BISPECIFIC ANTIBODIES AGAINST CD3EPSILON AND BCMA

• Main Authors: MESSNER EKKEHARD, ANNE FREIMOSER-GRUNDSCHOBER, JOERG REGULA, MINH DIEM VU, LYDIA JASMIN HANISCH, AST OLIVER, TANJA FAUTI, SABINE JUNG-IMHOF, KLEIN CHRISTIAN, STEFAN KLOSTERMANN, MICHAEL MOLHOJ, SAMUEL MOSER, MARINA BACAC, RAMONA MURR, RALF HOSSE, SCHAEFER WOLFGANG, PABLO UMANA, KLAUS STREIN
• Format: Patent
• Language: English; Japanese
• Published: 13.08.2020
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

To provide bispecific antibodies against CD3epsilon and BCMA.SOLUTION: There is provided a bispecific bi- or trivalent antibody specifically binding to the two targets which are the extracellular domain of human B cell maturation antigen (BCMA) and human CD3epsilon. The variable domains VL and VH in a light chain and the corresponding heavy chain are replaced by each other. The antibody comprises a constant domain CL. The amino acid at position 124 is substituted independently by lysine (K), arginine (R) or histidine (H) (numbering according to Kabat. In the corresponding constant domain CH1, the amino acid at position 147 and the amino acid at position 213 are substituted independently by glutamic acid (E), or aspartic acid (D) (numbering according to Kabat). Also provided are manufacture and use of the antibody.SELECTED DRAWING: None 【課題】ＣＤ３イプシロンおよびＢＣＭＡに対する二特異性抗体の提供。【解決手段】ヒトＢ細胞成熟抗原（ＢＣＭＡ）の細胞外ドメイン、およびヒトＣＤ３イプシロンである、２つの標的に特異的に結合する、二価または三価の二特異性抗体であって、軽鎖およびそれぞれの重鎖内の可変ドメインＶＬおよびＶＨが、互いに置きかえられており、定常ドメインＣＬを含むことを特徴とし、１２４位におけるアミノ酸が、リシン（Ｋ）、アルギニン（Ｒ）、またはヒスチジン（Ｈ）により独立に置換されており（Ｋａｂａｔに従う番号付け）、それぞれの定常ドメインＣＨ１内で、１４７位におけるアミノ酸および２１３位におけるアミノ酸が、グルタミン酸（Ｅ）、またはアスパラギン酸（Ｄ）により独立に置換されている（Ｋａｂａｔに従う番号付け）二特異性抗体。また、前記抗体の製造および使用。【選択図】なし