JP6404313B2 - ヘテロ二量体性二重特異性抗体 - Google Patents
ヘテロ二量体性二重特異性抗体 Download PDFInfo
- Publication number
- JP6404313B2 JP6404313B2 JP2016502206A JP2016502206A JP6404313B2 JP 6404313 B2 JP6404313 B2 JP 6404313B2 JP 2016502206 A JP2016502206 A JP 2016502206A JP 2016502206 A JP2016502206 A JP 2016502206A JP 6404313 B2 JP6404313 B2 JP 6404313B2
- Authority
- JP
- Japan
- Prior art keywords
- cells
- bispecific antibody
- polypeptide chain
- heterodimeric bispecific
- amino acid
- 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
Links
Images
Classifications
-
- 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
- C07K16/30—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- 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
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
-
- 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
- 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
- C07K2317/35—Valency
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- 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
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/626—Diabody or triabody
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
-
- 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
-
- 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)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Cell Biology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Transplantation (AREA)
- Virology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361791357P | 2013-03-15 | 2013-03-15 | |
| US61/791,357 | 2013-03-15 | ||
| US201461944841P | 2014-02-26 | 2014-02-26 | |
| US61/944,841 | 2014-02-26 | ||
| PCT/US2014/026658 WO2014151910A1 (en) | 2013-03-15 | 2014-03-13 | Heterodimeric bispecific antibodies |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018170391A Division JP6700354B2 (ja) | 2013-03-15 | 2018-09-12 | ヘテロ二量体性二重特異性抗体 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016513467A JP2016513467A (ja) | 2016-05-16 |
| JP2016513467A5 JP2016513467A5 (https=) | 2018-03-01 |
| JP6404313B2 true JP6404313B2 (ja) | 2018-10-10 |
Family
ID=50686150
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016502206A Active JP6404313B2 (ja) | 2013-03-15 | 2014-03-13 | ヘテロ二量体性二重特異性抗体 |
| JP2018170391A Active JP6700354B2 (ja) | 2013-03-15 | 2018-09-12 | ヘテロ二量体性二重特異性抗体 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018170391A Active JP6700354B2 (ja) | 2013-03-15 | 2018-09-12 | ヘテロ二量体性二重特異性抗体 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US11634502B2 (https=) |
| EP (2) | EP3424952A1 (https=) |
| JP (2) | JP6404313B2 (https=) |
| AU (1) | AU2014236769B2 (https=) |
| CA (1) | CA2903258C (https=) |
| MX (2) | MX357011B (https=) |
| TW (1) | TW201439117A (https=) |
| WO (1) | WO2014151910A1 (https=) |
Families Citing this family (147)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12466897B2 (en) | 2011-10-10 | 2025-11-11 | Xencor, Inc. | Heterodimeric human IgG1 polypeptides with isoelectric point modifications |
| AU2012355435A1 (en) * | 2011-12-21 | 2014-07-17 | Amgen Inc. | Variant Fc-polypeptides with enhanced binding to the neonatal Fc receptor |
| CA2898100C (en) | 2013-01-14 | 2023-10-10 | Xencor, Inc. | Novel heterodimeric proteins |
| JO3519B1 (ar) * | 2013-01-25 | 2020-07-05 | Amgen Inc | تركيبات أجسام مضادة لأجل cdh19 و cd3 |
| US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
| US9212225B1 (en) | 2014-07-01 | 2015-12-15 | Amphivena Therapeutics, Inc. | Bispecific CD33 and CD3 binding proteins |
