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    • 20. 发明申请
    • READILY ISOLATED BISPECIFIC BINDING MOLECULES WITH NATIVE FORMAT HAVING MUTATED CONSTANT REGIONS
    • 准备隔离的双特异性结合分子与本地格式具有变异的恒定区域
    • WO2015033223A3
    • 2015-10-29
    • PCT/IB2014002388
    • 2014-09-03
    • NOVIMMUNE SA
    • FISCHER NICOLASMAGISTRELLI GIOVANNIROUSSEAU FRANÇOISMASTERNAK KRZYSZTOFMALINGE PAULINE
    • C07K16/24C07K1/00C07K16/28C07K16/46
    • C07K16/468C07K16/244C07K16/2809C07K2317/21C07K2317/31C07K2317/50C07K2317/522C07K2317/526C07K2317/622C07K2317/94
    • The invention provides heterodimer bispecific antigen-binding molecules that include a first polypeptide thai does not include an IgG CH1 domain and a second polypeptide having an immunoglobulin constant region where there is at least one mutation in the IgG CH3 domain that abolishes the ability of the second polypeptide to bind CH3- specific affinity media such that the first and second polypeptides have different affinities with respect to CH1 and CH3 specific affinity reagents that allows rapid isolation by differential binding of the first and second polypeptides to these affinity reagents. The invention also provides bispeeific antibodies that have IgG CH1 and CH3 regions with different affinities with respect to affinity reagents that allows rapid isolation by differential binding of the IgG regions to these affinity reagents. The invention also concerns bispeeific antibodies which are heterodimers of heavy chains, i.e., two immunoglobulin heavy chains that differ by at least two amino acids that allowr for the isolation of the bispeeific antibody based on a differential affinity of one mutated immunoglobulin heavy chain and a second mutated immunoglobulin heavy chain toward two different affinity reagents.
    • 本发明提供了异二聚体双特异性抗原结合分子,其包括不包含IgG CH1结构域的第一多肽和具有免疫球蛋白恒定区的第二多肽,其中IgG CH3结构域中存在至少一个突变,其消除了第二 多肽结合CH3特异性亲和介质,使得第一和第二多肽对于CH1和CH3特异性亲和试剂具有不同的亲和力,其允许通过第一和第二多肽与这些亲和试剂的差异结合来快速分离。 本发明还提供具有对于亲和试剂具有不同亲和力的IgG CH1和CH3区的双特异性抗体,其允许通过IgG区与这些亲和试剂的差异结合来快速分离。 本发明还涉及作为重链异二聚体的双特异性抗体,即两条免疫球蛋白重链相差至少两个氨基酸,允许基于一种突变的免疫球蛋白重链与第二种突变的免疫球蛋白重链的差异亲和力分离双特异性抗体 突变的免疫球蛋白重链朝向两种不同的亲和试剂。