Recent Patents on Inflammation & Allergy Drug Discovery - Volume 5, Issue 3, 2011

Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable disease characterized mainly by pulmonary airflow limitation that is not fully reversible. New different pharmacological approaches to decrease inflammation of the airways and consequently disease progression and increase airway obstruction reversibility have been developed. In the present article, we review the new patents on phosphoinositide 3 kinase and NFκb inhibitors for future therapies.

Apo2 Ligand/TNF Related Apoptosis-Inducing Ligand (Apo2L/TRAIL) is a cytokine that belongs to the TNF superfamilily that was described as capable of inducing apoptosis on tumor cells through activation of the extrinsic pathway in a Fas-independent manner. Besides this function, Apo2L/TRAIL, like other members of the TNF superfamily, has been shown to exert important functions in the immune system. Depending on their status of activation, Apo2L/TRAIL can be expressed by various cells of the immune system such as natural killer cells, T cells, dendritic cells and macrophages and has been implicated in distinct immunoeffector, immunoregulatory functions. Whit respect to pathological conditions, the Apo2L/TRAIL signaling pathway plays an important role in the response to infections, in immune surveillance against tumors, and in autoimmune disorders. Moreover, its implication in suppression of autoimmunity suggests that Apo2L/TRAIL has potential as therapeutic agent not only in cancer but also in autoimmune diseases. In fact, Apo2L/TRAIL-based therapies have been shown effective in various animal models of autoimmune disease. This review summarizes the current knowledge on the biology of Apo2L/TRAIL and its role in the immune system. Finally, patent applications, mainly related with the use of Apo2L/TRAIL as therapeutic agent in several autoimmune diseases, are also summarized.

Flavonoids are a large group of polyphenolic compounds, which are ubiquitously expressed in plants. They are grouped according to their chemical structure and function into flavonols, flavones, flavan-3-ols, anthocyanins, flavanones and isoflavones. Many of flavonoids are found in fruits, vegetables and beverages. Flavonoids have been demonstrated to have advantageous effects on human health because their anti-allergic, anti-inflammatory, anti-platelet aggregation, antitumor and anti-oxidant behavior. This report reviews the current knowledge on the molecular mechanisms of action of flavonoids as anti-inflammatory agents and also discusses the relevant patents.

There are no current therapies that specifically target IgE production in human allergic disease. We found that tetracyclines and chemically modified tetracyclines (CMT) that lack antibiotic activity prevent IgE production, making them ideal candidates for anti-allergy therapy. This is based on our findings that minocycline treatment of allergic asthmatic humans significantly improves their asthma symptoms, reduces their oral steroid requirements, and strongly suppresses their ongoing IgE responses. Tetracyclines and CMT also suppress ongoing IgE responses of BPO-KLH sensitized mice in vivo and in vitro and humans IgE responses in vitro. We also found that highly increased levels of phosphorylated p38 MAP kinase, but not phosphorylated JNK or ERK, are expressed by blood T and B cells and monocytes of allergic asthmatic humans. Levels of phosphorylated p38 MAP kinase, but not ERK or JNK, correlated with their IgE. Tetracyclines significantly suppressed expression of phosphorylated p38 MAP kinase by CD4+ and CD8+ T cells but not B cells or monocytes in vivo and in vitro. Our findings open the door to development of new drugs and patents, especially for CMTs that lack antibiotic activity (US 7649113), for treatment of human allergic disease.

A daily supplement of vitamin E is recommended for the secondary prevention of cardiovascular events in endstage renal disease patients on maintenance hemodialysis. Vitamin E has been entrusted with therapeutic properties against cardiovascular disease for more than 60 years. Several epidemiological studies and intervention trials have been performed with vitamin E, and some of them showed that it prevents atherosclerosis. For a long time, vitamin E was assumed to act by decreasing the oxidation of low-density lipoproteins, a key step in atherosclerosis initiation. However, at the cellular level vitamin E interferes with smooth muscle cell proliferation, platelet aggregation, monocyte adhesion, and oxidized low-density lipoproteins uptake and cytokine production, all reactions implied in the progression of atherosclerosis. Recent research points out that these effects may be not only the result of the antioxidant activity of vitamin E but also of its distinct molecular actions. These biological properties of vitamin E may allow to design better strategies for primary and secondary prevention of cardiovascular disease, with a potential exploitation of vitamin E supplements in primary and secondary prevention of major adverse cardiovascular events in all uremic patients. In this review, we also outline relevant patents on vitamin E and lipoxygenase inhibitors.

Nasal polyposis is a chronic inflammatory disease of the nasal and paranasal sinus mucosa. Etiology remains unclear, but allergy, asthma, aspirin sensitivity, cystic fibrosis, and infection have been associated with the disease. Clinically, nasal obstruction, anosmia/hyposmia, rhinorrhea, postnasal drainage, headaches, facial pain, and sleep disorders constitute the main symptoms. Intranasal examination reveals bilateral, mobile, grey, smooth and semi translucent polypoid masses that usually originate in the ethmoid sinuses or the middle meatus. Differential diagnosis is important to rule out congenital anomalies, as well as benign or malignant tumors. In the evaluation of nasal polyps, computerized tomography is helpful especially in determining the extent of the disease and in planning the surgical approach. Management of nasal polyposis consists of medical therapy and surgery. Surgical treatment is performed in cases that are refractory to medical therapy. Recurrence of nasal polyps is quite common and medical therapy after surgery is often necessary for avoiding recurrences. This paper aims to summarize the current trends in the diagnosis, management of nasal polyposis and relevant patents.

The patents annotated in this section have been selected from various patent databases. These recent patents are relevant to the articles published in this journal issue, categorized by therapeutic areas/targets & therapeutic agents related to inflammation and allergy drug discovery.