IP Library › Granted Patent US 12,440,561
Granted Patent B2
US 12,440,561 · App. 16/858,301 · Granted Oct 14, 2025

Method of diagnosis and treatment of rheumatoid arthritis

Inventors: Anita Boyapati (Chappaqua, NY); Jérôme Msihid (Antony, FR); Moshe E. Zilberstein (North Caldwell, NJ)
Assignees: SANOFI BIOTECHNOLOGY; REGENERON PHARMACEUTICALS, INC.
A61K39/3955A61B5/4848A61K9/08A61K31/519A61P19/02C07K16/2866C07K2317/51C07K2317/515
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Quick Facts
Patent No.
US 12,440,561
App. No.
16/858,301
Granted
Oct 14, 2025
Kind
B2
Abstract

The present disclosure relates to the use of an anti-IL6 receptor antibody for treating rheumatoid arthritis in subjects with serum concentrations of certain biomarkers.

Claims (38)

1. A method of treating rheumatoid arthritis in a subject comprising:

A) (a) identifying a subject with rheumatoid arthritis whose serum sample is determined to have a pre-dose (baseline) serum concentration of serum amyloid A (SAA) greater than 105.2 ng/ml and less than 256.0 ng/ml,

(b) identifying a subject with rheumatoid arthritis whose serum sample is determined to have a pre-dose (baseline) serum concentration of matrix metalloproteinase-3 (MMP-3) greater than 77.0 ng/ml and less than 154.3 ng/ml, or

(c) identifying a subject with rheumatoid arthritis whose serum sample is determined to have a pre-dose (baseline) serum concentration of chemokine C-X-C motif ligand 13 (CXCL13) less than 72.0 pg/mL and a pre-dose (baseline) serum concentration of soluble intracellular adhesion molecule-1 (sICAM-1) less than 212.1 ng/ml; and

B) administering to the subject identified in any of (a)-(c) about 150 mg to about 200 mg of an anti-interleukin 6 receptor (anti-IL-6R) antibody once every two weeks, wherein the antibody comprises a heavy chain variable region comprising the sequence of SEQ ID NO: 1 and a light chain variable region comprising the sequence of SEQ ID NO: 2, and wherein the antibody is administered subcutaneously.

2. The method of claim 1 , wherein the subject has moderate to severe rheumatoid arthritis, or wherein the subject has had an inadequate response or is intolerant to one or more disease-modifying antirheumatic drugs (DMARDs) other than the antibody.

3. The method of claim 2 , wherein the one or more DMARDs comprise methotrexate.

4. The method of claim 1 , wherein the subject achieves an American College of Rheumatology 20 (ACR20), ACR50, or ACR70 after 24 weeks of treatment with the antibody.

5. The method of claim 1 , wherein the subject achieves a Disease Activity Score (28 joints) using C-reactive protein (DAS28-CRP) score of less than 3.2 after 24 weeks of treatment with the antibody.

6. The method of claim 1 , wherein the subject achieves an improvement in patient global VAS, HAQ-DI, Pain VAS, SF-36-PCS score, SF-36-PF domain or morning stiffness VAS or RAID score after 24 weeks of treatment with the antibody.

7. The method of claim 1 , comprising identifying a subject with rheumatoid arthritis whose serum sample is determined to have a pre-dose (baseline) serum concentration of SAA greater than 105.2 ng/ml and less than 256.0 ng/ml.

8. The method of claim 1 , comprising identifying a subject with rheumatoid arthritis whose serum sample is determined to have a pre-dose (baseline) serum concentration of MMP-3 greater than 77.0 ng/ml and less than 154.3 ng/ml.

9. The method of claim 1 , comprising identifying a subject with rheumatoid arthritis whose serum sample is determined to have a pre-dose (baseline) serum concentration of CXCL13 less than 72.0 pg/mL and a pre-dose (baseline) serum concentration of sICAM-1 less than 212.1 ng/ml.

10. The method of claim 1 , wherein the antibody is sarilumab.

11. The method of claim 1 , wherein the antibody is administered subcutaneously at about 150 mg once every two weeks to the subject.

12. The method of claim 1 , wherein the antibody is administered subcutaneously at about 200 mg once every two weeks to the subject.

13. The method of claim 1 , wherein the antibody is administered with a prefilled syringe or with an auto-injector.

14. The method of claim 1 , wherein the antibody is administered as an aqueous buffered solution at about pH 6.0 containing about 21 mM histidine, about 45 mM arginine, about 0.2% (w/v) polysorbate 20, and about 5% (w/v) sucrose.

15. The method of claim 14 , wherein the solution comprises at least about 130 mg/mL of the antibody, or wherein the solution comprises about 131.6 mg/ml of the antibody, or wherein the solution comprises about 175 mg/ml of the antibody.

16. The method of claim 1 , further comprising administering to the subject, methotrexate at about 6 mg to about 25 mg every week.

