Use of pirfenidone in therapeutic regimens

• US 20070117841A1
• Filed: 10/21/2004
• Published: 05/24/2007
• Est. Priority Date: 10/24/2003
• Status: Active Grant

• Current Assignee: Intermune Incorporated (Roche Holding AG)
• Original Assignee: Intermune Incorporated (Roche Holding AG)
• Inventors: Seiwert, Scott, Blatt, Lawrence, Ozes, Osman
• Granted Patent: US 7,407,973 B2
• Time in Patent Office: Days
• US Class Current: 514/310
• 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 31/4412 having oxo groups directly attached to the heterocyclic ring
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 38/212 IFN-alpha
• CPC Class Codes: A61K 38/217 IFN-gamma
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: G01N 33/5091 for testing the pathological state of an organism
• 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 present invention provides methods for treating a disorder, and methods for inhibiting a stress-activated protein kinase (SAPK) in a cell in an individual, the methods generally involving administering to an individual in need thereof an effective amount of pirfenidone or a pirfenidone analog; comparing a post-treatment SAPK activity level in a biological sample from the individual with a pre-treatment SAPK activity level; and adjusting the dose of the pirfenidone or pirfenidone analog based on the results of the comparison step. The present invention provides methods for treating a disorder, and methods for inhibiting a SAPK in a cell in an individual, the methods generally involving administering to an individual in need thereof an effective amount of pirfenidone or a pirfenidone analog; comparing a second post-treatment SAPK activity level in a biological sample from the individual with a first post-treatment SAPK activity level; and adjusting the dose of the pirfenidone or pirfenidone analog based on the results of the comparison step.

Claims

1. A method of treating a disorder in an individual, the method comprising administering to an individual in need thereof an effective amount of pirfenidone or a pirfenidone analog;

comparing a post-treatment level of stress-activated protein kinase (SAPK) activity in a biological sample from the individual to a pre-treatment level of SAPK activity; and

adjusting the dose of the pirfenidone or pirfenidone analog based on the results of the comparison step.

2. The method of claim 1, wherein the post-treatment SAPK activity level is from about 10% to about 40% lower than the pre-treatment SAPK activity level, and wherein the adjusting step comprises administering a second dosage of pirfenidone or pirfenidone analog that is at least about 10% higher than the first dosage of pirfenidone or pirfenidone analog.

3. The method of claim 1, wherein the biological sample is peripheral blood mononuclear cells.

4. The method of claim 1, wherein the disorder is a fibrotic disorder.

5. The method of claim 4, wherein said fibrotic disorder is pulmonary fibrosis, renal fibrosis, liver fibrosis, or heart fibrosis.

6. The method of claim 1, wherein the disorder is a cancer.

7. The method of claim 6, wherein the cancer comprises a solid tumor.

8. The method of claim 6, wherein the pirfenidone or pirfenidone analog are administered are administered as adjuvant therapy to a primary cancer therapy.

9. The method of claim 1, wherein the disorder is a viral infection.

10. The method of claim 1, wherein the disorder is an inflammatory disorder.

11. The method of claim 1, wherein the disorder is a TNF-mediated disorder.

12. The method of claim 1, further comprising administering an effective amount of a Type II interferon receptor agonist.

13. The method of claim 12, wherein the Type II interferon receptor agonist is IFN-γ

.

14. The method of claim 1, further comprising administering an effective amount of a Type I interferon receptor agonist.

15. The method of claim 14, wherein the Type I interferon receptor agonist is IFN-α

.

16. A method of treating a disorder in an individual, the method comprising administering to an individual in need thereof an effective amount of pirfenidone or a pirfenidone analog;

comparing a second post-treatment level of stress-activated protein kinase (SAPK) activity in a biological sample from the individual to a first post-treatment level of SAPK activity; and

adjusting the dose of the pirfenidone or pirfenidone analog based on the results of the comparison step.

17. A method of inhibiting a stress-activated protein kinase enzymatic activity in a cell of an individual, the method comprising administering to an individual in need thereof an effective amount of pirfenidone or a pirfenidone analog;

comparing a post-treatment level of stress-activated protein kinase (SAPK) activity in a biological sample from the individual to a pre-treatment level of SAPK activity; and

adjusting the dose of the pirfenidone or pirfenidone analog based on the results of the comparison step.