Methods of aiding in the diagnosis of diseases using anti-IL-6 antibodies

Patent metadata

Field	Value
Publication number	US-10117955-B2
Application number	US-201615276272-A
Country	US
Kind code	B2
Filing date	Sep 26, 2016
Priority date	Nov 25, 2008
Publication date	Nov 6, 2018
Grant date	Nov 6, 2018

Abstract

The present invention is directed to therapeutic methods using IL-6 antagonists such as an Ab1 antibody or antibody fragment having binding specificity for IL-6 to prevent or treat disease or 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, reduced serum albumin level, elevated D-dimer or other coagulation cascade related protein(s), cachexia, fever, weakness and/or fatigue prior to treatment. The subject therapies also may include the administration of other actives such as chemotherapeutics, anti-coagulants, statins, and others.

First claim

What is claimed is:

1. A method of aiding in the diagnosis of a disease or condition associated with elevated interleukin 6 (“IL-6”), comprising detecting for the presence of elevated amounts of IL-6 in a biological sample of a subject, and if said biological sample is determined to comprise elevated IL-6 levels identifying said subject as one having or suspected of having a disease associated with elevated IL-6, wherein said detection is effected by:
(i) contacting a biological sample of the patient putatively having a condition associated with elevated IL-6 with an amount of an anti-IL-6 antibody or antibody fragment, whereby said amount of antibody or antibody fragment binds to any IL-6 in the biological sample, wherein the antibody or antibody fragment comprises: a variable light chain polypeptide comprising: a polypeptide having at least 90% identity to SEQ ID NO: 709, and a variable heavy chain polypeptide comprising: a polypeptide having at least 90% identity to SEQ ID NO: 657, further wherein said anti-IL-6 antibody or antibody fragment comprises the variable light chain complementarity determining region (CDR) polypeptides of SEQ ID NO:4, 5 and 6 and comprises the variable heavy chain complementarity determining region (CDR) polypeptides of SEQ ID NO:7, 8 or 120, and 9 and
(ii) detecting the binding of any IL-6 present in the sample to said anti-IL-6 antibody or antibody fragment in order to determine whether the subject putatively has a condition associated with elevated IL-6.

2. The method of claim 1 , wherein the light chain possesses at least 95% sequence identity to the light chain polypeptide comprised in SEQ ID NO: 709.

3. The method of claim 1 , wherein the heavy chain possesses at least 95% sequence identity to the heavy chain polypeptide comprised in SEQ ID NO: 657.

4. The method of claim 1 , wherein the light chain possesses at least 97% sequence identity to the light chain polypeptide comprised in SEQ ID NO: 709.

5. The method of claim 1 , wherein the heavy chain possesses at least 97% sequence identity to the heavy chain polypeptide comprised in SEQ ID NO: 657.

6. The method of claim 1 , wherein the light chain possesses at least 99% sequence identity to the light chain polypeptide comprised in SEQ ID NO: 709.

7. The method of claim 1 , wherein the heavy chain possesses at least 99% sequence identity to the heavy chain polypeptide comprised in SEQ ID NO: 657.

8. The method of claim 1 , wherein the light chain possesses 100% sequence identity to the light chain polypeptide comprised in SEQ ID NO: 709.

9. The method of claim 1 , wherein the heavy chain possesses 100% sequence identity to the heavy chain polypeptide comprised in SEQ ID NO: 657.

10. The method of claim 1 wherein said antibody comprises light chain CDR1, CDR2 and CDR3 polypeptides and heavy chain CDR1, CDR2 and CDR3 identical to those on SEQ ID NO:4, 5 and 6 and SEQ ID NO:7, 120 and 9 respectively.

11. The method of claim 1 wherein said antibody comprises light chain CDR1, CDR2 and CDR3 polypeptides and heavy chain CDR1, CDR2 and CDR3 polypeptides identical to those on SEQ ID NO:4, 5 and 6 and SEQ ID NO:7, 8 and 9 respectively.

12. The method of claim 1 wherein said biological sample is selected from sera, plasma, urine, saliva, mucous, pleural fluid, synovial fluid and spinal fluid.

13. The method of claim 1 wherein said biological sample is sera or plasma.

14. The method of claim 1 wherein said detection is effected in vitro.

15. The method of claim 1 wherein said detection is effected in vivo.

16. The method of claim 1 wherein said method further includes the detection of a clinical marker other than IL-6.

17. The method of claim 16 , wherein the other clinical marker is a compound correlated to inflammation.

18. The method of claim 1 wherein the antibody is selected from a human, humanized, single chain, or chimeric antibody and the antibody fragment is selected from a Fab, Fab′, F(ab′) 2 , Fv, or scFv.

19. The method claim 1 wherein the disease or condition associated with elevated IL-6 is selected from cancer, a disease or condition associated with hypercoagulation, a disease or condition associated with elevated serum CRP, a disease or condition associated with hypoalbuminemia, an inflammatory disorder, a viral disorder, a wasting syndrome, an autoimmune disorder or any combination thereof.

Assignees

• Alderbio Holdings Llc

Inventors

• Garcia-Martinez Leon
• Carvalho Jensen Anne Elisabeth
• Anderson Katie Olson
• Dutzar Benjamin H
• Latham John A
• Kovacevich Brian R
• Smith Jeffrey T L
• Litton Mark
• Schatzman Randall C

Classifications

• C07K2317/24

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

• G01N2333/5412

  IL-6 · 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

• A61K49/0058

  Antibodies · CPC title

• Y02A50/412

  Cross-Sectional Technologies · mapped topic