The Supreme Court's Decision on Pregabalin

The Pregabalin Molecule

Jane Lambert
The Supreme Court (Lords Mance, Sumption, Reed, Hodge and Briggs) Warner-Lambert Company LLC v Generics (UK) Ltd [2018] UKSC 56 (118 4 Nov 2018)

This was an appeal from the decision of the Court of Appeal in Warner-Lambert Company LLC v Generics (UK) Ltd (t/a Mylan) and Others [2016] EWCA Civ 1006 which I discussed in The Pregabalin Appeal: Generics v Warner-Lambert 17 Oct 2016. In that appeal, the Court of Appeal upheld the decision of Mr Justice Arnold in Generics (UK) Ltd (t/a Mylan) v Warner-Lambert Company LLC   [2016] RPC 3, [2015] EWHC 2548 (Pat), [2015] CN 1499 which I blogged in
The Pregabalin Trial: Generics (UK) Ltd v Warner-Lambert Company LLC 18 Sept 2015 and his refusal to allow the patent to be amended in  Generics (UK) Ltd (t/a Mylan) v Warner-Lambert Company LLC  [2016] RPC 16, [2015] EWHC 3370 (Pat).

The Importance of this Appeal
In the first paragraph of his judgment, Lord Sumption said:

"An important objective of modern pharmaceutical research is the discovery of new medical uses for known molecules. This commonly involves expensive research programmes, which will not be rewarded and will therefore not happen unless patent protection is available. Patent protection for second use medical patents is, however, difficult to accommodate within the traditional scheme of patent law. Traditionally, there were two legal obstacles. First, both the product and the process by which it was prepared were known from the original patent and therefore failed the test of novelty. Secondly, its use for a new therapeutic purpose was not itself patentable because article 52 (4) of the European Patent Convention (the “EPC”) and section 4 (2) of the UK Patents Act 1977 prevented the grant of patents for a method of treatment of the human or animal body."

His Lordship added that the solution had been to allow patents for the use of a substance or composition for the manufacture of a medicament for a specified new and inventive therapeutic application, even in a case in which the process of manufacture as such does not differ from known processes using the same active ingredient.  That solution was known as a "Swiss -style" or a "Swiss-form" claim because the Swiss Patent Office was the first intellectual property office in the workd to adopt it.  The European Patent Office and other intellectual property offices around the world, including the British, followed the Swiss example.

The Swiss-style form was seen as a rather cumbersome and artificial approach and was eventually discontinued after the following paragraph was added to art 54 of the European Patent Convention ("EPC") on 28 June 2001:

"Paragraphs 2 and 3 shall also not exclude the patentability of any substance or composition referred to in paragraph 4 for any specific use in a method referred to in Article 53 (c), provided that such use is not comprised in the state of the art."

Notwithstanding this change to the Convention, there remain a number of patents with Swiss-style claims.  There were unresolved issues such as how the concepts of sufficiency and infringement are to be applied to a patent relating to a specified medical use of a known pharmaceutical compound and those were the subject of this litigation.  As Lord Sumption noted, this is the first time those issues have come before the courts of the United Kingdom.

Understanding this Appeal
For those who are new to this case and who do not have an extensive knowledge of patent law, a good place to start would be the Court's press release of 14 Nov 2018.  They can then watch a video of Lord Sumption's summary of the Court's written decision and the judges' reasons for reaching it.  That should help them understand the 92-page judgment and the videos of the parties' arguments which were heard between the 12 and 15 Feb 2018.  I hope that my case notes on the trial and appeal which I mentioned above will also help with the background.  

The Facts
Warner Lambert-Company LLC ("Warner-Lambert") is a subsidiary of Pfizer Inc ("Pfizer"). One of Pfizer's most successful products is pregabalin which it markets in the UK under the trade mark "Lyrica".  Pregabalin was originally used for the treatment of epilepsy and similar disorders and it was protected in this country by European patent (UK) number 0641330.  It was later found that it could also be used to alleviate pain.  Warner-Lambert applied to the US Patent and Trademark Office for a patent for isobutylgaba and its derivatives for the treatment of pain on 24 July 1996.  The corresponding European patent is EP0934061 and it is that patent that is the subject of the litigation.  

