公开(公告)号：US20230133554A1

公开(公告)日：2023-05-04

申请号：US17915689

申请日：2021-04-08

申请人： AUTOLUS LIMITED

发明人： Callum McKenzie ,  Shaun Cordoba ,  Martin Pulé

IPC分类号： C07K14/725 ,  C07K14/705 ,  C12N5/00

摘要： The present invention provides a method for selecting for cells transduced to express a nucleic acid sequence of interest (NOI), which comprises the following steps: (a) transducing a population of cells with a vector co-expressing the NOI and a nucleic acid sequence which inhibits Fas expression or activity in the cell; (b) exposing the cells from (a) to FasL such that untransduced cells are eliminated by apoptosis. The present invention also provides a molecule which comprises a Fas-binding domain linked to an intracellular retention signal which may be used in such a method to inhibit Fas expression.

公开(公告)号：US11591613B2

公开(公告)日：2023-02-28

申请号：US16326131

申请日：2017-08-16

申请人： AUTOLUS LIMITED

发明人： Vijay Peddareddigari ,  Richard Beswick ,  John Short ,  Martin Pulé ,  Ekaterini Kotsopoulou

IPC分类号： C12N15/867 ,  C12N5/0783 ,  C12N15/62 ,  C07K16/28 ,  A61P35/00 ,  A61K38/00 ,  C12N15/86 ,  C07K14/725 ,  C07K14/00 ,  C07K14/705

摘要： The present invention provides a retroviral or lentiviral vector having a viral envelope which comprises a mitogenic T-cell activating transmembrane protein which comprises: (i) a mitogenic domain which binds a mitogenic tetraspanin, and (ii) a transmembrane domain; wherein the mitogenic T-cell activating transmembrane protein is not part of a viral envelope glycoprotein. When cells such as T-cells or Natural Killer cells are transduced by such a viral vector, they are activated by the mitogenic T-cell activating transmembrane protein.

公开(公告)号：US20220356260A1

公开(公告)日：2022-11-10

申请号：US17746642

申请日：2022-05-17

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： C07K16/28 ,  A61P35/00 ,  A61K35/17

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：US11479613B2

公开(公告)日：2022-10-25

申请号：US16998756

申请日：2020-08-20

申请人： AUTOLUS LIMITED

发明人： Martin Pulé ,  Shaun Cordoba ,  Matteo Righi ,  James Sillibourne ,  Shimobi Onuoha ,  Simon Thomas

IPC分类号： A61K35/17 ,  C07K14/715 ,  C07K16/30 ,  C07K14/46 ,  A61K39/00

摘要： The present invention provides a chimeric cytokine receptor (CCR) comprising: (i) an exodomain which binds to a ligand selected from a tumour secreted factor, a chemokine and a cell-surface antigen; and (ii) a cytokine receptor endodomain.

公开(公告)号：US20220211830A1

公开(公告)日：2022-07-07

申请号：US17601684

申请日：2020-04-07

申请人： AUTOLUS LIMITED

发明人： Martin Pulé ,  Shaun Cordoba ,  Simon Thomas ,  Shimobi Onuoha ,  James Sillibourne ,  Farhaan Parekh

IPC分类号： A61K39/00

摘要： The present invention provides a cell which comprises; (i) a chimeric antigen receptor (CAR) or a transgenic T-cell receptor (TCR); and (ii) at least one polypeptide capable of co-localizing an MHC class I polypeptide or an MHC class II polypeptide with an intracellular signalling domain within the cell.

公开(公告)号：US11365262B2

公开(公告)日：2022-06-21

申请号：US15753505

申请日：2016-08-19

申请人： AUTOLUS LIMITED

发明人： Martin Pulé ,  Shaun Cordoba ,  Matteo Righi ,  James Sillibourne

IPC分类号： C07K16/30 ,  A61K35/17 ,  C07K16/18 ,  C12N5/0783 ,  A61K39/00 ,  A61K38/00

摘要： The present invention provides a cell which comprises a first chimeric antigen receptor (CAR) and a second CAR, wherein the first and second CARs bind different epitopes on the same ligand. The cell may be used in a method for treating a disease, such as cancer.

公开(公告)号：US11242377B2

公开(公告)日：2022-02-08

申请号：US15770110

申请日：2016-10-21

申请人： AUTOLUS LIMITED

发明人： Martin Pulé ,  Shaun Cordoba ,  Matteo Righi

IPC分类号： C07K14/715 ,  C07K14/705 ,  C07K19/00 ,  C07K16/30 ,  C12N5/0783 ,  C07K16/28 ,  C07K14/725 ,  A61K39/00 ,  A61K35/17

摘要： The present invention provides a chimeric receptor which comprises: a ligand-binding exodomain; and an endodomain which comprises: (i) a cytokine receptor endodomain; and (ii) an intracellular T cell signalling domain.

公开(公告)号：US20210348191A1

公开(公告)日：2021-11-11

申请号：US17192561

申请日：2021-03-04

申请人： AUTOLUS LIMITED

发明人： Martin Pulé ,  Leila Mekkaoui

IPC分类号： C12N15/86 ,  C07K14/725 ,  C07K16/28 ,  A61K35/76 ,  A61K38/00 ,  C07K16/00 ,  C07K14/00

摘要： The present invention provides a retroviral or lentiviral vector having a viral envelope which comprises: (i) a mitogenic T-cell activating transmembrane protein which comprises a mitogenic domain and a transmembrane domain; and/or (ii) a cytokine-based T-cell activating transmembrane protein which comprises a cytokine domain and a transmembrane domain, wherein the mitogenic or cytokine-based T-cell activating transmembrane protein is not part of a viral envelope glycoprotein. When cells such as T-cells of Natural Killer cells are transduced by such a viral vector, they are simultaneously activated by the mitogenic T-cell activating transmembrane protein and/or the cytokine-based T-cell activating transmembrane protein.

公开(公告)号：US11103532B2

公开(公告)日：2021-08-31

申请号：US16598652

申请日：2019-10-10

申请人： AUTOLUS LIMITED

发明人： Martin Pulé ,  Ryan Trowbridge ,  Edward Hodgkin

IPC分类号： A61K35/17 ,  C12N9/64 ,  A61K31/436 ,  C12N15/62 ,  C07K14/705 ,  C12N9/12 ,  A61K35/12

摘要： The present invention provides a chimeric protein having the formula: Casp-Ht1-Ht2 wherein Casp is a caspase domain; Ht1 is a first heterodimerization domain; and Ht2 is a second heterodimerization domain and wherein, in the presence of a chemical inducer of dimcrization (CID), an identical pair of the chimeric proteins interact such that Ht1 from one chimeric protein heterodimerizes with Ht2 from the other chimeric protein, causing homodimerization of the two caspase domains. The invention also provides a cell comprising such a protein and its use in adoptive cell therapy.

公开(公告)号：US11058722B2

公开(公告)日：2021-07-13

申请号：US15560558

申请日：2016-03-22

申请人： AUTOLUS LIMITED

发明人： Martin Pulé ,  Shaun Cordoba

IPC分类号： A61K35/17 ,  C07K14/705

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.