公开(公告)号：US20210154229A1

公开(公告)日：2021-05-27

申请号：US17012806

申请日：2020-09-04

申请人： AUTOLUS LIMITED

发明人： Martin Pulé ,  Khai Kong ,  Shaun Cordoba

IPC分类号： A61K35/17 ,  A61K39/00 ,  C07K14/725 ,  C07K14/705 ,  C07K16/28 ,  C12N5/0783 ,  C12N15/86 ,  C12N9/16

摘要： The present invention provides a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, 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.

公开(公告)号：US20200030379A1

公开(公告)日：2020-01-30

申请号：US16470968

申请日：2017-12-20

申请人： AUTOLUS LIMITED

发明人： Martin Pulé ,  Simon Thomas ,  Shaun Cordoba ,  Wen Chean Lim

IPC分类号： A61K35/17 ,  C12N15/85 ,  C12N5/0783 ,  C07K14/725 ,  C07K14/475

摘要： The present invention provides a cell which comprises a first exogenous nucleic acid molecule encoding a Chimeric Antigen Receptor (CAR) and a second exogenous nucleic acid molecule encoding a transcription factor.

公开(公告)号：US20190177412A1

公开(公告)日：2019-06-13

申请号：US16310121

申请日：2017-06-15

申请人： AUTOLUS LIMITED

发明人： Shimobi Onuoha ,  Martin Pulé ,  Simon Thomas ,  Shaun Cordoba ,  Evangelia Kokalaki

IPC分类号： C07K16/28 ,  C07K14/705 ,  A61K35/17 ,  A61P35/00 ,  A61P35/02 ,  C07K14/725

摘要： The present invention provides a chimeric antigen receptor (CAR) which binds human CD22, having an antigen-binding domain which comprises a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences: CDR1—NYWIH (SEQ ID No. 1); CDR2—GINPGNNYATYRRKFQG (SEQ ID No. 2) CDR3—EGYGNYGAWFAY (SEQ ID No. 3); and b) a light chain variable region (VL) having CDRs with the following sequences: CDR1—RSSQSLANSYGNTFLS (SEQ ID No. 4); CDR2—GISNRFS (SEQ ID No. 5) CDR3—LQGTHQPYT (SEQ ID No. 6). The present invention also provides a cell comprising such a CAR and the use of such a cell to treat cancer.

公开(公告)号：US10174099B2

公开(公告)日：2019-01-08

申请号：US15632119

申请日：2017-06-23

申请人： UCL BUSINESS PLC ,  AUTOLUS LIMITED

发明人： Martin Pulé ,  Shaun Cordoba ,  Shimobi Onuoha ,  Simon Thomas

IPC分类号： A61K35/00 ,  A61K35/17 ,  A61K38/17 ,  A61K39/00 ,  C07K16/28 ,  C07K16/30 ,  C07K14/725 ,  C12N5/0783 ,  C07K14/705 ,  C07K14/735

摘要： The present invention provides a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising an antigen-binding domain, wherein the antigen-binding domain of the first CAR binds to CD19 and the antigen-binding domain of the second CAR binds to CD22.

公开(公告)号：US20180305433A1

公开(公告)日：2018-10-25

申请号：US15770130

申请日：2016-10-21

申请人： AUTOLUS LIMITED

发明人： Martin Pulé ,  Shaun Cordoba

IPC分类号： C07K14/725 ,  A61K35/17 ,  C07K16/28 ,  C07K14/705 ,  C12N5/0783 ,  C12N9/16

CPC分类号： C07K14/7051 ,  A61K35/17 ,  A61K39/00 ,  A61K39/0011 ,  A61K2039/5156 ,  A61K2039/5158 ,  C07K14/70517 ,  C07K16/00 ,  C07K16/2803 ,  C07K16/2896 ,  C07K2317/622 ,  C07K2319/03 ,  C07K2319/33 ,  C12N5/0638 ,  C12N9/16 ,  C12N2510/00 ,  C12Y301/03048

摘要： The present invention relates to a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising: (i) an antigen-binding domain; (ii) a spacer (iii) a trans-membrane domain; and (iv) an endodomain wherein the first CAR is an activating CAR comprising an activating endodomain and the second CAR is an inhibitory CAR comprising a ligation-off inhibitory endodomain; wherein the first CAR binds to a first antigen and the second CAR binds to a second antigen, wherein both the first and second antigens are expressed on the surface of a target cell; wherein the first CAR binds to an epitope on the first antigen which is relatively proximal to the membrane of the target cell, the second CAR binds to an epitope on the second antigen which is relatively distal to the membrane of the target cell, in comparison with the epitope of the first antigen; and wherein the spacer of the first CAR is an equivalent size to the spacer of the second CAR.

