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1. 发明申请

WO2019122875A1 CHIMERIC ANTIGEN RECEPTOR 审中-公开
公开(公告)号：WO2019122875A1
公开(公告)日：2019-06-27
申请号：PCT/GB2018/053691
申请日：2018-12-19
申请人： UCL BUSINESS PLC
发明人： PULÉ, Martin , CHEUNG, Gordon Weng-Kit , CHESTER, Kerry
IPC分类号： C07K14/725
CPC分类号： C07K16/00 , C07K14/7051 , C07K2317/622 , C07K2317/624 , C07K2319/03 , C07K2319/33
摘要： The present invention relates to a chimeric antigen receptor comprising a disulphide bond between the VH and VL domains. The present invention also provides engineered cells, pharmaceutical compositions and pharmaceutical compositions for use in the treatment and/or prevention of disease.

2. 发明申请

WO2015150771A1 CHIMERIC ANTIGEN RECEPTOR (CAR) SIGNALLING SYSTEM 审中-公开
标题翻译： CHIMERIC抗原受体（CAR）信号系统
公开(公告)号：WO2015150771A1
公开(公告)日：2015-10-08
申请号：PCT/GB2015/050974
申请日：2015-03-31
申请人： UCL BUSINESS PLC
发明人： PULÉ, Martin , CORDOBA, Shaun , KONG, Khai
IPC分类号： C07K14/705 , C07K16/28 , C12N5/0783 , A61K48/00
CPC分类号： A61K39/3955 , A61K31/166 , A61K31/436 , A61K31/4545 , A61K38/177 , A61K38/1774 , A61K38/45 , A61K38/52 , A61K2039/5156 , A61K2039/5158 , C07K14/4702 , C07K14/705 , C07K14/7051 , C07K14/70517 , C07K14/70521 , C07K14/70578 , C07K16/2803 , C07K2317/622 , C07K2319/00 , C07K2319/02 , C07K2319/03 , C07K2319/70 , C07K2319/74 , C12N5/0636 , C12N5/0646 , C12N9/12 , C12N9/90 , C12Y207/11001 , C12Y502/01008
摘要： The present invention relates to a chimeric antigen receptor (CAR) signalling system comprising; (i) a receptor component comprising an extracellular antigen-binding domain, a transmembrane domain and a intracellular first chemical inducer of dimerization binding domain 1 (CBD1 ); and (ii) an intracellular signalling component comprising a signalling domain and a second chemical inducer of dimerization binding domain 2 (CBD2); wherein CBD1 and CBD2 are capable of simultaneously binding to a chemical inducer of dimerization (CID); wherein, in the absence of the CID, binding of the antigen-binding component to antigen does not result in signalling through the signalling component; whilst, in the presence of the CID, the receptor component and the signalling component heterodimerize and binding of the antigen-binding domain to antigen results in signalling through the signalling domain.
摘要翻译：本发明涉及嵌合抗原受体（CAR）信号传导系统，其包含：（i）受体组分，其包含细胞外抗原结合结构域，跨膜结构域和二聚结合结构域1（CBD1）的细胞内第一化学诱导剂; 和（ii）包含信号结构域和二聚结合结构域2（CBD2）的第二化学诱导剂的细胞内信号传导成分; 其中CBD1和CBD2能够同时与二聚化学诱导剂（CID）结合; 其中，在没有CID的情况下，抗原结合组分与抗原的结合不会导致通过信号传导成分的信号传导; 而在CID存在下，受体组分和信号组分将抗原结合结构域与抗原异源二聚化和结合导致通过信号结构域的信号转导。

3. 发明申请

WO2019220108A1 CHIMERIC ANTIGEN RECEPTOR 审中-公开
公开(公告)号：WO2019220108A1
公开(公告)日：2019-11-21
申请号：PCT/GB2019/051329
申请日：2019-05-15
申请人： UCL BUSINESS PLC
发明人： PULÉ, Martin
IPC分类号： C07K16/28 , C07K14/725 , C07K14/705 , C12N5/0783 , A61P35/00
摘要： The present invention provides a chimeric antigen receptor (CAR) comprising a CD21- binding domain, a transmembrane domain and an intracellular domain.

