Recent Patents on Biomarkers (Discontinued) - Volume 2, Issue 1, 2012

Diabetes is a chronic condition that often requires life-long treatment. Hyperglycemia resulting from lack of diagnosis or neglect of the condition can result in devastating consequences. Early diagnosis and close monitoring of the condition may be the key to combat this disease. Saliva may have a role in diagnosing and monitoring diabetes. Recent studies and patents suggest that there is a potential of using this fluid in conjunction with blood. While many patents claim to have an application for saliva samples, only a handful of proteomic studies and a few patents really define specific diabetes- associated proteins differentially expressed in saliva. These studies however were cross-sectional and had a relatively small sample size. A longitudinal cohort with larger subject population with various stages of diabetes correlating the salivary protein biomarkers to known clinical markers, e.g., plasma glucose, serum A1C, and clinical symptoms, will be required for future studies. Moreover, future studies are needed to define the biological link between salivary biomarkers and pathophysiology of diabetes. Some of the relevant patents are also summarized in this review.

The aim of this article is to investigate patents and patent applications to the US Patent and Trademark Office, which are related to chronic kidney disease mineral and bone disorder (CKD-MBD). This term stands for a certain concept, which interprets bone disease of chronic kidney disease in a wider clinical context including coronary artery disease, extraosseous calcification and endocrine disorders. This concept which was introduced in 2005 is explained in detail and the related patents and biomarkers are discussed. Included in the article are also patents claiming new roles, unrelated to CKD-MBD as such, for some of the key biomarkers in this area. These include such promising compounds as klotho and FGF-23, matrix-Gla protein or fetuin-A. The patents dealing with these biomarkers outline a great potential for diagnostics and therapy not only of CKD patients in the future. Thanks to advances in cloning and sequencing techniques of recent years, a big proportion of the listed biomarker patents describe gene products identified by the analysis of rare genetic conditions. Also, some new roles for already well established markers such as parathormone (PTH) or vitamin K claimed by patent applicants are discussed in the article.

A biomarker, or biological marker, is defined as a characteristic element that is objectively measured as an indicator of normal biological processes, pathogenic processes, or a pharmacological response to a therapeutic intervention. Oncology biomarkers are endogenous elements, present in tumor tissues or body fluids, whose amounts or modifications are indicative of tumor state, progression characteristics, and/or response to therapies. During the last decade, improved understanding of mechanisms of carcinogenesis and tumor progression has revealed a great number of potential effective oncology biomarkers with potential to reduce cancer mortality rates by facilitating early diagnosis of this pathology. Classical approaches, based in tissue biopsy, are often limited by restricted access to target tissues. In contrast, peripheral blood profiling has emerged as an attractive and accessible biomarker discovery source. The global market of biomarkers is expected to grow more than double over the next five years, reaching almost 12.8 bn $. Identification of specific and early peripheral blood biomarkers for many types of cancer is still a big challenge. In this paper, we also described some patented biomarkers for the early diagnosis of cancer.

SUMO-specific protease (SENP)1, a member of the SENPs family, has emerged as a potential target to reduce the development of various cancers. Importantly, SENP1 targets essential molecules involved in carcinogenesis. This article provides a review of current understanding of factors targeting and targeted by SENP1 in cancer. It also provides an overview of SENP1 and recently issued US patents that cover various strategies involving the use of SENP1 in the detection of bladder, colon or prostate cancer in a biological sample.

The identification of a minor cellular subpopulation responsible for the initiation, maintenance and expansion of tumors (the cancer stem cells -CSCs-) meant a radical paradigm shift, but at the same time the selection of specific biomarkers may have extraordinary prognostic value. Recently, circulating epithelial cells (CTCs) have been identified in peripheral blood of solid tumor patients, demonstrating their prognostic value in metastatic breast cancer and positive predictive value for treatment response. This identification is based on epithelial cell markers in peripheral blood through immunocytochemistry technology or PCR, with a clear prognostic goal. Since CSCs are responsible for the initiation of new tumor lesions, we propose that a subpopulation of CTCs is the CSCs that will initiate metastasis. It is reasonable to speculate that a subpopulation of CTCs with stem cell features, such as self-renewal, multipotency, tumorigenicity and likely showing markers of epithelial-mesenchymal transition (EMT), may be the relevant players during metastasis. Further research into molecular characterization of CSC specific CTCs will create opportunities for novel therapeutic intervention, but at the same time facilitate the detection of clinically relevant CTCs. In this review, recent patents on CTC biomarkers are summarized.

This review informs on current literature on patents for biomarkers for asthma from 2009 to 2011. Variable airflow obstruction in asthma is generally triggered by gene-environment interactions that can lead to key symptoms of cough, shortness of breath, chest tightness, and wheezing. The episodic and variable degrees of airway hyperresponsiveness arise from a variety of inflammatory pathways that can make diagnosis and management difficult. Standard pulmonary function tests used for the diagnosis of asthma may fail to predict individual responses to the standard bronchodilator and corticosteroid therapies. Phenotypic predispositions can alter the severity of the asthmatic condition and treatment response. Biomarkers from sputum, exhaled gases, exhaled breath condensates, urine, serum, and broncheolaveolar fluid lavage proteins are currently explored to provide objective metrics for identifying individuals at risk, provide therapy guidance, monitor disease progression and evaluate response to therapy, as a supplement to standard pulmonary function tests. Updates on the refinement of technologies, inherent limitations and benefits of these biomarkers are discussed to provide insights on how current understanding of pathologic mechanisms has been applied to provide information for addressing gaps in the diagnosis and management of asthma.

The aim of the study was to investigate bone metabolism after surgery through monitoring of bone turnover markers up to 1 year. Samples from 58 patients with diaphyseal fractures of the lower leg or tibia (group 1, n = 13), pertrochanteric femur fractures (group 2, n = 10), medial femoral neck fractures treated by cemented hip hemiarthroplasty (group 3, n = 13), soft tissue diseases (group 4, n = 12) and in patients who underwent abdominal surgery (group 5, n = 10) were analyzed. We measured serum bone alkaline phosphatase (BAP) and osteocalcin (OC) as markers of bone formation and serum type I collagen C-terminal telopeptide (ßCTX) as marker of bone degradation. We found a significant decrease of BAP in all groups within the first week after surgery. Potential mediators, responsible for this early decrease are cytokines of the acute phase response. After an initial fall, serum concentration of the degradation marker ßCTX increased at 10 - 14 days depending on group, while bone formation markers started to rise later. The increase of markers of bone metabolism seems to reflect bone resorption and bone remodeling initiated by the surgical procedure and damage to the bone. Markers of bone metabolism provide a new and promising tool for monitoring fracture and hip replacement. Here, we present a review of recent patents and markers of bone metabolism provide a new and promising tool for monitoring fracture and hip replacement.

The recent patents annotated in this section have been selected from various patent databases, and are relevant to the articles published in this journal issue. The patents are categorized in fast emerging patent biomarker applications e.g. discovery and validation in drug discovery, clinical development and molecular diagnostics, bioinformatics, preclinical biomarker discovery, personalized medicine, translational biomarkers and therapeutic interventions.