| 主权项 |
1. A bispecific antibody comprising an immunoglobulin G antibody (IgG) that binds tumor necrosis factor alpha (TNFα) conjugated to two single chain variable fragments (scFv) that bind the p19 subunit of IL-23 (IL23p19) wherein,
a.) said IgG comprises two heavy chains (HC) and two light chains (LC), each HC comprises a heavy chain variable region (HCVR1) comprising heavy chain CDRs (HCDR) 1-3 and each LC comprises a light chain variable region (LCVR1) comprising light chain CDRs (LCDR) 1-3, wherein the amino acid sequence of HCDR1 is SEQ ID NO:9, the amino acid sequence of HCDR2 is SEQ ID NO:10, the amino acid sequence of HCDR3 is SEQ ID NO:11, the amino acid sequence of LCDR1 is SEQ ID NO:15, the amino acid sequence of LCDR2 is SEQ ID NO:16, and the amino acid sequence of LCDR3 is SEQ ID NO:17; and b.) each scFv comprises a heavy chain variable region (HCVR2) and a light chain variable region (LCVR2), the HCVR2 comprising HCDRs 4-6 and the LCVR2 comprising LCDRs 4-6, wherein the amino acid sequence of HCDR4 is SEQ ID NO:12, the amino acid sequence of HCDR5 is SEQ ID NO:13, the amino acid sequence of HCDR6 is SEQ ID NO:14, the amino acid sequence of LCDR4 is SEQ ID NO:18, the amino acid sequence of LCDR5 is SEQ ID NO:19, and the amino acid sequence of LCDR6 is SEQ ID NO:20,wherein each scFv is independently conjugated to said IgG antibody via a polypeptide linker (L1) covalently attached to the C-terminus of each IgG HC and the N-terminus of HCVR2 of each scFv, and the HCVR2 of each scFv is covalently attached to the LCVR2 of the same scFv via a second polypeptide linker (L2) covalently attached to the C-terminus of the HCVR2 and the N-terminus of the LCVR2 of the same scFv. |
