# US 12,110,329 B2 · Anti-BTLA antibody > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,110,329 B2 - Document ID: US12110329B2 - Status: Granted - Kind: B2 - Application number: 17/164,597 - Filed: 2021-02-01 - Published: 2021-08-12 - Granted: 2024-10-08 - Earliest claimed: 2018-08-02 - Assignees: Shanghai Junshi Biosciences Co., Ltd.; Junmeng Biosciences Co., Ltd. - Applicants: Shanghai Junshi Biosciences Co., Ltd.; Junmeng Biosciences Co., Ltd. - Inventors: Hai Wu; Jian Yao; Sheng Yao; Hui Feng; Jing Zhang; Yuehua Zhou - Web page: https://patentgrep.com/patent/US12110329B2 ## CPC - C07K 16/2818: {against CD28 or CD152} - A61K 47/6803: {Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates} - A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant} - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - A61P 35/00: Antineoplastic agents - A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection - A61K 2039/505: {comprising antibodies} - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity - C07K 2317/565: Complementarity determining region [CDR] - C07K 2317/74: Inducing cell proliferation - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to an anti-BTLA antibody or an antigen-binding fragment thereof comprising: at least one light chain CDR domain selected from SEQ ID NOs: 7, 8, 9, 10, 11, 12, 16, 17, 18, 22, 23, 24, 31, 32 and 33, and/or at least one heavy chain CDR domain selected from SEQ ID NOs: 1, 2, 3, 4, 5, 6, 13, 14, 15, 19, 20, 21, 25, 26, 27, 28, 29 and 30. The present invention also relates to a nucleic acid molecule encoding the antibody or the antigen-binding fragment thereof, a corresponding expression vector and a host cell, as well as therapeutic use of the antibody or the antigen-binding fragment thereof, the nucleic acid molecule, the expression vector and the host cell. ## Claims ### Claim 1 An isolated anti-BTLA antibody or an antigen-binding fragment thereof wherein the amino acid sequences of the LCDR1, LCDR2 and LCDR3 of the light chain CDR and the amino acid sequences of the HCDR1, HCDR2 and HCDR3 of the heavy chain CDR of the isolated antibody or the antigen-binding fragment thereof are selected from any one of the following groups I-IX: Group LCDR1 LCDR2 LCDR3 I SEQ ID NO: 7 SEQ ID NO: 8 SEQ ID NO: 9 II SEQ ID NO: 10 SEQ ID NO: 11 SEQ ID NO: 12 III SEQ ID NO: 16 SEQ ID NO: 17 SEQ ID NO: 18 IV SEQ ID NO: 22 SEQ ID NO: 23 SEQ ID NO: 24 V SEQ ID NO: 22 SEQ ID NO: 23 SEQ ID NO: 24 VI SEQ ID NO: 31 SEQ ID NO: 32 SEQ ID NO: 33 VII SEQ ID NO: 7 SEQ ID NO: 8 SEQ ID NO: 9 VIII SEQ ID NO: 10 SEQ ID NO: 11 SEQ ID NO: 12 IX SEQ ID NO: 10 SEQ ID NO: 11 SEQ ID NO: 12 Group HCDR1 HCDR2 HCDR3 I SEQ ID NO: 1 SEQ ID NO: 2 SEQ ID NO: 3 II SEQ ID NO: 4 SEQ ID NO: 5 SEQ ID NO: 6 III SEQ ID NO: 13 SEQ ID NO: 14 SEQ ID NO: 15 IV SEQ ID NO: 19 SEQ ID NO: 20 SEQ ID NO: 21 V SEQ ID NO: 25 SEQ ID NO: 26 SEQ ID NO: 27 VI SEQ ID NO: 28 SEQ ID NO: 29 SEQ ID NO: 30 VII SEQ ID NO: 4 SEQ ID NO: 5 SEQ ID NO: 6 VIII SEQ ID NO: 1 SEQ ID NO: 2 SEQ ID NO: 3 IX SEQ ID NO: 13 SEQ ID NO: 14 SEQ ID NO: 15. ### Claim 2 (depends on 1) The anti-BTLA antibody or the antigen-binding fragment thereof according to claim 1, comprising: a light chain variable region having an amino acid sequence selected from any one of amino acid sequences set forth in SEQ ID NOs: 36, 37, 39, 41, 44, 46, 47 and 48; and a heavy chain variable region having an amino acid sequence selected from any one of amino acid sequences set forth in SEQ ID NOs: 34, 35, 38, 40, 42, 43 and 45. ### Claim 3 (depends on 2) The anti-BTLA antibody or the antigen-binding fragment thereof according to claim 2, wherein, the light chain variable region of the isolated antibody or the antigen-binding fragment thereof comprises an amino acid sequence set forth in SEQ ID NO: 36, and the heavy chain variable region comprises an amino acid sequence set forth in SEQ ID NO: 34 or 35; the light chain variable region of the isolated antibody or the antigen-binding fragment thereof comprises an amino acid sequence set forth in SEQ ID NO: 37, and the heavy chain variable region comprises an amino acid sequence set forth in SEQ ID NO: 34 or 35; the light chain variable region of the isolated antibody or the antigen-binding fragment thereof comprises an amino acid sequence set forth in SEQ ID NO: 39, and the heavy chain variable region comprises an amino acid sequence set forth in SEQ ID NO: 38; the light chain variable region of the isolated