Antagonists of IL-6 to raise albumin and/or lower CRP

Patent metadata

Field	Value
Publication number	US-9994635-B2
Application number	US-201614988337-A
Country	US
Kind code	B2
Filing date	Jan 5, 2016
Priority date	Nov 25, 2008
Publication date	Jun 12, 2018
Grant date	Jun 12, 2018

Abstract

The present invention is directed to therapeutic methods using IL-6 antagonists such as antibodies and fragments thereof having binding specificity for IL-6 to improve survivability or quality of life of a patient in need thereof. In preferred embodiments, the anti-IL-6 antibodies will be humanized and/or will be aglycosylated. Also, in preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level or a reduced serum albumin level prior to treatment. In another preferred embodiment, the patient's Glasgow Prognostic Score will be increased and survivability will preferably be improved.

First claim

What is claimed is:

1. A method of reducing serum C-reactive protein (“CRP”) level in a patient with an inflammatory condition wherein interleukin-6 (“IL-6”) is elevated by administering an effective amount of an anti-IL-6 antibody comprising the variable heavy and light chain polypeptides of SEQ ID NO:657 and SEQ ID NO:709 respectively and the constant regions of SEQ ID NO:588 and 586 and monitoring the patient to assess the reduction in the patient's serum CRP level.

2. The method of claim 1 , wherein the anti-IL-6 antibody is aglycosylated.

3. The method of claim 1 , wherein the anti-IL-6 antibody is administered to the patient with a frequency at most once per period of approximately four weeks.

4. The method of claim 3 , wherein the patient's serum CRP level remains decreased and/or serum albumin level remains raised for an entire period intervening two consecutive anti-IL-6 antibody administrations.

5. The method of claim 1 , wherein the patient has been diagnosed with a condition selected from juvenile rheumatoid arthritis, psoriasis, psoriatic arthropathy, ankylosing spondylitis, systemic lupus erythematosus, Crohn's disease, ulcerative colitis, pemphigus, dermatomyositis, polymyositis, polymyalgia rheumatica, giant cell arteritis, vasculitis, polyarteritis nodosa, Wegener's granulomatosis, Kawasaki disease, isolated CNS vasculitis, Churg-Strauss arteritis, microscopic polyarteritis, microscopic polyangiitis, Henoch-Schönlein purpura, essential cryoglobulinemic vasculitis, rheumatoid vasculitis, cryoglobulinemia, relapsing polychondritis, Behcet's disease, Takayasu's arteritis, ischemic heart disease, stroke, multiple sclerosis, sepsis, vasculitis secondary to a viral infection, Buerger's Disease, cancer, advanced cancer, Osteoarthritis, systemic sclerosis, CREST syndrome, Reiter's disease, Paget's disease of bone, Sjögren's syndrome, diabetes type 1, diabetes type 2, familial Mediterranean fever, autoimmune thrombocytopenia, autoimmune hemolytic anemia, autoimmune thyroid diseases, pernicious anemia, vitiligo, alopecia greata, primary biliary cirrhosis, autoimmune chronic active hepatitis, alcoholic cirrhosis, viral hepatitis including hepatitis B and C, burn, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, allergic asthma, or any combination thereof.

6. The method of claim 1 , further comprising: measuring the patient's serum CRP level prior to administration of the IL-6 antibody, and administering the IL-6 antibody if the patient's serum CRP level is at least approximately 5 mg/L.

7. The method of claim 1 , further comprising administration of one or more statins to the patient.

8. The method of claim 7 , wherein the one or more statins is selected from atorvastatin, cerivastatin, fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin, or any combination thereof.

9. A method of increasing serum albumin level in a patient with an inflammatory condition wherein interleukin-6 (“IL-6”) is elevated by administering an effective amount of an anti-IL-6 antibody comprising the variable heavy and light chain polypeptides of SEQ ID NO:657 and SEQ ID NO:709 respectively and the constant regions of SEQ ID NO:588 and 586, and monitoring the patient to assess the increase in the patient's serum albumin level.

10. The method of claim 9 , wherein the anti-IL-6 antibody is administered to the patient with a frequency at most once per period of approximately four weeks.

11. The method of claim 9 , further comprising: measuring the patient's serum albumin level prior to administration of the IL-6 antibody, and administering the IL-6 antibody if the patient's serum albumin level is less than approximately 35 g/L.

12. A method of reducing a patient's serum CRP level and increasing the patient's serum albumin level in a patient with an inflammatory condition wherein interleukin-6 (“IL-6”) is elevated by administering an effective amount of an anti-IL-6 antibody comprising the variable heavy and light chain polypeptides of SEQ ID NO:657 and SEQ ID NO:709 respectively and the constant regions of SEQ ID NO:588 and 586, and monitoring the patient to assess the reduction in the patient's serum CRP level and the increase in the patient's serum albumin level.

13. The method of claim 12 , wherein the anti-IL-6 antibody is administered to the patient with a frequency at most once per period of approximately four-weeks.

14. The method of claim 12 , wherein the patient has been diagnosed with psoriasis, psoriatic arthropathy, ankylosing spondylitis, systemic lupus erythematosus, Crohn's disease, ulcerative colitis, pemphigus, dermatomyositis, polymyositis, polymyalgia rheumatica, giant cell arteritis, vasculitis, polyarteritis nodosa, Wegener's granulomatosis, Kawasaki disease, isolated CNS vasculitis, Churg-Strauss arteritis, microscopic polyarteritis, microscopic polyangiitis, Henoch-Schönlein purpura, essential cryoglobulinemic vasculitis, rheumatoid vasculitis, cryoglobulinemia, relapsing polychondritis, Behcet's disease, Takayasu's arteritis, ischemic heart disease, stroke, multiple sclerosis, sepsis, vasculitis secondary to viral infection, Buerger's Disease, cancer, advanced cancer, Osteoarthritis, systemic sclerosis, CREST syndrome, Reiter's disease, Paget's disease of bone, Sjögren's syndrome, diabetes type 1, diabetes type 2, familial Mediterranean fever, autoimmune thrombocytopenia, autoimmune hemolytic anemia, autoimmune thyroid diseases, pernicious anemia, vitiligo, alopecia areata, primary biliary cirrhosis, autoimmune chronic active hepatitis, alcoholic cirrhosis, viral hepatitis, burns, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, allergic asthma, or any combination thereof.

Assignees

• Alderbio Holdings Llc

Inventors

• Smith Jeffrey T L

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61K2039/54

  characterised by the route of administration · CPC title