| ES2743809T3 (es) | 2014-07-31 | 2020-02-20 | Amgen Res Munich Gmbh | Constructos de anticuerpo monocatenarios biespecificos específicos de especies cruzadas optimizados |
| AR101669A1 (es) * | 2014-07-31 | 2017-01-04 | Amgen Res Munich Gmbh | Constructos de anticuerpos para cdh19 y cd3 |
| WO2016019969A1 (en) | 2014-08-08 | 2016-02-11 | Ludwig-Maximilians-Universität München | Subcutaneously administered bispecific antibodies for use in the treatment of cancer |
| EP3204416A1 (en) * | 2014-10-09 | 2017-08-16 | EngMab AG | Bispecific antibodies against cd3epsilon and ror1 for use in the treatment of ovarian cancer |
| RS61010B1 (sr) * | 2014-11-20 | 2020-11-30 | Hoffmann La Roche | Bispecifični antigen vezujući molekuli koji aktiviraju t ćelije protiv folr1 i cd3 |
| DK3221355T3 (da) | 2014-11-20 | 2020-12-07 | Hoffmann La Roche | Kombinationsbehandling med T-celleaktiverende bispecifikke antigenbindende molekyler CD3 og folatreceptor 1 (FolR1) samt PD-1-aksebindende antagonister |
| SI3221357T1 (sl) * | 2014-11-20 | 2020-09-30 | F. Hoffmann-La Roche Ag | Pogoste lahke verige in načini uporabe |
| BR112017011166A2 (pt) | 2014-11-26 | 2018-02-27 | Xencor, Inc. | anticorpos heterodiméricos que se ligam a cd3 e cd38 |
| CN110894240B (zh) | 2014-11-26 | 2022-04-15 | 森科股份有限公司 | 结合cd3和肿瘤抗原的异二聚体抗体 |
| US10259887B2 (en) | 2014-11-26 | 2019-04-16 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and tumor antigens |
| MA40938A (fr) | 2014-12-05 | 2017-10-11 | Hoffmann La Roche | Anticorps anti-cd79b et méthodes d'utilisation desdits anticorps |
| WO2016094881A2 (en) * | 2014-12-11 | 2016-06-16 | Abbvie Inc. | Lrp-8 binding proteins |
| AU2015364396B2 (en) * | 2014-12-19 | 2018-08-09 | Alkermes, Inc. | Single chain Fc fusion proteins |
| CR20170383A (es) | 2015-01-23 | 2017-11-22 | Sanofi Sa | Anticuerpos anti-cd3, anticuerpos anti-cd-123 y anticuerpos biespecíficos que se unen específicamente a cd3 y/o cd123 |
| EP3253790A4 (en) | 2015-02-06 | 2018-07-25 | University of Maryland, Baltimore | Tetra-specific, octameric binding agents and antibodies against clostridium difficile toxin a and toxin b for treatment of c. difficile infection |
| ES2945313T3 (es) | 2015-04-17 | 2023-06-30 | Amgen Res Munich Gmbh | Construcciones de anticuerpos biespecificos para CDH3 y CD3 |
| EA201792573A1 (ru) | 2015-05-21 | 2018-04-30 | Харпун Терапьютикс, Инк. | Триспецифические связанные белки и способы их применения |
| MX2017015380A (es) * | 2015-05-29 | 2018-03-28 | Amphivena Therapeutics Inc | Metodos para utilizar proteinas de enlace biespecificas cd3 y cd33. |
| TW201710286A (zh) | 2015-06-15 | 2017-03-16 | 艾伯維有限公司 | 抗vegf、pdgf及/或其受體之結合蛋白 |
| FR3038517B1 (fr) * | 2015-07-06 | 2020-02-28 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Utilisation de fragments fc modifies en immunotherapie |
| TWI829617B (zh) | 2015-07-31 | 2024-01-21 | 德商安美基研究(慕尼黑)公司 | Flt3及cd3抗體構築體 |
| TWI793062B (zh) | 2015-07-31 | 2023-02-21 | 德商安美基研究(慕尼黑)公司 | Dll3及cd3抗體構築體 |
| TWI796283B (zh) * | 2015-07-31 | 2023-03-21 | 德商安美基研究(慕尼黑)公司 | Msln及cd3抗體構築體 |
| TWI717375B (zh) | 2015-07-31 | 2021-02-01 | 德商安美基研究(慕尼黑)公司 | Cd70及cd3抗體構築體 |
| EA039859B1 (ru) | 2015-07-31 | 2022-03-21 | Эмджен Рисерч (Мюник) Гмбх | Биспецифические конструкты антител, связывающие egfrviii и cd3 |
| TWI744242B (zh) | 2015-07-31 | 2021-11-01 | 德商安美基研究(慕尼黑)公司 | Egfrviii及cd3抗體構築體 |
| JO3620B1 (ar) | 2015-08-05 | 2020-08-27 | Amgen Res Munich Gmbh | مثبطات نقطة فحص مناعية للاستخدام في علاج سرطانات محمولة عبر الدم |
