Methods of Preventing or Treating Respiratory Conditions

Abstract

The present invention provides prophylactic an therapeutic protocols designed to prevent, manage, treat, or ameliorate a respiratory condition or one or more symptoms thereof. In particular, the present invention provides methods for preventing, managing, treating, or ameliorating a respiratory condition or one or symptoms caused by environmental factors or a respiratory infection. The present invention encompasses combination therapies, pharmaceutical compositions, articles of manufacture, and kits.

Description

[0001]This application is a continuation and claims the benefit under 35 U.S.C. § 120 of U.S. patent application Ser. No. 10 / 823,810, filed Apr. 12, 2004, which claims the benefit under 35 U.S.C.§ 119(e) of the following U.S. Provisional Application Nos.: 60 / 477,801, filed Jun. 10, 2003 and 60 / 462,307, filed Apr. 11, 2003. The priority applications are hereby incorporated by reference in their entirety for all purposes.1. FIELD OF THE INVENTION[0002]The present invention provides prophylactic and therapeutic protocols designed to prevent, manage, treat, or ameliorate a respiratory condition or one or more symptoms thereof. In particular, the present invention provides methods for the prevention, management, treatment, or amelioration of a respiratory condition or one or more symptoms thereof, said methods comprising administering to a subject in need thereof an effective amount of one or more agents that modulate the expression and / or activity of interleukin-9 (“IL-9”). The inventio...

AI Technical Summary

Benefits of technology

[0089]The invention provides protocols for the administration of an effective amount of one or more IL-9 antagonists alone or in combination with an effective amount of one or more therapies, other than IL-9 antagonists, for the prevention, treatment, management, or amelioration of a respiratory condition or one or more symptoms thereof to a subject in need thereof. The therapies (e.g., prophylactic or therapeutic agents) of the combination therapies of the present invention can be administered concomitantly or sequentially to a subject. The therapy (e.g., prophylactic or therapeutic agents) of the combination therapies of the present invention can also be cyclically administered. Cycling therapy involves the administration of a first therapy (e.g., a first prophylactic or therapeutic agent) for a period of time, followed by the administration of a second therapy (e.g., a second prophylactic or therapeutic agent) for a period of time and repeating this sequential administration, i.e., the cycle, in order to reduce the development of resistance to one of the therapies (e.g., prophylactic or therapeutic agents), to avoid or reduce the side effects of one of the therapies (e.g., prophylactic or therapeutic agents), and / or to improve the efficacy of the therapies.

[0101]As used herein, the terms “antagonist” and “antagonists” refer to any protein, polypeptide, peptide, peptidomimetic, glycoprotein, antibody, antibody fragment, carbohydrate, nucleic acid, organic molecule, inorganic molecule, large molecule, or small molecule that blocks, inhibits, reduces or neutralizes the function, activity and / or expression of another molecule. In various embodiments, an antagonist reduces the function, activity and / or expression of another molecule by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% relative to a control such as phosphate buffered saline (PBS).

[0108]As used herein, the term “effective amount” refers to the amount of a therapy (e.g., a prophylactic or therapeutic agent) which is sufficient to reduce or ameliorate the severity and / or duration of a respiratory condition or one or more symptoms thereof, prevent the advancement of a respiratory condition, cause regression of a respiratory condition, prevent the recurrence, development, or onset of one or more symptoms associated with a respiratory condition, or enhance or improve the prophylactic or therapeutic effect(s) of another therapy (e.g., prophylactic or therapeutic agent).

[0137]As used herein, the term “prophylactically effective amount” refers to the amount of a therapy (e.g., prophylactic agent) which is sufficient to result in the prevention of the development, recurrence, onset or progression of a respiratory condition or one or more symptoms thereof, or to enhance or improve the prophylactic effect(s) of another therapy (e.g., a prophylactic agent).

[0144]As used herein, the term “synergistic” refers to a combination of therapies (e.g., prophylactic or therapeutic agents) which is more effective than the additive effects of any two or more single therapies (e.g., one or more prophylactic or therapeutic agents). A synergistic effect of a combination of therapies (e.g., a combination of prophylactic or therapeutic agents) permits the use of lower dosages of one or more of therapies (e.g., one or more prophylactic or therapeutic agents) and / or less frequent administration of said therapies to a subject with a respiratory condition. The ability to utilize lower dosages of therapies (e.g., prophylactic or therapeutic agents) and / or to administer said therapies less frequently reduces the toxicity associated with the administration of said therapies to a subject without reducing the efficacy of said therapies in the prevention or treatment of a respiratory condition. In addition, a synergistic effect can result in improved efficacy of therapies (e.g., prophylactic or therapeutic agents) in the prevention or treatment of a respiratory condition. Finally, the synergistic effect of a combination of therapies (e.g., prophylactic or therapeutic agents) may avoid or reduce adverse or unwanted side effects associated with the use of any single therapy.

