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US 2026/0297207 A1Published application
Anti-tl1a×il23 bispecific antibodies and their applications thereof
AssigneeSimcere Pharmaceutical Co., Ltd.
InventorsXiaofeng Zhao, Xiaoqing Liu, Fudong Wang, Yuxi Yan
Life of this patent
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Abstract
The present disclosure relates to an anti-TL1A×IL23 bispecific molecule and use thereof. Specifically, disclosed are a bispecific molecule specifically binding to human TNF-like ligand 1A (TL1A) and interleukin 23, and corresponding encoding nucleic acid molecules, vectors, cells, preparation methods, pharmaceutical compositions, pharmaceutical use, and treatment methods for diseases, which are of great significance for the development of a drug for treating an immune-mediated inflammatory disease (IMID) (e.g., autoimmune diseases and inflammatory diseases).
Claims15
A multispecific molecule binding to TL1A and IL23, comprising an antigen-binding domain specifically binding to TL1A, and an antigen-binding domain specifically binding to IL23, wherein the antigen-binding domain specifically binding to TL1A comprises:
- (1) an HCDR1, an HCDR2, and an HCDR3 of the sequence set forth in SEQ ID NO:
- 70;
- or
- (2) an HCDR1, an HCDR2, and an HCDR3 of the sequence set forth in SEQ ID NO:
- 69;
- or
- (3) an HCDR1, an HCDR2, and an HCDR3 of the sequence set forth in SEQ ID NO:
- 15;
- and
- wherein the HCDR1-3 and/or the LCDR1-3 are determined according to the Kabat, Chothia, or IMGT scheme.
7 more elements
A bispecific molecule that binds specifically to TL1A and IL23, comprising:
- (1) (i) an IL-23-targeting moiety, comprising:
- (a) a VH region having the sequence set forth in SEQ ID NO:16, linked to a CH1 region having the sequence set forth in SEQ ID NO:28;
- and (b) a VL region having the sequence set forth in SEQ ID NO:17, linked to a CL region having the sequence set forth in SEQ ID NO:30;
- (ii) an Fc region formed by polypeptides having the sequence set forth in SEQ ID NO:
- 23;
- (iii) a TL1A-targeting moiety having the sequence set forth in SEQ ID NO:70;
- and
- (iv) a linker region between the Fc region and the TL1A-targeting moiety, having the sequence set forth in SEQ ID NO:32;
- or
- (2) (i) an IL-23-targeting moiety, comprising:
- (a) a VH region having the sequence set forth in SEQ ID NO:71, linked to a CH1 region having the sequence set forth in SEQ ID NO:28;
- and (b) a VL region having the sequence set forth in SEQ ID NO:72, linked to a CL region having the sequence set forth in SEQ ID NO:30;
- (ii) an Fc region formed by polypeptides having the sequence set forth in SEQ ID NO:
- 23;
- (iii) a TL1A-targeting moiety having the sequence set forth in SEQ ID NO:69;
- and
- (iv) a linker region between the Fc region and the TL1A-targeting moiety, having the sequence set forth in SEQ ID NO:32;
- or
- (3) (i) an IL-23-targeting moiety, comprising:
- (a) a VH region having the sequence set forth in SEQ ID NO:73, linked to a CH1 region having the sequence set forth in SEQ ID NO:28;
- and (b) a VL region having the sequence set forth in SEQ ID NO:74, linked to a CL region having the sequence set forth in SEQ ID NO:30;
- (ii) an Fc region formed by polypeptides having the sequence set forth in SEQ ID NO:
- 23;
- (iii) a TL1A-targeting moiety having the sequence set forth in SEQ ID NO:69;
- and
- (iv) a linker region between the Fc region and the TL1A-targeting moiety, having the sequence set forth in SEQ ID NO:32;
- or
- (4) (i) an IL-23-targeting moiety, comprising:
- (a) a VH region having the sequence set forth in SEQ ID NO:73, linked to a CH1 region having the sequence set forth in SEQ ID NO:28;
- and (b) a VL region having the sequence set forth in SEQ ID NO:72, linked to a CL region having the sequence set forth in SEQ ID NO:30;
- (ii) an Fc region formed by polypeptides having the sequence set forth in SEQ ID NO:
- 23;
- (iii) a TL1A-targeting moiety having the sequence set forth in SEQ ID NO:69;
- and
- (iv) a linker region between the Fc region and the TL1A-targeting moiety, having the sequence set forth in SEQ ID NO:32;
- or
- (5) (i) an IL-23-targeting moiety, comprising:
- (a) a VH region having the sequence set forth in SEQ ID NO:16, linked to a CH1 region having the sequence set forth in SEQ ID NO:28;
- and (b) a VL region having the sequence set forth in SEQ ID NO:17, linked to a CL region having the sequence set forth in SEQ ID NO:30;
- (ii) an Fc region formed by polypeptides having the sequence set forth in SEQ ID NO:
- 23;