EP 0641330 expired on 17 May 2013 leaving generics manufacturers such as Mylan (Generics (UK) Ltd) and Actavis (Actavis Group PTC EHF) free to make and sell pregabalin for its original use. The problem for those companies was that EP 0934061 restricted its use for pain relief. The corresponding problem for Pfizer was that doctors prescribed pregabalin generically for pain relief which meant that Mylan's or Actavis's products were likely to be supplied instead of Pfizer's.  

The Litigation
Mylan and Actavis sued Warner-Lambert for the revocation of EP 0934061 on grounds of obviousness and insufficiency while Warner-Lambert sued  Mylan and Actavis for patent infringement.  At trial, Mr Justice Arnold rejected the allegations of obviousness but revoked several of the claims on grounds of insufficiency.   Had those claims been valid he would have dismissed Warner-Lambert's action for infringement. At a later hearing, the judge rejected an application to amend the patent as an abuse of the process of the court.  The Court of Appeal upheld the decisions of the judge below though in relation to infringement on slightly different grounds.  Warner-Lambert appealed to the Supreme Court against the Court of Appeal's findings on invalidity while Mylan and Actavis cross-appealed contending that none of the patent claims in respect of neuropathic pain was valid.

Third Party Submissions
In addition to argument from the parties to the appeal, the Supreme Court received submissions from the Secretary of State for Health, the European Federation of Pharmaceutical Industries and AssociationsThe Association of the British Pharmaceutical Industry, The Chartered Institute of Patent Attorneys, The BIA, Medicines for Europe, British Generic Manufacturers AssociationPharmaceutical Services Negotiating Committee, National Pharmacy Association and Fionan McCaul.

The Decision
By a majority, the Supreme Court dismissed Warner-Lambert's appeal on invalidity and the refusal to allow it to amend and allowed the cross-appeal.

The Issues
Although it was not necessary for the Court to consider all those issues in view of its decision on invalidity it addressed the following which Lord Sumption listed at paragraph 14:

"(1) The construction of the claims, and in particular Claim 3 (neuropathic pain).
(2) The sufficiency of the disclosure in the specification.
(3) Amendment and abuse of process.
(4) The test for infringement of a patent for a manufacturing for a limited use."

The Construction of Claims
Although Warner-Lambert contended that all the claims were valid, the parties were particularly concerned with claim 3.   That was the use of pregabalin for the preparation of a pharmaceutical composition for treating neuropathic pain.  At paragraph [6] of his judgment, Lord Sumption noted that neuropathic pain is notoriously difficult to treat because treatments for other kinds of pain such as non-steroidal anti-inflammatories are ineffective.

Lord Sumption noted that there are two kinds of neuropathic pain: "peripheral neuropathic pain, which arises from damage or dysfunction of the peripheral nervous system; and central neuropathic pain, which is rarer and arises from damage or dysfunction of the central nervous system, for example as a result of a stroke."  The question for the Court was whether “neuropathic pain” in its context meant all neuropathic pain, including central neuropathic pain as Actavis and Mylan contended, or only peripheral neuropathic pain as Warner-Lambert argued.

Both the trial judge and Court of Appeal had held that the words "neuropathic pain" connoted both kinds of neuropathic pain.   Warner-Lambert contended that that was the wrong approach for the following reasons:

"1. There was no settled usage among those skilled in the art at the priority date as between the broad and the narrow meaning, so that its meaning in the context of the Patent has to be derived from its detailed contents.
2. The specification, particularly in paragraphs 3 and 6, points to the narrower construction, both as a matter of definition and because it cites examples of peripheral neuropathic pain only, making no mention of the main examples of central neuropathic pain, so that the phrase neuropathic pain in Claim 3 should be construed eiusdem generis.
3. In the event that (1) and (2) leave the meaning ambiguous, the validating principle should be applied, in favour of the narrow construction."

Lord Briggs (with whom Lord Sumption, Lord Reed and Lord Hodge agreed) accepted the first proposition up to a point.   In accordance with s.125 of the Patents Act 1977, His Lordship compared paragraphs 3 and 6 of the description with the full list of claims and found that the language was inclusive and not exclusive.  He concluded that:

"Paragraphs 3 and 6 are in my view an example of torrential drafting designed to make the widest possible assertions of the utility of pregabalin for pain relief, ahead of a set of claims deliberately designed to go first for the broadest classes of use monopoly, (Claims 1 to 3), with more narrowly drawn fall-back claims (Claim 4 and following) if the broad classes should prove invalid."

