NOVEL ANTI-HUMAN IgB ANTIBODY

Patent metadata

Field	Value
Publication number	US-2017226207-A1
Application number	US-201515501626-A
Country	US
Kind code	A1
Filing date	Aug 5, 2015
Priority date	Aug 6, 2014
Publication date	Aug 10, 2017
Grant date	—

Abstract

[Problem] Provided is an anti-human Igβ antibody which crosslinks BCR and FcγRIIb and has an immunosuppressive function more enhanced than that of an antibody in the prior art.
[Means for Solution] An anti-human Igβ antibody comprising a heavy chain variable region comprising CDR1 consisting of the amino acid sequence of amino acid numbers 31 to 35 of SEQ ID NO: 2, CDR2 consisting of the amino acid sequence of amino acid numbers 50 to 65 of SEQ ID NO: 2, and CDR3 consisting of the amino acid sequence of amino acid numbers 98 to 108 of SEQ ID NO: 2, a light chain variable region comprising CDR1 consisting of the amino acid sequence of amino acid numbers 24 to 38 of SEQ ID NO: 4, CDR2 consisting of the amino acid sequence of amino acid numbers 54 to 60 of SEQ ID NO: 4, and CDR3 consisting of the amino acid sequence of amino acid numbers 93 to 101 of SEQ ID NO: 4, and a heavy chain constant region which is a human Igγ1 constant region having amino acid mutations of S239D, H268D, and L328W.

First claim

1 . An anti-human Igβ antibody comprising a heavy chain variable region comprising CDR1 consisting of the amino acid sequence of amino acid numbers 31 to 35 of SEQ ID NO: 2, CDR2 consisting of the amino acid sequence of amino acid numbers 50 to 65 of SEQ ID NO: 2, and CDR3 consisting of the amino acid sequence of amino acid numbers 98 to 108 of SEQ ID NO: 2, a light chain variable region comprising CDR1 consisting of the amino acid sequence of amino acid numbers 24 to 38 of SEQ ID NO: 4, CDR2 consisting of the amino acid sequence of amino acid numbers 54 to 60 of SEQ ID NO: 4, and CDR3 consisting of the amino acid sequence of amino acid numbers 93 to 101 of SEQ ID NO: 4, and a heavy chain constant region which is a human Igγ1 constant region having amino acid mutations of S239D, H268D, and L328W.

2 . The anti-human Igβ antibody according to claim 1 which is a humanized antibody.

3 . The anti-human Igβ antibody according to claim 1 , selected from the group consisting of the following (1) to (4):
(1) an anti-human Igβ antibody comprising a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 119 of SEQ ID NO: 6, a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 112 of SEQ ID NO: 8, and a heavy chain constant region which is a human Igγ1 constant region having amino acid mutations of S239D, H268D, and L328W;
(2) an anti-human Igβ antibody comprising a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 119 of SEQ ID NO: 2, a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 112 of SEQ ID NO: 4, and a heavy chain constant region which is a human Igγ1 constant region having amino acid mutations of S239D, H268D, and L328W;
(3) an anti-human Igβ antibody comprising a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 119 of SEQ ID NO: 10, a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 112 of SEQ ID NO: 12, and a heavy chain constant region which is a human Igγ1 constant region having amino acid mutations of S239D, H268D, and L328W; and
(4) an anti-human Igβ antibody which is derived from posttranslational modification of the anti-human Igβ antibody of any one of (1) to (3) above.

4 . The anti-human Igβ antibody according to claim 3 , comprising a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 119 of SEQ ID NO: 6, a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 112 of SEQ ID NO: 8, and a heavy chain constant region which is a human Igγ1 constant region having amino acid mutations of S239D, H268D, and L328W.

5 . The anti-human Igβ antibody according to claim 3 , comprising a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 119 of SEQ ID NO: 2, a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 112 of SEQ ID NO: 4, and a heavy chain constant region which is a human Igγ1 constant region having amino acid mutations of S239D, H268D, and L328W.

6 . The anti-human Igβ antibody according to claim 3 , comprising a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 119 of SEQ ID NO: 10, a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 112 of SEQ ID NO: 12, and a heavy chain constant region which is a human Igγ1 constant region having amino acid mutations of S239D, H268D, and L328W.

