Warner-Lambert Company LLC v Generics (UK) Limited (t/a Mylan) and ors
[2018] UKSC 56
Michaelmas Term
[2018] UKSC 56
On appeal from: [2016] EWCA Civ 1006
| JUDGMENT |
Warner-Lambert Company LLC (Appellant) v Generics (UK) Ltd t/a Mylan and another (Respondents) Warner-Lambert Company LLC (Respondent) v Generics (UK) Ltd t/a Mylan and another (Appellants) Warner-Lambert Company LLC (Respondent) v Generics (UK) Ltd t/a Mylan and another (Appellants)
before
Lord Mance
Lord Sumption
Lord Reed
Lord Hodge
Lord Briggs
JUDGMENT GIVEN ON
14 November 2018
Heard on 12, 13, 14 and 15 February 2018
Appellant 1st Respondent (Generics
(UK) Ltd t/a Mylan)
Lord Pannick QC Adrian Speck QC
Thomas Mitcheson QC Pushpinder Saini QC
Miles Copeland Kathryn Pickard Tim Austen
(Instructed by Allen & (Instructed by Taylor
Overy) Wessing LLP)
2nd Respondent (Actavis
Group PTC EHF)
Adrian Speck QC
Pushpinder Saini QC
Kathryn Pickard
(Instructed by Powell
Gilbert LLP)
Interveners
(1) SS Health Michael Silverleaf QC Nicholas Saunders (2) EFPIA
Christopher Stothers Written submissions only Laura Whiting Paul Abbott (3) ABPI
Christopher Stothers Written submissions only Laura Whiting Paul Abbott (4) CIPA
In-house Written submissions only (5) BIA
In-house Written submissions only (6) Medicines for Europe
Catherine Drew, Written submissions only (Pinsent Mason LLP) (7) British Generic
Christopher Sharp, Written submissions only Manufacturers Association (Pinsent Mason LLP) (8) PSNC
In-house Written submissions only (9) National Pharmacy
(Charles Russell Speechlys Written submissions only Association LLP) (10) Mr Fionan McCaul
In person Written submissions only LORD SUMPTION: (with whom Lord Reed agrees)
Second medical use patents
1. These proceedings raise, for the first time in the courts of the United Kingdom, the question 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. 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.
2. As is now well known, in 1984 the Swiss Federal Intellectual Property Office issued a statement of practice that it would be prepared to grant patents for second
use medical patents in the following form: “the use of compound X in the
manufacture of a medicament for the treatment of indication Y”: [1984] OJ EPO 581. Hence the expression “Swiss-form patents” for patents granted in this form.
The Enlarged Board of Appeal of the European Patent Office adopted this approach shortly afterwards in EISAI/Second Medical Indication G 05/83 [1979-85] EPOR B241. It ruled, at para 23, that it was
“legitimate in principle to allow claims directed to 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.”
Swiss-form patents were not product patents, but purpose-limited process patents. They surmounted both obstacles because the invention is identified as neither a product nor a method of treatment but a manufacturing process for a novel purpose.
3. This development responded to a real problem, namely the difficulty of obtaining patent protection for second uses that may have been truly inventive and involved costly research. But it has given rise to formidable analytical problems as a result of the need to apply to Swiss-form patents a statutory scheme which was not designed to accommodate them. For this reason they were regarded with suspicion as intellectually impure by patent lawyers in the United Kingdom. In John Wyeth
and Brother Ltd’s Application [1985] RPC 545, they were adopted with express
misgivings by the Patents Court in the interests of uniformity among states party to the EPC. But in spite of the misgivings, they have achieved a secure place in United Kingdom patent law, and neither party to this appeal challenges them in principle. Some of the difficulties associated with them were resolved when the EPC was revised in November 2000 to provide for (among other things) the grant of purpose- limited product patents: see article 54(5) of the revised Convention. Corresponding changes were made to the Patents Act 1977 by the Patents Act 2004. Once these changes came into effect, in 2011, Swiss-form patents ceased to be issued by the European Patent Office. EPC 2000 patents give rise to difficulties of their own, some of which are very similar. But this appeal is not concerned with them.
The patent in suit
4. Warner-Lambert is a company in the Pfizer Group. It is the proprietor of European Patent No 0641330 for Isobutylgaba for the treatment of seizure disorders, notably epilepsy. Pregabalin is a derivative of Isobutylgaba, which is also referred to by its chemical name (S)-3-(aminomethyl)-5-methylhexanoic acid. It is marketed
by Warner-Lambert under the brand name “Lyrica”. Patent No 0641330 expired in
the United Kingdom on 17 May 2013.
5. The present appeal concerns a second European Patent, EP(UK) No 0934061,
entitled “Isobutylgaba and its derivatives for the treatment of pain”, with a priority
date of 24 July 1996 (“the Patent”). The claims of the Patent are all purpose-limited.
Those which are principally relevant are Claims 1, 2 and 3, which are in the following terms:
“1. Use of (S)-3-(aminomethyl)-5-methylhexanoic acid or a
pharmaceutically acceptable salt thereof for the preparation of
a pharmaceutical composition for treating pain.
2. Use according to Claim 1 wherein the pain is
inflammatory pain.
3. Use according to Claim 1 wherein the pain is
neuropathic pain.”
It is common ground that the skilled person to whom the Patent is deemed to be addressed is a team consisting of a neuroscientist and a clinician specialising in the treatment of pain. To explain what the skilled team would understand by the terms used in the claims, it is necessary to say something about what was known at the priority date about the physiology of pain.
6. The second edition of Classification of Chronic Pain Syndromes and Definitions of Pain Terms, published in 1994 by the International Association for
the Study of Pain, defined “pain” very broadly. It is “an unpleasant sensory and
emotional experience associated with actual or potential tissue damage or described
in terms of such damage.” At the priority date, pain was classified into a number of
different types. The distinctions between them were neither absolute nor consistently understood. But it was generally recognised that pain fell into two broad categories: nociceptive and neuropathic pain.
Nociceptive pain is produced by noxious external stimuli such as heat, extreme cold, intense mechanical pressure or chemicals. These stimuli stimulate fibres known as nociceptors, which transmit impulses via the spinal cord to the brain, where they are perceived as pain. Nociceptive pain has a bio-protective function. It alerts the brain to the presence of noxious stimuli so that appropriate avoidance measures can be taken. This type of pain resolves with treatment of the underlying cause.
Inflammatory pain is a type of nociceptive pain. The body’s response to an
injury involves the release of chemical mediators which increase the sensitivity of nociceptors causing pain both at the site of the injury or in the surrounding area. Like other nociceptive pain, inflammatory pain resolves with the treatment of the underlying cause. In 1996, well known and efficacious treatments were available for treating inflammatory pain. They included analgesics (eg paracetamol), non-steroidal anti-inflammatory drugs (eg aspirin, ibuprofen) and opioids of various strengths.
Neuropathic pain, unlike nociceptive/inflammatory pain, is pathological. It has no bio-protective function. It is caused by damage to the nervous system
itself. Neuropathic pain was defined in the second edition of the IASP’s Classification of Chronic Pain as “pain initiated or caused by a primary lesion or dysfunction of the nervous system.” The nervous system comprises
the central nervous system, ie the brain and spinal cord, and the peripheral nervous system, ie the nerves outside those structures. Critical to the issues in these proceedings is the distinction between 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, multiple sclerosis or spinal cord injury. The symptoms of neuropathic pain (of either kind) are more severe than those of nociceptive/inflammatory pain. They include perceptions of burning, shooting pain and electric shock pain. Moreover, unlike nociceptive/inflammatory pain, neuropathic pain is persistent, sometimes for years or for life. It was in 1996, and still is, notoriously difficult to treat neuropathic pain. In particular, treatments which were efficacious against nociceptive/inflammatory pain, such as non- steroidal anti-inflammatory drugs, were not regarded as effective for the treatment of neuropathic pain.
Finally, it is necessary to mention allodynia and hyperalgesia, two terms which feature prominently in the evidence. Both are symptoms of pain. Allodynia is pain experienced in response to a stimulus that would not normally be expected to cause pain. Hyperalgesia is an increased response to a thermal or mechanical stimulus that one would normally expect to be painful, but less so. It may be primary hyperalgesia (occurring at the site of an injury) or secondary hyperalgesia (occurring in the area surrounding the site of the injury).
7. Lyrica received a marketing authorisation in the European Union for the treatment of peripheral neuropathic pain and epilepsy in July 2004 and for the treatment of central neuropathic pain in September 2006. It is also authorised for the treatment of generalised anxiety disorder (or GAD). Lyrica is one of four first-line treatments recommended by NICE for neuropathic pain. It is one of the Pfizer
Group’s most successful drugs in the United Kingdom.
The present proceedings
8. Generics (UK) Ltd (trading as Mylan) and Actavis Group PTC EHF are pharmaceutical companies that are mainly engaged in marketing generic pharmaceutical products. Actavis markets a generic pregabalin product under the
brand name “Lecaent”, which was launched in February 2015. Caduceus Pharma
Ltd hold the marketing authorisation for Lecaent in the European Union. For
convenience I will refer to Actavis and Caduceus together as “Actavis”. Lecaent is
marketed under a “skinny label”, ie for the treatment of some indications only. The
Summary of Product Characteristics prepared for the purpose of obtaining marketing authorisation and the Patient Information Leaflet included in the packet state that the conditions for which Lecaent is indicated are epilepsy and GAD, for which patent protection has expired.