- (iii) a TL1A-targeting moiety having the sequence set forth in SEQ ID NO:69;
- and
- (iv) a linker region between the Fc region and the TL1A-targeting moiety, having the sequence set forth in SEQ ID NO:32;
- or
- (6) (i) an IL-23-targeting moiety, comprising:
- (a) a VH region having the sequence set forth in SEQ ID NO:16, linked to a CH1 region having the sequence set forth in SEQ ID NO:28;
- and (b) a VL region having the sequence set forth in SEQ ID NO:17, linked to a CL region having the sequence set forth in SEQ ID NO:30;
- (ii) an Fc region formed by polypeptides having the sequence set forth in SEQ ID NO:
- 22;
- (iii) a TL1A-targeting moiety having the sequence set forth in SEQ ID NO:15;
- and
- (iv) a linker region between the Fc region and the TL1A-targeting moiety, having the sequence set forth in SEQ ID NO:32;
- or
- (7) (i) an IL-23-targeting moiety, comprising:
- (a) a VH region having the sequence set forth in SEQ ID NO:16, linked to a CH1 region having the sequence set forth in SEQ ID NO:28;
- and (b) a VL region having the sequence set forth in SEQ ID NO:17, linked to a CL region having the sequence set forth in SEQ ID NO:30;
- (ii) an Fc region formed by polypeptides having the sequence set forth in SEQ ID NO:
- 23;
- (iii) a TL1A-targeting moiety having the sequence set forth in SEQ ID NO:15;
- and
- (iv) a linker region between the Fc region and the TL1A-targeting moiety, having the sequence set forth in SEQ ID NO:32;
- or
- (8) (i) an IL-23-targeting moiety, comprising:
- (a) a VH region having the sequence set forth in SEQ ID NO:18, linked to a CH1 region having the sequence set forth in SEQ ID NO:28;
- and (b) a VL region having the sequence set forth in SEQ ID NO:19, linked to a CL region having the sequence set forth in SEQ ID NO:29;
- (ii) an Fc region formed by polypeptides having the sequence set forth in SEQ ID NO:
- 22;
- (iii) a TL1A-targeting moiety having the sequence set forth in SEQ ID NO:15;
- and
- (iv) a linker region between the Fc region and the TL1A-targeting moiety, having the sequence set forth in SEQ ID NO:32;
- or
- (9) (i) an IL-23-targeting moiety, comprising:
- (a) a VH region having the sequence set forth in SEQ ID NO:18, linked to a CH1 region having the sequence set forth in SEQ ID NO:28;
- and (b) a VL region having the sequence set forth in SEQ ID NO:19, linked to a CL region having the sequence set forth in SEQ ID NO:29;
- (ii) an Fc region formed by polypeptides having the sequence set forth in SEQ ID NO:
- 23;
- (iii) a TL1A-targeting moiety having the sequence set forth in SEQ ID NO:15;
- and
- (iv) a linker region between the Fc region and the TL1A-targeting moiety, having the sequence set forth in SEQ ID NO:32.
77 more elements
A bispecific molecule that binds specifically to TL1A and IL23, comprising:
- (1) (i) a first polypeptide and a second polypeptide, each comprising from N-terminus to C-terminus:
- (a) a VH region having the sequence set forth in SEQ ID NO:16;
- (b) a CH1 region having the sequence set forth in SEQ ID NO:28;
- (c) an Fc region sequence having the sequence set forth in SEQ ID NO:23;
- (d) a linker sequence having the sequence set forth in SEQ ID NO:32;
- and
- (e) a VHH region having the sequence set forth in SEQ ID NO:70;
- and
- (ii) a third polypeptide and a fourth polypeptide, each comprising from N-terminus to C-terminus:
- (a) a VL region having the amino acid sequence of SEQ ID NO:17;
- and
- (b) a CL region having the amino acid sequence of SEQ ID NO:30;
- or
- (2) (i) a first polypeptide and a second polypeptide, each comprising from N-terminus to C-terminus:
- (a) a VH region having the sequence set forth in SEQ ID NO:71;
- (b) a CH1 region having the sequence set forth in SEQ ID NO:28;
- (c) an Fc region sequence having the sequence set forth in SEQ ID NO:23;
- (d) a linker sequence having the sequence set forth in SEQ ID NO:32;
- and
- (e) a VHH region having the sequence set forth in SEQ ID NO:69;
- and
- (ii) a third polypeptide and a fourth polypeptide, each comprising from N-terminus to C-terminus:
- (a) a VL region having the amino acid sequence of SEQ ID NO:72;
- and
- (b) a CL region having the amino acid sequence of SEQ ID NO:30;
- or
- (3) (i) a first polypeptide and a second polypeptide, each comprising from N-terminus to C-terminus:
- (a) a VH region having the sequence set forth in SEQ ID NO:73;
- (b) a CH1 region having the sequence set forth in SEQ ID NO:28;
- (c) an Fc region sequence having the sequence set forth in SEQ ID NO:23;
- (d) a linker sequence having the sequence set forth in SEQ ID NO:32;
- and
