ANTIBODY-DRUG CONJUGATE HAVING CAMPTOTHECIN-BASED DRUG LINKED TO ANTIBODY HAVING LOW ANTIGEN-BINDING AFFINITY THROUGH LINKER

• Main Authors: SHIN, Seung Gun, KWEON, So Hui, LEE, Jin Soo, CHUN, Young Hwa, CHO, Hyun Yong, GO, Areum, JUNG, Doo Young, LEE, Byeong Sung
• Format: Patent
• Language: English; French; Korean
• Published: 07.03.2024
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIRCHEMICAL OR PHYSICAL PROPERTIES; MEASURING; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PHYSICS; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; TESTING

The present invention relates to an immunoconjugate or a pharmaceutically acceptable salt thereof characterized in that a camptothecin-based drug (A) is bound, through a linker (C), to: an antibody or an antigen-binding fragment (B-1) thereof having a dissociation constant Kd value of 1*10-8 M to 1*10-6 M (exclusive of 1*10-6 M) with respect to an epitope of a cell surface protein; or an antibody or antigen-binding fragment (B-2) thereof which binds to a cell surface protein expressed in both normal cells and cancer cells and which has a higher binding affinity with respect to an epitope of the cell surface protein when binding divalently than when binding monovalently. La présente invention concerne un immunoconjugué ou un sel pharmaceutiquement acceptable de celui-ci caractérisé en ce qu'un médicament à base de camptothécine (A) est lié, par l'intermédiaire d'un lieur (C), à : un anticorps ou un fragment de liaison à l'antigène (B-1) de celui-ci ayant une valeur constante de dissociation Kd de 1 * 10-8 M à 1 * 10-6 M (à l'exclusion de 1 * 10-6 M) par rapport à un épitope d'une protéine de surface cellulaire; ou un anticorps ou un fragment de liaison à l'antigène (B-2) de celui-ci qui se lie à une protéine de surface cellulaire exprimée à la fois dans des cellules normales et des cellules cancéreuses et dont l'affinité de liaison par rapport à un épitope de la protéine de surface cellulaire est plus élevée en cas de liaison divalente qu'en cas de liaison monovalente. 본 발명은 캄토테신계 약물(A)이, 세포 표면 단백질의 에피토프에 대해 해리 상수 Kd 값이 1*10-8 M 이상 1*10-6 M 미만인 항체 또는 이의 항원결합부위 함유 단편(B-1); 또는 정상세포 및 암세포에서 모두 발현되는 세포 표면 단백질에 결합하되 세포 표면 단백질의 에피토프에 대해 1가 보다 2가로 결합시 결합친화도가 더 높은 항체 또는 이의 항원결합부위 함유 단편(B-2)에 링커(C)를 통해 결합된 것이 특징인 면역접합체 또는 이의 약학적으로 허용가능한 염에 관한 것이다.