9. In these proceedings, Mylan and Actavis claimed the revocation of the Patent
on the ground of lack of inventive step and insufficiency, and Warner-Lambert
claimed against Actavis for infringement of Claims 1 and 3.
10. The judge, Arnold J [2015] EWHC 2548 (Pat), rejected the arguments based on lack of inventive step, and these are no longer in issue. But he held that Claim 1 (pain) and Claim 3 (neuropathic pain) were invalid. In summary, this was because he found that there was sufficient disclosure in the specification to support the claim that pregabalin was efficacious in the treatment of inflammatory pain and peripheral neuropathic pain, but not central neuropathic pain. Since the judge construed Claim 1 as extending to all pain and Claim 3 as extending to all neuropathic pain, including central neuropathic pain, both claims failed for insufficiency. It followed that Claim 4 (cancer pain), Claim 6 (phantom limb pain) and Claim 14 (fibromyalgia), all of
which in the judge’s view either were or could involve central neuropathic pain,
failed on the same ground. Claim 13 (idiopathic pain, ie pain of unknown origin) failed on a more fundamental ground: there was nothing whatever in the
specification which appeared to support it. The result of the judge’s decision was to
remove patent protection for the manufacture of pregabalin for the treatment of neuropathic pain, save for those subsidiary claims directed solely to peripheral neuropathic pain. The judge rejected as an abuse of process an application after judgment to amend the patent by narrowing the claims in terms which would arguably have made them valid.
11. The Court of Appeal (Floyd, Kitchin and Patten LJJ) [2016] EWCA Civ 1006
upheld the judge’s findings, except that they considered that fibromyalgia was not
neuropathic pain but an idiopathic pain. Since they agreed that the claim relating to idiopathic pain was invalid, this made no difference to the outcome. The Court of Appeal upheld his decision on abuse of process.
12. It followed that infringement did not arise, neither of the claims said to have been infringed being valid. The judge and the Court of Appeal differed on the test for infringement in a case where the monopoly conferred by the patent was confined to manufacture for a particular use. The judge held that if Claims 1 and 3 had been valid, they would not have been infringed. The Court of Appeal held that he had applied the wrong test, and declined to decide the point in the absence of the findings of fact which, on their preferred test, would have been required.
13. On the present appeals, Warner-Lambert contend that all the claims of the Patent were valid, although they have made no effort to justify Claim 1 (pain), Claim 13 (idiopathic pain) or Claim 14 (fibromyalgia). Their real object is to establish the validity of their claims in relation to neuropathic pain or, if they cannot achieve that, then at least those claims which relate to peripheral neuropathic pain, which is by far the commonest type. Actavis and Mylan for their part cross-appeal in support of their case that none of the claims in relation to neuropathic pain are valid. The only claims whose validity they accept are those which are limited to inflammatory pain, for which there is currently no marketing authorisation.
14. In these circumstances, the issues in the present appeal fall under four heads:
(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.
For reasons which will become apparent, on the view which this court takes of the law, not all of these issues arise in the circumstances of this case. However all of them raise unresolved questions of considerable general importance, which have been fully argued not only by the parties, but by the Secretary of State and other interveners potentially affected by statements of principle in the courts below. It is therefore proposed to deal with all of them.
15. Since we are not all agreed on every point, it may assist if I summarise the conclusions of the court at the outset:
(1) The court unanimously affirms the view of both courts below that Claim 1 extends to all pain and Claim 3 to all neuropathic pain, whether
peripheral or central. It unanimously affirms Arnold J’s decision rejecting Warner-Lambert’s application to amend the patent so as to limit the scope of
these claims.
(2) The court holds by a majority (Lord Sumption, Lord Reed and Lord Briggs), that the disclosure in the specification supports the claims so far as they extend to inflammatory pain but not to any kind of neuropathic pain. It
follows that Claims 1 and 3 fail for insufficiency, and that Warner-Lambert’s
appeal must be dismissed and Actavis’s and Mylan’s cross-appeal allowed.(3) I hold, together with Lord Reed, Lord Hodge and Lord Briggs, that if Claims 1 and 3 had been valid, they would not have been infringed. We differ, however, as to the reasons. I consider, together with Lord Reed, that the intention of the alleged infringer is irrelevant and that the sole criterion of infringement is whether the product as it emerges from the manufacturing process, including any labelling or accompanying leaflet, is presented as suitable for the uses which enjoy patent protection. The judge found (paras 443-447) that Lecaent was sold with patient information leaflets to the effect that it was for the treatment of seizure disorders and GAD. Lord Mance agrees that the test depends on the objective appearance and characteristics of the product as it is prepared, presented and put on the market, but leaves open the possibility (i) that in rare cases the context may make it obvious that these are not to be taken at face value, and (ii) that there may be circumstances in which the generic manufacturer should positively exclude use for the patent-protected purpose. Lord Hodge and Lord Briggs prefer the view of Arnold J that the test is whether the alleged infringer subjectively intended to target the patent-protected market. Arnold J found (para 661) that they did not.
This paragraph has been approved by the authors of all the other judgments.
Construction and amendment
16. Claim 3 claims “use of [pregabalin] for the preparation of a pharmaceutical
composition for treating neuropathic pain”. The question is whether “neuropathic pain” in its context means all neuropathic pain, including central neuropathic pain
(as Actavis and Mylan contend), or only peripheral neuropathic pain (as Warner- Lambert say). I will call these the broad and narrow constructions respectively. Both the judge and the Court of Appeal decided without, it seems, much difficulty, in favour of the broad construction. I agree with them. In my opinion they were plainly right about this. Lord Briggs has dealt fully with the reasons, in terms with which I agree, and I shall not lengthen this judgment by repeating them. I also agree, for the
reasons which he gives, that the judge was right to reject Warner-Lambert’s attempt
to amend the patent so as to confine Claim 3 to peripheral neuropathic pain. For reasons which will become apparent in the following section, the amendment would not have saved Claim 3 even if it had been allowed.
Sufficiency and plausibility
17. Elementary as it is, it is worth reminding oneself at the outset of the juridical
basis on which patents are granted, sometimes called the “patent bargain”. The
inventor obtains a monopoly in return for disclosing the invention and dedicating it to the public for use after the monopoly has expired. The point was succinctly made
by Lord Mansfield in Liardet v Johnson (1778), quoted in Hulme, “On the History
of Patent Law”, (1902) 18 LQR 280, 285:
“The condition of giving encouragement is this: that you must
specify upon record your invention in such a way as shall teach an artist, when your term is out, to make it - and to make it as well by your directions: for then at the end of the term, the public shall have benefit of it. The inventor has the benefit
during the term, and the public have the benefit after ...”
The principle remains the foundation of modern patent law, and is recognised in the case law of both the United Kingdom and the European Patent Office. In EXXON/Fuel Oils (T 409/91) [1994] OJ EPO 653, at paras 3.3 and 3.4, the EPO Technical Board of Appeal observed that it was
“the general legal principle that the extent of the patent
monopoly, as defined by the claims should correspond to the technical contribution to the article in order for it to be
supported, or justified. … This means that the definitions in the
claims should essentially correspond to the scope of the
invention as disclosed in the description. … Although the
requirements of articles 83 and 84 are directed to different parts of the patent application, since article 83 relates to the disclosure of the invention, whilst article 84 deals with the definition of the invention by the claims, the underlying purpose of the requirement of support by the description, insofar as its substantive aspect is concerned, and of the requirement of sufficient disclosure is the same, namely to ensure that the patent monopoly should be justified by the
actual technical contribution to the art.”
The principal conditions of validity, novelty, inventive step, industrial application and sufficiency are all, in one way or another, directed to satisfying the principle thus expressed.
18. Sufficiency is a condition of validity relating not to the underlying science but to its disclosure in the patent. Section 14 of the Patents Act 1977 provides:
“(3) The specification of an application shall disclose the invention in a manner which is clear enough and complete enough for the invention to be performed by a person skilled in the art.
…
(5) The claim or claims shall -
(a) define the matter for which the applicant seeks protection;
(b) be clear and concise; (c) be supported by the description; and (d) relate to one invention or to a group of inventions which are so linked as to form a single inventive
concept.”
These provisions correspond to EPC articles 83 and 84, which read:
“83. The European patent application shall disclose the
invention in a manner sufficiently clear and complete for it to
be carried out by a person skilled in the art.84. The claims shall define the matter for which protection is sought. They shall be clear and concise and be supported by
the description.”
Section 72(1) of the Act, which corresponds to EPC article 138, mirrors section
14(3). It provides for the revocation of the patent, inter alia on the ground that“(c) the specification of the patent does not disclose the invention clearly enough and completely enough for it to be
performed by a person skilled in the art.”
19. Lord Mance has expressed the view that sufficiency is a rule of judge-made law. It would I think be more exact to say that it is a statutory rule, which is fundamental to the public interest that justifies the issue of the patent. The contribution of judges has been to work out principles on which it can be applied to Swiss-form patents. Section 14 of the Patents Act and the corresponding provisions of the EPC assume that an invention will be sufficiently disclosed if the specification
enables it to be “performed”. In the case of a patent for a new product or process,
that assumption is almost always correct. The skilled person will discover that it works by replicating it in accordance with the specification. But the assumption is not correct in the case of a second use patent. The invention is not the compound or the process of its manufacture. The skilled person already knows how to make the product from the prior art disclosed in the original patent. The invention consists in the new purpose for which the product is to be manufactured. If sections 14(3) and 72(1)(c) are read literally and as an exhaustive statement of the requirement of sufficiency, all that needs to be disclosed is the new purpose, which is enough to enable it to be administered to a patient suffering from the relevant condition. The skilled person does not need to know how or why the invention works in order to replicate it. The result would be that the knowledge which made the identification of the new purpose inventive need not be disclosed at all.
