Post-Issue Patent "Quality Control": A Comparative Study of US Patent Re-examinations and European Patent Oppositions

We report the results of the first comparative study of the determinants and effects of patent oppositions in Europe and of re-examinations on corresponding patents issued in the United States. The analysis is based on a dataset consisting of matched EPO and US patents. Our analysis focuses on two broad technology categories - biotechnology and pharmaceuticals, and semiconductors and computer software. Within these fields, we collect data on all EPO patents for which oppositions were filed at the EPO. We also construct a random sample of EPO patents with no opposition in these technologies. We match these EPO patents with the 'equivalent' US patents covering the same invention in the United States. Using the matched sample of USPTO and EPO patents, we compare the determinants of opposition and of re-examination. Our results indicate that valuable patents are more likely to be challenged in both jurisdictions. But the rate of opposition at the EPO is more than thirty times higher than the rate of re-examination at the USPTO. Moreover, opposition leads to a revocation of the patent in about 41 percent of the cases, and to a restriction of the patent right in another 30 percent of the cases. Re-examination results in a cancellation of the patent right in only 12.2 percent of all cases. We also find that re-examination is frequently initiated by the patentholders themselves.

Post-Issue Patent "Quality Control": A Comparative Study of US Patent Re-examinations and European Patent Oppositions

We report the results of the first comparative study of the determinants and effects of patent oppositions in Europe and of re- examinations on corresponding patents issued in the United States. The analysis is based on a dataset consisting of matched EPO and US patents. Our analysis focuses on two broad technology categories - biotechnology and pharmaceuticals, and semiconductors and computer software. Within these fields, we collect data on all EPO patents for which oppositions were filed at the EPO. We also construct a random sample of EPO patents with no opposition in these technologies. We match these EPO patents with the “equivalent” US patents covering the same invention in the United States. Using the matched sample of USPTO and EPO patents, we compare the determinants of opposition and of reexamination. Our results indicate that valuable patents are more likely to be challenged in both jurisdictions. But the rate of opposition at the EPO is more than thirty times higher than the rate of reexamination at the USPTO.

Characterisation and activity of mixed metal oxide catalysts for the gas-phase selective oxidation of toluene

Mixed metal bi-component oxide catalysts, including Fe/Mo, U/Mo, U/W, Fe/U, U/V and U/Sb have been prepared, characterised and evaluated for gas phase selective toluene oxidation. Selective toluene oxidation activity to form benzaldehyde was exhibited by Fe/Mo, U/Mo and U/W mixed oxide catalysts. The Fe/Mo catalyst produced the highest benzaldehyde yield. Catalysts that formed benzaldehyde also produced a range of by-products, these were other partial oxidation and coupling products, and preliminary studies of benzaldehyde oxidation suggests they were formed from secondary reactions of benzaldehyde. The Fe/U, Sb/U and U/V catalysts produced only total oxidation to carbon oxides. Catalysts were characterised by X-ray diffraction, laser Raman spectroscopy and temperature programmed reduction. Single molybdate phases were identified for the Fe/Mo and U/Mo catalysts, and a mixture of uranium molybdate and WO3 was identified for the U/W catalyst. Results suggest that the formation of a molybdate phase is important for the selective oxidation of toluene. In contrast, the U/Fe catalyst was a mixture of U3O8 and V2O5, whilst the Fe/U catalyst was comprised of highly dispersed iron oxide on UO3. The presence of U3O8 was responsible for toluene total oxidation. The U/Sb catalyst did not exhibit selective toluene oxidation, but previous studies have demonstrated that the catalyst exhibits high activity for selective propene oxidation. Similar behaviour has been observed for the other catalysts in this study, and it is apparent that catalysts that were selective for toluene oxidation were not selective for propene/propane oxidation and vice versa

Low temperature solvent-free allylic oxidation of cyclohexene using graphitic oxide catalysts

A range of graphitic oxides have been utilised as metal free carbocatalysts for the low temperature oxidation of cyclohexene. The activity of the catalysts was correlated with the amount of surface oxygen on the graphitic oxide. In the case of cyclohexene oxidation, major selectivity is observed to allylic oxidation products. This is in contrast to the epoxide being the major product in linear alkene oxidation. This selectivity was maintained over long reaction times and at a conversion of above 50 %. Only small amounts of epoxide were observed, which eventually decreases at higher conversion due to hydrolysis to cyclohexane diol. The similarity between the non-catalysed and the catalysed product distribution suggests that these catalysts act as a solid initiator, and the role of the graphitic oxide is to decrease the lengthy induction period observed in the blank non-catalysed reaction

