Sandoz AG v Bayer Intellectual Property GmbH
| Jurisdiction | England & Wales |
| Judge | Hacon |
| Judgment Date | 12 April 2024 |
| Neutral Citation | [2024] EWHC 796 (Pat) |
| Court | Chancery Division (Patents Court) |
| Docket Number | Case Nos: HP-2022-000029 HP-2022-000034 HP-2023-000005 HP-2023-000006 HP-2023-000017 |
and
HIS HONOUR JUDGE Hacon
(Sitting as a High Court Judge)
Case Nos: HP-2022-000029
HP-2022-000032
HP-2022-000034
HP-2023-000005
HP-2023-000006
HP-2023-000017
IN THE HIGH COURT OF JUSTICE
CHANCERY DIVISION
BUSINESS AND PROPERTY COURTS OF ENGLAND AND WALES
PATENTS COURT
Royal Courts of Justice, Rolls Building
Fetter Lane, London, EC4A 1NL
Adrian Speck KC, Henry Ward, Adam Gamsa and Michael Conway (instructed by Pinsent Masons LLP, Bristows LLP, Penningtons Manches Cooper LLP, HGF Law LLP and Taylor Wessing LLP) for the Claimants/Part 20 Defendants and Third Parties
Andrew Waugh KC and Alice Hart (instructed by Allen & Overy LLP) for the Defendant/Part20 Claimant
Hearing dates: 9, 12–16 and 21–22 February 2024
Approved Judgment
HIS HONOUR JUDGE Hacon
Introduction
Rivaroxaban is the generic name of a pharmaceutical 1 used for the prevention or treatment of thromboembolic disorders. It was developed by the Bayer group of which the defendant forms part. I will refer to the defendant and other members of the group individually and collectively as “Bayer”.
The active ingredient of rivaroxaban is protected by product claims of a patent owned by Bayer. Consequently Bayer has had a monopoly of the rivaroxaban market, selling the product under its brand name Xarelto. That protection was extended by an SPC but expired on 1 April 2024. This provides an opportunity for those who wish to market generic rivaroxaban, not least the claimants and third parties in these proceedings, save that Bayer also owns European Patent (UK) No. 1 845 961 (“the Patent”).
The Patent has claims in Swiss form covering the use of the active ingredient for the manufacture of a medicament for the treatment of a thromboembolic disorder. The claims are limited, so far as is relevant, to (a) the use of a rapid release tablet and (b) administration no more than once daily for at least five days. There is no limitation as to the dose. The priority date of the Patent is 31 January 2005.
The claimants allege that the Patent is invalid and that it constitutes an attempt by Bayer to evergreen its lucrative monopoly in the manufacture and marketing of rivaroxaban, in other words to extend the monopoly through unjustified means.
Bayer has counterclaimed, alleging a threat on the part of the claimants and the third parties to infringe the Patent by the marketing of rivaroxaban products.
All six actions joined into the present proceedings were brought by one or more of the claimants, seeking revocation of the Patent. In every action Bayer counterclaimed alleging a threat to infringe the Patent, in some instances joining one or more third parties as alleged potential infringers. It is not necessary for me to distinguish between the claimants and third parties which I will collectively refer to as “the claimants”. The threat to infringe was in all instances conceded for the purposes of this trial. This action is solely about the validity of the Patent.
Adrian Speck KC, Henry Ward, Adam Gamsa and Michael Conway appeared for the claimants, Andrew Waugh KC and Alice Hart for Bayer.
Technical background
The following matters all formed part of the skilled person's common general knowledge (“CGK”) at the priority date.
Haemostasis and thromboembolism
Haemostasis is a process which gives rise to the formation of blood clots when an individual suffers injury and there is a need to close up damage to blood vessels. Haemostasis is a necessary local response to injury but vascular blood should otherwise flow freely. In healthy humans there is therefore a homeostatic balance, meaning a self-regulating process which adjusts to prevailing conditions to best suit the individual's survival, between procoagulant and anticoagulant mechanisms.
Thrombosis is a condition in which a clot, or thrombus, causes obstruction of the blood flow in part of the vascular system away from a site of injury. Thrombosis has long been treated by the administration of anticoagulants.
