# US 2025/0145718 A1 · Anti-pd-l1/anti-4-1bb bispecific antibodies and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2025/0145718 A1 - Document ID: US20250145718A1 - Status: Published application - Kind: A1 - Application number: 19/012,836 - Filed: 2025-01-07 - Published: 2025-05-08 - Earliest claimed: 2018-11-30 - Assignees: Abl Bio Inc.; I-Mab Biopharma US Limited - Applicants: Abl Bio Inc.; I-Mab Biopharma US Limited - Inventors: Eunyoung PARK; Yangsoon LEE; Hyejin CHUNG; Eunsil SUNG; Jiseon YOO; Minji PARK; Yong-Gyu SON; Hyoju CHOI; Eunjung KIM; Jaeho JUNG; Weon-Kyoo YOU; Sang Hoon LEE; Lei FANG; Wenqing JIANG - Web page: https://patentgrep.com/patent/US20250145718A1 ## CPC - C07K 16/2827: {against B7 molecules, e.g. CD80, CD86} - A61P 35/00: Antineoplastic agents - C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95} - C07K 16/468: {Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies} - A61K 2039/505: {comprising antibodies} - C07K 2317/21: from primates, e.g. man - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/31: multispecific - C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues - C07K 2317/565: Complementarity determining region [CDR] - C07K 2317/622: Single chain antibody (scFv) - C07K 2317/64: comprising a combination of variable region and constant region components - C07K 2317/75: Agonist effect on antigen - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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) ## Abstract The present disclosure provides a polynucleotide encoding the anti-PD-L1/anti-4-1BB bispecific antibody capable to effectively block the interactions between PD-L1 and its receptor PD-1 and between 4-1BB and its ligand. The bispecific antibody may have high binding affinity to both of a PD-L1 protein and a 4-1BB protein. ## Claims ### Claim 1 A polynucleotide encoding an anti-PD-L1/anti-4-1BB bispecific antibody, comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and an anti-4-1BB antibody or an antigen-binding fragment thereof, wherein the anti-PD-L1 antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 1; a VH CDR2 comprising the amino acid sequence selected from the group consisting of SEQ ID NOS: 2 and 3; a VH CDR3 comprising the amino acid sequence selected from the group consisting of SEQ ID NOS: 4, 5, 262, 263, 264, 265, 266 and 267; a VL CDR1 comprising the amino acid sequence selected from the group consisting of SEQ ID NOS: 6, 268 and 269; a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 7; and a VL CDR3 comprising the amino acid sequence selected from the group consisting of SEQ ID NOS: 8, 270, 271 and 272; and the anti-4-1BB antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence selected from the group consisting of SEQ ID NOS: 10 and 11; a VH CDR2 comprising the amino acid sequence selected from the group consisting of SEQ ID NOS: 12 and 13; a VH CDR3 comprising the amino acid sequence selected from the group consisting of SEQ ID NOS: 14, 15, 16 and 17; a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 18; a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 20. ### Claim 2 (depends on 1) The polynucleotide encoding the anti-PD-L1/anti-4-1BB bispecific antibody of claim 1, wherein the anti-PD-L1 antibody or antigen-binding fragment thereof is capable of specifically binding to an immunoglobulin C (Ig C) domain of a human Programmed death-ligand 1 (PD-L1) protein, wherein the Ig C domain consists of amino acid residues 133-225. ### Claim 3 (depends on 1) The polynucleotide encoding the anti-PD-L1/anti-4-1BB bispecific antibody of claim 1, wherein the anti-PD-L1 antibody or antigen-binding fragment thereof does not bind to an immunoglobulin V (Ig V) domain of the PD-L1 protein, wherein the Ig V domain consists of amino acid residues 19-127. ### Claim 4 (depends on 1) The polynucleotide encoding the anti-PD-L1/anti-4-1BB bispecific antibody of claim 1, wherein the anti-PD-L1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 103, and 104, or a polypeptide having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOS: 103, and 104. ### Claim 5 (depends on 1) The polynucleotide encoding the anti-PD-L1/anti-4-1BB bispecific antibody of claim 1, wherein the anti-PD-L1 antibody or antigen-binding fragment thereof comprises a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 105, and 106, or a peptide having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOS: 105, and 106. ### Claim 6 (depends on 1) The polynucleotide encoding the anti-PD-L1/anti-4-1BB bispecific antibody of claim 1, wherein the anti-4-1BB antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 21, 22, 23, and 24, or a polypeptide having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOS: 21, 22, 23, and 24. ### Claim 7 (depends on 1) The polynucleotide encoding the anti-PD-L1/anti-4-1BB bispecific antibody of claim 1, wherein the anti-4-1BB antibody or antigen-binding fragment thereof comprises a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 25 and 26, or a peptide having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOS: 25 and 26. ### Claim 8 (depends on 1) The polynucleotide encoding the anti-PD-L1/anti-4-1BB bispecific antibody of claim 1, which is in the form of IgG-scFv form. ### Claim 9 (depends on 1) A recombinant vector comprising the polynucleotide encoding the anti-PD-L1/anti-4-1BB bispecific antibody of claim 1. ### Claim 10 (depends on 9) A host cell comprising the recombinant vector of claim 9. ### Claim 11 (depends on 10) The host cell of claim 10, the host cell is a E. coli cell, simian COS cell, Chinese Hamster Ovary (CHO) cell or myeloma cell. ### Claim 12 (depends on 1) A method of preparing an anti-PD-L1/anti-4-1BB bispecific antibody, wherein the method comprises the step of expressing the polynucleotide of claim 1 in a cell. ### Claim 13 (depends on 12) The method of claim 12, wherein the step of expressing the polynucleotide comprises a step of culturing a host cell comprising a recombinant vector comprising a polynucleotide encoding an anti-PD-L1/anti-4-1BB bispecific antibody, comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and an anti-4-1BB antibody or an antigen-binding fragment thereof, wherein the anti-PD-L1 antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 1; a VH CDR2 comprising the amino acid sequence selected from the group consisting of SEQ ID NOS: 2 and 3; a VH CDR3 comprising the amino acid sequence selected from the group consisting of SEQ ID NOS: 4, 5, 262, 263, 264, 265, 266 and 267; a VL CDR1 comprising the amino acid sequence selected from the group consisting of SEQ ID NOS: 6, 268 and 269; a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 7; and a VL CDR3 comprising the amino acid sequence selected from the group consisting of SEQ ID NOS: 8, 270, 271 and 272; and the anti-4-1BB antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence selected from the group consisting of SEQ ID NOS: 10 and 11; a VH CDR2 comprising the amino acid sequence selected from the group consisting of SEQ ID NOS: 12 and 13; a VH CDR3 comprising the amino acid sequence selected from the group consisting of SEQ ID NOS: 14, 15, 16 and 17; a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 18; a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 20.