20. The main problem about this result is that it would enable a patent to be obtained on a wholly speculative basis. Without some disclosure of how or why the known product can be expected to work in the new application, it would be possible to patent the manufacture of known compounds for the purpose of treating every conceivably relevant condition without having invented anything at all, in the hope that trial and error might in due course show that the product was efficacious in treating at least some of them. For that reason, 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”. In their view, this
requirement was not exacting. The Court of Appeal (para 46) put the point as
follows:
“The EPO and domestic cases do, however, indicate that the
requirement of plausibility is a low, threshold test. It is designed to prohibit speculative claiming, which would otherwise allow the armchair inventor a monopoly over a field of endeavour to which he has made no contribution. It is not designed to prohibit patents for good faith predictions which have some, albeit manifestly incomplete, basis. Such claims may turn out to be insufficient nonetheless if the prediction turns out to be untrue. A patent which accurately predicts that an invention will work is, however, not likely to be revoked on the ground that the prediction was based on the slimmest of evidence. Thus, the claims will easily be seen not to be speculative where the inventor provides a reasonably credible theory as to why the invention will or might work. The same is true where the data in the specification is such that the reader
is encouraged to try the invention.”
21. Warner-Lambert’s primary case is that even this undemanding test is an impermissible addition to the text of the Patents Act and the European Patent Convention, and that the sole criterion of sufficiency is that the invention can be performed by the skilled person. Alternatively, they accept that some such test is necessary in order to exclude purely speculative claims, and to that extent they are prepared to add something to the literal language of sections 14(3) and 72(1)(c) of the Patents Act and EPC articles 83 and 138(1)(b). But they take issue with the courts below on two points. First, the courts below held that the patentee must show that his prediction of therapeutic efficacy was plausible in relation to everything falling within the scope of any claim if that claim was to be valid. Secondly, they held that the patentee may not demonstrate the plausibility of his prediction to the required standard by reference only to later published data. Mr Mitcheson QC, who appeared for Warner-Lambert, disputed both propositions.
22. The Court of Appeal’s reference to “armchair inventors” suggests that what
they meant by speculative claiming was claiming by persons who had done nothing new or inventive at all but had simply sought to patent abstract possibilities. That may well be a particular risk in the case of patents for new uses of known compounds, especially when they are commercially successful in their existing use. In reality, however, speculative claiming of this kind is simply one of a number of ways in which a patentee may attempt to claim a monopoly more extensive than anything which is justified by his contribution to the art. Other ways in which this can happen include claiming a monopoly wider than the disclosure in the patent can support. An over-broad claim will not necessarily be speculative. The inventor may really have invented something corresponding to the full breadth of the claim. Research may subsequently demonstrate this. But the claim will still exceed his contribution to the art if that contribution is not sufficiently disclosed in the patent.
23. The concept of plausibility originates in the case law of the EPO as a response to over-broad claims, in particular claims to whole classes of chemical compounds supported by a description which fails to show which compounds can be expected to work. The Technical Board of Appeal treats the condition of sufficiency under EPC article 83 as satisfied if it is possible to work the invention across the scope of the claim from the information in the specification, interpreted in the light of common general knowledge at the priority date. It addresses the broader question whether the disclosed contribution to the art is commensurate with the monopoly claimed under EPC article 56, in the context of inventive step. In that context, its case law requires the formulation of a problem which the claims of the patent could be said to solve: see T 939/32 AGREVO/Triazole sulphonamides [1996] EPOR 171. It imports a requirement that the patent should disclose not just what the invention is and how to replicate it, but some reason for expecting that it will work. Plausibility was the standard to which the patentee was expected to demonstrate this.
24. Thus in JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE/Growth differentiation factor-9 (T 1329/04) [2006] EPOR 8, the hypothetical problem calling for solution was whether a claimed polynucleotide was a member of the TGF-beta superfamily. The only evidence to support the contention that it was, consisted of material published after the priority date. The patent was held invalid for want of an inventive step. The Board observed at para 12:
“The definition of an invention as being a contribution to the
art, ie as solving a technical problem and not merely putting forward one, requires that it is at least made plausible by the disclosure in the application that its teaching solves indeed the problem it purports to solve. Therefore, even if supplementary post-published evidence may in the proper circumstances also be taken into consideration, it may not serve as the sole basis to establish that the application solves indeed the problem it
purports to solve.”
See also the Board’s observations to the same effect in BRISTOL-MYERS
SQUIBB/Dasatinib (T 0488/16) (1 February 2017, unpublished), at para 4.9.
25. English law diverges from this approach, although the divergence is more a question of labels than of substance. It distinguishes between so-called “classical insufficiency” (where the skilled person is unable to perform the invention from the
information disclosed in the specification) and so-called Biogen insufficiency (where the claim is said to be too broad, because it exceeds the disclosed contribution to the art). It deals with both under section 14(3), the statutory analogue of EPC article 83. The expression Biogen insufficiency is derived from the decision of the House of Lords in Biogen Inc v Medeva Plc [1997] RPC 1. The patent in suit in that case claimed a class of products, namely a molecule defined partly by the way that it had been made (by recombinant DNA). The trial judge and the EPO Technical Board of Appeal had found that the disclosure was sufficient to enable the invention to be performed across the whole scope of the claim, and the Appellate Committee proceeded on the basis that that was so. But the specification described only one method of making the molecule by recombinant DNA, whereas other methods were possible which owed nothing to the matters disclosed. The patent
therefore claimed more than the inventor’s contribution to the art warranted. The
House of Lords imported into section 14(3) of the Act a concept similar to the former
requirement of fair basis in section 32(1)(i) of the Patents Act 1949 (“that any claim
of the complete specification is not fairly based on the matter disclosed in the
specification”). It held that if the claim extended beyond the technical contribution
to the art disclosed in the patent, it failed for insufficiency independently of any objection based on want of an inventive step and notwithstanding that the skilled person could perform the invention across the whole scope of the claim. Lord Hoffmann, delivering the leading speech, said at p 50:
“But the fact that the skilled man following the teaching of
Biogen 1 would have been able to make HBcAg and HBsAg in bacterial cells, or indeed in any cells, does not conclude the matter. I think that in concentrating upon the question of
whether Professor Murray’s invention could, so to speak,
deliver the goods across the full width of the patent or priority document, the courts and the EPO allowed their attention to be diverted from what seems to me in this particular case the critical issue. It is not whether the claimed invention could deliver the goods, but whether the claims cover other ways in which they might be delivered: ways which owe nothing to the
teaching of the patent or any principle which it disclosed.”
He went on to make the same point in the context of the objection of insufficiency. Adopting the statement of principle cited above from EXXON/Fuel oils, he pointed out, at p 54, that the purpose of requiring sufficiency of disclosure could not be limited to enabling the public to work the invention after the patent had expired:
“Section 72(1)(c) of the 1977 is not only intended to ensure that
the public can work the invention after expiration of the monopoly. It is also intended to give the court in revocation proceedings a jurisdiction which mirrors that of the Patent Office under section 14(3) or the EPO under article 83 of the EPC, namely, to hold a patent invalid on the substantive ground that, as the EPO said in Exxon/Fuel Oils (T 409/91) [1994] OJ EPO 653, para 3.3, the extent of the monopoly claimed exceeds the technical contribution to the art made by the invention as
described in the specification.”
Lord Hoffmann was not, in these observations, addressing the question of second use patents. But such patents raise a similar problem. If it is enough to disclose how to make a known compound and for what conditions, the patentee has acquired a monopoly without adding anything to the sum of knowledge. He will have satisfied the condition of sufficiency but without satisfying its purpose.
26. The answer to this anomaly in the case of Swiss-form patents was supplied by a series of decisions in which the EPO Technical Board of Appeal held that there was to be implied into a purpose-limited claim an assertion of efficacy for the designated purpose, and that this was an intrinsic technical feature of the claim. This proposition was originally established in purpose-limited patents for non-medical uses. In two decisions published on the same date in 1989, G2/88 MOBIL/Friction reducing additive [1990] OJ EPO 93, at para 9, and G 6/88 BAYER/Plant Growth Regulating Agent [1990] OJ EPO 114, at para 7 the Board drew attention to the Protocol on the Interpretation of EPC article 69, which required a patent to be
“interpreted as defining a position … which combines a fair protection for the patent
proprietor with a reasonable degree of legal certainty for third parties”. From this
they concluded that
“… with such a claim, where a particular technical effect which
underlies such use is described in the patent, having regard to the Protocol, the proper interpretation of the claim will require that a functional feature should be implied into the claim, as a technical feature; for example, that the compound actually
achieves the particular effect.”
The principle was first applied to patents for new medical uses in T 158/96
PFIZER/Obsessive-compulsive disorder (28 Oct 1998, unpublished), at para 3.1.27. In Prendergast’s Applications [2000] RPC 446, 448 Neuberger J arrived
independently at the same conclusion. It followed that the specification must include
some basis for supposing that the claim to therapeutic efficacy was true:
“In relation to a ‘Swiss-type’ application, it appears to me that,
in the absence of any practical evidence of the idea working (that is the idea of using a well-established drug for the treatment of a condition for which it has not so far been used), the absence of any evidence of the idea working involves the
absence of a description. … [W]hether or not there is a
description or an adequate description, for the purposes of section 14(5)(c) of the 1977 Act, must be judged by reference to the nature of the application. There is obvious force in the contention that, where you have a claim for the use of a known active ingredient in the preparation of a medicament for the treatment of a particular condition, the specification must provide, by way of description, enough material to enable the relevantly skilled man to say this medicament does treat the
condition alleged, and that pure assertion is insufficient.”
