Recombinant human cc10 and compositions thereof for use in the treatment of nasal rhinitis

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 nasal rhinitis, nasal sinusitis, chronic rhinosinusitis, and nasal polyposis. More particularly, the invention provides methods, including broadly the critical dosage ranges of rhCC10 and intranasal route of administration, 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 claims benefit of and priority to, U.S. Provisional Patent Application 61 / 052,861, filed May 13, 2008, the disclosure of which is hereby incorporated by reference in its entirety.FIELD OF THE INVENTION[0002]The present invention relates to methods of reducing airflow obstruction in the nasal passages, clearing a sinus infection, and reducing sinus pain in a patient. More specifically the present invention relates to methods of treating nasal rhinitis, sinusitis and nasal polyposis in patients and compositions useful for the same. Yet more specifically, the present invention relates to methods of treating the above using intranasally-administered recombinant human CC10 and compositions thereof useful for the same.BACKGROUND[0003]Clara Cell “10 kDa” protein (CC10) or uteroglobin (UG) is a small, homodimeric secretory protein produced by several mucosal epithelia and other organs of epithelial origin (Mukherjee, 1999). CC10 ...

AI Technical Summary

Benefits of technology

[0020]It is a further object of the invention to provide a safe, well-tolerated and effective dosage range of rhCC10 which accomplishes the above objectives and does not significantly suppress the immune response or increase the frequency or severity of adverse events.

[0040]In another aspect, rhCC10 can be used as an excipient or to alleviate the irritation caused by intranasal administration of other drugs for either local or systemic delivery.

Problems solved by technology

Pulmonary epithelial cells, the body's primary source for endogenous CC10, are often adversely affected in these conditions, depleted or even ablated (Shijubo, 1999).

The obstruction of airflow in the nasal passages, as well as sinus pain and pressure, are known to be causes of significant morbidity in humans suffering from allergic rhinitis, non-allergic rhinitis, sinusitis, and nasal polyposis.

These permanent changes to the nasal tissues result in a vicious cycle in which decreased ability to fight infection, both viral and bacterial, as well as a decreased ability to clear inhaled allergens and irritants, lead to even more exaggerated inflammatory responses, further exacerbating remodeling and fibrosis, and more severe or persistent infections.

Chronic rhinitis, whether allergic or non-allergic, results in excess mucus production in, and swelling of, nasal passages that impairs breathing, disrupts sleep, and predisposes to repeated bacterial sinus infections.

The sinus pain and pressure causes significant morbidity in this disease.

In the most severe cases, nasal polyps grow in the nasal airways and slowly obstruct them.

However, determining whether rhCC10 can alleviate inflammation, and at what dosage, in patients suffering from nasal rhinitis, especially chronic rhinitis and rhinosinusitis, with or without nasal polyposis and in patients suffering from chronic or recurrent bacterial sinus infection has remained elusive.

Chromium nasal solutions, oral anti-histamines and leukotriene receptor antagonists treat symptoms but provide only a few hours of relief.

Nasal oxymetazoline solutions are very effective at opening nasal passages but overuse results in a “rebound effect” and rapid loss of efficacy with worsening of symptoms.

Side effects for these types of drugs include sore throat, dehydration of nasal tissues, and constipation, among others.

Antibiotics can also cause hypersensitivity reactions, particularly in patients with recurrent sinusitis who have to take antibiotics repeatedly and eventually become allergic to them.

Hypersensitivity reactions to antibiotics may occur without warning or previous signs of allergy and may be suddenly lethal.

For severe and / or chronic rhinosinusitis disease, physicians currently prescribe nasal corticosteroids, which reduce inflammation but often lose efficacy after a few weeks or months of continuous therapy.

Oral corticosteroids are also efficacious but have many undesirable side effects when used for long periods of time.

For example, in adults, cardiovascular complications, including hypertension and stroke, are major side effects of corticosteroid use.

In children, corticosteroids impair normal growth and development.

In all patients, corticosteroids lower the patient's immune function and leave them susceptible to infection of all types (bacterial, viral, fungal, etc.).

For example, when the nasal passages are blocked by thick mucus, local delivery of drugs is very difficult, if not impossible.

Therefore, it is a significant challenge to find an agent, and a correct dosage for that agent, which alleviates airway obstruction, sinus pain and discomfort for a pro-longed period of time without serious side effects.