# US 2014/0193432 A1 · Anti-hdlk-1 antibody having an antitumor activity in vivo > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0193432 A1 - Document ID: US20140193432A1 - Status: Published application - Kind: A1 - Application number: 14/045,326 - Filed: 2013-10-03 - Published: 2014-07-10 - Earliest claimed: 2012-10-03 - Assignees: Livtech, Inc. - Applicants: Livtech, Inc. - Inventors: Koji NAKAMURA; Hiroyuki YANAI; Toru KANKE; Naoya TSURUSHITA; Shankar KUMAR - Web page: https://patentgrep.com/patent/US20140193432A1 ## CPC - C07K 16/28: against receptors, cell surface antigens or cell surface determinants - A61P 35/00: Antineoplastic agents - G01N 33/5759: {involving compounds localised on the membrane of tumour or cancer cells} - A61K 2039/505: {comprising antibodies} - A61K 2039/545: {characterised by the dose, timing or administration schedule} - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - 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 - 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) - 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 invention provides: antibodies specifically reacting against hDlk-1 and having anti-tumor activity in vivo (anti-hDlk-1 antibodies, and in particular, humanized anti-hDlk-1 antibodies); fragments of the antibodies; hybridomas that produce the antibodies; a complex of the antibody or antibody fragment and an agent; a pharmaceutical composition, a tumor therapeutic agent, a tumor diagnostic agent and an agent for inducing apoptosis in tumor cells, each of which comprises the aforementioned antibody or the like; a method for treating tumor, a method for detecting tumor, a method for inducing apoptosis in tumor cells, a kit for detecting and/or diagnosing tumor and a kit for inducing apoptosis in tumor cells, each of which comprises the use of the aforementioned antibody or the like; etc. ## Claims ### Claim 1 An antibody against human Dlk-1, wherein the amino acid sequence of the H chain V region comprises the amino acid sequence as shown in any one of SEQ ID NOS: 35, 40, 69, 73, 77, 81, 85 and 89, and the amino acid sequence of the L chain V region comprises the amino acid sequence as shown in SEQ ID NO: 45. ### Claim 2 (depends on 1) The antibody according to claim 1, which has an anti-tumor activity in vivo. ### Claim 3 (depends on 2) The antibody according to claim 2, wherein the tumor is at least one type selected from the group consisting of human colon cancer, human breast cancer, human liver cancer, human pancreatic cancer, human small cell lung cancer and human neuroblastoma. ### Claim 4 (depends on 1) The antibody according to claim 1 which is a humanized antibody. ### Claim 5 (depends on 1) The antibody according to claim 1, which is a monoclonal antibody. ### Claim 6 (depends on 1) The antibody according to claim 1, which binds to at least a portion of a region comprising amino acids at positions 24 to 91 in the amino acid sequence of human Dlk-1 as shown in SEQ ID NO: 2. ### Claim 7 (depends on 1) An antibody fragment derived from the antibody according to claim 1. ### Claim 8 (depends on 7) The antibody fragment according to claim 7, which comprises the amino acid sequence as shown in any one of SEQ ID NOS: 35, 40, 69, 73, 77, 81, 85 and 89. ### Claim 9 (depends on 7) The antibody fragment according to claim 7, which comprises the amino acid sequence as shown in SEQ ID NO: 45. ### Claim 10 (depends on 7) The antibody fragment according to claim 7, which comprises both the amino acid sequence as shown in any one of SEQ ID NOS: 35, 40, 69, 73, 77, 81, 85 and 89 and the amino acid sequence as shown in SEQ ID NO: 45. ### Claim 11 (depends on 1) An antibody-agent complex, which comprises the antibody according to claim 1 and a compound having an anti-tumor activity and/or a cell-killing activity. ### Claim 12 (depends on 7) An antibody fragment-agent complex, which comprises the antibody fragment according to claim 7 and a compound having an anti-tumor activity and/or a cell-killing activity. ### Claim 13 (depends on 1) A pharmaceutical composition, which comprises at least one type selected from the group consisting of: an antibody according to claim 1, an antibody fragment derived from an antibody according to claim 1, a complex comprising an antibody according to claim 1 and a compound having an anti-tumor activity and/or a cell-killing activity, and a complex comprising an antibody fragment derived from an antibody according to claim 1 and a compound having an anti-tumor activity and/or a cell-killing activity. ### Claim 14 (depends on 13) The composition according to claim 13, which is used in the treatment of tumor. ### Claim 15 (depends on 14) The composition according to claim 14, which does not cause weight reduction as a side effect. ### Claim 16 (depends on 13) The composition according to claim 13, which is used in the diagnosis of tumor. ### Claim 17 (depends on 13) The composition according to claim 13, which is used in induction of apoptosis in tumor cells. ### Claim 18 (depends on 4) The composition according to claim 4, wherein the tumor is at least one type selected from the group consisting of human colon cancer, human breast cancer, human liver cancer, human pancreatic cancer, human small cell lung cancer and human neuroblastoma. ### Claim 19 (depends on 1) A tumor