Use of pirfenidone in therapeutic regimens

• US 7,407,973 B2
• Filed: 10/21/2004
• Issued: 08/05/2008
• Est. Priority Date: 10/24/2003
• Status: Expired due to Fees

• Current Assignee: Intermune Incorporated (Roche Holding AG)
• Original Assignee: Intermune Incorporated (Roche Holding AG)
• Inventors: Seiwert, Scott D., Blatt, Lawrence M., Ozes, Osman N.
• Primary Examiner(s): Henley, III; Raymond J
• Application Number:
  US10/574,631
• Publication Number:
  US 20070117841A1
• Time in Patent Office: 1,384 Days
• Field of Search: None
• US Class Current: 514/327
• 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 who has the disorder 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;

wherein the disorder is selected from the group consisting of fibrotic disorder, carcinoma, sarcoma, leukemia, lymphoma, viral infection, inflammatory disorder and TNF-mediated disorder, and wherein said carcinoma is selected from the group consisting of esophageal carcinoma, hepatocellular carcinoma, basal cell carcinoma, bladder carcinoma, including transitional cell carcinoma which is a malignant neoplasm of the bladder, squamous cell carcinoma, bronchogenic carcinoma, colon carcinoma, colorectal carcinoma, gastric carcinoma, lung carcinoma, including small cell carcinoma and non-small cell carcinoma of the lung, adrenocortical carcinoma, thyroid carcinoma, pancreatic carcinoma, breast carcinoma, ovarian carcinoma, prostate carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinoma, cystadenocarcinoma, medullary carcinoma, renal cell carcinoma, ductal carcinoma in situ or bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilm'"'"'s tumor, cervical carcinoma, uterine carcinoma, testicular carcinoma, osteogenic carcinoma, epithelieal carcinoma, and nasopharyngeal carcinoma.

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 said fibrotic disorder is pulmonary fibrosis, renal fibrosis, liver fibrosis, or heart fibrosis.

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

6. The method of claim 5, wherein the Type II interferon receptor agonist is IFN-γ

.

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

8. The method of claim 7, wherein the Type I interferon receptor agonist is IFN-α

.

11. The method of claim 1, wherein the carcinoma comprises a solid tumor.

12. The method of claim 1, wherein the sarcoma comprises a solid tumor.

13. The method of claim 1, wherein the leukemia comprises a solid tumor.

14. The method of claim 1, wherein the lymphoma comprises a solid tumor.

15. The method of claim 11, wherein the pirfenidone or pirfenidone analog are administered as adjuvant therapy to a primary carcinoma therapy.

16. The method of claim 12, wherein the pirfenidone or pirfenidone analog are administered as adjuvant therapy to a primary sarcoma therapy.

17. The method of claim 13, wherein the pirfenidone or pirfenidone analog are administered as adjuvant therapy to a primary leukemia therapy.

18. The method of claim 14, wherein the pirfenidone or pirfenidone analog are administered as adjuvant therapy to a primary lymphoma therapy.

9. A method of treating a disorder in an individual, the method comprising administering to an individual who has the disorder 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;

wherein the disorder is selected from the group consisting of fibrotic disorder, carcinoma, sarcoma, leukemia, lymphoma, viral infection, inflammatory disorder and TNF-mediated disorder, and wherein said carcinoma is selected from the group consisting of esophageal carcinoma, hepatocellular carcinoma, basal cell carcinoma, bladder carcinoma, including transitional cell carcinoma which is a malignant neoplasm of the bladder, squamous cell carcinoma, bronchogenic carcinoma, colon carcinoma, colorectal carcinoma, gastric carcinoma, lung carcinoma, including small cell carcinoma and non-small cell carcinoma of the lung, adrenocortical carcinoma, thyroid carcinoma, pancreatic carcinoma, breast carcinoma, ovarian carcinoma, prostate carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinoma, cystadenocarcinoma, medullary carcinoma, renal cell carcinoma, ductal carcinoma in situ or bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilm'"'"'s tumor, cervical carcinoma, uterine carcinoma, testicular carcinoma, osteogenic carcinoma, epithelieal carcinoma, and nasopharyngeal carcinoma.

10. 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;

wherein the individual in need thereof has a disorder selected from the group consisting of fibrotic disorder, carcinoma, sarcoma, leukemia, lymphoma, viral infection, inflammatory disorder and TNF-mediated disorder, and wherein said carcinoma is selected from the group consisting of esophageal carcinoma, hepatocellular carcinoma, basal cell carcinoma, bladder carcinoma, including transitional cell carcinoma which is a malignant neoplasm of the bladder, squamous cell carcinoma, bronchogenic carcinoma, colon carcinoma, colorectal carcinoma, gastric carcinoma, lung carcinoma, including small cell carcinoma and non-small cell carcinoma of the lung, adrenocortical carcinoma, thyroid carcinoma, pancreatic carcinoma, breast carcinoma, ovarian carcinoma, prostate carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinoma, cystadenocarcinoma, medullary carcinoma, renal cell carcinoma, ductal carcinoma in situ or bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilm'"'"'s tumor, cervical carcinoma, uterine carcinoma, testicular carcinoma, osteogenic carcinoma, epithelieal carcinoma, and nasopharyngeal carcinoma.