Anti-human PAI-1 antibody

Patent metadata

Field	Value
Publication number	US-9803024-B2
Application number	US-201515120257-A
Country	US
Kind code	B2
Filing date	Feb 20, 2015
Priority date	Feb 21, 2014
Publication date	Oct 31, 2017
Grant date	Oct 31, 2017

Abstract

[Problem] To provide an anti-human PAI-1 antibody for preventing or treating pulmonary fibrosis by binding to active human PAI-1 and inhibiting effects mediated by the active human PAI-1.
[Means for Solution] The present inventors have investigated anti-PAI-1 antibodies and consequently have provided an anti-human PAI-1 antibody comprising a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 118 of SEQ ID NO: 2 and a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 108 of SEQ ID NO: 4.

First claim

The invention claimed is:

1. An anti-human PAI-1 antibody or an antigen-binding fragment thereof, 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 66 of SEQ ID NO: 2, and CDR3 consisting of the amino acid sequence of amino acid numbers 99 to 107 of SEQ ID NO: 2; and
a light chain variable region comprising CDR1 consisting of the amino acid sequence of amino acid numbers 24 to 34 of SEQ ID NO: 4, CDR2 consisting of the amino acid sequence of amino acid numbers 50 to 56 of SEQ ID NO: 4, and CDR3 consisting of the amino acid sequence of amino acid numbers 89 to 97 of SEQ ID NO: 4.

2. The anti-human PAI-1 antibody or an antigen-binding fragment thereof according to claim 1 , comprising a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 118 of SEQ ID NO: 2, and a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 108 of SEQ ID NO: 4.

3. The anti-human PAI-1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 118 of SEQ ID NO: 2, in which glutamic acid at amino acid number 1 of SEQ ID NO: 2 is modified to pyroglutamic acid, and a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 108 of SEQ ID NO: 4.

4. The anti-human PAI-1 antibody or an antigen-binding fragment thereof according to claim 2 , which is selected from any one of the following (1) and (2):
(1) an anti-human PAI-1 antibody comprising a heavy chain consisting of the amino acid sequence set forth in SEQ ID NO: 2 and a light chain consisting of the amino acid sequence set forth in SEQ ID NO: 4; and
(2) an anti-human PAI-1 antibody comprising a heavy chain consisting of the amino acid sequence of SEQ ID NO: 2, in which glutamic acid of the amino acid number 1 of SEQ ID NO: 2 is modified to pyroglutamic acid and/or lysine of the amino acid number 448 of SEQ ID NO: 2 is deleted and a light chain consisting of the amino acid sequence set forth in SEQ ID NO: 4.

5. The anti-human PAI-1 antibody according to claim 4 , comprising a heavy chain consisting of the amino acid sequence set forth in SEQ ID NO: 2, and a light chain consisting of the amino acid sequence set forth in SEQ ID NO: 4.

6. The anti-human PAI-1 antibody according to claim 4 , comprising a heavy chain consisting of the amino acid sequence of amino acid numbers 1 to 447 of SEQ ID NO: 2, and a light chain consisting of the amino acid sequence set forth in SEQ ID NO: 4.

7. A pharmaceutical composition comprising
(1) (a) anti-human PAI-1 antibody or antigen-binding fragment thereof according to claim 2 , and/or
(b) an anti-human PAI-1 antibody or an antigen-binding fragment thereof comprising a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 118 of SEQ ID NO: 2, in which glutaminic acid of the amino acid number 1 of SEQ ID NO: 2 is modified to pyroglutamic acid, and a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 108 of SEQ ID NO: 4, and (2) a pharmaceutically acceptable excipient.

8. A pharmaceutical composition comprising:
(i)(a) the anti-human PAI-1 antibody according to claim 5 and/or
(b) an anti-human PAI-1 antibody comprising a heavy chain consisting of the amino acid sequence of amino acid numbers 1 to 447 of SEQ ID NO: 2, and a light chain consisting of the amino acid sequence set forth in SEQ ID NO: 4, and
(ii) a pharmaceutically acceptable excipient.

9. A polynucleotide comprising a base sequence encoding the heavy chain variable region of the anti-human PAI-1 antibody or the antigen-binding fragment thereof according to claim 2 .

10. A polynucleotide comprising a base sequence encoding the light chain variable region of the anti-human PAI-1 antibody or the antigen-binding fragment thereof according to claim 2 .

11. An expression vector comprising a polynucleotide comprising a base sequence encoding the heavy chain variable region of the anti-human PAI-1 antibody or the antigen-binding fragment thereof according to claim 2 and/or a polynucleotide comprising a base sequence encoding the light chain variable region of the anti-human PAI-1 antibody or the antigen-binding fragment thereof according to claim 2 .

12. A host cell transformed with an expression vector, which is selected from the group consisting of the following (a) and (b):
(a) a host cell transformed with an expression vector comprising a polynucleotide comprising a base sequence encoding the heavy chain variable region of the anti-human PAI-1 antibody or the antigen-binding fragment thereof according to claim 2 and a polynucleotide comprising a base sequence encoding the light chain variable region of the antibody or the antigen-binding fragment thereof; and
(b) a host cell transformed with an expression vector comprising a polynucleotide comprising a base sequence encoding the heavy chain variable region of the anti-human PAI-1 antibody or the antigen-binding fragment thereof according to claim 2 and an expression vector comprising a polynucleotide comprising a base sequence encoding the light chain variable region of the antibody or the antigen-binding fragment thereof.

13. A host cell transformed with an expression vector, which is selected from the group consisting of the following (a) and (b):
(a) a host cell transformed with an expression vector comprising a polynucleotide comprising a base sequence encoding the heavy chain of the anti-human PAI-1 antibody according to claim 5 and a polynucleotide comprising a base sequence encoding the light chain of the antibody; and
(b) a host cell transformed with an expression vector comprising a polynucleotide comprising a base sequence encoding the heavy chain of the anti-human PAI-1 antibody according to claim 5 and an expression vector comprising a polynucleotide comprising a base sequence encoding the light chain of the antibody.

14. A method for producing an anti-human PAI-1 antibody or an antigen-binding fragment thereof, comprising culturing host cell(s) according to claim 12 .

15. A method for producing an anti-human PAI-1 antibody, comprising culturing host cell(s) according to claim 13 .

16. An anti-human PAI-1 antibody or an antigen-binding fragment thereof produced by the method according to claim 14 .

17. An anti-human PAI-1 antibody produced by the method according to claim 15 .

18. A pharmaceutical composition comprising the anti-human PAI-1 antibody or the antigen-binding fragment thereof according to claim 1 , and a pharmaceutically acceptable excipient.

Assignees

• Astellas Pharma Inc

Inventors

• Tanaka Hirotsugu
• Yoshino Masayasu

Classifications

• A61P41/00

  Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title