# US 11,306,141 B2 · Antibody against human DLK1 and use thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,306,141 B2 - Document ID: US11306141B2 - Status: Granted - Kind: B2 - Application number: 16/644,764 - Filed: 2018-09-10 - Published: 2021-07-15 - Granted: 2022-04-19 - Earliest claimed: 2017-09-08 - Assignees: Y-Biologics Inc. - Applicants: Y-Biologics Inc. - Inventors: Jung Chae Lim; Ji-Young Shin; Sunha Yoon; Sang Pil Lee; Yunseon Choi; Jisu Lee; Young-Gyu Cho; Seok Ho Yoo; Yeung chul Kim; Si Hyung Lee; Jae Eun Park; Youngja Song; Gi Sun Baek; Bum-chan Park; Young Woo Park - Web page: https://patentgrep.com/patent/US11306141B2 ## CPC - C07K 16/28: against receptors, cell surface antigens or cell surface determinants - A61K 47/68: the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment - A61K 47/6801: {Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent} - A61P 35/00: Antineoplastic agents - C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)} - G01N 33/575: for cancer - C07K 2317/21: from primates, e.g. man - C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity - C07K 2317/622: Single chain antibody (scFv) - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - C07K 2317/77: Internalization into the cell - 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 - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract The present invention relates to an antibody against delta-like 1 homolog (Drosophila) (DLK1) or an antigen-binding fragment thereof, a nucleic acid encoding the same, a vector comprising the nucleic acid, a cell transformed with the vector, a method for producing the antibody or an antigen-binding fragment thereof, an antibody drug conjugate (ADC) comprising the same, a pharmaceutical composition for treating cancer, a composition for diagnosing cancer, and a chimeric antigen receptor (CAR) and a T-cell engager comprising the same. ## Claims ### Claim 1 An antibody or an antigen-binding fragment thereof specifically binding to delta-like 1 homolog (DLK1), comprising the following heavy-chain variable region and light-chain variable region: a heavy-chain variable region comprising heavy-chain CDR1 of SEQ ID. NO: 16, heavy-chain CDR2 of SEQ ID. NO: 18, heavy-chain CDR3 of SEQ ID. NO: 20, a light-chain variable region comprising light-chain CDR1 of SEQ ID. NO: 23, light-chain CDR2 of SEQ ID. NO: 25, light-chain CDR3 of SEQ ID. NO: 27, a heavy-chain variable region comprising heavy-chain CDR1 of SEQ ID. NO: 72, heavy-chain CDR2 of SEQ ID. NO: 74, heavy-chain CDR3 of SEQ ID. NO: 76, a light-chain variable region comprising light-chain CDR1 of SEQ ID. NO: 79, light-chain CDR2 of SEQ ID. NO: 81, light-chain CDR3 of SEQ ID. NO: 83, a heavy-chain variable region comprising heavy-chain CDR1 of SEQ ID. NO: 16, heavy-chain CDR2 of SEQ ID. NO: 18, heavy-chain CDR3 of SEQ ID. NO: 20, a light-chain variable region comprising light-chain CDR1 of SEQ ID. NO: 115, light-chain CDR2 of SEQ ID. NO: 95, light-chain CDR3 of SEQ ID. NO: 116, or a heavy-chain variable region comprising heavy-chain CDR1 of SEQ ID. NO: 16, heavy-chain CDR2 of SEQ ID. NO: 18, heavy-chain CDR3 of SEQ ID. NO: 20, a light-chain variable region comprising light-chain CDR1 of SEQ ID. NO: 121, light-chain CDR2 of SEQ ID. NO: 39, light-chain CDR3 of SEQ ID. NO: 124. ### Claim 2 (depends on 1) The antibody or an antigen-binding fragment thereof according to claim 1, comprising: heavy chain FR1 selected from the group consisting of SEQ ID NOS: 1, 15, 29, 43, 57, 71, 85, and 119; heavy chain FR2 selected from the group consisting of SEQ ID NOS: 3, 17, 31, 45, 59, 73, and 87; heavy chain FR3 selected from the group consisting of SEQ ID NOS: 5, 19, 33, 47, 61, 75, and 89; heavy chain FR4 