COMBINATION THERAPY WITH PEPTIDE EPOXYKETONES

• US 20110236428A1
• Filed: 10/21/2009
• Published: 09/29/2011
• Est. Priority Date: 10/21/2008
• Status: Abandoned Application

• Current Assignee: Onyx Therapeutics, Inc. (Amgen Inc.)
• Original Assignee: Onyx Therapeutics, Inc. (Amgen Inc.)
• Inventors: Bennett, Mark K., Kirk, Christopher J., Demo, Susan D.
• Application Number:
  US13/125,292
• Publication Number:
  US 20110236428A1
• Time in Patent Office: Days
• US Class Current: 424/277.1
• 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 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/335 having oxygen as the only ring hetero atom, e.g. fungichromin
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/45 having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 38/07 Tetrapeptides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 : Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/04 : for myasthenia gravis
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 35/04 : specific for metastasis
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The invention provides combination therapy, wherein one or more other therapeutic agents are administered agents are administered with peptide epoxyketones or a pharmaceutically acceptable salt thereof. Another aspect of the invention relates to treating cancer with a peptide epoxyketone administered in combination with another therapeutic agent.

Claims

1. A method for treating cancer, comprising administering a peptide epoxyketone proteasome inhibitor or a pharmaceutically acceptable salt thereof;

and one or more other therapeutic agents, wherein the combination shows efficacy that is greater than the efficacy of either agent being administered alone.

2. A method of claim 1, wherein the peptide epoxyketone has a structure of Formula (2), or a pharmaceutically acceptable salt thereof,

3. A method of claim 1, wherein the peptide epoxyketone has a structure of Formula (4), or a pharmaceutically acceptable salt thereof,

4. A method of claim 1, wherein the peptide epoxyketone has a structure of Formula (10), or a pharmaceutically acceptable salt thereof,

5. A method of claim 1, wherein the peptide epoxyketone has a structure of Formula (12), or a pharmaceutically acceptable salt thereof,

6. A method of claim 1, wherein the peptide epoxyketone has the following structure, or a pharmaceutically acceptable salt thereof:

7. A method of claim 1, wherein the effects of the peptide epoxyketone and the one or more other therapeutic agents are synergistic.

8. A method of claim 1, wherein the effects of the peptide epoxyketone and the one or more other therapeutic agents are additive.

9. A method of claim 1, wherein the peptide epoxyketone and the one or more other therapeutic agents are administered simultaneously.

10. A method of claim 1, wherein the one or more other therapeutic agents are administered within about 5 minutes to within about 48 hours prior to or after administration of the peptide epoxyketone.

11. A method of claim 10, wherein the one or more other therapeutic agents are administered within about 5 minutes to within about 1 hour prior to or after administration of the peptide epoxyketone.

12. A method of claim 1, wherein the cancer is selected from hematological malignancies, solid tumors, neuroblastoma, or melanoma.

13. A method of claim 12, wherein the cancer is selected from mantle cell lymphoma, diffuse large B-cell lymphoma (DLBCL), T-cell lymphomas or leukemias (e.g., cutaneous T-cell lymphoma (CTCL), noncutaneous peripheral T-cell lymphoma, lymphoma associated with human T-cell lymphotrophic virus (HTLV), and adult T-cell leukemia/lymphoma (ATLL)), acute lymphocytic leukemia, acute myelogenous leukemia (e.g., acute monocytic leukemia and acute promyelocytic leukemia), chronic lymphocytic leukemia (e.g., chronic B cell leukemia), chronic myelogenous leukemia, Hodgkin'"'"'s disease, non-Hodgkin'"'"'s lymphoma (e.g., Burkitt'"'"'s lymphoma), myeloma, multiple myeloma, and myelodysplastic syndrome.

