Anti-PAD4 antibody

Patent metadata

Field	Value
Publication number	US-12448464-B2
Application number	US-202217933229-A
Country	US
Kind code	B2
Filing date	Sep 19, 2022
Priority date	Mar 6, 2015
Publication date	Oct 21, 2025
Grant date	Oct 21, 2025

Abstract

Provided are anti-PAD4 antibodies having excellent properties and an excellent method for treatment of RA. Used are anti-PAD4 antibodies that specifically bind to an epitope containing positions 345, 347, and 348 of PAD4. These anti-PAD4 antibodies may inhibit the citrullination activity of PAD4. In addition, these anti-PAD4 antibodies may have a KD (M) of 9.0×10 −9 or less. Optionally, the anti-PAD4 antibody and a TNFα inhibitor are used in combination.

First claim

The invention claimed is:

1. A method of treating rheumatoid arthritis (RA) or arthritis comprising administering to a patient in need thereof an anti-PAD4 (peptidylarginine deiminase 4) antibody in combination with a TNFα inhibitor, wherein the antibody specifically binds to positions 345, 347, and 348 of human PAD4.

2. The method according to claim 1 , wherein the patient has already received the TNFα inhibitor.

3. The method according to claim 1 , wherein the antibody is a humanized antibody.

4. The method according to claim 1 , wherein the TNFα inhibitor is an anti-TNFα antibody, a TNF receptor-fusion protein, a dominant negative TNFα mutant, an RNAi molecule against TNFα, a miRNA molecule against TNFα, an antisense nucleic acid against TNFα, a polynucleotide encoding an RNAi molecule against TNFα, or a polynucleotide encoding an miRNA molecule against TNFα.

5. The method according to claim 1 , wherein the TNFα inhibitor is an anti-TNFα antibody or a TNF receptor-fusion protein.

6. A method of treating arthritis, comprising administering to a patient in need thereof an anti-PAD4 (peptidylarginine deiminase 4) antibody which specifically binds to an epitope containing positions 345, 347, and 348 of human PAD4.

7. The method according to claim 6 , wherein the antibody inhibits citrullination activity of PAD4.

8. The method according to claim 6 , wherein the antibody binds human PAD4 with a KD (M) of 9.0×10 −9 or less.

9. The method according to claim 6 , wherein the epitope is identified by alanine scan in which a single amino acid is replaced.

10. The method according to claim 6 , wherein the antibody is a monoclonal antibody.

11. The method according to claim 6 , wherein the antibody is a humanized antibody.

12. An anti-human PAD4 antibody which binds to a peptide, the amino acid sequence of which is set forth in SEQ ID NO: 1, but cannot bind to a peptide, the amino acid sequence of which is set forth in SEQ ID NO: 32, 34, or 35.

13. The anti-human PAD4 antibody according to claim 12 , wherein the antibody inhibits citrullination activity of PAD4.

14. The anti-human PAD4 antibody according to claim 12 , wherein the antibody binds human PAD4 with a KD (M) of 9.0×10 −9 or less.

15. The anti-human PAD4 antibody according to claim 12 , wherein the antibody is a humanized antibody.

16. A method of treating rheumatoid arthritis or arthritis, comprising administering to a patient in need thereof the anti-human PAD4 antibody according to claim 12 .

Assignees

• Public Univ Corp Yokohama City Univ
• Univ Nagoya City Public Univ Corp
• Pharma Foods Int Co Ltd

Inventors

• Sato Mamoru
• Yamada Michiyuki
• Kanazawa Satoshi
• Toyoura Masayoshi
• Shoya Yuji
• Saito Kenji
• Yamazaki Chihiro

Classifications

• C12Y305/03015

  Protein-arginine deiminase (3.5.3.15) · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title