Methane Oxidation to Methanol in Water

Conspectus Methane represents one of the most abundant carbon sources for fuel or chemical production. However, remote geographical locations and high transportation costs result in a substantial proportion being flared at the source. The selective oxidation of methane to methanol remains a grand challenge for catalytic chemistry due to the large energy barrier for the initial C–H activation and prevention of overoxidation to CO2. Indirect methods such as steam reforming produce CO and H2 chemical building blocks, but they consume large amounts of energy over multistage processes. This makes the development of the low-temperature selective oxidation of methane to methanol highly desirable and explains why it has remained an active area of research over the last 50 years. The thermodynamically favorable oxidation of methane to methanol would ideally use only molecular oxygen. Nature effects this transformation with the enzyme methane monooxygenase (MMO) in aqueous solution at ambient temperature with the addition of 2 equiv of a reducing cofactor. MMO active sites are Fe and Cu oxoclusters, and the incorporation of these metals into zeolitic frameworks can result in biomimetic activity. Most approaches to methane oxidation using metal-doped zeolites use high temperature with oxygen or N2O; however, demonstrations of catalytic cycles without catalyst regeneration cycles are limited. Over the last 10 years, we have developed Fe-Cu-ZSM-5 materials for the selective oxidation of methane to methanol under aqueous conditions at 50 °C using H2O2 as an oxidant (effectively O2 + 2 reducing equiv), which compete with MMO in terms of activity. To date, these materials are among the most active and selective catalysts for methane oxidation under this mild condition, but industrially, H2O2 is an expensive oxidant to use in the production of methanol. This observation of activity under mild conditions led to new approaches to utilize O2 as the oxidant. Supported precious metal nanoparticles have been shown to be active for a range of C–H activation reactions using O2 and H2O2, but the rapid decomposition of H2O2 over metal surfaces limits efficiency. We identified that this decomposition could be minimized by removing the support material and carrying out the reaction with colloidal AuPd nanoparticles. The efficiency of methanol production with H2O2 consumption was increased by 4 orders of magnitude, and crucially it was demonstrated for the first time that molecular O2 could be incorporated into the methanol produced with 91% selectivity. The understanding gained from these two approaches provides valuable insight into possible new routes to selective methane oxidation which will be presented here in the context of our own research in this area

Folding-competent and folding-defective forms of Ricin A chain have different fates following retrotranslocation from the endoplasmic reticulum

We report that a toxic polypeptide retaining the potential to refold upon dislocation from the endoplasmic reticulum (ER) to the cytosol (ricin A chain; RTA) and a misfolded version that cannot (termed RTAΔ), follow ER-associated degradation (ERAD) pathways in Saccharomyces cerevisiae that substantially diverge in the cytosol. Both polypeptides are dislocated in a step mediated by the transmembrane Hrd1p ubiquitin ligase complex and subsequently degraded. Canonical polyubiquitylation is not a prerequisite for this interaction because a catalytically inactive Hrd1p E3 ubiquitin ligase retains the ability to retrotranslocate RTA, and variants lacking one or both endogenous lysyl residues also require the Hrd1p complex. In the case of native RTA, we established that dislocation also depends on other components of the classical ERAD-L pathway as well as an ongoing ER–Golgi transport. However, the dislocation pathways deviate strikingly upon entry into the cytosol. Here, the CDC48 complex is required only for RTAΔ, although the involvement of individual ATPases (Rpt proteins) in the 19S regulatory particle (RP) of the proteasome, and the 20S catalytic chamber itself, is very different for the two RTA variants. We conclude that cytosolic ERAD components, particularly the proteasome RP, can discriminate between structural features of the same substrate

The formation of methanol from glycerol bio-waste over doped ceria based catalysts

A series of ceria-based solid-solution metal oxides were prepared by co-precipitation and evaluated as catalysts for glycerol cleavage, principally to methanol. The catalyst activity and selectivity to methanol were investigated with respect to the reducibility of the catalysts. Oxides comprising of Ce-Pr and Ce-Zr were prepared, calcined and compared to CeO2, Pr6O11 and ZrO2. The oxygen storage capacity of the catalysts was examined with analysis of Raman spectroscopic measurements and a temperature programmed reduction, oxidation and reduction cycle. The incorporation of Pr resulted in significant defects, as evidenced by Raman spectroscopy. The materials were evaluated as catalysts for the glycerol to methanol reaction and it was found that an increased defect density or reducibility was beneficial. The space time yield of methanol normalised to surface area over CeO2 was found to be 0.052 mmolMeOH m-2 h-1 and over CeZrO2 and CePrO2 this was to 0.029 and 0.076 mmolMeOH m-2 h-1 respectively. The inclusion of Pr reduced the surface area, however, the carbon mole selectivity to methanol and ethylene glycol remained relatively high, suggesting a shift in the reaction pathway compared to that over ceria. This article is part of a discussion meeting issue “Science to enable the circular economy”

The mechanism of glycosphingolipid degradation revealed by a GALC-SapA complex structure.

