Problem pharmaceutical patents

These days, the number of pharmaceutical patent applications which do not specify the principal active ingredient in the form of a chemical name or structure is increasing. These patents are difficult to retrieve in retrospective on-line searches using chemical structures or keywords. Furthermore, even if you could find them, the situation with regard to patentability is obscure and this causes considerable problems for the experts in charge of the patent search. If you are a searcher for a large pharmaceutical company, you might already be apprehensive of infringing such patents. We, the JFA,^* gathered these patents together and studied the differences between their patentability in Japan, the US and the EPO.     

Superplastic behaviour of Ti-48at.%Al two-phase titanium aluminide compacts made from mechanically alloyed powder

An HIP compact of MA-processed powder having a nominal composition of Ti-48at.% Al was produced. The compact consisted of a large amount of TiAl(λ) and a small amount of Ti₃Al (₂), in a completely ultra-fine equiaxed grain structure. This two-phase compact showed typical superplastic deformation behaviour. A maximum elongation of 550% was obtained. A strain exponent, n = 2, and grain size exponent, p = 2, were determined from the results of a strain-rate-change test and a creep test at constant initial stress using samples having various grain sizes, respectively. The activation energy for creep, Q_c at constant stress was calculated to be 350 kJ/mole. It is concluded that the superplastic deformation mechanism of the material under study is grain boundary sliding controlled by lattice diffusion in the TiAl phase.     

Design optimization of tall tubular lead/acid cells based on an analysis of the reaction distribution

In order to estimate the discharge performance of tall lead/acid cells (with tubular positives), changes in current and potential distributions with discharge progress were calculated with a computer on the basis of plate resistance and the current—potential—time relationship between small facing parts of positive and negative plates. The taller the cell, the larger the voltage drop along the plates. Thus, the discharge time became shorter despite a large amount of available active mass remaining in the bottom part of the plates.Various current-collector designs were evaluated, e.g., one with varying resistance at each height; a side conductor placed along the plates and connected to them at the top, centre and bottom, etc. Results revealed an optimum collector design with which the maximum discharge capacity could be obtained. Furthermore, it was shown that the side conductor markedly improved the discharge performance because the active mass near the connecting parts was appreciably used.     

Reexamination of grain-boundary sliding by diffusion

Steady-state sliding of grain boundaries is discussed by taking into account the change in the potential energy of an applied stress, when the sliding occurs by diffusional accommodation. The present analysis enables us to derive the sliding rates at boundaries of various shapes in a simple manner without knowing local stress fields. Sliding rate of a boundary containing second phase particles is also derived by similar calculations. The results are compared with previous calculations by other investigators, and it is found that the resultant expressions for the sliding rates are essentially identical to those derived from more complex analyses.     

Pixel-selected ray tracing

An acceleration method based on an idea that T. Whitted (Commun. ACM, vol.23, no.6 pp.343-349, June 1980) presented on ray tracing is discussed. He proposed making antialiased images by hierarchical adaptive oversampling. The present authors use hierarchical adaptive undersampling to reduce the number of pixels whose intensity must be calculated by ray tracing. To implement pixel-selected ray tracing (PSRT), homogeneous regions in images must first be found. Generally, adaptive undersampling can result in some image-quality defects, because small objects and parts of thin or wedge-shaped objects may disappear when they are located between the initially sampled pixels. PSRT has an improved algorithm that uses pixels with the correct object information from among the sampled pixels to find pixels with erroneous color and correct them. Moreover, PRST uses ray-object intersection trees for precise classification of the homogeneity of regions and for fast intensity calculation in homogeneous regions. Experimental results are presented. They show that PSRT is two to nine times faster than standard ray tracing     

Discharge behaviour of electrodeposited PbO2 and Pb electrodes

The discharge behaviour of electrodeposited lead dioxide and lead electrodes was investigated under various conditions; the surfaces of the discharged electrodes were observed with a scanning electron microscope. Both the positive and negative electrodes were passivated by a covering of deposited lead sulphate crystals. The amount of lead sulphate required for passivation depended on the size of the crystals.     

A Novel Artificially Humanized Anti-Cripto-1 Antibody Suppressing Cancer Cell Growth

Cripto-1 is a member of the EGF-CFC/FRL1/Cryptic family and is involved in embryonic development and carcinogenesis. We designed a novel anti-Cripto-1 artificial antibody and assessed the recognition to the antigen and the potential to suppress the growth of cancer stem cells. First, single chain antibody clones were isolated by bio-panning with the affinity to recombinant Cripto-1 protein from our original phage-display library. Then, the variable regions of heavy chain VH and light chain VL in each clone were fused to constant regions of heavy chain CH and light chain CL regions respectively. These fused genes were expressed in ExpiCHO-S cells to produce artificial humanized antibodies against Cripto-1. After evaluation of the expression levels, one clone was selected and the anti-Cripto-1 antibody was produced and purified. The purified antibody showed affinity to recombinant Cripto-1 at 1.1 pmol and immunoreactivity to cancer tissues and cell lines. The antibody was available to detect the immunoreactivity in tissue microarrays of malignant tumors as well as in Cripto-1 overexpressing cells. Simultaneously, the antibody exhibited the potential to suppress the growth of human colon cancer derived GEO cells overexpressing Cripto-1 with IC₅₀ at approximately 110 nM. The artificially humanized antibody is proposed to be a good candidate to target cancer cells overexpressing Cripto-1.     

Studies on catalysis by molten metals. 14. Catalytic cracking of asphalts at low temperature

The catalytic effects of liquid metals for low-temperature (336 °C) asphalt-cracking have been examined using a semi-batch reactor. All the liquid metals examined (Bi, Cd, Ga, In, Pb and Sn) effectively catalysed the reduction of molecular weight with minimal gasification (<1 wt%). Gasification had a positive correlation with the reduction in molecular weight in the processed asphalts. The catalytic activities of liquid metals tor these two reactions were proportional to a parameter which represents the interaction between the atoms of the catalyst metal and the radicals formed in the course of the reaction. Mass flow among four fractions (saturates, aromatics, resins and asphaltenes) had two independent paths: conversion of resins to saturates and of aromatics to asphaltenes. The former path dominated when catalytic dehydrogenation activity was relatively low, whereas the latter dominated when the catalytic activity was high.     

Interfacial Reactions between Sapphire and Silver—Copper—Titanium Thin Film Filler Metal

Wetting and brazing studies of sputtering-deposited, submicrometer thin film filler metal in an Ag—Cu—Ti/Al₂O₃ system were performed. The interfacial reaction layer between the filler metal and Al₂O₃ was investigated. It is possible to make a brazing joint even with a reaction layer of less than 100 nm thickness. Different types of interfacial reaction layers were observed when the Ti content in the filler metal was varied. The Cu—Ti—O system compounds were observed in the samples with high wetting capabilities, but not in the sample with low wetting characteristics. It was found that these compounds are substances that promote effective brazing.