14. A method of claim 12, wherein the cancer is selected from multiple myeloma and lymphoma.

15. A method of claim 12, wherein the cancer is selected from mesothelioma, brain neuroblastoma, retinoblastoma, glioma, Wilms'"'"' tumor, bone cancer and soft-tissue sarcomas, head and neck cancers (e.g., oral, laryngeal and esophageal), genitourinary cancers (e.g., prostate, bladder, renal, uterine, ovarian, testicular, rectal, and colon), lung cancer (e.g., small cell carcinoma and non-small cell lung carcinoma, including squamous cell carcinoma and adenocarcinoma), breast cancer, pancreatic cancer, basal cell carcinoma, metastatic skin carcinoma, squamous cell carcinoma (both ulcerating and papillary type), stomach cancer, brain cancer, liver cancer, adrenal cancer, kidney cancer, thyroid cancer, medullary carcinoma, osteosarcoma, soft-tissue sarcoma, Ewing'"'"'s sarcoma, reticulum cell sarcoma, and Kaposi'"'"'s sarcoma.

16. A method of claim 15, wherein the cancer is selected from ovarian cancer, non-small cell lung cancer, and colorectal cancer.

17. A method of claim 1, wherein the other therapeutic agent is an HDAC inhibitor.

18. A method of claim 17, wherein the HDAC inhibitor is selected from trichostatin A, depsipeptide, apicidin, A-161906, scriptaid, PXD-101, CHAP, butyric acid, depudecin, oxamflatin, phenylbutyrate, valproic acid, SAHA (Vorinostat), MS275 (N-(2-Aminophenyl)-4-[N-(pyridine-3-ylmethoxy-carbonyl)aminomethyl]benzamide), LAQ824/LBH589, C1994, and MGCD0103.

19. A method of claim 18, wherein the HDAC inhibitor is SAHA.

20. A method of claim 1, wherein the other therapeutic agent is an antibiotic.

21. A method of claim 20, wherein the antibiotic is selected from dactinomycin (actinomycin D), daunorubicin, doxorubicin and idarubicin.

22. A method of claim 21, wherein the antibiotic comprises doxorubicin.

23. A method of claim 1, wherein the other therapeutic agent is a taxane.

24. A method of claim 23, wherein the taxane is selected from paclitaxel and docetaxel.

25. A method of claim 1, wherein the other therapeutic agent is an antiproliferative/antimitotic alkylating agents.

26. A method of claim 25, wherein the antiproliferative/antimitotic alkylating agent is a nitrogen mustard.

27. A method of claim 26, wherein the nitrogen mustard is selected from mechlorethamine, ifosphamide, cyclophosphamide and analogs, melphalan, and chlorambucil.

28. A method of claim 1, wherein the other therapeutic agent is a platinum coordination complex.

29. A method of claim 28, wherein the platinum coordination complex is selected from cisplatin and carboplatin.

30. A method of claim 1, wherein the other therapeutic agent is a steroid.

31. A method of claim 30, wherein the steroid is selected from hydrocortisone, dexamethasone, methylprednisolone and prednisolone.

32. A method of claim 31, wherein the steroid is dexamethasone.

33. A method of claim 1, wherein the other therapeutic agent is an immunomodulator.

34. A method of claim 33, wherein the immunomodulator is selected from thalidomide, CC-4047 (Actimid), and lenalidomide (Revlimid).

35. A method of claim 34, wherein the immunomodulator is lenalidomide.

36. A method of claim 1, wherein the other therapeutic agent is a topoisomerase inhibitor.

37. A method of claim 36, wherein the topoisomerase inhibitor is selected from irinotecan, topotecan, camptothecin, lamellarin D, and etoposide.

38. A method of claim 1, wherein the other therapeutic agent is an m-TOR inhibitor.

39. A method of claim 38, wherein the m-TOR inhibitor is selected from CCI-779, AP23573 and RAD-001.

40. A method of claim 1, wherein the other therapeutic agent is a protein kinase inhibitor.

41. A method of claim 40, wherein the protein kinase inhibitor is selected from sorafenib, imatinib, dasatinib, sunitinib, pazopanib, and nilotinib.

42. A method of claim 41, wherein the protein kinase inhibitor is sorafenib.

43. A method for treating autoimmune diseases, comprising administering a peptide epoxyketone or a pharmaceutically acceptable salt thereof;

and one or more other therapeutic agents, wherein the combination shows efficacy that is greater than the efficacy of either agent being administered alone.