17. A method of treating a subject with rheumatoid arthritis (RA) that has an increased propensity for effective treatment, comprising:

A) (a) measuring a pre-dose (baseline) serum concentration of SAA in a serum sample from a subject with rheumatoid arthritis, wherein if the serum sample has a pre-dose (baseline) serum concentration of SAA greater than 105.2 ng/ml and less than 256.0 ng/ml, the subject has an increased propensity for effective treatment of RA with an anti-IL-6R antibody, or

(b) measuring a pre-dose (baseline) serum concentration of MMP-3 in a serum sample from a subject with rheumatoid arthritis, wherein if the serum sample has a pre-dose (baseline) serum concentration of MMP-3 greater than 77.0 ng/ml and less than 154.3 ng/ml, the subject has an increased propensity for effective treatment of RA with an anti-IL-6R antibody, or

(c) measuring a pre-dose (baseline) serum concentration of CXCL13 and a pre-dose (baseline) serum concentration of sICAM-1 in a serum sample from a subject with rheumatoid arthritis, wherein if the serum sample has a pre-dose (baseline) serum concentration of CXCL13 less than 72.0 pg/mL and a pre-dose (baseline) serum concentration of sICAM-1 less than 212.1 ng/ml, the subject has an increased propensity for effective treatment of RA with an anti-IL-6R antibody; and

B) administering an anti-IL-6R antibody to the subject who is determined in any of (a)-(c) to have an increased propensity for effective treatment of RA with an anti-IL-6R antibody, wherein the anti-IL-6R antibody comprises a heavy chain variable region comprising the sequence SEQ ID NO: 1 and a light chain variable region comprising the sequence SEQ ID NO: 2, wherein the antibody is administered at about 150 mg to about 200 mg once every two weeks, and wherein the antibody is administered subcutaneously.

18. The method of claim 17 , wherein the subject who is determined to have an increased propensity for effective treatment of RA with the anti-IL-6R antibody has an increased propensity of achieving

(a) ACR20, ACR50 or ACR70 after 24 weeks of treatment with the antibody;

(b) DAS28-CRP score of less than 3.2 after 24 weeks of treatment with the antibody; or

(c) an improvement in patient global VAS, HAQ-DI, Pain VAS, SF-36-PCS score, SF-36-RE domain, morning stiffness VAS or RAID score after 24 weeks of treatment with the antibody.

19. The method of claim 17 , wherein the subject has moderate to severe rheumatoid arthritis.

20. The method of claim 17 , wherein the subject is intolerant to one or more DMARDs other than the antibody.

21. The method of claim 20 , wherein the one or more DMARDs comprise methotrexate.

22. The method of claim 17 , wherein the subject has moderate to severe rheumatoid arthritis and has had an inadequate response or is intolerant to one or more DMARDs.

23. The method of claim 22 , wherein the one or more DMARDs comprise methotrexate.

24. The method of claim 17 , wherein the antibody is sarilumab.

25. The method of claim 17 , comprising measuring a pre-dose (baseline) serum concentration of SAA in a serum sample from a subject with rheumatoid arthritis, wherein if the serum sample has a pre-dose (baseline) serum concentration of SAA greater than 105.2 ng/ml and less than 256.0 ng/ml, the subject has an increased propensity for effective treatment of RA with the anti-IL-6R antibody.

26. The method of claim 17 , comprising measuring a pre-dose (baseline) serum concentration of MMP-3 in a serum sample from a subject with rheumatoid arthritis, wherein if the serum sample has a pre-dose (baseline) serum concentration of MMP-3 greater than 77.0 ng/ml and less than 154.3 ng/ml, the subject has an increased propensity for effective treatment of RA with the anti-IL-6R antibody.

27. The method of claim 17 , comprising measuring a pre-dose (baseline) serum concentration of CXCL13 and a pre-dose (baseline) serum concentration of sICAM-1 in a serum sample from a subject with rheumatoid arthritis, wherein if the serum sample has a pre-dose (baseline) serum concentration of CXCL13 less than 72.0 pg/mL and a pre-dose (baseline) serum concentration of sICAM-1 less than 212.1 ng/ml, the subject has an increased propensity for effective treatment of RA with the anti-IL-6R antibody.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 22, 2025
From: ZILBERSTEIN, MOSHE E.
To: SANOFI BIOTECHNOLOGY
Reel/Frame 069958/0637 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 22, 2025
From: MSIHID, JÉRÔME
To: SANOFI-AVENTIS GROUPE
Reel/Frame 069958/0708 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 22, 2025
From: SANOFI-AVENTIS GROUPE
To: SANOFI BIOTECHNOLOGY
Reel/Frame 069958/0875 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 22, 2025
From: BOYAPATI, ANITA
To: REGENERON PHARMACEUTICALS, INC.
Reel/Frame 069958/0901 →
Priority Claims (1)
EP 20305193 · Feb 27, 2020 · regional
Continuity (2)
Provisional Application 62837793 · Apr 24, 2019
Related Publication 20200405851A1 · Dec 31, 2020
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