# US 11,111,300 B2 · Anti PD-L1 antibodies > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,111,300 B2 - Document ID: US11111300B2 - Status: Granted - Kind: B2 - Application number: 16/538,440 - Filed: 2019-08-12 - Published: 2020-01-30 - Granted: 2021-09-07 - Earliest claimed: 2014-08-05 - Assignees: Apollomics Inc. - Applicants: CB Therapeutics, Inc. - Inventors: Jiping Zha; Ziyong Sun; Junzhuan Qiu - Web page: https://patentgrep.com/patent/US11111300B2 ## CPC - C07K 16/2827: {against B7 molecules, e.g. CD80, CD86} - A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant} - A61P 31/04: Antibacterial agents - A61P 31/06: for tuberculosis - A61P 31/10: Antimycotics - A61P 31/12: Antivirals - A61P 31/16: for influenza or rhinoviruses - A61P 33/00: Antiparasitic agents - A61P 33/06: Antimalarials - A61P 33/12: Schistosomicides - A61P 35/00: Antineoplastic agents - A61P 35/02: specific for leukemia - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - 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 disclosure relates to antibodies and antigen-binding fragments thereof that bind to PD-L1, and to methods of using such antibodies and antigen-binding fragments. For example, the present invention provides humanized anti-PD-L1 antibodies and methods of use thereof. ## Claims ### Claim 1 A method for treating a PD-L1 expressing cancer in a human subject having the PD-L1 expressing cancer, the method comprising administering to the subject an antibody or fragment thereof that binds to PD-L1, wherein the antibody or fragment thereof comprises: (i) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 93, 94, and 95, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 96, 97, and 98, respectively; (ii) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 81, 82, and 83, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 84, 85, and 86, respectively; (iii) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 87, 88, and 89, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 90, 91, and 92, respectively; (iv) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 99, 100, and 101, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 102, 103, and 104, respectively; (v) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 105, 106, and 107, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 108, 109, and 110, respectively; (vi) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 111, 112, and 113, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 114, 115, and 116, respectively; (vii) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 117, 118, and 119, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 120, 121, and 122, respectively; (viii) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 123, 124, and 125, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 126, 127, and 128, respectively; (ix) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 129, 130, and 131, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 132, 133, and 134, respectively; or (x) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 135, 136, and 137, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 138, 139, and 140, respectively. ### Claim 2 (depends on 1) The method of claim 1, wherein the antibody or fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 93, 94, and 95, respectively; and a light chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 96, 97, and 98, respectively. ### Claim 3 (depends on 1) The method of claim 1, wherein the antibody or fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 81, 82, and 83, respectively; and a light chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 84, 85, and 86, respectively. ### Claim 4 (depends on 1) The method of claim 1, wherein the antibody or fragment thereof is humanized. ### Claim 5 (depends on 1) The method of claim 1, wherein the antibody or fragment thereof comprises (i) a heavy chain variable region comprising SEQ ID NO:10 and a light chain variable region comprising SEQ ID NO: 12; (ii) a heavy chain variable region comprising SEQ ID NO: 2 and a light chain variable region comprising SEQ ID NO: 4; (iii) a heavy chain variable region comprising SEQ ID NO: 6 and a light chain variable region comprising SEQ ID NO: 8; (iv) a heavy chain variable region comprising SEQ ID NO: 14 and a light chain variable region comprising SEQ ID NO: 16; (v) a heavy chain variable region comprising SEQ ID NO: 18 and a light chain variable region comprising SEQ ID NO: 20; (vi) a heavy chain variable region comprising SEQ ID NO: 22 and a light chain