B7-H1
US8961967B2 (en) 2009-11-30 2015-02-24 Janssen Biotech, Inc. Antibody Fc mutants with ablated effector functions
CN102770456B (zh) 2009-12-04 2018-04-06 弗·哈夫曼-拉罗切有限公司 多特异性抗体、抗体类似物、组合物和方法
SG182408A1 (en) 2010-01-11 2012-08-30 Alexion Pharma Inc Biomarkers of immunomodulatory effects in humans treated with anti-cd200 antibodies
WO2011091078A2 (en) 2010-01-19 2011-07-28 Xencor, Inc. Antibody fc variants with enhanced complement activity
PT3904391T (pt) 2010-03-10 2024-10-14 Genmab As Anticorpos monoclonais contra c-met
AR080794A1 (es) 2010-03-26 2012-05-09 Hoffmann La Roche Anticuerpos bivalentes biespecificos anti- vegf/ anti-ang-2
HRP20241208T1 (hr) 2010-04-20 2024-11-22 Genmab A/S Heterodimerni proteini koji sadrže fc fragment protutijela i postupci za njihovu proizvodnju
US9527926B2 (en) 2010-05-14 2016-12-27 Rinat Neuroscience Corp. Heterodimeric proteins and methods for producing and purifying them
CA2800769C (en) 2010-05-27 2021-11-02 Genmab A/S Monoclonal antibodies against her2 epitope
EP2576621B1 (en) 2010-05-27 2019-04-10 Genmab A/S Monoclonal antibodies against her2
BR112012031727B1 (pt) 2010-06-15 2022-03-29 Genmab A/S Conjugado de droga-anticorpo, composição farmacêutica, e, uso do conjugado de droga- anticorpo
CN103068847B (zh) 2010-08-24 2019-05-07 罗切格利卡特公司 可活化的双特异性抗体
CN103068846B9 (zh) 2010-08-24 2016-09-28 弗·哈夫曼-拉罗切有限公司 包含二硫键稳定性Fv片段的双特异性抗体
ES2758994T3 (es) 2010-11-05 2020-05-07 Zymeworks Inc Diseño anticuerpo heterodimérico estable con mutaciones en el dominio Fc
EP2678358B1 (en) * 2011-02-23 2015-07-22 F.Hoffmann-La Roche Ag Antibodies against human il33r and uses thereof
EP2686345B1 (en) 2011-03-16 2018-04-25 Amgen Inc. Fc variants
AU2012245116A1 (en) * 2011-04-20 2013-11-07 Genmab A/S Bispecific antibodies against HER2 and CD3
KR102060389B1 (ko) * 2011-05-21 2019-12-31 마크로제닉스, 인크. 사람 및 비-사람 cd3에 결합할 수 있는 cd3-결합 분자
CN102250246A (zh) 2011-06-10 2011-11-23 常州亚当生物技术有限公司 抗VEGF/PDGFRβ双特异性抗体及其应用
UA117901C2 (uk) * 2011-07-06 2018-10-25 Ґенмаб Б.В. Спосіб посилення ефекторної функції вихідного поліпептиду, його варіанти та їх застосування
US9248181B2 (en) 2012-04-20 2016-02-02 Merus B.V. Methods and means for the production of Ig-like molecules
CN104736174B (zh) 2012-07-06 2019-06-14 根马布私人有限公司 具有三重突变的二聚体蛋白质
KR20200024345A (ko) 2013-01-10 2020-03-06 젠맵 비. 브이 인간 IgG1 Fc 영역 변이체 및 그의 용도
ME03675B (me) 2013-07-05 2020-10-20 Genmab As Humanizovana ili himerna anтi-cd3 antiтela
US10544220B2 (en) 2015-01-08 2020-01-28 Genmab A/S Bispecific antibodies against CD3 and CD20
IL256562B2 (en) 2015-07-15 2024-07-01 Genmab As Human CD3 antibodies or chimeras
US20200017600A1 (en) 2018-07-13 2020-01-16 Genmab A/S Variants of cd38 antibody and uses thereof

Also Published As

Publication number Publication date
BR112015000167A2 (pt) 2017-08-08
AU2020202410A1 (en) 2020-04-30
US20150337049A1 (en) 2015-11-26
EP2869845B1 (en) 2019-08-28
AU2013285355A1 (en) 2015-01-29
JP2022115955A (ja) 2022-08-09
AU2022259785B2 (en) 2025-12-18
US10590206B2 (en) 2020-03-17
BR112015000167B1 (pt) 2021-11-23
JP2015524387A (ja) 2015-08-24
WO2014006217A9 (en) 2015-02-26
SG10201605703TA (en) 2016-09-29
JP2016508153A (ja) 2016-03-17
EP3738979A1 (en) 2020-11-18
SG11201408646VA (en) 2015-01-29
EP2943507A1 (en) 2015-11-18
WO2014108483A1 (en) 2014-07-17
US20230322947A1 (en) 2023-10-12
US20150175707A1 (en) 2015-06-25
SI2943507T1 (sl) 2020-07-31
CN104736174A (zh) 2015-06-24
WO2014006217A1 (en) 2014-01-09
CN104736174B (zh) 2019-06-14
PL2943507T3 (pl) 2020-07-27
JP6604851B2 (ja) 2019-11-13
AU2018203510A1 (en) 2018-06-07
EP2943507B1 (en) 2020-02-26
AU2022259785A1 (en) 2022-12-01
US11180572B2 (en) 2021-11-23
US20200332022A1 (en) 2020-10-22
EP2869845A1 (en) 2015-05-13
US11485796B2 (en) 2022-11-01

Similar Documents

Publication Publication Date Title
AU2022259785B2 (en) Dimeric protein with triple mutations
JP6586442B2 (ja) 抗体変異体およびその使用
JP6377635B2 (ja) ヒトＩｇＧ１Ｆｃ領域変異体およびその使用
US20210230301A1 (en) Dimeric protein with triple mutations
JP2018138022A (ja) ヒトＩｇＧ１ Ｆｃ領域変異体およびその使用
KR20200120743A (ko) 항체 변이체 및 그의 용도
EP3632462A1 (en) Dimeric protein with triple mutations
HK1217719B (en) Human igg1 fc region variants and uses thereof

Legal Events

Date Code Title Description
RD04 Notification of resignation of power of attorney

Free format text: JAPANESE INTERMEDIATE CODE: A7424

Effective date: 20150507

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20160704

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20160704

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20170524

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20170601

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20170831

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20171129

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20180411

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20180710

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20181010

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20190128

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20190130

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: 20190213

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20190311

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20190411

R150 Certificate of patent or registration of utility model

Ref document number: 6514103

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

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250