Patent application EP19305678A (EP), filed 2019-05-28
Publication number: EP3744400A1
Title: CAR-T CELLS TARGETING IL-1RAP AND THEIR USE IN ACUTE MYELOID LEUKEMIA (AML)
Abstract: The present invention is relative to a cell comprising a nucleic acid molecule encoding a chimeric antigen receptor (CAR) for use in the treatment of acute myeloid leukemia (AML), wherein the CAR comprises an antibody or antibody fragment which includes an anti-IL-lRAP binding domain, a transmembrane domain, and an intracellular signaling domain comprising at least a stimulatory domain
IPC codes: A61P  35/    02            A I
C07K  14/   715            A I
C07K  16/    28            A I
Claims: number: 1
text: A cell comprising a nucleic acid molecule encoding a chimeric antigen receptor (CAR) for use in the treatment of acute myeloid leukemia (AML), wherein the CAR comprises an antibody or antibody fragment which includes an anti-IL-1RAP binding domain, a transmembrane domain, and an intracellular signaling domain comprising at least a stimulatory domain, and wherein said anti-IL-1RAP binding domain comprises:
number: 2
text: The cell for use according to claim 1, wherein the anti-IL-1RAP binding domain comprises :
number: 3
text: The cell for use according to claim 1 or 2, wherein the anti-IL-1RAP binding domain comprises :
number: 4
text: The cell for use according to any of claims 1 to 3, wherein the cell is a T cell, preferably a CD8+ T cell.
number: 5
text: The cell for use according to any of claims 1 to 4, wherein the cell expresses the CAR at its membrane.
number: 6
text: The cell for use according to any of claims 1 to 5, wherein the IL-1RAP binding domain is selected from the group consisting of an antibody, a Fv, a scFv, a Fab, or another antibody fragment, preferably a scFv.
number: 7
text: The cell for use according to any of claims 1 to 6, wherein said transmembrane domain is a transmembrane domain of a protein selected from the group consisting of the alpha, beta or zeta chain of the T-cell receptor, CD28, CD3 epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137 and CD154, preferably CD28.
number: 8
text: The cell for use according to any of claims 1 to 7, wherein the anti-IL-1RAP binding domain is connected to the transmembrane domain by a hinge region, preferably the hinge region comprises the hinge sequence of IgG1 or a sequence with 95-99% identity thereof.
number: 9
text: The cell for use according to any of claims 1 to 8, said intracellular signaling domain comprises at least one costimulatory domain, preferably said at least one costimulatory domain of the functional intracellular signaling domain is obtained from one or more protein selected from the group consisting of OX40, CD2, CD27, CD28, CDS, CD3 zeta, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278), and 4-1BB (CD137), preferably obtained from 4-1BB (CD137) and/or obtained from CD3 zeta.
number: 10
text: The cell for use according to any of claims 1 to 9, wherein the AML is (i) refractory/relapsed AML or (ii) AML with complex cytogenetic abnormalities and/or AML with TP53 mutations.
number: 11
text: The cell for use according to any of claims 1 to 10, wherein the AML is IL1-RAP expressing AML, such as refractory/relapsed IL1-RAP expressing AML.
number: 12
text: The cell for use according to any of claims 1 to 11, in association with at least one monoclonal antibody, such as anti-checkpoint inhibitors (i.e. Anti PD-1, anti-PDL-1 or anti-CTL4).
Office action: search_report, dated 2020-12-02
Rejection reasons: novelty_epc_54
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Final disposition: pending (2020-12-02)