variable region comprising SEQ ID NO: 24; (vii) a heavy chain variable region comprising SEQ ID NO: 26 and a light chain variable region comprising SEQ ID NO: 28; (viii) a heavy chain variable region comprising SEQ ID NO: 30 and a light chain variable region comprising SEQ ID NO: 32; (ix) a heavy chain variable region comprising SEQ ID NO: 34 and a light chain variable region comprising SEQ ID NO: 36; (x) a heavy chain variable region comprising SEQ ID NO: 38 and a light chain variable region comprising SEQ ID NO: 40; (xi) a heavy chain variable region comprising SEQ ID NO: 42 and a light chain variable region comprising SEQ ID NO: 44; or (xii) a heavy chain variable region comprising SEQ ID NO: 46 and a light chain variable region comprising SEQ ID NO: 48. ### Claim 6 (depends on 1) The method of claim 1, wherein the antibody or fragment thereof comprises a heavy chain variable region according to SEQ ID NO: 42 and a light chain variable region according to SEQ ID NO: 44. ### Claim 7 (depends on 1) The method of claim 1, wherein the antibody or fragment thereof comprises a heavy chain variable region according to SEQ ID NO: 46 and a light chain variable region according to SEQ ID NO: 48. ### Claim 8 (depends on 1) The method claim 1, wherein the antibody or fragment thereof comprises a heavy chain according to SEQ ID NO: 70 and a light chain according to SEQ ID NO: 74. ### Claim 9 (depends on 1) The method of claim 1, wherein the antibody or fragment thereof comprises a heavy chain according to SEQ ID NO: 72 and a light chain according to SEQ ID NO: 74. ### Claim 10 (depends on 1) The method of claim 1, wherein the antibody or fragment thereof comprises a heavy chain according to SEQ ID NO: 76 and a light chain according to SEQ ID NO: 80. ### Claim 11 (depends on 1) The method of claim 1, wherein the antibody or fragment thereof comprises a heavy chain according to SEQ ID NO: 78 and a light chain according to SEQ ID NO: 80. ### Claim 12 (depends on 1) The method of claim 1, wherein the antibody or fragment thereof is selected from the group consisting of a monoclonal antibody, an scFv, a Fab fragment, an Fab′ fragment, and an F(ab)′ fragment. ### Claim 13 (depends on 1) The method of claim 1, wherein the antibody or fragment thereof is linked or conjugated to a therapeutic agent. ### Claim 14 (depends on 13) The method of claim 13, wherein the therapeutic agent is a cytotoxic drug, a radioactive isotope, an immunomodulator, or an antibody. ### Claim 15 (depends on 1) The method of claim 1, wherein the method further comprises administering the antibody or fragment thereof to the subject in combination with an additional therapeutic agent. ### Claim 16 (depends on 1) The method of claim 1, wherein the cancer is selected from the group consisting of lymphoma, leukemia, melanoma, glioma, breast cancer, lung cancer, colon cancer, bone cancer, ovarian cancer, bladder cancer, kidney cancer, liver cancer, stomach cancer, rectal cancer, testicular cancer, salivary cancer, thyroid cancer, thymic cancer, epithelial cancer, head or neck cancer, gastric cancer, and pancreatic cancer; or any combination thereof. ### Claim 17 A method for reducing PD-L1 expressing tumors or inhibiting the growth of PD-L1 expressing tumor cells in a subject, the method comprising administering to the subject an antibody or fragment thereof that binds to PD-L1, wherein the antibody or fragment thereof comprises: (i) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 93, 94, and 95, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 96, 97, and 98, respectively; (ii) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 81, 82, and 83, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 84, 85, and 86, respectively; (iii) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 87, 88, and 89, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 90, 91, and 92, respectively; (iv) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 99, 100, and 101, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 102, 103, and 104, respectively; (v) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 105, 106, and 107, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 108, 109, and 110, respectively; (vi) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 111, 112, and 113, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 114, 115, and 116, respectively; (vii) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 117, 118, and 119, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 120, 121, and 