Recent Patents on Anti-Infective Drug Discovery (v.6, #3)

Current Update on Eosinophilic Lung Diseases and Anti-IL-5 Treatment by Konstantinos Samitas, Madeleine Radinger, Apostolos Bossios (189-205).
Peripheral blood eosinophilia and eosinophilic lung inflammation are common in a variety of pulmonary conditions,including eosinophilic pneumonia and asthma, hypereosinophilic syndrome and Churg-Strauss syndrome. Therapyin most of these clinical entities consists of long-term treatment with systemic corticosteroids, which is not always successfuland has substantial side-effects. Interest has increased considerably regarding alternative corticosteroid-sparing"smart" regimens in these diseases that target IL-5, an important regulator of eosinophilic development and function. Todate, two humanized monoclonal antibodies, mepolizumab and reslizumab, have been developed that bind to human IL-5.In addition a new monoclonal antibody (MEDI-563) has been recently developed targeting the IL-5 receptor. This reviewwill investigate the current status on IL-5 targeted therapy and related patents regarding eosinophil-driven respiratory diseases,primarily eosinophilic asthma but also CSS and HES. Recent advances and information from clinical trials will bepresented in a way that will allow the reader to approach the role of the eosinophil in the lung diseases presented in thisreview.

Traumatic injuries present a major public health concern worldwide. A role of gut and/or its derived factors hasbeen suggested in the pathogenesis associated with injury. Injury causes the activation of various signaling pathwaysalong with the release and activation of pro-inflammatory cytokines, chemokines and adhesion molecules in the intestine.This mediates infiltration of neutrophils into the intestine. Primed and subsequently activated neutrophils release variousproteolytic enzymes and superoxide anion which ultimately result in intestinal inflammation and/or injury. This reviewwill discuss the various factors contributing to intestinal inflammation following injury. Some of the patents relevant tointestinal inflammation have also been discussed in the present manuscript.

Chagas disease, a parasitic infection typically spread by triatomine bugs, affects millions of people throughoutLatin America. Current chemotherapy based on the nitroaromatic compounds, benznidazole and nifurtimox provides unsatisfactoryresults and suffers from considerable side effects. Therefore, there is still an urgent need for new drugs to treatthis neglected disease. During the last decade, the advances and understanding in the biology and biochemistry of Trypanosomacruzi have allowed the identification of multiple new targets for Chagas disease chemotherapy. Among themost promising targets for antiparasitic drugs are: cruzipain, the main cysteine protease of T. cruzi, essential for parasitesurvival and proliferation in mammalian host; ergosterol biosynthesis pathway; trypanothione synthesis and thioldependantredox metabolism. Specific enzymes of the glycolytic, pentose phosphate, polyisoprenoid (farnesylpyrophosphatesynthase) and other particular biosynthetic pathways as well as enzymes from purine salvage (hypoxanthine-guanine phosphoribosyl-transferase, dihydrofolate reductase) have also been intensively studied in T. cruzi. In particular,trypanocidal agents that target the validated biochemical pathways of the parasite including cysteine proteinase inhibitorsand inhibitors capable to block ergosterol biosynthesis are currently in the pipeline. Among the latter, posaconazoleand ravuconazole, are planned to enter in clinical trials for trypanocidal chemotherapy in the near future. This reviewwill summarize advances on antichagasic agents directed to specific parasite targets such as metabolic pathways or specificenzymes. Related patents filed and issued from 2000 to 2010 claiming inhibitors for specific parasite targets will bealso discussed. Among them, the most represented were those related with cysteine proteinase inhibitors.

Insulin resistance is an important and under..recognized consequence of HIV treatment. Different studies haveyielded widely varying estimates of the prevalence of impaired glucose metabolism in people on highly active antiretroviraltherapy (HAART). The risk increases further with hepatitis C co..infection. Although Protease inhibitors (PIs) are themain drug class implicated in insulin resistance, some studies have shown an association of increased risk of diabetes withcumulative exposure of nucleoside reverse transcriptase inhibitors (NRTIs). The effect of switching to other antiretroviralshas not been fully determined and the long-term consequences of insulin resistance in this population are not known.Treatment of established diabetes mellitus should generally follow existing guidelines. It is therefore reasonable to recommendgeneral measures to increase insulin sensitivity in all patients infected with HIV, such as regular aerobic exerciseand weight reduction for overweight persons. The present review article has the information of some recent patents regardingthe insulin resistance in HIV infection.

Patent Selections: by Bentham Science Publishers (269-270).
The patents annotated in this section have been selected from various patent databases. These recent patents are relevant tothe articles published in this journal issue, categorized by therapeutic areas/targets and therapeutic agents related to antiinfectivedrug discovery.