Recent Patents on Inflammation & Allergy Drug Discovery - Volume 5, Issue 2, 2011

Alopecia aerata (AA) is an autoimmune disease that presents as well defined patches of nonscarring hair loss with no overt epidermal changes. The life-time risk of AA in the general population is approximately 1.7%. As many as 60% of patients with AA have disease onset before 20 years of age. AA most commonly manifests as sudden loss of hair in well demarcated, localized area in the scalp. The hair loss is usually limited to a single patch. The lesion is usually round or oval. “Exclamation point hairs” are frequently seen at the periphery of the lesion. Because of the high rate of spontaneous recovery especially in those with small areas of hair loss or with a recent onset, not all patients require pharmacological treatment. A “watch-and- wait” approach is often recommended. Psychological support may be offered if necessary. For patients who actively desire treatment, topical corticosteroids and/or minoxidil are the treatment of choice. Interleukin (IL)-31 antibodies and 308-nm Excimer laser as novel treatment modalities appear promising in the armamentarium against this distressing disease. The review also outlined recent patents on the treatment of alopecia.

Rheumatoid arthritis (RA), although widely considered to be the most commonly occurring autoimmune disease, has only truly been substantiated as a distinct autoimmune disease very recently. The lack of understanding of the specific autoimmune system/s at work in rheumatoid patients resulted in an absence of robust diagnostic tools and had meant that the rational choice for use and design of therapy was based on broad-spectrum immunosuppression. The revelation that the autoimmune response specific for patients with RA is to particular protein antigens bearing the posttranslational modification ‘citrulline’ has therefore revolutionized diagnostics and has helped explain why patients carrying particular MHC alleles are predisposed to the disease. The last two decades have seen the characterization of citrullinated antigens targeted by both antibodies and T cells in rheumatoid patients. In more recent years, we have also witnessed the success of biological therapies in the treatment of RA that specifically target T cells and B cells. Ongoing mapping of antibody targets is increasing the percentage of patients who can be definitively diagnosed with, and prognosed to develop, RA. These advances have led to a great number of patents for citrullinated peptides that have been and may be, in the coming years, used in diagnostic test kits. More recently, characterization of T cell targets (citrullinated peptides) has resulted in the patenting of peptides that could be used in antigen specific therapy. This review focuses on the characterization of the autoimmune response to citrullinated protein targets in RA and how the community is translating this knowledge to improve diagnostics, prognostics and therapy.

Diagnosis and treatment of hypersensitivity to Hymenoptera venom took a landmark step forward in the late 1970s with the introduction of venom as an adequate material instead of whole body extracts. Since then, venom immunotherapy (VIT) has provided allergic subjects with a complete protection from fatal anaphylaxis and prevented about 90% of all reactions to stings. The cross-reactivity among some venom components, particularly important in the case of cross-reacting carbohydrate determinants, has often made it difficult to recognize the true causative venom to be used in VIT. Recently, the introduction of purified and recombinant allergens, such as Api m 1 from honeybee venom, Ves v 5 from yellow jacket venom, and Pol d 5 from wasp venom, have allowed a more precise diagnosis with identification of the causative venom component. This paves the way for a patient-tailored VIT in the near future. Another issue which needs to be addressed is the improvement in the safety of VIT with honeybee venom, which is significantly less favourable in comparison to vespid venom. A number of molecular approaches are under investigation in order to achieve this objective. Alternative routes of administration, such as the sublingual and the intralymphatic, have also been proposed, but there are not yet sufficient data available to demonstrate their feasibility. This review also presents patents on new trends in therapies for the management of hypersensitivity to hymenoptera venom.