| AR106188A1 (es) | 2015-10-01 | 2017-12-20 | Hoffmann La Roche | Anticuerpos anti-cd19 humano humanizados y métodos de utilización |
| CN116063544A (zh) | 2016-02-03 | 2023-05-05 | 安进研发(慕尼黑)股份有限公司 | Bcma和cd3双特异性t细胞接合抗体构建体 |
| EP3411404B1 (en) | 2016-02-03 | 2022-11-09 | Amgen Research (Munich) GmbH | Psma and cd3 bispecific t cell engaging antibody constructs |
| GB201604458D0 (en) | 2016-03-16 | 2016-04-27 | Immatics Biotechnologies Gmbh | Peptides and combination of peptides for use in immunotherapy against cancers |
| HRP20230528T1 (hr) | 2016-03-22 | 2023-08-04 | F. Hoffmann - La Roche Ag | Bispecifične molekule t stanica aktivirane proteazom |
| CR20180453A (es) * | 2016-03-22 | 2018-12-05 | Hoffmann La Roche | Moleculas biespecíficas de células t activadas por proteasas |
| JOP20170091B1 (ar) | 2016-04-19 | 2021-08-17 | Amgen Res Munich Gmbh | إعطاء تركيبة ثنائية النوعية ترتبط بـ cd33 وcd3 للاستخدام في طريقة لعلاج اللوكيميا النخاعية |
| JP7101621B2 (ja) | 2016-05-20 | 2022-07-15 | ハープーン セラピューティクス,インク. | 単一ドメイン血清アルブミン結合タンパク質 |
| CN116987189A (zh) | 2016-05-20 | 2023-11-03 | 哈普恩治疗公司 | 单链可变片段cd3结合蛋白质 |
| US11623958B2 (en) | 2016-05-20 | 2023-04-11 | Harpoon Therapeutics, Inc. | Single chain variable fragment CD3 binding proteins |
| KR20190022632A (ko) | 2016-06-20 | 2019-03-06 | 에프-스타 베타 리미티드 | Lag-3 결합 구성원 |
| JP7084881B2 (ja) | 2016-06-22 | 2022-06-15 | アルカームス インコーポレーテッド | Il-10の免疫刺激特性および抗炎症特性を調節するための組成物および方法 |
| WO2018005706A1 (en) | 2016-06-28 | 2018-01-04 | Xencor, Inc. | Heterodimeric antibodies that bind somatostatin receptor 2 |
| EP3544629A4 (en) | 2016-11-23 | 2020-06-17 | Harpoon Therapeutics, Inc. | PSMA TO BE TRISPECIFIC PROTEINS AND METHOD FOR USE THEREOF |
| CN110198955A (zh) | 2016-11-23 | 2019-09-03 | 哈普恩治疗公司 | 前列腺特异性膜抗原结合蛋白质 |
| TN2019000225A1 (en) | 2017-02-02 | 2021-01-07 | Amgen Res Munich Gmbh | Low ph pharmaceutical composition comprising t cell engaging antibody constructs |
| EP3589662A4 (en) | 2017-02-28 | 2020-12-30 | Harpoon Therapeutics, Inc. | INDUCTIBLE MONOVALENT ANTIGEN BINDING PROTEIN |
| MX2019013142A (es) | 2017-05-05 | 2019-12-16 | Amgen Inc | Composicion farmaceutica que comprende construcciones de anticuerpos biespecificas para mejorar el almacenamiento y la administracion. |
| WO2018209304A1 (en) * | 2017-05-12 | 2018-11-15 | Harpoon Therapeutics, Inc. | Msln targeting trispecific proteins and methods of use |
| AU2018265856B2 (en) | 2017-05-12 | 2023-04-27 | Harpoon Therapeutics, Inc. | Mesothelin binding proteins |
| HRP20241268T1 (hr) | 2017-10-13 | 2024-12-06 | Harpoon Therapeutics, Inc. | Trispecifični proteini i postupci primjene |
| IL315737A (en) | 2017-10-13 | 2024-11-01 | Harpoon Therapeutics Inc | B-cell maturation antigen-binding proteins |
| CA3287794A1 (en) | 2017-10-14 | 2025-10-27 | Cytomx Therapeutics, Inc. | Antibodies, activatable antibodies, bispecific antibodies, and bispecific activatable antibodies and methods of use thereof |
| JP2021502100A (ja) | 2017-11-08 | 2021-01-28 | ゼンコア インコーポレイテッド | 新規抗pd−1配列を用いた二重特異性および単一特異性抗体 |
| KR20250111232A (ko) | 2017-12-11 | 2025-07-22 | 암젠 인크 | 이중특이적 항체 생성물의 연속 제조 공정 |
| DK3728328T5 (da) | 2017-12-22 | 2025-02-17 | Argenx Bvba | Bispecifik antigenbindende konstruktion |
| CN109957026A (zh) * | 2017-12-22 | 2019-07-02 | 成都恩沐生物科技有限公司 | 共价多特异性抗体 |
| UY38041A (es) | 2017-12-29 | 2019-06-28 | Amgen Inc | Construcción de anticuerpo biespecífico dirigida a muc17 y cd3 |
| GB201802487D0 (en) | 2018-02-15 | 2018-04-04 | Argenx Bvba | Cytokine combination therapy |
