Patent search on biologics as potential biosimilar candidates

The biological pharmaceutical market is one of the fastest growing sectors in the health care business. Sales of biologic drugs reached $120 billion in 2008 [1] and the worldwide market of biologics continues to grow (IMS Health). As patents on first generation of biologic drugs, including epoetin, insulin granulocyte colony-stimulating factor (G-CSF) and interferon alpha, will soon expire, if they have not already, and patents on some of the second generation of biological drugs, such as antibody drugs, are going to be expire in the next few years, there exists a great opportunity in developing biosimilars, especially for large pharmaceutical companies which face great challenges in developing new blockbuster drugs. In the past few years, the United States, Canada, and Japan have debated or passed legislation on biosimilars with active involvement from top pharmaceutical and generic drug companies. The successful leader in this field will be the one that has the foresight and resources to position themselves well to gain in the future. So what are biosimilars? What are the technological differences between biosimilars and small molecule generic drugs? Finally, what are the considerations for biosimilars in terms of patent searching? An example on a biosimilar study is given here.     

Tuning of magnetic parameters in cobalt-polystyrene nanocomposites by reduction cycling

Cobalt nanoparticles were prepared by a reduction process inside polymer pores using CoSO₄·7H₂O and NaBH₄. A porous polymer network (sulphonated polystyrene) was chosen, as the template for the synthesis of elementary cobalt as high surface area cobalt nanoparticles are prone to oxidation. The preliminary studies reveal that the cobalt is first formed with an oxide protective layer outside and upon repeating the reduction cycles, inner pores of the polymers are opened which enhanced the yield of metallic cobalt. These high surface area cobalt nanoparticles embedded in a polymer are ideal for the synthesis of carbon nanotubes as cobalt can act as a catalyst for the nanotube synthesis. The concentration of cobalt can be tuned in this technique by repeating the cycling process.     

Evidence for intergranular tunnelling in polyaniline passivated α-Fe nanoparticles

Nanoparticles are of immense importance both from the fundamental and application points of view. They exhibit quantum size effects which are manifested in their improved magnetic and electric properties. Mechanical attrition by high energy ball milling (HEBM) is a top down process for producing fine particles. However, fineness is associated with high surface area and hence is prone to oxidation which has a detrimental effect on the useful properties of these materials. Passivation of nanoparticles is known to inhibit surface oxidation. At the same time, coating polymer film on inorganic materials modifies the surface properties drastically. In this work a modified set-up consisting of an RF plasma polymerization technique is employed to coat a thin layer of a polymer film on Fe nanoparticles produced by HEBM. Ball-milled particles having different particle size ranges are coated with polyaniline. Their electrical properties are investigated by measuring the dc conductivity in the temperature range 10-300?K. The low temperature dc conductivity (I-V) exhibited nonlinearity. This nonlinearity observed is explained on the basis of the critical path model. There is clear-cut evidence for the occurrence of intergranular tunnelling. The results are presented here in this paper.     

Lubrication properties of trimethylolpropane esters based on palm oil and palm kernel oils

Due to the global drive towards biodegradable products, trimethylolpropane [2‐ethyl‐2‐(hydroxymethyl)‐1, 3‐propanediol] (TMP) esters based on palm and palm kernel oils were synthesized, their lubrication properties evaluated, and their potential as base stock for biodegradable lubricants assessed. Two types of TMP esters were considered: palm kernel (PKOTE) and palm oil (PPOTE) TMP esters, derived from palm oil and palm kernel methyl esters, respectively. Lubrication properties such as viscosity, viscosity index (VI) and pour point (PP) were determined according to methods of the American Society for Testing and Materials. Wear and friction properties were evaluated using a four‐ball test machine, while oxidative stability was studied with the Penn State Micro‐oxidation thin‐film test. High VI ranges between 170 to 200 were recorded for these base stocks. PP were relatively high, between 4 to —1 °C, but were improved to at least —33 °C in high oleic palm oil TMP esters. The effects of chemical structure and impurities on wear properties and oxidative stability were also studied. The presence of methyl esters was found to improve wear, but hydroxyl groups in mono‐ and diesters had negative effects at high concentrations. Differences in chemical structures of PKOTE and PPOTE were shown to affect friction and wear results. Both base fluids exhibit oxidative stability comparable to other high oleic base fluids.     