[0147]As used herein, the term “therapeutically effective amount” refers to the amount of a therapy (e.g., an IL-9 antagonist, preferably, an antibody or a fragment thereof that immunospecifically binds to an IL-9 polypeptide), that is sufficient to reduce the severity of a respiratory condition, reduce the duration of a respiratory condition, ameliorate one or more symptoms of a respiratory condition, prevent the advancement of a respiratory condition, cause regression of a respiratory condition, or enhance or improve the therapeutic effect(s) of another therapy.

Problems solved by technology

Unfortunately, these therapies may cause side effects, such as hypertension and drowsiness or may not be effective.

If the reaction is prolonged, the subject may develop arrhythmias or cardiogenic shock.

Long-term immunotherapy is effective for preventing anaphylaxis from insect stings, but is rarely available for patients with drug or serum anaphylaxis.

Immediate administration of epinephrine is the most common treatment for anaphylaxis, but may cause side effects including headache, tremulousness, nausea, and arrhythmias.

These therapies are associated with side effects such as drug interactions, dry mouth, blurred vision, growth suppression in children, and osteoporosis in menopausal women.

However, there are no current therapies available that prevent the development of asthma in subjects at increased risk of developing asthma.

Symptoms of upper respiratory infection include runny or stuffy nose, irritability, restlessness, poor appetite, decreased activity level, coughing, and fever.

Unfortunately, in regard to certain infections, there are no therapies available, infections have been proven to be refractory to therapies, or the occurrence of side effects outweighs the benefits of the administration of a therapy to a subject.

The use of anti-bacterial agents for treatment of bacterial respiratory infections may also produce side effects or result in resistant bacterial strains.

The administration of anti-fungal agents may cause renal failure or bone marrow dysfunction and may not be effective against fungal infection in patients with suppressed immune systems.

Thus, as a result of drug resistance, many infections prove refractory to a wide array of standard treatment protocols.

Therapies available for the treatment of established RSV disease are limited.

While a vaccine might prevent RSV infection, no vaccine is yet licensed for this indication.

A major obstacle to vaccine development is safety.

Finally, primary RSV infection and disease do not protect well against subsequent RSV disease (Henderson et al., 1979, New Engl. J. Med. 300:530-534).

Furthermore, passive infusion of immune serum or immune globulin did not produce enhanced pulmonary pathology in cotton rats subsequently challenged with RSV.

While this is a major advance in preventing RSV infection, this therapy poses certain limitations in its widespread use.

Second, the concentrations of active material in hyperimmune globulins are insufficient to treat adults at risk or most children with comprised cardiopulmonary function.

Third, intravenous infusion necessitates monthly hospital visits during the RSV season.

Finally, it may prove difficult to select sufficient donors to produce a hyperimmune globulin for RSV to meet the demand for this product.

Alcoholics, institutionalized persons, cigarette smokers, patients with heart failure, patients with chronic obstructive airway disease, the elderly, children, infants, infants born prematurely, patients with compromised immune systems, and patients with dysphagia are at greater risk of developing pneumonia.

Determination of the specific pathogen causing the pneumonia cannot be made in about 30-50% of patients and specimens may be misleading because of normal flora may contaminate samples through the upper airways.

The administration of antibiotics may result in side effects, toxicity, and the development of antibiotic resistant strains.

In addition, because the pathogen causing pneumonia is difficult to diagnose, the use of antibiotics may be ineffective since both viruses and fungi also cause pneumonia.

In addition, fatal and severe liver injury has been associated with treatment of latent TB with rifampcin and pyranzinamide.

All forms of candidiasis are considered serious, progressive, and potentially fatal.

Unfortunately, acute renal failure has been associated with amphotericin B therapy.

Fluconazole, however, has led to increasing treatment failures and anti-fungal resistance.

Aspergillus fumigatus is the most common cause of invasive pulmonary aspergillosis that extends rapidly, causing progressive, and ultimately fatal respiratory failure.

However, invasive infections often progress rapidly and are fatal, thus aggressive therapy comprising IV amphotericin B or oral itraconazole is required.

Unfortunately, high-dose amphotericin B may cause renal failure and itraconazole is effective only in moderately severe cases.

AIDS patients, patients with Hodgkin's or other lymphomas or sarcoidosis, and patients undergoing long-term corticosteroid therapy are at increased risk for cryptococcosis.

Renal and hematologic function of all patients receiving amphotericin B with or without flucytosine must be evaluated before and during therapy since flucytosine blood levels must be monitored to limit toxicity and administration of flucytosine may not be safe for patients with preexisting renal failure or bone marrow dysfunction.

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