| WO2019195623A2 (en) | 2018-04-04 | 2019-10-10 | Xencor, Inc. | Heterodimeric antibodies that bind fibroblast activation protein |
| CN108610417B (zh) * | 2018-04-28 | 2021-01-26 | 暨南大学 | 抗破伤风毒素中和抗体、其制备方法及用途 |
| KR20210020903A (ko) | 2018-05-14 | 2021-02-24 | 하푼 테라퓨틱스, 인크. | 면역글로불린 분자의 조건부 활성화를 위한 결합 모이어티 |
| GB201811404D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | Anti-CD137 Antibodies |
| BR112021000282A2 (pt) | 2018-07-12 | 2021-04-06 | F-Star Beta Limited | Moléculas de anticorpo que se ligam a cd137 e ox40 |
| PL3820569T3 (pl) | 2018-07-12 | 2025-07-14 | Invox Pharma Limited | Cząsteczki przeciwciał, które wiążą PD-L1 oraz CD137 |
| GB201811410D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | OX40 Binding molecules |
| GB201811415D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | Anti-Mesothelin Anti bodies |
| GB201811450D0 (en) | 2018-07-12 | 2018-08-29 | F Star Delta Ltd | Mesothelin and CD137 binding molecules |
| GB201811403D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | Antibody molecules |
| GB201811408D0 (en) | 2018-07-12 | 2018-08-29 | F Star Beta Ltd | CD137 Binding Molecules |
| WO2020025532A1 (en) | 2018-07-30 | 2020-02-06 | Amgen Research (Munich) Gmbh | Prolonged administration of a bispecific antibody construct binding to cd33 and cd3 |
| CA3105729A1 (en) | 2018-07-31 | 2020-02-06 | Amgen Research (Munich) Gmbh | Dosing regimen for bcma-cd3 bispecific antibodies |
| JOP20210022A1 (ar) | 2018-08-03 | 2021-01-28 | Amgen Inc | بنيات جسم مضاد لـ cldn18.2وcd3 |
| WO2020061482A1 (en) | 2018-09-21 | 2020-03-26 | Harpoon Therapeutics, Inc. | Egfr binding proteins and methods of use |
| SG11202103022WA (en) | 2018-09-25 | 2021-04-29 | Harpoon Therapeutics Inc | Dll3 binding proteins and methods of use |
| US11505614B2 (en) | 2018-09-28 | 2022-11-22 | Amgen Inc. | Antibodies binding to soluble BCMA |
| AU2019356564A1 (en) | 2018-10-11 | 2021-04-29 | Amgen Inc. | Downstream processing of bispecific antibody constructs |
| PT3870957T (pt) | 2018-10-23 | 2025-09-01 | Amgen Inc | Calibração automática e manutenção automática de modelos espetroscópicos para previsões em tempo real |
| KR20210108421A (ko) * | 2018-12-24 | 2021-09-02 | 사노피 | 돌연변이 Fab 도메인을 포함하는 다중특이성 결합 단백질 |
| TWI871300B (zh) | 2019-01-28 | 2025-02-01 | 美商安進公司 | 藉由將藥物物質和藥物產品過程整體化的生物製劑製造之連續製造過程 |
| CA3139346A1 (en) | 2019-05-07 | 2020-11-12 | Gracell Biotechnologies (Shanghai) Co., Ltd. | Engineered immune cell targeting bcma and use thereof |
| US12516128B2 (en) | 2019-05-14 | 2026-01-06 | Harpoon Therapeutics, Inc. | EpCAM binding proteins and methods of use |
| MX2021014644A (es) | 2019-06-13 | 2022-04-06 | Amgen Inc | Control de perfusion basado en biomasa automatizado en la fabricacion de productos biologicos. |
| CN112111012B (zh) * | 2019-06-20 | 2023-07-04 | 成都恩沐生物科技有限公司 | 共价多特异性抗体 |
| US20210032370A1 (en) | 2019-08-02 | 2021-02-04 | Immatics Biotechnologies Gmbh | Recruiting agent further binding an mhc molecule |
| DE102019121007A1 (de) | 2019-08-02 | 2021-02-04 | Immatics Biotechnologies Gmbh | Antigenbindende Proteine, die spezifisch an MAGE-A binden |
| AU2020345787A1 (en) | 2019-09-10 | 2022-03-24 | Amgen Inc. | Purification method for bispecific antigen-binding polypeptides with enhanced protein L capture dynamic binding capacity |
| WO2021091906A1 (en) | 2019-11-04 | 2021-05-14 | Amgen Inc. | Methods for treating leukemia |
| EP3819007B1 (en) | 2019-11-11 | 2024-07-10 | Amgen Research (Munich) GmbH | Dosing regimen for anti-bcma agents |