- (e) a VHH region having the sequence set forth in SEQ ID NO:69;
- and
- (ii) a third polypeptide and a fourth polypeptide, each comprising from N-terminus to C-terminus:
- (a) a VL region having the amino acid sequence of SEQ ID NO:74;
- and
- (b) a CL region having the amino acid sequence of SEQ ID NO:30;
- or
- (4) (i) a first polypeptide and a second polypeptide, each comprising from N-terminus to C-terminus:
- (a) a VH region having the sequence set forth in SEQ ID NO:73;
- (b) a CH1 region having the sequence set forth in SEQ ID NO:28;
- (c) an Fc region sequence having the sequence set forth in SEQ ID NO:23;
- (d) a linker sequence having the sequence set forth in SEQ ID NO:32;
- and
- (e) a VHH region having the sequence set forth in SEQ ID NO:69;
- and
- (ii) a third polypeptide and a fourth polypeptide, each comprising from N-terminus to C-terminus:
- (a) a VL region having the amino acid sequence of SEQ ID NO:72;
- and
- (b) a CL region having the amino acid sequence of SEQ ID NO:30;
- or
- (5) (i) a first polypeptide and a second polypeptide, each comprising from N-terminus to C-terminus:
- (a) a VH region having the sequence set forth in SEQ ID NO:16;
- (b) a CH1 region having the sequence set forth in SEQ ID NO:28;
- (c) an Fc region sequence having the sequence set forth in SEQ ID NO:23;
- (d) a linker sequence having the sequence set forth in SEQ ID NO:32;
- and
- (e) a VHH region having the sequence set forth in SEQ ID NO:69;
- and
- (ii) a third polypeptide and a fourth polypeptide, each comprising from N-terminus to C-terminus:
- (a) a VL region having the amino acid sequence of SEQ ID NO:17;
- and
- (b) a CL region having the amino acid sequence of SEQ ID NO:30;
- or
- (6) (i) a first polypeptide and a second polypeptide, each comprising from N-terminus to C-terminus:
- (a) a VH region having the sequence set forth in SEQ ID NO:16;
- (b) a CH1 region having the sequence set forth in SEQ ID NO:28;
- (c) an Fc region sequence having the sequence set forth in SEQ ID NO:22;
- (d) a linker sequence having the sequence set forth in SEQ ID NO:32;
- and
- (e) a VHH region having the sequence set forth in SEQ ID NO:15;
- and
- (ii) a third polypeptide and a fourth polypeptide, each comprising from N-terminus to C-terminus:
- (a) a VL region having the amino acid sequence of SEQ ID NO:17;
- and
- (b) a CL region having the amino acid sequence of SEQ ID NO:30;
- or
- (7) (i) a first polypeptide and a second polypeptide, each comprising from N-terminus to C-terminus:
- (a) a VH region having the sequence set forth in SEQ ID NO:16;
- (b) a CH1 region having the sequence set forth in SEQ ID NO:28;
- (c) an Fc region sequence having the sequence set forth in SEQ ID NO:23;
- (d) a linker sequence having the sequence set forth in SEQ ID NO:32;
- and
- (e) a VHH region having the sequence set forth in SEQ ID NO:15;
- and
- (ii) a third polypeptide and a fourth polypeptide, each comprising from N-terminus to C-terminus:
- (a) a VL region having the amino acid sequence of SEQ ID NO:17;
- and
- (b) a CL region having the amino acid sequence of SEQ ID NO:30;
- or
- (8) (i) a first polypeptide and a second polypeptide, each comprising from N-terminus to C-terminus:
- (a) a VH region having the sequence set forth in SEQ ID NO:18;
- (b) a CH1 region having the sequence set forth in SEQ ID NO:28;
- (c) an Fc region sequence having the sequence set forth in SEQ ID NO:22;
- (d) a linker sequence having the sequence set forth in SEQ ID NO:32;
- and
- (e) a VHH region having the sequence set forth in SEQ ID NO:15;
- and
- (ii) a third polypeptide and a fourth polypeptide, each comprising from N-terminus to C-terminus:
- (a) a VL region having the amino acid sequence of SEQ ID NO:19;
- and
- (b) a CL region having the amino acid sequence of SEQ ID NO:29;
- or
- (9) (i) a first polypeptide and a second polypeptide, each comprising from N-terminus to C-terminus:
- (a) a VH region having the sequence set forth in SEQ ID NO:18;
- (b) a CH1 region having the sequence set forth in SEQ ID NO:28;
- (c) an Fc region sequence having the sequence set forth in SEQ ID NO:23;
- (d) a linker sequence having the sequence set forth in SEQ ID NO:32;
- and
- (e) a VHH region having the sequence set forth in SEQ ID NO:15;
- and
- (ii) a third polypeptide and a fourth polypeptide, each comprising from N-terminus to C-terminus:
- (a) a VL region having the amino acid sequence of SEQ ID NO:19;
- and
- (b) a CL region having the amino acid sequence of SEQ ID NO:29.
113 more elements
Dependencies are inferred from the claim text.