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

Patent metadata

Field	Value
Publication number	US-10053506-B2
Application number	US-201514833973-A
Country	US
Kind code	B2
Filing date	Aug 24, 2015
Priority date	Nov 25, 2008
Publication date	Aug 21, 2018
Grant date	Aug 21, 2018

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 (a) administering to the patient an anti-IL-6 antibody or antibody fragment comprising a variable light (V L ) polypeptide comprising CDR polypeptides having the amino acid sequences of SEQ ID NO:4, 5 and 6, and a variable heavy (V H ) polypeptide comprising CDR polypeptides having the amino acid sequences of SEQ ID NO:7, 8 or 120 and 9, and (b) detecting cachexia, weakness, fatigue, and/or fever in the patient before, during or after antibody administration.

2. The method of claim 1 , wherein the anti-IL-6 antibody or antibody fragment comprises an anti-IL-6 antibody or antibody fragment comprising a variable light (V L ) polypeptide comprising CDR polypeptides having the amino acid sequences of SEQ ID NO:4, 5 and 6, and a variable heavy (V H ) polypeptide comprising CDR polypeptides having the amino acid sequences of SEQ ID NO:7, 120 and 9.

3. The method of claim 2 , wherein the anti-IL-6 antibody or antibody fragment comprises a human IgG1 constant region.

4. The method of claim 2 , wherein the anti-IL-6 antibody comprises the constant regions having the amino acid sequences of SEQ ID NO:588 and 586.

5. The method of claim 1 , wherein the anti-IL-6 antibody or antibody fragment comprises an anti-IL-6 antibody or antibody fragment comprising a variable light (V L ) polypeptide comprising CDR polypeptides having the amino acid sequences of SEQ ID NO:4, 5 and 6, and a variable heavy (V H ) polypeptide comprising CDR polypeptides having the amino acid sequences of SEQ ID NO:7, 8 and 9.

6. The method of claim 5 , wherein the anti-IL-6 antibody or antibody fragment comprises a human IgG1 constant region.

7. The method of claim 5 , wherein the anti-IL-6 antibody comprises the constant regions having the amino acid sequences of SEQ ID NO:588 and 586.

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

9. The method of claim 1 , further comprising administering another therapeutic compound 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.

10. 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.

11. The method of claim 1 , wherein the anti-IL-6 antibody comprises the constant regions having the amino acid sequences of SEQ ID NO:588 and 586.

12. The method of claim 1 , wherein detecting-cachexia, weakness, fatigue, and/or fever in the patient as recited in step (b) is effected before anti-IL-6 antibody administration.

13. The method of claim 1 , wherein detecting cachexia, weakness, fatigue, and/or fever in the patient as recited in step (b) is effected after anti-IL-6 antibody administration.

14. The method of claim 1 , wherein detecting cachexia, weakness, fatigue, and/or fever in the patient as recited in step (b) is effected both before and after anti-IL-6 antibody administration.

Assignees

• Alderbio Holdings Llc

Inventors

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

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K16/248 Primary

  IL-6 · CPC title

• A61K2039/545

  characterised by the dose, timing or administration schedule · CPC title