Eli Lilly's erectile dysfunction patent stands up to scrutiny

01 September 2016


The English High Court (Patents Court) has ruled in a patent dispute concerned with the treatment of erectile dysfunction. Actavis and Mylan had commenced "clear the way" litigation by seeking to revoke Eli Lilly's patent in order to launch generic versions of its CIALIS medicine upon expiry of the relevant SPC protection (November 2017).

One of Eli Lilly's patents, regarding the dosage of CIALIS (EP(UK) 1,173,181), was found to be valid and infringed. The other patent, regarding microparticulate formulation of the active ingredient (tadalafil) (EP(UK) 1,200,092), was invalid.

The case involved multiple claimants, including Actavis and Mylan, across several joined cases. The judgment is long and complex, but there are some take-home messages for patentees and potential litigants that should not be missed.

The burden of establishing legal priority

Firstly, when considering validity, a particular dispute formed around whether a piece of prior art ("Stoner") could be citable against Lilly's dosage patent. Stoner was an international ("PCT") patent application filed by a third party (Merck) and was a co-pending patent application with the patent in suit. As such it could be only be cited for the purposes of a novelty attack under s.2(3) of the Patents Act 1977 ("PA"). However, it would only count as prior art against the patent if the PCT was entitled to its claimed priority.

To establish priority, two things are required; substantive and legal priority. Substantive priority is concerned with whether the "same invention" is disclosed in the priority document as the patent under scrutiny, whereas legal priority is concerned with whether the proper legal formalities have been followed to establish a chain of documents through which priority can be claimed.

Substantive priority of Stoner was not in issue, but legal priority was disputed. Was the documentary chain of title in order? And who had the burden of establishing this? Birss J considered this and found that the legal burden of proof lay with the Claimants, as the parties attacking validity. However, if sufficient evidence was available to support an inference that legal priority existed, the evidential burden would shift to the party (Lilly) seeking to rebut that inference.

The Stoner applicants were Merck & Co and Ms Waldstreicher. Ms Waldstreicher was also named as an inventor. The applicants on the face of the priority document were Ms Waldstreicher and Ms Stoner. The judge noted that the difference was likely to arise from US practice whereby patent applications have to be made in the name of the inventor although they can be assigned subsequently to their employer. Merck's claim to legal priority was likely to be on the basis that they derived title from Ms Stoner. The judge said:

When the applicant is a major international pharmaceutical company, the court is entitled to take notice of the fact that organisations of that kind have professional patent departments, part of whose function is to ensure that these sorts of formalities are complied with correctly. The same would be true if the applicant was professionally represented. The fact that Merck's patent department (whose existence is mentioned on the cover sheet of the priority document) has gone to the trouble of carefully distinguishing between Ms Stoner and Ms Waldstriecher on the face of the PCT supports the inference that someone has taken care about the formalities.

Absent evidence to the contrary, said the judge, this was sufficient to support the inference that legal priority exists. The evidential onus had therefore shifted to Lilly to call evidence to rebut that inference. It had not done so. Accordingly, the judge concluded that Stoner was entitled to legal priority from its priority document.

The judge cautioned that it would not be right to say that the inference would always be drawn in this way based on the face of an application and priority document. He would, however, expect the court to be able to draw an inference of this kind from this sort of material in most cases when the prior art in question is a patent application by a third party.

It should be noted, however, that this guidance concerns the procedural management of legal priority issues which relate to third party prior art. Should the documentary record be within the remit of one of the parties to the litigation, for example because it is the legal priority of the patent subject to the revocation action which is in issue, the approach taken by the court could well diverge.

This guidance is important for claimants and defendants alike. However, in the context of this case it helped the claimants little as, even though it maintained its claim to priority, Stoner was only citable for novelty and ultimately it fell short of anticipating the patent.

The obvious to try test

Next, Birss J turned to inventive step. He indicated (once again) that Jacob LJ's full description of the obvious to try test in St Gobain (that it must be "more or less self-evident that what is being tested ought to work") is unlikely to be followed by the courts in the future. Litigants should instead look to the shorter guidance in Gedeon Richter v Bayer that whilst "some experiments undertaken without a particular expectation as to the result, are obvious, [other are not]", and "in the end, once one has analysed each step individually it is still necessary to stand back and look overall".

The need to step back and assess "obvious to try" as a single overall question of fact was a theme throughout Birss J's judgment.

He also further indicated the importance of the statement of the doctrine given by of the Court of Appeal in Teva v Leo; that when it comes to considering a "fair expectation of success" in the context of "obvious to try"; merely including something in a research programme is not enough.

However, as long as the programme was truly routine, the fact that the outcome of the programme was uncertain would not automatically be enough to turn anything discovered by it into an invention.

In addition, Birss J also said that paragraph 49 of the House of Lords' judgment in Conor v Angiotech, which lists a number of factors to consider including "motive, multiple avenues, the effort involved and expectation of success", was "significant and useful" in the assessment of "obvious to try". To this list Birss J added "the occurrence of unexpected and even surprising results, and also the need for and nature of any value judgments which have to be made along the way."

Following this helpful analysis, Birss J turned to the facts. While Lilly's micronized formulation patent did not survive the Teva v Leo test, Birss J found that the development work in relation to tadalafil dosing levels involved surprising results and so was inventive.

Lilly's patent taught that tadalafil was a useful treatment for erectile dysfunction, and with minimal side effects, at a dosage of 5mg. The prior art taught a dosing regimen of 50mg and the judge was also "sure" that a 25mg dose "involves no inventive step". However, even though the skilled team would have tested a 5mg dose they would not have had "a reasonable expectation that 5mg would produce a clinically relevant effect at all nor one with minimal side effects", and so the 5mg dosing regimen did not satisfy the test of "obvious to try with a reasonable expectation of success".

Standing to bring a claim for infringement derived from marketing authorisation process

Finally, there was a dispute as to whether Eli Lilly had standing to bring a counterclaim for infringement on a quia timet (i.e. "because he fears") basis. This was derived from the existence of the marketing authorisation processes, pursuant to which Actavis and Mylan were seeking approval for their generic products. In effect; by seeking marketing approval had a threat to infringe been made sufficient to justify the counterclaim?

Neither side produced evidence on this issue, nor cited authority. However, on the facts, Birss J found that Eli Lilly did have standing to bring the counterclaim.

Actavis and Mylan asserted that intention to launch their products was contingent upon success in their revocation action. However, the judge concluded that if they were able to obtain marketing authorisation, itself an expensive process to embark upon, then the circumstances in the market might create an opportunity in which launching tadalafil "at risk" of infringing Eli Lilly's patent, rather than waiting for expiry of the relevant SPC protection (November 2017), was not only possible, but "attractive". After all, the market for CIALIS was large, around $100m for 2014 in the United Kingdom alone.

A "surreptitious" launch of a generic product, said the judge, can be very attractive and profitable even if it is subsequently stopped by an emergency injunction. Furthermore, when the counterclaim was brought, no undertaking was offered to abandon the marketing authorisation if they lost the revocation action.

Overall, this meant that there was a sufficiently strong probability that an injunction would ultimately be required to prevent Actavis and Mylan infringing after the expiry of the relevant SPC, to justify the bringing of the counterclaim for infringement. The counterclaim was therefore allowed to proceed.

The logic of "clearing the way", said the judge, covered both infringement and validity.

Read Birss J's judgment, Actavis & Ors v ICOS & Eli Lilly [2016] EWHC 1955 (Pat) (10 August 2016), in full.


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