Cephalon Inc. v Orchid Europe

Hearing date: 11 November 2010

Approved Judgment

I direct that pursuant to CPR PD 39A para 6.1 no official shorthand note shall be taken of this Judgment and that copies of this version as handed down may be treated as authentic.

Mr Justice Floyd:

I have before me an application notice dated 14 September 2010 seeking an order restraining the defendants until judgment or further order from selling or offering for sale modafinil tablets under certain marketing authorisations. The claimants (collectively “Cephalon”) are respectively (1) the proprietor, (2) an exclusive licensee in the UK and (3) a sub-licensee of a number of patents related to the drug modafinil. They claim that two of these patents would be infringed if the defendants were to market modafinil in the UK. The third claimant currently markets the drug under the brand name Provigil through its sub-distributor Teva. The drug is prescribed for hypersomnia and narcolepsy.

The action, as patent actions go, is not a complicated one. The claimants contend that the action could be brought to trial in June 2011. The defendants contend that a trial on an expedited basis in April 2011 is possible. Accordingly, the trial is between six and eight months away.

The first defendant, Orchid, is the UK subsidiary of an Indian pharmaceutical manufacturer. On 22 ^nd January 2010 it obtained regulatory approval to launch a modafinil product in the United Kingdom. That product has been supplied to Orifarm Generics A/S, a Scandinavian generic company, which subsequently launched the product in Sweden and Denmark. Preliminary injunctions have been sought by Cephalon in those two countries. The Swedish court has recently granted an injunction pending trial.

The second defendant (“Mylan”) is a UK pharmaceutical company. Mylan has also obtained marketing authorisations for a modafinil product in a number of European countries. Its UK marketing authorisation was also granted on 22 January 2010. The Mylan product is manufactured by Orchid. On 4th September 2010 the trade publication Chemist and Druggist announced that Mylan was offering modafinil 100 mg tablets in the UK. That announcement led to the issuing of the application notice which came before Lewison J on 20 ^th September when the defendants gave undertakings until the effective hearing.

The active substance modafinil was discovered by Lafon in France in 1976. The drug was licensed to Cephalon in the US in 1994. In the course of clinical trials in the United States Cephalon found increased side effects as compared with equivalent doses tested in European clinical trials. The different effect was traced to particle size. It was appreciated that the increased potency of the smaller particle size could reduce the amount administered to the patient.

In 2005 there was litigation between Cephalon and Teva Pharmaceutical Industries Limited (Teva) in the US and UK which was settled on terms that that the Teva companies could enter the market with their own generic modafinil in October 2012. Given that 698 does not expire until 2015, it would appear that Cephalon were compelled for some reason to accept a considerable inroad into their monopoly in the UK. This is not explained in the evidence, but I am not entitled to infer anything from that, as it may depend in part on the position in the US. Pending October 2012, Teva have an exclusive distribution agreement with Cephalon for modafinil in the UK and elsewhere. It is a term of the settlement agreement that, if another generic product is launched in any territory before that date, the relevant Teva company could terminate the distribution agreement and have a licence so long as that other generic is on the market. Before doing so they are required to negotiate in good faith with Cephalon, but if the parties cannot agree within 30 days the distribution agreement will terminate.

The patents

The two patents of which infringement is alleged are EP (UK) 0 731 698 (“698”) and EP (UK) 0 966 962 (“962”). The defendants have counterclaimed for revocation of a third patent, EP (UK) 1 088 549 (“549”) which need not be considered further.

It is sufficient to consider 698 for present purposes. The patent describes the invention at [0006] in the following terms:

“Our invention discloses 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 patent tracks the history of the making of the invention, showing how particle size distribution was examined as between the early and late lots of modafinil. In all the experiments in the patent the particle size is measured on the bulk drug substance, even though in some tests the product is incorporated into capsules. The patent explains at [11] that:

“The size of the particles can be determined, e.g., by the methods provided below, and by other conventional methods known to those of skill in the art”.

Claim 1 is in the following form:

“A pharmaceutical composition comprising a substantially homogeneous mixture of modafinil particles, wherein at least about 95% of the cumulative total of modafinil particles in the 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.”

The claim uses the cumulative total measure of particle size. Figure 1 in the patent shows that 95% under 200 microns was the cumulative total demonstrated by the two late samples which had median particle diameters of between 30 and 50 µm. It is on this basis that claim 2 is to

“The composition of claim one wherein said particles have a median diameter of between about 2 micrometers and about 60 micrometers.”

A short question of construction arises. When the claims speak of the particle size, does that mean the particle size (by whatever measurement) in the composition or the particle size of the active ingredient used to make the composition? The claimants contend for the former construction, the defendants for the latter. The point matters because the claimants have performed their measurements of the defendants particles on modafinil extracted from their tablets. It is possible that mechanical shearing and crushing forces experienced by the particles of modafinil during tabletting will alter their size and size distribution.

Mr Carr QC, who appeared for the claimants with Mr Thomas Mitcheson, submits that as the claim is a product claim, it is natural to suppose that it is the particle size in the product which is intended. That is what the claim says. Moreover, as the benefits of the invention are concerned with the administration of the composition of the claim, it is the particle size in the composition which matters for the purposes of the invention. He says that the specification is written on the assumption that particle size stays the same when the bulk active ingredient is made into tablets or other formulations. But that does not mean that if a tablet in fact contains modafinil with a particle size within the claim, that it does not infringe.

Mr Tappin QC, who appeared for the defendants with Mr Adrian Speck, submits that the specification is consistent throughout in referring to particle size of the bulk active ingredient. No other method is taught for measuring particle size. The discoveries in question were made by measurements on the bulk active ingredient. He says that it is so clear that that is what the claim means, that I should so decide on this application.

For present purposes I need to do more than decide whether Mr Carr's construction is arguable. In my judgement it is manifestly so. The two arguments advanced (that the claim is to the composition, and that it is the point at which the drug is administered which is important) seem to me to be more than enough to get him over that hurdle.

Arguable case of infringement?

Although, for the purposes of determining whether there is an arguable case of infringement, it is the particle size in the tablet which matters, I will first summarise the evidence about the bulk active pharmaceutical ingredient (“API”).

Tests done for the defendants under the supervision of Professor Buckton, who is Professor of Pharmaceutics at the School of Pharmacy in the University of London, showed that the median, mean and mode diameters of the API provided were 218, 235 and 308 microns respectively, and that only 50% of particles were below 200 microns. On this basis the API would not fall within any claim. A sample of the API has been provided to Cephalon, but they have not disclosed the results of any testing on any untreated test sample. Instead they have chosen to question whether the sample provided to them is representative. They have however apparently conducted some tests on the Orchid API, because these are shown in an exhibit to their reply evidence, although not commented on by any of their witnesses. In those tests the API has been treated by sonication (see below), and so the results may not be representative of the untreated API which was tested by Professor Buckton.

If the claim were...