Anti-IL-6 antibodies or fragments thereof to treat or inhibit cachexia, associated with chemotherapy toxicity
View Patent ↗The present invention is directed to therapeutic methods and compositions, especially subcutaneous and intravenous composition 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 or inhibiting cachexia in a patient exhibiting chemotherapy toxicity, comprising administering to the patient an anti-IL-6 antibody or an IL-6 binding antibody fragment comprising the variable light (V L ) chain CDR1 of SEQ ID NO:4, CDR2 of SEQ ID NO:5 and CDR3 of SEQ ID NO:6, and the variable heavy (V H ) chain CDR1 of SEQ ID NO:7, CDR2 of SEQ ID NO:8 or 120, and CDR3 of SEQ ID NO:9, wherein the patient's cachexia associated with the chemotherapy toxicity is effectively treated or inhibited.
2. The method of claim 1 , wherein the anti-IL-6 antibody or IL-6 binding antibody fragment is aglycosylated and/or contains an Fc region that has been modified to alter effector function, half-life, proteolysis, and/or glycosylation.
3. The method of claim 1 , wherein the anti-IL-6 antibody or IL-6 binding antibody fragment is human, humanized, single chain or chimeric.
4. The method of claim 1 , wherein the anti-IL-6 antibody or IL-6 binding antibody fragment is administered to the patient with a frequency of about once every four weeks or eight weeks.
5. The method of claim 1 , wherein said anti-IL-6 antibody or IL-6 binding antibody fragment comprises a human Fc derived from IgG1, IgG2, IgG3, or IgG4.
6. The method of claim 1 , wherein the anti-IL-6 antibody or IL-6 binding antibody fragment has an elimination half-life of at least about 22 days, at least about 25 days or at least about 30 days.
7. The method of claim 1 , wherein the anti-IL-6 antibody or IL-6 binding antibody fragment is coadministered with a chemotherapy.
8. The method of claim 1 , wherein the patient has been diagnosed with an autoimmune disorder, infectious disorder or cancer.
9. The method of claim 1 , wherein the anti-IL-6 antibody or IL-6 binding antibody fragment comprises a V H chain having at least 98% identity with the V H chain of SEQ ID NO:18 or 19, and a V L chain having at least 98% identity with the V L chain of SEQ ID NO:20.
10. The method of claim 1 , wherein the anti-IL-6 antibody or IL-6 binding antibody fragment is administered intravenously or subcutaneously to the patient at a dose of about (+/−20%>) 80, 160 or 320 mg.
11. The method of claim 10 , wherein the patient is administered said dosage every 8 weeks or 2 months.
12. The method of claim 10 , wherein said dosage is administered at least twice.
13. The method of claim 10 , wherein the second dose is administered 8 weeks after the first dose.
14. The method of claim 1 , wherein the anti-IL-6 antibody or IL-6 binding antibody fragment comprises a V H chain having at least 95% identity with the V H chain of SEQ ID NO:18 or 19, and a V L chain having at least 95% identity with the V L chain of SEQ ID NO:20.
15. The method of claim 1 , wherein the anti-IL-6 antibody or IL-6 binding antibody fragment comprises the V H chain of SEQ ID NO:18 or 19, and the V L chain of SEQ ID NO:20.
16. The method of claim 1 , wherein the patient is administered a composition comprising the anti-IL-6 antibody or IL-6 binding antibody fragment, and wherein the composition is formulated for subcutaneous or intravenous injection.
17. The method of claim 1 , wherein the patient has been diagnosed with cancer.
18. The method of claim 1 , wherein the chemotherapy agent is selected from VEGF antagonists, EGFR antagonists, platins, taxols, irinotecan, 5-fluorouracil, gemcytabine, leucovorine, steroids, cyclophosphamide, melphalan, vinca alkaloids, vinblastine, mustines, tyrosine kinase inhibitors, radiotherapy, sex hormone antagonists, selective androgen receptor modulators, selective estrogen receptor modulators, PDGF antagonists, TNF antagonists, IL-1 antagonists, interleukins, IL-12R antagonists, Toxin conjugated monoclonal antibodies, tumor antigen specific monoclonal antibodies, Erbitux™, Avastin™, Pertuzumab, anti-CD20 antibodies, Rituxan®, ocrelizumab, ofatumumab, DXL625, Herceptin®, or any combination thereof.
19. The method of claim 1 , wherein the chemotherapy agent comprises an inhibitor of JAK1, JAK2, JAK3, or SYK.
20. The method of claim 1 , further comprising: measuring the patient's body weight prior to administration of the anti-IL-6 antibody or IL-6 binding antibody fragment, and administering the anti-IL-6 antibody or antibody fragment to the patient if the patient's weight has declined by greater than approximately 5% within approximately 30 days, or if the patient's lean body mass index is less than about 17 kg/m 2 (male patient) or less than about 14 kg/m 2 (female patient).
21. The method of claim 1 , further comprising: measuring the patient's muscular strength prior to administration of the anti-IL-6 antibody or IL-6 binding antibody fragment, and administering the anti-IL-6 antibody or antibody fragment to the patient if the patient's muscular strength has declined by greater than approximately 20% within approximately 30 days.
22. The method of any one of claim 9 , 14 or 15 , wherein the anti-IL-6 antibody or IL-6 binding antibody fragment comprises the V H chain of SEQ ID NO:19.
23. The method of claim 1 , wherein the V H chain CDR2 is SEQ ID NO:120.
24. The method of claim 1 , wherein the anti-IL-6 antibody or IL-6 binding antibody fragment comprises the V H chain of SEQ ID NO:19 and the V L chain of SEQ ID NO:20 and human IgG1 constant domains.
25. The method of claim 1 , wherein the anti-IL-6 antibody or IL-6 binding antibody fragment comprises the V H chain of SEQ ID NO:18 and the V L chain of SEQ ID NO:20 and human IgG1 constant domains.