Methods of treating idiopathic pulmonary fibrosis

• US 20070092488A1
• Filed: 05/14/2004
• Published: 04/26/2007
• Est. Priority Date: 05/16/2003
• Status: Abandoned Application

• Current Assignee: Intermune Incorporated (Roche Holding AG)
• Original Assignee: Intermune Incorporated (Roche Holding AG)
• Inventors: Starko, Karen, Strieter, Robert
• Application Number:
  US10/557,110
• Publication Number:
  US 20070092488A1
• Time in Patent Office: Days
• US Class Current: 424/85.6
• 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 38/195 Chemokines, e.g. RANTES
• 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: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2333/78 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• CPC Class Codes: G01N 2800/12 Pulmonary diseases
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/6863 Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
• CPC Class Codes: G01N 33/74 involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors

Abstract

The present invention provides methods of treating idiopathic pulmonary fibrosis (IPF); methods of increasing survival time in an individual with IPF; and methods of reducing risk of death in an individual with IPF. The methods generally involve administering a therapeutically effective amount of IFN-γ to an individual with IPF.

Claims

1-42. -42. (canceled)

43. A method of determining patient response to treatment with interferon gamma, comprising:

(a) analyzing expression of an IFN-gamma-regulated biomarker in an IFN-gamma-treated patient; and

(b) correlating the expression of one or more up-regulated biomarkers, or the expression of one or more down-regulated biomarkers, or both, relative to control expression, with patient response to interferon gamma treatment.

44. The method of claim 43, wherein said one or more up-regulated biomarkers comprise a CXCR3 ligand.

45. The method of claim 43, wherein said one or more up-regulated biomarkers comprise one or more biomarkers selected from the group consisting of I-TAC/CXCL11, IP-10/CXCL10, and MIG/CXCL9.

46. The method of claim 43, wherein said one or more down-regulated biomarkers comprise one or more biomarkers selected from the group consisting of ENA-78/CXCL5, IL-4, PDGFB, elastin, and procollagen.

47. The method of claim 43, wherein said up-regulated biomarker is I-TAC/CXCL11 and said down-regulated biomarker is ENA-78/CXCL5.

48. The method of claim 43, wherein said control expression is expression in a pre-IFN-gamma treatment patient sample.

49. The method of claim 43, wherein said correlating is between two or more samples obtained from the IFN-gamma treatment patient at different time periods post-treatment.

50. The method of claim 43, wherein mRNA expression is analyzed in transbronchial biopsy tissue.

51. The method of claim 43, wherein mRNA expression is analyzed in bronchoalveolar lavage cells.

52. The method of claim 43, wherein expression is analyzed by measuring protein in bronchoalveolar lavage fluid.

53. The method of claim 43, wherein expression is analyzed by measuring protein in blood or blood components.

54. The method of claim 43, wherein biomarker expression is analyzed about 2 hours to about 4 weeks after initiation of the interferon-gamma treatment.

55. The method of claim 43, wherein the patient suffers from idiopathic pulmonary fibrosis.

68. The method of claim 43, further comprising the step of:

(c) maintaining, increasing or decreasing the dosage of interferon gamma in the treatment of the patient based on the results of step (b).

69. The method of claim 43, wherein expression is analyzed by measuring protein or mRNA in breath condensate.

56. A method of treating a patient suffering from a pulmonary fibrotic disorder, comprising administering to the patient a therapeutic amount of I-TAC/CXCL11 and/or a therapeutic amount of an antagonist of ENA-78/CXCL5.

57. The method of claim 56, comprising co-administering to the patient a therapeutic amount of I-TAC/CXCL11 and a therapeutic amount of an antagonist of ENA-78/CXCL5.

58. The method of claim 57, wherein the amount of I-TAC/CXCL11 and the amount of the antagonist of ENA-78/CXCL5 antagonist are synergistically effective.

59. The method of claim 56, wherein the treatment is effective to reduce or avoid one or more selected from the group consisting of risk of death of the patient;

dysregulated angiogenesis in the pulmonary vasculature of the patient; and

morbidity or mortality due to infection in the patient.

60. The method of claim 56, further comprising co-administering to the patient a therapeutic amount of interferon gamma.

61. The method of claim 56, wherein the ENA-78/CXCL5 antagonist is an anti-ENA-78/CXCL5 antibody or antibody fragment.

62. The method of claim 61, wherein the anti-ENA-78/CXCL5 antibody or antibody fragment is a monoclonal antibody or fragment thereof.

63. The method of claim 56, further comprising co-administering to the patient a therapeutic amount of pirfenidone or a pirfenidone analog for the duration of therapy.

64. The method of claim 56, wherein the pulmonary fibrotic disorder is idiopathic pulmonary fibrosis.

65. The method of claim 64, wherein the patient exhibits a forced expiratory volume (FVC) of at least 55% of the patient'"'"'s predicted normal FVC prior to treatment.

66. The method of claim 65, wherein the patient exhibits a FVC of at least 60% of the predicted normal FVC.

67. The method of claim 56, wherein treatment is maintained for the remainder of the patient'"'"'s life.

70. Use of ITAC/CXC11 and/or an antagonist of ENA78/CXCL5, and optionally IFN-gamma in the manufacture of a medicament for treating a pulmonary fibrotic disorder.