Recent Patents on Biomarkers (Discontinued) - Volume 1, Issue 1, 2011

Ovarian cancer is responsible for the highest fatality rate among the gynecologic malignancies, and there is a great urgency in defining screening tests for its early detection. Presently, CA125 is the only serum marker recommended for early detection (in combination with transvaginal ultrasonography) in hereditary syndromes and for differential diagnosis in suspicious pelvic mass. However, given the complexity of the pathogenesis and of the tumor-host interaction, it is unlikely that a single serum biomarker bears sufficient information for the specific discrimination of ovarian cancer at its very early stage form other non-malignant pelvic lesions. Consistently, CA125 has demonstrated its utility for monitoring the therapy and prognosis, but owing to its scarce sensitivity and specificity it is not recommended for screening of ovarian cancer in asymptomatic patients. Recently, the introduction of high-throughput multiplex technologies, that allow to measure simultaneously a large number of molecules in the femtomolar range of concentration in the serum, has led to the definition of panels of biomarkers for the early detection of ovarian cancer. Here, we review the latest patents in this field.

During the last decade, complex methodologies have been developed in order to identify patterns of biomarkers with clinical relevance. It is commonly agreed that in early diagnosis, due to the complex nature of the neoplastic process, a single analyte cannot provide information regarding the complex array of cellular physiological status during the outcome of a disease. A proteomic/genomic pattern composed of many individual proteins can better differentiate patients from healthy individuals. For this declared purpose, individual proteomic platforms or platform combinations are often used to uncover the enormous array of intact and cleaved proteins contained by the human proteome. In the last 10 years, the patents disclosing early diagnosis biomarker panels in cancer have been steadily increasing from just one in 2002, to 14 in 2009, while in the first 6 months of 2010, 13 patents have already been disclosed. In the published papers regarding early diagnosis biomarkers, the same logarithmically growing number has been acknowledged. Among solid tumors, the gynaecological cancers are the most investigated and patented ones in the biomarker discovery area, with focus on breast, ovarian and endometrial cancers. Besides this type of cancer, colorectal and lung cancer are also subjects of some recent patents.

Osteoarthritis (OA) is the most common type of arthritis in humans and animals. It is a major cause of pain and disability and has significant consequences for public health. The burden of OA is expected to increase with ageing of the population and the present obesity epidemic. Therefore, there is an acute need for reliable biomarkers that can facilitate earlier diagnosis of OA, and inform the prognosis, monitoring and therapeutic strategies for chronic forms of this disease. However, the field is hampered by a lack of reliable, quantifiable, easily measured biomarkers that provide an earlier diagnosis of OA, inform on the prognostic of the disease and monitor and predict the responses of a patient to a therapeutic modality. Biomarkers of tissue turnover in joints have the capacity to reflect disease relevant biological activity and provide information that may be useful diagnostically and therapeutically, potentially enabling a more rational and personalised approach to healthcare management. In this paper, we review recent progress in the area of OA biochemical marker research. We hope that this review stimulates further research into OA biomarkers and contributes to the development of new and innovative tests for early disease diagnosis, facilitating individualised treatment and improving clinical outcome. We also review a selected number of recent patents relevant to the area of OA biomarkers highlighting areas for commercial development.

Long-term exposure to environmental pollution has been associated with an increased incidence of diabetes. In addition, environmental pollution has been associated with higher relative risk of mortality among people with diabetes compared to the general population. An association between exposure to air pollution and markers of cardiovascular risk has been shown including decreased heart rate variability, and increased levels of thrombotic and inflammatory factors. Since there is a growing body of evidence regarding the role of environmental pollution and smoking to the pathogenesis of diabetes mellitus, we tried to review the literature and patents to provide current literature data on the relationship between environmental pollution and diabetes mellitus.

Acute kidney injury (AKI) causes increased morbidity in critically ill children and damage to the kidney, a central mediator of homeostasis in the body, affects survival. The incidence of AKI in pediatrics is significant and despite alarming data, therapeutic interventions have failed to affect a meaningful difference in outcomes. In this review, we will discuss the epidemiology of AKI in pediatrics, treatment strategies attempted to date, experimental therapies targeting molecular patterns associated with AKI, and highlight the needed direction of AKI research and management. Prospective trials in pediatrics are needed to test the validity of diagnostic tools, to identify the point of most efficacious intervention, and to underscore the therapies that can be effective in the different downstream effects of AKI. In this review, we will discuss recent patents and advancements in diagnosis, management, and prevention.