| AU2020381536A1 (en) | 2019-11-13 | 2022-04-21 | Amgen Inc. | Method for reduced aggregate formation in downstream processing of bispecific antigen-binding molecules |
| EP4065585B1 (en) | 2019-11-25 | 2025-08-20 | Alkermes, Inc. | Substituted macrocyclic compounds and related methods of treatment |
| MX2022007688A (es) | 2019-12-20 | 2022-07-19 | Amgen Inc | Constructos de anticuerpo multiespecificos agonistas de cd40 dirigidos a mesotelina para el tratamiento de tumores solidos. |
| JP2023525423A (ja) | 2020-01-15 | 2023-06-16 | イマティクス バイオテクノロジーズ ゲーエムベーハー | Prameに特異的に結合する抗原結合タンパク質 |
| EP4093771A1 (en) | 2020-01-22 | 2022-11-30 | Amgen Research (Munich) GmbH | Combinations of antibody constructs and inhibitors of cytokine release syndrome and uses thereof |
| US20230071627A1 (en) | 2020-02-03 | 2023-03-09 | Amgen Inc. | Multivariate Bracketing Approach for Sterile Filter Validation |
| TWI888487B (zh) | 2020-02-14 | 2025-07-01 | 日商協和麒麟股份有限公司 | 與cd3結合之雙特異性抗體 |
| CA3170833A1 (en) | 2020-02-21 | 2021-08-26 | Harpoon Therapeutics, Inc. | Flt3 binding proteins and methods of use |
| WO2021183861A1 (en) | 2020-03-12 | 2021-09-16 | Amgen Inc. | Method for treatment and prophylaxis of crs in patients comprising a combination of bispecifc antibodies binding to cds x cancer cell and tnfalpha or il-6 inhibitor |
| KR20220155338A (ko) | 2020-03-19 | 2022-11-22 | 암젠 인크 | 뮤신 17에 대한 항체 및 이의 용도 |
| WO2021231969A1 (en) * | 2020-05-14 | 2021-11-18 | Xencor, Inc. | Heterodimeric antibodies that bind msln and cd3 |
| WO2021231976A1 (en) | 2020-05-14 | 2021-11-18 | Xencor, Inc. | Heterodimeric antibodies that bind prostate specific membrane antigen (psma) and cd3 |
| US12312412B2 (en) | 2020-05-19 | 2025-05-27 | Amgen Inc. | MAGEB2 binding constructs |
| AU2021281554A1 (en) | 2020-05-29 | 2022-12-15 | Amgen Inc. | Adverse effects-mitigating administration of a bispecific antibody construct binding to CD33 and CD3 |
| BR112022025856A2 (pt) | 2020-06-19 | 2023-01-10 | Hoffmann La Roche | Anticorpo que se liga a cd3 e cd19, polinucleotídeo isolado, célula hospedeira, método de produção de um anticorpo que se liga a cd3 e cd19, composição farmacêutica, uso do anticorpo, método para tratar uma doença em um indivíduo e invenção |
| AU2021331170A1 (en) | 2020-08-27 | 2023-03-23 | Juntendo Educational Foundation | Anti-cleaved mutant calr-cd3 bispecific antibody and pharmaceutical composition |
| WO2022060878A1 (en) | 2020-09-16 | 2022-03-24 | Amgen Inc. | Methods for treating prostate cancer |
| EP4214233A1 (en) | 2020-09-16 | 2023-07-26 | Amgen Inc. | Methods for administering therapeutic doses of bispecific t-cell engaging molecules for the treatment of cancer |
| EP4240767A1 (en) | 2020-11-06 | 2023-09-13 | Amgen Inc. | Polypeptide constructs binding to cd3 |
| IL301926A (en) | 2020-11-06 | 2023-06-01 | Amgen Inc | Antigen binding domain with reduced clipping rate |
| AU2021374036A1 (en) | 2020-11-06 | 2023-06-08 | Amgen Inc. | Polypeptide constructs selectively binding to cldn6 and cd3 |
| CN116323671A (zh) | 2020-11-06 | 2023-06-23 | 安进公司 | 具有增加的选择性的多靶向性双特异性抗原结合分子 |
| US20250136704A1 (en) | 2020-11-10 | 2025-05-01 | Amgen Inc. | Methods for administering a bcmaxcd3 binding molecule |
| US11760747B2 (en) | 2020-12-21 | 2023-09-19 | Alkermes, Inc. | Substituted piperidino compounds and related methods of treatment |
| JP2024511319A (ja) | 2021-03-09 | 2024-03-13 | ゼンコア インコーポレイテッド | Cd3及びcldn6に結合するヘテロ二量体抗体 |
| JP2024509274A (ja) | 2021-03-10 | 2024-02-29 | ゼンコア インコーポレイテッド | Cd3及びgpc3に結合するヘテロ二量体抗体 |
| JP2024509877A (ja) | 2021-03-10 | 2024-03-05 | アムジエン・インコーポレーテツド | 組換えタンパク質の精製方法 |
