Crystalline tripeptide epoxy ketone protease inhibitors

• US 8,822,512 B2
• Filed: 09/20/2011
• Issued: 09/02/2014
• Est. Priority Date: 03/20/2009
• Status: Expired due to Fees

• Current Assignee: Onyx Therapeutics, Inc. (Amgen Inc.)
• Original Assignee: Onyx Therapeutics, Inc. (Amgen Inc.)
• Inventors: Phiasivongsa, Pasit, Sehl, Louis C.
• Primary Examiner(s): HEARD, THOMAS SWEENEY
• Application Number:
  US13/237,655
• Publication Number:
  US 20120077855A1
• Time in Patent Office: 1,078 Days
• US Class Current: 514/365
• CPC Class Codes: A61K 31/427 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• 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 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• 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 7/00 Drugs for disorders of the blood or the extracellular fluid
• 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
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07K 1/026 by fragment condensation in solution
• CPC Class Codes: C07K 5/0802 : with the first amino acid being neutral
• CPC Class Codes: C07K 5/0821 : with the first amino acid being heterocyclic, e.g. His, Pro, Trp
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The disclosure features crystalline tripeptide keto epoxide compounds, methods of their preparation, and related pharmaceutical compositions.

Claims

1. A crystalline compound having Formula (II)

2. The crystalline compound of claim 1, wherein the X-ray powder diffraction pattern is substantially the same as that shown in FIG. 2.

3. The crystalline compound of claim 1, wherein the crystalline compound also has a differential scanning calorimetry pattern comprising a melting onset of about 140°

C.

4. The crystalline compound of claim 1, having a melting point of from about 140 to about 155°

C.

5. The crystalline compound of claim 4, having a melting point of from about 145 to about 150°

C.

6. The crystalline compound of claim 1, wherein the crystalline compound also has a differential scanning calorimetry pattern comprising a sharp endothermic maximum at about 147°

C.

7. The crystalline compound of claim 1, wherein the crystalline compound also has a differential scanning calorimetry pattern that is substantially the same as that shown in FIG. 1.

8. The crystalline compound of claim 1, wherein the crystalline compound also has a thermogravimetric analysis pattern that is substantially the same as that shown in FIG. 3.

9. The crystalline compound of claim 1, wherein the crystalline compound is in substantially pure form.

10. A pharmaceutical composition comprising a crystalline compound having Formula (II) as claimed in claim 1 and a pharmaceutically acceptable carrier.

11. (Withdrawn, currently amended) A method for treating cancer, the method comprising administering:

(i) a crystalline compound having Formula (II) as claimed in claim 1;

or

(ii) a pharmaceutical composition as claimed in claim 10.

12. The method of claim 11, wherein the cancer is selected from the group consisting of hematological cancers, Waldenströ

m'"'"'s macroglobulinemia, multiple myeloma, diffuse B cell lymphoma, mantle cell lymphoma, pancreatic cancer, and lung cancer.

13. The method of claim 12, wherein the cancer is multiple myeloma.

14. The method of claim 11, wherein the cancer is a hematological cancer.

15. The method of claim 11, wherein the cancer is Waldenströ

m'"'"'s macroglobulinemia.

16. The method of claim 11, wherein the cancer is a solid tumor.

17. The pharmaceutical composition of claim 10, wherein the crystal line compound is present in a dosage amount ranging from about 0.01 mg/kg to about 50 mg/kg by weight of the subject to whom the composition is administered.

18. The pharmaceutical composition of claim 10, wherein the composition is a parenterally administrable composition.

19. The pharmaceutical composition of claim 10, wherein the composition is an orally administrable composition.

20. The pharmaceutical composition of claim 19, wherein the orally administrable composition is selected from the group consisting of a tablet, a capsule, a granule, a powder and a syrup.

21. The pharmaceutical composition of claim 19, wherein the orally administrable composition is a tablet.

22. The pharmaceutical composition of claim 19, wherein the orally administrable composition is a capsule.

23. The pharmaceutical composition of claim 19, wherein the orally administrable composition is a granule.

24. The pharmaceutical composition of claim 19, wherein the orally administrable composition is a powder.