公开(公告)号：US20220017462A1

公开(公告)日：2022-01-20

申请号：US17296088

申请日：2019-11-21

申请人： Wuxi Biologics Ireland Limited ,  Versitech Limited

发明人： Xuechen LI ,  Mingzhi JIN ,  Yue ZHANG ,  Li YIN ,  Jun WANG

IPC分类号： C07D207/452 ,  C07C235/78 ,  C07D241/04 ,  C07C233/61 ,  C07K1/113 ,  A61K47/68

摘要： Provided herein are novel ortho-Phthalaldehyde (OPA) containing linkers (OPA-L) and the use of OPA-L for the preparation of Antibody-drug conjugate (ADC) via the formation of Phthalimidine through the reaction of primary amine on antibody (e.g., residue of Lysine) and ortho-Phthalaldehyde. The advantage of this OPA-L is high reactivity and can be applied in different types of antibodies to form stably-linked conjugates. The use of OPA-L for the preparation of ADC is advantageous for mild and wide condition of conjugation, for instance, low percentage of organic solvent required, wide range of pH and temperature can be used.

公开(公告)号：US20220267467A1

公开(公告)日：2022-08-25

申请号：US17628008

申请日：2020-07-17

申请人： WUXI BIOLOGICS IRELAND LIMITED

发明人： Mingzhi JIN ,  Xiaoyue CHEN ,  Yue ZHANG ,  Chen ZHANG ,  Li YIN ,  Jiexing CAI ,  Jun WANG ,  Weichang ZHOU

IPC分类号： C07K16/32 ,  C07K16/28 ,  A61P35/00 ,  A61K47/68

摘要： The disclosure generally relates to the fields of immunology, cell biology, molecular biology and medicine. More particularly, it concerns polypeptide complex for conjugation and use thereof. A polypeptide complex comprising, from N-terminus to C-terminus, a Fab domain operably linked to a hinge region is provided, wherein the Fab domain and the hinge region are derived from different IgG isotypes, or part thereof. The polypeptide complex further comprises a Fc polypeptide which is operably linked to the hinge region. The present disclosure provides an antibody drug conjugate comprising a polypeptide complex of the present disclosure. A pharmaceutical composition comprising an antibody drug conjugate of the present disclosure and a pharmaceutically acceptable carrier or excipient, a method of preparing the antibody drug conjugate, the use of the polypeptide complex in the manufacture of the antibody drug conjugate, a method of treating a condition in a subject in need thereof with a therapeutically effective amount of the antibody drug conjugate are also provided. The subject inventions according to the present disclosure provide improved payload-antibody ratio of antibody bio-conjugation, in particular for therapeutic applications.