| WO2022191971A1 (en) | 2021-03-10 | 2022-09-15 | Amgen Inc. | Parallel chromatography systems and methods |
| EP4314075A4 (en) * | 2021-03-24 | 2025-04-09 | Twist Bioscience Corporation | VARIANT NUCLEIC ACID BANKS FOR CD3 |
| MX2023011690A (es) | 2021-04-02 | 2023-12-15 | Amgen Inc | Construcciones de unión a mageb2. |
| JP7717832B2 (ja) * | 2021-04-10 | 2025-08-04 | ジェンマブ エー/エス | Folr1結合剤、そのコンジュゲートおよびこれを使用する方法 |
| EP4334361A1 (en) | 2021-05-05 | 2024-03-13 | Immatics Biotechnologies GmbH | Antigen binding proteins specifically binding prame |
| CN117279947A (zh) | 2021-05-06 | 2023-12-22 | 安进研发(慕尼黑)股份有限公司 | 用于在增殖性疾病中使用的靶向cd20和cd22的抗原结合分子 |
| US20230190806A1 (en) | 2021-10-06 | 2023-06-22 | Immatics Biotechnologies Gmbh | Methods of treating metastatic lesions and compositions thereof |
| JP2025500732A (ja) | 2021-10-27 | 2025-01-15 | アムジエン・インコーポレーテツド | 分光法を使用して薬剤を監視するための深層学習ベースの予測 |
| AU2022382368A1 (en) | 2021-11-03 | 2024-05-02 | Affimed Gmbh | Bispecific cd16a binders |
| JP2024543828A (ja) | 2021-11-03 | 2024-11-26 | アフィメド ゲーエムベーハー | 二重特異性cd16aバインダー |
| EP4448108A1 (en) | 2021-11-08 | 2024-10-23 | Immatics Biotechnologies GmbH | Adoptive cell therapy combination treatment and compositions thereof |
| CN118742324A (zh) | 2022-02-25 | 2024-10-01 | 学校法人顺天堂 | 抗突变calr抗体与其他药剂组合而成的医药 |
| US20250354995A1 (en) | 2022-04-29 | 2025-11-20 | Immatics Biotechnologies Gmbh | Mammalian display platform for multispecific antigen binding proteins |
| WO2023218027A1 (en) | 2022-05-12 | 2023-11-16 | Amgen Research (Munich) Gmbh | Multichain multitargeting bispecific antigen-binding molecules of increased selectivity |
| AU2023301087A1 (en) * | 2022-06-30 | 2025-02-13 | Modex Therapeutics, Inc. | Anti-sars-cov-2 antigen binding polypeptides, polypeptide complexes and methods of use thereof |
| US20260083841A1 (en) | 2022-09-14 | 2026-03-26 | Amgen Inc. | Bispecific Molecule Stabilizing Composition |
| EP4598958A1 (en) | 2022-10-05 | 2025-08-13 | Amgen Inc. | Combination therapies comprising t-cell redirecting therapies and agonistic anti-il-2r antibodies or fragments thereof |
| EP4676947A1 (en) | 2023-03-08 | 2026-01-14 | Amgen Inc. | Controlled-ice nucleation lyophilization process for bispecific molecules |
| MX2025014635A (es) | 2023-06-14 | 2026-02-03 | Amgen Inc | Moleculas captadoras de enmascaramiento de celulas t |
| TW202506719A (zh) | 2023-07-27 | 2025-02-16 | 德商艾瑪提克生物技術有限公司 | 針對mageb2之抗原結合蛋白 |
| TW202521428A (zh) | 2023-08-22 | 2025-06-01 | 美商安進公司 | 用於高效包裝藥物產品之方法及組件 |
| US20250146017A1 (en) | 2023-11-06 | 2025-05-08 | City Of Hope | Methods comprising oncolytic viruses expressing cd19t and bispecific t cell engagers |
| WO2025226901A1 (en) | 2024-04-25 | 2025-10-30 | Amgen Inc. | Pairing of two-chain constructs |
| WO2025233420A1 (en) | 2024-05-07 | 2025-11-13 | Immatics Biotechnologies Gmbh | Use of anti-cancer molecules |
| WO2025257588A1 (en) | 2024-06-10 | 2025-12-18 | Affimed Gmbh | Cd16a/tumor antigen polyspecific binder for use in the treatment of immune checkpoint inhibitor resistance |
| WO2025259515A2 (en) | 2024-06-11 | 2025-12-18 | Amgen Inc. | Combination treatment |
| WO2026025031A1 (en) | 2024-07-26 | 2026-01-29 | Modernatx, Inc. | Mrna encoding mageb2 tcer molecule |
| WO2026072671A1 (en) | 2024-09-24 | 2026-04-02 | City Of Hope | Methods comprising oncolytic viruses expressing bcmat and bcma-targeted therapies |
Family Cites Families (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0368684B2 (en) | 1988-11-11 | 2004-09-29 | Medical Research Council | Cloning immunoglobulin variable domain sequences. |
