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US 12,577,313 B2Granted
Anti-claudin 18.2 and anti-4-1BB bispecific antibodies and uses thereof
AssigneesI-Mab Biopharma US Limited, Abl Bio Inc.
InventorsWenqing Jiang, Lei Fang, Zhengyi Wang, Bingshi Guo, Eunyoung Park, Eunsil Sung, Byungje Sung
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Abstract
Provided are bispecific and multi-specific antibodies that target both claudin 18.2 (CLDN18.2) and 4-1BB. These antibodies, in the absence of CLDN18.2-expressing cells, can bind to 4-1BB but are unable to activate 4-1BB signaling. In the presence of CLDN18.2-expressing cells, however, these antibodies can trigger CLDN18.2-dependent 4-1BB signaling, leading to potent immune response to the CLDN18.2-expressing tumor cells.
Claims15
An antibody, comprising:
- an anti-claudin 18.2 (CLDN18.2) unit having binding specificity to a CLDN18.2 protein, wherein the anti-CLDN18.2 unit comprises a heavy chain variable region (VH) comprising a CDRH1, a CDRH2, and a CDRH3, and a light chain variable region (VL) comprising a CDRL1, a CDRL2 and a CDRL3, wherein:
- (a) the CDRH1 comprises the amino acid sequence of SEQ ID NO:7:
- the CDRH2 comprises the amino acid sequence of SEQ ID NO:8;
- the CDRH3 comprises the amino acid sequence of SEQ ID NO:9;
- the CDRL1 comprises the amino acid sequence of SEQ ID NO:10;
- the CDRL2 comprises the amino acid sequence of SEQ ID NO:11;
- and
- and the CDRL3 comprises the amino acid sequence of SEQ ID NO:12;
- (b) the CDRH1 comprises the amino acid sequence of SEQ ID NO:
- 13;
- the CDRH2 comprises the amino acid sequence of SEQ ID NO:14;
- the CDRH3 comprises the amino acid sequence of SEQ ID NO:15;
- the CDRL1 comprises the amino acid sequence of SEQ ID NO:16;
- the CDRL2 comprises the amino acid sequence of SEQ ID NO:
- 17;
- and
- and the CDRL3 comprises the amino acid sequence of SEQ ID NO:18;
- or
- (c) the CDRH1 comprises the amino acid sequence of SEQ ID NO:
- 19;
- the CDRH2 comprises the amino acid sequence of SEQ ID NO:20;
- the CDRH3 comprises the amino acid sequence of SEQ ID NO:21;
- the CDRL1 comprises the amino acid sequence of SEQ ID NO:22;
- the CDRL2 comprises the amino acid sequence of SEQ ID NO:11;
- and
- the CDRL3 comprises the amino acid sequence of SEQ ID NO:23;
- and
- an anti-4-1BB unit having binding specificity to a 4-1BB protein, wherein the anti-4-1BB unit comprises a heavy chain variable region (VH) comprising a CDRH1, a CDRH2, and a CDRH3, and a light chain variable region (VL) comprising a CDRL1, a CDRL2 and a CDRL3, and wherein:
- the CDRH1 comprises the amino acid sequence of SEQ ID NO:60;
- the CDRH2 comprises the amino acid sequence of SEQ ID NO:61;
- the CDRH3 comprises the amino acid sequence of SEQ ID NO:62;
- the CDRL1 comprises the amino acid sequence of SEQ ID NO:4;
- the CDRL2 comprises the amino acid sequence of SEQ ID NO:5;
- and
- the CDRL3 comprises the amino acid sequence of SEQ ID NO:6.
32 more elements
An antibody comprising two first polypeptides and two second polypeptides,
- wherein each first polypeptide comprises, from N- to C-terminus, a heavy chain variable region (VH), a CH1, a CH2, a CH3, and a single chain fragment (scFv) having specificity to a 4-1BB protein;
- wherein each second polypeptide comprises a light chain variable region (VL) and a light chain constant region (CL);
- wherein each VH is paired with one of the VL and has specificity to a claudin 18.2 (CLDN18.2) protein;
- wherein the VH of the VH/VL pair comprises a CDRH1, a CDRH2, and a CDRH3, and the VL of the VH/VL pair comprises a CDRL1, a CDRL2 and a CDRL3, wherein:
- (a) the CDRH1 comprises the amino acid sequence of SEQ ID NO:7;
- the CDRH2 comprises the amino acid sequence of SEQ ID NO:8;
- the CDRH3 comprises the amino acid sequence of SEQ ID NO:9;
- the CDRL1 comprises the amino acid sequence of SEQ ID NO:10;
- the CDRL2 comprises the amino acid sequence of SEQ ID NO:11;
- and
- the CDRL3 comprises the amino acid sequence of SEQ ID NO:12;
- (b) the CDRH1 comprises the amino acid sequence of SEQ ID NO:13;
- the CDRH2 comprises the amino acid sequence of SEQ ID NO:14;
- the CDRH3 comprises the amino acid sequence of SEQ ID NO:15;
- the CDRL1 comprises the amino acid sequence of SEQ ID NO:16;
- the CDRL2 comprises the amino acid sequence of SEQ ID NO:
- 17;
- and
- the CDRL3 comprises the amino acid sequence of SEQ ID NO:
- 18;
- or
- (c) the CDRH1 comprises the amino acid sequence of SEQ ID NO:
- 19;
- the CDRH2 comprises the amino acid sequence of SEQ ID NO:20;
- the CDRH3 comprises the amino acid sequence of SEQ ID NO:21;
- the CDRL1 comprises the amino acid sequence of SEQ ID NO:22;
- the CDRL2 comprises the amino acid sequence of SEQ ID NO:
- 11;
- and
- the CDRL3 comprises the amino acid sequence of SEQ ID NO:23;
- and
- wherein the scFv comprises a heavy chain variable region (VH) comprising a CDRH1, a CDRH2, and a CDRH3, and a light chain variable region (VL) comprising a CDRL1, a CDRL2 and a CDRL3, wherein:
- the CDRH1 comprises the amino acid sequence of SEQ ID NO:60;
- the CDRH2 comprises the amino acid sequence of SEQ ID NO:61;
- the CDRH3 comprises the amino acid sequence of SEQ ID NO:62;
- the CDRL1 comprises the amino acid sequence of SEQ ID NO:4;
- the CDRL2 comprises the amino acid sequence of SEQ ID NO:5;
- and
- the CDRL3 comprises the amino acid sequence of SEQ ID NO:6.
36 more elements
Dependencies are inferred from the claim text.