US 11,885,806 B2
Method for depleting malignant T-cells
Martin Pulé, London (GB); and Paul Maciocia, London (GB)
Assigned to AUTOLUS LIMITED, London (GB)
Filed by AUTOLUS LIMITED, London (GB)
Filed on Jun. 3, 2022, as Appl. No. 17/832,225.
Application 17/832,225 is a continuation of application No. 16/229,684, filed on Dec. 21, 2018, granted, now 11,385,233.
Application 16/229,684 is a continuation of application No. 15/606,480, filed on May 26, 2017, abandoned.
Application 15/606,480 is a continuation of application No. 15/123,287, abandoned, previously published as PCT/GB2015/050643, filed on Mar. 5, 2015.
Claims priority of application No. 1403905 (GB), filed on Mar. 5, 2014; and application No. 1416908 (GB), filed on Sep. 25, 2014.
Prior Publication US 2023/0019650 A1, Jan. 19, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. G01N 33/574 (2006.01); G16H 50/30 (2018.01); C12Q 1/6886 (2018.01); C12Q 1/686 (2018.01); A61K 39/00 (2006.01)
CPC G01N 33/57492 (2013.01) [C12Q 1/6886 (2013.01); G16H 50/30 (2018.01); A61K 2039/515 (2013.01); C12Q 1/686 (2013.01)] 10 Claims
 
1. A method of depleting malignant T-cells in a human subject with a TRBC1 positive T-cell lymphoma or leukaemia, the method comprising:
determining the percentage of total T-cells in a sample from the subject which is TRBC1 positive and determining the percentage of total T-cells in the sample which is TRBC2 positive,
detecting a percentage of TRBC1 positive T-cells that is greater than 80% or detecting a percentage of TRBC2 positive T-cells that is greater than 80%,
diagnosing the subject as having a TRBC1 positive T-cell lymphoma or leukaemia when the percentage of TRBC1 positive cells is greater than 80%, and
selectively depleting T-cells in the subject determined to have the TRBC1 positive T cell lymphoma or leukaemia by administering an agent that selectively binds to and depletes malignant and normal T cells that are TRBC1-positive,
wherein the agent is an engineered T-cell expressing a CAR which selectively binds TRBC1 and which comprises (a) an antigen-binding domain comprising a variable heavy chain (VH) comprising: a VH CDR1 of SEQ ID NO: 7, a VH CDR2 of SEQ ID NO: 8, and a VH CDR3 of SEQ ID NO: 9, and a variable light chain (VL) comprising a VL CDR1 of SEQ ID NO: 10, a VL CDR2 of SEQ ID NO: 11, and a VL CDR3 of SEQ ID NO: 12, and (b) a spacer comprising an IgG1 hinge or a CD8 stalk.