Actavis UK Ltd v Novartis AG
| Jurisdiction | England & Wales |
| Judge | Lord Justice Jacob,Lord Justice Stanley Burnton,Lord Justice Lloyd |
| Judgment Date | 17 February 2010 |
| Neutral Citation | [2010] EWCA Civ 82 |
| Docket Number | Case No: A3/2009/0675 |
| Court | Court of Appeal (Civil Division) |
| Date | 17 February 2010 |
[2010] EWCA Civ 82
IN THE HIGH COURT OF JUSTICE
COURT OF APPEAL (CIVIL DIVISION)
ON APPEAL FROM THE HIGH COURT OF JUSTICE
CHANCERY DIVISION PATENTS COURT
The Hon Mr Justice Warren
Before: The Rt Hon Lord Justice Jacob
The Rt Hon Lord Justice Lloyd
and
The Rt Hon Lord Justice Stanley Burnton
Case No: A3/2009/0675
HC 07 C 01753
Richard Meade QC and Mark Chacksfield (instructed by Bristows)
for the Appellant/Defendant
Roger Wyand QC and Piers Acland (instructed by Bird & Bird)
for the Respondent/Claimant
Hearing dates: 27/28 January 2010
Lord Justice Jacob:
Novartis appeals Warren J's decision of 16 th January 2009, [2009] EWHC 41 (Ch), that its EP (UK) 0948320 is invalid for obviousness.
Mr Richard Meade QC (replacing Mr Richard Arnold QC following his appointment as a judge) and Mr Mark Chacksfield appear for Novartis. Actavis, the respondent, is represented as it was below by Mr Roger Wyand QC and Mr Piers Acland.
The Patent and its background
The Patent, whose priority date is October 1996, is for a sustained release formulation of fluvastatin. In 1996 fluvastatin was a well-known statin available in an immediate release formulation consisting of capsules containing 20 or 40 mg of the sodium salt. By that date there was a strong and well-known school of thought in favour of a dosage regime consisting of a 40 mg capsule to be taken twice a day.
Also at the priority date there was extensive knowledge of sustained release formulations generally. The Patent puts it this way under the heading “background art”:
[0002] In recent years there has been a large increase in the development and use of sustained-release tablets which are designed to release the drug slowly after ingestion. With these types of dosage forms, the clinical utility of drugs can be improved by means of improved therapeutic effects, reduced incidence of adverse effects and simplified dosing regimens.
Mr Meade suggested that this paragraph should be read as specific to the invention and was saying that the invention would lead to improved therapeutic effects, reduced adverse effects and simplified dosing regimens. But it is clear that it is no more than a general background statement about the increasing use of sustained release drugs and the reasons therefor. It is saying you may or may not get improved therapy (for one or other or both reasons) and you will (obviously) get a simplified dosing regime. That was common general knowledge.
The Patent then explains that by “sustained release” is meant a release which takes typically more than 3 and less than 30 hours. It then points out that there are several different known types of sustained release formulation and describes three types: use of an insoluble matrix, an eroding matrix, and release through a semipermeable membrane. Just before it describes these it says:
[0004] …. The actual approach taken for a given drug depends inter alia on the physical chemical properties of the drug. One of these is the solubility of the drug, which has a major impact on the pharmaceutical formulation strategy. A high solubility of the drug substance may induce problems, as discussed further below.
The Patent later returns to high solubility and the problems it may cause:
[0008] As mentioned above, the drug release from sustained release formulations is related to the drug solubility. The higher the water solubility of the drug, the faster the drug release and the shorter the duration of drug delivery. A fast release of the drug might mean that the desired rate and duration can not be obtained and that the beneficial effects of sustained release administration are lost. Thus, a special challenge is met when trying to formulate water soluble substances for sustained release formulations. One way to try to solve this problem would be to include large amounts of slow release excipients in the formulation. However, this approach has drawbacks such as increased costs and increased size of the formulation. Increased physical size of the dosage form may present problems for some patients, since the tablet will be more difficult to swallow. Another possibility is to use a less water soluble salt. However, such a change requires a more extensive development work and may also lead to bioavailability problems due to incomplete dissolution.