Since the 1990s, autoimmune pancreatitis (AIP) has been increasingly recognized as a special type of chronic pancreatitis. Clinically, AIP patients commonly present with jaundice, weight loss and abdominal pain. Radiologically, there is diffuse or focal enlargement of the pancreas, often with narrowing of the pancreas and bile duct. Histologically, AIP is characterized by periductal infiltrates of lymphocytes and plasma cells, cellular fibrosis and obliterative phlebitis. Recently, two types of AIP were distinguished and called type 1 and type 2 AIP. They share the symptomatology and some histopathological features such as periductal lymphoplasmacytic infiltrate and storiform fibrosis, but differ in a particular duct change, called granulocytic epithelial lesion, which characterizes type 2 AIP. In addition, type 2 AIP usually has none or very few (<10 cells/ high power field (hpf)) IgG4-positive plasma cells. Clinically, type 1 AIP patients are roughly 10 years older than type 2 AIP patients, show a slight preponderance of men and reveal extrapancreatic manifestations of IgG4 associated systemic disease in approximately 50% of the cases. Type 2 AIP patients frequently show an association with inflammatory bowel disease and usually lack serological elevation of IgG4. The main differential diagnosis of AIP is pancreatic ductal adenocarcinoma. In many instances the diagnosis of AIP can be made by imaging together with serological markers. In difficult cases, particularly in type 2 AIP, the diagnosis has to be established by core needle biopsy. Both type 1 and type 2 AIP patients respond to steroid treatment, but a significant proportion of type 1 AIP patients suffer from recurrence of the disease. We describe the clinical and histological features of the two types of AIP as well as the treatment. In connection with pathogenesis and diagnosis, recent findings on immune complex deposition, autoantibodies in AIP and relevant patents are discussed.

Effective management of wound healing is a considerable challenge for clinicians. Patients underlying condition, accurate assessment of the wound and exudate, as well as selection of an appropriate dressing is all important factors for success. A variety of dressings are available to the clinician for the management of exudates. Hydrofiber dressings are a relatively new concept, and can be very cost effective because they can be worn for several days at a time. This report will review clinical evidences on the use of Hydrofiber dressing for the management of epithelial lesions, deal with current knowledge on the mechanism of action of this compound towards the epithelial wound healing process, immunological aspects and will also discuss relevant patents.

Mild or moderate hypothermia is a useful therapeutic method for improving the outcome for patients who have suffered brain injuries including traumatic brain injury and strokes, as well as secondary damages such as neuroinflammation and edema. The feasibility and safety of therapeutic hypothermia have been evaluated in experimental settings and clinical trials. Because the efficacy of therapeutic hypothermia, however, is dependent on the cooling method, application time, duration, and strategies, a continuous effort for obtaining optimal standard protocols of controlling temperature and the documentation of hypothermic devices and drugs are required. Here, we discuss the most recent hypothermia applications in brain injury and related diseases, and review the latest patents in hypothermic devices and cannabinoid-based hypothermia-inducing drugs. Ultimately, we conclude that a localized hypothermia may overcome the limitations, risks, and side effects of systemic hypothermia, and the combination of local hypothermia and drug treatment may improve clinical benefits.

The advent of new drugs can rapidly increase the number of substances causing acute pancreatitis. This is the case of tyrosine kinase inhibitors; these drugs are currently used for chronic myeloid leukemia, gastrointestinal stromal tumors, unresectable hepatocellular carcinomas and advanced renal cell carcinomas that and they have been reported to cause acute pancreatitis or asymptomatic elevations of serum pancreatic enzymes. Of the classes of drugs capable of inducing acute pancreatitis, we aimed to evaluate, in which class tyrosine kinase inhibitors can be allocated. A search was carried out using the MEDLINE database in order to select the data existing in the literature on pyrimidines and acute pancreatitis or serum lipase/amylase elevation covering the period from January 1966 to January 2010; thirteen papers were found and utilized for this review. Based on the data in the literature, we found that tyrosin kinase inhibitors may often cause an increase in pancreatic enzymes in plasma and patients treated with these drugs, especially those who are treated with sorafenib, might be at risk of developing acute pancreatitis. Whether acute pancreatitis due to tyrosine kinase inhibitors is associated only with sorafenib or may also be caused by other drugs of the same class remains an open question. Recent patents on tyrosine kinase inhibitors and acute pancreatitis are pointed out in this review.

Randomized controlled trials (RCT) have been recognized as the gold standard for interventional clinical trials. In many clinical trials of herbal medicine, it is very difficult to create a quality placebo. To achieve the purpose of blinding, the characteristics of the real drug and placebo should be identical in color, appearance, smell and taste. The quality placebo should be identical to the real drug in physical form, sensory perception, packaging, and labeling, and it should have no pharmaceutical activity. The aim of this study was to evaluate a placebo capsule and its matching herbal medicine D&G capsule in physical form, chemical nature, appearance, packaging and labeling. The assessment results suggested that the placebo was satisfactory in these aspects. The results demonstrated that a placebo could be created for a RCT involving herbal medicine. This report also discusses the means to acquire patent.

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.