Anti-ctla4 and anti-pd-1 bifunctional antibody, pharmaceutical composition thereof and use thereof
AssigneeAkeso Pharmaceuticals, Inc.
InventorsBaiyong LI, Yu XIA, Zhongmin Maxwell WANG, Peng ZHANG
Life of this patent
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Abstract
An anti-CTLA4 (cytotoxic T lymphocyte associated antigen4) and anti-PD-1 (programmed cell death 1) bifunctional antibody. a pharmaceutical composition thereof and use thereof. Particularly, the anti-CLTA4 and anti-PD-1 bifunctional antibody comprises a first protein functional domain that targets PD-1 and a second protein functional domain that targets CTLA-4. The bifunctional antibody can bind to CTLA-4 and PD-1 specifically, relieve immunosuppression of CTLA4 and PD-1 on an organism specifically, activate T lymphocytes, and thus has good application prospects.
Claims9
-25. (canceled)
An isolated nucleic acid molecule comprising one more nucleic acid sequences encoding 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 a heavy chain complementarity determining region (HCDR) 1 of SEQ ID NO:
- 29, an HCDR2 of SEQ ID NO:
- 30, and an HCDR3 of SEQ ID NO:
- 31, and a heavy chain constant region,
- wherein the light chain comprises a first light chain variable region comprising a light chain complementarity determining region (LCDR) 1 of SEQ ID NO:
- 32, an LCDR2 of SEQ ID NO:
- 33, and an 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 an HCDR1 of SEQ ID NO:
- 35, an HCDR2 of SEQ ID NO:
- 36, and an HCDR3 of SEQ ID NO:
- 37, and a second light chain variable region comprising an LCDR1 of SEQ ID NO:
- 38, an LCDR2 of SEQ ID NO:
- 39, and an LCDR3 of SEQ ID NO:
- 40;
- (ii) a second heavy chain variable region comprising an HCDR1 of SEQ ID NO:
- 35, an HCDR2 of SEQ ID NO:
- 41, and an HCDR3 of SEQ ID NO:
- 37, and a second light chain variable region comprising an LCDR1 of SEQ ID NO:
- 38, an LCDR2 of SEQ ID NO:
- 39, and an LCDR3 of SEQ ID NO:
- 40;
- or
- (iii) a second heavy chain variable region comprising an HCDR1 of SEQ ID NO:
- an 42, an HCDR2 of SEQ ID NO:
- 43, and an HCDR3 of SEQ ID NO:
- 44, and a second light chain variable region comprising an LCDR1 of SEQ ID NO:
- 45, an LCDR2 of SEQ ID NO:
- 46, and an LCDR3 of SEQ ID NO:
- 47.
A conjugate comprising 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 an HCDR1 of SEQ ID NO:
- 29, an HCDR2 of SEQ ID NO:
- 30, and an HCDR3 of SEQ ID NO:
- 31, and a heavy chain constant region,
- wherein the light chain comprises a first light chain variable region comprising an LCDR1 of SEQ ID NO:
- 32, an LCDR2 of SEQ ID NO:
- 33, and an 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 an HCDR1 of SEQ ID NO:
- 35, an HCDR2 of SEQ ID NO:
- 36, and an HCDR3 of SEQ ID NO:
- 37, and a second light chain variable region comprising an LCDR1 of SEQ ID NO:
- 38, an LCDR2 of SEQ ID NO:
- 39, and an LCDR3 of SEQ ID NO:
- 40;
- (ii) a second heavy chain variable region comprising an HCDR1 of SEQ ID NO:
- 35, an HCDR2 of SEQ ID NO:
- 41, and an HCDR3 of SEQ ID NO:
- 37, and a second light chain variable region comprising an LCDR1 of SEQ ID NO:
- 38, an LCDR2 of SEQ ID NO:
- 39, and an LCDR3 of SEQ ID NO:
- 40;
- or
- (iii) a second heavy chain variable region comprising an HCDR1 of SEQ ID NO:
- 42, an HCDR2 of SEQ ID NO:
- 43, and an HCDR3 of SEQ ID NO:
- 44, and a second light chain variable region comprising an LCDR1 of SEQ ID NO:
- 45, an LCDR2 of SEQ ID NO:
- 46, and an LCDR3 of SEQ ID NO:
- 47;
- and a detectable marker.
A kit comprising 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 an HCDR1 of SEQ ID NO:
- 29, an HCDR2 of SEQ ID NO:
- 30, and an HCDR3 of SEQ ID NO:
- 31, and a heavy chain constant region,
- wherein the light chain comprises a first light chain variable region comprising an LCDR1 of SEQ ID NO:
- 32, an LCDR2 of SEQ ID NO:
- 33, and an 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 an HCDR1 of SEQ ID NO:
- 35, an HCDR2 of SEQ ID NO:
- 36, and an HCDR3 of SEQ ID NO:
- 37, and a second light chain variable region comprising an LCDR1 of SEQ ID NO:
- 38, an LCDR2 of SEQ ID NO:
- 39, and an LCDR3 of SEQ ID NO:
- 40;
- (ii) a second heavy chain variable region comprising an HCDR1 of SEQ ID NO:
- 35, an HCDR2 of SEQ ID NO:
- 41, and an HCDR3 of SEQ ID NO:
- 37, and a second light chain variable region comprising an LCDR1 of SEQ ID NO:
- 38, an LCDR2 of SEQ ID NO:
- 39, and an LCDR3 of SEQ ID NO:
- 40;
- or
- (iii) a second heavy chain variable region comprising an HCDR1 of SEQ ID NO:
- 42, an HCDR2 of SEQ ID NO:
- 43, and an HCDR3 of SEQ ID NO:
- 44, and a second light chain variable region comprising an LCDR1 of SEQ ID NO:
- 45, an LCDR2 of SEQ ID NO:
- 46, and an LCDR3 of SEQ ID NO:
- 47.
Dependencies are inferred from the claim text.