Claims for Patent: 9,926,370

Summary for Patent: 9,926,370

Title:	Antagonists of IL-6 to prevent or treat thrombosis
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.
Inventor(s):	Smith; Jeffrey T. L. (Bellevue, WA)
Assignee:	Alderbio Holdings LLC (Las Vegas, NV)
Application Number:	14/679,767
Patent Claims:	1. A method for reducing the risk of hypercoagulation or thrombosis in a subject having an elevated IL-6 level and an elevated D-dimer level comprising (i) administering an amount of an IL-6 antagonist, wherein said IL-6 antagonist is an antibody or antibody fragment that specifically binds human IL-6, wherein said antibody or antibody fragment comprises a light chain comprising CDR1, CDR2 and CDR3 polypeptides having the amino acid sequences of SEQ ID NO:4, 5 and 6 respectively and a heavy chain comprising CDR1, CDR2 and CDR3 polypeptides having the amino acid sequences of SEQ ID NO:7, 8 or 120 and 9 respectively and (ii) administering another active selected from an statin or anti-coagulant, wherein said IL-6 antagonist and other active may be in the same or different compositions. 2. The method of claim 1, wherein the anti-IL-6 antibody or antibody fragment comprises a variable light polypeptide comprising CDR1, CDR2 and CDR3 polypeptides respectively having the amino acid sequences of SEQ ID NO:4, 5 and 6; and a variable heavy polypeptide comprising CDR1, CDR2 and CDR3 polypeptides respectively having the amino acid sequences of SEQ ID NO:7, 8 and 9. 3. The method of claim 2, 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. 4. The method of claim 1, wherein the anti-IL-6 antibody or antibody fragment comprises a variable light polypeptide comprising CDR1, CDR2 and CDR3 polypeptides respectively having the amino acid sequences of SEQ ID NO:4, 5 and 6; and a variable heavy polypeptide comprising CDR1, CDR2 and CDR3 polypeptides respectively having the amino acid sequences of SEQ ID NO:7, 120, and 9. 5. The method of claim 4, 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. 6. The method of claim 1, wherein the anti-IL-6 antibody or antibody fragment comprises a variable light polypeptide comprising the amino acid sequences of SEQ ID NO:20; and a variable heavy polypeptide comprising the amino acid sequences of SEQ ID NO:18 or 19. 7. The method of claim 6, 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. 8. The method of claim 1, wherein the anti-IL-6 antibody or antibody fragment comprises IgG1, IgG2, IgG3 or IgG4 constant regions. 9. The method of claim 8, 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. 10. The method of claim 1, wherein the anti-IL-6 antibody or antibody fragment comprises IgG1 constant regions. 11. The method of claim 10, 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. 12. The method of claim 1, wherein the anti-IL-6 antibody or antibody fragment comprises a light constant region polypeptide comprising the amino acid sequences of SEQ ID NO:586; and a heavy constant region polypeptide comprising the amino acid sequences of SEQ ID NO:588. 13. The method of claim 12, 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. 14. The method of claim 1, wherein the statin is selected from pravastatin, lovastatin, simvastatin, fluvastatin, atorvastatin, simvastatin, nystatin, pentostatin, cerivastatin or an combination thereof. 15. The method of claim 14, 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. 16. The method of claim 1, wherein the anticoagulant is selected from abciximab (ReoPro), acenocoumarol, antithrombin III, argatroban, aspirin, bivalirudin (Angiomax), clopidogrel, dabigatran, dabigatran etexilate (Pradaxa/Pradax), desirudin (Revasc/Iprivask), dipyridamole, eptifibatide (Integrilin), fondaparinux, heparin, hirudin, idraparinux, lepirudin (Refludan), low molecular weight heparin, melagatran, phenindione, phenprocoumon, ticlopidine, tirofiban (Aggrastat), warfarin, ximelagatran, ximelagatran (Exanta/Exarta), or any combination thereof. 17. The method of claim 16, 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. 18. The method of claim 1, wherein the anticoagulant is low molecular weight heparin. 19. The method of claim 1, which further comprises thalidomide, lenalidomide, or any combination thereof. 20. 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. 21. The method of claim 1 wherein said hypercoagulation or thrombosis is associated with chronic inflammation.

Details for Patent 9,926,370

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bausch Health Us, Llc	IPRIVASK	desirudin	For Injection	021271	04/04/2003		2027-05-21
Janssen Biotech, Inc.	REOPRO	abciximab	Injection	103575	12/22/1994		2027-05-21