28. The implications of this approach for sufficiency were considered by the EPO Technical Board of Appeal in SALK INSTITUTE FOR BIOLOGICAL STUDIES/AP- I complex (T 609/02) (27 October 2004, unpublished). At para 9, the Board observed:
“Where a therapeutic application is claimed in the form
allowed by the Enlarged Board of Appeal in its decision G 5/83 (OJ EPO 1985, 64), ie in the form of the use of a substance or composition for the manufacture of a medicament for a defined therapeutic application, attaining the claimed therapeutic effect is a functional technical feature of the claim (see G 2/88 and G 6/88, OJ EPO 1993, 93 and 114, Headnote III. And point 9 of the reasons, for non-medical applications, see also T 158/96 of 28 October 1998, point 3.1 of the reasons). As a consequence, under article 83 EPC, unless this is already known to the skilled person at the priority date, the application must disclose the suitability of the product to be manufactured for the claimed
therapeutic application.”
29. The Board went on to mitigate this principle so as to reflect the fact that in the case of purpose-limited medical patents definitive evidence of therapeutic effect would not be available until clinical trials had been carried out. Since these would have to be disclosed, it was practically inevitable that the patent application would have to be made before any trials. This implied that sufficiency could be demonstrated by the disclosure of material supporting the claimed therapeutic effect which was less than definitive:
“The patent system takes account of the intrinsic difficulties for
a compound to be officially certified as a drug by not requiring an absolute proof that the compound is approved as a drug before it may be claimed as such. The Boards of Appeal have accepted that for a sufficient disclosure of a therapeutic application, it is not always necessary that results of applying the claimed composition in clinical trials, or at least to animals are reported. Yet, this does not mean that a simple verbal statement in a patent specification that compound X may be used to treat disease Y is enough to ensure sufficiency of disclosure in relation to a claim to a pharmaceutical. It is required that the patent provides some information in the form of, for example, experimental tests, to the avail that the claimed compound has 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. Showing a pharmaceutical effect in vitro may be sufficient if for the skilled person this observed effect directly and unambiguously reflects such a therapeutic application (T 241/95, OJ EPO 2001, 103, point 4.1.2 of the reasons, see also T 158/96 of 28 October 1998, point 3.5.2 of the reasons) or, as
decision T 158/96 also put it, if there is a ‘clear and accepted
established relationship’ between the shown physiological
activities and the disease (loc cit).”
After discussing the potential value of in vitro tests for this purpose, the Board observed, at para 10:
“This means that the skilled person is made aware of the
structure of the active ingredient proposed for the pharmaceutical composition as well as, in technical terms, of a definite link between the ingredient and the mechanism allegedly involved in the disease state. The presence of a
cause/effect relationship is, thus, made plausible.”
It was somewhat tentatively suggested to us by Mr Mitcheson that this principle did not justify the application of a plausibility test beyond the application stage, or authorise its use as a ground for revocation. But the correspondence between EPC articles 83 and 138 makes this kind of argument difficult to accept.
30. Mr Mitcheson’s main submission under this head was a different one. This was that the subsequent case law of the EPO indicates that the SALK principle applies only where the therapeutic effect suggested in the patent is inherently implausible. The argument is that it is necessary for the patentee to disclose reasons for regarding the claimed therapeutic effect as plausible only when the skilled person reading the patent would be sceptical about it in the absence of such disclosure. This submission is consistent with some turns of phrase in the cases. But it would have been a strange thing for the Technical Board of Appeal to have meant. It would be inconsistent with the reason why plausibility of the claimed therapeutic effect is required, namely to support the implied claim to therapeutic efficacy and to justify
the monopoly by reference to the patentee’s contribution to the art. If Warner-
Lambert’s argument were sound, it would mean that if nothing was known either for
or against the claimed therapeutic effect, no disclosure need be made in support of
it.31. The leading case relied on in the jurisprudence of the EPO is T 0578/06
IPSEN/Pancreatic cells (29 June 2011, unpublished). This concerned a compound for extending the functional life of pancreatic islet cells. The patent comprised no
experimental data supporting the drug’s claimed therapeutic effect, but it did contain
a technical explanation of its effect and an experimental methodology by which this could be verified: see para 11. The Board was concerned with the circumstances in which the specification could be sufficient without experimental data. It held, at paras 14-15:
“14. The Boards of Appeal have indeed dealt with cases
where, in the context of the assessment of inventive step, there could only be an invention if the application made it at least plausible that its teaching did indeed solve the problem it purported to solve and in which to establish plausibility the disclosure of experimental results in a patent application, or, under certain circumstances, by post-published evidence, was considered necessary (see decision T 716/08 of 19 August 2010, points 14 to 16 for a summary of the case law).
15. The board re-emphasises in this context however that this case law considers the establishment of plausibility only relevant when examining inventive step if the case at hand allows the substantiation of doubts about the suitability of the claimed invention to solve the technical problem addressed and when it is thus far from straightforward that the claimed
invention solves the formulated problem.”
This decision is authority for the proposition that plausibility can be demonstrated in the specification without experimental evidence, if there is no substantiated doubt about the theoretical case made for the efficacy of the invention. This is the only relevant proposition for which it is authority. As the Board observed in INTERVET/Infectious salmon anaemia virus vaccine (T 0716/08) (19 August 2010, unpublished), para 15, (the case cited in the passage quoted above from IPSEN),
“common general knowledge at the priority date may be used to interpret the
teaching in an application or a patent”, but there must be something in the patent to
interpret. This is no more than the Board had said in SALK itself.
32. These principles may be illustrated by the decisions of the Board in T 1437/07
ALLERGAN/ Botulinum toxin for treating smooth muscle spasm (26 October 2009, unpublished), and T 950/13 BRISTOL MYERS SQUIBB/Dasatinib in the treatment of chronic myelogenous leukaemia (3 February 2017, unpublished).
33. In ALLERGAN, it is unclear from the report what technical information was disclosed in support of the claim to therapeutic efficacy, except that it did not include any experimental data. The recital of the arguments shows that the sole ground on which the disclosure was said to be insufficient was that the absence of experimental
data was alone enough to make the claim to therapeutic efficacy “not credible”. The
Board dealt with this objection as follows:
“38. The respondents argue that it was not credible that the
therapeutic effect could be achieved because the treatment
disclosed in Example 9 had not actually been carried out.
38.1 However, article 83 EPC stipulates that an invention
must be disclosed ‘in a manner sufficiently clear and complete
for it to be carried out by a person skilled in the art’ (emphasis
added by the board). Thus, article 83 EPC does not stipulate that a claimed invention must have actually been carried out by the applicant or the inventor. Moreover, according to rule 42(1)(e) EPC, even the presence of an example is not mandatory. Therefore, just because a patent discloses an effect which has not in reality been achieved, there is no reason - in the absence of convincing evidence that the effect cannot be achieved - for the board to doubt that the effect can be achieved.
Thus, the respondents’ argument does not convince the board.”
The decision, like the decision in IPSEN, is authority for the proposition that experimental data are not essential to sufficiency unless it is being positively alleged
with “convincing” supporting evidence that the invention does not work. In that
event it may be necessary for the patentee to point to experimental data to rebut the allegation. But this does not mean that the specification is sufficient if there is neither experimental data nor any other reason to deduce from the specification that the claim to therapeutic efficacy is plausible. The decision is not authority for saying that the objector has the onus of showing that it is implausible. Sufficiency turns on what the patentee has disclosed. It must always be necessary for the patentee to demonstrate that he has included in the specification something that makes the claim to therapeutic efficacy plausible. Otherwise a mere assertion of efficacy would be enough.
34. The same point was made by the Board of Appeal in BRISTOL MYERS SQUIBB. The compound the subject of the patent was dasatinib for the treatment of chronic myelogenous leukaemia. The patent taught that dasatinib worked by inhibiting certain protein tyrosine kinases associated with chronic myelogenous leukaemia. No experimental data were disclosed in the specification. At para 3.6, the Board observed:
“The disclosure of experimental results in the application is not
always required to establish sufficiency, in particular if the application discloses a plausible technical concept and there are no substantiated doubts that the claimed concept can be put into
practice.”
The objection was that there were “substantial doubts” about the product’s efficacy
for the designated purpose in the absence of either (i) experimental data, or (ii) “a
coherent theory which could explain such an effect”, ie what the Board called a
“plausible technical concept”. The Board of Appeal upheld the patent because it
disagreed on point (ii). It thought that there was a coherent theory. This was because it was common general knowledge in the art that the inhibition of certain kinases associated with chronic myelogenous leukaemia was an effective way to treat that condition. Dasatinib had significant functional and chemical affinities with another kinase inhibitor known to be effective. This was more than a mere assertion of efficacy. The patent disclosed a coherent theory to support it in the light of common general knowledge.
35. All of these judgments deal with highly fact-specific issues arising from objections or potential objections on the ground of insufficiency. When reading them, it is important not to miss the wood for the trees. The fundamental principle which they illustrate is that the patentee cannot claim a monopoly of a new use for an existing compound unless he not only makes but discloses a contribution to the art. None of them casts doubt on the proposition that the disclosure in the patent must demonstrate in the light of the common general knowledge at the priority date that the claimed therapeutic effect is plausible. On the contrary, they affirm it: see ALLERGAN at paras 26, 37, and BRISTOL at para 3.2.
