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

Inactive Publication Date: 2006-12-14
CC10 SWEDEN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0023] It is a further object of the invention to treat, cure or prevent RDS, BDP, chronic lung disease and/or pulmonary fibrosis, asthma, and COPD in humans by reducing total cell counts, neutrophil counts, total protein concentration IL-6 levels and/or IL-8 levels in the serum or tracheal fluid, and therefore the lungs, of patients.
[0024] It is a further object of the invention to provide a safe, well-tolerated

Problems solved by technology

The influx of neutrophils into the lung is known to be a cause of the destruction of functional lung tissue and the harmful symptoms of RDS, BPD, chronic lung disease, pulmonary fibrosis, asthma and COPD.
In RDS, BPD, chronic lung disease and/or pulmonary fibrosis, asthma and COPD total cell influx and neutrophil influx results in damage to and destruction of pulmonary tissue, ultimately causing functional lung tissue to be replaced with non-functioning fibrotic tissue.
Thus, neutrophil influx is ultimately responsible for causing pulmonary fibrosis to the lungs, which lead to damaged lung tissue and possibly death.
These, and other, powerful non-specific destructive mediators released by neutrophils damage all cell types and destroy lung tissue, including breaking down the bronchiolar and alveolar structure, resulting in decreased lung function and respiratory distress.
Local vascular structure is also damaged, resulting in increased vascular permeability and leakage of serum proteins into the lung and tracheal fluid, further impairing function.
This non-specific neutrophil response results in greater damage to respiratory tissue than the original irritant or infectious agent.
BPD and RDS are associated with substantial morbidity and mortality as well as extremely high health care costs.
Still further it is known that higher levels of fibronectin are present in the tracheal fluid and lungs of patients suffering from RDS and BPD and thus it causes and contributes to respiratory distress.
This makes it difficult for the air to move in and out.
This narrowing or obstruction causes the symptoms of asthma.
COPD is a lung disease in which the lungs are damaged, making it hard to breathe.
In COPD, the air

Method used

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

Examples

Experimental program
Comparison scheme
Effect test

example 1

Administration of rhCC10 to Premature Infants

[0051] Patients were enrolled in a placebo-controlled, blinded, dose ranging study at four hospital sites.

[0052] rhCC10 was produced in E. coli bacteria and purified by a proprietary process (Claragen, Inc., College Park, Md.), described in U.S. Application Publication Nos. US 2003-0109429 and US 2003-0207795, both of which are incorporated by reference in their entirety. The protein for the study was provided as a >98% pure solution of recombinant human CC 10 homodimer. The biological activity of each batch was compared using a proprietary secretory PLA2 inhibition assay, described in U.S. Application Publication Nos. US 2002-0169108 which is incorporated herein by reference.

[0053] Newborn infants who met the following criteria were enrolled: 1) age ≦24 h; 2) birth weight between 700 and 1,300 g; 3) gestational age ≧24 wk; 4) diagnosis of RDS based on clinical and radiographic criteria; 5) requirement for intubation and mechanical ven...

example 2

TAF Concentrations of CC10 in Patients Treated with rhCC10

[0061] With reference to FIG. 1 it has been found that during the first 48 hours of life, after an initial dose of rhCC10, significantly increased overall CC10 concentration occurred in patients receiving rhCC10 in dosages comprising either 1.5 mg / kg of body mass or 5 mg / kg of body mass versus placebo. Thus, administration of rhCC10 during the first 24 hours of life has a significant positive impact on CC10 levels in patients during the first two days of life. Furthermore, administration of rhCC10 will increase overall CC10 concentrations in patients.

[0062] Reference is now made to Table 2, as well as to FIG. 1, the contents of which are further described in this example.

TABLE 2Average TAF CC10 ConcentrationsCC10CC10CC10CC10 Conc. inConc. inConc. inConc. inTAF**TAFTAFTAF12 Hours24 Hours48 Hours72 HoursPlacebo 476 ng / ml 753 ng / ml 916 ng / ml3435 ng / ml1.5 mg / kg*2336 ng / ml1639 ng / ml2492 ng / ml1522 ng / mlrhCC105 mg / kg*2400 ng / ml1...

example 3

Serum Concentrations of CC10 in Patients Treated with rhCC10

[0064] Furthermore, with reference to FIG. 2, in one embodiment, rhCC10 may be administered intratracheally such that peak serum levels of CC10 are achieved within 6 hours of administration. Peak serum levels occur within 6 hours, irrespective of the dose of rhCC10 administered. Based on the results described below and in FIG. 2, peak serum levels will occur within about 6 hours after administration across all dosage ranges.

[0065] Reference is now made to Table 3, as well as to FIG. 2, the contents of which are further described in this example.

TABLE 3Average Serum CC10 ConcentrationsCC10CC10CC10CC10CC10CC10Conc. inConc. inConc. inConc. inConc. inConc. inserum**serum**serum**serum**serum**serum**Elimination0 Hours6 Hours12 Hours24 Hours36 Hours48 HoursHalf-lifePlacebo42 ng / ml 43 ng / ml 46 ng / ml 40 ng / ml 37 ng / ml 38 ng / mlNotapplicable1.5 mg / kg*76 ng / ml1289 ng / ml782 ng / ml354 ng / ml196 ng / ml101 ng / ml11.6 hoursrhCC10  5 mg / kg...

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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.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation-in-part of pending application Ser. No. 11 / 189,229, filed Jul. 25, 2005, which is a continuation-in-part of application Ser. No. 09 / 835,784, filed Apr. 13, 2001, now abandoned, which is a continuation-in-part of application Ser. No. 09 / 549,926, filed Apr. 14, 2000, now abandoned, which is a continuation-in-part of application Ser. No. 09 / 120,264, filed Jul. 21, 1998, now abandoned, which is a continuation-in-part of application Ser. No. 09 / 087,210, filed May 28, 1998, now abandoned, which is a continuation-in-part of application Ser. No. 08 / 864,357, filed May 28, 1997, U.S. Pat. No. 6,255,281. Each of the aforementioned applications and patent are incorporated herein by reference in their entirety.FIELD OF THE INVENTION [0002] The present invention relates to methods of reducing the influx of neutrophils into the lungs of a human. More specifically the present invention relates to methods of treating r...

Claims

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Application Information

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IPC IPC(8): A61K38/17
CPCA61K38/17A61K38/1709A61P11/00
Inventor PILON, APRILE L.
Owner CC10 SWEDEN
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