# US 2020/0399373 A1 · Antigen-binding molecule and combination > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2020/0399373 A1 - Document ID: US20200399373A1 - Status: Published application - Kind: A1 - Application number: 16/968,633 - Filed: 2019-02-14 - Published: 2020-12-24 - Earliest claimed: 2018-02-14 - Applicants: Chugai Seiyaku Kabushiki Kaisha - Inventors: Tomoyuki IGAWA; Naoka HIRONIWA; Shogo KAMIKAWAJI; Tatsuya KIBAYASHI; Nasa SAVORY; Futa MIMOTO - Web page: https://patentgrep.com/patent/US20200399373A1 ## CPC - C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex} - C07K 16/4208: {against an idiotypic determinant on Ig} - A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells - A61K 40/4202: {Receptors, cell surface antigens or cell surface determinants} - A61K 40/4205: {Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ ErbB4} - A61K 40/4261: {Proteoglycans, e.g. glypican, brevican or CSPG4} - C07K 16/2815: {against CD8} - C07K 16/303: {Liver or Pancreas} - C07K 16/32: against translation products of oncogenes - C07K 16/44: against material not provided for elsewhere {, e.g. haptens, metals, DNA, RNA, amino acids} - C12N 5/0634: {Cells from the blood or the immune system} - A61K 2239/31: characterized by the route of administration - A61K 2239/38: characterised by the dose, timing or administration schedule - C07K 2317/30: characterized by aspects of specificity or valency - C07K 2317/31: multispecific - C07K 2317/55: Fab or Fab' - C07K 2317/70: characterized by effect upon binding to a cell or to an 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) - 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) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract The present invention relates to a first antigen-binding molecule, a second antigen-binding molecule, and a combination thereof. The second antigen-binding molecule binds to an antigen/antigen-binding molecule complex containing a first antigen and the first antigen-binding molecule, and enhances the binding activity of the first antigen-binding molecule to the first antigen. ## Claims ### Claim 1 A second antigen-binding molecule, which binds to an antigen/antigen-binding molecule complex comprising a first antigen and a first antigen-binding molecule that binds to the first antigen, and enhances the binding activity of the first antigen-binding molecule to the first antigen. ### Claim 2 (depends on 1) The second antigen-binding molecule of claim 1, which has higher binding activity to the first antigen in the presence of the first antigen-binding molecule than in the absence of the first antigen-binding molecule. ### Claim 3 (depends on 1, 2) The second antigen-binding molecule of claim 1 or claim 2, wherein the first antigen is an immune-related molecule or a cellular metabolite. ### Claim 4 (depends on 3) The second antigen-binding molecule of claim 3, wherein the immune-related molecule is a molecule present on the cell membrane of an immune cell. ### Claim 5 (depends on 4) The second antigen-binding molecule of claim 4, wherein the immune cell is at least one selected from the group consisting of a granulocyte, a macrophage, a dendritic cell, a T cell, and a B cell. ### Claim 6 (depends on 3, 4, 5) The second antigen-binding molecule of any one of claims 3 to 5, wherein the immune-related molecule is CD3. ### Claim 7 (depends on 6) The second antigen-binding molecule of claim 6, wherein the first antigen-binding molecule comprises: a CD3-binding polypeptide consisting of any combination of heavy chain variable region and light chain variable region amino acid sequences selected from SEQ ID NO: 1 and SEQ ID NO: 122, SEQ ID NO: 114 and SEQ ID NO:115, SEQ ID NO: 116 and SEQ ID NO: 117, SEQ ID NO: 118 and SEQ ID NO: 119, and SEQ ID NO: 120 and SEQ ID NO: 121, respectively; or a first modified polypeptide produced by modifying the CD3-binding polypeptide, wherein the CD3-binding activity of the first modified polypeptide is lower than that of the CD3-binding polypeptide. ### Claim 8 (depends on 3) The second antigen-binding molecule of claim 3, wherein the cellular metabolite is adenosine or a derivative thereof. ### Claim 9 (depends on 8) The second antigen-binding molecule of claim 8, wherein the first antigen-binding molecule comprises: an adenosine-binding polypeptide consisting of any combination of heavy chain variable region and light chain variable region amino acid sequences selected from SEQ ID NO: 106 and SEQ ID NO: 107, SEQ ID NO: 108 and SEQ ID NO:109, SEQ ID NO: 110 and SEQ ID NO: 111, and SEQ ID NO: 112 and SEQ ID NO: 113, respectively; or a second modified polypeptide produced by modifying the adenosine-binding polypeptide, wherein the adenosine-binding activity of the second modified polypeptide is lower or higher than that of the adenosine-binding polypeptide. ### Claim 10 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9) The second antigen-binding molecule of any one of claims 1 to 9, wherein the first antigen-binding molecule has multiple antigen specificity and further binds to at least a second antigen. ### Claim 11 (depends on 10) The second antigen-binding molecule of claim 10, wherein the second antigen is a cancer antigen or an immune-related molecule. ### Claim 12 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11) The second antigen-binding molecule of any one of claims 1 to 11, which has multiple antigen specificity and further binds to at least a third antigen. ### Claim 13 (depends on 12) The second antigen-binding molecule of claim 12, wherein the third antigen is a cancer antigen or an immune-related molecule. ### Claim 14 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13) The second antigen-binding molecule of any one of claims 1 to 13, wherein the first antigen-binding molecule has multiple antigen specificity and further binds to at least a second antigen, wherein the second antigen-binding molecule has multiple antigen specificity and further binds to at least a third antigen, and wherein the combination of the first antigen, the second antigen, and the third antigen is any one of the combinations (1) to (5) below: (1) a combination in which the first antigen is an immune-related molecule, the second antigen is a first cancer antigen, and the third antigen is a second cancer antigen; (2) a combination in which the first antigen is a cellular metabolite of a target cell, the second antigen is a cancer antigen, and the third antigen is an immune-related molecule; (3) a combination in which the first antigen is a cellular metabolite of a target cell, the second antigen is an immune-related molecule, and the third antigen is a cancer antigen; (4) a combination in which the first antigen is a first immune-related molecule, the second antigen is a cancer antigen, and the third antigen is a second immune-related molecule; and (5) a combination in which the first antigen is a first immune-related molecule, the second antigen is a second immune-related molecule, and the third antigen is a cancer antigen. ### Claim 15 (depends on 1) A combination of the first antigen-binding molecule and the second antigen-binding molecule of claim 1.