| ATE199392T1 (de) | 1992-12-04 | 2001-03-15 | Medical Res Council | Multivalente und multispezifische bindungsproteine, deren herstellung und verwendung |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| US20020137890A1 (en) | 1997-03-31 | 2002-09-26 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
| US20020062010A1 (en) | 1997-05-02 | 2002-05-23 | Genentech, Inc. | Method for making multispecific antibodies having heteromultimeric and common components |
| CN101289511A (zh) | 2000-04-11 | 2008-10-22 | 杰南技术公司 | 多价抗体及其应用 |
| CA2410551A1 (en) | 2000-06-30 | 2002-01-10 | Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw (Vib) | Heterodimeric fusion proteins |
| PT1355919E (pt) | 2000-12-12 | 2011-03-02 | Medimmune Llc | Moléculas com semivida longa, composições que as contêm e suas utilizações |
| US7053202B2 (en) | 2001-10-19 | 2006-05-30 | Millennium Pharmaceuticals, Inc. | Immunoglobulin DNA cassette molecules, monobody constructs, methods of production, and methods of use therefor |
| ES2263984T3 (es) * | 2002-06-28 | 2006-12-16 | Domantis Limited | Ligandos doble-especificos con una vida media serica aumentada. |
| US8367805B2 (en) | 2004-11-12 | 2013-02-05 | Xencor, Inc. | Fc variants with altered binding to FcRn |
| KR100609578B1 (ko) | 2004-12-28 | 2006-08-08 | 주식회사 하이닉스반도체 | 플래쉬 메모리소자의 플로팅 게이트전극 형성방법 |
| US9963510B2 (en) | 2005-04-15 | 2018-05-08 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
| EP3479844B1 (en) | 2005-04-15 | 2023-11-22 | MacroGenics, Inc. | Covalent diabodies and uses thereof |
| US9284375B2 (en) | 2005-04-15 | 2016-03-15 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
| KR20130108481A (ko) | 2005-08-19 | 2013-10-02 | 아보트 러보러터리즈 | 이원 가변 도메인 면역글로불린 및 이의 용도 |
| US7612181B2 (en) | 2005-08-19 | 2009-11-03 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
| AR056142A1 (es) | 2005-10-21 | 2007-09-19 | Amgen Inc | Metodos para generar el anticuerpo igg monovalente |
| WO2008119565A2 (en) | 2007-04-03 | 2008-10-09 | Micromet Ag | Cross-species-specific binding domain |
| WO2008119566A2 (en) | 2007-04-03 | 2008-10-09 | Micromet Ag | Cross-species-specific bispecific binders |
| EP3424951A1 (en) | 2007-06-21 | 2019-01-09 | MacroGenics, Inc. | Covalent diabodies and uses thereof |
| EP2050764A1 (en) * | 2007-10-15 | 2009-04-22 | sanofi-aventis | Novel polyvalent bispecific antibody format and uses thereof |
| ES2563027T3 (es) * | 2008-01-07 | 2016-03-10 | Amgen Inc. | Método para fabricación de moléculas heterodímeras Fc de anticuerpos utilizando efectos de conducción electrostática |
| PE20100092A1 (es) | 2008-06-03 | 2010-03-12 | Abbott Lab | Inmunoglobulina con dominio variable dual y usos de la misma |
| JP6126782B2 (ja) * | 2008-10-01 | 2017-05-10 | アムゲン リサーチ (ミュンヘン) ゲーエムベーハー | 異種間特異的psma×cd3二重特異性単鎖抗体 |
| EP2376109B1 (en) | 2008-12-19 | 2019-01-23 | MacroGenics, Inc. | Covalent diabodies and uses thereof |
| WO2012025530A1 (en) | 2010-08-24 | 2012-03-01 | F. Hoffmann-La Roche Ag | Bispecific antibodies comprising a disulfide stabilized - fv fragment |
| JP5768147B2 (ja) | 2011-02-28 | 2015-08-26 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 一価抗原結合タンパク質 |
| EP2681242B1 (en) * | 2011-03-01 | 2018-01-24 | Amgen Inc. | Sclerostin and dkk-1 bispecific binding agents |
| EP2686345B1 (en) | 2011-03-16 | 2018-04-25 | Amgen Inc. | Fc variants |
| TWI588156B (zh) * | 2011-03-28 | 2017-06-21 | 賽諾菲公司 | 具有交叉結合區定向之雙重可變區類抗體結合蛋白 |