Sphingolipids are essential components of cellular membranes and defects in their synthesis or degradation cause severe human diseases. The efficient degradation of sphingolipids in the lysosome requires lipid-binding saposin proteins and hydrolytic enzymes. The glycosphingolipid galactocerebroside is the primary lipid component of the myelin sheath and is degraded by the hydrolase β-galactocerebrosidase (GALC). This enzyme requires the saposin SapA for lipid processing and defects in either of these proteins causes a severe neurodegenerative disorder, Krabbe disease. Here we present the structure of a glycosphingolipid-processing complex, revealing how SapA and GALC form a heterotetramer with an open channel connecting the enzyme active site to the SapA hydrophobic cavity. This structure defines how a soluble hydrolase can cleave the polar glycosyl headgroups of these essential lipids from their hydrophobic ceramide tails. Furthermore, the molecular details of this interaction provide an illustration for how specificity of saposin binding to hydrolases is encoded

Supercritical antisolvent precipitation of amorphous copper–zinc georgeite and acetate precursors for the preparation of ambient‐pressure water‐gas‐shift copper/zinc oxide catalysts

A series of copper-zinc acetate and zincian georgeite precursors have been produced by supercritical CO2 anti-solvent (SAS) precipitation as precursors to Cu/ZnO catalysts for the water gas shift (WGS) reaction. The amorphous materials were prepared by varying the water/ethanol volumetric ratio in the initial metal acetate solutions. Water addition promoted georgeite formation at the expense of mixed metal acetates, which are formed in the absence of the water co-solvent. Optimum SAS precipitation occurs without water to give high surface areas, whilst a high water content gives inferior surface areas and copper-zinc segregation. Calcination of the acetates is exothermic, producing a mixture of metal oxides with high crystallinity. However, thermal decomposition of zincian georgeite resulted in highly dispersed CuO and ZnO crystallites with poor structural order. The georgeite-derived catalysts give superior WGS performance in comparison to the acetate-derived catalysts, which is attributed to enhanced copper-zinc interactions that originate from the precursor

Relationship between bulk phase, near surface and outermost atomic layer of VPO catalysts and their catalytic performance in the oxidative dehydrogenation of ethane

A set of vanadium phosphorous oxide (VPO) catalysts, mainly consisting of (VO)₂P₂O₇, VO(PO₃)₂ or VOPO₄∙2H₂O bulk crystalline phases, has been investigated for the oxidative dehydrogenation (ODH) of ethane to ethylene, a key potential reaction for a sustainable industrial and socioeconomic development. The catalytic performance on these VPO catalysts has been explained on the basis of the main crystalline phases and the corresponding suface features found by XPS and LEISS at 400 ˚C, i.e. within the temperature range used for ODH reaction. The catalysts based on (VO)₂P₂O₇ phase presented the highest catalytic activity and productivity to ethylene. Nevertheless, the catalysts consisting of VO(PO₃)₂ structure showed higher selectivity to ethylene, reaching 90% selectivity at ca. 10% ethane conversion. To the best of our knowledge, this is the highest selectivity reported on a vanadium phosphorous oxide at similar conversions for the ethane ODH. In general, catalysts consisting of crystalline phases with vanadium present as V⁴⁺, i.e. (VO)₂P₂O₇ and VO(PO₃)₂, were found to be significantly more selective to ethylene than those containing V⁵⁺ phases. The surface analysis by XPS showed an inverse correlation between the mean oxidation state of vanadium near surface and the selectivity to ethylene. The lower averaged oxidation states of vanadium appear to be favoured by the presence of V³⁺ species near the surface, which was only found in the catalysts containing V⁴⁺ phases. Among those catalysts the one based on VO(PO₃)₂ phase shows the highest selectivity, which could be related to the most isolated scenario of V species (the lowest V content relative to P) found at the outermost surface by low energy ion scattering spectroscopy (LEISS), a "true" surface technique only sensitive to the outermost atomic layer