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

• US 20120014955A1
• Filed: 09/22/2011
• Published: 01/19/2012
• Est. Priority Date: 05/21/2007
• Status: Active Grant

• Current Assignee: Vitaeris Inc. (CSL Limited)
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Smith, Jeffrey T.L.
• Granted Patent: US 8,535,671 B2
• Time in Patent Office: Days
• US Class Current: 424/135.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/248 IL-6
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: G01N 2333/4737 C-reactive protein
• CPC Class Codes: G01N 2333/765 Serum albumin, e.g. HSA
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

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.

Claims

1-81. -81. (canceled)

82-1. The method of any one of claims 82-84, wherein the anti-IL-6 antibody or antibody fragment has an elimination half-life of at least about 22 days.

83. A method of improving survivability or quality of life of a patient in need thereof having reduced serum albumin levels, comprising administering to the patient an anti-IL-6 antibody or antibody fragment wherein the antibody or antibody fragment specifically binds to an epitope on an intact human IL-6 polypeptide, wherein said epitope when ascertained by epitopic mapping using overlapping linear peptide fragments which span the full length of the native human IL-6 polypeptide includes one or more residues comprised in IL-6 fragments selected from those respectively encompassing amino acid residues 37-51, amino acid residues 70-84, amino acid residues 169-183, amino acid residues 31-45 and amino acid residues 58-72, whereby the patient'"'"'s serum albumin level is increased, and further whereby this administration results in improving survivability or quality of life in said patient.

84. A method of improving survivability or quality of life of a patient in need thereof having increased C reactive protein and reduced serum albumin levels, comprising administering to the patient an anti-IL-6 antibody or antibody fragment, wherein the antibody or antibody fragment that specifically binds to an epitope on an intact human IL-6 polypeptide, wherein said epitope when ascertained by epitopic mapping using overlapping linear peptide fragments which span the full length of the native human IL-6 polypeptide includes one or more residues comprised in IL-6 fragments selected from those respectively encompassing amino acid residues 37-51, amino acid residues 70-84, amino acid residues 169-183, amino acid residues 31-45 and amino acid residues 58-72, and, and whereby this administration results in improving survivability or quality of life in said patient and whereby the patient'"'"'s serum C-reactive protein (“

CRP”

) level is reduced and the patient'"'"'s serum albumin level is increased, and whereby this administration results in improving survivability or quality of life in said patient.