selected from the group consisting of SEQ ID NOS: 7, 21, 35, 49, 63, 77, and 91; light chain FR1 selected from the group consisting of SEQ ID NOS: 8, 22, 36, 50, 64, 78, 92, 117, and 120; light chain FR2 selected from the group consisting of SEQ ID NOS: 10, 24, 38, 52, 66, 80, 94, and 122; light chain FR3 selected from the group SEQ ID NOS: 12, 26, 40, 54, 68, 82, 96, 118, and 123; or light chain FR4 selected from the group consisting of SEQ ID NO: 14, 28, 42, 56, 70, 84, 98, and 125. ### Claim 3 (depends on 1) The antibody or an antigen-binding fragment thereof according to claim 1, comprising a heavy-chain variable region having a sequence selected from the group consisting of SEQ ID NOS: 101, 109, and 127. ### Claim 4 (depends on 1) The antibody or an antigen-binding fragment thereof according to claim 1, comprising a light-chain variable region having a sequence selected from the group consisting of SEQ ID NOS: 102, 110, 126, and 128. ### Claim 5 (depends on 1) A nucleic acid encoding the antibody or an antigen-binding fragment thereof according to claim 1. ### Claim 6 (depends on 5) An expression vector comprising the nucleic acid according to claim 5. ### Claim 7 (depends on 6) A cell transformed with the expression vector according to claim 6. ### Claim 8 (depends on 7) A method of producing an antibody or an antigen-binding fragment thereof specifically binding to DLK1 comprising: (a) culturing the cells according to claim 7; and (b) recovering an antibody or an antigen-binding fragment thereof from the cell culture. ### Claim 9 (depends on 1) An antibody-drug conjugate (ADC) comprising the antibody or an antigen-binding fragment thereof according to claim 1, and a drug. ### Claim 10 (depends on 9) The antibody-drug conjugate (ADC) according to claim 9, wherein the drug is selected from the group consisting of cytotoxins, radioisotopes, antiproliferative agents, pro-apoptotic agents, chemotherapeutic agents, and therapeutic nucleic acids. ### Claim 11 (depends on 9) A pharmaceutical composition comprising, as an active ingredient, the antibody or an antigen-binding fragment thereof according to the antibody-drug conjugate according to claim 9. ### Claim 12 (depends on 1) A bispecific antibody comprising the antibody or an antigen-binding fragment thereof according to claim 1. ### Claim 13 (depends on 12) A pharmaceutical composition comprising, as an active ingredient, the antibody or an antigen-binding fragment thereof according to the bispecific antibody according to claim 12. ### Claim 14 (depends on 1) A pharmaceutical composition comprising, as an active ingredient, the antibody or an antigen-binding fragment thereof according to claim 1. ### Claim 15 (depends on 1) A chimeric antigen receptor (CAR) comprising the antibody or an antigen-binding fragment thereof according to claim 1 as an antigen-binding domain. ### Claim 16 (depends on 1) A T-cell engager comprising the antibody or an antigen-binding fragment thereof according to claim 1, specifically binding to DLK1 expressed in tumor cells. ### Claim 17 (depends on 1) The antibody or an antigen-binding fragment thereof according to claim 1, comprising a heavy-chain variable region including a sequence of SEQ ID NO: 101, and a light-chain variable region including a sequence of SEQ ID NO: 102, a heavy-chain variable region including a sequence of SEQ ID NO: 109, and a light-chain variable region including a sequence of SEQ ID NO: 110, a heavy-chain variable region including a sequence of SEQ ID NO: 101, and a light-chain variable region including a sequence of SEQ ID NO: 126, or a heavy-chain variable region including a sequence of SEQ ID NO: 127, and a light-chain variable region including a sequence of SEQ ID NO: 128.