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.     

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.     

Contrasting effects of water-soluble and water-insoluble dietary fibers on bile acid conjugation and taurine metabolism in the rat

The effect of the type of dietary fiber on the bile acid and taurine metabolism was examined in rats. Diets containing 10% of various water-soluble fibers (citrus pectin, konjak mannan, guar gum) as compared to a fiber-free diet increased biliary excretion of total bile acids. In contrast, water-insoluble dietary fibers (cellulose, corn bran, chitin; 10% in the diets) as well as cholestyramine (5% in the diet) considerably, decreased bile acid excretion. Water-soluble dietary fibermediated increases in bile acid excretion were totally attributable to increases in glycine-conjugates. Thus, these fibers greatly increased by the bile acid glycine-to-taurine ratio (G/T). Excretio of glycine conjugates decreased more than that of taurine conjugates in rats fed various water-insoluble dietary fibers. As a results, G/T in rats fed water-insoluble fibers was significantly lowered as compared to G/T in animals fed a fiber-free diet. Cholestyramine did not affect the G/T ratio of bile acids. Fecal bile acid excretion and the activities of hepatic cholesterol 7α-hydroxylase (EC 1.14.13.17) in rats fed various water-soluble dietary fibers approximately doubled as compared to the respective values for rats fed a fiber-free diet. Whereas cholestyramine greatly increased these parameters, water-insoluble fibers did not significantly affect them. Various water-soluble fibers decreased hepatic concentration and urinary excretion of taurine as well as the activity of hepatic cysteine dioxygenase (EC 1.13.11.20). In contrast, water-insoluble fibers considerably increased hepatic taurine concentrations and enzyme activities. The parameters for taurine metabolism were unaffected by cholestyramine. It was suggested that the types of dietary fiber affected hepatic taurine synthesis and thus modified bile acid glycine/taurine ratios.     

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.     

Comparative study on the preparation and properties of radiation‐grafted polymer electrolyte membranes based on fluoropolymer films

In this study the fluoropolymers, poly(ethylene‐co‐tetrafluoroethylene) (ETFE) and poly(vinylidene fluoride) (PVDF) films, together with the radiation‐induced crosslinked polytetrafluoroethylene (cPTFE) film were compared on the basis of their preparation and properties of radiation‐grafted polymer electrolyte membranes. The polymer electrolyte membranes were prepared by radiation grafting of styrene into the base films and subsequent sulfonation. The proton conductivity and chemical stability of the three types of membranes with a similar ion exchange capacity (IEC) near 1.0 mmol/g were investigated and are discussed in detail. Although the ETFE‐based polymer electrolyte membrane was relatively more stable, its proton conductivity was lower than those of the PVDF‐ and cPTFE‐based membranes. On the other hand, the cPTFE‐based membrane showed a significantly higher proton conductivity, but its chemical stability was shorter than that of the ETFE‐based membrane. It is considered that the difference in the preparation and properties of the polymer electrolyte membranes was due to the difference in the degree of crystallinity as well as in the chemical structure of the fluoropolymer base films. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1966–1972, 2007     

Effect of crosslinkers on the preparation and properties of ETFE‐based radiation‐grafted polymer electrolyte membranes

This study concerns a comparative study of three crosslinkers, divinylbenzene (DVB), 1,2‐bis(p,p‐vinylphenyl)ethane (BVPE), and triallyl cyanurate (TAC) crosslinked poly(ethylene‐co‐tetrafluoroethylene) (ETFE)‐based radiation‐grafted membranes, which were prepared by radiation grafting of p‐methylstyrene onto ETFE films and subsequent sulfonation. The effect of the different types and contents of the crosslinkers on the grafting and sulfonation, and the properties such as water uptake, proton conductivity, and thermal/chemical stability of the resulting polymer electrolyte membranes were investigated in detail. Introducing crosslink structure into the radiation‐grafted membranes leads to a decrease in proton conductivity due to the decrease in water uptake. The thermal stability of the crosslinked radiation‐grafted membranes is also somewhat lower than that of the noncrosslinked one. However, the crosslinked radiation‐grafted membranes show significantly higher chemical stability characterized in the 3% H₂O₂ at 50°C. Among the three crosslinkers, the DVB shows a most pronounced efficiency on the crosslinking of the radiation‐grafted membranes, while the TAC has no significant influence; the BVPE is a mild and effective crosslinker, showing the moderate influence between the DVB and TAC crosslinkers. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 4565–4574, 2006