He found no ambiguity but in any even rejected the validating principle - a principle well established in contracts and the interpretation of subordinate legislation that, where possible, a construction should be preferred which results in the relevant claim being treated as valid (ut res magis valeat quam pereat) -was unnecessary and inappropriate for upholding monopolies.  In Lord Briggs's view, that was particularly true of second medical use patents.    He said at paragraph [98]:

"There is a positive public interest in the active ingredient becoming available to be used freely for the original use after the patent for that use has expired, because that is the quid pro quo for the prior 20 years monopoly granted to the patentee. It follows that there is a particular need for legal certainty in fixing the dividing line between the original use and the new one. There are therefore sound reasons of policy for requiring clarity in the claims of patents of this kind. None of this means that claims are to be construed with a predisposition to find fault, or the description read with a mind that is not willing to learn. But it does require that an issue as to the construction of a claim should be addressed, as far as possible, by deciding what it really does mean, rather than by too easily accepting that there is ambiguity, and resolving it by inventing a meaning which saves the claim from invalidity."

Lord Mance said at paragraph [190] that he had been tempted by Warner-Lambert’s case that, on a true construction of the patent, Claim 3 should be understood as limited to peripheral neuropathic pain but he reminded himself that patents have to be construed in accordance with s.125 of the Patents Act, art 69 of the EPC and the Protocol on the Interpretation of Article 69 EPC.  He added:

"All my colleagues are persuaded that the skilled person would understand Claim 3 as extending to central as well as peripheral neuropathic pain. Their reasonable opinion carries weight. I am not in the circumstances prepared to press my reservations to a conclusion that they are wrong."

The Sufficiency of the Disclosure in the Specification
Lords Sumption, Reed and Briggs held that the disclosure in the specification supported the claims so far as they extended to inflammatory pain but not to any kind of neuropathic pain with the result that claims 1 and 3 of the patent failed for insufficiency, Consequently, Warner-Lambert’s appeal had to be dismissed and Actavis’s and Mylan’s cross-appeal allowed.

Starting from first principles, Lord Sumption observed that a patent is a reward for dedicating an invention to the public.  It follows that the protection afforded by the claims in a patent specification should be commensurate with the description of the invention.  An applicant for a patent is required by s.14 (3) of the Patents Act 1977 or art 83 of the EPC to disclose the invention in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art.  In the case of most inventions, the applicant has to explain how a product can be made or a process can be used but all that a skilled addressee needs to know about a second medical use is the additional use to which a known preparation is to be put.  That opens the possibility of abuse as there is nothing to stop anyone claiming any number of additional uses for known compounds without taking any steps to ascertain whether their claims are true. "For that reason" Lord Sumption reasoned, "both Arnold J and the Court of Appeal concluded that it was not enough simply to refer to a known compound and assert that it was efficacious for treating a specified condition. The patentee must disclose some reason for regarding this assertion as 'plausible.'”

One of the points of difference in this litigation was whether the courts below had been correct.  Warner-Lambert argued that the only criterion of sufficiency was whether the invention could be performed by a skilled person.  Alternatively, it disputed that it was necessary to show that every aspect of a claim was plausible in order to be valid and that it could rely on evidence that might come to light after the application for the patent had been filed.

Lord Sumption considered the case law of the Boards of Appeal and the English courts and expounded the following principles at para [37]:

