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