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    CHIMERIC ANTIGEN RECEPTOR
    1.
    发明授权
    CHIMERIC ANTIGEN RECEPTOR 有权

    公开(公告)号：EP3274366B1

    公开(公告)日：2019-12-11

    申请号：EP16712424.7

    申请日：2016-03-22

    申请人： UCL Business Plc.

    发明人： PULÉ, Martin ,  CORDOBA, Shaun

    IPC分类号： C07K14/705 ,  A61K35/17

    摘要： The present invention provides a chimeric antigen-receptor (CAR)-forming polypeptide comprising: (i) an antigen-binding domain; (ii) a coiled-coil spacer domain; (iii) a transmembrane domain; and (iv) an endodomain. The invention also provides a multimeric CAR formed by association of a plurality of CAR-forming polypeptides by virtue of association of their coiled-coil spacer domains.

    SIGNALLING SYSTEM
    7.
    发明公开
    SIGNALLING SYSTEM 审中-公开
    信号系统

    公开(公告)号：EP3185875A1

    公开(公告)日：2017-07-05

    申请号：EP15757558.0

    申请日：2015-08-28

    申请人： UCL Business Plc.

    发明人： PULÉ, Martin ,  CORDOBA, Shaun ,  KONG, Khai

    IPC分类号： A61K35/17 ,  C07K14/725 ,  C12N5/0783

    CPC分类号： C07K16/2803 ,  A61K31/65 ,  A61K35/17 ,  C07K14/7051 ,  C07K14/70514 ,  C07K2317/622 ,  C07K2319/80 ,  C12N5/0636 ,  C12N2510/00

    摘要： The present invention provides a chimeric antigen receptor (CAR) signalling system comprising; (i) a receptor component comprising an antigen binding domain, a transmembrane domain and a first binding domain; and (ii) an intracellular signalling component comprising a signalling domain and a second binding domain which specifically binds the first binding domain of the receptor component; wherein, binding of the first and second binding domains is disrupted by the presence of an agent, such that in the absence of the agent the receptor component and the signalling component heterodimerize and binding of the antigen binding domain to antigen results in signalling through the signalling domain, whereas in the presence of the agent the receptor component and the signalling component do not heterodimerize and binding of the antigen binding domain to antigen does not result in signalling through the signalling domain.

    摘要翻译： 本发明提供了嵌合抗原受体（CAR）信号系统，其包含： （i）包含抗原结合结构域，跨膜结构域和第一结合结构域的受体组分; 和（ii）细胞内信号传导组分，其包含特异性结合受体组分的第一结合结构域的信号传导结构域和第二结合结构域; 其中所述第一和第二结合结构域的结合被试剂的存在所破坏，使得在所述试剂不存在的情况下，所述受体组分和所述信号传导组分异源二聚化并且所述抗原结合结构域与抗原的结合导致通过所述信号传导 而在试剂存在下，受体组分和信号传导组分不会异源二聚化，并且抗原结合结构域与抗原的结合不会导致通过信号传导结构域的信号传导。

    NUCLEIC ACID CONSTRUCT FOR EXPRESSING MORE THAN ONE CHIMERIC ANTIGEN RECEPTOR
    9.
    发明公开
    NUCLEIC ACID CONSTRUCT FOR EXPRESSING MORE THAN ONE CHIMERIC ANTIGEN RECEPTOR 审中-公开

    公开(公告)号：EP3288970A1

    公开(公告)日：2018-03-07

    申请号：EP16721211.7

    申请日：2016-04-26

    申请人： UCL Business PLC

    发明人： PULÉ, Martin ,  CORDOBA, Shaun

    IPC分类号： C07K14/705 ,  C07K16/28 ,  C07K19/00 ,  A61K39/00 ,  C12N5/0783

    摘要： The present invention provides a nucleic acid construct comprising the following structure: A-X-B in which X is a nucleic acid sequence which encodes a cleavage site; and A and B are nucleic acid sequences encoding a first and a second chimeric antigen receptor (CAR), each CAR comprising: (i) an antigen-binding domain; (ii) a spacer (iii) a trans-membrane domain; and (iv) an endodomain wherein the antigen binding domains of the first and second CARs bind to different antigens, wherein the spacer of the first CAR is different to the spacer of the second CAR and wherein one of the first or second CARs is an activating CAR comprising an activating endodomain and the other CAR is an inhibitory CAR comprising a ligation-off inhibitory endodomain; and wherein: (a) the first and/or second CAR comprises an intracellular retention signal; and/or (b) the signal peptide of the first or second CAR comprises one or more mutation(s) such that it has fewer hydrophobic amino acids.