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

Patent metadata

Field	Value
Publication number	US-10227404-B2
Application number	US-201715622225-A
Country	US
Kind code	B2
Filing date	Jun 14, 2017
Priority date	Nov 25, 2008
Publication date	Mar 12, 2019
Grant date	Mar 12, 2019

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 transplant patient in need thereof, comprising administering to the patient an anti-IL-6 antibody for anti-IL-6 antibody fragment, wherein the antibody or fragment comprises (i) a variable light chain comprising the complementarity determining region (CDR) 1 sequence of SEQ ID NO:4, the CDR 2 sequence of SEQ ID NO:5, and the CDR 3 sequence of SEQ ID NO:6; and (ii) a variable heavy chain comprising the CDR 1 sequence of SEQ ID NO.7, the CDR 2 sequence of SEQ ID NO.8 or 120, and the CDR 3 sequence of SEQ ID NO:9.

2. The method of claim 1 , wherein prior to the administration of the antibody or fragment the patient has elevated C-reactive protein (CRP) levels, reduced serum albumin levels, or both, and wherein the administration of the antibody or fragment results in a reduction in the patient's CRP levels, an increase in the patient's serum albumin levels, or both.

3. The method of claim 1 , wherein the antibody or fragment comprises (i) a variable light chain which is at least 95% identical to the variable light chain sequence of SEQ ID NO:2 or SEQ ID NO:20; and (ii) a variable heavy chain which is at least 95% identical to the variable heavy chain sequence of SEQ ID NO:3, SEQ ID NO: 18 or SEQ ID NO:19.

4. The method of claim 1 , wherein the antibody or fragment comprises (i) the variable light chain sequence of SEQ ID NO:2 or SEQ ID NO:20; and (ii) the variable heavy chain sequence of SEQ ID NO:3, SEQ ID NO:18 or SEQ ID NO:19.

5. The method of claim 1 , wherein the antibody or fragment comprises (i) the variable light chain sequence of SEQ ID NO:20; and (ii) the variable heavy chain sequence of SEQ ID NO:19.

6. The method of claim 1 , wherein the antibody or fragment is aglycosylated.

7. The method of claim 1 , wherein the antibody or fragment comprises a human constant domain.

8. The method of claim 7 , wherein the antibody or fragment comprises a human gamma 1 constant domain.

9. The method of claim 1 , further comprising monitoring CRP levels, serum albumin levels or both before, during or after the administration of said antibody or fragment.

10. The method of claim 1 , wherein prior to the administration of said antibody or fragment said patient has an elevated CRP level or a reduced serum albumin level or both.

11. The method of claim 10 , wherein the patient's serum CRP level is reduced to less than approximately 5 mg/L within 1 week of administration of the antibody or fragment.

12. The method of 1 , further comprising measuring the patient's serum albumin level prior to administration of the antibody or fragment, and administering the antibody or fragment if the patient's serum albumin level is less than approximately 35 g/L.

13. The method of claim 12 , wherein the patient's serum albumin level is increased to more than 35 g/L within 5 weeks of administration of the antibody or fragment.

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

15. The method of claim 1 , wherein the antibody or fragment is administered intravenously, intraperitoneally, intramuscularly, or subcutaneously.

16. The method of claim 1 , wherein the patient is suffering from GVHD.

17. The method of claim 1 , wherein the patient comprises a bone marrow transplant.

Assignees

• Alderbio Holdings Llc

Inventors

• Smith Jeffrey T L

Classifications

• G01N2333/4737

  C-reactive protein · CPC title

• C07K2317/94

  Stability, e.g. half-life, pH, temperature or enzyme-resistance · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C07K2317/56

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