7 . An anti-human Igβ antibody which is derived from posttranslational modification of the anti-human Igβ antibody according to any one of claims 4 to 6 .

8 . The anti-human Igβ antibody according to claim 3 or 7 , wherein the posttranslational modification is pyroglutamylation at the N terminal of the heavy chain variable region and/or deletion of lysine at the C terminal of the heavy chain.

9 . The anti-human Igβ antibody according to any one of claims 1 to 8 , comprising a light chain constant region which is a human Igκ constant region.

10 . The anti-human Igβ antibody according to claim 1 , comprising a heavy chain consisting of the amino acid sequence shown by SEQ ID NO: 6 and a light chain consisting of the amino acid sequence shown by SEQ ID NO: 8.

11 . The anti-human Igβ antibody according to claim 1 , comprising a heavy chain consisting of the amino acid sequence shown by SEQ ID NO: 2 and a light chain consisting of the amino acid sequence shown by SEQ ID NO: 4.

12 . The anti-human Igβ antibody according to claim 1 , comprising a heavy chain consisting of the amino acid sequence shown by SEQ ID NO: 10 and a light chain consisting of the amino acid sequence shown by SEQ ID NO: 12.

13 . An anti-human Igβ antibody which is derived from posttranslational modification of the anti-human Igβ antibody according to any one of claims 10 to 12 .

14 . The anti-human Igβ antibody according to claim 13 , wherein the posttranslational modification is pyroglutamylation at the N terminal of the heavy chain variable region and/or deletion of lysine at the C terminal of the heavy chain.

15 . The anti-human Igβ antibody according to claim 13 , comprising a heavy chain consisting of the amino acid sequence of amino acid numbers of 1 to 448 of SEQ ID NO: 6 in which glutamine of amino acid number 1 is modified to pyroglutamic acid and a light chain consisting of the amino acid sequence shown by SEQ ID NO:8.

16 . The anti-human Igβ antibody according to claim 13 , comprising a heavy chain consisting of the amino acid sequence of amino acid numbers 1 to 448 of SEQ ID NO:2 and a light chain consisting of the amino acid sequence shown by SEQ ID NO:4.

17 . The anti-human Igβ antibody according to claim 13 , comprising a heavy chain consisting of the amino acid sequence of amino acid numbers 1 to 448 of SEQ ID NO:10 and a light chain consisting of the amino acid sequence shown by SEQ ID NO:12.

18 . A polynucleotide comprising a base sequence encoding the heavy chain of the anti-human Igβ antibody according to any one of claims 1 to 6 .

19 . A polynucleotide comprising a base sequence encoding the light chain of the anti-human Igβ antibody according to any one of claims 1 to 6 .

20 . An expression vector comprising the polynucleotide according to claim 18 and/or 19 .

21 . A host cell transformed with the expression vector according to claim 20 , selected from the group consisting of the following (a) to (d):
(a) a host cell transformed with an expression vector comprising a polynucleotide comprising a base sequence encoding the heavy chain of the anti-human Igβ antibody according to any one of claims 1 to 6 and a polynucleotide comprising a base sequence encoding the light chain of the antibody; (b) a host cell transformed with an expression vector comprising a polynucleotide comprising a base sequence encoding the heavy chain of the anti-human Igβ antibody according to any one of claims 1 to 6 and an expression vector comprising a polynucleotide comprising a base sequence encoding the light chain of the antibody; (c) a host cell transformed with an expression vector comprising a polynucleotide comprising a base sequence encoding the heavy chain of the anti-human Igβ antibody according to any one of claims 1 to 6 ; and (d) a host cell transformed with an expression vector comprising a polynucleoti

Assignees

• Astellas Pharma Inc

Inventors

• Yamajuku Daisuke
• Seki Mutsumi
• Honda Takashi
• Kubo Satoshi
• Soga Shinji
• Morinaka Akifumi

Classifications

• C07K16/46

  Hybrid immunoglobulins (hybrids of an immunoglobulin with a peptide not being an immunoglobulin C07K19/00) · CPC title

• C12N15/63

  Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression · CPC title

• C07K16/28

  against receptors, cell surface antigens or cell surface determinants · CPC title

• A61K39/395

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

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title