Seventy-five percent of all cases of renal cell carcinoma have clear cell histology (CCRCC). In CCRCC alterations of the promoter of the VHL gene are the defining somatic genetic event. The high vascularity of RCC suggests a fundamental role of angiogenesis to its pathogenesis and is deeply associated with proliferation and metastasis. Many HIF-α target genes appear to be involved in these pathways, targeting VEGF and resulting in angiogenesis, increased vascular permeability, endothelial cell (EC) proliferation, survival, migration, and differentiation and promotion of degradation of the extracellular matrix. Molecular markers might predict the responsiveness of molecular targeted therapy. While in case of localised disease, radical nephrectomy is a highly effective therapy, for locally invasive tumors, surgical approaches are less effective and not curative for metastatic disease. In advanced cases, immune systematic cytokine therapies have resulted in low response rates, with a smaller percentage exhibiting complete remission upon treatment. Systemic treatments with traditional chemotherapy, radiation, and hormonal therapy have not been effective. The recent development of molecularly target agents has radically changed the management of metastatic CCRCC and the availability of reliable biomarkers to monitor therapy response and of anti-angiogenic drugs evasive to resistance could render targeted therapy more effective. We also review current patents on diagnosis and treatments of renal cancer.

Chronic mitral valvular insufficiency (CMVI) is probably the most common cause of congestive heart failure (CHF) in dogs. Although, recent advances in veterinary diagnostic imaging technology have enabled us to detect CHF earlier and more accurately, the accuracy and reliability of this technology heavily hinders on the experience and skill of the operator. Assays for cardiac biomarkers are a reliable method for the detection and evaluation of cardiac diseases in humans and dogs. Although, several cardiac biomarkers have been used and being widely used in small animal practice, several problems are encountered and hinders the clinical application of cardiac biomarker assays in small animal practice. Therefore, recent studies focus on developing new type of cardiac biomarkers, which can overcome limitations of pre-existing markers such as NT-pro BNP, cardiac troponins. This review focused on new cardiac biomarkers and patents about calcium related genes involving in myocardial contraction in dogs.

γδ T cells have several innate cell-like features that allow their early activation following recognition of conserved stress-induced ligands. Vγ9Vδ2 T cells, the dominant subset of γδ T cell in human peripheral blood, recognize phosphoantigens such as isopentenyl pyrophosphate generated in the mevalonate pathway. Upon activation, γδ cells display strong cytotoxicity towards various hemopoietic and nonhemopoietic tumors. Synthetic compounds have been recently patented which efficiently activate γδ cells in vitro and in vivo. In addition, the mevalonate pathway in mammalian cells can be manipulated by drugs such as aminobisphosphonates, giving rise to the development of new strategies in tumor immunotherapy. Thus, the recent developments in the discoveries of new molecules capable of activating these subsets of innate-like lymphocytes open new avenues for T cell based immunotherapy of tumors.

An early detection of cancer may provide the best eradicable treatment, hence, detection methods play a crucial role in cancer treatment. This article describes the role of chromatography for the separation and identification of breast cancer biomarkers. Biomarkers provide an assessment of prognosis, monitoring the effectiveness of therapy and predicting cancer reoccurrence. The important biomarkers of breast cancer detected by chromatography are genetic (single nucleotide polymorphism), proteomics (prostate-specific antigen, estrogen receptor, Human Kallikrein 14, progesterone receptor, Galectin-3-binding protein, alpha-1- Antichymotrypsin, Elafin, CA15.3, CEA, CA27.29, Her-2/neu, AAG, GCDFP-15 and GCDFP-24 etc.), metabolites (glucose, cholesterol, carbohydrate antigen 15-3, etc.) and breathing agents (2-propanol, 2, 3-dihydro-1- phenyl-4(1H)-quinazolinone,1-phenyl-ethanone, heptanal, isopropyl myristate etc.). In view of these points, attempts have been made to discuss the state-of-art of chromatography for biomarkers detection in breast cancer patients. Some modern chromatographic techniques such as nano-HPLC, LC-MS and DPHPLC have been discussed. Besides, efforts have been made to discuss sensitivity, specificity and protein profiles of these biomarkers. The future perspectives of chromatography for cancer treatment and important patents have also been discussed.

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.