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Compositions for use in the treatment of chronic obstructive pulmonary diseases and asthma

a technology for obstructive pulmonary disease and compositions, applied in immunological disorders, instruments, antibody medical ingredients, etc., can solve the problems of limited airflow to and from the lungs, shortness of breath, and inability to reverse the limitation of airflow, so as to prevent the development of chronic obstructive pulmonary disease

Inactive Publication Date: 2013-08-01
INDIANA UNIV RES & TECH CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The invention provides a method for preventing the development or worsening of chronic obstructive pulmonary disease (COPD) or asthma in subjects who are at risk for these conditions. The method involves administering to the subject a therapeutically effective amount of type V collagen or a tolerogenic fragment thereof. This can be done orally, by intravenous injection, or through other routes such as inhalation or intramuscular injection. The subject can receive a daily dose of 0.1-0.5 mg of type V collagen or a tolerogenic fragment thereof for several weeks or longer to achieve the desired effect. The invention has the potential to reduce the risk of COPD and asthma in individuals who are at risk and to provide a beneficial treatment for these diseases in patients already suffering from them.

Problems solved by technology

This leads to a limitation of the flow of air to and from the lungs causing shortness of breath.
In contrast to asthma, the limitation of airflow is poorly reversible and usually gets progressively worse over time.
In emphysema, the walls between many of the air sacs are damaged, causing them to lose their shape and become floppy.
This damage also can destroy the walls of the air sacs, leading to fewer and larger air sacs instead of many tiny ones.
This causes the lining to thicken.
Lots of thick mucus forms in the airways, making it hard to breathe.
COPD is a significant cause of death and disability.
However, early detection and diagnosis has been difficult for a number of reasons.
Many patients exhibit features of more than one disease (e.g. chronic bronchitis or asthmatic bronchitis) making precise diagnosis a challenge, particularly in early disease.
Also, many patients do not seek medical help until they are experiencing more severe symptoms associated with reduced lung function, such as dyspnea, persistent cough, and sputum production.
Moderately severe asthma is defined as wheezing and dyspnea, and can be with or without cough and expectoration, but generally interferes with daily activities and / or sleeping.
Severe asthma is characterized by incapacitation due to dyspnea, and the afflicted patient typically is unable to eat or sleep normally, is very anxious, and is often exhausted.
A condition known as status asthmaticus is the most severe form of asthma, and generally requires intensive hospital care, and may even prove fatal.
While there are several treatments available for relieving the symptoms and discomfort associated with asthma, there are no cures.
Moreover, the current treatments often cause side effects that exacerbate the discomfort and precipitate other debilitating conditions.
Other actions caused by antiasthmatic agents which limit their widespread use include headache, fatigue, dry mouth, nervousness, and in some cases addiction and substance abuse.

Method used

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  • Compositions for use in the treatment of chronic obstructive pulmonary diseases and asthma
  • Compositions for use in the treatment of chronic obstructive pulmonary diseases and asthma
  • Compositions for use in the treatment of chronic obstructive pulmonary diseases and asthma

Examples

Experimental program
Comparison scheme
Effect test

example 1

Anti-Collagen V Antibodies are Increased in COPD Patients

[0182]Plasma was obtained from normal volunteers (non smoking adults, age 18-55), and volunteers with documented emphysema. Levels of anti-colV antibodies in COPD patients and control healthy subjects were detected by the flow cytometry bead assay as described in WO 2007 / 120947.

[0183]Briefly, 1) Streptavidin-coated beads (5 μm, binding capacity 10-20 μg / 1×107 beads (Polyscience, Warrington, Pa.)) were washed two times with sterile PBS. Beads (1×107) were suspended in 100 μl of PBS with 40 μg of human Type V collagen and incubated for 60 minutes at 4° C. 2) A positive control was generated by following the same procedures in 1 above, using 20 μm of rabbit antibody to human collagen V antibody (bioten) (Abeam, Cambridge, Mass.). 3) For each assay, 1×106 conjugated beads were washed two times in PBS, and incubated in 100 μl PBS plus 50 μl serum. After incubating for 30-minutes at room temperature, the beads were washed three time...

example 2

Anti-Collagen V Antibodies are Increased in Asthma Patients

[0185]Plasma was obtained from normal volunteers (non smoking adults, age 18-55), and volunteers with documented chronic asthma. Levels of anti-colV antibodies in the asthma patients and control volunteer subjects were measured using the bead assay as outlined in Example 1.

[0186]As shown in FIG. 2, elevated levels of anti-type V collagen antibodies were found in 8 of 20 asthmatics.

example 3

Intravenous Collagen V Prevents Ovalbumin-Induced Airway Hyper-Responsiveness in Mice

[0187]This Example demonstrates that intravenous administration of collagen V prevents ovalbumin-induced airway hyper-responsiveness in this well-established murine asthma model.

[0188]Balb / c mice were injected via tail vein with 100 μg col (V), alone, or col(V) mixed in complete Freund's adjuvant, (CFA), or PBS, or CFA, alone. Seven days later mice received an IP injection of ovalbumin in alum and this was repeated seven days later. Seven days after the last ova / alum injection, mice in each group were challenged with increasing doses of aerosolized ova followed by measurements of airways resistance (PenH).

[0189]The results showed that col(V), alone, abrogated ova-induced airway hyperresponsiveness (see FIG. 3). Further experiments were conducted which confirm these results. These results are summarized below in Table 2.

TABLE 2Col(V) alone abrogates ova-induced airway hyperresponsivenessPBSCol(V)2-WA...

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Abstract

The present invention provides compounds and methods for treating or preventing pulmonary diseases include COPD and asthma. In particular, the present invention provides for compounds comprising type V collagen, or tolerizing fragments thereof, for the treatment of COPD and asthma.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This is a continuation of U.S. application Ser. No. 13 / 265,847 filed on Oct. 21, 2011; which is a U.S. national phase application of International PCT Patent Application No. PCT / US2010 / 032007, which was filed on Apr. 22, 2010; which application claims the benefit under 35 U.S.C. 119(e) of U.S. Provisional Patent Application No. 61 / 171,705, filed Apr. 22, 2009; and U.S. Provisional Patent Application No. 61 / 266,048, filed Dec. 2, 2009; which are incorporated herein by reference in their entireties.STATEMENT REGARDING SEQUENCE LISTING[0002]The Sequence Listing associated with this application is provided in text format in lieu of a paper copy, and is hereby incorporated by reference into the specification. The name of the text file containing the Sequence Listing is IURT—004—03US_ST25.txt. The text file is 67 KB, was created on Mar. 12, 2013, and is being submitted electronically via EFS-Web, concurrent with the filing of the specification....

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/00G01N33/68
CPCA61K38/39G01N33/6854G01N2333/78A61K39/0008G01N2800/50G01N2800/52G01N2800/56G01N2800/122A61P11/00A61P11/06A61P11/08A61P37/02A61P43/00A61K9/0019A61K9/0053A61K9/0073
Inventor WILKES, DAVID S.
Owner INDIANA UNIV RES & TECH CORP