Petition for revocation - Obviousness - Inventive step

Cephalon Inc and other companies v Orchid Europe Ltd and another company [2011] All ER (D) 206 (Jun) [2011] EWHC 1591 (Pat)

The claimant companies were collectively the proprietor and exclusive licensee in the United Kingdom and a sub-licensee of three patents, namely European Patents (UK) No. 0 731 698 (the 698 patent), 0 966 962 (the 962 patent) and 1 088 549 (the 549 patent), all related to the drug 'modafinil'.

The first defendant company was the manufacturer of generic modafinil, a drug used to treat sleep disorders which the second defendant intended to market in the UK.

Claims 1 and 2 of the 698 patent stated: '1. A pharmaceutical composition comprising a substantially homogeneous mixture of modafinil particles, wherein at least about 95% of the cumulative total of modafinil particles in said composition have a diameter of less than about 200 micrometers and said composition contains between about 50 milligrams and about 700 milligrams of said modafinil.

'2. The composition of claim 1 wherein said particles have a median diameter of between about 2 micrometers and about 60 micrometers.'

Claims 1 and 16 of the 962 patent stated: '1. The use of modafinil for the manufacture of a pharmaceutical composition comprising modafinil particles having a median particle size of about 2 to about 60 micrometres for use in altering the somnolent state of a mammal involving administering about 50 to 700 milligrams of said modafinil particles to said mammal.

'16. The use of a substantially homogeneous mixture of modafinil particles whereof at least about 95% of the cumulative total of said particles have a diameter of less than about 200 micrometers for the manufacture of a pharmaceutical composition containing between about 50 mg and about 700 mg of modafinil for use in altering the somnolent state of a mammal.'

Claim 1 of the 549 patent stated: '1. A process for the preparation of a pharmaceutical composition comprising incorporating an effective amount of modafinil particles wherein at least about 95% of the cumulative total of said modafinil particles in said composition have a diameter of less than about 200 µm and wherein the median particle size is about 10 to 60 µm into said composition and forming the same into a tablet, capsule, powder or pill.'

The three patents contained very similar disclosure, disclosing 'a pharmaceutical composition comprising modafinil in the form of particles of a defined size, and the use of such composition. We have discovered that the size of modafinil particles is important to the potency and safety profile of the drug' (the specification).

The claimants brought an action against the defendants for infringement of the patents. The action was stayed against the first defendant pending judgment in the action against the second defendant.

An issue arose regarding the potency of drug molecules and the size of particles in modafinil. Smaller particle size of the input active pharmaceutical ingredient (API) in the drug would enable a smaller amount of that drug to be used in a solid formulation to achieve the same effect.

The second defendant contended that the claimant had not proved that there were particles present in the solid formation (as opposed to those extracted from the solid formation) which fell within the claims.

It relied on the fact that the tabletting process was known to cause particles to bind together, and submitted that such bonds could fracture when the tablet disintegrated, so that the particles measured by the claimants would not represent whatever existed within the tablet (the construction issue).

The second defendant further claimed that the patents were invalid for lack of inventive step and obviousness over, inter alia, an article in a publication named 'Drugs of the Future' (the article).

The article had identified modafinil, a method for its manufacture and its dosage range and had contained summaries of some clinical trials.

The claimant submitted that, as the benefits of the invention were concerned with the administration of the drug, it was the particle size in that composition which mattered for the purposes of the invention.

It submitted that the specification had been written on the assumption that the particle size remained the same when the bulk active ingredient was made into tablets or other formulations, but that it did not follow that a tablet which contained modafinil with a particular size within the claim would not infringe it.

It was common ground that if the second defendant's construction of the claims was the correct one, there would be no infringement.

The court ruled:(1) In the instant case, the patent was addressed to a team involved in developing the drug modafinil.

Such a team would include a formulation scientist. It would also have access to the wider drug discover and development team as and when necessary for the development of the drug being formulated.

Further, with respect to the construction of a patent, it was well established that the task for the court was to determine what a person skilled in the art would have understood the patentee to have used the language of the claim to mean (see [23], [32] of the judgment).

In the instant case, the common general knowledge would include, inter alia, the following matters: (i) the development of a commercial dosage form of a drug began with pre-formulation studies; (ii) the formulation process would seek to produce a dosage form that would deliver the drug to the patient in a therapeutically optimal manner; (iii) a formulator would seek to increase bioavailability by ensuring that the drug was delivereed completely and rapidly into the bloodstream; (iv) the formulator would investigate the solubility of the drug, typically in a variety of solvents; and (v) bioavailability of the drug would depend on the rate at which it could be absorbed.

Having considered the language used in each of the individual claims of the patents, it was clear that the skilled person would understand that, in the case of the process, it was the bulk API which he had to measure, and not in that formulation.

Accordingly, since the first defendant's API fell outside the scope of all the claims if construed to mean the particle size in the input API (with a 95 per cent cululative particle size of greater than 220µm), there had been no infringement (see [24], [49], [50] of the judgment).

On the basis of the correct construction of the claims, there was no infringement of the claims relied upon (see [56] of the judgment).

Kirin Amgen Inc v Transkaryotic Therapies Inc [2002] All ER (D) 491 (Jul) applied; Virgin Atlantic Airways Ltd v Premium Aircraft Interiors UK Ltd [2009] All ER (D) 235 (Oct) applied; Technip France's Patent [2004] All ER (D) 63 (April) considered.

(2) In the instant case, the inventive concept would be the use of modafinil particles with reduced particle size to make a modafinil formulation.

The inventive concept of each of the claims relied on was obvious in the light of Drugs of the Future and common general knowledge.

Firstly, the definitions of target dissolution rates set by regulators were definitions of what would be acceptable rather than optimal. It had not been suggested that they represented any sort of limit of what would be achievable in dissolution rate.

Secondly, a skilled person would understand that it was desirable to achieve rapid and complete dissolution and hence better bioavailability.

Thirdly, the skilled person would approach the formulation exercise in the expectation that reducing particle size would improve bioavailability, and would therefore provide benefits in terms of achieving the optimal formulation.

Fourthly, the skilled person would conduct dissolution tests that would confirm the benefits of reducing particle size.

Fifthly, the skilled person who had conducted such tests would not encounter any significant obstacle to reducing particle size into the range of the claims.

Sixthly, the fact that that some companies would be satisfied with a sub-optimal product that cleared the regulatory threshold did not mean that it would be inventive to produce an optimised one.

However, on the evidence, there was no established mindset that anything which met the target dissolution rate would be good enough. The actual position had been to the contrary.

The technical mindset had been that improvements in bioavailability could be made by reducing particle size, and that the target dissolution rates did not represent any sort of limit (see [75]-[82] of the judgment).

The patents were invalid for obviousness in the light of Drugs of the Future and common general knowledge (see [94] of the judgment).

Pozzoli SPA v BDMO SA [2007] All ER (D) 275 (Jun) applied; Conor Medsystems Inc v Angiotech Pharmaceuticals Inc [2008] 4 All ER 621 applied; Generics (UK) Ltd v H Lundbeck A/S [2009] 2 All ER 955 applied; Dyson Appliances Ltd v Hoover Ltd [2001] All ER (D) 41 (Oct) considered.

Henry Carr QC, Piers Ackland QC and Thomas Alkin (instructed by Simmons & Simmons LLP) for the claimants. Michael Tappin QC and Adrian Speck (instructed by Taylor Wessing LLP) for the second defendant.