JPWO2021207709A5

JPWO2021207709A5 -

Info

Publication number: JPWO2021207709A5
Application number: JP2022562048A
Authority: JP
Publication date: 2024-07-25

Claims

An antibody, antigen-binding fragment or antibody domain,
(i) a heavy chain variable domain or region comprising the amino acid sequence set forth in SEQ ID NO: 217 (or the amino acid sequence set forth in SEQ ID NO: 217 having one, two or three amino acid additions, deletions or substitutions), the amino acid sequence set forth in SEQ ID NO: 218 (or the amino acid sequence set forth in SEQ ID NO: 218 having one, two or three amino acid additions, deletions or substitutions), and the amino acid sequence set forth in SEQ ID NO: 219 (or the amino acid sequence set forth in SEQ ID NO: 219 having one, two or three amino acid additions, deletions or substitutions);
(ii) a heavy chain variable domain or region comprising the amino acid sequence set forth in SEQ ID NO: 203 (or the amino acid sequence set forth in SEQ ID NO: 203 with one, two or three amino acid additions, deletions or substitutions), the amino acid sequence set forth in SEQ ID NO: 204 (or the amino acid sequence set forth in SEQ ID NO: 204 with one, two or three amino acid additions, deletions or substitutions), and the amino acid sequence set forth in SEQ ID NO: 205 (or the amino acid sequence set forth in SEQ ID NO: 205 with one, two or three amino acid additions, deletions or substitutions);
(iii) a heavy chain variable domain or region comprising the amino acid sequence set forth in SEQ ID NO: 210 (or the amino acid sequence set forth in SEQ ID NO: 210 having one, two or three amino acid additions, deletions or substitutions), the amino acid sequence set forth in SEQ ID NO: 211 (or the amino acid sequence set forth in SEQ ID NO: 211 having one, two or three amino acid additions, deletions or substitutions), and the amino acid sequence set forth in SEQ ID NO: 212 (or the amino acid sequence set forth in SEQ ID NO: 212 having one, two or three amino acid additions, deletions or substitutions);
(iv) a heavy chain variable domain or region comprising the amino acid sequence set forth in SEQ ID NO: 196 (or the amino acid sequence set forth in SEQ ID NO: 196 having one, two or three amino acid additions, deletions or substitutions), the amino acid sequence set forth in SEQ ID NO: 197 (or the amino acid sequence set forth in SEQ ID NO: 197 having one, two or three amino acid additions, deletions or substitutions), and the amino acid sequence set forth in SEQ ID NO: 198 (or the amino acid sequence set forth in SEQ ID NO: 198 having one, two or three amino acid additions, deletions or substitutions);
(v) a heavy chain variable domain or region comprising the amino acid sequence set forth in SEQ ID NO: 161 (or the amino acid sequence set forth in SEQ ID NO: 161 having one, two or three amino acid additions, deletions or substitutions), the amino acid sequence set forth in SEQ ID NO: 162 (or the amino acid sequence set forth in SEQ ID NO: 162 having one, two or three amino acid additions, deletions or substitutions), and the amino acid sequence set forth in SEQ ID NO: 163 (or the amino acid sequence set forth in SEQ ID NO: 163 having one, two or three amino acid additions, deletions or substitutions);
(vi) a heavy chain variable domain or region comprising the amino acid sequence set forth in SEQ ID NO: 169 (or the amino acid sequence set forth in SEQ ID NO: 169 having one, two or three amino acid additions, deletions or substitutions), the amino acid sequence set forth in SEQ ID NO: 170 (or the amino acid sequence set forth in SEQ ID NO: 170 having one, two or three amino acid additions, deletions or substitutions), and the amino acid sequence set forth in SEQ ID NO: 171 (or the amino acid sequence set forth in SEQ ID NO: 171 having one, two or three amino acid additions, deletions or substitutions);
(vii) a heavy chain variable domain or region comprising the amino acid sequence set forth in SEQ ID NO: 177 (or the amino acid sequence set forth in SEQ ID NO: 177 having one, two or three amino acid additions, deletions or substitutions), the amino acid sequence set forth in SEQ ID NO: 178 (or the amino acid sequence set forth in SEQ ID NO: 178 having one, two or three amino acid additions, deletions or substitutions), and the amino acid sequence set forth in SEQ ID NO: 179 (or the amino acid sequence set forth in SEQ ID NO: 179 having one, two or three amino acid additions, deletions or substitutions); or (viii) An antibody, antigen-binding fragment, or antibody domain comprising a heavy chain variable domain or heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 185 (or the amino acid sequence set forth in SEQ ID NO: 185 having one, two or three amino acid additions, deletions or substitutions), the amino acid sequence set forth in SEQ ID NO: 186 (or the amino acid sequence set forth in SEQ ID NO: 186 having one, two or three amino acid additions, deletions or substitutions), and the amino acid sequence set forth in SEQ ID NO: 187 (or the amino acid sequence set forth in SEQ ID NO: 187 having one, two or three amino acid additions, deletions or substitutions).