therapeutic agent, which comprises at least one type selected from the group consisting of: an antibody according to claim 1, an antibody fragment derived from an antibody according to claim 1, a complex comprising an antibody according to claim 1 and a compound having an anti-tumor activity and/or a cell-killing activity, and a complex comprising an antibody fragment derived from an antibody according to claim 1 and a compound having an anti-tumor activity and/or a cell-killing activity. ### Claim 20 (depends on 19) The therapeutic agent according to claim 19, which does not cause weight reduction as a side effect. ### Claim 21 (depends on 19) The therapeutic agent according to claim 19, wherein the tumor is at least one type selected from the group consisting of human colon cancer, human breast cancer, human liver cancer, human pancreatic cancer, human small cell lung cancer and human neuroblastoma. ### Claim 22 (depends on 1) An agent for inducing apoptosis in tumor cells, which comprises at least one type selected from the group consisting of: an antibody according to claim 1, an antibody fragment derived from an antibody according to claim 1, a complex comprising an antibody according to claim 1 and a compound having an anti-tumor activity and/or a cell-killing activity, and a complex comprising an antibody fragment derived from an antibody according to claim 1 and a compound having an anti-tumor activity and/or a cell-killing activity. ### Claim 23 (depends on 22) The apoptosis-inducing agent according to claim 22, wherein the tumor is at least one type selected from the group consisting of human colon cancer, human breast cancer, human liver cancer, human pancreatic cancer, human small cell lung cancer and human neuroblastoma. ### Claim 24 (depends on 1) A method for treating a tumor, which comprises administering to a patient at least one type selected from the group consisting of: an antibody according to claim 1, an antibody fragment derived from an antibody according to claim 1, a complex comprising an antibody according to claim 1 and a compound having an anti-tumor activity and/or a cell-killing activity, and a complex comprising an antibody fragment derived from an antibody according to claim 1 and a compound having an anti-tumor activity and/or a cell-killing activity. ### Claim 25 (depends on 24) The method according to claim 24, which does not cause weight reduction as a side effect to the patient. ### Claim 26 (depends on 1) A method for detecting a tumor, which comprises: allowing at least one type selected from the group consisting of: an antibody according to claim 1, an antibody fragment derived from an antibody according to claim 1, a complex comprising an antibody according to claim 1 and a compound having an anti-tumor activity and/or a cell-killing activity, and a complex comprising an antibody fragment derived from an antibody according to claim 1 and a compound having an anti-tumor activity and/or a cell-killing activity, to react with a sample collected from a living body; and detecting a signal(s) of the reacted antibody and/or antibody fragment. ### Claim 27 (depends on 1) A method for inducing apoptosis in tumor cells, which comprises administering to a patient at least one type selected from the group consisting of: an antibody according to claim 1, an antibody fragment derived from an antibody according to claim 1, a complex comprising an antibody according to claim 1 and a compound having an anti-tumor activity and/or a cell-killing activity, and a complex comprising an antibody fragment derived from an antibody according to claim 1 and a compound having an anti-tumor activity and/or a cell-killing activity. ### Claim 28 (depends on 24) The method according to claim 24, wherein the tumor is at least one type selected from the group consisting of human colon cancer, human breast cancer, human liver cancer, human pancreatic cancer, human small cell lung cancer and human neuroblastoma. ### Claim 29 (depends on 1) A kit for treating, diagnosing, or detecting a tumor, which comprises at least one type selected from the group consisting of: an antibody according to claim 1, an antibody fragment derived from an antibody according to claim 1, a complex comprising an antibody according to claim 1 and a compound having an anti-tumor activity and/or a cell-killing activity, and a complex comprising an antibody fragment derived from an antibody according to claim 1 and a compound having an anti-tumor activity and/or a cell-killing activity. ### Claim 30 (depends on 1) A kit for inducing apoptosis in tumor cells, which comprises at least one type selected from the group consisting of: an antibody according to claim 1, an antibody fragment derived from an antibody according to claim 1, a complex comprising an antibody according to claim 1 and a compound having an anti-tumor activity and/or a cell-killing activity, and a complex comprising an antibody fragment derived from an antibody according to claim 1 and a compound having an anti-tumor activity and/or a cell-killing activity. ### Claim 31 (depends on 29) The kit according to claim 29, wherein the tumor is at least one type selected from the group consisting of human colon cancer, human breast cancer, human liver cancer, human pancreatic cancer, human small cell lung cancer and human neuroblastoma.