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US 2024/0309112 A1Published application
Novel anti-pad4 antibody
AssigneesMitsubishi Tanabe Pharma Corporation, Pharma Foods International Co., Ltd.
InventorsYuya MIYAMOTO, Koichi WADA, Yuichi IMURA, Kenji SAITO, Tomoko SAKATA, Takanari SHIGEMITSU
Life of this patent
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Abstract
Provided is an anti-PAD4 antibody or an antibody fragment thereof, wherein HCDR1 comprises an amino acid sequence of SEQ ID NO: 1, HCDR2 comprises an amino acid sequence of SEQ ID NO: 2, HCDR3 comprises an amino acid sequence of SEQ ID NO: 3, LCDR1 comprises an amino acid sequence of SEQ ID NO: 4, LCDR2 comprises an amino acid sequence of SEQ TD NO: 5, and LCDR3 comprises an amino acid sequence of SEQ ID NO: 6.
Claims37
1:
- An anti-PAD4 antibody or an antibody fragment thereof, comprising:
- HCDR1 comprising an amino acid sequence of SEQ ID NO:
- 1;
- HCDR2 comprising an amino acid sequence of SEQ ID NO:
- 2;
- HCDR3 comprising an amino acid sequence of SEQ ID NO:
- 3;
- LCDR1 comprising an amino acid sequence of SEQ ID NO:
- 4;
- LCDR2 comprising an amino acid sequence of SEQ ID NO:
- 5;
- and
- LCDR3 comprising an amino acid sequence of SEQ ID NO:
- 6,
- wherein each of the HCDR1, HCDR2 and HCDR3 is a heavy chain complementarity determining region, and each of the LCDR1, LCDR2 and LCDR3 is a light chain complementarity determining region.
12 more elements
2:
- The anti-PAD4 antibody or the antibody fragment thereof according to claim 1, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:
- 1, the HCDR2 comprises any one of amino acid sequences of SEQ ID NOs:
- 7-10, the HCDR3 comprises an amino acid sequence of SEQ ID NO:
- 11 or 12, the LCDR1 comprises the amino acid sequence of SEQ ID NO:
- 4, the LCDR2 comprises the amino acid sequence of SEQ ID NO:
- 5, and the LCDR3 comprises any one of amino acid sequences of SEQ ID NOs:
- 13-15.
4 more elements
3:
- The anti-PAD4 antibody or the antibody fragment thereof according to claim 1, wherein said anti-PAD4 antibody or the antibody fragment thereof is selected from the group consisting of:
- an anti-PAD4 antibody or an antibody fragment thereof, comprising HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 1, HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 7, HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 11, LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 4, LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 5, and LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 13;
- an anti-PAD4 antibody or an antibody fragment thereof, comprising HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 1, HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 8, HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 11, LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 4, LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 5, and LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 13;
- an anti-PAD4 antibody or an antibody fragment thereof, comprising HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 1, HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 9, HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 12, LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 4, LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 5, and LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 14;
- and
- an anti-PAD4 antibody or an antibody fragment thereof, comprising HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 1, HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 10, HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 11, LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 4, LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 5, and LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 15.