36. The Court of Appeal’s statement of the effect of the plausibility test has
already been quoted (para 20 above). They considered that the threshold was not
only low, but that the test could be satisfied by a “prediction … based on the
slimmest of evidence” or one based on material which was “manifestly incomplete”.
Consistently with that approach, they considered (paras 40, 130) that the Board’s
observations in SALK laid down no general principle. I respectfully disagree. The principle is that the specification must disclose some reason for supposing that the implied assertion of efficacy in the claim is true. Plausibility is not a distinct condition of validity with a life of its own, but a standard against which that must be demonstrated. Its adoption is a mitigation of the principle in favour of patentability. It reflects the practical difficulty of demonstrating therapeutic efficacy to any higher standard at the stage when the patent application must in practice be made. The test is relatively undemanding. But it cannot be deprived of all meaning or reduced, as
Floyd LJ’s statement does, to little more than a test of good faith. Indeed, if the
threshold were as low as he suggests, it would be unlikely to serve even the limited
purpose that he assigns to it of barring speculative or armchair claims.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.
38. I turn to Warner-Lambert’s alternative arguments. In the light of the general
principles which I have considered, they can be addressed quite briefly.
39. The first argument is that whatever standard of plausibility is applied, the Court of Appeal were wrong to say that it had to be demonstrated across the whole scope of the claim. In my opinion, they were not wrong. As I have said, plausibility is not a distinct condition of validity, but one element in the test of sufficiency. As such, its application is governed by the same principles which apply to sufficiency generally. In a case such as this, where the claim is said to exceed the disclosed contribution to the art, it is of the essence that the specification must justify the full extent of the claim to the requisite standard. Where a feature of the claim is an assertion of therapeutic efficacy for a given condition, a monopoly is being claimed for the process of manufacturing the compound for the treatment of that condition. This does not mean that it must work for all patients suffering from that condition, or work on every occasion when it is applied by way of treatment. But it does mean that where the condition identified embraces a number of different pathologies, and the claim is construed as asserting the efficacy of the product for each of them, the assertion must be plausible in relation to them all. It must, as Kitchin LJ put it in Regeneron Pharmaceuticals Inc v Genentech Inc [2013] RPC 28, para 100 -
“be possible to make a reasonable prediction the invention will
work with substantially everything falling within the scope of the claim or, put another way, the assertion that the invention will work across the scope of the claim must be plausible or
credible.”
40. Warner-Lambert’s second argument is that the courts below were wrong to
reject later published data as relevant. This submission also is contrary to the legal basis of this particular head of insufficiency. We know that pregabalin works for the treatment of both peripheral and central neuropathic pain, because like any other medicament on the market, it underwent demanding clinical trials after the priority date, the results of which were made public. On that basis it received marketing authorisation for all neuropathic pain. This is always the case for a commercially valuable medicament, and no other kind will be worth litigating about. The question is not whether it works but whether the contribution to the art consisting in the discovery that it can be expected to work has been sufficiently disclosed in the patent. The inherent difficulty of demonstrating this before clinical trials is taken into account in the modest standard (ie plausibility) which is applied to test it. This point was made by the EPO Technical Board of Appeal in SALK, at para 8:
“Sufficiency of disclosure must be satisfied at the effective date
of the patent, ie on the basis of the information in the patent application together with the common general knowledge then available to the skilled person. Acknowledging sufficiency of disclosure on the basis of relevant technical information produced only after this date would lead to granting a patent for a technical teaching which was achieved, and, thus, for an invention which was made, at a date later than the effective date of the patent. The general principle that the extent of monopoly conferred by a patent should correspond to, and be justified by,
the technical contribution to the art, has to be kept in mind.”
This does not mean that subsequent data is never admissible in a dispute about sufficiency, but the purpose for which it is admitted is strictly limited. Where the asserted therapeutic effect is plausible in the light of the disclosure in the patent, subsequent data may sometimes be admissible either to confirm that or else to refute
a challenger’s contention that it does not actually work: see, for example,
ASTRAZENECA/Omeprazole Na (T 1677/11) (27 November 2012, unpublished),
MERCK, SHARP & DOHME/Pharmaceutical nanoparticulate composition of a
Tachykinin receptor antagonist (T 0210/11) (17 July 2014, unpublished). But it cannot be a substitute for sufficient disclosure in the specification. As the EPO Technical Board of Appeal observed in JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE/Growth differentiation factor-9 (T 1329/04) [2006] EPOR 8 at para 12, (cited above), it cannot be a substitute for sufficient disclosure in the specification.
Application to the present case
41. In what follows, unless otherwise stated, references to paragraph numbers are to the judgment of Arnold J.
42. The empirical data disclosed in the patent in support of the claim to therapeutic efficacy consisted of references to a number of pre-clinical animal models used to test drugs for various kinds of pain. The following facts about these models are either agreed or found by the judge:
1. The most significant model was the rat paw formalin test. This
involves the injection of a noxious agent (formalin) into a rat’s paw. The rat
is monitored for the next hour and the amount of time that it spends licking or biting the paw is recorded. There are two phases. The first phase, which lasts about ten minutes, models the acute nociceptive pain caused by the injection itself. The second phase, which lasts about 45 minutes, models inflammatory pain. Nonsteroidal anti-inflammatory drugs were not effective for neuropathic pain, but were known to be efficacious in the second phase. The Patent specification accordingly recorded that the test results showed that pregabalin was effective in treating inflammatory pain. At the trial Warner- Lambert contended that nonetheless it was common general knowledge that the second phase could also be predictive of efficacy in treating neuropathic pain. The judge found, at para 235, that the evidence did not establish this.
2. The carrageenin test also models inflammatory pain. Carrageenin, an
inflammatory agent, is injected into the sole of a rat’s paw and tests are
carried out to determine the extent of thermal or mechanical hyperalgesia. The Patent specification recorded that test results showed that pregabalin was effective in treating inflammatory pain. There is nothing in the literature to suggest that the carrageenin test could be used to predict efficacy for neuropathic pain, either on its own or in conjunction with the rat paw formalin test.
3. The post-operative pain model tests for pain responses following
surgery. The rat’s paw’s plantaris muscle is incised under anaesthetic. After
24 hours the rat is assessed for mechanical hyperalgesia and tactile allodynia. Both are referred to in the Patent as nociceptive responses. Nothing in the literature suggests that this model can be used to predict efficacy for neuropathic pain, either on its own or in conjunction with the rat paw formalin test.
4. The specification also refers to two well-known models for peripheral
neuropathy, the Bennett model and the Kim and Chung model. However, no
data are presented from either model.
It follows that the experimental data in the specification was predictive of efficacy for the treatment of inflammatory pain. But the specification does not claim that the experimental data presented makes it plausible that pregabalin is effective for the treatment of any kind of neuropathic pain.
43. In these circumstances, the specification supported Claim 3 only if it would have suggested to the skilled person that there was some unifying principle which made it plausible that pregabalin would also work with neuropathic pain. The judge had already found, at para 161, in the context of the challenge for obviousness, that the skilled person would not have considered that there was any reasonable basis for thinking that an anticonvulsant like pregabalin, known to be effective for the treatment of epilepsy, would for that reason alone be effective for treating neuropathic pain. Warner-Lambert identified the relevant unifying principle as central sensitisation, a phenomenon discovered by Professor Clifford Woolf, one of their expert witnesses at trial, and published by him in 1983. Central sensitisation was a well-known concept at the priority date. It refers to the sensitisation of neurons in the dorsal horn to peripheral painful stimuli. For present purposes it is unnecessary to describe the detailed physiological processes involved. Essentially, pain signals originating in injury at the periphery are transmitted to the spine and intensified, resulting in allodynia and secondary hyperalgesia. The experts were agreed that central sensitisation is common to inflammatory pain and peripheral neuropathic pain but was not known to be causative of either (para 191). Moreover, there is no necessary correlation between allodynia and secondary hyperalgesia on the one hand and either central sensitisation or neuropathic pain on the other. The judge found (para 205) that allodynia and secondary hyperalgesia were present in a
“large majority” of patients suffering from neuropathic pain, but there was a
“significant minority” of cases in which they were not present. Moreover, although
allodynia and secondary hyperalgesia involved central augmentation, in some cases this would be central sensitisation, in others not. Central sensitisation is not the only mechanism of central augmentation (para 61).
44. A significant part of the evidence at trial was concerned with the role of central sensitisation in the second phase of the rat paw formalin test. This, as I have pointed out, models inflammatory pain. The judge found (para 235) that it was not known to be predictive of efficacy for neuropathic pain. The evidence established that central sensitisation played a role in the pain experienced in the second phase. But the judge found that it was not generally understood to be a dominant role (paras 211, 213-214). By this I understand him to have meant (since this was the issue between the experts) that it amplified but did not cause the pain experienced in the second phase.
45. Against this background, the judge dealt first with central neuropathic pain. He rejected the suggestion that central sensitisation could serve as a unifying principle embracing it. This was because although central sensitisation was understood to contribute to inflammatory pain and peripheral neuropathic pain, both of which originate in the peripheral nervous system, it cannot contribute to central neuropathic pain, which has nothing to do with damage to the peripheral nerves (paras 193, 348). There was an issue at trial about the correct classification of fibromyalgia and phantom limb pain. They were said to be exceptions to this proposition. But the judge (para 194) was not satisfied that this was common general knowledge. These findings are fatal to the argument that central sensitisation can
serve as a unifying principle embracing central neuropathic pain. The judge’s
reasons for rejecting that argument seem to me to be unanswerable.
