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    Hybrid Constant Regions
    3.
    发明申请
    Hybrid Constant Regions 有权
    混合恒定区域

    公开(公告)号：US20130089547A1

    公开(公告)日：2013-04-11

    申请号：US13627929

    申请日：2012-09-26

    Applicant: J. Yun Tso ,  Naoya Tsurushita

    Inventor： J. Yun Tso ,  Naoya Tsurushita

    IPC: C07K16/46 ,  C07K16/00

    CPC classification number: C07K16/468 ,  A61K2039/505 ,  C07K14/70596 ,  C07K14/7151 ,  C07K14/7155 ,  C07K16/00 ,  C07K16/2803 ,  C07K16/283 ,  C07K16/2878 ,  C07K16/46 ,  C07K19/00 ,  C07K2317/35 ,  C07K2317/51 ,  C07K2317/52 ,  C07K2317/64 ,  C07K2317/73 ,  C07K2319/00 ,  C07K2319/21 ,  C07K2319/33

    Abstract: The invention provides hybrid constant regions and antibodies or fusion proteins incorporating the same. The hybrid constant regions include at least CH2 and CH3 regions of an IgG or IgA constant region and Cμ3 and Cμ4 regions of a Cμ constant region. The hybrids retain properties of both component constant regions. The hybrids retain the ability of a Cμ constant region to form multivalent complexes, e.g., pentameric or hexameric structures. IgG hybrids also retain IgG properties including pH-dependent FcRn binding, which is associated with a relatively long in vivo half-life, and specific binding to protein G, which facilitates purification. Depending on the isotype and subtype, the nature of the antigen and presence of additional IgG CH1 and hinge domains, IgG hybrids may also retain properties of specific binding to protein A, and effector functions ADCC, CDC and opsonization. IgA hybrids retain the property of IgA of binding to an Fc-alpha receptor CD89.

    Abstract translation: 本发明提供了混合恒定区和包含其的抗体或融合蛋白。 杂交恒定区至少包括IgG或IgA恒定区的CH2和CH3区以及Cμ恒定区的Cμ3和Cμ4区。 混合物保持两个组分恒定区的性质。 杂种保留Cμ恒定区形成多价复合物例如五聚体或六聚体结构的能力。 IgG杂交体还保留IgG性质，包括pH依赖性FcRn结合，其与体内相当长的半衰期相关，并且与蛋白G的特异性结合有利于纯化。 取决于同种型和亚型，抗原的性质和额外的IgG CH1和铰链结构域的存在，IgG杂交体也可以保留与蛋白A的特异性结合以及效应子功能ADCC，CDC和调理作用的性质。 IgA杂交体保留与Fc-α受体CD89结合的IgA的性质。

    Expression vectors
    8.
    发明申请
    Expression vectors 有权
    表达载体

    公开(公告)号：US20090320149A1

    公开(公告)日：2009-12-24

    申请号：US12456007

    申请日：2009-06-10

    Applicant: Naoya Tsurushita ,  J. Yun Tso

    Inventor： Naoya Tsurushita ,  J. Yun Tso

    IPC: A01K67/027 ,  C12N15/11 ,  C07K16/00 ,  C12N15/00 ,  C12N5/06

    CPC classification number: C07K16/00 ,  A01K2217/072 ,  A01K2227/105 ,  A01K2267/01 ,  C07K16/241 ,  C07K16/2866 ,  C07K2319/03 ,  C07K2319/035 ,  C07K2319/30 ,  C07K2319/32 ,  C12N15/85 ,  C12N2840/44 ,  C12N2840/85

    Abstract: This present invention provides an expression vector system that uses alternative RNA processing to express in a single cell a polypeptide in both membrane-bound and soluble forms. By incorporating a mimetic structure of the 3′ terminal region of human mu gene and introducing other exogenous genetic elements, an artificial gene can be constructed that is capable of simultaneously expressing membrane-bound and secreted forms of polypeptides in myeloma cells and other cells of the B lymphocyte lineage, as well as in non-B cells. If an immunoglobulin heavy chain is co-expressed with a light chain using this vector, whole antibodies can be produced that are both displayed on the surface of a single cell and secreted into the cell culture supernatant. Membrane-bound antibodies facilitate isolation and expansion of those cells displaying antibodies with desired antigen binding characteristics, while secreted antibodies facilitate identification of antibodies having desired biological function(s).

    Abstract translation: 本发明提供了一种表达载体系统，其使用替代的RNA加工来在单细胞中以膜结合和可溶形式表达多肽。 通过掺入人mu基因的3'末端区域的模拟结构并引入其他外源遗传元件，可以构建人造基因，其能够同时表达骨髓瘤细胞和其它细胞中的多肽的膜结合和分泌形式 B淋巴细胞谱系，以及非B细胞。 如果使用该载体使免疫球蛋白重链与轻链共同表达，则可以产生全部抗体，其均显示在单个细胞的表面并分泌到细胞培养上清液中。 膜结合的抗体促进显示具有所需抗原结合特征的抗体的那些细胞的分离和扩增，而分泌的抗体便于鉴定具有所需生物学功能的抗体。

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