122, respectively; (viii) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 123, 124, and 125, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 126, 127, and 128, respectively; (ix) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 129, 130, and 131, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 132, 133, and 134, respectively; or (x) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 135, 136, and 137, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 138, 139, and 140, respectively. ### Claim 18 (depends on 17) The method of claim 17, wherein the antibody or fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 93, 94, and 95, respectively; and a light chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 96, 97, and 98, respectively. ### Claim 19 (depends on 17) The method of claim 17, wherein the antibody or fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 81, 82, and 83, respectively; and a light chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 84, 85, and 86, respectively. ### Claim 20 (depends on 17) The method of claim 17, wherein the antibody or fragment thereof is humanized. ### Claim 21 (depends on 17) The method of claim 17, wherein the antibody or fragment thereof comprises (i) a heavy chain variable region comprising SEQ ID NO:10 and a light chain variable region comprising SEQ ID NO: 12; (ii) a heavy chain variable region comprising SEQ ID NO: 2 and a light chain variable region comprising SEQ ID NO: 4; (iii) a heavy chain variable region comprising SEQ ID NO: 6 and a light chain variable region comprising SEQ ID NO: 8; (iv) a heavy chain variable region comprising SEQ ID NO: 14 and a light chain variable region comprising SEQ ID NO: 16; (v) a heavy chain variable region comprising SEQ ID NO: 18 and a light chain variable region comprising SEQ ID NO: 20; (vi) a heavy chain variable region comprising SEQ ID NO: 22 and a light chain variable region comprising SEQ ID NO: 24; (vii) a heavy chain variable region comprising SEQ ID NO: 26 and a light chain variable region comprising SEQ ID NO: 28; (viii) a heavy chain variable region comprising SEQ ID NO: 30 and a light chain variable region comprising SEQ ID NO: 32; (ix) a heavy chain variable region comprising SEQ ID NO: 34 and a light chain variable region comprising SEQ ID NO: 36; (x) a heavy chain variable region comprising SEQ ID NO: 38 and a light chain variable region comprising SEQ ID NO: 40; (xi) a heavy chain variable region comprising SEQ ID NO: 42 and a light chain variable region comprising SEQ ID NO: 44; or (xii) a heavy chain variable region comprising SEQ ID NO: 46 and a light chain variable region comprising SEQ ID NO: 48. ### Claim 22 (depends on 17) The method of claim 17, wherein the antibody or fragment thereof comprises a heavy chain variable region according to SEQ ID NO: 42 and a light chain variable region according to SEQ ID NO: 44. ### Claim 23 (depends on 17) The method of claim 17, wherein the antibody or fragment thereof comprises a heavy chain variable region according to SEQ ID NO: 46 and a light chain variable region according to SEQ ID NO: 48. ### Claim 24 (depends on 17) The method claim 17, wherein the antibody or fragment thereof comprises a heavy chain according to SEQ ID NO: 70 and a light chain according to SEQ ID NO: 74. ### Claim 25 (depends on 17) The method of claim 17, wherein the antibody or fragment thereof comprises a heavy chain according to SEQ ID NO: 72 and a light chain according to SEQ ID NO: 74. ### Claim 26 (depends on 17) The method of claim 17, wherein the antibody or fragment thereof comprises a heavy chain according to SEQ ID NO: 76 and a light chain according to SEQ ID NO: 80. ### Claim 27 (depends on 1) The method of claim 1, wherein the antibody or fragment thereof comprises a heavy chain according to SEQ ID NO: 78 and a light chain according to SEQ ID NO: 80. ### Claim 28 (depends on 17) The method of claim 17, wherein the antibody or fragment thereof is selected from the group consisting of a monoclonal antibody, an scFv, a Fab fragment, an Fab′ fragment, and an F(ab)′ fragment. ### Claim 29 (depends on 17) The method of claim 17, wherein the antibody or fragment thereof is linked or conjugated to a therapeutic agent. ### Claim 30 (depends on 29) The method of claim 29, wherein the therapeutic agent is a cytotoxic drug, a radioactive isotope, an immunomodulator, or an antibody. ### Claim 31 (depends on 17) The method of claim 17, wherein the method further comprises administering the antibody or fragment thereof to the subject in combination with an additional therapeutic agent.