Antagonists of IL-6 to prevent or treat thrombosis
The present invention is directed to therapeutic methods using IL-6 antagonists such as antibodies and fragments thereof having binding specificity for IL-6 to prevent or treat thrombosis in diseases associated with abnormal blood coagulation or fibrinolysis. In preferred embodiments these patients will comprise those exhibiting elevated D-dimer or other coagulation cascade related proteins and optionally will further exhibit elevated C reactive protein prior to treatment. The subject therapies also may include the administration of other actives such as chemotherapeutics, anti-coagulants, statins, et al.
1. A method of reducing platelet counts in a patient in need thereof comprising administering an effective amount of an anti-IL-6 antibody or antibody fragment which contains the variable light chain polypeptide CDRs of SEQ ID NO: 4, 5 and 6 and the variable heavy chain polypeptide CDRs of SEQ ID NO: 7, 8 or 120, and 9.
2. The method of claim 1 , wherein the anti-IL-6 antibody or antibody fragment comprises the variable heavy chain polypeptide of SEQ ID NO: 657 and the variable light chain polypeptide of SEQ ID NO: 709.
3. The method of claim 1 , wherein the anti-IL-6 antibody or antibody fragment comprises the heavy chain polypeptide of SEQ ID NO: 704 and the light chain polypeptide of SEQ ID NO: 702.
4. The method of claim 1 wherein the patient has a condition associated with thrombosis or hypercoagulation.
5. The method of claim 1 which comprises assessing platelet numbers in the patient after the administration of the anti-IL-6 antibody or antibody fragment.
6. The method of claim 1 wherein the patient has cancer.
7. The method of claim 1 wherein the patient has an allergic or autoimmune condition.
8. The method of claim 1 , whereby the patient's coagulation profile is improved or restored to normal, and includes monitoring the patient to assess coagulation profile.
9. The method of claim 1 , wherein the patient comprises aberrant serum levels of one or more of D-dimer, Factor II, Factor V, Factor VIII, Factor IX, Factor XI, Factor XII, F/fibrin degradation products, thrombin-antithrombin III complex, fibrinogen, plasminogen, prothrombin, and von Willebrand factor.
10. The method of claim 1 , wherein the subject's coagulation profile is assessed before or after treatment by measurement of the subject's serum level of one or more of D-dimer, Factor II, Factor V, Factor VIII, Factor IX, Factor XI, Factor XII, F/fibrin degradation products, thrombin-antithrombin III complex, fibrinogen, plasminogen, prothrombin, and von Willebrand factor.
11. The method of claim 1 wherein the patient has elevated serum D-dimer levels prior to treatment, and/or elevated C-reactive protein (CRP) levels prior to treatment.
12. The method of claim 1 wherein said method further comprises the administration of at least one statin or anti-coagulant.
13. The method of claim 1 wherein the anti-IL-6 antibody or antibody fragment contains an Fc region that has been modified to alter effector function, half-life, proteolysis, and/or glycosylation.
14. The method of claim 1 wherein the anti-IL-6 antibody or antibody fragment is a human, humanized, single chain or chimeric antibody.
15. The method of claim 1 wherein the patient's coagulation profile is assessed after antibody administration by measurement of the patient's serum level of D-dimer.