Anti-human Igβ antibody

Patent metadata

Field	Value
Publication number	US-10316086-B2
Application number	US-201515501626-A
Country	US
Kind code	B2
Filing date	Aug 5, 2015
Priority date	Aug 6, 2014
Publication date	Jun 11, 2019
Grant date	Jun 11, 2019

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

The invention claimed is:

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 Igγl constant region having amino acid mutations of S239D, H268D, and L328W.

2. The anti-human Igβ antibody according to claim 1 , selected from the group consisting of the following (a) to (d):
(a) 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 Igγl constant region having amino acid mutations of S239D, H268D, and L328W;
(b) 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 Igγl constant region having amino acid mutations of S239D, H268D, and L328W;
(c) 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, and 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 Igγl constant region having amino acid mutations of S239D, H268D, and L328W; and
(d) an anti-human Igβ antibody which is derived from posttranslational modification of the anti-human Igβ antibody of any one of (a) to (c) above, 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.

3. The anti-human Igβ antibody according to claim 2 , selected from the group consisting of the following (a) to (d):
(a) an anti-human Igβ antibody 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;
(b) an anti-human Igβ antibody 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;
(c) an anti-human Igβ antibody 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; and
(d) an anti-human Igβ antibody which is derived from posttranslational modification of the anti-human Igβ antibody of any one of (a) to (c) above, 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.

4. The anti-human Igβ antibody according to claim 2 , selected from the group consisting of the following (a) to (f):
(a) an anti-human Igβ antibody 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 ;
(b) an anti-human Igβ antibody 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;
(c) an anti-human Igβ antibody 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;
(d) an anti-human Igβ antibody 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;
(e) an anti-human Igβ antibody 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; and
(f) an anti-human Igβ antibody 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.

5. The anti-human Igβ antibody according to claim 4 , wherein the anti-human Igβ antibody comprises 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.

6. The anti-human Igβ antibody according to claim 4 , wherein the anti-human Igβ antibody comprises 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.

7. The anti-human Igβ antibody according to claim 2 , wherein the antibody is fused to another peptide.

8. The anti-human Igβ antibody according to claim 2 , wherein the antibody is modified with polyethylene glycol, sugar chains, phospholipids, liposomes, or low-molecular compounds.

9. A pharmaceutical composition comprising: an anti-human Igβ antibody according to claim 1 , and a pharmaceutically acceptable excipient.

10. A pharmaceutical composition comprising an anti-human Igβ antibody selected from the group consisting of the following (a) to (c), and a pharmaceutically acceptable excipient:
(a) an anti-human Igβ antibody 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, and/or an anti-human Igβ antibody 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;
(b) an anti-human Igβ antibody 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, and/or an anti-human Igβ antibody 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; and
(c) an anti-human Igβ antibody 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, and/or an anti-human Igβ antibody 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.

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

• A61K39/395

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

• A61P37/06

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