The present invention provides an asymmetric antibody comprising two heavy or heavy chain fragments each comprising at least a variable region, a hinge region and a C H 1 domain, The first heavy chain or fragment thereof is class IgG4, a. In the C H 1 domain, when numbered according to the Kabat numbering system, the interchain cysteine at position 127 is substituted with another amino acid; b. Optionally, at least one of the amino acids located in the upper hinge region is substituted with cysteine, The second heavy chain or fragment thereof has at least part of the chain having an amino acid sequence different from the first heavy chain in at least a region outside the variable region (eg, the constant region), a formulation comprising the both, or both For therapeutic use, and methods of making said antibodies and formulations.
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机译：本发明提供了一种不对称抗体，其包含两个重链或重链片段，每个重链或重链片段至少包含可变区，铰链区和C H 1结构域，第一重链或其片段是IgG4类，一种。在C H 1域中，当按照Kabat编号系统进行编号时，第127位的链间半胱氨酸被另一个氨基酸取代; b。任选地，位于上部铰链区中的至少一个氨基酸被半胱氨酸取代。第二重链或其片段在至少一个区域中具有至少一部分具有不同于第一重链的氨基酸序列的氨基酸序列。在可变区（例如恒定区）之外，包含两者或两者的制剂用于治疗用途，以及制备所述抗体和制剂的方法。
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