27 more elements
4:
- The anti-PAD4 antibody or the antibody fragment thereof according to claim 1, wherein said anti-PAD4 antibody or the antibody fragment thereof is selected from the group consisting of:
- an anti-PAD4 antibody or an antibody fragment thereof, wherein the HCDR1 consists of the amino acid sequence of SEQ ID NO:
- 1, the HCDR2 consists of the amino acid sequence of SEQ ID NO:
- 7, the HCDR3 consists of the amino acid sequence of SEQ ID NO:
- 11, the LCDR1 consists of the amino acid sequence of SEQ ID NO:
- 4, the LCDR2 consists of the amino acid sequence of SEQ ID NO:
- 5, and the LCDR3 consists of the amino acid sequence of SEQ ID NO:
- 13;
- an anti-PAD4 antibody or an antibody fragment thereof, wherein the HCDR1 consists of the amino acid sequence of SEQ ID NO:
- 1, the HCDR2 consists of the amino acid sequence of SEQ ID NO:
- 8, the HCDR3 consists of the amino acid sequence of SEQ ID NO:
- 11, the LCDR1 consists of the amino acid sequence of SEQ ID NO:
- 4, the LCDR2 consists of the amino acid sequence of SEQ ID NO:
- 5, and the LCDR3 consists of the amino acid sequence of SEQ ID NO:
- 13;
- an anti-PAD4 antibody or an antibody fragment thereof, wherein the HCDR1 consists of the amino acid sequence of SEQ ID NO:
- 1, the HCDR2 consists of the amino acid sequence of SEQ ID NO:
- 9, the HCDR3 consists of the amino acid sequence of SEQ ID NO:
- 12, the LCDR1 consists of the amino acid sequence of SEQ ID NO:
- 4, the LCDR2 consists of the amino acid sequence of SEQ ID NO:
- 5, and the LCDR3 consists of the amino acid sequence of SEQ ID NO:
- 14;
- and
- an anti-PAD4 antibody or an antibody fragment thereof, wherein the HCDR1 consists of the amino acid sequence of SEQ ID NO:
- 1, the HCDR2 consists of the amino acid sequence of SEQ ID NO:
- 10, the HCDR3 consists of the amino acid sequence of SEQ ID NO:
- 11, the LCDR1 consists of the amino acid sequence of SEQ ID NO:
- 4, the LCDR2 consists of the amino acid sequence of SEQ ID NO:
- 5, and the LCDR3 consists of the amino acid sequence of SEQ ID NO:
- 15.
27 more elements
5:
- An anti-PAD4 antibody or an antibody fragment thereof, wherein said anti-PAD4 antibody or the antibody fragment thereof is selected from the group consisting of:
- an anti-PAD4 antibody or an antibody fragment thereof, comprising a heavy chain variable region comprising an amino acid sequence of amino acid numbers 1-120 of SEQ ID NO:
- 16, and a light chain variable region comprises an amino acid sequence of amino acid numbers 1-105 of SEQ ID NO:
- 17;
- an anti-PAD4 antibody or an antibody fragment thereof, comprising a heavy chain variable region comprising an amino acid sequence of amino acid numbers 1-120 of SEQ ID NO:
- 18, and a light chain variable region comprising an amino acid sequence of amino acid numbers 1-105 of SEQ ID NO:
- 19;
- an anti-PAD4 antibody or an antibody fragment thereof, comprising a heavy chain variable region comprising an amino acid sequence of amino acid numbers 1-120 of SEQ ID NO:
- 20, and a light chain variable region comprising an amino acid sequence of amino acid numbers 1-105 of SEQ ID NO:
- 21;
- and
- an anti-PAD4 antibody or an antibody fragment thereof, comprising a heavy chain variable region comprising an amino acid sequence of amino acid numbers 1-120 of SEQ ID NO:
- 22, and a light chain variable region comprising an amino acid sequence of amino acid numbers 1-105 of SEQ ID NO:
- 23.
11 more elements
6:
- The anti-PAD4 antibody or the antibody fragment thereof according to claim 5, wherein said anti-PAD4 antibody or the antibody fragment thereof is selected from the group consisting of:
- an anti-PAD4 antibody or an antibody fragment thereof, comprising a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1-120 of SEQ ID NO:
- 16, and a light chain variable region consisting of the amino acid sequence of amino acid numbers 1-105 of SEQ ID NO:
- 17;
- an anti-PAD4 antibody or an antibody fragment thereof, comprising a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1-120 of SEQ ID NO:
- 18, and a light chain variable region consisting of the amino acid sequence of amino acid numbers 1-105 of SEQ ID NO:
- 19;
- an anti-PAD4 antibody or an antibody fragment thereof, comprising a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1-120 of SEQ ID NO:
- 20, and a light chain variable region consisting of the amino acid sequence of amino acid numbers 1-105 of SEQ ID NO:
- 21;
- and
- an anti-PAD4 antibody or an antibody fragment thereof, comprising a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1-120 of SEQ ID NO:
- 22, and a light chain variable region consisting of the amino acid sequence of amino acid numbers 1-105 of SEQ ID NO:
- 23.
