Anti-IL-6 antibodies for the treatment of arthritis

Patent metadata

Field	Value
Publication number	US-10858424-B2
Application number	US-201715704848-A
Country	US
Kind code	B2
Filing date	Sep 14, 2017
Priority date	Nov 25, 2008
Publication date	Dec 8, 2020
Grant date	Dec 8, 2020

Abstract

The present invention is directed to therapeutic methods using IL-6 antagonists such as anti-IL-6 antibodies and fragments thereof having binding specificity for IL-6 to prevent or treat rheumatoid arthritis.

First claim

What we claim is:

1. A method of treating an idiopathic condition associated with elevated interleukin (IL-6) levels other than rheumatoid arthritis comprising:
administering to a patient comprising an idiopathic condition associated with elevated IL-6 levels other than rheumatoid arthritis an antibody formulation comprising an anti-IL-6 antibody or antibody fragment wherein the variable light (V L ) chain CDR1, CDR2 and CDR3 polypeptides thereof respectively comprise the amino acid sequence of SEQ ID NO:4, 5 and 6 and the variable heavy (V H ) chain CDR1, CDR2 and CDR3 polypeptides thereof which respectively comprise the amino acid sequence of SEQ ID NO:7, 8 or 120, and 9, wherein the administered anti-IL-6 antibody or antibody fragment containing formulation comprises about 5 mM Histidine base, about 5 mM Histidine HCl to make final pH 6, 250 mM sorbitol, and 0.015% (w/w) Polysorbate 80, and the administered amount of said anti-IL-6 antibody or antibody fragment containing formulation is effective to treat said idiopathic condition associated with elevated IL-6 levels other than rheumatoid arthritis.

2. The method of claim 1 , wherein the concentration of said anti-IL-6 antibody or antibody fragment in the administered antibody formulation is at least about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 mg/mL or at least about 10-100 mg/mL.

3. The method of claim 1 , wherein the antibody formulation is administered subcutaneously or intravenously.

4. The method of claim 1 , wherein the antibody or antibody fragment containing said CDR polypeptides comprises a variable light chain polypeptide comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 709.

5. The method of claim 1 , wherein the antibody or antibody fragment containing said CDR polypeptides comprises a variable light chain polypeptide comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 709.

6. The method of claim 1 , wherein the antibody or antibody fragment containing said CDR polypeptides comprises a variable light chain polypeptide comprising an amino acid sequence of SEQ ID NO: 709.

7. The method of claim 1 , wherein said antibody or antibody fragment containing said CDR polypeptides comprises a variable heavy chain polypeptide comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 657.

8. The method of claim 1 , wherein said antibody or antibody fragment containing said CDR polypeptides comprises a variable heavy chain polypeptide comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 657.

9. The method of claim 1 , wherein said antibody or antibody fragment containing said CDR polypeptides comprises a variable heavy chain polypeptide comprising an amino acid sequence of SEQ ID NO: 657.

10. The method of claim 1 , wherein said anti-IL-6 antibody comprises the constant light chain amino acid sequence contained in SEQ ID NO: 586 and the constant heavy chain amino acid sequence contained in SEQ ID NO: 588.

11. The method of claim 1 , wherein said administered antibody formulation further comprises methotrexate or the method further comprises the administration of methotrexate.

12. The method of claim 1 , wherein said administered antibody formulation further comprises at least one anti-inflammatory agent, analgesic agent, or disease-modifying antirheumatic drug (DMARD) or the method further comprises the administration of at least one anti-inflammatory agent, analgesic agent, or disease-modifying antirheumatic drug (DMARD).

