Recent Patents on Inflammation & Allergy Drug Discovery - Volume 5, Issue 1, 2011

Chemokine-ligand/receptor axes play pivotal roles in a myriad of inflammatory, allergic and autoimmune diseases, as well as in the promotion of tumor growth and metastasis. Upon insult, tissue resident cells (and cancer cells in general) release a defined set of inflammatory chemokines that are responsible for the recruitment of activated pathological leukocytes. Recruited leukocytes synthesize and release a host of inflammatory mediators such as chemokines, cytokines, reactive oxygen and nitrogen species, and proteinases. These agents are responsible for the maintenance and amplification of inflammatory responses, and are directly responsible for secondary tissue damage, promotion of autoimmunity, fibrosis and tissue remodelling. Many cancers are associated with the expression of chemokine ligands that co-opt leukocytes such as tumor associated macrophages which in turn provide mediators including growth factors, chemokines and proteinases that promote angiogenesis, tumor growth, and cancer metastasis. Here, we discuss the relevant patents, development and the mechanism of action of a range of therapeutic and potential therapeutic agents that specifically target the chemokine ligand and receptor network. The main approaches that will be highlighted here are antagonism, cell depletion and the relatively unexplored fields of anti-sense, gene and stem cell therapies.

Due to improved treatment strategies mortality in multiple trauma patients has been decreased over the last decades. However, posttraumatic complications like sepsis and subsequent multiple organ dysfunction syndrome (MODS) remain a major problem on intensive care units following major trauma. The clinical course after multiple trauma depends on the balance or imbalance of the pro- and anti-inflammatory immune response. The predominance of the proinflammatory response leads to the “Systemic Inflammatory Response Syndrome” (SIRS), whereas the “Compensatory Anti-inflammatory Response Syndrome” (CARS) might result in immune suppression with an enhanced risk for infectious complications. Both, SIRS and CARS, play a pivotal role in the development of sepsis and the “Multiple Organ Dysfunction Syndrome” (MODS). A gender dimorphism in the host response after multiple trauma and sepsis has already been described. In experimental as well as clinical studies, a protective effect of female sex hormones and precursors like androstenediol has been revealed. Moreover, blockade of androgen receptors and the inhibition of dihydrotestosterone (DHT) synthesis were shown to provide beneficial effects on the immune response. Beside sex hormones, modulation of the Toll Like Receptor (TLR) pathway by macrophage-activating lipopeptide-2 (MALP-2) has sufficiently been described. Furthermore, hydrogen sulfide (H2S) and substance P have recently been revealed important for proinflammatory action in animal models of inflammation. Thus, these agents might be potential candidates for new treatment strategies in septic patients in order to improve the still unsatisfactory outcome of multiple trauma patients. If applicable, patents of each described agent are provided within the text.

Ocular allergy is an inflammatory response of the conjunctival mucosa that also affects the cornea and eyelids. Allergic conjunctivitis includes seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC) and giant papillary conjunctivitis (GPC). In general, allergic conditions involve mast cell degranulation that leads to release of inflammatory mediators and activation of enzymatic cascades generating pro-inflammatory mediators. In chronic ocular inflammatory disorders associated with mast cell activation such as VKC and AKC constant inflammatory response is observed due to predominance of inflammatory mediators such as eosinophils and Th2-generated cytokines. Antihistamines, mast-cell stabilizers, nonsteroidal anti-inflammatory agents, corticosteroids and immunomodulatory agents are commonly indicated for the treatment of acute and chronic allergic conjunctivitis. In recent years newer drug molecules have been introduced in the treatment of allergic conjunctivitis. This article reviews recent patents and emerging therapeutics in the treatment of allergic conjunctivitis.

Nowadays, occupational asthma is the most common form of occupational lung disease in the world. In some countries the textile industry remains an important source of potential agents causing occupational asthma. In the textile industry several agents such as cotton dust and dyes may cause occupational asthma. In this review, we discuss the epidemiology, pathogenesis/mechanisms, clinical presentations, management and prevention specific to occupational asthma in the textile industry.Work-related asthma risk is considerable. Current understanding of the mechanisms by which many textile agents cause occupational asthma is limited, especially for low molecular-weight sensitizers and irritants. The diagnosis is generally established on the basis of a suggestive history of a temporal association between exposure and the onset of symptoms and objective evidence that these symptoms are related to airflow limitation. Early diagnosis, elimination or reduction of exposure to the offending agent and early use of convenient therapy according to disease severity may play an important role in the prevention of long-term persistence of asthma. Its prevention in the textile industry should be both technical and medical. It depends on the difficulties to reduce dust level, the limits in arranging work station or in occupational rehabilitation. These difficulties are increased in small textile industry companies. Persistent occupational asthma in this sector is often associated with substantial disability and consequent impacts on income and quality of life. Prevention of new cases is the best approach to reduce the burden of asthma attributable to occupational exposures. This review also outlines different patents on the diagnosis and treatment of asthma.

