International collaboration generates high quality clusters of pharmaceutical patents.

The worldwide active patent portfolio has nearly doubled in numbers and strength since 2000. The number of active pharmaceutical patent families has tripled in the same time period. The quantitative growth results mostly from a surge of patents from China, half of them classified in A61K36 ('medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants'). High-quality patents exhibit a slower growth curve, and cluster within the three areas biologicals; heterocyclic compounds, and cancer drugs. However, the highest concentration of high-quality patents was found when selecting patents listing inventors from at least two out of the five most important countries of origin for pharmaceutical patents: China, EP countries, Japan, South Korea and the USA.

Choline and phosphatidylcholine fluorescent derivatives localization in carcinoma cells studied by laser scanning confocal fluorescence microscopy.

In this study, we have shown the intracellular distribution of choline and phosphatidylcholine fluorescent derivatives in human breast carcinoma cells using confocal microscopy. The fluorescent choline derivatives ethanamimium 2-hydroxy-N,N-dimethyl-N-[2-N-(2,1,3-benzoxadiazol-4-amine,-N-methyl,-7- nitro)-ethyl] bromide (NBD-choline) and C(6)-NBD-phosphatidylcholine (C(6)-NBD-PC) were used in this work. NBD-choline was easily internalised into drug sensitive MCF-7 and in multidrug resistant MCF-7/DX cells. The probe was found to localise in the endoplasmic reticulum of sensitive cells and in the Golgi of multidrug resistant cells. In contrast, very low accumulation was found in normal MCF10A cells. For C(6)-NBD-PC, a similar pattern of localisation was found in tumour cells, but a significant uptake was also observed in normal cells. Unlike NBD-choline, C(6)-NBD-PC appears not to discriminate between normal and tumour cells. These results are consistent with previously published results showing higher levels of (11)C-choline uptake in malignant lesions seen with positron emission tomography (PET) in vivo imaging. Our results suggest that using NBD-choline and laser scanning confocal fluorescence microscopy (LSCFM) could be a useful tool to study choline metabolism in cancer cells and to consolidate PET imaging findings.