4. 发明申请

WO2017144892A1 NUCLEIC ACID CONSTRUCTS FOR PRODUCING RETROVIRAL VECTORS 审中-公开
标题翻译：用于产生逆转录病毒载体的核酸构建体
公开(公告)号：WO2017144892A1
公开(公告)日：2017-08-31
申请号：PCT/GB2017/050481
申请日：2017-02-24
申请人： UCL BUSINESS PLC
发明人： PULÉ, Martin , MEKKAOUI, Leila
IPC分类号： C12N15/86
CPC分类号： C12N15/86 , C12N2740/10043 , C12N2740/10052 , C12N2740/16043 , C12N2740/16052
摘要： The present invention relates to a nucleic acid construct comprising: (i) a first nucleic acid sequence which either comprises a retroviral transfer vector or which encodes a retroviral protein; and (ii) a second nucleic acid sequence which encodes a detectable marker which is a cell surface protein comprising an extracellular domain and a membrane targeting domain.
摘要翻译：本发明涉及一种核酸构建体，其包含：（i）第一核酸序列，其包含逆转录病毒转移载体或编码逆转录病毒蛋白; 和（ii）编码可检测标记的第二核酸序列，所述可检测标记是包含细胞外结构域和膜靶向结构域的细胞表面蛋白。

5. 发明申请

WO2016174405A1 NUCLEIC ACID CONSTRUCT FOR EXPRESSING MORE THAN ONE CHIMERIC ANTIGEN RECEPTOR 审中-公开
标题翻译：核酸结构表达超过一个重要的抗原受体
公开(公告)号：WO2016174405A1
公开(公告)日：2016-11-03
申请号：PCT/GB2016/051161
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
CPC分类号： C07K14/70596 , C07K14/075 , C07K14/705 , C07K14/70503 , C07K16/2803 , C07K19/00 , C07K2319/02 , C07K2319/33 , C12N9/0071 , C12N2740/10043 , C12N2830/60
摘要： The present invention provides a nucleic acid construct comprising the following structure: A – X – B in which A and B are nucleic acid sequences encoding a first and a second chimeric antigen receptor (CAR); and X is a nucleic acid sequence which encodes a cleavage site, wherein the first and second CAR recognise different antigens; the first and second CAR comprise or associate with activating endodomains; and (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.
摘要翻译：本发明提供了包含以下结构的核酸构建体：A-X-B，其中A和B是编码第一和第二嵌合抗原受体（CAR）的核酸序列; X是编码切割位点的核酸序列，其中第一和第二CAR识别不同的抗原; 第一和第二CAR包含或结合活化内切体; 和（a）第一和/或第二CAR包括细胞内保留信号; 和/或（b）第一或第二CAR的信号肽包含一个或多个突变，使得其具有较少的疏水性氨基酸。

6. 发明申请

WO2016030691A1 SIGNALLING SYSTEM 审中-公开
标题翻译：信号系统
公开(公告)号：WO2016030691A1
公开(公告)日：2016-03-03
申请号：PCT/GB2015/052494
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：本发明提供嵌合抗原受体（CAR）信号系统，其包含：（i）受体组分，其包含抗原结合结构域，跨膜结构域和第一结合结构域; 和（ii）包含特异性结合受体成分的第一结合结构域的信号结构域和第二结合结构域的细胞内信号传导成分; 其中，第一和第二结合结构域的结合被试剂的存在破坏，使得在不存在试剂的情况下，受体组分和信号组分异源二聚化和抗原结合结构域与抗原的结合导致通过信号传导的信号转导而在试剂存在下，受体组分和信号组分不会使抗原结合结构域与抗原的异二聚化和结合不会导致通过信号结构域的信号传导。

7. 发明申请

WO2015132598A1 CHIMERIC ANTIGEN RECEPTOR (CAR) WITH ANTIGEN BINDING DOMAINS TO THE T CELL RECEPTOR BETA CONSTANT REGION 审中-公开
标题翻译：具有抗原结合域的CHIMERIC抗原受体（CAR）到恒定区域的T细胞受体
公开(公告)号：WO2015132598A1
公开(公告)日：2015-09-11
申请号：PCT/GB2015/050643
申请日：2015-03-05
申请人： UCL BUSINESS PLC
发明人： PULÉ, Martin , MACIOCIA, Paul
IPC分类号： A61K39/395 , A61K47/48 , C07K16/28 , C07K14/725
CPC分类号： C07K16/2809 , A61K47/6803 , A61K47/6849 , C07K14/7051 , C07K2317/21 , C07K2317/34 , C07K2317/56 , C07K2317/565 , C07K2317/622 , G01N33/57426 , G01N2333/7051
摘要： The present disclosure relates to a chimeric antigen receptor (CAR) which comprises an antigen-binding domain which selectively binds TCR beta constant region 1 (TRBC1) or TRBC2; cells; such a T cells comprising such a CAR; and the use of such cells for the treatment of a T-cell lymphoma or leukaemia in a subject.
摘要翻译：本公开涉及嵌合抗原受体（CAR），其包含选择性结合TCRβ恒定区1（TRBC1）或TRBC2的抗原结合结构域; 细胞; 这样的包含这种CAR的T细胞; 以及这些细胞在受试者中用于治疗T细胞淋巴瘤或白血病的用途。

