IP Library Granted Patent US 11,278,618
Granted Patent B2
US 11,278,618 · App. 15/508,441 · Granted Mar 22, 2022

Use of IL-17 antagonists to inhibit the progression of structural damage in psoriatic arthritis patients

Inventors: Shephard Mpofu (Oberwil, CH); Hanno Richards (Therwil, CH); Gregory Ligozio (Basking Ridge, NJ)
Assignee: NOVARTIS AG
A61K39/3955A61K39/00C07K16/18C07K16/244A61K45/00A61K2039/505A61K2039/545
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Quick Facts
Patent No.
US 11,278,618
App. No.
15/508,441
Granted
Mar 22, 2022
Kind
B2
Abstract

The present disclosure relates to methods, uses, medicaments, pharmaceutical formulations, dosage forms, and kits for inhibiting the progression of structural damage in psoriatic arthritis (PsA) patients using Interleukin-17 (IL-17) antagonists, e.g., IL-17 antibodies and antigen-binding fragments thereof, e.g., secukinumab.

Claims (38)

1. A method of inhibiting the progression of structural damage in a patient having psoriatic arthritis (PsA), comprising selectively administering to the patient a dose of about 300 mg of an anti-Interleukin-17 (IL-17) antibody by subcutaneous injection every 4 weeks, wherein the patient is selected for treatment with the dose of about 300 mg based on the patient previously failing treatment with a Tumor Necrosis Factor (TNF) alpha antagonist or previously responding inadequately to treatment with a TNF alpha antagonist, and wherein:

i) the anti-IL-17 antibody comprises an immunoglobulin V H domain comprising the amino acid sequence set forth as SEQ ID NO:8 and an immunoglobulin V L domain comprising the amino acid sequence set forth as SEQ ID NO:10;

ii) the anti-IL-17 antibody comprises an immunoglobulin V H domain comprising the hypervariable regions set forth as SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3 and an immunoglobulin V L domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6;

iii) the anti-IL-17 antibody comprises an immunoglobulin V H domain comprising the hypervariable regions set forth as SEQ ID NO:11, SEQ ID NO:12 and SEQ ID NO:13 and an immunoglobulin V L domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6;

iv) the anti-IL-17 antibody comprises an immunoglobulin light chain comprising the amino acid sequence set forth as SEQ ID NO:14 and an immunoglobulin heavy chain comprising the amino acid sequence set forth as SEQ ID NO:15; or

v) the anti-IL-17 antibody is secukinumab.

2. The method according to claim 1 , wherein the anti-IL-17 antibody is administered concomitantly with a disease-modifying anti-rheumatic drug (DMARD) selected from the group consisting of hydroxychloroquine, chloroquine, sulfasalazine, leflunomide, azathioprine, cyclosporine, gold salts, minocycline, cyclophosphamide, D-penicillamine, minocycline, auranofin, tacrolimus, myocrisin, methotrexate, and chlorambucil.

3. The method according to claim 1 , wherein the progression of erosion, joint space narrowing, pencil-in-cup phenomena, joint widening, joint narrowing, subluxation, bony proliferation, osteolysis, or ankylosis is inhibited in the patient.

4. The method according to claim 1 , wherein following administration of the anti-IL-17 antibody, the patient experiences:

a) a change from baseline in the van der Heijde psoriatic arthritis-modified total Sharp score (mTSS) of ≤0.5;

b) a change from baseline in erosion score of ≤0.3; and/or

c) a change from baseline in joint space narrowing (JSN) score of ≤0.2.

5. The method according to claim 1 , wherein the anti-IL-17 antibody is secukinumab.

6. The method according to claim 5 , wherein secukinumab is disposed in a liquid pharmaceutical composition that is not reconstituted from a lyophilisate.

7. The method according to claim 6 , wherein the concentration of secukinumab in the liquid pharmaceutical composition is 150 mg/ml.

8. The method according to claim 7 , wherein 1 or 2 milliliters of the liquid pharmaceutical composition is disposed within an injection pen, a pre-filled syringe, or an autoinjector.

9. The method according to claim 6 , wherein the liquid pharmaceutical composition further comprises a buffer, carrier, diluent, filler, salt, stabilizer, or solubilizer.

10. The method according to claim 1 , wherein the anti-IL-17 antibody is administered concomitantly with a non-steroidal anti-inflammatory drug (NSAID) selected from the group consisting of a propionic acid derivative, acetic acid derivative, enolic acid derivative, fenamic acid derivative, Cox inhibitor, lumiracoxib, ibuprophen, fenoprofen, ketoprofen, flurbiprofen, oxaprozin, indomethacin, sulindac, etodolac, ketorolac, nabumetone, aspirin, naproxen, valdecoxib, etoricoxib, rofecoxib, acetominophen, celecoxib, diclofenac, tramadol, piroxicam, meloxicam, tenoxicam, droxicam, lornoxicam, isoxicam, mefanamic acid, meclofenamic acid, flufenamic acid, tolfenamic, valdecoxib, parecoxib, etodolac, indomethacin, aspirin, ibuprophen, and firocoxib.

11. The method according to claim 1 , wherein the anti-IL-17 antibody is administered concomitantly with a steroid selected from the group consisting of prednisolone, prednisone, dexamethasone, cortisol, cortisone, hydrocortisone, methylprednisolone, betamethasone, triamcinolone, beclometasome, fludrocortisone, deoxycorticosterone, and aldosterone.

