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

Patent metadata

Field	Value
Publication number	US-10040851-B2
Application number	US-201514968098-A
Country	US
Kind code	B2
Filing date	Dec 14, 2015
Priority date	May 21, 2007
Publication date	Aug 7, 2018
Grant date	Aug 7, 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 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 improving survivability or quality of life of a patient in need thereof, comprising administering to the patient an IL-6 antibody or fragment thereof, whereby the patient's serum C-reactive protein (“CRP”) level is reduced, wherein the anti-IL-6 antibody or antibody fragment comprises a variable light (V L ) polypeptide comprising the V L complementarity-determining regions (CDRs) of SEQ ID NO: 87, SEQ ID NO: 88, and SEQ ID NO: 89; which correspond to the V L CDRs of the V L chain sequence of SEQ ID NO: 85, and further comprises a variable heavy (V H ) polypeptide comprising the CDRs of sequences of SEQ ID NO: 90, SEQ ID NO: 91, and SEQ ID NO: 92; which correspond to the V H CDRs of the variable heavy chain sequence of SEQ ID NO: 86.

2. The method of claim 1 , wherein the patient has asthma.

3. The method of claim 1 , wherein said patient has an elevated serum CRP level prior to treatment.

4. The method of claim 1 , wherein the method further comprises monitoring the patient to assess the reduction in the patient's serum CRP level.

5. A method of improving survivability or quality of life of a patient in need thereof, comprising administering to the patient an IL-6, antibody or fragment thereof, whereby the patient's serum albumin level is increased, wherein the anti-IL-6 antibody or antibody fragment comprises a variable light (V L ) polypeptide comprising the V L complementarity-determining regions (CDRs) of SEQ ID NO: 87, SEQ ID NO: 88, and SEQ ID NO: 89; which correspond to the V L CDRs of the V L chain sequence of SEQ ID NO: 85, and further comprises a variable heavy (V H ) polypeptide comprising the CDRs of sequences of SEQ ID NO: 90, SEQ ID NO: 91, and SEQ ID NO: 92; which correspond to the V H CDRs of the variable heavy chain sequence of SEQ ID NO: 86.

6. The method of claim 5 , wherein the patient has asthma.

7. The method of claim 5 , wherein said patient has a decreased serum albumin level prior to treatment.

8. The method of claim 5 , wherein the method further comprises monitoring the patient to assess the increase in the patient's serum albumin level.

9. A method of improving survivability or quality of life of a patient in need thereof, comprising administering to the patient an IL-6 antibody or fragment thereof, whereby the patient's serum CRP level is reduced and the patient's serum albumin level is increased, wherein the anti-IL-6 antibody or antibody fragment comprises a variable light (V L ) polypeptide comprising the V L complementarity-determining regions (CDRs) of SEQ ID NO: 87, SEQ ID NO: 88, and SEQ ID NO: 89; which correspond to the V L CDRs of the V L chain sequence of SEQ ID NO: 85, and further comprises a variable heavy (V H ) polypeptide comprising the CDRs of sequences of SEQ ID NO: 90, SEQ ID NO: 91 and SEQ ID NO: 92; which correspond to the V H CDRs of the variable heavy chain sequence of SEQ ID NO: 86.

10. The method of claim 9 , wherein the patient has asthma.

11. The method of claim 9 , wherein said patient has an elevated serum CRP level prior to treatment.

12. The method of claim 9 , wherein said patient has a decreased serum albumin level prior to treatment.

13. The method of claim 9 , wherein the method further comprises monitoring the patient to assess the reduction in the patient's serum CRP level and the increase in the patient's serum albumin level.

14. A method of improving survivability or quality of life of a patient diagnosed with a disease associated with increased CRP, said disease selected from 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, Behçet'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 greata, primary biliary cirrhosis, autoimmune chronic active hepatitis, alcoholic cirrhosis, viral hepatitis, burns, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, allergic asthma, and any combination thereof, by decreasing the patient's serum C reactive protein (“CRP”) level, comprising administering to the patient an effective amount of an anti-IL-6 antibody or antibody fragment that blocks the binding of human IL-6 to IL-6R1 and the binding of IL-6 to gp130, whereby the patient's serum CRP level is reduced, wherein the anti-IL-6 antibody or antibody fragment comprises a variable light (V L ) polypeptide comprising the V L complementarity-determining regions (CDRs) of SEQ ID NO: 87, SEQ ID NO: 88 and SEQ ID NO: 89; which correspond to the V L CDRs of the V L chain sequence of SEQ ID NO: 85, and further comprises a variable heavy (V H ) polypeptide comprising the CDRs of sequences of SEQ ID NO: 90, SEQ ID NO: 91, and SEQ ID NO: 92; which correspond to the V H CDRs of the variable heavy chain sequence of SEQ ID NO: 86.

15. A method of improving survivability or quality of life of a patient diagnosed with a disease associated with increased CRP and/or decreased serum albumin, said disease selected from 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, Behçet'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 greata, primary biliary cirrhosis, autoimmune chronic active hepatitis, alcoholic cirrhosis, viral hepatitis, burns, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, allergic asthma, and any combination thereof, by decreasing the patient's serum C reactive protein (“CRP”) levels and/or by increasing the patients's serum albumin levels, comprising administering to the patient an effective amount of an anti-IL-6 antibody or antibody fragment that blocks the binding of human IL-6 to IL-6R1, and the binding of IL-6 gp130, whereby the patient's serum albumin levels are increased and/or the patient's serum C reactive protein (“CRP) levels are reduced, wherein the anti-IL-6 antibody or antibody fragment comprises a variable light (V L ) polypeptide comprising the V L complementarity-determining regions (CDRs) of SEQ ID NO: 87, SEQ ID N

Assignees

• Alderbio Holdings Llc

Inventors

• Smith Jeffrey T L

Classifications

• G01N2333/765

  Serum albumin, e.g. HSA · CPC title

• G01N2333/4737

  C-reactive protein · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C07K2317/34

  Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues · CPC title

• C07K2317/56

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