Teva Pharmaceutical Industries Ltd v Novartis AG
| Jurisdiction | England & Wales |
| Judge | Hacon |
| Judgment Date | 10 November 2022 |
| Neutral Citation | [2022] EWHC 2847 (Pat) |
| Court | Chancery Division (Patents Court) |
[2022] EWHC 2847 (Pat)
HIS HONOUR JUDGE Hacon
IN THE HIGH COURT OF JUSTICE
BUSINESS AND PROPERTY COURTS OF ENGLAND AND WALES (ChD)
INTELLECTUAL PROPERTY LIST
PATENTS COURT
Royal Courts of Justice, Rolls Building
Fetter Lane, London, EC4A 1NL
Tom Moody-Stuart KC and Katherine Moggridge (instructed by Pinsent Masons LLP) for the Claimants
Andrew Waugh KC and Henry Ward (instructed by Bristows LLP) for the Defendants
Hearing dates: 22–25 February, 28 February, 1 March, 3–4 March 2022
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.
HIS HONOUR JUDGE Hacon
Introduction
The claimants (collectively “Teva”) bring this action for revocation of two patents (“the Patents”) owned by the first defendant, European Patent (UK) No. 2,964,202 (“EP 202”) and European Patent (UK) No. 3,124,018 (“EP 018”). Teva also seek a declaration of non-infringement in relation to their product Teva DFX, used for iron chelation.
The second defendant is the exclusive licensee of the patents. I will refer to the defendants collectively as “Novartis”. They counterclaim, alleging infringement of both patents. They say Teva DFX is an equivalent of the product protected by each of the patents.
Background to the invention
Since the 1960s iron chelation treatments, removing excess iron from a patient's blood, have been available using a compound called deferoxamine. Removing iron is typically required where the patient has been given a blood transfusion or is suffering from certain blood conditions. Up to the late 1980s the treatments required subcutaneous infusions lasting 8–12 hours at least 5 days a week. Aside from the major inconvenience in its administration and associated issues with patient compliance, deferoxamine had side effects which could be severe and even fatal.
In 1987 a product called deferiprone came into use with dosing needed 3 times a day. This was still far from ideal and there remained side effects.
A third drug, deferasirox was first marketed in the EU in 2006. It came as a dispersible tablet with the brand name Exjade and marked a significant advance since it could be taken just once a day, with correspondingly improved patient compliance. Less helpfully, each dose required between 3 and 7 tablets which had to be dispersed in water or other liquid, creating an unpalatable sludgy drink to be consumed on an empty stomach. Some patients suffered from side effects, principally in the form of nausea, vomiting, diarrhoea or abdominal pain.
The Patents claim a further improvement, being a swallowable film-coated tablet formulation of deferasirox.
Applications to amend the patents
The application for EP 018 was divided out of that for EP 202 and so they share the same priority date, 8 March 2013. Their specifications are almost identical; no material difference was identified during the trial.
Both Patents have been upheld in the Opposition Division of the EPO with amended claims. Appeals are pending. Before this court there are unconditional applications to amend the claims to bring them into line with the claims allowed by the Opposition Division. The proposed amendments to the claims of EP 018 bring them close to those of EP 202. Novartis has also made a conditional application to further amend the claims of both Patents.
Such is the overlap between the specifications and proposed unconditional amendments of the two Patents that for the most part I can treat the two as one and will do so unless I state otherwise.
The skilled team
The parties were agreed that the skilled team consisted of three notional individuals: a clinician, a formulator and a pharmacokineticist. The formulator is the primary addressee since the Patents are teaching new formulations. He or she would be assisted by the clinician's advice on the medical view of iron chelation therapy, clinical requirements and any difficulties with existing therapies. The pharmacokineticist would provide input in the form of pharmacokinetic data relating to the active pharmaceutical ingredient (“API”), e.g. its bioavailability and half-life.
Common general knowledge
The law
Both sides referred to Arnold J's summary of the law on common general knowledge in KCI Licensing Inc v Smith & Nephew plc [2010] EWHC 1487 (Pat) at [105]–[112], approved on appeal: [2010] EWCA Civ 1260 at [6].
It was agreed that the following formed part of the common general knowledge in March 2013.
