JPWO2021202726A5 - - Google Patents

Claims (20)

Complementary of 9G2, 1H7, 6H9, 2D5, 5D12, 3A5 variant 1, 3A5 variant 2, 7D5 variant 1, 7D5 variant 2, 8F5, 12B12, 11D11, 7E7, 11D5 or 13E11 as defined by IMGT, Kabat, North or Chothia An antibody or antigen-binding fragment thereof comprising a set of sex-determining regions (CDRs). anti-CD33 immunotoxin, anti-CD33 antibody-drug conjugate, antibody-fluorophore conjugate, anti-CD33 antibody-radioisotope conjugate, anti-CD33 bispecific antibody, anti-CD33 bispecific immune cell-inducing antibody, anti-CD33 9G2, 1H7, 6H9, 2D5, 3A5 variant 1, 3A5 variant 2, 7D5 variant 1 as defined by IMGT, Kabat, North or Chothia as part of the CD33 trispecific antibody and/or anti-CD33 tetraspecific antibody , 7D5 variant 2, 5D12, 8F5, 12B12, 11D11, 7E7, 11D5 or 13E11. anti-CD33 immunotoxin, anti-CD33 antibody-drug conjugate, antibody-fluorophore conjugate, anti-CD33 anti-CD33 antibody-radioisotope conjugate, anti-CD33 bispecific antibody, anti-CD33 bispecific immune cell-inducing antibody , as part of an anti-CD33 trispecific antibody and/or an anti-CD33 tetraspecific antibody,
variable light chain of 9G2, 1H7, 6H9, 2D5, 3A5 variant 1, 3A5 variant 2, 7D5 variant 1, 7D5 variant 2, 5D12, 8F5, 12B12, 11D11, 7E7, 11D5 or 13E11, and 9G2, 1H7, 6H9, 2D5 , 5D12, 3A5 variant 1, 3A5 variant 2, 7D5 variant 1, 7D5 variant 2, 8F5, 12B12, 11D11, 7E7, 11D5 or 13E11, or
At least 90% sequence identity with the variable light chain of 9G2, 1H7, 6H9, 2D5, 3A5 variant 1, 3A5 variant 2, 7D5 variant 1, 7D5 variant 2, 5D12, 8F5, 12B12, 11D11, 7E7, 11D5 or 13E11. and the corresponding variable heavy chain of 9G2, 1H7, 6H9 , 2D5, 3A5 variant 1, 3A5 variant 1, 7D5 variant 2, 7D5 variant 2, 5D12, 8F5, 12B12, 11D11, 7E7, 11D5 or 13E11 and at least 90 A CD33 targeting agent comprising a binding domain comprising sequences having % sequence identity. 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, NK-T cells, or macrophages. The CD33 targeting agent according to claim 5 , which has a sequence set forth in SEQ ID NO: 1 or any one of 162 to 171. 6. The CD33 targeting agent of claim 5 , wherein the binding domain activates T cells and comprises the CDR of the OKT3 antibody, the 4B4-D7 antibody, the 4E7-C9 antibody , the 18F5- H10 antibody, the TGN1412 antibody, the OKT8 antibody, or the TCR . 4. The CD33 targeting agent of claim 2 or 3, comprising an Fv, Fab, Fab', F(ab')2 or single chain Fv fragment (scFv) of 9G2, 1H7, 6H9, 2D5, 3A5 variant 1, 3A5 variant 2, 7D5 variant 1, 7D5 variant 2, 5D12, 8F5, 12B12, 11D11, 7E7, 11D5 or 13E11 having a sequence as set forth in any one of SEQ ID NOs : 152-161. The humanized antibody or antigen-binding fragment according to claim 1 . The antibody or antigen-binding fragment of claim 1 which 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. A cell genetically modified to express the antibody or antigen-binding fragment thereof of claim 1 or the multispecific antibody of claim 4 . 14. The cell of claim 13 , which is a T cell, B cell, natural killer (NK) cell, NK-T cell, monocyte/macrophage, hematopoietic stem cell (HSC) or hematopoietic progenitor cell (HPC). 14. The cell according to claim 13 , which is a CD8+ T cell. 14. A formulation comprising a population of cells according to claim 13 and a pharmaceutically acceptable carrier. 13. A pharmaceutical composition for use in a method of treating a CD33-related disorder in a subject in need of treatment, said pharmaceutical composition comprising a therapeutically effective amount of the composition of claim 12 and/or or a formulation according to claim 16, said method comprising administering to a subject a therapeutically effective amount of a composition according to claim 12 and/or a formulation according to claim 16 , thereby A pharmaceutical composition for treating a CD33-related disorder in a subject in need thereof. 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 ( 18. The pharmaceutical composition according to claim 17 , 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 comprising selecting a combination therapy comprising a composition comprising one or more binding domains of 9G2, 1H7, 6H9, 3A5, 7D5, and 2D5 and one or more binding domains of 5D12 and 8F5. , or
(ii) if the subject does not express the V set domain of CD33;
A combination therapy comprising a composition comprising one or more binding domains of 9G2, 1H7, 6H9, 3A5, 7D5, and 2D5 and one or more binding domains of 12B12, 11D5, 13E11, 11D11 and 7E7. further including selecting;
The pharmaceutical composition according to claim 17 . A composition comprising one or more binding domains of 9G2, 1H7, 6H9, 3A5 , 7D5, and 2D5 and one or more binding domains of 5D12, 8F5, 12B12, 11D5, 13E11, 11D11 and 7E7 ; or A kit comprising a composition comprising a binding domain of one or more of 5D12, 8F5, 12B12, 11D5, 13E11, 11D11 and 7E7.