46. The judge refused to allow Warner-Lambert to argue by way of alternative that the presence of hyperalgesia or allodynia itself served as a unifying principle embracing central neuropathic pain, because it had not been pleaded, advanced in evidence or put to the relevant witnesses. But in any event he considered (para 349) that the evidence did not support it, mainly because it was difficult to reconcile with the fact that nonsteroidal anti-inflammatory drugs were known to be effective for the treatment of inflammatory pain but not neuropathic pain.
47. Turning to peripheral neuropathic pain, which is the subject of Actavis and
Mylan’s cross-appeal, the judge evidently found this to be a difficult issue. He
considered the evidence to be “finely balanced”, but concluded on balance (para
351) that the specification enabled a plausible prediction to be made that pregabalin would be effective for treating peripheral neuropathic pain. His reasoning was as follows:
“In addition to the general points made above, Warner-
Lambert’s case suffers from the problem that it has not been
established that it was common general knowledge that the rat paw formalin test was predictive of efficacy for neuropathic pain. Moreover, as discussed above, Professor Woolf accepted that the carrageenin and post-operative pain models did not assist in this regard. Nevertheless, I have concluded on balance that, given that plausibility is a relatively low threshold, the data contained in the specification, when read with the common general knowledge, just make it plausible that pregabalin would be effective to treat peripheral neuropathic pain. This is because the common general knowledge as to (i) the involvement of central sensitisation (at least as an amplifying mechanism) in both inflammatory pain and peripheral neuropathic pain and (ii) the role played by central sensitisation in the rat paw formalin test would have suggested to the skilled team that it was possible that a drug which was effective for inflammatory pain, in particular as modelled by the second phase of the formalin test, would also be effective in peripheral neuropathic pain, although this would not necessarily be the case. This conclusion is supported by the evidence not only of Professor Woolf, but also of Dr Scadding and Professor Wood in cross-examination. Dr Scadding said that, when he read the
Patent, he thought that it ‘could be the case’ that pregabalin
would be effective for (peripheral) neuropathic pain, although a demonstration of that was missing. Professor Wood more or less accepted that it was a credible suggestion, although he
made it clear that he would want to test it experimentally.”
48. An appellate court should not normally interfere with conclusions of a trial judge which depend on his evaluation of a substantial body of expert evidence: see Biogen Inc v Medeva Plc [1997] RPC 1, 50 (Lord Hoffmann). I consider, however, that Actavis and Mylan are entitled to succeed on their cross-appeal, not because
there was anything wrong with the judge’s findings, but because those findings do
not support his conclusion that the specification makes it plausible to predict that pregabalin will be efficacious for treating neuropathic pain. The question, it must be remembered, is not whether it is plausible but whether the specification discloses something that would make it so in the eyes of the skilled person.
49. The starting point was pointed out by the judge himself (para 255) in the context of the challenge based on obviousness. Because the only evidence of therapeutic efficacy presented in the specification is the results of the four animal models, the skilled person would understand that the patentee was relying on these as being predictive of efficacy. Those results were, however, predictive only of efficacy for inflammatory pain. The specification does not in terms claim more than this. No data are presented for the two recognised models of neuropathic pain, the Bennett model and the Kim and Chung model. There is no mention of central sensitisation, or indeed of any unifying principle that might embrace any condition other than inflammatory pain. This is an unpromising basis for a submission that there is a unifying principle which enables any kind of conclusion about efficacy for neuropathic pain to be derived from results of the animal models.
50. The judge’s analysis of the implications for peripheral neuropathic pain of
the data presented in the specification was based entirely on the common general
knowledge that central sensitisation was “involved” in both inflammatory and peripheral neuropathic pain. The judge concluded from this that it was “possible”
that a drug which the specification showed to be effective for the first would also be
effective for the second, “although this would not necessarily be the case.” In my
opinion this is a logical non-sequitur. The reason for seeking a unifying principle embracing neuropathic as well as inflammatory pain is that the unifying principle may suggest a common cause or metabolic mechanism embracing both, whose operation may be affected by the drug. That might in turn suggest that a drug which was effective for one condition might also be effective for the other. The
“involvement” of central sensitisation in both inflammatory and peripheral
neuropathic pain does not prove or even suggest that they have a common cause. Indeed, it is clear that they do not. The involvement of central sensitisation in both inflammatory and peripheral neuropathic pain does suggest that there may be a common metabolic mechanism at work, at least in intensifying the pain. But neither the specification nor the common general knowledge of the art supplies any reason for supposing that pregabalin affects the operation of that mechanism or even that it might well do. In particular, there is nothing to suggest, even as a hypothesis, that pregabalin works with peripheral neuropathic pain by blocking central sensitisation.
51. The information presented in the specification about the rat paw formalin test does not assist on this point. The rat paw formalin test, as I have said, models inflammatory pain. It shows a diminution of pain in the second phase, associated with the administration of pregabalin. But in the absence of anything in the specification about the effect of pregabalin on the mechanism of pain, there is no reason to suppose that the diminution of pain is associated with its effect on central sensitisation as opposed to its effect on any other agent of inflammatory pain. The judge had found (paras 211, 214) that central sensitisation was not the dominant factor in the second phase of the test. If, notwithstanding the involvement of central sensitisation in both inflammatory and neuropathic pain, the rat paw formalin model is not predictive of efficacy for neuropathic pain, I find it difficult to see how the model can assist in making such a prediction plausible. The judge was obviously conscious of the logical inconsistency, and believed that he had found a way of resolving it. With respect, I do not think that he had.
52. More generally, it cannot in my view be enough to justify a monopoly that it
is “possible” a priori that a drug which was effective for inflammatory pain would
also be effective for neuropathic pain, in the absence of any reason to suppose that the possibility had some scientific basis or that it was more than speculative.
Everything is possible that is not impossible, but “not impossible” is very far from
being an acceptable test for sufficiency. Plausibility may be easy to demonstrate, but
it calls for more than that.53. Floyd LJ said (para 133) that he was “fortified” in his conclusions by a further
consideration, which the judge had not relied on, namely that
“… it was established through the evidence that the skilled
team would be encouraged by the data in the patent to carry out simple tests (which are themselves identified in the patent) to confirm the suitability of pregabalin for peripheral neuropathic pain. I would have thought, on the basis of that evidence (as I think the judge did) that the specification had thereby made a contribution to the art which would justify a claim to peripheral
neuropathic pain.”
The “simple tests” that Floyd LJ was referring to were the Bennett and the Kim and
Chung tests for peripheral neuropathic pain; and the evidence that he had in mind was that of Dr Scadding, the expert clinician called by Actavis and Mylan: see paras
119-120 and 127. Dr Scadding had accepted that “the skilled person would be
encouraged by the data in the patent to ask the neuroscientist to test pregabalin for
neuropathic pain.” Professor Wood, the expert neuroscientist called by Actavis and
Mylan who would notionally have been asked to carry out these tests, gave more guarded answers when he was asked to deal with the point in cross-examination:
Day 2, pp 265-269. His evidence, in summary, was that there were “no data whatever about neuropathic pain in the patent”, but that he would be encouraged by
the broad terms of the claims to try many tests, including the Bennett and the Kim
and Chung tests. There were, he said, “many different pain mechanisms that can
give apparently similar symptoms”, for which there were different models, and it
would be necessary to test for all of them. Some were difficult to test for. It was put to him that even the Bennett and the Kim and Chung tests would not provide
definitive proof of efficacy, because it was a “step by step process”. His final
answers on this point fairly reflect the tenor of his evidence, so far as one can judge
from the transcript:
“A. … So one would just carry out an analysis of all these different models, to see where the drug had better utility than
present medication.Q. The data in the patent would give you sufficient motivation to carry out further tests and step-by-step you would reach the stage where you have demonstrated that pregabalin was effective for the treatment of pain?
A. It would certainly inspire you to analyse its activity in a broad range of pain models. Of course, this would be useful for the clinician attempting to exploit the drug in treating various different types of human pain. Animal models are not ideal, but they are always a useful pointer for the clinician.
Q. A useful starting point? A. Absolutely.”
I am conscious of the danger of an appellate court analysing extracts from a transcript of evidence on complex and inter-related technical questions, where so
much depends on the impression that the witness’s evidence as a whole has made
on the trial judge. But in the absence of any discussion of this point by the judge, I feel unable to attach the same importance to it as Floyd LJ did. There is, however, a more fundamental objection to it, which is well brought out by the evidence which I have cited from Professor Wood. In classical insufficiency cases, where the question is whether the disclosure in the patent enables the skilled person to perform the invention, the skilled person may be assumed to supplement the disclosure by carrying out simple tests. In cases like this one, where the invention is novel but the objection of insufficiency is that the claim exceeds the disclosed contribution to the
art, the role of hypothetical “simple tests” is necessarily more limited. As the EPO
Technical Board of Appeal observed in JOHNS HOPKINS, at para 12, the specification can be said to contribute to the art if it solves a problem, but not if it merely poses one. Or as Lord Hoffmann observed in a passage that I have already
quoted, the notion that something is “worth trying” cannot be enough without more
to justify a monopoly. The specification in the present case says nothing about neuropathic pain of any kind. It says nothing about central sensitisation, which is said to provide a link between neuropathic and inflammatory pain. The mere fact that the skilled team, faced with an apparent discrepancy between the breadth of the claims and the absence of supporting data in the specification, would be encouraged to fill the gap by carrying out tests of its own, serves only to confirm the absence of any disclosed contribution to the art.
