Hospira UK Ltd v Cubist Pharmaceuticals LLC

A patent claim is entitled to priority only where the skilled person can derive its subject matter directly and unambiguously, using common general knowledge, from the priority document as a whole. Disclosure of a broad range does not necessarily disclose a later sub-range or combination. For obviousness, the court assesses the facts as a whole, including motivation, available research routes and whether the skilled person would have a fair expectation of success. A proposed clinical trial may provide that expectation where its regulatory approval and phase indicate supporting efficacy and safety data. Standard purification techniques may be obvious when applied in a routine sequence to improve an existing process. A technical prejudice must be widely or universally held. The three patents concerning daptomycin dosage, purification and micelle formation were invalid for lack of inventive step.

Hospira sought revocation of three Cubist patents concerning daptomycin: a dosage regimen of 3–10 mg/kg once every 24 hours, purification processes using chromatographic techniques and modified buffers, and purification through formation and dissociation of micelles.

The court considered priority, anticipation, obviousness, added matter, clarity and sufficiency. The dosage patent was not entitled to its first priority document but was entitled to its second. It was not anticipated by the Cubist press release or Woodworth, although it was obvious over both. The purification patents were obvious over US 843 and, in one respect, over common general knowledge alone; the micelle patent was obvious over Lin & Jiang. The insufficiency challenge based on the description of daptomycin failed.

1. 417 Patent. The first priority document disclosed 2–10 mg/kg at intervals between 12 and 24 hours, but did not directly and unambiguously disclose 3–10 mg/kg once every 24 hours. The claim therefore lacked the first priority date. The second priority document disclosed the same invention through its dog studies, once-daily teaching and specific dose disclosures. The amended claims were consequently entitled to the second priority date.
2. The Cubist Press Release and Woodworth disclosed proposed or predicted once-daily dosage regimens but did not disclose the required therapeutic efficacy in treating bacterial infections. They therefore did not anticipate the claims. Nevertheless, the Press Release, its FDA-approved clinical programme and the known background of daptomycin gave the skilled team a fair expectation of success. Woodworth disclosed 4–6 mg/kg once-daily dosing and, read with the pharmacokinetic, pharmacodynamic and post-antibiotic-effect information, likewise made the claims obvious. Claims 6 and 7 were not saved by paediatric dosing considerations.
3. The amended dosage claims did not add matter. Proposed claim 2 lacked clarity because excluding 3 mg/kg left the lower boundary of the claimed range uncertain. The sufficiency squeeze failed because the patent made it plausible that the regimen would reduce muscle toxicity and the skilled team would expect increased efficacy at higher doses.
4. 179 Patent. US 843 was not a complete purification process and did not teach that anion exchange chromatography was unsuitable for daptomycin. In light of the common general knowledge that different purification modes should be combined, the skilled team had an obvious motivation and fair prospect of success in improving US 843 by using anion exchange chromatography before and after hydrophobic interaction chromatography, with standard buffers and urea to address aggregation. The claims were obvious over US 843. Claim 1 was also obvious over common general knowledge alone, but claim 3 and its dependent claims were not.
5. 047 Patent. Lin & Jiang disclosed a general method for purifying biosurfactants by forming micelles and using ultrafiltration. The skilled team would expect daptomycin, a cyclic lipopeptide, to be a biosurfactant and could confirm that by routine testing. Replacing methanol with pH control to dissociate micelles was a routine alternative. The claim was obvious over Lin & Jiang.
6. The alleged insufficiency arising from the stereochemical description of daptomycin failed. In context, daptomycin meant the product obtained by fermentation of Streptomyces roseosporus, not a compound defined by the erroneous stereochemical assignment in Baltz. Hospira’s claim for revocation succeeded and all three patents were invalid.