Antibody binding to LAG3 and its uses

Abstract

The present invention provides an isolated monoclonal antibody that specifically binds to human LAG3 or an antigen-binding site thereof. Furthermore, the invention provides a nucleic acid molecule encoding the antibody or its antigen-binding site, an expression vector, a host cell, and a method for expressing the antibody or its antigen-binding site. Additionally, the present invention further provides an immunoconjugate comprising the antibody or its antigen-binding site, a bispecific molecule, a chimeric antigen receptor, and a pharmaceutical composition, as well as a therapeutic method using the same.

Claims

Claim 1 An isolated monoclonal antibody capable of binding to LAG3 or an antigen-binding site thereof comprising a heavy chain variable region including a VH CDR1 region, a VH CDR2 region, and a VH CDR3 region; and a light chain variable region including a VL CDR1 region, a VL CDR2 region, and a VL CDR3 region, wherein the VH CDR1 region, the VH CDR2 region, the VH CDR3 region, the VL CDR1 region, the VL CDR2 region, and the VL CDR3 region each comprise (1) the amino acid sequences described in SEQ ID NOs 1, 2, 3, 5, 6, and 7; (2) the amino acid sequences described in SEQ ID NOs 1, 2, 4, 5, 6, and 8; or (3) the amino acid sequences described in SEQ ID NOs 21, 22, 23, 24, 25, and 26, respectively. Claim 2 An antibody or an antigen-binding site thereof, wherein the heavy chain variable region comprises an amino acid sequence described in SEQ ID NO. 9, 10, 11, 12, 13, 14, 27, 28, 29, or 30, or retains the VH CDR1 region, VH CDR2 region, VH CDR3 region, VL CDR1 region, VL CDR2 region, and VL CDR3 region, but comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with respect to the amino acid sequence described in SEQ ID NO. 9, 10, 11, 12, 13, 14, 27, 28, 29, or 30. Claim 3 An antibody or its antigen-binding site, wherein the light chain variable region comprises an amino acid sequence described in SEQ ID NO. 15, 16, 17, 18, 19, 20, 31, 32, 33, or 34, or retains the VH CDR1 region, VH CDR2 region, VH CDR3 region, VL CDR1 region, VL CDR2 region, and VL CDR3 region, and comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with respect to the amino acid sequence described in SEQ ID NO. 15, 16, 17, 18, 19, 20, 31, 32, 33, or 34. Claim 4 In paragraph 2, the heavy chain variable region and the light chain variable region are (1) Sequence Nos. 9 and 15, respectively; (2) Sequence Nos. 10 and 16, respectively; (3) Sequence Nos. 11 and 17, respectively; (4) Sequence Nos. 11 and 19, respectively; (5) Sequence Nos. 12 and 17, respectively; (6) Sequence Nos. 12 and 19, respectively; (7) Sequence Nos. 13 and 18, respectively; (8) Sequence Nos. 13 and 20, respectively; (9) Sequence Nos. 14 and 20, respectively; (10) Sequence Nos. 27 and 31, respectively; (11) Sequence Nos. 28 and 32, respectively; (12) Sequence Nos. 29 and 33, respectively; (13) Sequence Nos. 29 and 34, respectively; (14) Sequence Nos. 30 and 33, respectively; or (15) an antibody or its antigen-binding site comprising the amino acid sequences described in SEQ ID NOs 30 and 34, respectively, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with respect thereto. Claim 5 An antibody or its antigen-binding site, comprising, in claim 1, a heavy chain constant region comprising the amino acid sequence described in SEQ ID NO. 35 connected to the heavy chain variable region, and / or a light chain constant region comprising the amino acid sequence described in SEQ ID NO. 36 connected to the light chain variable region. Claim 6 In paragraph 1, the antibody or its antigen-binding site, which is a mouse, chimeric, or humanized antibody or its antigen-binding site. Claim 7 An antibody according to any one of claims 1 to 6, or a nucleic acid molecule encoding an antigen-binding site thereof. Claim 8 An expression vector comprising a nucleic acid molecule according to claim 7. Claim 9 Isolated host cell comprising an expression vector according to paragraph 8. Claim 10 A pharmaceutical composition for treating solid tumors, comprising an antibody or an antigen-binding site thereof according to any one of claims 1 to 6, and a pharmaceutically acceptable carrier. Claim 11 A pharmaceutical composition comprising, in addition to an anti-tumor agent, an anti-tumor agent in claim 10. Claim 12 delete Claim 13 A pharmaceutical composition according to claim 10, wherein the solid tumor is colorectal adenocarcinoma, breast cancer, renal cell carcinoma, melanoma, pancreatic cancer, non-small cell lung cancer, glioblastoma, or gastric cancer. Claim 14 delete Claim 15 delete

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