11 more elements
7:
- The anti-PAD4 antibody or the antibody fragment thereof according to claim 5, wherein said anti-PAD4 antibody or the antibody fragment thereof is selected from the group consisting of:
- an anti-PAD4 antibody or an antibody fragment thereof, comprising a heavy chain consisting of an amino acid sequence of SEQ ID NO:
- 16, and a light chain consisting of an amino acid sequence of SEQ ID NO:
- 17;
- an anti-PAD4 antibody or an antibody fragment thereof, comprising a heavy chain consisting of an amino acid sequence of SEQ ID NO:
- 18, and a light chain consisting of an amino acid sequence of SEQ ID NO:
- 19;
- an anti-PAD4 antibody or an antibody fragment thereof, comprising a heavy chain consisting of an amino acid sequence of SEQ ID NO:
- 20, and a light chain consisting of an amino acid sequence of SEQ ID NO:
- 21;
- and
- an anti-PAD4 antibody or an antibody fragment thereof, comprising a heavy chain consisting of an amino acid sequence of SEQ ID NO:
- 22, and a light chain consisting of an amino acid sequence of SEQ ID NO:
- 23.
11 more elements
8:
- The anti-PAD4 antibody or the antibody fragment thereof according to claim 1, wherein an amino acid corresponding to the 84th amino acid of a heavy chain is serine.
9:
- The anti-PAD4 antibody or the antibody fragment thereof according to claim 1, wherein a KD value with respect to PAD4 is 100 pM or less.
10:
- The anti-PAD4 antibody or the antibody fragment thereof according to claim 1, wherein said anti-PAD4 antibody or the antibody fragment thereof has a binding amount of 90% or more when the anti-PAD4 antibody or the antibody fragment thereof is stored at 40° C. for one month as compared to a PAD4-binding amount of the anti-PAD4 antibody or the antibody fragment thereof before the storage.
11:
- An anti-PAD4 antibody or an antibody fragment thereof, comprising:
- HCDR1 comprising an amino acid sequence of SEQ ID NO:
- 1;
- HCDR2 comprising an amino acid sequence of SEQ ID NO:
- 24;
- HCDR3 comprising an amino acid sequence of SEQ ID NO:
- 11;
- LCDR1 comprising an amino acid sequence of SEQ ID NO:
- 4;
- LCDR2 comprising an amino acid sequence of SEQ ID NO:
- 5;
- and
- LCDR3 comprising an amino acid sequence of SEQ ID NO:
- 25,
- wherein each of the HCDR1, HCDR2 and HCDR3 is a heavy chain complementarity determining region, each of the LCDR1, LCDR2 and LCDR3 is a light chain complementarity determining region, and an amino acid corresponding to the 84th amino acid of a heavy chain is serine.
12 more elements
12:
- The anti-PAD4 antibody or the antibody fragment thereof according to claim 11, wherein the HCDR1 consists of the amino acid sequence of SEQ ID NO:
- 1, the HCDR2 consists of the amino acid sequence of SEQ ID NO:
- 24, the HCDR3 consists of the amino acid sequence of SEQ ID NO:
- 11, the LCDR1 consists of the amino acid sequence of SEQ ID NO:
- 4, the LCDR2 consists of the amino acid sequence of SEQ ID NO:
- 5, the LCDR3 consists of the amino acid sequence of SEQ ID NO:
- 25, wherein and the amino acid corresponding to the 84th amino acid of a heavy chain is serine.
