Anti eotaxin-2 antibodies that recognize additional CCR3-binding chemokines

{
  "publication_number": "US10479830B2",
  "country": "US",
  "kind": "B2",
  "title": "Anti eotaxin-2 antibodies that recognize additional CCR3-binding chemokines",
  "abstract": "The invention concerns isolated polyspecific antibodies directed to a unique epitope in the chemokine eotaxin 2, whereby the antibodies bind additional CCR3-binding chemokines. The invention further concerns use of these antibodies for attenuating the migration of various cells and for treating fibrotic diseases, autoimmune inflammatory disorders, monocyte related disorders or allergic atopic disorders.",
  "claims": [
    "1. An isolated antibody that binds a conformational epitope in the N-loop region of a CCR3-binding chemokine, wherein said conformational epitope is characterized by a relatively high concentration of positive amino acid residues located between amino acid positions 14 and 24 in the amino acid sequence of said CCR3-binding chemokine as denoted by SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 14 and wherein said antibody is a fully humanized antibody comprising a heavy chain variable region comprising: a) the complementary determining region VH CDR1 comprising the amino acid sequence denoted by SEQ ID NO. 5; b) the complementary determining region VH CDR2 comprising the amino acid sequence denoted by SEQ ID NO. 6; and c) the complementary determining region VH CDR3 comprising the amino acid sequence denoted by SEQ ID NO. 7; and a light chain variable region comprising d) the complementary determining region VK CDR1 comprising the amino acid sequence denoted by SEQ ID NO. 8; e) the complementary determining region VK CDR2 comprising the amino acid sequence denoted by SEQ ID NO. 9; and f) the complementary determining region VK CDR3 comprising the amino acid sequence denoted by SEQ ID NO. 10.",
    "2. The isolated antibody of claim 1, wherein said conformational epitope comprises at least three positive amino acid residues between amino acid positions 14 and 24 in the amino acid sequence of said CCR3-binding chemokine as denoted by SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 14.",
    "3. The isolated antibody of claim 1, wherein said positive amino acid residues are selected from the group consisting of Arg, Lys and His.",
    "4. The isolated antibody of claim 1, wherein the conformational epitope comprises an amino acid sequence selected from: the amino acid sequences denoted by SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18 or SEQ ID NO: 19.",
    "5. The isolated antibody of claim 1, wherein said antibody is a polyspecific antibody, or any antigen-binding fragment thereof, that binds to at least two CCR3-binding chemokines.",
    "6. The isolated antibody of claim 5, wherein said antigen-binding fragment thereof is selected from the group consisting of Fv, single chain Fv (scFv), heavy chain variable region capable of binding the antigen, light chain variable region capable of binding the antigen, Fab, F(ab) 2 ′ and any combination thereof.",
    "7. The isolated antibody of claim 5, wherein said antibody binds Eotaxin 1, Eotaxin-2, Rantes and MCP-3.",
    "8. The isolated antibody of claim 5, wherein said antibody attenuates the migratory properties of CCR3, CCR1, CCR2 and CCR5 expressing cells.",
    "9. A pharmaceutical composition comprising the antibody of claim 1, and a pharmaceutically acceptable carrier.",
    "10. The isolated antibody of claim 1, wherein said antibody is a fully humanized antibody comprising the heavy chain variable region denoted by SEQ ID NO:3 and the light chain variable region denoted by SEQ ID NO: 4.",
    "11. An isolated fully humanized antibody comprising a heavy chain variable region comprising: a) the complementary determining region VH CDR1 comprising the amino acid sequence denoted by SEQ ID NO. 5; b) the complementary determining region VH CDR2 comprising the amino acid sequence denoted by SEQ ID NO. 6; and c) the complementary determining region VH CDR3 comprising the amino acid sequence denoted by SEQ ID NO. 7; and a light chain variable region comprising d) the complementary determining region VK CDR1 comprising the amino acid sequence denoted by SEQ ID NO. 8; e) the complementary determining region VK CDR2 comprising the amino acid sequence denoted by SEQ ID NO. 9; and f) the complementary determining region VK CDR3 comprising the amino acid sequence denoted by SEQ ID NO. 10, wherein said antibody binds Eotaxin 1, Eotaxin-2, Rantes and/or MCP-3.",
    "12. An isolated fully humanized antibody comprising the heavy chain variable region denoted by SEQ ID NO:3 and the light chain variable region denoted by SEQ ID NO: 4, wherein said antibody binds Eotaxin 1, Eotaxin-2, Rantes and/or MCP-3."
  ],
  "description_excerpt": "The present invention concerns the use of anti eotaxin-2(CCL24) monoclonal antibodies that possess poly-specific binding properties to other chemokines in the treatment of fibrotic, inflammatory, autoimmune and allergic diseases.\n\nAutoimmune disorders result from an overactive immune response of the body working against its own cells (1). Almost all autoimmune diseases are chronic and have no permanent cure. Over 300 million patients across the globe suffer from these disorders. Women constitute around 70%-75% of all autoimmune patients.\n\nEotaxin-2 is a chemokine that promotes cell trafficking and regulates inflammatory activities at the CCR3 gene complex site especially by inducing chemotaxis of eosinophils (2-4), basophils (4), and Th2-type lymphocytes (5).\n\nSo far, Eotaxin-2 was well known in the context of allergy. It was well documented that there is a significant increase in the levels of Eotaxin-2 during the allergic response (6-8). Recently, the inventors discovered that Eotaxin-2 is also involved in autoimmune and inflammatory diseases (WO 2010/086854) As described in Ablin et al. (9), inhibition of Eotaxin-2 demonsrated a protective effect in the Rat model of Rheumatod arthritis. In addition it was observed that Eotaxin-2 blockade attenuated experimental autoimmune encephalomyelitis as published by Mausner et al. (10).\n\nScleroderma, or systemic sclerosis (SSc), is a chronic, rare multisystem autoimmune disease characterized by immune system activation, endothelial dysfunction, and an active fibrotic process involving fibroblasts (11).",
  "cpc": [
    "C07K 16/24",
    "A61K 2039/505",
    "A61K 2039/545",
    "A61K 39/395",
    "A61P 1/10",
    "A61P 11/00",
    "A61P 13/12",
    "A61P 17/00",
    "A61P 29/00",
    "A61P 3/10",
    "A61P 37/00",
    "A61P 37/02",
    "A61P 37/08",
    "A61P 43/00",
    "A61P 9/10",
    "C07K 14/47",
    "C07K 2317/24",
    "C07K 2317/31",
    "C07K 2317/565",
    "C07K 2317/76",
    "C07K 2317/92"
  ],
  "ipc": [
    "C07K 16/24",
    "A61K 39/00"
  ],
  "assignees": [
    "Chemomab Ltd"
  ],
  "inventors": [
    "Adi MOR"
  ],
  "filing_date": "2019-02-07",
  "publication_date": "2019-11-19",
  "grant_date": "2019-11-19",
  "priority_date": "2014-03-04",
  "application_number": "US-201916270231-A",
  "family_id": "52815066",
  "cited_by_count": 1,
  "citations": [
    "WO2000027880A2",
    "WO2010086854A1",
    "WO2011025962A1"
  ]
}