METHODS FOR TREATING IDIOPATHIC PULMONARY FIBROSIS
The present invention relates to methods and medicaments useful for treating idiopathic pulmonary fibrosis (IPF) by administering anti-CTGF antibodies. Methods for prognosing individuals with IPF are also provided.
1 . A method for treating idiopathic pulmonary fibrosis (IPF) in a subject in need thereof, the method comprising administering an effective amount of an anti-CTGF antibody, thereby treating IPF.
2 . The method of claim 1 , wherein treating IPF comprises reducing the pathologic rate of decline of a pulmonary function parameter by at least 5%.
3 . The method of claim 2 , wherein the pulmonary function parameter is selected from the group consisting of vital capacity (VC), residual volume (RV), forced expiratory volume (FEV), forced vital capacity (FVC), forced vital capacity percent (FVC %) predicted, forced expiratory flow (FEF), peak expiratory flow rate (PEFR), inspiratory reserve volume (IRV), functional residual capacity (FRC), inspiratory capacity (IC), total lung capacity (TLC), expiratory reserve volume (ERV), tidal volume (TV), and maximum voluntary ventilation (MVV).
4 . The method of claim 1 , wherein treating IPF comprises increasing the subject's FVC by at least 0.05 liters compared to a baseline FVC measurement.
5 . The method of claim 1 , wherein treating IPF comprises increasing the subject's FVC % predicted by at least 0.5% compared to a baseline FVC % predicted measurement.
6 . The method of claim 1 , wherein treating IPF comprises producing at least a 5% increase, compared to a baseline measurement, in diffusing capacity of the lung for carbon monoxide (DLCO) corrected for hemoglobin, DLCO percent (DLCO %) predicted, or arterial oxyhaemoglobin saturation (SaO 2 ).
7 . The method of claim 1 , wherein treating IPF comprises producing at least a 5% decrease, compared to a baseline measurement, in alveolar-arterial oxygen tension gradient (A−a) PO 2 .
8 . The method of claim 1 , wherein treating IPF comprises producing at least a 5% reduction, compared to a baseline measurement, in the extent of pulmonary infiltration of fibroblasts or myofibroblasts, in the rate of collagen deposition, in the degree type II pneumocyte hyperplasia, in the degree of smooth muscle hyperplasia or the formation of fibroblastic foci.
9 . The method of claim 1 , wherein treating IPF comprises stabilizing or producing at least a 2% reduction, compared to a baseline measurement, in one or more pulmonary radiographic parameters selected from the group consisting of ground glass opacities, fibrosis and honeycomb formation.
10 . The method of claim 1 , wherein treating IPF comprises the extension of the subject's progression-free survival or overall survival of at least 1 month compared to historic controls.
11 . The method of claim 1 , wherein treating IPF comprises decreasing the subject's risk of death at 1 year post-diagnosis by at least 10% compared to historical controls.
12 . The method of claim 1 , wherein treating IPF comprises the prevention of a worsening of dyspnea, the prevention of the development of new dyspnea, the reduction in the frequency or intensity of coughing, the prevention of a worsening of hypoxemia, the reduction in the number or severity of acute exacerbations of IPF, the reduction in the number of IPF-related hospital admissions, the reduction in the need for supplemental oxygen, or the improvement in the assessment of health-related quality of life.
13 . The method of claim 1 , wherein the anti-CTGF antibody has the same amino acid sequence as the antibody produced by the cell line identified by ATCC Accession No. PTA-6006.
14 . The method of claim 1 , wherein the anti-CTGF antibody binds to CTGF competitively with an antibody produced by the cell line identified by ATCC Accession No. PTA-6006.
15 . The method of claim 1 , wherein the effective amount of an anti-CTGF antibody is at least 15 mg/kg.
16 . The method of claim 1 , wherein the effective amount of an anti-CTGF antibody is at least 1.00 g.
17 . The method of claim 1 , wherein the effective amount of an anti-CTGF antibody produces at least a C min of 10.0 μg/ml when measured at 21 days post-administration.
18 . The method of claim 1 , wherein the effective amount of an anti-CTGF antibody produces at least an area under the curve for the period of 0-21 days post-administration of 1,000 μg*h/ml.
19 . The method of claim 1 , further comprising the administration of an additional therapeutic agent selected from the group consisting of corticosteroids, antibiotics, immunosuppressive drugs, supplemental oxygen, and mechanical ventilation.
20 . The method of claim 1 , wherein the subject has a forced vital capacity percent (FVC %) predicted of greater than about 55%.
21 . The method of claim 1 , wherein the subject has less than 50% parenchymal fibrosis.
22 . The method of claim 1 , wherein the subject has less than 25% honeycombing within the whole lung.
23 . The method of claim 1 , wherein the subject has been diagnosed with IPF for less than 5 years.
24 . A pharmaceutical composition for treating IPF comprising an anti-CTGF antibody.