Method of improving patient survivability and quality of life by administering an anti-IL-6 antibody

Patent metadata

Field	Value
Publication number	US-9717793-B2
Application number	US-201514604305-A
Country	US
Kind code	B2
Filing date	Jan 23, 2015
Priority date	Nov 24, 2009
Publication date	Aug 1, 2017
Grant date	Aug 1, 2017

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 improving survivability or quality of life of a patient diagnosed with a disease associated with reduced serum albumin, wherein said disease is selected from cancer, advanced cancer, liver disease, renal disease, inflammatory bowel disease, celiac's disease, trauma, burns, or any combination thereof, by increasing the patient's serum albumin level, said method 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 albumin level is increased, and further wherein the anti-IL-6 antibody or antibody fragment comprises a V L polypeptide comprising CDR1, CDR2 and CDR3 polypeptides respectively having the amino acid sequences of SEQ ID NO:4, 5 and 6 and a V H polypeptide comprising CDR1, CDR2 and CDR3 polypeptides respectively having the amino acid sequences of SEQ ID NO:7, 8 or 120, and 9.

2. The method of claim 1 , wherein the anti-IL-6 antibody or fragment comprises the variable heavy and light chain amino acid sequences of SEQ ID NO: 657 and 709, respectively.

3. The method of claim 1 , wherein the anti-IL-6 antibody or fragment comprises the variable heavy and light chain polypeptides comprising the amino acid sequences of SEQ ID NO: 657 and 709 respectively, and further comprises the heavy chain and light chain constant regions comprising the amino acid sequences of SEQ ID NO: 588 and SEQ ID NO: 586 respectively.

4. The method of claim 1 , which further includes monitoring the patient to assess the increase in the patient's serum albumin levels.

5. The method of claim 1 , wherein the anti-IL-6 antibody or antibody fragment is a human, humanized, single chain or chimeric antibody.

6. The method of claim 1 , wherein the anti-IL-6 antibody or antibody fragment is aglyclosylated and/or contains an Fc region that has been modified to alter effector function, half-life, proteolysis, and/or glycosylation.

7. The method of claim 1 , wherein said antibody comprises a human Fc derived from IgG1, IgG2, IgG3, or IgG4.

8. The method of claim 1 , wherein said antibody comprises a human Fc derived from IgG1.

9. 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, 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 greata, 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, 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 CRP-level is reduced, and the patient's serum C reactive protein (“CRP”) level is reduced, wherein the anti-IL-6 antibody or antibody fragment comprises a V L polypeptide comprising CDR1, CDR2 and CDR3 polypeptides respectively having the amino acid sequences of SEQ ID NO:4, 5 and 6 and a V H polypeptide comprising CDR1, CDR2 and CDR3 polypeptides respectively having the amino acid sequences of SEQ ID NO:7, 8 or 120, and 9.

10. The method of claim 9 , wherein the anti-IL-6 antibody or fragment comprises the variable heavy and light chain amino acid sequences of SEQ ID NO: 657 and 709, respectively.

11. The method of claim 9 , wherein the anti-IL-6 antibody or fragment comprises the variable heavy and light chain polypeptides comprising the amino acid sequences of SEQ ID NO: 657 and 709 respectively, and further comprises the heavy chain and light chain constant regions comprising the amino acid sequences of SEQ ID NO: 588 and SEQ ID NO: 586 respectively.

12. The method of claim 9 , which further includes monitoring the patient to assess the reduction in the patient's serum CRP levels.

13. The method of claim 9 , wherein the anti-IL-6 antibody or antibody fragment is a human, humanized, single chain or chimeric antibody.

14. The method of claim 9 , wherein the anti-IL-6 antibody or antibody fragment is aglyclosylated and/or contains an Fc region that has been modified to alter effector function, half-life, proteolysis, and/or glycosylation.

15. The method of claim 9 , wherein said antibody comprises a human Fc derived from IgG1, IgG2, IgG3, or IgG4.

16. The method of claim 9 , wherein said antibody comprises a human Fc derived from IgG1.

17. 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, 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 greata, 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, by decreasing the patient's serum C reactive protein (“CRP”) levels and/or by increasing 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 to 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 V L polypeptide comprising CDR1, CDR2 and CDR3 polypeptides respectively having the amino acid sequences of SEQ ID NO:4, 5 and 6 and a V H polypeptide

Assignees

• Alderbio Holdings Llc

Inventors

• Smith Jeffrey T L

Classifications

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P7/06

  Antianaemics · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title