The coagulation cascade
Blood has a liquid component, plasma, and three solid components: red blood cells, white blood cells and platelets. The primary purpose of red blood cells is to carry oxygen but they have a secondary function in that they become passively trapped in thrombi, forming the bulk of a thrombus. The primary purpose of white blood cells is to combat infection. Some classes of one type of white blood cell, leukocytes, express on their surface a protein called “tissue factor” during haemostasis which activates blood coagulation. Platelets are very small cell fragments which, when activated, aggregate and adhere to nearby surfaces, forming part of a thrombus.
The “coagulation cascade” is the name given to a series of reactions culminating in the formation of an insoluble clot. The enzymes which catalyse the reactions are known as “factors”, identified by Roman numerals and given the suffix “a” when the factor is in its active form. The following provides an overview of the coagulation cascade:
The upper part of the diagram shows two pathways, each contributing and leading to the activation of Factor X to Factor Xa (“FXa”). The one on the left is known as the extrinsic pathway, the one on the right is the intrinsic pathway. FXa in association with Factor Va converts prothrombin (Factor II) to thrombin (Factor IIa). Thrombin feeds back into the cascade to activate other factors and platelets, an effect shown by the dotted lines. Thrombin also converts fibrinogen to fibrin. Fibrin is an insoluble polymer in the form of threads which stabilize the structure of a clot.
Thromboembolic disorders
The primary causes of thrombosis are the improper functioning of the coagulation cascade and/or excessive platelet activation, commonly because the anticoagulation system is overwhelmed by thrombotic stimuli. A thrombus may break loose and be carried elsewhere in the circulatory system. In that form it is known as an “embolus”, the condition is “embolism”. “Thromboembolism” describes the combined conditions of thrombosis and embolism.
Patients undergoing major surgery are at particularly high risk of venous thromboembolism (“VTE”). One form is deep vein thrombosis (“DVT”), the most serious complication of which is pulmonary embolism (“PE”) in the lung. PE remains a significant cause of death in both surgical and medical patients.
The human body has its own mechanisms to modulate clot formation. There are three, each inactivating factors in the coagulation cascade and in one case also inactivating thrombin. Where urgent anticoagulation in a patient is needed, drugs are used to prevent the formation of thrombi and/or to degrade them.
The therapeutic window
An important feature of anticoagulant drugs is that if they are not sufficiently effective, clots will remain and new clots may form. If they are too effective, clots required at the site of injury will not form, particularly after surgery, and the patient will suffer excessive bleeding. Both possibilities are dangerous for the patient and either may be fatal. There is thus a “therapeutic window” in which the drug is available enough to have a sufficiently anticoagulant effect, but not so available and effective such that the patient suffers from unwanted bleeding.
The wider the therapeutic window afforded by a drug, the more attractive it is for clinical use. But it is never possible to know in advance where the therapeutic window lies and how wide the window will turn out to be.
Prior art anticoagulant drugs
The following anticoagulant drugs were in clinical use at the priority date of the Patent, 31 January 2005:
(1) Warfarin is an orally administered vitamin K antagonist. It inhibits a liver enzyme that blocks the recycling of vitamin K, which has the effect of reducing the production of Factors II, VII, IX and X in the liver. First marketed as a rat poison, it was approved for use in humans as an anticoagulant in the 1950s. It is relatively slow-acting and its effect varies between patients, so close monitoring and dose adjustment is necessary. However it remains widely prescribed in the UK and elsewhere.
(2) Heparin indirectly inactivates thrombin and FXa. There are two forms, unfractionated heparin, usually referred to in the evidence as just “heparin”, and low molecular weight heparin (LMWH). Both are administered by intravenous or subcutaneous injection. Heparin, like warfarin, exhibits variability in its effect and so requires patient monitoring and dose adjustment. LMWH is more predictable in its effect so no patient monitoring is required. Enoxaparin is a commonly used LMWH.
(3) Fondaparinux also indirectly inhibits FXa. It is administered subcutaneously once daily. By January 2005 it had been evaluated extensively for the prevention of VTE in patients undergoing orthopaedic surgery, i.e. surgery concerned with conditions involving the musculoskeletal system. It was found to be more effective than enoxaparin in preventing post-operative thrombosis.
Three other anticoagulants had been licensed for treatment by January 2005, namely hirudin, bivalirudin...
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