Recent Patents on Biotechnology - Volume 2, Issue 1, 2008

Cardiovascular diseases, such as heart valve dysfunction and coronary artery stenosis, are next to cancer the leading cause of death in the US. Treatments involve replacement of the heart valve or bypassing the obstructed coronary artery with a small-diameter vascular graft. The major limitation of currently used replacements is their inability to grow, adapt and repair in the patient. Considering the increasing age of the population and the subsequent increase in cardiovascular disease incidence, efforts to improve existing replacements and unraveling novel types of replacements are of paramount importance. Cardiovascular tissue engineering represents a rapid evolving field of research, providing living heart valve and small-diameter vascular substitutes with the ability to grow, adapt and repair after implantation. Various tissue engineering approaches are being employed, based on in vivo and/or in vitro tissue formation. This review provides an overview of the current heart valve and small-diameter vascular replacements and presents the status and future developments within the various tissue engineering approaches. The potential of tissue engineering for the development of living heart valve and small-diameter vascular substitutes is reflected in the numerous patents related to this emerging field of research.

Laccases are an interesting group of multi copper enzymes, which have received much attention of researchers in last decades due to their ability to oxidize both phenolic and non-phenolic lignin related compounds as well as highly recalcitrant environmental pollutants. This makes these biocatalysts very useful for their application in several biotechnological processes. Such applications include the detoxification of industrial effluents, mostly from the paper and pulp, textile and petrochemical industries, polymer synthesis, bioremediation of contaminated soils, wine and beverage stabilization. Laccases are also used as catalysts for the manufacture of anticancer drugs and even as ingredients in cosmetics. Recently, the utility of laccases has also been applied to nanobiotechnology. This paper reviews recent and important patents related to the properties, heterologous production, molecular cloning, and applications of laccases within different industrial fields as well as their potential extension to the nanobiotechnology area.

Biodiesel is an alternative energy source and could be a substitute for petroleum-based diesel fuel. To be a viable alternative, a biofuel should provide a net energy gain, have environmental benefits, be economically competitive, and be producible in large quantities without reducing food supplies. Most of the sources, methods and apparatus to produce biodiesel are reviewed here. Some of the patents propose the use of oils and fats of animal or vegetal origin and other kind of sources. Many others focus on the methods for the production or oxidation stability of the biofuel in order to make its production economically competitive. Several apparatus comprising reactors and refineries are also presented. This review article summarizes recent and important patents relating to the production of biodiesel to make its production a viable alternative.

Optically pure D- or L-amino acids are used as intermediates in several industries. D-amino acids are involved in the synthesis of antibiotics, pesticides, sweeteners and other biologically active peptides. L-amino acids are used as feed and food additives, as intermediates for pharmaceuticals, cosmetics, pesticides and as chiral synthons in organic synthesis. The specific activity of these optically pure amino acids depends on their structure, chirality and purity. There are two main approaches to obtain optically pure amino acids, namely chemical and enzymatic synthesis. Chemical synthesis gives racemic mixtures of amino acids of low yield and is not environment friendly. One of the most widely-used enzymatic method is the “Hydantoinase Process”. In this cascade of reactions, the chemically synthesized D,L-5-monosubstituted hydantoin ring is first hydrolyzed by a stereoselective hydantoinase enzyme to give the corresponding N-carbamoyl α-amino acid that is hydrolyzed by highly enantiospecific N-carbamoyl α-amino acid amidohydrolase (Ncarbamoylase) to yield the free amino acid. At the same time, the remaining non-hydrolyzed 5-monosubstituted hydantoin is racemized by the hydantion racemase enzyme. This process has evolved over the years from the isolation of microorganisms with one or several of these enzymes to the construction of recombinant systems for industrial application.

Rearranged during transfection, RET, is a receptor tyrosine kinase expressed in neural crest derived cell lineages. RET is activated by dimerisation facilitated by its binding to the heterodimeric complex formed by Glial cell-derived neurotrophic factor (GDNF) -family ligand (GFL) and GNDF-family receptor (GFR). Both GDNFs and their co-receptors are a small protein family of four members. RET kinase mediated signaling can lead to survival, cell growth, differentiation, and migration. Pharmaceutically RET is of interest due to its involvement in several disease conditions. Oncogenic RET activation by mutations or rearragements predisposes to cancers like multiple endocrine neoplasia type 2 (A and B) and medullary thyroid carcinoma. Loss-of-function mutations in RET are a strong susceptibility factor for Hirschsprung disease, which is characterized by lack of ganglion cells in gastrointestinal tract. All the GFLs promote neuronal survival and GDNF is one of the most potent neurotrophic factors for dopaminergic neurons. Therefore, the neuroprotective capacity of RET activation to override the apoptotic program in neurodegenerative diseases, like in dying midbrain dopaminergic neurons in Parkinson's disease, is of great interest. This article reviews the recent international patents on modulation of RET kinase activity by small-molecule and peptide-based agonists and antagonists.

A nanoparticle is a microscopic particle with at least one dimension less than 100 nm,which plays an important role in the area of intense scientific research. In recent years, the application of gold nanoparticles instead of fluorescence dyes and enzyme-conjugation in biochips is very common. For example, Au nanoparticles labeling method was applied in many DNA-detection methods, and a novel readout scheme for gold nanoparticle-based DNA microarrays was studied relying on “Laser-Induced Scattering around a nanoAbsorber” and nanogold electrode, and the colorimetric detection using gold label plus silver stain was also developed. The technology is a good combination of gene technology and nanotechnology. At the same time, a number of scientists from different countries have paid more attention to the application of nanoparticles in biochips and gotten some new patents for it.

Hemoglobin, the protein responsible for the red color of blood plays a very important part in ‘life’- it transports oxygen, without which humans cannot survive. The idea of using purified Hemoglobin as a possible universal substitute for red blood cells has been around for almost a century. Hemoglobin formulations have important therapeutic applications, especially in case of trauma and war when requirements for blood may be very large. Manufacture of hemoglobin for use as a biopharmaceutical poses practical challenges, owing to dependence on human expired blood and fragility of the protein molecule. Biotechnology can play a critical role in breaking these barriers, by not only ensuring recombinant production of hemoglobin, but also enhancing stability of the molecule. The present article, based on a review of patents and available literature gives an insight into the IPR and technological issues involved in the commercial production of this ‘life-saving’ protein. There are more than 250 patents worldwide related to hemoglobin formulation, crosslinking and determination.

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