Recent Patents on Biomarkers (Discontinued) - Volume 4, Issue 1, 2014

Osteoarthritis is a multifactorial joint disease affecting millions of patients all around the world. Some inflammatory mediators as interleukin-1 beta and tumor necrosis factor-alpha, among others, are involved in stimulating the metalloproteinases production in the osteoarthritis disease process. These enzymes degrade all the articular cartilage extracellular matrix components; such as collagen, aggrecan and non-collagen proteins. In osteoarthritis, the expression of metalloproteinases is elevated and some considerable efforts have been made in order to design effective inhibitors of enzymes activity and/or synthesis with the intention of limiting the connective tissues destruction within the joints. As of yet, there are no effective clinical inhibitors; however, published patents employing metalloproteinases as early osteoarthritis biomarkers and/or targets for effective therapies might be able to provide new opportunities to prevent joint destruction related to osteoarthritis.

Background: Hepatitis C virus is a serious global health problem affecting more than 170 million patients who are at risk of developing liver cirrhosis and/or hepatocellular carcinoma. Egypt has the highest prevalence of HCV (genotype 4) as about 14.7% of Egyptian populations are positive for HCV antibodies. Aim: To review recent data and patents concerning cytokine polymorphism that affect the likelihood of achieving SVR and can be used as biomarkers for predicting the treatment response to overcome the unnecessary cost, time, and side effects of antiviral therapy for nonresponders. Methods: Data were pooled from 36 studies carried out internationally in which patients with chronic HCV receiving PEG IFN/RBV therapy were evaluated regarding cytokine polymorphism and/or its mRNA expression profile in relation to therapy response. Results and Conclusions: Studies to date have shown that cytokine gene polymorphism plays an important role in the natural clearance of HCV. Most of polymorphisms are in cytokine gene regulatory regions and are consequently involved directly in controlling the transcription rates. Type 1-like cytokines, such as IL-1β, IL-2, IL-6, IL-18, TNF-α, and IFN-γ were up-regulated in chronic HCV infection. The poor response was found to be associated with high producing genotype of IL-10, up-regulation of IL-28B and most of IGS genes, and associated with downregulation of TGF- β, IFN-γ. Good response was noticed to be associated with high level IL-6, IL-8, and certain genotypes of IL-6, IL-12, IFN-γ, TNF-α IFN λ4 and IFN λ3.

Identification of putative biomarkers is a need of modern society today. Biomarker measures a biological or pathogenic process that can predict disease prognosis. It is important for monitoring drug safety, identification of individuals who are most likely to respond to specific treatments, stratification of presymptomatic patients and quantification of treatment benefits. The peripheral blood based identification of biomarkers or disease signatures from psychiatric patients possesses an immense potential towards drug developmental process. Biomarkers have been used as an early diagnostic tool for neuropsychiatric disorders. Identification of potential biomarkers of psychiatric disorders has become most important when it comes to biological psychiatry related research area. Patent provides a legal protection given to a new invention which gives the holder exclusive right to use or sell the patented product. Hence, deep understanding towards patent system is important as it protects novel research outputs that may lead to invention of new drugs. The present review describes patents, its methods and validations focused on peripheral biomarkers including cerebrospinal fluid (CSF), plasma, serum and various neuropsychiatric disorders.

Though the first case of oral cancer related to HPV was reported in 1983, it was only in 2007, when WHO confirmed the role of human papilloma virus (HPV) in oropharyngeal cancer. Before this, the considered arch criminal for oropharyngeal cancer was primarily tobacco. In the last decade, there has been a sudden increase in oropharyngeal carcinoma in young individuals not being associated with tobacco and alcohol history. The reason could be delayed exploration of the association of HPV and oropharyngeal cancer. Out of about 100 types of HPV strains discovered at least 15 have an oncogenic potential. Of these, 90% of oropharyngeal cancer has been found to be caused by HPV 16 type strain. In recent years, many biomarkers have published on diagnosis, investigations and therapy of HPV associated oropharyngeal cancer. These biomarkers range from simple Messenger Ribonucleic Acid (RNA) of Early phase (E) E6 and E7 protein to Testicular Cell Adhesion Molecule 1 (TCAM1), Synaptonemal Complex Protein 2 (SYCP2) and Stromal Antigen 3 (STAG3). This review will encompass the molecular mechanisms associated with HPV and its carcinogenesis. The mechanisms included are interference in WNT and Notch signaling pathway leading to alteration in keratinocyte differentiation and activation of Phosphatidylinositol 3-Kinase (PI-3K) pathway. The other mechanism includes the patterns of methylation of HPV DNA and its impact over prognosis. The main aim of this review is to focus on recent patents on biomarkers for diagnosis and assessment of prognosis of HPV associated oropharyngeal cancer.

Oxidative stress is considered to be a prime cause of many diseases and is due to imbalance between the production of reactive oxygen species and the body's ability to detoxify these reactive intermediates. Current research on oxidative stress is to evaluate the reasons for the imbalance between oxygen species and antioxidants. Free radicals are generated within the living organisms and are involved in various cellular activities. Increases in the concentration of free radicals result in oxidative damage. Different antioxidant protective mechanisms evolved in parallel, to protect organisms from the imbalance of oxidative stress. Glutathione peroxidase (GPx), plays an important role against oxidative stress and diseases. Different isoforms of this enzyme, either as monomeric or tetrameric forms, have been distributed in different organs, tissues or cellular compartments. In disease states, GPx expression either gets activated or diminished based on several proposed mechanisms. Thus, glutathione peroxidase may function as a marker for different diseases. In this review, we are focusing on the role and regulation of glutathione peroxidase in different diseases based on relevant patents.

The calcium-sensing receptor is expressed almost ubiquitously throughout the human body, and is essential for calcium homeostasis and is involved in several disease pathomechanisms. Mainly in nephrology, therapeutic compounds acting on the receptor are already in use in clinical routine practice. The era of calcimimetic therapy, which commenced 10 years ago with the approval of the first-in-class compound cinacalcet HCl, has recently entered into a new phase with the arrival of velcalcetide (AMG416). Since both compounds bind to different sites at the receptor molecule, genetic polymorphism panels could conceivably play a role in future for the prediction of the best choice for any given patient. If velcalcetide, which has currently just passed phase-III-trials, is also approved for therapeutic use, this will increase the spectrum of choices and the clinician will have to make decisions about which calcimimetic drug to give to which patient. This decision would probably have to be based on various considerations including biomarkers. This article summarizes the present situation regarding patents on biomarkers dealing with the calcium-sensing receptor and genetic polymorphisms.