COMBINATION OF INTERLEUKIN-6 ANTAGONISTS AND ANTIPROLIFERATIVE DRUGS

• US 20090035281A1
• Filed: 03/07/2006
• Published: 02/05/2009
• Est. Priority Date: 03/10/2005
• Status: Abandoned Application

• Current Assignee: Universita Degli Studi "Magna Graccia" Di Catanzaro
• Original Assignee: Universita Degli Studi "Magna Graecia" Di Catanzaro
• Inventors: Savino, Rocco, Venuta, Salvatore, Tassone, Pierfrancesco
• Application Number:
  US11/908,022
• Publication Number:
  US 20090035281A1
• Time in Patent Office: Days
• US Class Current: 424/93.700
• 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 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 35/545 Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
• CPC Class Codes: A61K 38/204 IL-6
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The combination of an interleukin-6 (IL-6) antagonist and an antiproliferative drug is described. In its preferred embodiment, the present invention describes the combination of an IL-6 superantagonist, particularly a superantagonist totally incapable of binding gp130 and an antiproliferative drug belonging to the glucocorticoid class (SANT-7 and dexamethasone). The combination according to the present invention has shown surprising synergism in an animal model of multiple myeloma and the ability to overcome the resistance to the antiproliferative drug developed by myeloid cells. The combination according to the present invention is useful for the preparation of a medicament for the treatment of tumours, particularly IL-6-dependent tumours.

Claims

1. Combination of an antiproliferative drug and an interleukin-6 receptor antagonist.

2. Combination according to claim 1, in which said antagonist is a superantagonist totally incapable of binding gpl 30.

3. Combination according to claim 2, in which said superantagonist is a protein selected from the group described by the respective sequences SEQ ID No 1, SEQ ID No 2, SEQ ID No 3 and SEQ ID No 4.

4. Combination according to claim 3, in which said superantagonist is the protein called SANT-7, with sequence SEQ ID No 4.

5. Combination according to claim 1, in which said antiproliferative drug is a glucocorticoid.

6. Combination according to claim 5, in which said glucocorticoid is dexamethasone.

7. Combination according to claim 6, in which said superantagonist is the protein called SANT-7 and said glucocorticoid is dexamethasone.

8. A medicament comprising the combination of claim 1.

9. A method of treatment of tumours comprising administering an effective amount of a medicament of claim 8 to a human in need thereof.

10. The method according to claim 9, in which said tumours are interleukin-6-dependent tumours.

11. The method according to claim 10, in which said tumours are haematological tumours.

12. The method according to claim 11, in which said tumours are multiple myclomas.

13. The method according to claim 12, in which said combination consists of SANT-7 according to claim 4 and dexamethasone.

14. The method according to claim 9, in which said medicament is used in combination with other known medicaments used for the treatment of said tumours.

15. The method according to claim 14, in which said known medicament is a medicament whose active ingredient is of the biological type.

16. The method according to claim 15, in which said active ingredient is an anti-interleukin-6 antibody.

17. The method according to claim 14, in which said known medicament is a medicament whose active ingredient is a chemotherapeutic agent.

18. The method according to claim 17, in which said chemotherapeutic agent is selected from the group consisting of alkylating agents, all-transretinoic acid, thalidomide and biphosphonates.

19. The method according claim 18, in which said biphosphonate is zoledronic acid.

20. The method according to claim 17, in which said chemotherapeutic agent is used at a high dosage in combination with autologous transplantation with stem cells.

21. Pharmaceutical composition containing the combination according to claim 1 in a mixture with at least one pharmaceutically acceptable vehicle and/or excipient.

22-30. -30. (canceled)