Clinical CGK
Principally three disorders – thalassaemia, sickle cell anaemia and some blood cancers – require repeated blood transfusions. The introduction of new blood on a large scale will cause a build-up of iron in the patient. The body has no mechanism for excreting iron and its accumulation, if left unchecked, can be fatal. Hence the need to remove excess iron by means of iron chelation therapy.
Thalassaemia is a genetic disorder which inhibits the production of haemoglobin. The severity of the condition varies. A distinction is made between transfusion dependent thalassaemia (“TDT”) and non-transfusion dependent thalassaemia (“NTDT”). Patients requiring 8 transfusions or fewer per year are typically said to have NTDT, those requiring more than 8, and it may be many more than 8, have TDT. Thalassaemia is most common among people of Mediterranean, African (including North African), Southeast Asian and Chinese descent.
Sickle cell anaemia is also a genetic disorder. Red blood cells are produced in a deformed, sickle shape and become rigid in low oxygen environments. They pass less easily through narrow capillaries than do healthy, more malleable red blood cells, giving rise to occlusion of capillaries and ischaemia – the insufficient supply of blood to an organ or tissue. Sickled cells have a typical life span of only 16–20 days, compared with 120 days for healthy cells. This means that the rate of destruction of sickled cells can outpace replenishment, leading to anaemia. The condition is more common in those of African, Middle Eastern, Indian, Caribbean, South and Central American and Mediterranean descent.
Myelodysplastic syndromes (“MDS”) are blood cancers which affect the production of blood cells in the bone marrow. Patients with MDS have an increased risk of developing acute myeloid leukaemia. MDS may be due to genetic mutation and in such instances is most common among patients over 70 years old. Alternatively it may be caused by chemotherapy or radiotherapy inducing damage to bone marrow.
Formulation CGK
The approaches available to a formulator at the priority date were all standard but there were alternatives to be selected. There were at least two textbooks which formed part of the CGK and which would be consulted by a formulator. It was more straightforward to reformulate an existing approved medical product than to formulate for the first time.
The preferred and most common route of administration of a drug is the oral route, either using a swallowable tablet or by taking the drug dissolved or dispersed in a liquid. Swallowable tablets are the most popular among patients. Both swallowable and dispersible tablets are made from powdered, crystalline or granular API, almost always compressed, together with one or more excipients, i.e. binders, disintegrants, lubricants, diluents, glidants or surfactants. All relevant excipients were within the CGK. The Handbook of Pharmaceutical Excipients was also part of the CGK, providing information as to the properties, typical use, incompatibilities and the safety and regulatory status of all excipients used.
If the proportion of API in the tablet is to be high, the formulator must select excipients which maintain the processing attributes of the tablet despite their being present in relatively reduced quantity. To be avoided are excipients which negatively affect the pharmacokinetics of the formulation or which themselves cause adverse side effects.
Two commonly used fillers are microcrystalline cellulose (“MCC”) and lactose. MCC has no significant toxic potential. Patients with lactose intolerance may react adversely to lactose in a formulation.
The two most commonly used surfactants are sodium lauryl sulphate (“SLS”), sometimes called sodium dodecyl sulphate (“SDS”), and Poloxamer 188 aka Pluronic F-68.
Some tablets are coated with a film. The coats fall into three categories. The first are simple water-soluble coats which serve to provide a characteristic colour or other appearance to protect the product from attrition during handling and transportation, to make counterfeiting difficult, to mask the taste of the drug, or all or any of the foregoing.
In the second category are enteric film coats. Such coats are functional in that they prevent dissolution in the stomach where pH is low and allow dissolution in the intestinal tract where pH is higher. This avoids acid degradation of the drug in the stomach and/or protects the stomach from the irritant effect of the drug and/or allows the drug to be preferentially absorbed downstream of the stomach.
The third category consists of sustained release coats. The coat is formulated to slow the rate of release of the drug and to sustain a consistent release over, typically, 6 to 12 hours.
800mg total weight is generally considered the ceiling for a tablet that remains easy to swallow, although using a caplet shape may increase the ceiling to 1000mg. Self-evidently the API load is lower than the total weight.
Dispersible tablets are similarly formed by the compression of API and excipients....
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