公开(公告)号：US20240309400A1

公开(公告)日：2024-09-19

申请号：US18504554

申请日：2023-11-08

申请人： AUTOLUS LIMITED

发明人： Martin Pulé ,  James Sillibourne ,  Shaun Cordoba

IPC分类号： C12N15/86 ,  A61K35/17 ,  A61K48/00

CPC分类号： C12N15/86 ,  A61K35/17 ,  A61K48/00 ,  C12N2740/10043 ,  C12N2800/40

摘要： The present invention provides a kit of vectors for transducing an immune cell with multiple transgenes comprising: (i) a first vector which comprises a first transgene and a nucleotide sequence encoding a transcription factor and; and (ii) a second vector which comprises a second transgene wherein expression of the second transgene within a host cell is dependent upon expression of the transcription factor.

公开(公告)号：US12049510B2

公开(公告)日：2024-07-30

申请号：US17279874

申请日：2019-09-26

申请人： AUTOLUS LIMITED

发明人： Martin Pulé ,  Shaun Cordoba ,  Simon Thomas ,  Shimobi Onuoha ,  Mathieu Ferrari ,  Wen Chean Lim ,  Biao Ma

IPC分类号： A61P35/00 ,  A61K35/17 ,  C07K16/28

CPC分类号： C07K16/2878 ,  A61K35/17 ,  A61P35/00 ,  C07K16/2803 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2319/03

摘要： The present invention provides a chimeric antigen receptor (CAR) which binds a low density target antigen, which comprises a Fab antigen binding domain. The invention also relates to cells expressing such a CAR and their use in the treatment of disease.

公开(公告)号：US11963981B2

公开(公告)日：2024-04-23

申请号：US17054670

申请日：2019-05-15

申请人： AUTOLUS LIMITED

发明人： Martin Pulé ,  Evangelia Kokalaki ,  Shaun Cordoba ,  Shimobi Onuoha ,  Simon Thomas ,  Biao Ma ,  Mathieu Ferrari

IPC分类号： A61K35/17 ,  A61P35/00 ,  C07K16/28

CPC分类号： A61K35/17 ,  A61P35/00 ,  C07K16/2803 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2317/76

摘要： The present invention provides a chimeric antigen receptor (CAR) which binds a target antigen having a bulky extracellular domain, wherein the CAR comprises a Fab antigen binding domain. The present invention also provides nucleic acid sequences and constructs encoding such a CAR, cells expressing such a CAR and their therapeutic uses.

公开(公告)号：US20230331810A1

公开(公告)日：2023-10-19

申请号：US18158754

申请日：2023-01-24

申请人： AUTOLUS LIMITED

发明人： Martin Pulé ,  Shaun Cordoba ,  Shimobi Onuoha ,  Simon Thomas

IPC分类号： C07K14/705 ,  C12N5/0783 ,  C07K14/725 ,  C07K16/28 ,  A61K39/00 ,  C07K14/735 ,  C07K16/30 ,  A61K35/17 ,  A61K38/17

CPC分类号： C07K14/70521 ,  C12N5/0636 ,  C07K14/7051 ,  C07K16/2803 ,  A61K39/001113 ,  A61K39/0011 ,  C07K14/70535 ,  C07K16/2863 ,  C07K16/3061 ,  C12N5/0638 ,  A61K35/17 ,  A61K38/1774 ,  C12N2510/02 ,  A61K2039/505 ,  C07K2317/31 ,  C07K2317/622 ,  C07K2319/03 ,  A61K35/00

摘要： The present invention provides a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising an antigen-binding domain, wherein the antigen-binding domain of the first CAR binds to CD19 and the antigen-binding domain of the second CAR binds to CD22.

公开(公告)号：US20230256093A1

公开(公告)日：2023-08-17

申请号：US17924345

申请日：2021-05-12

申请人： AUTOLUS LIMITED

发明人： Marco Della Peruta ,  Matteo Righi ,  Giulia Agliardi ,  Martin Pulé ,  Shaun Cordoba ,  James Sillibourne

IPC分类号： A61K39/00 ,  A61K38/20 ,  A61K38/19 ,  A61P35/00

CPC分类号： A61K39/4632 ,  A61K38/208 ,  A61K39/4631 ,  A61K39/4611 ,  A61K38/2046 ,  A61K38/2086 ,  A61K38/195 ,  A61P35/00

摘要： The present invention provides a method for treating a solid cancer which comprises the step of administering a cell to a subject, wherein the cell comprises a nucleic acid sequence encoding interleukin 12 (IL-12) downstream of a frame-slip motif (FSM) or a translational readthrough motif (TRM).