Allergic asthma is a chronic inflammatory disease of the lung airways caused by genetic and environmental factors. Two quantifiable phenotypes of this disease are airway hyperresponsiveness and atopy. TOLL-like receptors (TLRs) are a family of intracellular and cell surface receptors that can respond to pathogen associated molecular patterns involved in the pathogenesis of asthma. Macrophages, one of the main immune cells involved in asthma, express a variety of TLRs, including TLR2, 4, 5, 6, 7, 8 and 9. This review focuses on polymorphisms found in TLR genes expressed in macrophages, and their role in asthma. Human studies have detected polymorphisms in TLR genes associated with asthma phenotypes, and studies using murine models have shown that some receptors and their agonistic or antagonistic ligands are capable of modulating the cytokine profile in asthmatics in a protective manner. Therefore, certain receptors and their ligands are being explored as potential immunotherapies for asthma. Recently, several patents have been filed protecting inventions for treating asthma through the use of TLRs and their ligands.

Despite the continuous increase in the prevalence of asthma in the most underdeveloped parts of the world, nowadays, we can generally speak of a better understanding and management of this disease. The remarkable role played by the inflammatory process in asthmatic patients is well known. The aim of most asthma guidelines is to suppress inflammatory process with a combination of anti-inflammatory drugs and immunotherapy. The management of asthma in children is a challenge because of their inability to express warning signs and seek medical attention in a timely manner. Unlike adults, asthmatic children must rely on their parents or caregivers for the administration of asthma medications. This inability to carry and self-administer asthma drugs may increase the risk of non-compliance. Glucocorticosteroids, the most important drugs for patients with asthma, are associated with an increased level of side effects and compliance issues mostly in children. In an attempt to solve that dilemma, emphasis is being placed on the modification of current management tactics and the introduction of other drugs. This review presents more recent patent therapies for the management of asthma in children.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system and the most common cause of neurological disability in young adults, along with a considerable clinical and pathological heterogeneity. Since, current therapies appear to be modest in the magnitude of their treatment effects, particularly in the progressive phase of this disease, thus novel promising therapeutic strategies might open a light horizon in approaching to an efficient treatment in MS. In this review, we will discuss about relevant patents and novel designed immunosuppressive and anti-inflammatory oral drugs promising for treatment of multiple sclerosis.

Topical application of honey to burn and wounds has been found to be effective in controlling infection and producing a clean granulating bed. It is suggested that the wound healing effect of honey may in part be related to the release of inflammatory cytokines from surrounding tissue cells, mainly monocytes and macrophages. It has been reported that honey hastens wound healing by accelerating wound contractions. Microscopic evaluation demonstrated that there was a significant acceleration of dermal repair in wound treated with honey. Macroscopic and microscopic observations under in vivo assessment suggested that the topical application of honey might have favourable influences on the various phases of burn and wound healing hence accelerating the healing process. The regulatory effects of honey are related to components other than the sugars. However, the mechanisms by which honey affects the release of anti inflammatory agents and growth factors from monocytic cells are as yet unclear. Whether honey affects other cell types, particularly endothelial cells and fibroblasts, involved in wound healing also needs to be clarified. The present article is a short review of recent patents on the healing effect of honey in wound and burn management.

RNA-protein interactions have been characterized often. Above all, the proteins which are associated with the studied RNA should be precisely identified. The pharmaceutical compositions containing nucleic acids and/or other compounds can be administered by any suitable route for administering medications. The immunostimulatory oligonucleotides play the role of antisense drugs which are being researched to treat cancers (including lung cancer, colorectal carcinoma, pancreatic carcinoma, malignant glioma and malignant melanoma), diabetes, Amyotrophic lateral sclerosis (ALS), and diseases such as asthma and arthritis with an inflammatory component. The immunostimulatory oligonucleotides may contain one or more natural or unnatural amino acid residues which are connected to the polymer by peptide (amide) linkages. The vaccine against cancer which has been produced during this work can be prophylactic or therapeutic. Since most studies so far have been performed with first-generation antisense oligonucleotides (ODNs), it is interesting to observe how second-generation immune stimulatory drug candidates with enhanced potency and efficacy can further improve the utility of this class of therapeutic agents. The aim of this article is to review most significant patents on immunostimulatory oligonucleotides.

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.