Methods and compositions for the reduction of neutrophil influx and the treatment of bronchopulmonary displasia, respiratory distress syndrome, chronic lung disease, pulmonary fibrosis, asthma and chronic obstructive pulmonary disease

Abstract

The present invention relates generally to the use of recombinant human CC10 (rhCC10), also known as recombinant human uteroglobin, for use as a therapeutic in the treatment of Respiratory Distress Syndrome (RDS), Bronchopulmonary dysplasia (BPD), chronic lung disease and/or pulmonary fibrosis, Asthma and Chronic Obstructive Pulmonary Disease (COPD). More particularly, the invention provides methods, including broadly the critical dosage ranges of rhCC10, which may be administered to safely and effectively treat the aforementioned conditions. The invention further provides a composition useful in administering rhCC10 to humans.

1 . A method for treatment of a patient having respiratory distress syndrome, bronchopulmonary dysplasia, chronic lung disease, pulmonary fibrosis, asthma or chronic obstructive pulmonary disease and in need of treatment, comprising: administering a treatment-effective amount of rhCC10 to said patient. 
     
     
         2 . A method for treatment of a patient having respiratory distress syndrome, bronchopulmonary dysplasia, chronic lung disease, pulmonary fibrosis, asthma or chronic obstructive pulmonary disease and in need of treatment, comprising the steps of:
 (a) monitoring said patient's serum concentration of CC10 and   (b) administering a treatment-effective dose of rhCC10   which causes the patient to reach a peak serum concentration of CC10 within about 6 hours.   
     
     
         3 . A method for treatment of a premature infant having respiratory distress syndrome, bronchopulmonary dysplasia, asthma or chronic obstructive pulmonary disease and in need of treatment, comprising administering rhCC10 intratracheally to a premature infant at a dose of between about 0.15 mg/kg to about 5 mg/kg of patient body mass. 
     
     
         4 . A method for treatment of a premature infant having respiratory distress syndrome, bronchopulmonary dysplasia, asthma or chronic obstructive pulmonary disease and in need of treatment, comprising administering rhCC10 intratracheally to a premature infant at a dose of between about 1.5 mg/kg to about 5 mg/kg of patient body mass. 
     
     
         5 . A method for treatment of a premature infant having respiratory distress syndrome, bronchopulmonary dysplasia, asthma or chronic obstructive pulmonary disease and in need of treatment, comprising administering rhCC10 intratracheally to a premature infant at a dose of between about 1.5 mg/kg to about 5 mg/kg of patient body mass before, during, or after surfactant therapy. 
     
     
         6 . A safe and well-tolerated method of treating at least one of respiratory distress syndrome, bronchopulmonary dysplasia, chronic lung disease, pulmonary fibrosis, asthma or chronic obstructive pulmonary disease in a patient comprising: administering rhCC10 to the patient. 
     
     
         7 . The method of  claim 6  wherein between about 15 ng to about 10 mg rhCC10 per kg of patient body mass is administered. 
     
     
         8 . The method of  claim 6  wherein between about 0.15 mg to about 5 mg rhCC10 per kg of patient body mass is administered. 
     
     
         9 . The method of  claim 6  wherein between about 1.5 mg and about 5 mg rhCC10 per kg of patient body mass is administered. 
     
     
         10 . The method of  claim 6  wherein IL-8 levels are less than about 120 μg/ml of serum after administration. 
     
     
         11 . The method of  claim 6  wherein the patient has a serum concentration of CC10 of about 100 ng/ml of serum to about 2800 ng/ml of serum or a urine concentration of CC10 of about 100 ng/ml to about 10,000 ng/ml during treatment. 
     
     
         12 . The method of  claim 6  wherein the patient's peak serum concentration of CC10 is about 1280 ng/ml of serum to about 2800 ng/ml of serum after administration. 
     
     
         13 . The method of  claim 6  wherein the patient reaches a peak serum concentration of CC10 within about 6 hours after initial dosage. 
     
     
         14 . The method of  claim 6  wherein the patient reaches a peak tracheal aspirate fluid concentration of CC10 between about 12 and about 48 hours after initial dosage. 
     
     
         15 . The method of  claim 6  wherein the administration of rhCC10 is repeated about once every 48 hours. 
     
     
         16 . A safe and well-tolerated method of reducing total cell counts in the tracheal fluid of a patient comprising: administering rhCC10 to the patient. 
     
     
         17 . The method of  claim 16  wherein neutrophil levels in the lungs of a patient are reduced. 
     
     
         18 . The method of  claim 16  wherein rhCC10 between about 15 ng to about 10 mg per kg of patient body mass is administered. 
     
     
         19 . The method of  claim 16  wherein rhCC10 between about 0.15 mg to about 5 mg per kg of patient body mass is administered. 
     
     
         20 . The method of  claim 16  wherein rhCC10 between about 1.5 mg and about 5 mg per kg of patient body mass is administered. 
     
     
         21 . The method of  claim 16  wherein the patient's serum IL-8 level is less than 120 μg/ml after administration. 
     
     
         22 . The method of  claim 16  wherein the patient has a serum concentration of CC10 of about 100 ng/ml of serum to 2800 ng/ml of serum or a urine concentration of CC10 of about 100 ng/ml to about 10,000 ng/ml during treatment. 
     
     
         23 . The method of  claim 16  wherein the patient's peak serum concentration of CC10 is about 1280 ng/ml of serum to about 2800 ng/ml of serum after administration. 
     
     
         24 . The method of  claim 16  wherein a peak serum concentration of CC10 is reached within about 6 hours after initial dosage. 
     
     
         25 . The method of  claim 16  wherein the patient reaches a peak TAF concentration of CC10 between about 12 and about 48 hours after initial dosage. 
     
     
         26 . The method of  claim 16  wherein the administration of rhCC10 is repeated about once every 48 hours. 
     
     
         27 . A safe and well-tolerated method of reducing total protein concentration in the tracheal fluid of a patient comprising: administering rhCC10 to the patient. 
     
     
         28 . The method of  claim 27  wherein neutrophil levels in the lungs of a patient are reduced. 
     
     
         29 . The method of  claim 27  wherein between about 15 ng to about 10 mg rhCC10 per kg of patient body mass is administered. 
     
     
         30 . The method of  claim 27  wherein between about 0.15 mg to about 5 mg rhCC10 per kg of patient body mass is administered. 
     
     
         31 . The method of  claim 27  wherein between about 1.5 mg and about 5 mg rhCC10 per kg of patient body mass is administered. 
     
     
         32 . The method of  claim 27  wherein the patient's serum IL-8 level is less than 120 μg/ml after administration. 
     
     
         33 . The method of  claim 27  wherein the patient has a serum concentration of CC10 of about 100 ng/ml of serum to 2800 ng/ml of serum or a urine concentration of CC10 of about 100 ng/ml to about 10,000 ng/ml during treatment. 
     
     
         34 . The method of  claim 27  wherein the patient's peak serum concentration of CC10 is about 1280 ng/ml of serum to about 2800 ng/ml of serum after administration. 
     
     
         35 . The method of  claim 27  wherein a peak serum concentration of CC10 is reached within about 6 hours after initial dosage. 
     
     
         36 . The method of  claim 27  wherein the patient reaches a peak tracheal aspirate fluid concentration of CC10 between about 12 and about 48 hours after initial dosage. 
     
     
         37 . The method of  claim 27  wherein the administration of rhCC10 is repeated about once every 48 hours.