Gilead Sciences Inc. (a company registered in the US State of Delaware) v Nucana Plc

Hearing dates: 20 and 23–27 January and 1–3 February 2023

APPROVED JUDGMENT

Remote hand-down: This judgment will be handed down remotely by circulation to the parties or their representatives by email and release to The National Archives. A copy of the judgment in final form as handed down should be available on The National Archives website shortly thereafter but can otherwise be obtained on request by email to the Judicial Office (press.enquiries@judiciary.uk).

INTRODUCTION

In this action the Claimants (together, “Gilead”) seek the revocation of two patents owned by the Defendant, NuCana. They are European Patent (UK) 2 955 190 B1 (“EP190”) and European Patent (UK) 3 904 365 B1 (“EP365”). I will refer to them together as “the Patents”. They are from the same family and although their specifications differ, the differences mostly do not matter and I pick up those points of significance as they arise below. Where I refer to specification paragraph numbers without expressly saying which of the Patents, then I mean EP190.

EP190 and EP365 also differ in their claims, with EP365 being narrower.

The Patents have the same unchallenged priority date of 21 July 2003. As I explain in more detail below, EP190 is under opposition in the EPO with a Technical Board of Appeal (“TBA”) hearing due on 24 March this year. EP365 was only granted on 7 September 2022.

NuCana counterclaims for infringement by Gilead's commercially very successful drug compound sofosbuvir, which is the active ingredient, or one of the active ingredients in its Sovaldi, Harvoni, Vosevi and Epclusa products, which are anti-virals.

NuCana had its own product covered by the claims of the Patents, Acelarin, intended as a cancer drug. It has run into difficulties with clinical trials. That is not of any direct relevance to the issues before me although Gilead sought to emphasise that the Patents teach that the compounds disclosed are cytotoxic, which is desirable in a cancer drug but, Gilead submits, positively to be avoided in an anti-viral.

There is no real challenge to infringement if the claims of the Patents are valid and Gilead took the role of claimant at the trial.

The Patents arise from the work of the late Prof Chris McGuigan of Cardiff University. It will help an understanding of this judgment if I explain at this early stage and at a very high level the technology involved.

For decades it has been known that cancer can be treated with drugs based on nucleoside analogues (also referred to as “NAs”, I will use the full term and the abbreviation interchangeably in this judgment and both are used extensively in the papers in the case). These are compounds which are similar to natural nucleosides but which are modified so that, by one or more mechanisms, they interfere with cells' normal replication and kill them or stop them from growing. This process affects healthy as well as cancerous cells but cancer cells replicate much faster so are hit harder.

A common general knowledge (“CGK”) nucleoside analogue drug which had been successfully used in treating cancer was gemcitabine:

A problem with nucleoside analogues arose with getting them into cells. The reasons for this are relatively complex and are discussed in more detail below. At this introductory level what is significant is that Prof McGuigan's work was concerned with making prodrugs, referred to as ProTides, to try to overcome this problem. The ProTide approach involves phosphoramidate modifications (again, explained below) to nucleoside analogues.

The claims of the Patents are product claims; they are defined by a Markush formula (the permitted substituents vary from claim to claim) and cover ProTide nucleoside analogues as just described in which the nucleoside moiety is gemcitabine or gemcitabine-like. Sofosbuvir falls within the Markush group:

In prosecution and in the opposition proceedings NuCana has successively narrowed its patent claims. At this trial it seeks to amend EP190 in two proposed amended forms (one unconditional and one conditional, the latter being a small extra limitation over the former), and EP365 has claims that are narrower still. NuCana floated a further set of amendments to EP190 in late December 2022, shortly before trial, but abandoned it on the first day of trial.

Gilead attacks the Patents on the following grounds:

i) Added matter: Gilead says that the Markush group definitions of the claims of the Patents are not clearly and unambiguously disclosed in the relevant original application.

ii) Lack of plausibility: Gilead says that the Patents do not plausibly disclose any technical contribution common to substantially all the claimed compounds. NuCana says that there is a plausible technical contribution in relation to the compounds having cytotoxic activity or improved intracellular delivery; it says that the cytotoxicity means that the compounds have the potential to be used in the treatment of cancer. Lack of plausibility is run under the legal heads of:

a) Obviousness over US 2003/0109697 (“Shepard”) on the basis that given the lack of plausibility there is no technical contribution;

b) Insufficiency.

iii) Lack of industrial applicability. This is very...