The antibody, antigen-binding fragment or antibody domain of claim 1, wherein the heavy chain variable domain or heavy chain variable region comprises an amino acid sequence having at least 90% sequence identity with any of the amino acid sequences set forth in SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:160, SEQ ID NO:168, SEQ ID NO:176 and SEQ ID NO:184, and the heavy chain variable domain or heavy chain variable region may comprise an amino acid sequence having at least 90% sequence identity with the amino acid sequence set forth in SEQ ID NO:1 or SEQ ID NO:4.

A nucleic acid encoding the antibody, antigen-binding fragment or antibody domain of claim 1 or 2.

A cell engager comprising a first antigen-binding domain, a linker, and a second antigen-binding domain, the first antigen-binding domain comprising an antibody, antigen-binding fragment, or antibody domain according to claim 1 or 2.

the linker comprises an IgG1 hinge, an IgG2 hinge, an IgG4 hinge, a CD8 hinge, a CD28 hinge, or an amino acid sequence set forth in any of SEQ ID NOs: 72-94 and 115-123;
the second antigen-binding domain specifically binds to CD3, CD16a, NKG2A, NKG2D, NKp30, NKp44, or NKp46;
The cell engager of claim 4, wherein the second antigen-binding domain comprises an amino acid sequence as set forth in SEQ ID NOs: 140-143 and 144-149; and/or further comprises a third antigen-binding region.

An antibody-drug conjugate (ADC) comprising an antigen-binding domain covalently linked to a drug, the antigen-binding domain comprising an antibody, antigen-binding fragment or antibody domain according to claim 1 or 2.

The antibody-drug conjugate of claim 6, wherein the drug is selected from the group consisting of auristatins, mertansines, and pyrrolobenzodiazepine (PBD) dimers.

An antibody, antigen-binding fragment or antibody domain according to claim 1 or 2, or a cell engager according to claim 4, which is bound to a radioisotope.

The antibody, antigen-binding fragment or antibody domain of claim 1 or 2, comprising a radioactive label.

A chimeric antigen receptor (CAR) capable of specifically binding to interleukin 1 receptor accessory protein (IL1RAP),
An antigen-binding domain;
spacer;
a transmembrane domain; and an intracellular signaling domain,
A chimeric antigen receptor, wherein the antigen-binding domain comprises an antibody, antigen-binding fragment or antibody domain according to claim 1 or 2.

the spacer comprises an IgG1 hinge, an IgG2 hinge, an IgG4 hinge, a CD8 hinge, a CD28 hinge, or an amino acid sequence set forth in any of SEQ ID NOs: 72-94 and 115-123;
11. The chimeric antigen receptor of claim 10, wherein the transmembrane domain comprises a transmembrane domain derived from CD3 gamma, CD4, CD8 alpha, CD28 or CD278, or an amino acid sequence as set forth in any of SEQ ID NOs: 13 and 124-131; and/or the intracellular signaling domain comprises a combination of a costimulatory domain selected from the group consisting of CD27, CD28, 4-1BB, OX-40, CD30, CD40, PD-1, ICOS, LFA-1, CD2, CD7, NKG2C and B7-H3 with a CD3 zeta domain or a functional portion thereof, or an amino acid sequence as set forth in any of SEQ ID NOs: 15, 17 and 132-139.

A polynucleotide encoding the chimeric antigen receptor of claim 10 or 11.

A vector comprising the polynucleotide according to claim 12, which may be a viral vector, and which may be a lentiviral vector, a retroviral vector, an adenoviral vector, or an adeno-associated viral vector.

A cell comprising the chimeric antigen receptor according to claim 10 or 11, which may be a T cell, a stem cell, a NK cell, a precursor T cell or a hematopoietic stem cell.

15. The antibody, antigen-binding fragment or antibody domain of claim 1 or 2, the cell engager of claim 4 or 5, the antibody drug conjugate of claim 6, or the cell of claim 14 for use in treating, alleviating or suppressing an IL1RAP ⁺ cancer in a subject, which may be a cancer selected from the group consisting of breast cancer, brain cancer, colon cancer, kidney cancer, pancreatic cancer, ovarian cancer, sarcoma, leukemia, acute myeloid leukemia (AML), chronic myeloid leukemia (CML) and Ewing's sarcoma.