Recent Patents on DNA & Gene Sequences (Discontinued) - Volume 5, Issue 2, 2011

AMP v. USPTO otherwise known as the ACLU/Myriad “gene patenting” case has famously pitted the American Civil Liberties Union (ACLU) against Myriad Genetics. DNA patent litigation is not novel, but this case is distinct from typical cases involving commercial rivals; heretofore neither side has an interest in the commercially suicidal attacking of the underlying concept of DNA patents. The ACLU, representing the plaintiffs, has no such qualms. And the ACLU is fighting dirty: the United Sates patent system is effectively moral and social-context neutral, but the ACLU has succeeded in making social and political concerns the highlight of their legal case, even reframing DNA as per our human understanding, as information, and as distinct from a simple double helical macromolecule. The relevance of the case exceeds the bounds of DNA patents, as reflected in the number of amicus briefs filed, and threatens many other industries, particularly those that rely on extracted biomaterials.

Mutations, Single Nucleotide Polymorphisms (SNPs), deletions and genetic rearrangements in specific genes in the human genome account for not only our physical characteristics and behavior, but can lead to many in-born and acquired diseases. Such changes in the genome can also predispose people to cancers, as well as significantly affect the metabolism and efficacy of many drugs, resulting in some cases in acute toxicity to the drug. The testing of the presence of such genetic mutations and rearrangements is of great practical and commercial value, leading many of these genes and their mutations/deletions and genetic rearrangements to be patented. A recent decision by a judge in the Federal District Court in the Southern District of New York, has created major uncertainties, based on the revocation of BRCA1 and BRCA2 gene patents, in the eligibility of all human and presumably other gene patents. This article argues that while patents on BRCA1 and BRCA2 genes could be challenged based on a lack of utility, the patenting of the mutations and genetic rearrangements is of great importance to further development and commercialization of genetic tests that can save human lives and prevent suffering, and should be allowed.

MicroRNAs are a class of non-coding small RNAs, which posttranscriptionally regulate gene expression through mainly binding to 3' untranslated region of mRNA. Most microRNAs are evolutionally conserved cross species; whereas, novel microRNAs expressed in different organisms are also identified with next generation sequencing technology. MicroRNAs play crucial roles in development, stem cells self-renewal, apoptosis and cell cycle. Aberrant microRNA expression in cancer and other diseases has been extensively investigated; the specific microRNAs have been developed for cancer diagnosis, prediction of drug-response and therapeutic outcome. Given the roles of microRNAs in pathophysiological conditions, it is conceivable that development of “miR-drugs” with different strategies (miR mimics, anti-miR, small molecule inhibitors of specific miRs) provides great hope to fight against cancer in combination of conventional treatment. In this review, the course of microRNA research to understand cancer biology is briefly introduced, the translation of miRNA studies from bench to bedside, particularly, microRNA implication in cancer with patents for diagnosis, prognosis will be described; the current status and challenges of “miR-drugs” development will be discussed.

DNA vaccines are a major breakthrough in the field of vaccination with several advantages over traditional vaccines. Unlike traditional vaccines, DNA vaccines stimulate both arms of the immune system offering long lasting immunity. DNA vaccines not only have the potential to fight against infectious diseases such as influenza and hepatitis but they can also be used to prevent autoimmune diseases such as multiple sclerosis. In general, this article is intended as a mini-review to discuss DNA vaccination, as well as patents on different types of DNA vaccines.

