ANTITHROMBOTIC AGENTS

• US 20070224198A1
• Filed: 01/16/2007
• Published: 09/27/2007
• Est. Priority Date: 01/17/1996
• Status: Abandoned Application

• Current Assignee: University of Vermont & State Agricultural College
• Original Assignee: Smithkline Beecham Corporation (Smithkline Beecham PLC)
• Inventors: Blackburn, Michael, Patel, Arunbhai, Feuerstein, Giora
• Application Number:
  US11/623,496
• Publication Number:
  US 20070224198A1
• Time in Patent Office: Days
• US Class Current: 424/145.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: C07K 16/36 against blood coagulation factors
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

Monoclonal antibodies directed against coagulation factors and their use in inhibiting thrombosis in combination with plasminogen activators are disclosed.

Claims

1. A method for inhibiting thrombosis in an animal comprising administering an effective dose of an anti-coagulation factor monoclonal antibody having self-limiting neutralizing activity in combination with a plasminogen activator.

2. The method of claim 1 wherein the coagulation factor is from the intrinsic or common coagulation pathway.

3. The method of claim 2 wherein the anti-coagulation factor monoclonal antibody is an anti-Factor IX, anti-Factor IXa, anti-Factor X, anti-Factor Xa, anti-Factor XI, anti-Factor XIa, anti-Factor VIII, anti-Factor VIIIa, anti-Factor V, anti-Factor Va, anti-thrombin or anti-prothrombin.

4. The method of claim 2 wherein the anti-coagulation factor monoclonal antibody is an anti-Factor IX.

5. The method of claim 4 wherein the anti-Factor IX monoclonal antibody has the identifying characteristics of SB 249413, SB 249415, SB 249416, SB 249417, SB 257731 or SB 257732.

6. The method of claim 4 wherein the anti-Factor IX monoclonal antibody has the identifying characteristics of SB 249417.

7. The method of claim 1 wherein the plasminogen activator is tissue plasminogen activator (tPA), tPA variants, streptokinase or urokinase.

8. The method of claim 1 wherein the plasminogen activator is tPA.

9. The method of claim 1 wherein the thrombosis is associated with myocardial infarction, unstable angina, atrial fibrillation, stroke, renal damage, pulmonary embolism, deep vein thrombosis, percutaneous translumenal coronary angioplasty, disseminated intravascular coagulation, sepsis, artificial organs, shunts or prostheses.

10. The method of claim 9 wherein the thrombosis is associated with myocardial infarction or stroke.

11. The method of claim 10 wherein the thrombosis is associated with myocardial infarction.

12. The method of claim 4 wherein the anti-Factor IX antibody binds with an epitope of the Factor IX gla domain.

13. The method of claim 12 wherein the epitope is located within residues 3-11 of Factor IX.

14. A method of reducing a required dose of a thrombolytic agent in treatment of thrombosis in an animal comprising administering an anticoagulant specifically targeting a component of the intrinsic coagulation pathway in combination with the thrombolytic agent.

15. The method of claim 14 wherein the anticoagulant is an anti-Factor XI, anti-Factor XIa, anti-Factor IX, anti-Factor IXa, anti-Factor VIII or anti-Factor VIIIa.

16. The method of claim 14 wherein the thrombolytic agent is tPA.

17. A method of reducing a required dose of a thrombolytic agent in treatment of thrombosis in an animal comprising administering an anti-Factor IX monoclonal antibody in combination with the thrombolytic agent.

18. The method of claim 17 wherein the anti-Factor IX monoclonal antibody has the identifying characteristics of SB 249413, SB 249415, SB 249416, SB 249417, SB 257731 or SB 257732.

19. The method of claim 17 wherein the anti-Factor IX monoclonal antibody has the identifying characteristics of SB 249417.

20. The method of claim 17 wherein the thrombolytic agent is tPA.