8. 发明申请

WO2017081479A1 MULTI-SPAN CHIMERIC ANTIGEN RECEPTOR 审中-公开
标题翻译：多跨性嵌合抗原受体
公开(公告)号：WO2017081479A1
公开(公告)日：2017-05-18
申请号：PCT/GB2016/053544
申请日：2016-11-11
申请人： UCL BUSINESS PLC
发明人： PULÉ, Martin , CHEUNG, Gordon , RODDIE, Claire
IPC分类号： C07K14/705 , A61K48/00 , C07K16/28
CPC分类号： C07K14/705 , A61K48/00 , C07K16/00 , C07K16/2803 , C07K2317/622 , C07K2319/03
摘要： The present invention relates to a multi-span chimeric antigen receptor (CAR) which comprises: i) at least one extracellular antigen binding domain; ii) a plurality of linked transmembrane domains; and iii) at least one intracellular signalling domain.
摘要翻译：本发明涉及多跨距嵌合抗原受体（CAR），其包含：i）至少一个胞外抗原结合结构域; ii）多个连接的跨膜结构域; 和iii）至少一个细胞内信号传导结构域。

9. 发明申请

WO2016174408A1 NUCLEIC ACID CONSTRUCT 审中-公开
标题翻译：核酸结构
公开(公告)号：WO2016174408A1
公开(公告)日：2016-11-03
申请号：PCT/GB2016/051164
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 , C12N15/85
CPC分类号： C12N15/86 , C07K14/70521 , C07K14/70596 , C07K16/2803 , C07K2317/622 , C07K2319/03 , C07K2319/04 , C07K2319/06 , C07K2319/33 , C07K2319/50 , C12N15/85
摘要： The present invention provides a nucleic acid construct comprising the following structure: A – X – B in which A and B are nucleic acid sequences encoding a first and a second polypeptide of interest (POI); and X is a nucleic acid sequence which encodes a cleavage site, wherein either the first or second POI is a transmembrane protein which comprises an intracellular retention signal.
摘要翻译：本发明提供了包含以下结构的核酸构建体：A-X-B，其中A和B是编码目标第一和第二多肽（POI）的核酸序列; 并且X是编码切割位点的核酸序列，其中所述第一或第二POI是包含细胞内保留信号的跨膜蛋白。

10. 发明申请

WO2016174407A1 NUCLEIC ACID CONSTRUCT FOR EXPRESSING MORE THAN ONE CHIMERIC ANTIGEN RECEPTOR 审中-公开
标题翻译：核酸结构表达超过一个重要的抗原受体
公开(公告)号：WO2016174407A1
公开(公告)日：2016-11-03
申请号：PCT/GB2016/051163
申请日：2016-04-26
申请人： UCL BUSINESS PLC
发明人： PULÉ, Martin , CORDOBA, Shaun
IPC分类号： A61K39/00 , C07K14/705 , C07K16/28 , C07K19/00
CPC分类号： C07K16/2803 , A61K35/17 , A61K39/0011 , A61K2039/5156 , A61P35/00 , C07K14/70503 , C07K14/7051 , C07K14/70517 , C07K14/70521 , C07K16/2863 , C07K16/3084 , C07K2317/622 , C07K2319/02 , C07K2319/03 , C07K2319/033 , C07K2319/04 , C07K2319/05 , C12N7/00 , C12N9/16 , C12N2710/10333 , C12Y301/03048
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 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.
摘要翻译：本发明提供了包含以下结构的核酸构建体：其中X是编码切割位点的核酸序列的A-X-B; A和B是编码第一和第二嵌合抗原受体（CAR）的核酸序列，每个CAR包含：（i）抗原结合结构域; （ii）间隔物（iii）跨膜结构域; 和（iv）其中所述第一和第二CAR的抗原结合结构域与不同抗原结合的endodomain; 其中所述第一CAR或第二CAR中的一个是包含活化内结构域的活化CAR，而另一个CAR是包含连接关闭抑制性内切结构域的抑制性CAR; 并且其中：（a）所述第一和/或第二CAR包含细胞内保留信号; 和/或（b）第一或第二CAR的信号肽包含一个或多个突变，使得其具有较少的疏水性氨基酸。

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