Viruses have evolved strategies to counteract host defenses. Some tactics employ viral proteins to neutralize host immune effector proteins such as cytokines, chemokines and their receptors, which help coordinate the host responses against the virus. Tumor necrosis factor (TNF) is one of the crucial pro-inflammatory/anti-viral cytokines involved in inflammatory and autoimmune diseases. Poxvirus anti-immune proteins represent some of the most complex and efficient mechanisms of regulating TNF and its pathological effects. These proteins have considerable potential for treating TNF-related diseases. Here we discuss two major classes of poxvirus-TNF inhibitors focusing on the tanapoxvirus (TPV)-2L protein, previously called TPV-gp38. TPV-2L has been shown to interact and biologically neutralize human (h)TNF, and has been indirectly associated with the inhibition of other cytokines (hIFN-γ, hIL-2 and hIL-5). The TPV-2L protein alone has been expressed, purified and shown to bind with high affinity to hTNF, but lacked binding to the other cytokines. Further studies identified sequential binding of hβ2-microglobulin and hα2-macroglobulin to TPV-2L. The ability of a single viral protein to form multi-protein complexes suggests that TPV might also possess other novel strategies of evading the immune system. Reviewed here are patented poxvirus TNF-binding proteins and their genes to evaluate their potential therapeutic value.

This review focuses on recent patents on the exploration and quantification of microbial diversity. Only the patents based on DNA analysis techniques are considered. In general terms, the analysis of environmental samples can be investigated by using three main approaches: microarrays based technologies, genomes/metagenomes comparison and amplification and detection of operative taxonomic units. All patents can relate to the estimation of the microbial diversity, however, many of them were initially designed to detect important medical or agronomic microorganisms. Here, we briefly review recent technological achievements for DNA analysis that offer great potentials for the identification of species.

STR genotyping from degraded DNA samples requires genetic profiles to be obtained from DNA fragments no bigger than 200-300 bp. It requires the use of miniSTRs, which are smaller than the STRs used in standard typing. This paper reviews recent advances in miniSTR genotyping, beginning with a brief introduction to the processes involved in DNA fragmentation and how it hinders standard STR genotyping before proceeding further to the loci included in the main DNA databases and finishing with the International Workgroups' recommended design strategies for developing miniSTR reactions. The results of the efforts of many laboratories achieving different STR multiplexes and patents are also described and compared. Finally, a consideration of the perspectives for the future in this area is presented.

In DNA microarray experiments, discovering groups of genes that share similar transcriptional characteristics is instrumental in functional annotation, tissue classification and motif identification. However, in many situations a subset of genes only exhibits a consistent pattern over a subset of conditions. Although used extensively in gene expression data analysis, conventional clustering algorithms that consider the entire row or column in an expression matrix can therefore fail to detect useful patterns in the data. Recently, biclustering has been proposed as a powerful computational tool to detect subsets of genes that exhibit consistent pattern over subsets of conditions. In this article, we review several recent patents in bicluster analysis, and in particular, highlight a recent patent from our group about a novel geometric-based biclustering method that handles the class of bicluster patterns with linear coherent variation across the row and/or column dimension. This class of bicluster patterns is of particular importance since it subsumes all constant, additive, and multiplicative bicluster patterns normally used in gene expression data analysis.

IL-1β is one of the major cytokines implicated in the pathogenesis of many inflammatory-associated diseases. Recent studies demonstrate that IL-1 β is activated through inflammasomes, which are formed upon recognition of danger signals by the immune system. IL-1 β is, therefore, becoming a focus for the development of new anti-inflammatory drug products. Current issued patents mainly covered the methods and the use of four types of IL-1 β blockade compounds, namely anti-IL-1 β antibody, IL-1 receptor antagonists such as sIL-1Ra and icIL-1Ra and IL1 trap. Two agents, Rilonacept and canakinumab were approved by the US FDA and others are in trial, in which beneficial results have been reported. One can expect that upcoming patents in the field of inflammasome research will facilitate the development of new therapeutic interventions.

Phage display technology has advanced considerably since its inception and the number of research projects using this technique is constantly increasing, generating numerous antibody and antigen libraries. These libraries, besides expediting library screening, improving selection methods and allowing evaluation of novel applications, have great potential for the development of new vaccines, drugs and diagnosis tests. Consequently, patent registries for the protection of these sequences are essential.

The patents annotated in this section have been selected from various patent data bases. These recent patents are relevant to the articles published in this journal issue, categorized by different biotechnology methods, processes and techniques involved.