Monoclonal antibody against kir2ds1

Patent metadata

Field	Value
Publication number	US-2017350892-A1
Application number	US-201515507698-A
Country	US
Kind code	A1
Filing date	Aug 27, 2015
Priority date	Aug 29, 2014
Publication date	Dec 7, 2017
Grant date	—

Abstract

A monoclonal antibody to KIR2DS1 or a fragment containing an antigen-binding region thereof has VL having an amino acid sequence of SEQ ID NO: 1 or an amino acid sequence having the same amino acid sequence as the amino acid sequence except that one or several amino acids are conservatively substituted as CDR1, having an amino acid sequence of SEQ ID NO: 2 or an amino acid sequence having the same amino acid sequence as the amino acid sequence except that one or several amino acids are conservatively substituted as CDR2, and having an amino acid sequence of SEQ ID NO: 3 or an amino acid sequence having the same amino acid sequence as the amino acid sequence except that one or several amino acids are conservatively substituted as CDR3; and VH having an amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 5 or an amino acid sequence having the same amino acid sequence as the amino acid sequence except that one or several amino acids are conservatively substituted as CDR1, having an amino acid sequence of SEQ ID NO: 6 or an amino acid sequence having the same amino acid sequence as the amino acid sequence except that one or several amino acids are conservatively substituted as CDR2, and having an amino acid sequence of any one selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9 or an amino acid sequence having the same amino acid sequence as the amino acid sequence except that one or several amino acids are conservatively substituted as CDR3.

First claim

1 . A monoclonal antibody to KIR2DS1 or a fragment comprising an antigen-binding region thereof that includes:
a VL comprising an amino acid sequence of SEQ ID NO: 1 or an amino acid sequence comprising the same amino acid sequence as the amino acid sequence except that one or several amino acids are conservatively substituted as CDR1, comprising an amino acid sequence of SEQ ID NO: 2 or an amino acid sequence comprising the same amino acid sequence as the amino acid sequence except that one or several amino acids are conservatively substituted as CDR2, and comprising an amino acid sequence of SEQ ID NO: 3 or an amino acid sequence comprising the same amino acid sequence as the amino acid sequence except that one or several amino acids are conservatively substituted as CDR3; and a VH, wherein: the VH comprises an amino acid sequence of SEQ ID NO: 4 or an amino acid sequence comprising the same amino acid sequence as the amino acid sequence except that one or several amino acids are conservatively substituted as CDR1, comprises an amino acid sequence of SEQ ID NO: 6 or an amino acid sequence comprising the same amino acid sequence as the amino acid sequence except that one or several amino acids are conservatively substituted as CDR2, and comprises an amino acid sequence of SEQ ID NO: 7 or an amino acid sequence comprising the same amino acid sequence as the amino acid sequence except that one or several amino acids are conservatively substituted as CDR3; the VH comprises an amino acid sequence of SEQ ID NO: 5 or an amino acid sequence comprising the same amino acid sequence as the amino acid sequence except that one or several amino acids are conservatively substituted as CDR1, comprises an amino acid sequence of SEQ ID NO: 6 or an amino acid sequence comprising the same amino acid sequence as the amino acid sequence except that one or several amino acids are conservatively substituted as CDR2, and comprises an amino acid sequence of SEQ ID NO: 8 or an amino acid sequence comprising the same amino acid sequence as the amino acid sequence except that one or several amino acids are conservatively substituted as CDR3; or the VH comprises an amino acid sequence of SEQ ID NO: 5 or an amino acid sequence comprising the same amino acid sequence as the amino acid sequence except that one or several amino acids are conservatively substituted as CDR1, comprises an amino acid sequence of SEQ ID NO: 6 or an amino acid sequence comprising the same amino acid sequence as the amino acid sequence except that one or several amino acids are conservatively substituted as CDR2, and comprises an amino acid sequence of SEQ ID NO: 9 or an amino acid sequence comprising the same amino acid sequence as the amino acid sequence except that one or several amino acids are conservatively substituted as CDR3.