12. A method of inhibiting the progression of structural damage in a patient having psoriatic arthritis (PsA), comprising selectively administering to the patient a dose of about 300 mg of an anti-Interleukin-17 (IL-17) antibody by subcutaneous injection with dosing at week 0, 1, 2, 3, and 4, followed by dosing every 4 weeks, wherein the patient is selected for treatment with the dose of about 300 mg based on the patient previously failing treatment with a Tumor Necrosis Factor (TNF) alpha antagonist or previously responding inadequately to treatment with a TNF alpha antagonist, and wherein:

i) the anti-IL-17 antibody comprises an immunoglobulin V H domain comprising the amino acid sequence set forth as SEQ ID NO:8 and an immunoglobulin V L domain comprising the amino acid sequence set forth as SEQ ID NO:10;

ii) the anti-IL-17 antibody comprises an immunoglobulin V H domain comprising the hypervariable regions set forth as SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3 and an immunoglobulin V L domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6;

iii) the anti-IL-17 antibody comprises an immunoglobulin V H domain comprising the hypervariable regions set forth as SEQ ID NO:11, SEQ ID NO:12 and SEQ ID NO:13 and an immunoglobulin V L domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6;

iv) the anti-IL-17 antibody comprises an immunoglobulin light chain comprising the amino acid sequence set forth as SEQ ID NO:14 and an immunoglobulin heavy chain comprising the amino acid sequence set forth as SEQ ID NO:15; or

v) the anti-IL-17 antibody is secukinumab.

13. The method according to claim 12 , wherein the anti-IL-17 antibody is administered concomitantly with a disease-modifying anti-rheumatic drug (DMARD) selected from the group consisting of hydroxychloroquine, chloroquine, sulfasalazine, leflunomide, azathioprine, cyclosporine, gold salts, minocycline, cyclophosphamide, D-penicillamine, minocycline, auranofin, tacrolimus, myocrisin, methotrexate, and chlorambucil.

14. The method according to claim 12 , wherein the progression of erosion, joint space narrowing, pencil-in-cup phenomena, joint widening, joint narrowing, subluxation, bony proliferation, osteolysis, or ankylosis is inhibited in the patient.

15. The method according to claim 12 , wherein following administration of the anti-IL-17 antibody, the patient experiences:

a) a change from baseline in the van der Heijde psoriatic arthritis-modified total Sharp score (mTSS) of ≤0.5;

b) a change from baseline in erosion score of ≤0.3; and/or

c) a change from baseline in joint space narrowing (JSN) score of ≤0.2.

16. The method according to claim 12 , wherein the anti-IL-17 antibody is secukinumab.

17. The method according to claim 16 , wherein secukinumab is disposed in a liquid pharmaceutical composition that is not reconstituted from a lyophilisate.

18. The method according to claim 17 , wherein the concentration of secukinumab in the liquid pharmaceutical composition is 150 mg/ml.

19. The method according to claim 18 , wherein 1 or 2 milliliters of the liquid pharmaceutical composition is disposed within an injection pen, a pre-filled syringe, or an autoinjector.

20. The method according to claim 17 , wherein the liquid pharmaceutical composition further comprises a buffer, carrier, diluent, filler, salt, stabilizer, or solubilizer.

21. The method according to claim 12 , wherein the anti-IL-17 antibody is administered concomitantly with a non-steroidal anti-inflammatory drug (NSAID) selected from the group consisting of a propionic acid derivative, acetic acid derivative, enolic acid derivative, fenamic acid derivative, Cox inhibitor, lumiracoxib, ibuprophen, fenoprofen, ketoprofen, flurbiprofen, oxaprozin, indomethacin, sulindac, etodolac, ketorolac, nabumetone, aspirin, naproxen, valdecoxib, etoricoxib, rofecoxib, acetominophen, celecoxib, diclofenac, tramadol, piroxicam, meloxicam, tenoxicam, droxicam, lornoxicam, isoxicam, mefanamic acid, meclofenamic acid, flufenamic acid, tolfenamic, valdecoxib, parecoxib, etodolac, indomethacin, aspirin, ibuprophen, and firocoxib.

22. The method according to claim 12 , wherein the anti-IL-17 antibody is administered concomitantly with a steroid selected from the group consisting of prednisolone, prednisone, dexamethasone, cortisol, cortisone, hydrocortisone, methylprednisolone, betamethasone, triamcinolone, beclometasome, fludrocortisone, deoxycorticosterone, and aldosterone.

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 11, 2026
From: NOVARTIS AG
To: NOVARTIS PHARMA AG
Reel/Frame 075712/0291 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 2, 2018
From: MPOFU, SHEPHARD; RICHARDS, HANNO
To: NOVARTIS PHARMA AG
Reel/Frame 045094/0641 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 2, 2018
From: NOVARTIS PHARMA AG
To: NOVARTIS AG
Reel/Frame 045094/0650 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 2, 2018
From: LIGOZIO, GREGORY
To: NOVARTIS PHARMACEUTICALS CORPORATION
Reel/Frame 045094/0658 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 2, 2018
From: NOVARTIS PHARMACEUTICALS CORPORATION
To: NOVARTIS AG
Reel/Frame 045094/0663 →
Continuity (2)
Provisional Application 62048512 · Sep 10, 2014
Related Publication 20170281762A1 · Oct 5, 2017