Antagonists of IL-6 to treat cachexia, weakness, fatigue, and/or fever

Patent metadata

Field	Value
Publication number	US-9187560-B2
Application number	US-201213681501-A
Country	US
Kind code	B2
Filing date	Nov 20, 2012
Priority date	Nov 25, 2008
Publication date	Nov 17, 2015
Grant date	Nov 17, 2015

Abstract

The present invention is directed to therapeutic methods using antibodies and fragments thereof having binding specificity for IL-6 to prevent or treat cachexia, fever, weakness and/or fatigue in 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. In another preferred embodiment, the patient's survivability or quality of life will preferably be improved.

First claim

What is claimed is:

1. A method of treating cachexia, weakness, fatigue, and/or fever in a patient diagnosed with an interleukin-6 (IL-6) associated disorder, comprising administering to the patient an anti-IL-6 antibody or antibody fragment, whereby the patient's cachexia, weakness, fatigue, and/or fever is improved, and monitoring the patient to assess cachexia, weakness, fatigue, and/or fever, wherein the anti-IL-6 antibody or antibody fragment comprises an anti-IL-6 antibody comprising a variable light (VL) polypeptide and a variable heavy (VH) polypeptide respectively comprising the identical CDRs as of (i) SEQ ID NO:85 and 86, or (ii) SEQ ID NO:101 and 102.

2. The method of claim 1 , wherein the anti-IL-6 antibody or antibody fragment comprises V L and V H complementarity determining regions (CDRs) identical to those in V L and V H polypeptides in of (i) SEQ ID NO:85 and 86, respectively.

3. The method of claim 1 , wherein the anti-IL-6 antibody or antibody fragment comprises VL chain and VH CDRs that are identical to those of SEQ ID NO:101 and 102, respectively.

4. The method of claim 3 , wherein the anti-IL-6 antibody or antibody fragment has an elimination half-life of at least about 22 days.

5. The method of claim 3 , wherein the anti-IL-6 antibody or antibody fragment comprises a human constant region.

6. The method of claim 3 , wherein the anti-IL-6 antibody or antibody fragment comprises a human IgG1 constant region.

7. The method of claim 3 , further comprising administering an antagonist of a cachexia-associated factor, weakness-associated factor, fatigue-associated factor, and/or fever-associated factor.

8. The method of claim 7 , wherein the cachexia-associated factor, weakness-associated factor, fatigue-associated factor, and/or fever-associated factor is selected from tumor necrosis factor-alpha, Interferon gamma, Interleukin 1 alpha, Interleukin 1 beta, Interleukin 6, proteolysis inducing factor, leukemia-inhibitory factor, or any combination thereof.

9. The method of claim 1 , wherein the anti-IL-6 antibody or antibody fragment contains VL chain and VH polypeptides which are both at least 90% identical to (i) SEQ ID NO:85 and 86, respectively, or (ii) SEQ ID NO:101 and 102, respectively.

10. The method of claim 1 , wherein the anti-IL-6 antibody or antibody fragment contains a VL chain and VH chain which are both at least 95% identical to (i) SEQ ID NO:85 and 86, respectively, or (ii) SEQ ID NO:101 and 102, respectively.

11. The method of claim 1 , wherein the anti-IL-6 antibody or antibody fragment contains a VL chain and VH chain which are both identical to (i) SEQ ID NO:85 and 86, respectively, or (ii) SEQ ID NO:101 and 102, respectively.

12. The method of claim 1 , wherein the anti-IL-6 antibody or antibody fragment is administered to the patient with a frequency of at most once per period of approximately four weeks.

13. The method of claim 1 , wherein at least one of the framework residues (FR residues) in said VH or VL chain polypeptides has been substituted with another amino acid residue resulting in an anti-IL-6 antibody or antibody fragment that specifically binds human IL-6.

14. The method of claim 13 , wherein one or more of said FR residues are substituted with an amino acid present at the corresponding site in a parent rabbit anti-IL-6 antibody from which the complementarity determining regions (CDRs) contained in said VH or VL polypeptides have been derived or by a conservative amino acid substitution.

15. The method of claim 1 , wherein the anti-IL-6 antibody or antibody fragment has an elimination half-life of at least about 22 days.

16. The method of claim 1 , wherein the anti-IL-6 antibody or antibody fragment comprises a human constant region.

17. The method of claim 1 , wherein the anti-IL-6 antibody or antibody fragment comprises a human IgG1 constant region.

18. The method of claim 1 , further comprising administering an antagonist of a cachexia-associated factor, weakness-associated factor, fatigue-associated factor, and/or fever-associated factor.

19. The method of claim 18 , wherein the cachexia-associated factor, weakness-associated factor, fatigue-associated factor, and/or fever-associated factor is selected from tumor necrosis factor-alpha, Interferon gamma, Interleukin 1 alpha, Interleukin 1 beta, Interleukin 6, proteolysis inducing factor, leukemia-inhibitory factor, or any combination thereof.

Assignees

• Alderbio Holdings Llc

Inventors

• Smith Jeffrey T L
• Latham John A
• Litton Mark
• Schatzman Randall

Classifications

• A61K2039/545

  characterised by the dose, timing or administration schedule · 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

• A61K2039/505

  comprising antibodies · CPC title

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title