2 .- 4 . (canceled)

5 . A monoclonal antibody to KIR2DS1 that is produced by at least one hybridoma selected from the group consisting of a hybridoma with Accession No. NITE BP-01853, a hybridoma with Accession No. NITE BP-01855, and a hybridoma with Accession No. NITE BP-01854 or a fragment comprising an antigen-binding region thereof.

6 . The monoclonal antibody or the fragment comprising an antigen-binding region thereof according to claim 1 wherein the monoclonal antibody is a chimeric antibody or a humanized antibody.

7 . A nucleic acid comprising a base sequence encoding the monoclonal antibody or the fragment comprising an antigen-binding region thereof according to claim 1 .

8 . An expression vector comprising the nucleic acid according to claim 7 .

9 . A transformant comprising the nucleic acid according to claim 7 or the expression vector according to claim 8 and producing the monoclonal antibody or the fragment comprising an antigen-binding region thereof according to claim 1 .

10 . A method of producing the monoclonal antibody or the fragment comprising an antigen-binding region thereof according to claim 1 , the method comprising a step of culturing the transformant according to claim 9 to collect the antibody or the fragment comprising an antigen-binding region thereof from a culture.

11 . A cell producing the monoclonal antibody or the fragment comprising an antigen-binding region thereof according to claim 1 .

12 . The cell according to claim 11 that is at least one hybridoma selected from the group consisting of a hybridoma with Accession No. NITE BP-01853, a hybridoma with Accession No. NITE BP-01855, and a hybridoma with Accession No. NITE BP-01854.

13 . A pharmaceutical composition comprising the monoclonal antibody or the fragment comprising an antigen-binding region thereof according to claim 1 .

14 . The monoclonal antibody or the fragment comprising an antigen-binding region thereof according to claim 1 that acts as an agonist for KIR2DS1.

15 . The monoclonal antibody or the fragment comprising an antigen-binding region thereof according to claim 1 that acts as antagonist against KIR2DS1.

16 . The monoclonal antibody or the fragment comprising an antigen-binding region thereof according to claim 1 that neither acts as an agonist for KIR2DS1 nor acts as an antagonist against KIR2DS1.

17 . A method for screening a substance that binds to KIR2DL1 comprising:
a step of administering the monoclonal antibody or the fragment comprising an antigen-binding region thereof according to claim 16 to a cell population; a step of measuring the level A of KIR2DL1 activity in the cell population; a step of administering a candidate substance to the cell population; a step of measuring the level B of KIR2DL1 activity after administering the candidate substance to the cell population; and a step of comparing the level A with the level B.

18 . A method for detecting KIR2DS1 in a sample comprising:
a step of bringing the monoclonal antibody or the fragment comprising an antigen-binding region thereof according to claim 1 into contact with a sample from a subject; and a step of determining whether or not the monoclonal antibody or the fragment comprising an antigen-binding region thereof binds to KIR2DS1 in the sample.

19 . A method for measuring a population of KIR2DS1 and KIR2DL1 in a sample comprising:
a step of bringing the monoclonal antibody or the fragment comprising an antigen-binding region thereof according to claim 1 into contact with a sample from a subject to measure the amount of KIR2DS1 in the sample; and a step of measuring the amount of KIR2DL1 in the sample.

Assignees

• Univ Hokkaido Nat Univ Corp

Inventors

• Maenaka Katsumi
• Kuroki Kimiko
• Maita Hiroshi
• Fukuhara Hideo

Classifications

• C12N15/09

  Recombinant DNA-technology · CPC title

• G01N33/53

  Immunoassay; Biospecific binding assay; Materials therefor · CPC title

• C12N15/02

  Preparation of hybrid cells by fusion of two or more cells, e.g. protoplast fusion {(monoclonal antibodies C07K16/00; apparatus for cell fusion C12M)} · CPC title

• C07K16/00

  Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies · CPC title

• C12N5/10

  Cells modified by introduction of foreign genetic material · CPC title