54. I conclude that Claim 3 of the patent and the other claims relating to neuropathic pain were invalid for insufficiency. 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.
Decisions in other jurisdictions
55. Mr Mitcheson reminded us more than once in the course of his submissions that if we were to hold Claim 3 insufficient we would be the only court to do so in the various jurisdictions party to the EPC. In issuing the Patent, the EPO had rejected the suggestion that it might be insufficient, albeit without giving detailed reasons. Warner-Lambert also rely on decisions of the courts of France, Germany and Sweden, all of which have subsequently upheld Claim 3 as sufficient. This is more than a forensic point. If courts in other jurisdictions have upheld Claim 3, that may serve as a reality check against my own, less favourable conclusions. Other things being equal, it would be unfortunate if different jurisdictions party to the EPC arrived at different conclusions concerning the same patent. However, other things are rarely equal, and the force of this point depends entirely on how far the factual and technical evidence before the foreign court was the same as the material before Arnold J, and how far their domestic statutes were comparable.
56. In France, the Tribunal de Grande Instance of Paris published its judgment on 8 July 2016. They appear to have had before them transcripts of at least part of the evidence given to Arnold J. They held that the Patent was sufficient because the occurrence of allodynia and hyperalgesia provided a unifying principle embracing both neuropathic and nociceptive pain. There are difficulties about this theory, as Arnold J pointed out (para 349), but for present purposes it is enough to say that this was the alternative argument which he refused to allow Warner-Lambert to run, a ruling which was not challenged before us.
57. In Germany, the Federal Patent Court ruled on 24 January 2017 that the Patent was invalid for lack of inventive step. It dealt only briefly with the objection
of insufficiency, holding that it was “probable” that the disclosure was sufficient to
enable the invention to be carried out. The court does not appear to have grappled with what in England would be called Biogen insufficiency. This judgment is also under appeal.
58. In Sweden, the Stockholm District Court, sitting as a Patent Court, gave judgment on 12 August 2016. This decision is final. The District Court came closer than those of France and Germany to grappling with the issues before us, but it received expert evidence which was not before Arnold J. The court applied the classic sufficiency test, asking whether the claim was plausible across the whole scope of the claim. It considered that the mere mention of Bennett and the Kim and Chung test made the assertion of efficacy for treating neuropathic pain plausible, but it did not distinguish for this purpose between central and peripheral neuropathic pain. The Court of Appeal in the present case disagreed, on the ground that these were tests for peripheral neuropathic pain which could not justify a claim to efficacy for all neuropathic pain. I also disagree, both for that reason and for the wider reasons which I have already given.
domains are to a certain extent similar” (para 3.8). The Board of Appeal
placed weight on the fact that assays and methods of testing to establish the activity of dasatinib as an inhibitor of PTKs, including BRC-ABL were known in the art (para 3.8). The teaching that dasatinib was suitable for the
treatment of CML was not rendered implausible by the fact that “it may not have been obvious in view of the prior art” (para 3.8). Further, at para 3.10.4,
in these circumstances:
“… post-published documents may be used as evidence that the
invention was indeed reproducible without undue burden.”
7. The Board of Appeal drew a careful distinction between the position in BRISTOL MYERS SQUIBB and the position in the earlier case of SALK. It pointed out (para 3.9.1) that the Board of Appeal in SALK, at para 11, had summarised the situation as one where the claimed subject-matter
“covers limitless and untried downstream developments in
relation to yet to be demonstrated molecular mechanisms. In
the board’s judgment, it amounts to no more than an invitation
to set up further research programs for which no guidance is
forthcoming.”
In contrast, the Board said, the position in BRISTOL MYERS SQUIBB was that
“a structurally well-defined compound and a plausible concept
for its suitability in the treatment of CML has been disclosed.”
Similarly, in rejecting the opponent’s case that the skilled person was left to
guess whether dasatinib exhibited any PTK inhibitory activity, let alone
against BCR-ABL kinase, the Board pointed out, at para 3.10.2, that this“disregards that the present application clearly teaches that
dasatinib is suitable in the treatment of CML, which is
tantamount to dasatinib being a BRC-ABL kinase inhibitor. …
Hence, ... the skilled person was not left to guess, which of the various PTKs was inhibited by dasatinib. Accordingly, no
further ‘research programme’ was necessary in order to carry
out the invention. The allegedly observed failure of some compounds according to formula I to inhibit the protein kinase
Lck … or the poor or reduced oral absorption properties of
other compounds falling within the scope of formula I is irrelevant in this context. Equally irrelevant is the low activity of dasatinib on certain other PTKs such as HER1 or HER2 kinase.
The [opponent’s] arguments may have been relevant, if the
application had been limited to the general disclosure relied on by the [opponent], ie the provision of an extremely broadly defined group of compounds for the treatment of a plethora of diseases or disorders based on the inhibition of different types of PTKs with no further guidance at all as to which compounds inhibits [sic] which PTK. However, as set out above this is
presently not the case.”
8. In summary, being told that there was a functional analogy between dasatinib and imatinib in that they both inhibited BRC-ABL kinase was
sufficient information for the skilled reader to consider dasatinib’s suitability
in the treatment of CML to be a plausible teaching.
195. For these reasons, I consider that it puts the test too high to suggest that “the
specification must disclose some reason for supposing that the implied assertion of
efficacy in the claim is true” (Lord Sumption’s judgment, para 36). That amounts
on its face to, or certainly risks being read as, a requirement that the plausibility of the claim must appear to be established prima facie through scientifically cogent reasoning or experimental evidence set out in the specification. Admittedly, Lord
Sumption goes on in para 36 to suggest that the test is “relatively undemanding”. But he continues in para 37 to say that it is sufficient if the specification “would
cause the skilled person to think that there was a reasonable prospect that the
assertion would prove to be true”, and then that “[the] reasonable prospect must be
based on what the [Board of Appeal] 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”. It also explains
that, in so far as no experimental data is produced, it can be:
“demonstrated by a priori reasoning. For 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.”
Despite the use of phrases such as “reasonable prospect” and “might well produce”,
there is a real risk that the test as described by Lord Sumption would amount to, or be understood as, involving a requirement to establish a prima facie case on the material contained in the specification. In my opinion, the authorities analysed above do not put the standard so high. They certainly reject speculative or wide-ranging unsubstantiated claims. But they accept as sufficient a tailored claim which appears scientifically possible, even though it cannot be said to be even prima facie established, without for example testing or assays according to the state of the art. Only if a person skilled in the art would have significant doubts about the workability of the invention would it, in such a case, fail for insufficiency of disclosure.
196. I therefore consider that Lord Sumption’s judgment puts the test of
sufficiency of disclosure too high. I agree with the way in which Lord Hodge puts the position in para 181 of his judgment. I am also persuaded that, applying the correct test, Arnold J cannot be said to have erred in concluding there was enough
material “just [to] make it plausible that pregabalin would be effective to treat
peripheral neuropathic pain” (para 351). My reasons correspond with those given
more fully by Lord Hodge in paras 182 to 184 of his judgment, which I have had the
benefit of reading since writing a first draft of my own.
Infringement
197. I turn finally to infringement. I need add nothing to what Lord Sumption and Lord Briggs have said on indirect infringement under section 60(2) of the Patents Act 1977. They are agreed that the prescription, dispensing or use of generic
pregabalin to treat neuropathic pain does not “put into effect” the patented invention,
or involve any supply to doctors, pharmacists or others of the means of putting it into effect. The patented invention is, under English law, the process completed by manufacture of the composition for the patent-protected use. Any subsequent use is not itself patented.
198. On the subject of direct infringement under section 60(1)(c), the other members of the court are however equally divided. Lord Sumption, with whom Lord Reed agrees, is on the one side and Lord Briggs and Lord Hodge are on the other. I
am the “swing” voice, and it is with some unwillingness that I pronounce on the
issue at all. All our remarks on it will be obiter, and it is often better to leave a truly contentious and difficult issue to a case where it matters. I also confess that my own view has swung between the two sides.
199. Nevertheless, I will, in the circumstances, express my present conclusions. The issue has been fully argued, and it may at least diminish, though I fear not exclude, the prospect of further litigation if some indication is given to resolve the split of views exposed in this court. The issue remains relevant to old-style Swiss- patent cases - though it will not arise in the same form, and we will not be addressing the position, under article 54(5) of the European Patent Convention. Patentability
under article 54(5) is of a product (a “substance or composition”) for any specific
use, whereas English law regards patentability under a Swiss-form patent as attaching to a process, namely the process of manufacture of a product for a specific purpose.
200. Both sides agree that the issue whether infringement of a Swiss-form patent
involves any and if so what mental element depends on the construction of such a
patent. Claim 3, which it is in this connection relevant to consider, relates to:
“use of [pregabalin] for the preparation of a pharmaceutical
composition for treating neuropathic pain.”
201. The second word “for” must under such a claim relate to one of two different
subjects. First, it may attach to the process consisting of the “use of pregabalin for
the preparation of” the composition or product. Alternatively, it may attach to the
pharmaceutical composition or product, as prepared, presented and put on the market. Whichever approach is taken, some relevance will attach to how the pharmaceutical composition is presented and put on the market. But, if one reads the claim in the first way, it is natural to enquire into the subjective intention of the manufacturer in preparing the composition. If one reads it in the second, it is natural to focus on objective appearances or characteristics, and in particular on the way in which the composition is prepared, presented and marketed.
