Recent Patents on Biomarkers (Discontinued) - Volume 1, Issue 3, 2011

Glycosylation is one of the most common post-translational modifications on proteins and lipids. The functions of glycosylation include immune regulation and pathogen invasion, signaling, protein structure regulation, protein quality control and degradation, and cell adhesion and migration. Due to these diverse functions, detecting glycosylation has recently become a target of biomedical research. Many recent advances have been made in glycosylation analysis. Microarray and mass spectrometry improvements have made whole glycoproteome analysis possible and the identification of abnormal glycosylation patterns associated with various diseases. Cancer associated glycan structures, glycosylation changes, and glycoforms of proteins are becoming increasingly used for biomarker development and treatment options. This article discusses recent patents involving technology and methodology advances in glycosylation analysis along with cancer-specific glycosylation-based biomarkers. Owing to the recent development of the field, pending patents detailing glycosylation analysis methods and glycan-based biomarkers are included in this review.

Cancer is a malady that ranks high in causing significant morbidity and mortality. Due to the complex genetic alterations and consequential biochemical and cellular changes that accompany the tumorigenic process, detection and treatment of this disease has been a formidable task. Extensive research over the last several decades has brought to light some of the key signature modifications that are specific to cancer cells or to patients with cancer and were broadly termed tumor markers or tumor biomarkers. These biomarkers have been useful in the diagnosis and prognosis of cancers, thereby aiding in efficacious therapies. Oral cancer is the sixth leading cause of cancer with 900,000 cases detected every year; most of them presented clinically in advanced stages. Thus, the tumor burden plays a deleterious role leading to treatment failure and high rates of mortality as well as morbidity. Thus, key molecular biomarkers in oral cancer have been identified and a number of inventions have emanated from the studies in this context. They range from detection of microRNA and interleukins in saliva of the patients with oral cancer, to changes in gene expression of salivary proteins. Further, some of the transcriptional changes have similarities to other cancers such as melanoma (example, MAGE transcripts). Also at the cellular level, indicators of proliferation have been touted as valuable markers in oral neoplasia. Here we highlight some of the unique molecular biomarkers related to oral cancers. With the advances in technologies as well as an intense basic research in this field more candidates are bound to emerge. This would translate into better diagnosis and more individualized therapies for management of oral cancer. The current review also specifically highlights the patent applications that could have an impact in the management of oral cancers.

Probiotics are intestinal microorganisms that enhance gastrointestinal homeostasis by positively affecting the intestinal microbiota balance. The commensal gut microbiota confer health benefits to their host by helping dietary digestion, regulating gut immunity, maintaining the microbial balance, and preventing pathogen colonization. Probiotics are increasingly being used for irritable bowel syndrome, inflammatory bowel diseases, necrotizing enterocolitis, acute infectious diarrhea and antibiotic-associated diarrhea. Several studies suggest that probiotics may be clinically used as a prophylactic treatment to prevent colon cancer development. Although, many of the health-promoting aspects have yet to be definitively proven in humans, eliciting a change away from gut flora dominated by potentially harmful bacteria toward a more benign, or beneficial, composition appears to have great value. The mechanisms of action of probiotics against gastrointestinal pathogens addressed in diverse patent applications include modulation of the immune and non-immune defense mechanisms of the host. The use of innovative biomarkers at mRNA or protein levels to predict whether immunomodulatory bacteria are likely to be successful in treating certain types of diseases is also reviewed. Moreover, elucidations of the molecular interactions and mechanisms that underlie the host-health effects observed are discussed.

Butyrylcholinesterase (BChE) and acetylcholinesterase belong to the esterase family. They have roles in neurotransmission and in metabolizing drugs and toxins. Sharing similar biochemical and structural properties, they have overlapping functions. Patents obtained on these enzymes relate to the sequence of genes coding for the proteins, as well as methodological issues about screening of individuals who are susceptible to anticholinesterase drugs. Newer methods were described for production of large quantities of the protein that could be used in cocaine toxicity and overdose. The proteins were produced both in transgenic animals and in plant sources. In animals, they are excreted in milk and in urine. In view of their pathogenic roles in neurodegenerative diseases, methods were developed to identify Alzheimer's disease and to treat the fibril related diseases using antisense compounds related to the group of proteins. Lastly BChE was proposed to be a marker of low-grade systemic inflammation. In summary, for proteins with so few definitely known functions, there has been extensive work to utilize it in diagnosis and treatment. Some important patents on cholinesterases have been summarized in this review.

TWEAK is a cytokine that belongs to the TNF superfamily. TWEAK binds to the Fn14 receptor to activate alternative and classical NFκB pathways, MAPKs, TAK1 and PI3K/Akt intracellular signaling pathways. TWEAK regulates cell proliferation, cell death, cell differentiation, angiogenesis and inflammation. Functional studies targeting TWEAK and/or Fn14 implicate the system in acute and chronic tissue injury, tissue repair and cancer. Circulating soluble TWEAK has been postulated as a biomarker of endothelial injury, atherosclerosis and clinical outcomes in chronic kidney disease patients. In addition, urinary TWEAK has been suggested to be a biomarker of lupus nephritis activity. A database search yielded one patent on TWEAK as a biomarker of subclinical cardiovascular injury. Further research is needed to validate the relevance of TWEAK assessment as a decision-making clinical tool.

The use of biomarkers for the diagnosis, prognosis, and monitoring of disease; as well as to guide the choice of therapeutic regimens is predicted to be one of the leading priorities in clinical practice. The sheer complexity of the human cell, including its growth and signaling pathways, has made one of the biggest challenges in the cancer field the identification and characterization of such biomarkers and their translation into informative and reproducible diagnostic/prognostic tests. The increasing amounts of data, generated by experimental methods, challenges researchers to extract biologically applicable information. The authors, who represent academia, industry, and governmental organizations, discuss the current potential of translating cancer biomarker discoveries into suitable clinical tests. This review includes current information based on the latest patents in the cancer biomarker field relating to the different types of biomarkers (genomic, proteomics, epigenetics and microRNAs). It also describes the importance of strong intellectual property protection, current trends in patenting biomarkers, and future intellectual property strategies in the biomarker-related field. Finally, a summary of the recent relevant patentsand primary barriers to the translation of new biomarkers into viable clinical diagnostic tests is presented.

Chromosomal translocations are primary events in the development of leukemias and are used as biomarkers of various hematological malignancies. Biomarkers enable rational modifications of primary cancer therapies and provide new opportunities for early intervention. A biomarker is a gene/altered gene, protein, or other change that acts as a precursor of a biomedical phenotype before that phenotype is clinically apparent. Tests based on biomarkers have been around for more than half a century, but interest in their application for diagnostics and drug discovery as well as development, has increased remarkably since the beginning of the 21st century. Biomarkers are useful not only for diagnosis of some diseases but also for understanding pathogenetic mechanisms as well as the basis for development of therapeutics. Chromosome translocations are important in both diagnosis and targeted therapy in leukemia. Currently only a few translocations are being used for diagnostic and targeted therapy purposes (e.g., Philadelphia chromosome in CML and PML/RARα in APL), but several others may be identified in the future. Selecting chromosome translocations as biomarkers for targeted therapy for leukemia is an important area for evaluation. Some patents disclosing chromosomal translocations and their role in diagnosis and therapy of leukemia are also reviewed in this article.

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....