# US 10,246,510 B2 · KIR3DL2 binding agents > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,246,510 B2 - Document ID: US10246510B2 - Status: Granted - Kind: B2 - Application number: 14/429,416 - Filed: 2013-09-17 - Published: 2015-10-15 - Granted: 2019-04-02 - Earliest claimed: 2012-09-19 - Assignees: Innate Pharma - Applicants: Innate Pharma - Inventors: Laurent Gauthier; Benjamin Rossi; Hélène Sicard; Carine Paturel - Web page: https://patentgrep.com/patent/US10246510B2 ## CPC - C07K 16/2803: {against the immunoglobulin superfamily} - A61K 47/68031: {the drug being an auristatin} - A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant} - G01N 33/56972: {White blood cells} - A61K 2039/505: {comprising antibodies} - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity - 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 2317/51: Complete heavy chain or Fd fragment, i.e. VH + CH1 - C07K 2317/565: Complementarity determining region [CDR] - C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC] - C07K 2317/734: Complement-dependent cytotoxicity [CDC] - C07K 2317/77: Internalization into the cell - C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value - G01N 2333/70503: Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3 - G01N 2800/24: Immunology or allergic disorders - G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis - G01N 2800/7028: Cancer - G01N 2800/7095: Inflammation - 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) - 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 methods for the treatment of cancer and inflammatory disease using antibodies (e.g. monoclonal antibodies), antibody fragments, and derivatives thereof that specifically bind KIR3DL2. The invention also relates to antibodies, cells producing such antibodies; methods of making such antibodies; fragments, variants, and derivatives of the antibodies; pharmaceutical compositions comprising the same. ## Claims ### Claim 1 An isolated monoclonal antibody selected from the group consisting of: (a) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 4 (HCDR1), SEQ ID NO: 7 (HCDR2) and SEQ ID NO: 9 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 10, 11 and 12, respectively; (b) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 15 (HCDR1), SEQ ID NO: 18 (HCDR2) and SEQ ID NO: 20 (HCDR3) respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 21, 22 and 23, respectively; (c) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 16 (HCDR1), SEQ ID NO: 18 (HCDR2) and SEQ ID NO: 28 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 29, 30 and 31, respectively; (d) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 26 (HCDR1), SEQ ID NO: 36 (HCDR2) and SEQ ID NO: 38 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 39, 40 and 41, respectively; (e) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 16 (HCDR1), SEQ ID NO: 36 (HCDR2) and SEQ ID NO: 38 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 44, 45 and 41, respectively; and (f) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 48 (HCDR1), SEQ ID NO: 51 (HCDR2) and SEQ ID NO: 53 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 54, 55 and 56, respectively. ### Claim 2 (depends on 1) The antibody of claim 1, wherein said antibody has reduced binding to a mutant KIR3DL2 polypeptide comprising a mutation at residues V178 and P179, a mutant KIR3DL2 polypeptide comprising a mutation at residues H180 and S181, and/or a mutant KIR3DL2 polypeptide comprising a mutation at residues E130, H131 and R145, relative to binding between the antibody and a wild-type KIR3DL2 polypeptide of SEQ ID NO: 1. ### Claim 3 (depends on 1) The antibody of claim 1, wherein said antibody comprises a human IgG heavy chain constant region. ### Claim 4 (depends on 1) The antibody of claim 1, wherein said antibody is a chimeric, human or humanized antibody. ### Claim 5 (depends on 1) The antibody of claim 1, wherein said antibody is conjugated or covalently bound to a toxic agent. ### Claim 6 (depends on 1) A pharmaceutical composition comprising an antibody of claim 1, and a pharmaceutically acceptable carrier. ### Claim 7 A method for the treatment of a KIR3DL2-expressing CD4+ T cell cancer in a patient in need thereof, the method comprising administering to said patient an effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a monoclonal antibody selected from the group consisting of: (a) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 4 (HCDR1), SEQ ID NO: 7 (HCDR2) and SEQ ID NO: 9 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 10, 11 and 12, respectively; (b) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 15 (HCDR1), SEQ ID NO: 18 (HCDR2) and SEQ ID NO: 20 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 21, 22 and 23, respectively; (c) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 16 (HCDR1), SEQ ID NO: 18 (HCDR2) and SEQ ID NO: 28 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 29, 30 and 31, respectively; (d) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 26 (HCDR1), SEQ ID NO: 36 (HCDR2) and SEQ ID NO: 38 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 39, 40 and 41, respectively; (e) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 16 (HCDR1), SEQ ID NO: 36 (HCDR2) and SEQ ID NO: 38 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 44, 45 and 41, respectively; and (f) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 48 (HCDR1), SEQ ID NO: 51 (HCDR2) and SEQ ID NO: 53 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 54, 55 and 56, respectively. ### Claim 8 (depends on 7) The method of claim 7, wherein said cancer is selected from Mycosis fungoides and Sézary Syndrome. ### Claim 9 (depends on 7) The method of claim 7, said monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 4 (HCDR1), SEQ ID NO: 7 (HCDR2) and SEQ ID NO: 9 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 10, 11 and 12, respectively. ### Claim 10 (depends on 7) The method of claim 7, said monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 15 (HCDR1), SEQ ID NO: 18 (HCDR2) and SEQ ID NO: 20 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 21, 22 and 23, respectively. ### Claim 11 (depends on 7) The method of claim 7, said monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 16 (HCDR1), SEQ ID NO: 18 (HCDR2) and SEQ ID NO: 28 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 29, 30 and 31, respectively. ### Claim 12 (depends on 7) The method of claim 7, said monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 26 (HCDR1), SEQ ID NO: 36 (HCDR2) and SEQ ID NO: 38 (HCDR3), respectively, and (ii) a 7 light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 39, 40 and 41, respectively. ### Claim 13 (depends on 7) The method of claim 7, said monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 16 (HCDR1), SEQ ID NO: 36 (HCDR2) and SEQ ID NO: 38 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 44, 45 and 41, respectively. ### Claim 14 (depends on 7) The method of claim 7, said monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 48 (HCDR1), SEQ ID NO: 51 (HCDR2) and SEQ ID NO: 53 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 54, 55 and 56, respectively. ### Claim 15 (depends on 1) The isolated monoclonal antibody of claim 1, said monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 4 (HCDR1), SEQ ID NO: 7 (HCDR2) and SEQ ID NO: 9 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 10, 11 and 12, respectively. ### Claim 16 (depends on 1) The isolated monoclonal antibody of claim 1, said monoclonal an antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 15 (HCDR1), SEQ ID NO: 18 (HCDR2) and SEQ ID NO: 20 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 21, 22 and 23, respectively. ### Claim 17 (depends on 1) The isolated monoclonal antibody of claim 1, said monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 16 (HCDR1), SEQ ID NO: 18 (HCDR2) and SEQ ID NO: 28 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 29, 30 and 31, respectively. ### Claim 18 (depends on 1) The isolated monoclonal antibody of claim 1, said monoclonal an antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 26 (HCDR1), SEQ ID NO: 36 (HCDR2) and SEQ ID NO: 38 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 39, 40 and 41, respectively. ### Claim 19 (depends on 1) The isolated monoclonal antibody of claim 1, said monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 16 (HCDR1), SEQ ID NO: 36 (HCDR2) and SEQ ID NO: 38 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 44, 45 and 41, respectively. ### Claim 20 (depends on 1) The isolated monoclonal antibody of claim 1, said monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 48 (HCDR1), SEQ ID NO: 51 (HCDR2) and SEQ ID NO: 53 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 54, 55 and 56, respectively.