"Plausibility is not a term of art, and its content is inevitably influenced by the legal context. In the present context, the following points should be made. First, the proposition that a product is efficacious for the treatment of a given condition must be plausible. Second, it is not made plausible by a bare assertion to that effect, and the disclosure of a mere possibility that it will work is no better than a bare assertion. As Lord Hoffmann observed in Conor Medsystems Inc v Angiotech Pharmaceuticals Inc [2008] RPC 28, para 28, “it is hard to see how the notion that something is worth trying or might have some effect can be described as an invention in respect of which anyone would be entitled to a monopoly”. But, third, the claimed therapeutic effect may well be rendered plausible by a specification showing that something was worth trying for a reason, ie not just because there was an abstract possibility that it would work but because reasonable scientific grounds were disclosed for expecting that it might well work. The disclosure of those grounds marks the difference between a speculation and a contribution to the art. This is in substance what the Technical Board of Appeal has held in the context of article 56, when addressing the sufficiency of disclosure made in support of claims extending beyond the teaching of the patent. In my opinion, there is no reason to apply a lower standard of plausibility when the sufficiency of disclosure arises in the context of EPC articles 83 and 84 and their analogues in section 14 of the Patents Act. In both contexts, the test has the same purpose. Fourth, although the disclosure need not definitively prove the assertion that the product works for the designated purpose, there must be something that would cause the skilled person to think that there was a reasonable prospect that the assertion would prove to be true. Fifth, that reasonable prospect must be based on what the TBA in SALK (para 9) called “a direct effect on a metabolic mechanism specifically involved in the disease, this mechanism being either known from the prior art or demonstrated in the patent per se.” Sixth, in SALK, this point was made in the context of experimental data. But the effect on the disease process need not necessarily be demonstrated by experimental data. It can be demonstrated by a priori reasoning. For example, and it is no more than an example, the specification may point to some property of the product which would lead the skilled person to expect that it might well produce the claimed therapeutic effect; or to some unifying principle that relates the product or the proposed use to something else which would suggest as much to the skilled person. Seventh, sufficiency is a characteristic of the disclosure, and these matters must appear from the patent. The disclosure may be supplemented or explained by the common general knowledge of the skilled person. But it is not enough that the patentee can prove that the product can reasonably be expected to work in the designated use, if the skilled person would not derive this from the teaching of the patent."

As for Warner-Lambert's alternative arguments, plausibility was not a distinct condition of validity but part of the requirement of sufficient disclosure, As Lord Sumption had already observed, the breadth of a claim must correlate to the extent of the disclosure.  With regard to the second, His Lordship thought that an invention that relies on evidence of plausibility that comes to light after the date of filing is unlikely to have been disclosed sufficiently.

Applying these principles to the evidence that had been before the trial judge, Lord Sumption concluded at [54] that "the disclosure did not contribute any knowledge of the art capable of justifying a claim to a monopoly of the manufacture of pregabalin for the treatment of neuropathic pain of any kind." Accordingly, claim 3 and other claims relating to neuropathic pain failed for insufficiency.

Lord Hodge and Lord Mance took a different view.   They agreed with the majority that there is no onus on an objector to show that the implied assertion of therapeutic efficacy is implausible, that a patentee must disclose in his or her patent the contribution to the art that justifies a monopoly and that the specification must disclose some scientific reason for thinking that the medicament might well have the claimed therapeutic effect but they did not believe it necessary for a patentee to demonstrate within its patent a prima facie case of therapeutic efficacy.

In their view the EPO's case law requires that the therapeutic effect of the medication appears plausible from the data in the patent interpreted in the light of the common general knowledge, (b) do not require that the patent discloses experimental evidence to demonstrate that plausibility unless there is an allegation, supported by sufficient evidence, that the invention does not work, but (c) allow the plausibility to be reinforced by considering evidence which post-dates the patent (although later-published data are not admissible if they alone render the therapeutic effect plausible), (d) take account of the ease with which the therapeutic effect can be ascertained using straightforward tests which are known in the prior art, and (e) where the data in the specification have made the claimed therapeutic effect plausible, place a burden on an objector to substantiate doubt that the desired effect can be achieved.

Those justices believed that the Court of Appeal and trial judge had been right and would have dismissed the cross-appeal.

Amendment and Abuse of Process
After Mr Justice Arnold had delivered judgment, Warner-Lambert sought permission to amend claim 3 of the patent by adding the words “caused by injury or infection of peripheral sensory nerves”.  The judge refused permission on the ground that it would give rise to issues of clarity, added matter and sufficiency requiring a further trial, that that could have been avoided by an application to amend before or even during the trial and that it was an abuse of process to leave the application until after the handing down of judgment and the Court of Appeal agreed. 

Warner-Lambert appealed on the ground that the principle upon which Mr Justice Arnold denied permission fettered his discretion under o s.75 of the 1977 Act and art 138 (3) of the EPC, that the judge had found the claim to be partially valid and the amendment would have given effect to his finding and any prejudice to Actavis and Mylan could have been compensated in costs.