This is all perfectly general, still under the general heading “Background, sustained release formulations.”
The Patent then goes on to discuss statins generally and then fluvastatin, which it acknowledges is known. It then suggests that its solubility is so great that one would expect problems in creating a sustained release formulation:
[0012] Fluvastatin is a water soluble drug. For example, the solubility of the sodium salt of fluvastatin in water extends to more than 50 g/l. Biopharmaceutical requirements of a sustained release product of this water soluble drug would then at first sight impose formulation problems as discussed above.
The Patent then explains why, in relation to each of the types of sustained release formulation, high solubility causes problems.
The Patent then says what problem the invention is aimed at:
[0015] Consequently, there is a need for pharmaceutical formulations of HMG-CoA reductase inhibitors which avoid the above mentioned drawbacks and are possible to prepare, e.g., without including large amounts of slow release excipients or the use of highly advanced techniques. Preferably, the production costs of the formulations should be low.
Clearly in context the “need” referred to is a need for slow-release formulations, not merely any kind of formulation. That is the problem the invention of the Patent seeks to overcome
The clear message of all this is simple: there is a need for a sustained release formulation of fluvastatin but its solubility is so high that there is at least a perception that any of the conventional methods would not work.
The Patent now moves on to “Disclosure of the invention”. The first paragraph under this heading sets out what the inventors claim to have discovered and the second the consequential invention:
[0017] It has surprisingly been found that sustained-release compositions, comprising fluvastatin as a water soluble salt, exhibit particularly favorable release characteristics such as unexpectedly long duration and slow rate of drug release. In the present context, the term “water soluble” should be understood as a solubility of more than 30 mg/ml in water at +37°C.
[0018] Consequently, the present invention provides a pharmaceutical composition for sustained release comprising a water soluble salt, preferably the sodium salt, of f1uvastatin as an active ingredient. The sustained-release f1uvastatin compositions for which these favorable properties are obtained are selected from the group comprising matrix formulations, diffusion-controlled membrane coated formulations; and combinations thereof.
This is saying that, contrary to what the skilled person would have thought from its high solubility, you can in fact make sustained release formulations of fluvastatin by using any of the three conventional techniques already acknowledged.
After some detail which does not matter the Patent says this, and only this, about the utility of the invention:
[0027] The pharmaceutical formulations according to the invention are useful for lowering the blood cholesterol level in animals, in particular mammals, e.g. humans. They are therefore useful as hypercholesterolemic and anti-atherosclerotic agents.
The Patent presents some data which shows that fluvastatin is released more slowly from a sustained release formulation than two other, less soluble drugs. This is done “to exemplify the unexpectedly favorable properties of fluvastatin in matrix and membrane coated formulations.”
It is worth noting that there is no comparison with a drug which has such a high solubility that it cannot put into a sustained release form.
Examples of sustained release formulations are given (nothing turns on these) and then the Patent comes to its claims. Although there were lurking in the background some arguments about other claims, the only claim which really matters is claim 1, as permitted to be amended by Warren J:
A sustained release pharmaceutical composition comprising a water soluble salt of fluvastatin as active ingredient and being selected from the group consisting of matrix formulations, diffusion-controlled membrane coated formulations and combinations thereof, wherein the sustained release formulation releases the active ingredient over more than 3 hours.
Obviousness: the Law
The statutory question is beguilingly simple and is set out in the European Patent Convention, enacted by the Patents Act 1977. The Convention says:
Art 52 Patentable Inventions
(1) European patents shall be granted for any inventions which are susceptible of industrial application, which are new and which involve an inventive step.
Art 56 Inventive Step
An invention shall be considered as involving an inventive step if, having regard to the state of the art, it is not obvious to a person skilled in the art.
So at bottom the question is simply whether the invention is obvious. Any paraphrase or other test is only an aid to answering the statutory question.
In our courts we have found a structure helpful to approach – not answer—the question. In its latest refinement (see Pozzoli v BDMO [2007] FSR 37) it runs as follows:
(1)(a)...
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