| AU2012355435A1 (en) | 2011-12-21 | 2014-07-17 | Amgen Inc. | Variant Fc-polypeptides with enhanced binding to the neonatal Fc receptor |
| EP2938637A2 (en) | 2012-12-28 | 2015-11-04 | AbbVie Inc. | Multivalent binding protein compositions |
| CA2902739C (en) | 2013-03-15 | 2022-11-22 | Xencor, Inc. | Heterodimeric proteins |
| US20140308285A1 (en) * | 2013-03-15 | 2014-10-16 | Amgen Inc. | Heterodimeric bispecific antibodies |
| US20160038588A1 (en) * | 2013-03-15 | 2016-02-11 | Amgen Inc. | Myostatin Antagonism in Human Subjects |
| US20140302037A1 (en) * | 2013-03-15 | 2014-10-09 | Amgen Inc. | BISPECIFIC-Fc MOLECULES |
| EP3733710A1 (en) * | 2013-09-25 | 2020-11-04 | Amgen, Inc | Hetrodimeric v-c-fc-v-c antibody |
-
2014
- 2014-03-13 AU AU2014236769A patent/AU2014236769B2/en active Active
- 2014-03-13 US US14/774,320 patent/US11634502B2/en active Active
- 2014-03-13 CA CA2903258A patent/CA2903258C/en active Active
- 2014-03-13 EP EP18168747.6A patent/EP3424952A1/en active Pending
- 2014-03-13 JP JP2016502206A patent/JP6404313B2/ja active Active
- 2014-03-13 MX MX2015012439A patent/MX357011B/es active IP Right Grant
- 2014-03-13 EP EP14722862.1A patent/EP2970484B2/en active Active
- 2014-03-13 WO PCT/US2014/026658 patent/WO2014151910A1/en not_active Ceased
- 2014-03-14 TW TW103109334A patent/TW201439117A/zh unknown
-
2015
- 2015-09-11 MX MX2018007206A patent/MX2018007206A/es unknown
-
2018
- 2018-09-12 JP JP2018170391A patent/JP6700354B2/ja active Active
Also Published As
| Publication number | Publication date |
|---|---|
| EP2970484B2 (en) | 2022-09-21 |
| TW201439117A (zh) | 2014-10-16 |
| US20160115241A1 (en) | 2016-04-28 |
| JP2016513467A (ja) | 2016-05-16 |
| JP6700354B2 (ja) | 2020-05-27 |
| MX2018007206A (es) | 2021-11-16 |
| CA2903258C (en) | 2019-11-26 |
| AU2014236769B2 (en) | 2018-09-27 |
| MX357011B (es) | 2018-06-22 |
| US11634502B2 (en) | 2023-04-25 |
| CA2903258A1 (en) | 2014-09-25 |
| EP3424952A1 (en) | 2019-01-09 |
| JP2019022497A (ja) | 2019-02-14 |
| EP2970484B1 (en) | 2018-05-16 |
| AU2014236769A1 (en) | 2015-09-10 |
| WO2014151910A1 (en) | 2014-09-25 |
| EP2970484A1 (en) | 2016-01-20 |
| MX2015012439A (es) | 2016-04-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6700354B2 (ja) | ヘテロ二量体性二重特異性抗体 | |
| US20230077648A1 (en) | Heterodimeric Bispecific Antibodies | |
| JP6732988B2 (ja) | 二重特異性二価scFv−Fc分子 | |
| US20230055407A1 (en) | V-c-fc-v-c antibody | |
| JP7842528B2 (ja) | プロテアーゼにより活性化可能な二重特異性タンパク質 | |
| US20220242962A1 (en) | 4-1bb and ox40 binding proteins and related compositions and methods, antibodies against 4-1bb, antibodies against ox40 | |
| WO2025201240A1 (en) | Antibodies targeting cd3, cd28, and pd-l1 and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170310 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20170310 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180116 |
|
| A871 | Explanation of circumstances concerning accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A871 Effective date: 20180116 |
|
| A975 | Report on accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A971005 Effective date: 20180119 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180131 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20180427 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180622 |
|
| 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: 20180816 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20180912 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6404313 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 |