Sandoz Ltd v Bristol-Myers Squibb Holdings Ireland Unlimited Company

Hearing dates: 31 January, 1–4 and 9–10 February 2022

I direct that no official shorthand note shall be taken of this Judgment and that copies of this version as handed down may be treated as authentic.

INTRODUCTION

This is the trial of two actions in which the Claimants, respectively Sandoz Limited (“Sandoz”) and Teva Pharmaceutical Industries Limited (“Teva”) seek the revocation of European Patent (UK) 1 427 415 B1 (“the Patent”) in the name of Bristol-Myers Squibb Holdings Ireland Unlimited Company (“BMS”). The priority date is 21 September 2001.

The claims of the Patent relate to a compound called apixaban, sold by BMS under the name ELIQUIS and which is used for thromboembolic disorders.

There is also a corresponding SPC (SPC/GB11/042) but nothing separate turns on that: it is invalid if the Patent is invalid.

BMS has counterclaimed for infringement. Infringement is admitted by Sandoz and Teva in the event that the Patent is valid. So in substance this was a patent revocation trial.

Sandoz and Teva are separately represented but have made common cause, submitting joint skeleton arguments and sharing expert witnesses, and with their Counsel splitting the oral advocacy at trial. They have run the same arguments with one exception, an obviousness attack made by Teva alone. I will refer to Sandoz and Teva together as “the Claimants”.

Apixaban's use in therapy depends on its activity as a factor Xa inhibitor. It is not in dispute that in fact apixaban has proven to be a potent factor Xa inhibitor and a useful therapeutic, but the central attack on the Patent is that it did not make plausible that apixaban would have any useful factor Xa inhibitory activity, or be useful in therapy, or for any other purpose.

It was common ground that the issue of plausibility should be tested by reference to the application for the Patent, published as WO 2003/026652 A1 (“' 652”), because if plausibility had to be based on something that was only in the Patent and not in '652, there would be added matter. On that basis, an added matter squeeze fell away.

BMS has also applied to amend the Patent's claims.

There has been related litigation in Canada, where BMS has been successful. But BMS did not submit that it could rely on the result there in this litigation and from what I have seen a very different legal standard applies there. Dr Camp, BMS's medicinal chemistry expert, was involved in the Canadian litigation and that forms part of the background to his evidence in this case.

THE ISSUES

The issues were:

10.1 Some issues over common general knowledge (“CGK”). Much more was agreed than was in dispute.

10.2 Lack of plausibility. Lack of plausibility is not a ground for revocation in itself and it was run both as Agrevo obviousness and insufficiency. Neither side said it made a difference which head applies, and I agree in the light of the case law to which I refer below, in particular Warner-Lambert and Fibrogen. So I will just refer to lack of plausibility.

10.3 Obviousness over WO 00/39131 “Nitrogen Containing Heterobicycles as Factor Xa Inhibitors” (“'131”). This was not a “classical” obviousness attack: the Claimants do not say it was positively obvious to get to apixaban specifically from '131. Rather, they said that '131 contains very similar teaching to '652 about broad classes of compounds that include apixaban, and that there is no technical contribution in '652 over what '131 discloses.

10.4 (Teva only) That claims 1–6 exceed the technical contribution of the Patent and that in particular the claims to products per se are invalid even if some usefulness were to be plausible.

10.5 Allowability of the amendments, where the points were:

10.5.1 Whether the amendments were capable of curing any invalidity.

10.5.2 Lack of clarity.

10.5.3 Added matter.

THE WITNESSES AND THE SKILLED TEAM

The parties each called three experts. They were in:

11.1 Medicinal chemistry;

11.2 “The coagulation cascade”, which refers to the pharmacology/biochemistry of relevance;

11.3 Pharmacokinetics or DMPK (“drug metabolism and pharmacokinetics”).

Permission for the third of those, DMPK, was pressed for by BMS at the directions stage because it intended to argue that there was a contribution in relation to pharmacokinetics in '652. That argument collapsed with the oral evidence and I think the Claimants were right all along that the Patent is nothing to do with DMPK issues. There was no material dispute over the skilled team by the end of trial in any event: it would be a drug design/development team comprising (i) a medicinal chemist and (ii) a biochemist or pharmacologist, who would have relevant experience in industry. I have paid some minimal attention to evidence from the DMPK witnesses below, but it could easily have been given by one of the other experts and does not change my view on the skilled team.

There was no fact evidence.

The Claimants' experts were:

14.1 Dr Sally Redshaw (medicinal chemistry);

14.2 Dr Robert Leadley (pharmacology/biochemistry);

14.3 Prof Kevin Read (DMPK).

BMS's experts were:

15.1 Dr Nicholas Camp (medicinal chemistry);

15.2 Prof James Morrissey (pharmacology/biochemistry);

15.3 Dr David Taft (DMPK).

The only witness of whom personal criticism was made was Dr Taft. The Claimants submitted that his evidence was not credible, to such an extent that he must have been insincere in his defence of it. I reject any personal criticism of Dr Taft. The position he supported was indeed extreme and if it had not been given up on by BMS I would have rejected it, but I think he honestly believed it.

As to the other witnesses, points of detail were made about their approach and about their specific experiences. I will deal with those where they arise and to the extent I think them important, which they generally were not. My assessment of these specific points takes place against the backdrop of my more general view that the witnesses were well qualified and gave their evidence fairly and honestly.

A basic divergence between the parties was that the factor Xa knowledge was spread differently among their witnesses. For the Claimants, the factor Xa knowledge was possessed by Dr Leadley, with Dr Redshaw having no previous experience in relation to it. For BMS, Dr Camp had a lot of contemporaneous involvement relevant to factor Xa inhibition and Prof Morrissey had none of any significance. Although this probably meant that the Claimants' witnesses together represented the notional skilled team better, in that medicinal chemists often have no direct experience of the specific target of a given project, I did not think it mattered.

SOME IRRELEVANT MATTERS

Both sides raised matters which I think are irrelevant and which I will mention now so as to dismiss them.

For its part, BMS emphasised that apixaban has proved to be a very important and...