JPWO2020252208A5

JPWO2020252208A5 -

Info

Publication number: JPWO2020252208A5
Application number: JP2021573387A
Authority: JP
Publication date: 2023-06-16

Claims

A composition comprising a therapeutic agent, the therapeutic agent comprising:
(a) a first binding domain, which is the binding domain of the first antibody that specifically interacts with the antigen on the target cell; and (b) a second antibody that specifically interacts with myeloid cells. A composition comprising a second binding domain , which is a binding domain ; wherein said first and second binding domains are operably linked by one or more linkers.

2. The composition of claim 1 , wherein said myeloid cells are monocyte cells or macrophage cells.

wherein said first binding domain is a _VH domain, a VL domain, a _VNAR domain, a _VHH domain, a single chain variable fragment (scFv), a Fab, a single domain antibody (sdAb), a nanobody, a bispecific antibody; or a diabody ; said second binding domain is a VH domain, a VL _domain , a VNAR _domain , a VHH domain _, a single chain variable fragment (scFv), a Fab, a single domain antibody (sdAb), a Nanobody, 2. The composition of claim 1 , which is a bispecific antibody, or diabody .

2. The composition of claim 1 , wherein the antigen on the target cell to which the first binding domain binds is a cancer antigen , viral antigen, or autoimmune antigen.

5. The composition of claim 4 , wherein the antigen on the target cell to which said first binding domain binds is a cancer antigen.

6. The composition of claim 5, wherein the antigen on said target cell is an ovarian cancer antigen.

6. The composition of claim 5, wherein said antigen is a T lymphoma antigen.

wherein said first binding domain is thymidine kinase (TK1), hypoxanthine-guanine phosphoribosyltransferase (HPRT), receptor tyrosine kinase-like orphan receptor 1 (ROR1), mucin-1, mucin-16 (MUC16); MUC1, epidermal growth factor receptor vIII (EGFRvIII), mesothelin, human epidermal growth factor receptor 2 (HER2) , EBNA-1, LEMD1, phosphatidylserine, carcinoembryonic antigen (CEA), B cell maturation antigen (BCMA) , glypican 3 (GPC3), follicle-stimulating hormone receptor, fibroblast-activating protein (FAP), erythropoietin-producing hepatocellular carcinoma A2 (EphA2), EphB2, natural killer group 2D (NKG2D) ligand, disialoganglioside 2 (GD2) ), CD2, CD3, CD4, CD5, CD7, CD8, CD19, CD20, CD22, CD24, CD30, CD33, CD38, CD44v6, CD45, CD56, CD79b, CD97, CD117, CD123, CD133, CD138, CD171, CD179a, CD213A2, CD248, CD276, PSCA, CS-1, CLECL1, GD3, PSMA, FLT3, TAG72, EPCAM, IL-1, integrin receptor, PRSS21, VEGFR2, PDGFR-beta, SSEA-4, EGFR, NCAM, protease, 6. The composition of claim 5 , which binds to a protein selected from the group consisting of PAP, ELF2M, GM3, TEM7R, CLDN6, TSHR, GPRC5D, ALK, and IGLL1.

6. The antigen of claim 5 , wherein the antigen on the target cell to which said first binding domain binds is selected from the group consisting of CD2, CD3, CD4, CD5, CD7, CCR4, CD8, CD30, CD45 and CD56. Composition.

2. The composition of claim 1, wherein said first binding domain has a sequence with at least 80% sequence identity to any one of SEQ ID NOS: 27, 28, 111, 112, 113, 115, 143 and 144. .

said therapeutic agent promotes phagocytic activity of myeloid cells; promotes inflammatory signaling by myeloid cells; promotes adhesion of myeloid cells to target cells; myeloid cells mediated by target cells and/or inhibit the anti-inflammatory activity of myeloid cells mediated by target cells .

binding of the therapeutic agent to the myeloid cells increases the killing or phagocytic activity of the myeloid cells by at least 10 % compared to myeloid cells not bound by the therapeutic agent, as measured by a particle uptake assay; A composition according to claim 1 .

