Recent Patents on DNA & Gene Sequences (Discontinued) - Volume 3, Issue 2, 2009

MicroRNAs (miRNAs) are small non-protein-coding transcripts that regulate gene expression posttranscriptionally by pairing with target messenger RNAs (mRNAs). It is predicted that humans express thousands of miRNAs and, although only a few hundred have been identified, there is already mounting evidence suggesting that they play an important role in several different developmental processes. It is therefore not surprising that miRNAs have been found to be deregulated in many diseases. The discovery of miRNAs has uncovered a natural form of controlling RNA transcription and translation, which could provide new avenues for diagnosis, prognostic, and therapeutic applications. This review summarizes some of the key recently published patents and relevant research advances on miRNA target identification, strategies to modulate their activity and the potential applications in human diseases such as cancer and viral infections, as well as methods and techniques for purification, detection and quantification of miRNAs.

The most critical issue for the application of high affinity monoclonal antibodies is their creation. Here, we summarize the cellular and molecular mechanisms by which high affinity antibodies are generated, and then review the attempts of many investigators to create high affinity monoclonal antibodies against various target molecules. High affinity monoclonal antibodies are generated by one or a combination of the following three major methods. (1) The improvement of antibody affinity by introducing mutations in the immunoglobulin V-region genes by in vitro mutagenesis. (2) Screening many clones from a random combinatory repertoire of IgV-region genes using a phage library established in yeast or bacteria. (3) Attempting to introduce many somatic hypermutation of IgV-region genes. We summarize the advantages and applications of each of these methods including recent patents to facilitate informed individual choice. We also extend our review to the current creation of antibodies for HIV research.

Protein kinase C (PKC) belongs to the serine and threonine kinase family. At least ten PKC isoforms have been identified and subdivided into three groups: classical (alpha, beta I, beta II and gamma), novel (delta, epsilon, theta and eta), and atypical (zeta and iota/lambda). Two calcium-insensitive isoforms of novel PKC, PKC delta and epsilon, have received particular attention as promising targets for new drugs. PKCs play a multifaceted role in cellular responses in a range of tissues. Professor Mochly-Rosen's group and KAI Pharmaceuticals Inc. have developed drugs targeted against PKC delta (KAI-9803) and epsilon (KAI-1678). These drugs ameliorate pathological conditions in acute myocardial infarction and reduce pain via specific modulation of membrane-translocation of PKC delta or epsilon. Another research group has recently used the KinAceTM approach to produce PKC epsilon-abrogating peptides (KCe-12 and KCe-16) that are based on the catalytic domain of PKC. These peptides specifically inhibit PKC epsilon and ameliorate pathological conditions in a rodent insulin resistance model. This review describes the development of these therapeutic drugs targeting PKC delta and epsilon by two independent groups in the light of recent patents.

Age Related Macular Degeneration (AMD) is a complex neurodegenerative disorder accounting for 50% of blind registrations in the western world. Its substantial impact on quality of life has been a main driver in research to understand its etiology, which up until recently was mostly unknown. In the last three years our understanding of the molecular pathology of AMD has increased dramatically with the identification of two major AMD loci comprising of, Complement Factor H (CFH) and a chromosome 10q26 locus consisting of the Heat Shock Serine Protease (HTRA1) and LOC387715 genes. These two loci have been described as associated with over 50% of disease in certain ethnicities. The rapid pace in our understanding of the complex biology of this disease has placed a large emphasis on gene patenting, especially with the licensing of the CFH and chromosome 10 patents to a private life science company called Optherion Inc. The patents discussed in this review highlight the important discoveries that have contributed to our understanding of AMD and provide valuable information as to where research in this area will be heading in the future.

Age-related macular degeneration (AMD) represents the leading cause of central blindness in developed countries. The majority of severe vision loss occurs in the neovascular form of AMD, generally characterized by the presence of choroidal neovascularization (CNV) beneath the fovea. Photodynamic therapy with verteporfin (PDT-V) and drugs acting against vascular endothelial growth factor are the most commonly employed treatments for AMD-related subfoveal CNV. The combined use of both these strategies is the most promising therapeutic approach towards this harmful disease. The therapeutic action of PDT-V depends to a photochemical perturbation of thrombo-coagulative processes within CNV. Predictive correlations between peculiar coagulation-balance gene polymorphisms and different levels of post-PDT-V benefit have been recently documented in Caucasian patients with neovascular AMD. Particularly, heterozygous A-allele carriers of factor V Leiden 1691 or prothrombin 20210 gene are characterized by a greater possibility to exhibit clinical benefit after PDT-V. Both mutations induce thrombophilia increasing the thrombin generation in plasma and, thus, they can consistently intensify the photothrombotic phase of the therapeutic CNV occlusion. In prospect, considering the different individual susceptibility to PDT-V, a preoperative assessment of the genotypic thrombophilic background could optimize the eligibility criteria of this intriguing treatment. This review summarizes some of the recent published patents on treatment of neovascular AMD, with a particular attention to PDT-V application in combined therapeutic modalities.

By controlling mitochondrial membrane permeability, the Bcl-2 family of proteins plays a crucial role in the regulation of cell death. Members of this family are functionally categorized as either pro- or anti-apoptotic based on their ability to promote or inhibit mitochondrial-dependent cell death signals. The critical role of Bcl-2 family proteins in human diseases has made them the focus of intense research by the pharmaceutical industry and academia. Anti-apoptotic Bcl-2 homologues have been widely explored as potential therapeutic targets for anticancer therapy through the development of nucleic-acid and peptide-based inhibitory molecules. Recently, strategies for the development of peptides or polypeptides derived from specific Bcl-2 family members have also been devised. This paper provides a brief review of the most recent patents that have been published relating to this area.

Here, we review patents that have emerged in the field of DNA-based computing focusing thereby on the discoveries using the concept of molecular finite state automata. A finite state automaton, operating on a finite sequence of symbols and converting information from one to another, provides a basis for developing molecular-scale autonomous programmable models of biomolecular computation at cellular level. We also provide a brief overview on inventions which methodologically support the DNA-based computational approach.

Breast cancer is the most prevalent disease and second leading cause of death among women in many countries. Mutations and consequent DNA damage in several genes such as oncogenes and tumour suppressor genes have been implicated with abnormal behavior of somatic cells, resulting into malignant growth termed cancer. DNA damage/changes in chromosomal DNA and failure of DNA repair mechanism are important factors for cancer causation. Aberrant behavior of cells leading to uncontrolled proliferation causing cancer is attributable to amplicon formation, large deletions in some genes, mutations, and recombination breakpoints etc. which cause aberrant gene expression. Several patented genes found to be associated with breast cancer, have been discussed, such as BRCA1, BRCA2, DAP kinase, MYH, BCSGs, BCW 2 and Id-2 etc. Several of the genes/markers associated with breast cancer can be considered as appropriate candidates for developing early detection systems/protocols for breast cancer.

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