谈中国的游戏职业教育——访汇众益智总裁李新科

四年前，李新科的汇众益智刚刚起步，他根据全国游戏产业的现状率先创建了“游戏学院”，四年后的今天，已经进入成熟期的汇众益智又将迎来哪些新的挑战？未来将有哪些进一步的规划呢？为此，本刊特别采访了汇众益智的总裁李新科先生，他将从汇众益智这几年的发展历程、教育品牌塑造以及教育本身等三个方面带领我们一起回顾汇众益智走过的路。     

The effects of MgO and Al2O3 behaviours on softening–melting properties of high basicity sinter

Because the behaviours of MgO and Al₂O₃ during slag formation of high basicity sinter are not clearly understood, the effects of MgO and Al₂O₃ on softening-melting properties are always arguable. In this paper, four kinds of sinter containing different MgO and Al₂O₃ content are investigated. Some observations are obtained. The mechanism of the influence of MgO and Al₂O₃ on softening properties of sinter are different. Al₂O₃ has priority over MgO to enter into slag phase and forms low-melting point phase while MgO remains unslagged state and mainly exists in wustite as FeO–MgO solid solution. When sinter melts, the viscosity of the slag generated from sinter containing high MgO and Al₂O₃ content is low, which could result in low pressure drop. As MgO and Al₂O₃ content increase, the main minerals of residual slag change from 2CaO?SiO₂ to merwinte and melilite. The changes of the minerals in slag phase can well explain the trend of softening-melting characteristic temperatures.     

Coastal water quality impact of stormwater runoff from an urban watershed in southern California

Field studies were conducted to assess the coastal water quality impact of stormwater runoff from the Santa Ana River, which drains a large urban watershed located in southern California. Stormwater runoff from the river leads to very poor surf zone water quality, with fecal indicator bacteria concentrations exceeding California ocean bathing water standards by up to 500%. However, cross-shore currents (e.g., rip cells) dilute contaminated surf zone water with cleaner water from offshore, such that surf zone contamination is generally confined to < 5 km around the river outlet. Offshore of the surf zone, stormwater runoff ejected from the mouth of the river spreads out over a very large area, in some cases exceeding 100 km2 on the basis of satellite observations. Fecal indicator bacteria concentrations in these large stormwater plumes generally do not exceed California ocean bathing water standards, even in cases where offshore samples test positive for human pathogenic viruses (human adenoviruses and enteroviruses) and fecal indicator viruses (F+ coliphage). Multiple lines of evidence indicate that bacteria and viruses in the offshore stormwater plumes are either associated with relatively small particles (< 53 microm) or not particle-associated. Collectively, these results demonstrate that stormwater runoff from the Santa Ana River negatively impacts coastal water quality, both in the surf zone and offshore. However, the extent of this impact, and its human health significance, is influenced by numerous factors, including prevailing ocean currents, within-plume processing of particles and pathogens, and the timing, magnitude, and nature of runoff discharged from river outlets over the course of a storm.     

Statistical analysis on three-dimensional MHD convective Carreau nanofluid flow due to bilateral nonlinear stretching sheet with heat source and zero mass flux condition

This study focuses on analyzing the response of a magnetohydrodynamic convective Carreau nanofluid flow over a bilateral nonlinear stretching sheet in the presence of a heat source and zero mass flux condition. The problem has been solved numerically using the MATLAB built-in function bvp5c. The findings of velocity, temperature, and concentration profiles based on the various parameters are illustrated using graphs. The impact of various parameters on the heat transfer rate is scrutinized using statistical techniques, like, correlation coefficient, probable error, and regression. The effect of various parameters on skin friction coefficients is studied via tables and slope of linear regression. It is observed that the statistical results coincide with the numerical results. It is also noticed that the stretching ratio parameter increases the Y-directional velocity profile. Accuracy of the numerical procedure has been validated through a restrictive comparison of the present work with previous published results and is found to be in good agreement.     

Protein isoaspartate methyltransferase-mediated 18O-labeling of isoaspartic acid for mass spectrometry analysis

Arising from spontaneous aspartic acid (Asp) isomerization or asparagine (Asn) deamidation, isoaspartic acid (isoAsp, isoD, or beta-Asp) is a ubiquitous nonenzymatic modification of proteins and peptides. Because there is no mass difference between isoaspartyl and aspartyl species, sensitive and specific detection of isoAsp, particularly in complex samples, remains challenging. Here we report a novel assay for Asp isomerization by isotopic labeling with (18)O via a two-step process: the isoAsp peptide is first specifically methylated by protein isoaspartate methyltransferase (PIMT, EC 2.1.1.77) to the corresponding methyl ester, which is subsequently hydrolyzed in (18)O-water to regenerate isoAsp. The specific replacement of (16)O with (18)O at isoAsp leads to a mass shift of 2 Da, which can be automatically and unambiguously recognized using standard mass spectrometry, such as collision-induced dissociation (CID), and data analysis algorithms. Detection and site identification of several isoAsp peptides in a monoclonal antibody and the β-delta sleep-inducing peptide (DSIP) are demonstrated.