Hospira UK Ltd v Cubist Pharmaceuticals LLC

In assessing obviousness, the court must consider whether the skilled person would have pursued the proposed modification with a fair expectation of success. A route may remain obvious even though testing is needed and the precise effect of a variable cannot be predicted in advance, provided the investigation is straightforward and the evidence supports a realistic prospect of success. The availability of a short list of technically suitable alternatives, the motivation to avoid an unsuitable process ingredient, and the controllability of the proposed alternative may all be relevant. The first-instance assessment will stand where it has an adequate evidential basis and contains no error of principle.

The proprietor appealed against the decision of Henry Carr J, dated 10 June 2016, that European Patent (UK) 2,264,047 was invalid for lack of inventive step, and against the order for revocation made on 17 October 2016. The patent claimed a two-stage method for purifying daptomycin by forming and dissociating micelles through pH adjustment and using ultrafiltration.

The prior article by Lin and Jiang disclosed a substantially similar purification process for surfactin, using methanol to dissociate the micelles, and stated that the process could be modified for most surfactants. The appeal challenged whether the skilled team would have expected daptomycin to form micelles and whether replacing methanol with pH adjustment was obvious.

1. Appeal dismissed. The judge had an ample evidential basis for finding claim 1 obvious over Lin and Jiang and had made no error of principle.
2. The relevant differences were that Lin and Jiang concerned surfactin rather than daptomycin and used methanol rather than pH adjustment. The skilled team would have had a real expectation that daptomycin was a biosurfactant capable of forming micelles. Lipopeptides were commonly known as biosurfactants; there was no example in the evidence of a non-biosurfactant lipopeptide; and daptomycin’s primary structure supported that prediction. The expectation could be tested by straightforward laboratory methods, including a properly conducted shake test and electrical-conductivity testing to identify the critical micelle concentration (paras 27–42).
3. It was accepted on appeal that changing pH was common general knowledge as a means of controlling micelle formation and dissociation in a lipopeptide biosurfactant. The skilled team would have been motivated to replace methanol because it was toxic and created solvent-recovery difficulties. Although the precise effect of pH on the critical micelle concentration could not be predicted before testing, pH was a controllable and attractive variable, and the necessary testing was simple. That was sufficient to support a fair expectation of success; obviousness did not require certainty of outcome (paras 43–52).
4. The possibility of degradation at low pH did not alter the conclusion. The claims were not confined to industrial-scale purification, and the evidence did not show that the skilled team would have been deterred from investigating pH adjustment at laboratory or pilot scale, which fell within the claims (para 53).
5. The judge was aware that fair expectation of success is relevant where an invention is alleged to be obvious to try. He evaluated that issue in light of all the evidence and circumstances. The Court of Appeal therefore dismissed the appeal and upheld the finding of invalidity and the revocation order.

• Court of Appeal (Civil Division): [2018] EWCA Civ 12. Appeal dismissed.
• High Court, Chancery Division, Patents Court: Henry Carr J held the patent invalid for lack of inventive step on 10 June 2016 and made an order for revocation on 17 October 2016: [2016] EWHC 1285 (Pat).