13. The method of claim 12 , wherein said anti-inflammatory agent is selected from the group consisting of steroids, Cortisone, Glucocorticoids, prednisone, prednisolone, Hydrocortisone (Cortisol), Cortisone acetate, Methylprednisolone, Dexamethasone, Betamethasone, Triamcinolone, Beclomethasone, and Fludrocortisone acetate, non-steroidal anti-inflammatory drug (NSAIDs), ibuprofen, naproxen, meloxicam, etodolac, nabumetone, sulindac, tolementin, choline magnesium salicylate, diclofenac, diflunisal, indomethacin, Ketoprofen, Oxaprozin, piroxicam, and nimesulide, Salicylates, Aspirin (acetylsalicylic acid), Diflunisal, Salsalate, p-amino phenol derivatives, Paracetamol, phenacetin, Propionic acid derivatives, Ibuprofen, Naproxen, Fenoprofen, Ketoprofen, Flurbiprofen, Oxaprozin, Loxoprofen, Acetic acid derivatives, Indomethacin, Sulindac, Etodolac, Ketorolac, Diclofenac, Nabumetone, Enolic acid (Oxicam) derivatives, Piroxicam, Meloxicam, Tenoxicam, Droxicam, Lornoxicam, Isoxicam, Fenamic acid derivatives (Fenamates), Mefenamic acid, Meclofenamic acid, Flufenamic acid, Tolfenamic acid, Selective COX-2 inhibitors (Coxibs), Celecoxib, Rofecoxib, Valdecoxib, Parecoxib, Lumiracoxib, Etoricoxib, Firocoxib, Sulphonanilides, Nimesulide, and Licofelone, the analgesic agent is selected from the group consisting of NSAIDs, COX-2 inhibitors, Celecoxib, Rofecoxib, Valdecoxib, Parecoxib, Lumiracoxib, Etoricoxib, Firocoxib, acetaminophen, opiates, Dextropropoxyphene, Codeine, Tramadol, Anileridine, Pethidine, Hydrocodone, Morphine, Oxycodone, Methadone, Diacetylmorphine, Hydromorphone, Oxymorphone, Levorphanol, Buprenorphine, Fentanyl, Sufentanyl, Etorphine, Carfentanil, dihydromorphine, dihydrocodeine, Thebaine, Papaverine, diproqualone, Flupirtine, Tricyclic antidepressants, and lidocaine, the said DMARD is selected from the group consisting of mycophenolate mofetil (CellCept), calcineurin inhibitors, cyclosporine, sirolimus, everolimus, oral retinoids, azathioprine, fumaric acid esters, D-penicillamine, cyclophosphamide, immunoadsorption column, Prosorba® column, a gold salt, auranofin, sodium aurothiomalate (Myocrisin), hydroxychloroquine, chloroquine, leflunomide, methotrexate (MTX), minocycline, sulfasalazine (SSZ), tumor necrosis factor alpha (TNFa) blockers, etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia), golimumab (Simponi)), anakinra (Kineret), monoclonal antibodies against B cells, rituximab (Rituxan)), T cell costimulation blockers, abatacept (Orencia), Interleukin 6 (IL-6) blockers, tocilizumab, RoActemra, and Actemra.

14. The method of claim 1 , wherein the anti-IL-6 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:704 and a light chain comprising the amino acid sequence of SEQ ID NO:702.

15. A method of treating an idiopathic condition associated with elevated interleukin (IL-6) levels other than rheumatoid arthritis comprising:
administering to a patient comprising an idiopathic condition associated with elevated IL-6 levels other than rheumatoid arthritis an antibody formulation comprising a therapeutically effective dosage of an anti-IL-6 antibody or antibody fragment wherein the variable light (V L ) chain CDR1, CDR2 and CDR3 polypeptide thereof respectively comprise the amino acid sequence of SEQ ID NO:4, 5 and 6 and the variable heavy (V H ) chain CDR1, CDR2 and CDR3 polypeptides thereof respectively comprise the amino acid sequence of SEQ ID NO:7, 8 or 120, and 9, and wherein the administered anti-IL-6 antibody or antibody fragment containing formulation comprises about 5 mM Histidine base, about 5 mM Histidine HCl to make final pH 6, 250 to 280 mM sorbitol or sorbitol in combination with sucrose, and 0.015% (w/w) Polysorbate 80, and the administered amount of said anti-IL-6 antibody or antibody fragment containing formulation is effective to treat said idiopathic condition associated with elevated IL-6 levels other than rheumatoid arthritis.

16. The method of claim 15 , wherein the concentration of said anti-IL-6 antibody or antibody fragment in the administered antibody fo

Assignees

• Alderbio Holdings Llc

Inventors

• Smith Jeffrey T L

Classifications

• G01N33/57557

  of other specific parts of the body, e.g. brain · CPC title

• G01N33/5758

  involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites · CPC title

• A61K38/16 Primary

  Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)} · CPC title

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• C07K2317/51

  Complete heavy chain or Fd fragment, i.e. VH + CH1 · CPC title