wherein said second binding domain is lectin, dectin 1, CD206, scavenger receptor A1 (SRA1), MARCO, CD36, CD163, MSR1, SCARA3, COLEC12, SCARA5, SCARB1, SCARB2, CD68, OLR1, SCARF1, SCARF2, CXCL16 , STAB1, STAB2, SRCRB4D, SSC5D, CD205, CD207, CD209, RAGE, CD14, CD64, F4/80, CCR2, CX3CR1, CSF1R, Tie2, HuCRIg(L), CD64, CD32a, CD16a, CD89, Fc-alpha receptor 2. The composition of claim 1 , which binds Body I, CR1, CD35, CR3, CR4, Tim-1, Tim-4 or CD169.

2. The composition of claim 1 , wherein said second binding domain binds to the extracellular domain of FcγRI, FcγRIIA, FcγRIIB, FcγRIIC, FcγRIIIA, FcγRIIIB, FcRn, TRIM21 or FcRL5.

12. The composition of claim 11 , wherein said second binding domain has a sequence with at least 80 % sequence identity with SEQ ID NO: 141 or 142.

2. The composition of claim 1, wherein said one or more linkers comprise linkers that are ligands for TLR receptors.

2. The composition of claim 1, wherein said one or more linkers comprise linkers that are ligands for TLR4 receptors.

2. The composition of claim 1, wherein said one or more linkers comprise linkers having amino acid sequences selected from the group consisting of SEQ ID NOS: 105-110 and 123-140.

2. The composition of claim 1, wherein said first binding domain binds HER2, said second binding domain binds Fc[gamma]RIIIA or Fc[gamma]RIIIB, and said linker is a ligand for a TLR4 receptor.

2. The composition of claim 1, wherein said first binding domain binds CD5, said second binding domain binds Fc[gamma]RIIIA or Fc[gamma]RIIIB, and said linker is a ligand for a TLR4 receptor.

2. The composition of claim 1, wherein said first binding domain binds GPC3, said second binding domain binds Fc[gamma]RIIIA or Fc[gamma]RIIIB, and said linker is a ligand for a TLR4 receptor.

2. The composition of claim 1 , wherein said therapeutic agent is a single polypeptide 200-1000 amino acids in length .

2. The therapeutic of claim 1, wherein said therapeutic further comprises a third binding domain, said third binding domain specifically interacting with the same myeloid cells with which said second binding domain interacts. Composition.

The extracellular domain of the receptor expressed by the target cell specifically interacts with the first binding domain, and the extracellular domain of the first receptor expressed by the myeloid cell and the second binding domain are specific and said third binding domain specifically interacts with the extracellular domain of a second receptor expressed by the same myeloid cell with which said second binding domain interacts. Item 24. The composition of Item 23.

25. The composition of claim 24, wherein said third binding domain binds to an integrin receptor.

wherein said third binding domain comprises α1, α2, αIIb, α3, α4, α5, α6, α7, α8, α9, α10, α11, αD, αE, αL, αM, αV, αX, β1, β2, β3, 26. The composition of claim 25, which binds to an integrin receptor selected from the group consisting of β4, β5, β6, β7, and β8.

2. The composition of claim 1, wherein the antigen on the target cell to which said first binding domain binds is the extracellular domain of a receptor.

said therapeutic agent promotes phagocytic activity of myeloid cells , promotes inflammatory signaling by myeloid cells , promotes adhesion of myeloid cells to target cells , is mediated by target cells 24. The composition of claim 23 , which inhibits the antiphagocytic activity of myeloid cells and/or inhibits the anti-inflammatory activity of myeloid cells mediated by target cells.

A bispecific or trispecific engager comprising an amino acid sequence having at least 80 % sequence identity with SEQ ID NO:151 or SEQ ID NO:152.

30. A pharmaceutical composition for the treatment of cancer comprising the composition of claim 1 or the bispecific or trispecific engager of claim 29.