PIRFENIDONE/TOLL-LIKE RECEPTOR (TLR) AGONIST COMPOSITIONS AND METHODS FOR USING THEM TO STIMULATE PRODUCTION OF GRANULOCYTE COLONIZING STIMULATING FACTOR (G-CSF)

• US 20090170804A1
• Filed: 10/30/2006
• Published: 07/02/2009
• Est. Priority Date: 10/31/2005
• Status: Abandoned Application

• Current Assignee: Intermune Incorporated (Roche Holding AG)
• Original Assignee: Intermune Incorporated (Roche Holding AG)
• Inventors: Phillips, Roderick, Blatt, Lawrence M.
• Application Number:
  US12/091,153
• Publication Number:
  US 20090170804A1
• Time in Patent Office: Days
• US Class Current: 514/45
• 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 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/7028 Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid

Abstract

The invention disclosed herein relates to compositions and methods for treating subjects suffering from or at risk of developing neutropenia. In some embodiments, the methods comprise administering to a subject suffering from or at risk of developing neutropenia, an effective amount of pirfenidone and one or more toll-like receptor (TLR) agonists.

Claims

1. A method of treating or inhibiting neutropenia in a subject in need thereof, the method comprising administering to said subject a therapeutically effective amount of pirfenidone and one or more toll-like receptor (TLR) agonists.

2. The method of claim 1, wherein the subject is a human.

3. The method of claim 1, wherein said administering comprises administering pirfenidone and said one or more TLR agonists in an amount effective for increasing the number of neutrophils in the subject.

4. The method of claim 1, wherein the therapeutically effective amount is less than 50% of an amount that causes an undesirable side effect in the subject.

8. The method of claim 1, wherein said administering comprises orally administering pirfenidone and said one or more TLR agonists.

11. The method of claim 1, wherein the administering comprises administering twice per day.

12. The method of claim 1, wherein the administering comprises administering three times per day.

13. The method of claim 1, wherein the administering comprises providing the pirfenidone in a dose of from about 100 to about 400 milligrams.

14. The method of claim 1, wherein the administering comprises administering the pirfenidone such that the daily intake is from about 800 to about 4000 mg/day.

15. The method of claim 1, wherein said administering comprises administering the pirfenidone such that the daily intake is about 1200 mg/day or higher.

16. The method of claim 1, wherein said neutropenia is severe neutropenia.

17. The method of claim 1, wherein said neutropenia is selected from the group consisting of neutropenia associated with chemotherapy, neutropenia associated with conventional oncology therapy, drug-induced neutropenia, disease-induced neutropenia, genetic neutropenia, toxin-induced neutropenia, congenital neutropenia, cyclic neutropenia, idiopathic neurtropenia, and radiation-induced neutropenia.

21. The method of claim 1, wherein the one or more TLR agonists comprises at least one TLR7 agonist.

22. The method of claim 21, wherein the TLR 7 agonist is selected from the group consisting of 7-thia-8-oxoguanosine, 7-deazaguanosine, 7-allyl-8-oxoguanosine, 7-dezaguanosine, imiquimod, and R848.

5-7. -7. (canceled)

9-10. -10. (canceled)

18-21. -21. (canceled)

23-49. -49. (canceled)

50. A composition comprising a therapeutically effective amount of pirfenidone co-formulated with one or more toll-like receptor agonists.

51. The composition of claim 50, wherein said effective amount of pirfenidone is an amount effective for increasing the number of neutrophils in a subject.

52. The composition of claim 50, wherein the effective amount is less than 50% of an amount that causes an undesirable side effect in a subject.

54. The composition of claim 50, wherein the composition is for oral administration.

56. The composition of claim 50, wherein the pirfenidone is in a dose of from about 100 to about 400 milligrams.

57. The composition of claim 50, wherein the one or more TLR agonists comprises at least one TLR7 agonist.

58. The composition of claim 57, wherein the TLR 7 agonist is selected from the group consisting of 7-thia-8-oxoguanosine, 7-deazaguanosine, 7-allyl-8-oxoguanosine, 7-dezaguanosine, imiquimod, and R848.

53. (canceled)

55. (canceled)

59-60. -60. (canceled)