antibody or the antigen-binding fragment thereof comprises an amino acid sequence set forth in SEQ ID NO: 41, and the heavy chain variable region comprises an amino acid sequence set forth in SEQ ID NO: 40 or 42; the light chain variable region of the isolated antibody or the antigen-binding fragment thereof comprises an amino acid sequence set forth in SEQ ID NO: 44, and the heavy chain variable region comprises an amino acid sequence set forth in SEQ ID NO: 43; or the light chain variable region of the isolated antibody or the antigen-binding fragment thereof comprises an amino acid sequence set forth in SEQ ID NO: 46, 47 or 48, and the heavy chain variable region comprises an amino acid sequence set forth in SEQ ID NO: 45. ### Claim 4 (depends on 1) The anti-BTLA antibody or the antigen-binding fragment thereof according to claim 1, wherein the antibody is a chimeric antibody, or a humanized antibody. ### Claim 5 (depends on 1) An isolated nucleic acid molecule, comprising (1) a polynucleotide sequence encoding the anti-BTLA antibody or the antigen-binding fragment thereof according to claim 1, and (2) a complementary sequence of the polynucleotide sequence of (1). ### Claim 6 (depends on 5) The isolated nucleic acid molecule of claim 5, wherein the light chain variable region of the antibody or the antigen-binding fragment thereof comprises an amino acid sequence as set forth in SEQ ID NO: 46, 47 or 48; and the heavy chain variable region of the antibody or the antigen-binding fragment thereof comprises an amino acid sequence as set forth in SEQ ID NO: 45. ### Claim 7 (depends on 5) An expression vector comprising the isolated nucleic acid molecule according to claim 5. ### Claim 8 (depends on 7) The expression vector of claim 7 comprising the nucleic acid molecule encoding an antibody comprising a heavy chain variable region selected from the amino acid sequence of SEQ ID NO: 45, and a light chain variable region selected from the group consisting of the amino acid sequence of SEQ ID NO: 46, SEQ ID NO: 47 and SEQ ID NO: 48, or an antigen-binding fragment thereof. ### Claim 9 (depends on 5) A host cell comprising the nucleic acid molecule according to claim 5. ### Claim 10 (depends on 9) The host cell of claim 9 comprising the nucleic acid molecule encoding an antibody comprising a heavy chain variable region selected from the amino acid sequence of SEQ ID NO: 45, and a light chain variable region selected from the group consisting of the amino acid sequence of SEQ ID NO: 46, SEQ ID NO: 47 and SEQ ID NO: 48, or an antigen-binding fragment thereof. ### Claim 11 (depends on 1) A pharmaceutical composition comprising the anti-BTLA antibody or the antigen-binding fragment thereof according to claim 1, a nucleic acid molecule encoding the antibody or the antigen-binding fragment thereof, an expression vector comprising the nucleic acid molecule, or a host cell comprising the nucleic acid molecule or the expression vector, or any combination thereof; and a pharmaceutically acceptable carrier. ### Claim 12 (depends on 1) A method for treating a BTLA-mediated disease by eliminating, inhibiting, or reducing BTLA activity, comprising administering to a subject in need thereof a therapeutically effective amount of antibodies or the antigen-binding fragments thereof of claim 1, or an nucleic acid molecule encoding the antibody or the antigen-binding fragment thereof, an expression vector comprising the nucleic acid molecule, or a host cell comprising the nucleic acid molecule or the expression vector, an immunoconjugate comprising the antibody an antigen-binding fragment thereof, or a pharmaceutical composition comprising the antibody or the antigen-binding fragment thereof, the expression vector, the host cell or the immunoconjugate, wherein the BTLA-mediated disease is a cancer. ### Claim 13 (depends on 1) An immunoconjugate comprising the antibody or an antigen-binding fragment thereof according to claim 1 conjugated with a therapeutic agent. ### Claim 14 (depends on 13) The immunoconjugate of claim 13, wherein the antibody comprises a heavy chain variable region selected from the amino acid sequence of SEQ ID NO: 45, and a light chain variable region selected from the group consisting of the amino acid sequence of SEQ ID NO: 46, SEQ ID NO: 47 and SEQ ID NO: 48. ### Claim 15 (depends on 13) The immunoconjugate of claim 13, wherein the therapeutic agent is a toxin, a radioisotope, or a cytotoxic agent.