In refusing permission to amend, Mr Justice Arnold followed the Court of Appeal's judgments in Nikken Kosakusho Works and another v Pioneer Trading Company and another  [2006] FSR 4, [2005] EWCA Civ 906 which drew a distinction between applications to amend before judgment and afterwards and Nokia GmbH v IPCOM GmbH & Co KG  [2011] Bus LR 1488, [2011] FSR 15, [2011] EWCA Civ 6 which held that the trial was the appropriate time to raise amendments.  Lord Briggs saw no reason for the Supreme Court to take a different view.

Lord Sumption and Lord Reed began their analysis by observing that a Swiss-style claim is a process claim and not a product claim.  Lord Sumption summarized it at paragraph [63] as a claim for a monopoly of preparation or manufacture of a known product for a new designated purpose. It is not a claim for a monopoly of the subsequent use of the product for that purpose.   Any allegation of infringement must be based on s.60 (1) (c) of the Patents Act 1977:

“60. (1)   Subject to the provisions of this section, a person infringes a patent for an invention if, but only if, while the patent is in force, he does any of the following things in the United Kingdom in relation to the invention without the consent of the proprietor of the patent, that is to say -
(c) where the invention is a process, he disposes of, offers to dispose of, uses or imports any product obtained directly by means of that process or keeps any such product whether for disposal or otherwise."

It was common ground that there must be a mental elemnet because the claim requires that the manufacture of the product must be for a partiular purpose.  That was a problem because doctors prescribe drugs generically and not by reference to a drug trade mark or the condition for which the drog is prescribed.  In the absence of an indication to the contrary, pharmacists will dispense a generic medicament where one is availanble rather than a branded one because the former are cheaper.  Warner-Lambert argued that a patent was infringed if was foreseeable to a manufacturer that a more than de minimis amount of it would in due course be used for the treatment of neuropathic pain. Actavis and Mylan argued  that the test of a manufacturer’s intention was subjective and that the manufacturer must make the product with intent to target the patent-protected market.

Lord Sumption considered both of those tests and also the test proposed by the Court of Appeal.  His Lordship and Lord Reed preferred what Lord Sumption called an "outward presentation test", that is to say one in which the purpose of manufacture is deduced from its formulation and dosage, packaging and labelling and the patient information leaflet which will identify the conditions for which the product is intended. Lord Sumption acknowledged that that test was not perfect but regarded it at paragraph [86] as the least imperfect. Lord Briggs and Lord Hodge preferred the subjective test offered by Actavis and Mylan and applied by the trial judge.  Lord Mance criticized both the subjective and objective tests. While he did not express a definitive view as the issue was obiter he appeared to incline towards Lord Sumption's outward presentation test.

Warner-Lambert had pleaded an alternative case under s.60 (2):

"Subject to the following provisions of this section, a person (other than the proprietor of the patent) also infringes a patent for an invention if, while the patent is in force and  ithout the consent of the proprietor, he supplies or offers to supply in the United Kingdom a person other than a licensee or other person entitled to work the invention with any of the means, relating to an essential element of the invention, for putting the invention into effect when he knows, or it is obvious to a reasonable person in the circumstances, that those means are suitable for putting, and are intended to put, the invention into effect in the United Kingdom."

Lord Sumption dealt with it shortly.  Claim 3 was for the manufacture of a product for a particular purpose and not the use of the product for such purpose.  The protection afforded by a second medical use patent was very limited and did not extend to the dispensing of a generic drug by a pharmacist.  Lord Briggs arrived at a similar conclusion at paragraph [136], Lord Hodge agreed with both Lord Sumption and Lord Briggs at [186] and Lord Mance expressed a similar view at [197].

As most Swiss-form patents will be approaching the end of their term there are unlikely to be many more cases of this kind. However, there is a lot of material of more general application. There will continue to be sufficiency and construction issues with second medical use patents. There will be similar discussions on how a second medical can be infirnged.  The link berween disclosure and claims is of general application. So, too, wil the discretion to allow patents to be amended after a full lenth trial. Anyone wishing to discuss this case further should call me on +44 (0)20 7404 5252 during office hours or send me a message through my contact form.


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