Crystalline tripeptide epoxy ketone protease inhibitors

• US 9,403,868 B2
• Filed: 03/05/2015
• Issued: 08/02/2016
• 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): Barker, Michael
• Assistant Examiner(s): Cheng, Karen
• Application Number:
  US14/639,603
• Publication Number:
  US 20150175656A1
• Time in Patent Office: 516 Days
• US Class Current: 1/1
• 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 invention relates to crystalline tripeptide keto epoxide compounds, methods of their preparation, and related pharmaceutical compositions.

Claims

1. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a crystalline compound of Formula (II)

2. The pharmaceutical composition of claim 1, wherein the melting point is about 145°

C. to about 150°

C.

3. The pharmaceutical composition of claim 1, wherein the composition is a parenterally administrable composition.

4. The pharmaceutical composition of claim 1, wherein the composition is an orally administrable composition.

5. The pharmaceutical composition of claim 4, wherein the orally administrable composition is selected from the group consisting of a tablet, a capsule, a granule, a powder and a syrup.

6. The pharmaceutical composition of claim 4, wherein the orally administrable composition is a tablet.

7. The pharmaceutical composition of claim 4, wherein the orally administrable composition is a capsule.

8. The pharmaceutical composition of claim 4, wherein the orally administrable composition is a granule.

9. The pharmaceutical composition of claim 4, wherein the orally administrable composition is a powder.

10. The pharmaceutical composition of claim 3, wherein the crystalline compound exhibits a differential scanning calorimetry (DSC) thermogram characterized with an endothermic peak at 147°

C.

11. The pharmaceutical composition of claim 3, wherein the crystalline compound exhibits from 0.0 to 0.3% weight loss in the temperature range of 25°

C. to 125°

C. in a thermogravimetric analysis.