JPWO2021202770A5

JPWO2021202770A5 -

Info

Publication number: JPWO2021202770A5
Application number: JP2022559585A
Authority: JP
Publication date: 2024-03-28

Claims

An antibody or antigen-binding fragment thereof comprising a set of 1B9, 1H10, 1A9, 1E6 , 1D2, 1H8, 2D3, or 2E3 complementarity determining regions (CDRs) as defined by IMGT, Kabat, North, or Chothia.

anti-CD33 immunotoxin, anti-CD33 antibody-drug conjugate, anti-CD33 antibody-radioisotope conjugate, anti-CD33 bispecific antibody, anti-CD33 bispecific immune cell-inducing antibody, anti-CD33 trispecific antibody, and or the complementarity determining regions (CDRs) of 1B9, 1H10, 1A9, 1E6 , 1D2, 1H8, 2D3, or 2E3 as defined by IMGT, Kabat, North, or Chothia as part of an anti-CD33 tetraspecific antibody A CD33 targeting agent comprising a binding domain comprising a set of.

anti-CD33 immunotoxin, anti-CD33 antibody-drug conjugate, anti-CD33 antibody-radioisotope conjugate, anti-CD33 bispecific antibody, anti-CD33 bispecific immune cell-inducing antibody, anti-CD33 trispecific antibody, and / or as part of an anti-CD33 tetraspecific antibody
1B9, 1H10, 1A9, 1E6 , 1D2, 1H8 , 2D3, or 2E3 variable light chain and variable heavy chain; or
Sequences having at least 90% sequence identity to the variable light chain of 1B9, 1H10 , 1A9 , 1E6, 1D2 , 1H8, 2D3, or 2E3; A CD33 targeting agent comprising a binding domain comprising a sequence having at least 90% sequence identity to a corresponding variable heavy chain.

The CD33 targeting agent according to claim 2 or 3 , comprising a multispecific antibody.

5. The CD33 targeting agent of claim 4, wherein the multispecific antibody comprises a binding domain that activates immune cells.

The CD33 targeting agent according to claim 5 , wherein the immune cells are T cells, natural killer (NK) cells, or macrophages.

The CD33 targeting agent according to claim 5 , which has a sequence set forth in SEQ ID NO: 157 or any one of 238-245.

The binding domain activates T cells, CDR of OKT3 antibody, CDR of 4B4-D7 antibody, CDR of 4E7-C9 antibody, CDR of 18F5-H10 antibody, CDR of TGN1412 antibody, CDR of OKT8 antibody, described in SEQ ID NO: 162. The CD33 targeting agent according to claim 5 , comprising a variable light chain having the sequence set forth in SEQ ID NO: 161 and a variable heavy chain having the sequence set forth in SEQ ID NO: 161, or a TCR.

Fv, Fab, Fab', F(ab') ₂ of 1B9, 1H10, 1A9, 1E6 , 1D2, 1H8, 2D3, or 2E3 having the sequence set forth in any one of SEQ ID NOS: 230 to 237, or The CD33 targeting agent according to claim 2 or 3, comprising a single chain Fv fragment (scFv).

2. The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof is PEGylated or comprises an Fc modification .

4. A composition comprising the antibody or antigen-binding fragment thereof according to claim 1 and/or the CD33 targeting agent according to claim 2 or 3, formulated for administration to a subject.

Cells genetically modified to express the antibody or antigen-binding fragment thereof according to claim 1 and/or the CD33 targeting agent according to claim 2 or 3, formulated for administration to a subject. .

13. The cell according to claim 12 , which is a T cell, a B cell, a natural killer (NK) cell, a monocyte/macrophage, a hematopoietic stem cell (HSC) or a hematopoietic progenitor cell (HPC).

13. The cell according to claim 12 , wherein the cell is a CD8+ T cell.

13. A formulation comprising a population of cells according to claim 12 and a pharmaceutically acceptable carrier.

A pharmaceutical composition for use in a method of treating a CD33-related disorder in a subject in need thereof, said pharmaceutical composition comprising a therapeutically effective amount of a composition according to claim 11 and/or claim 15. wherein the method comprises administering to a subject a therapeutically effective amount of the composition of claim 11 and/or the formulation of claim 15 , thereby requiring the same. A pharmaceutical composition for treating a CD33-related disorder in a subject.

CD33-related disorders include acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), chronic myelomonocytic leukemia (CML), mast cell leukemia, myelodysplastic syndrome ( 17. The pharmaceutical composition according to claim 16 , comprising B-cell acute lymphoblastic leukemia (B-ALL), T-cell acute lymphoblastic leukemia (T-ALL) or megakaryocytic leukemia.

The method includes:
determining whether the subject expresses or lacks the V set domain of CD33; and
(i) if the subject expresses the V set domain of CD33;
further selecting a combination therapy comprising a composition comprising one or more binding domains of 1B9, 1H10, 1A9, 1E6, and 1D2 and one or more binding domains of 1H8, 2D3, and 2E3; contains or
(ii) if the subject does not express the V set domain of CD33;
Compositions comprising one or more binding domains of 1B9, 1H10, 1A9, 1E6, and 1D2
further comprising selecting a therapy comprising;
A pharmaceutical composition according to any one of claims 16 to 17.

(i) a composition comprising one or more binding domains of 1B9, 1H10, 1A9, 1E6, and 1D2 and one or more binding domains of 1H8, 2D3, and 2E3 , or
(ii) compositions comprising one or more binding domains of 1B9, 1H10, 1A9, 1E6, and 1D2 and compositions comprising one or more binding domains of 1H8, 2D3, and 2E3;
kit including.