ANTI HUMAN Gas6 MONOCLONAL ANTIBODY

Patent metadata

Field	Value
Publication number	US-2018339041-A1
Application number	US-201515520623-A
Country	US
Kind code	A1
Filing date	Oct 20, 2015
Priority date	Oct 21, 2014
Publication date	Nov 29, 2018
Grant date	—

Abstract

The present invention relates to an antibody specifically binding to human growth arrest specific 6 (hGas6). Specifically, the present invention relates to a monoclonal antibody or an antibody fragment thereof which binds to at least one of amino acid residues at positions 314, 315, and 316 of human Gas6, a nucleic acid comprising a nucleotide sequence encoding the antibody or the antibody fragment, a transformed cell comprising a vector comprising the nucleic acid, a method for producing the antibody or the antibody fragment, a reagent for detection or assay of Gas6, comprising the antibody or the antibody fragment, a therapeutic agent or a diagnostic agent for a Gas6-related disease, comprising the antibody or the antibody fragment as an active ingredient, and use of the antibody or the antibody fragment for the production of a therapeutic agent or a diagnostic agent for a Gas6-related disease.

First claim

1 . A monoclonal antibody or an antibody fragment thereof which binds to at least one of amino acid residues at positions 314, 315, and 316 in the amino acid sequence of human Gas6.

2 . The monoclonal antibody or the antibody fragment thereof according to claim 1 , wherein the monoclonal antibody is a monoclonal antibody binding to amino acid residues at positions 314, 315, and 316 of human Gas6.

3 . The monoclonal antibody or the antibody fragment thereof according to claim 1 , wherein the monoclonal antibody is any one antibody selected from the following antibodies (a) to (e):
(a) an antibody in which the amino acid sequences of heavy chain (hereinafter, abbreviated to H chain) variable region (hereinafter, abbreviated to VH) complementarity determining region (CDR; hereinafter, abbreviated to CDR) 1 to CDR3 are the amino acid sequences shown in SEQ ID NOs: 79, 80, and 81, respectively, and the amino acid sequences of light chain (hereinafter, abbreviated to L chain) variable region (hereinafter, abbreviated to VL) CDR1 to CDR3 are the amino acid sequences shown in SEQ ID NOs: 82, 83, and 84, respectively; (b) an antibody in which the amino acid sequences of VH CDR1 to CDR3 are the amino acid sequences shown in SEQ ID NOs: 85, 86, and 87, respectively, and the amino acid sequences of VL CDR1 to CDR3 are the amino acid sequences shown in SEQ ID NOs: 88, 89, and 90, respectively; (c) an antibody which competes with the antibody (a) or (b) for binding to human Gas6; (d) an antibody which binds to an epitope comprising an epitope to which the antibody (a) or (b) binds; and (e) an antibody which binds to the same epitope as an epitope to which the antibody (a) or (b) binds.

4 . The monoclonal antibody or the antibody fragment thereof according to claim 1 , wherein the monoclonal antibody is any one antibody selected from the following antibodies (a) to (e):
(a) an antibody in which the amino acid sequence of VH is the amino acid sequence shown in SEQ ID NO: 69, and the amino acid sequence of VL is the amino acid sequence shown in SEQ ID NO: 72; (b) an antibody in which the amino acid sequence of VH is the amino acid sequence shown in SEQ ID NO: 75, and the amino acid sequence of VL is the amino acid sequence shown in SEQ ID NO: 78; (c) an antibody in which the amino acid sequence of VH is the amino acid sequence shown in SEQ ID NO: 135, and the amino acid sequence of VL is the amino acid sequence shown in SEQ ID NO: 123; (d) an antibody in which the amino acid sequence of VH is the amino acid sequence shown in SEQ ID NO: 195, and the amino acid sequence of VL is the amino acid sequence shown in SEQ ID NO: 174; and (e) an antibody in which the amino acid sequence of VH is the amino acid sequence shown in SEQ ID NO: 186, and the amino acid sequence of VL is the amino acid sequence shown in SEQ ID NO: 180.

5 . The monoclonal antibody or the antibody fragment thereof according to claim 1 , wherein the monoclonal antibody is a recombinant antibody.

6 . The monoclonal antibody or the antibody fragment thereof according to claim 5 , wherein the recombinant antibody is a recombinant antibody selected from a human chimeric antibody, a humanized antibody, and a human antibody.

7 . The antibody fragment according to claim 1 , wherein the antibody fragment is selected from Fab, Fab′, (Fab′) 2 , single chain Fv (scFv), diabody, disulfide-stabilized Fv (dsFv), and a peptide comprising CDRs.

8 . A nucleic acid having a nucleotide sequence encoding the antibody or the antibody fragment thereof according to claim 1 .

9 . A transformed cell comprising a vector comprising the nucleic acid according to claim 8 .

10 . A method for producing the antibody or the antibody fragment thereof which binds to at least one of amino acid residues at positions 314, 315, and 316 in the amino acid sequence of human Gas6, comprising culturing the cell according to claim 9 in a medium and collecting the antibody or the antibody fragment thereof from the culture medium.

11 . A reagent for detection or assay of Gas6, comprising the antibody or the antibody fragment thereof according to claim 1 .

12 . A therapeutic agent comprising the antibody or the antibody fragment thereof according to claim 1 as an active ingredient.

13 .- 15 . (canceled)

16 . A diagnostic agent for comprising the antibody or the antibody fragment thereof according to claim 1 as an active ingredient.

17 . A method for diagnosing a Gas6-related disease, comprising detecting or assaying Gas6 using the antibody or the antibody fragment thereof according to claim 1 .

18 .- 19 . (canceled)

20 . A method for treating Gas6-related disease, comprising administering an effective amount of the antibody or the antibody fragment thereof according to claim 1 to a mammal.

21 . The method according to claim 20 , wherein the Gas6-related disease is a kidney or cancer disease.

22 . The method according to claim 21 , wherein the kidney disease is glomerulonephritis, diabetic nephropathy, or IgA nephropathy.

Assignees

• Kyowa Hakko Kirin Co Ltd

Inventors

• Ube Yuko
• Yamada Tsuyoshi
• Yamazaki Yuji
• Kimura Kaname
• Hariguchi Akiko
• Ogawa Shinya

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P13/12

  of the kidneys · CPC title

• G01N33/53

  Immunoassay; Biospecific binding assay; Materials therefor · CPC title

• C07K16/22

  against growth factors {; against growth regulators} · CPC title