Antagonists of IL-6 to prevent or treat thrombosis

Patent metadata

Field	Value
Publication number	US-10875917-B2
Application number	US-201816131216-A
Country	US
Kind code	B2
Filing date	Sep 14, 2018
Priority date	Nov 25, 2008
Publication date	Dec 29, 2020
Grant date	Dec 29, 2020

Abstract

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.

First claim

What is claimed is:

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.

Assignees

• Alderbio Holdings Llc
• Vitaeris Inc

Inventors

• Smith Jeffrey T L

Classifications

• C07K2317/51

  Complete heavy chain or Fd fragment, i.e. VH + CH1 · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• A61K39/3955

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

• C07K2317/76

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

• C07K16/248 Primary

  IL-6 · CPC title