(EN) The present invention concerns multimeric complexes based on antibody fusion proteins comprising an AD moiety attached to the C-terminal end of each antibody light chain. The complexes further comprise effector moities attached to DDD moieties. Two copies of the DDD moiety form a dimer that binds to the AD moiety. The complexes may be trimers, pentamers, hexamers or other multimers. The effector moieties may be selected from a second antibody or antigen-binding fragment thereof, a cytokine, an interferon, a toxin, an antigen, a xenoantigen, a hapten, a protamine, a hormone, an enzyme, a ligand-binding protein, a pro-apoptotic agent and an anti-angiogenic agent. Surprisingly, attachment of the AD moiety to the C-terminal end of the antibody light chain results in improved pharmacokinetics and in vivo stability and efficacy, compared to homologous complexes wherein the AD moiety is attached to the antibody heavy chain.
(ZH)
本发明涉及基于抗体融合蛋白的多聚体复合物，其包含附着至每条抗体轻链的C-末端的AD部分。所述复合物进一步包含附着至DDD部分的效应子部分。所述DDD部分的两个拷贝形成结合所述AD部分的二聚体。所述复合物可为三聚体、五聚体、六聚体或其它多聚体。所述效应子部分可选自第二抗体或其抗原结合片段、细胞因子、干扰素、毒素、抗原、异种抗原、半抗原、鱼精蛋白、激素、酶、配体结合蛋白、促凋亡剂以及抗血管生成剂。出人意料地，与其中所述AD部分附着至所述抗体重链的同源复合物相比，所述AD部分附着至所述抗体轻链的C-末端引起改进的药物代谢动力学和体内稳定性以及功效。
