Monoclonal antibodies against KIR2DS1

Patent metadata

Field	Value
Publication number	US-10429394-B2
Application number	US-201515507698-A
Country	US
Kind code	B2
Filing date	Aug 27, 2015
Priority date	Aug 29, 2014
Publication date	Oct 1, 2019
Grant date	Oct 1, 2019

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

The invention claimed is:

1. A monoclonal antibody to KIR2DS1, or the fragment comprising an antigen-binding region thereof, that includes a VL and a VH, wherein:
the VL comprises the amino acid sequence of SEQ ID NO: 1 as CDR1, the amino acid sequence of SEQ ID NO: 2 as CDR2, and the amino acid sequence of SEQ ID NO: 3 as CDR3; and
the VH comprises the amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 5 as CDR1, the amino acid sequence of SEQ ID NO: 6 as CDR2, and the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9, as CDR3;
wherein said antibody or fragment comprising an antigen-binding region thereof binds to KIR2DS1 specifically, in distinction to KIR2DL1, KIR2DS2, KIR2DL2, and KIR2DL3.

2. The monoclonal antibody to KIR2DS1, or fragment comprising an antigen-binding region thereof, according to claim 1 wherein:
the VL comprises the amino acid sequence of SEQ ID NO: 1 as CDR1, the amino acid sequence of SEQ ID NO: 2 as CDR2, and the amino acid sequence of SEQ ID NO: 3 as CDR3; and wherein:
the VH comprises the amino acid sequence of SEQ ID NO: 4 as CDR1, the amino acid sequence of SEQ ID NO: 6 as CDR2, and the amino acid sequence of SEQ ID NO: 7 as CDR3;
the VH comprises the amino acid sequence of SEQ ID NO: 5 as CDR1, the amino acid sequence of SEQ ID NO: 6 as CDR2, and the amino acid sequence of SEQ ID NO: 8 as CDR3; or
the VH comprises the amino acid sequence of SEQ ID NO: 5 as CDR1, the amino acid sequence of SEQ ID NO: 6 as CDR2, and the amino acid sequence of SEQ ID NO: 9 as CDR3.

3. 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.

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

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

6. 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.

7. 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.

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

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

10. An expression vector comprising the nucleic acid according to claim 9 .

11. A transformant comprising the nucleic acid according to claim 9 or the expression vector according to claim 10 and producing the monoclonal antibody or the fragment comprising an antigen-binding region thereof according to claim 1 .

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

13. The cell according to claim 12 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.

14. 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 11 to collect the antibody or the fragment comprising an antigen-binding region thereof from a culture.

Assignees

• Univ Hokkaido Nat Univ Corp
• National Univ Corporation Hokkaido

Inventors

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

Classifications

• A61K39/395

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title

• C07K16/00

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

• C07K16/28

  against receptors, cell surface antigens or cell surface determinants · 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

• C07K1/00

  General methods for the preparation of peptides {, i.e. processes for the organic chemical preparation of peptides or proteins of any length} · CPC title