Anti-CTLA4 and anti-PD-1 bifunctional antibody, pharmaceutical composition thereof and use thereof

A bispecific antibody, comprising:

• an immunoglobulin comprising a heavy chain and a light chain,
• wherein the heavy chain comprises a first heavy chain variable region comprising heavy chain complementarity determining region (HCDR) 1 of SEQ ID NO:
• 29, HCDR2 of SEQ ID NO:
• 30, and HCDR3 of SEQ ID NO:
• 31, and a heavy chain constant region,
• wherein the light chain comprises a first light chain variable region comprising light chain complementarity determining region (LCDR) 1 of SEQ ID NO:
• 32, LCDR2 of SEQ ID NO:
• 33, and LCDR3 of SEQ ID NO:34, and a light chain constant region,
• wherein a C-terminus of the heavy chain is attached to at least one single-chain antibody via a first linker fragment,
• wherein the at least one single-chain antibody comprises,
• (i) a second heavy chain variable region comprising HCDR1 of SEQ ID NO:
• 35, HCDR2 of SEQ ID NO:
• 36, and HCDR3 of SEQ ID NO:
• 37, and a second light chain variable region comprising LCDR1 of SEQ ID NO:
• 38, LCDR2 of SEQ ID NO:
• 39, and LCDR3 of SEQ ID NO:
• 40;
• (ii) a second heavy chain variable region comprising HCDR1 of SEQ ID NO:
• 35, HCDR2 of SEQ ID NO:
• 41, and HCDR3 of SEQ ID NO:
• 37, and a second light chain variable region comprising LCDR1 of SEQ ID NO:
• 38, LCDR2 of SEQ ID NO:
• 39, and LCDR3 of SEQ ID NO:
• 40;
• or
• (iii) a second heavy chain variable region comprising HCDR1 of SEQ ID NO:
• 42, HCDR2 of SEQ ID NO:
• 43, and HCDR3 of SEQ ID NO:
• 44, and a second light chain variable region comprising LCDR1 of SEQ ID NO:
• 45, LCDR2 of SEQ ID NO:
• 46, and LCDR3 of SEQ ID NO:
• 47.