4 more elements
13:
- An anti-PAD4 antibody or an antibody fragment thereof, comprising:
- a heavy chain variable region comprising an amino acid sequence of amino acid numbers 1-120 of SEQ ID NO:
- 28, and
- a light chain variable region comprising an amino acid sequence of amino acid numbers 1-105 of SEQ ID NO:
- 27.
2 more elements
14:
- The anti-PAD4 antibody or the antibody fragment thereof according to claim 13, wherein the heavy chain variable region consists of the amino acid sequence of amino acid numbers 1-120 of SEQ ID NO:
- 28, and the light chain variable region consists of the amino acid sequence of amino acid numbers 1-105 of SEQ ID NO:
- 27.
15:
- The anti-PAD4 antibody or the antibody fragment thereof according to claim 13, wherein the heavy chain consists of SEQ ID NO:
- 28 and the light chain consists of SEQ ID NO:
- 27.
16:
- The anti-PAD4 antibody or the antibody fragment thereof according to claim 11, wherein cleavage occurring during generation is less than 3% of a total generation amount.
17:
- The anti-PAD4 antibody or the antibody fragment thereof according to claim 1, wherein the antibody is a neutralizing antibody.
18:
- The anti-PAD4 antibody or the antibody fragment thereof according to claim 1, wherein the antibody is a PAD4 binding antibody represented by SEQ ID NO:
- 29.
19:
- A nucleic acid molecule, comprising:
- a base sequence encoding the anti-PAD4 antibody or the antibody fragment thereof of claim 1.
20:
- A recombinant vector, comprising:
- the nucleic acid molecule of claim 19.
21:
- A transformant, comprising:
- the recombinant vector of claim 20.
22:
- A pharmaceutical composition, comprising:
- the anti-PAD4 antibody or the antibody fragment thereof of claim 1.
23:
- A preventive agent or a therapeutic agent for rheumatoid arthritis or arthritis, systemic lupus erythematosus, lupus nephritis, or graft-versus-host disease, comprising:
- the pharmaceutical composition of claim 22.
24:
- An inhibiting agent of citrullination in a protein, comprising:
- the pharmaceutical composition of claim 22.
25:
- An inhibiting agent of netosis in cells, comprising:
- the pharmaceutical composition of claim 22.
26-27. (canceled)
28:
- A method for preventing or treating rheumatoid arthritis or arthritis, systemic lupus erythematosus, lupus nephritis, or graft-versus-host disease, comprising:
- administering an effective amount of the anti-PAD4 antibody or the antibody fragment thereof of claim 1 to a subject in need thereof.
29:
- The method according to claim 28, wherein citrullination is inhibited in a protein.
30:
- The method according to claim 28, wherein netosis is inhibited in cells.
31:
- A nucleic acid molecule, comprising:
- a base sequence encoding the anti-PAD4 antibody or the antibody fragment thereof of claim 11.
32:
- A recombinant vector, comprising:
- the nucleic acid molecule of claim 31.
33:
- A transformant, comprising:
- the recombinant vector of claim 32.
34:
- A pharmaceutical composition, comprising:
- the anti-PAD4 antibody or the antibody fragment thereof of claim 11.
35:
- A method for preventing or treating rheumatoid arthritis or arthritis, systemic lupus erythematosus, lupus nephritis, or graft-versus-host disease, comprising:
- administering an effective amount of the pharmaceutical composition of claim 34 to a subject in need thereof.
36:
- A method for preventing or treating rheumatoid arthritis or arthritis, systemic lupus erythematosus, lupus nephritis, or graft-versus-host disease, comprising:
- administering an effective amount of the anti-PAD4 antibody or the antibody fragment thereof of claim 11 to a subject in need thereof.
37:
- The method according to claim 36, wherein citrullination is inhibited in a protein.
38:
- The method according to claim 37, wherein netosis is inhibited in cells.