Reasonable expectation of success

Apotex wove these facts into a prima facie case of obviousness as follows It would be obvious to separate an enantiomer from a known racemate using generally known techniques. Furthermore, there was motivation [19] to do so because enantiomers can have different properties from those displayed by the racemate, and because of a possible future FDA regulatory requirement for separation of enantiomers. Additionally, there was a reasonable expectation of success [20] in achieving the separation because techniques for separating enantiomers from racemates are known. And finally, it would be obvious to form an addition salt of the enantiomer to optimize selected physical properties. Thus, concluded Apotex, dextrorotatory clopidogrel bisulfate was obvious, it is therefore unpatentable, and this renders the 265 patent invalid. 

In general, the EPO consider inventive step on a so-called problem-and solution basis if the solution to a known problem is not obvious to the person skilled in the art then there is an inventive step. The single closest prior disclosttre is iderrtified and the obviousness or non-obviousness of the solution is assessed in relation to that disclosttre. The US courts have generally considered whether the prior disclostttes wottld have suggested to those of skill in the art that they should make the claimed compositiorr, or carry out the claimed process and whether the prior disclosure would have revealed that in making the claimed invention or carrying out the claimed process, those of skill in the art would have a reasonable expectation of success. 

The CAFC also commented on the absence of a reasonable expectation of success. In this particular instant, the CAFC rejected Danbury s reasoning that an expectation of success merely required an expectation of minimal activity. Rather, the CAFC held that the success of discovering famotidine was not the expectation of discovering one of the tens of thousands of compounds that exhibit baseline H2 antagonist activity but was the finding of a compound that had high activity, few side effects, and lacked toxicity. ... 

In the instant case, the Court apparently did not find a prima facie case of obviousness because the Court believed that Mylan had failed to provide evidence that the prior art would have provided a reasonable expectation of success for levofloxacin. In this regard, the Court recited the exemplary properties of the compound and argued that those properties could not have been reasonably expected. The Court further explained that even if a prima facie case of obviousness did exist, the case would be effectively rebutted by the many secondary indicia of obviousness, including unexpected results, which are the subject of the rest of the case summary presented here. This interpretation of reasonable expectation of success by the District Court may have set the bar too high for establishing prima facie obviousness and has been criticized. See JJ. Sparrow, Stan. Tech. L. Rev. 2 (2007). 

The prior art expressly teaches one of ordinary skill in the art to combine an opioid with an NSAID.123 Furthermore, based on the prior art, a person of ordinary skill in the art of pain management would have had a reasonable expectation of success in combining hydrocodone, a narcotic analgesic, with ibuprofen, an NSAID. 

When considering the suitability of a bead production technique for imprinting, it is essential to evaluate the compatibility of the conditions used for polymerisation with those required for complex formation between functional monomers and templates. Where covalent imprinting methods are used, the covalent adducts are often highly stable and need quite harsh conditions to disrupt them. Such adducts could be used in most of the procedures described below with reasonable expectation of success. The same can be said for many metal-chelate complexes, which have stabilities approaching covalently bonded structures. The use of cyclic boronate esters is an exception. This adduct is unstable in water and hence cannot be combined efficiently with aqueous suspension polymerisation. 

The power of quantum mechanics is revealed by experimental confirmation of the predicted spectroscopic properties of atomic hydrogen. The reasonable expectation of successfully extending the method to many-electron atoms and molecules has been thwarted by mathematical complexity. It has never been possible to solve the wave equation for the motion of more than one particle. The most complex chemical system that has been solved (numerically) is for the single electron in the field of two protons, clamped in place, to define the molecular ion hJ. In order to apply the methods of quantum mechanics to any atom or molecule, apart from H and H, it is necessary to apply approximation methods or introduce additional assumptions based on chemical intuition. 

A key challenge in evaluating the quality of the chemical probes resulting from the MLI initiative is a lack of skilled experts who can individually determine, with a reasonable expectation of success, the quality of these probes. In the absence of a completely objective way to evaluate these chemical probes, we used the wisdom of the crowd to crowdsource (Box 2)... 

In this process, you will be looldng both for areas that need improvement and for those where results exceed expectation. Most important, you will need to determine what the test results suggest about the PSM system as a whole, and devise solutiorrs. As part of this process, you should explore the reasons for particular successes or failures it s important to distinguish findings that apply to the system as a whole from those that maybe unique to the pilot site itself. 

Although deprotonation at the benzylic position of arenes coordinated to ruthenium and chromium was reported,27 in the case of the coordinated oxo-ri5-dienyl unit, nucleophilic attack at one terminus of the complexed r 5-dienyl ligand, rather than deprotonation, was expected.28 The reason for the successful deprotonation (even at relatively hindered isopropyl sites) is, according to the authors, the cationic nature of the Cp M fragment. In addition, the transition state for the deprotonation might involve stabilization by the metal (Scheme 3.15). 

The ligand radii in Table 5.6 for ligands bonded to carbon agree well with Bartell s values, as would be expected, but the other radii are different. This is the reason for the lack of success of the 1,3 radii when applied to a range of molecules. Glidewell had assumed that the 1,3 radius was independent of the central atom, so the radii he obtained were not a consistent set, since the radii for different ligands were obtained for different central atoms. 

Evidence was further presented that "eventual success [in separating the enantiomers] came only after several failures using known strategies for enantiomer separation" and that it "could be. .. difficult to separate the enantiomers of PC 4099. .. because it would be understood by chemists that the methyl ester substituent in PCR 4099 could make it more susceptible to re-racemizations, and thus resistant to successfully obtaining a separated product [22]." Accordingly, "neither the chemists at Sanofi nor a person of ordinary skill in the art could have reasonably expected that the separate enantiomers of PCR 4099 could be obtained. .. and if obtained, by what method and configuration [22]." Thus, Apotex s contention that separating the enantiomers was obvious was also refuted. 

The hydrolytic decomposition of a potential fluorophosphite ligand would generate free fluoride ions which would be expected to be detrimental to the activity of a hydroformylation catalyst. The patent literature contains abundant references to the detrimental effects of halogens (6) on hydroformylation catalysts, and based on the patent information, one could not reasonably expect a halophosphite to be a successful hydroformylation ligand. However, a second publication by Klender (7) shows that exposure of / and other fluorophosphites to moisture at temperatures of 250°C to 350°C does not generate fluoride, even at part per million levels. 

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