202. In deciding what protection a Swiss-form patent offers and what will constitute infringement, it is appropriate to consider the implications of each interpretation, against the background of the legislative aim of striking a fair balance between the opposing desiderata of incentivising and rewarding inventors and enabling manufacturers to compete lawfully and pharmacists and end users to carry on their affairs without incurring unbargained for liabilities against which they cannot sensibly protect themselves. The risk that anyone will actually pursue any liability claim against any particular pharmacist and/or end user may be slight in any individual case. But, if liability exists, some may well be pursued, to demonstrate the risks of dealing in generic goods, and all will be affected by the resulting deterrent effect. In any event, one would not as a matter of principle expect the law to involve uncovenanted and unavoidable liabilities.
203. Each way of reading the claim identified in para 201 gives rise to questions. What is meant by subjective intention? And what circumstances would fall to be considered, in order to ascertain how a product is prepared, presented and marketed? As to subjective intention, Lord Sumption and Lord Briggs agree that mere foreseeability that some generic pregabalin would be used for treating neuropathic pain could not suffice to render the maker of the composition an infringer. A Swiss- form patent entitles the maker to prepare the composition for the new purpose identified in it. The subsequent use of the composition involves persons outside the
maker’s control. Lord Sumption and Lord Briggs also agree in rejecting the Court
of Appeal’s solution of adding a qualification, so that foreseeability would suffice,
if a generic manufacturer failed to take reasonable steps to prevent intentional use
of the generic pregabalin by “downstream” prescribers or users for the treatment of
neuropathic pain. I have nothing to add to their agreement on these points.
204. So, if subjective intention is the test, it must be found in something more positive than foreseeability, that is in some form of design or desire on the part of the manufacturer. It seems unsatisfactory that patent infringement should depend on investigation of a subjective intention, internal to the manufacturer. That would also leave open the possibility of entirely blameless pharmacists and end users being liable under section 60(1)(c) for, say, disposal or use of generic pregabalin made by a manufacturer, whose subjective intentions the pharmacist and user would have had no means of gauging.
205. It is true that section 60(1)(c) of the Patents Act 1977 has inherent in it the possibility of unwitting liability of a third party for disposing of, offering to dispose of, or using or importing a product made by a manufacturer by an infringing process. But the thinking behind section 60(1)(c) was certainly not focused on the later invented Swiss-form patent. Rather it was, one supposes, assumed that the process by which a product was made would generally be obvious or easily ascertainable.
206. In the case of a Swiss-form patent, it would be far from obvious or easily ascertainable whether there had been infringement, if the test were whether
manufacture (“use for the preparation”) of the composition had taken place by the
manufacturer with the subjective intention that the composition be used for the
specific purpose identified in the claim (ie here, “for treating neuropathic pain”).
Further, if subjective intention were the test, what would this mean? Suppose that a manufacturer were deliberately to make more pregabalin than could be required for patent-free uses, there would be no means of saying whether any particular batch would be used for patented or for patent-free use. Would this mean that all manufactured batches infringed? So it would seem. These and other consequences are discussed by Lord Sumption and, I understand, recognised by Lord Briggs (see his para 171). They are to my mind powerful reasons for rejecting subjective intention as the test in any form.
207. What then of a test focused on the way in which the pharmaceutical composition is prepared, presented and marketed? This must include in particular its packaging and the instructions given for its use, since the actual pharmaceutical composition is by definition identical to that produced by the patented process which it is said to infringe. Again, it is necessary to consider what such a test would mean. Here, some guidance is, in my view, available from German authority, identified by Lord Sumption in para 85 and by Lord Briggs in para 149. The German authority must be read with the understanding that a Swiss-form patent is under German law regarded as protecting a purpose-limited product, not (as under English law) a purpose-limited process. Accordingly, the protection is treated as arising under section 9(1) of the German Patentgesetz, the German equivalent of section 60(1)(a) of the Patents Act 1977 (rather than under section 60(1)(c)): see Pemetrexed (Case
No X ZR 29/15) (14 June 2016) in the Bundesgerichtshof (“BGH”), para 84,
Östrogenblocker (Case I-2/W 6/17) in the Düsseldorf Oberlandesgericht (“OLG”),
para 38 and Dexmedetomidin (Case I-2 U 30/17) (Düsseldorf OLG) (1 March 2018),
(BeckRS 2018, 2410, paras 41 to 43).208. Swiss-form patents are therefore treated in Germany on the same basis as the ordinary patents of a product for a specific use (where such patents are otherwise permissible) which were considered in Antivirusmittel (Case X ZR 51/86) (16 June 1987) (BGH): see the reference made to Antivirusmittel in the Swiss-form patent case of Chronic Hepatitis C Treatment (Case 4a O 145/12) (14 March 2013) (Düsseldorf OLG), paras 51 to 54.
209. Since the German analysis treats a Swiss-form patent as protecting a product, rather than a process, it follows that third parties disposing of or using a generic product for the patented use are potentially exposed to liability under article 9(1) of the Patentgesetz: see also Chapter A, para 342 of Kühnen, Handbuch der Patentverletzung, 10th ed (2017), a work extensively cited in Dexmedetomidin. However, under article 139(2) of the German Patentgesetz, damages for patent infringement are only available against a person who has deliberately or negligently committed the infringement. German law could not therefore expose a doctor, pharmacist or end user to potential liability to damages in the way that section
60(1)(c) of the English Act would on Warner-Lambert’s case. (Such a person could
however still be injuncted against further infringement under article 139(1) of the
German Patentgesetz.)210. If the protection sought by a Swiss-form claim is treated, as English law treats it, as arising under section 60(1)(c), but is, at the same time, seen as operating in the second way identified in para 201 above (ie as attaching to the pharmaceutical composition as prepared, presented and marketed), then, despite the differences identified above, the German approach appears to me capable of illuminating what it would mean. Essentially, a Swiss-form claim would, under English law, still be understood as protecting a process, but the scope of the protection would depend not on the subjective intention with which the process was undertaken, but on the objective characteristics of the resulting composition or product, judged by reference to the way in which it was packaged and marketed.
211. The German authorities originally took a narrow view of what that could embrace, speaking in Chronic Hepatitis C Treatment, Cistus (Case I-2 U 53/11) (31 January 2103) (Düsseldorf OLG) and Warner-Lambert Co LLC v Aliud Pharma GmbH (Case 327 O 140/15) (2 April 2015) (Hamburg OLG) of sinnfällige Herrichtung, ie manifest outward presentation. This approach was echoed by the
Technical Board of Appeal in GENZYME/Treatment of Pompe’s disease [2016]
EPOR 33, where the Board distinguished purpose-limited product claims from Swiss-form process claims, treating the latter (contrary to the view taken by the German courts) as falling within article 64(2) of the European Patent Convention (which equates with section 60(1)(c) of the Patents Act 1977). The distinction it drew was that the former offered protection whenever the patented product was used for the patented purpose, whereas the latter offered protection only in respect of a product which was produced by the patented process and was, in the instant case,
“packaged and/or provided with instructions for use in the treatment of infantile
Pompe’s disease” (para 9.1). In drawing this general distinction, the Board of Appeal
was not however concerned with the precise limitations of the requirement under a Swiss-form claim that, to achieve protection, the product produced by the process
should be “for” the patented use.
212. As Lord Sumption and Lord Briggs point out, the more recent German authorities, Östrogenblocker and Dexmedetomidin, take a broader view of the protection generated by a Swiss-form patent. They do not focus on the external presentation (including the instructions for its use) of the allegedly infringing product, but rather on its inherent suitability for the patented use. However, they underline an additional requirement of any infringement, viz that the distributor
“needs to take advantage of circumstances which - in a similar
way to an active obvious preparation - ensure that the purpose- related therapeutic use of the preparation offered or sold
actually takes place.”
and
“The latter requires a sufficient and not just occasional use
according to the patent in suit, as well as the supplier’s
respective knowledge, or at least its bad faith ignorance
thereof:”
See Östrogenblocker para 39 and Dexmedetomidin (BeckRS 2018, 2410, para 44). The example given in the latter case is use in practice of the generic product for the
patent-protected indication to a considerable extent “in most cases due to a corresponding prescription by a doctor”, in circumstances of which its supplier is or
should have been aware, and which it “still exploits … for itself by supplying its distributors”: para 44. The limitation relating to knowledge, bad faith taking
advantage or exploitation, introduced in para 39 of Östrogenblocker and para 44 of Dexmedetomidin, appears as a pre-condition to any infringement, rather than as a reflection of the general limitation of damages claims provided by article 139(2) of the Patentgesetz, to which I have referred in para 209 above.
213. In my view, the preferable starting point under English law is to view a Swiss- form claim in the second way identified in para 201 above. In other words, it protects the process of manufacturing a composition or product, which, as prepared,
presented and put on the market, can be said objectively to be “for” the patent-
protected use. A process leading to a composition or product, which does not make clear that its permitted use is limited will infringe. In the light of submissions received from counsel on this judgment as circulated in draft in the usual way before issue, I prefer however to leave open whether there might be some circumstances in which a generic manufacturer could or should be expected to go further, by a notice positively excluding the patent-protected use. All I would say in relation to the present case is that (i) although the parties appear, now, to differ on whether this would be either permissible or permitted, this is only the result of a very belated
objection by Warner-Lambert to a note filed by Actavis at the court’s request as long
ago as 23 February 2018 and (ii) at trial and in the admittedly slightly different context of the steps that Actavis should reasonably have taken to avoid being treated as intending to infringe, Warner-Lambert did not even pursue any suggestion that such steps should have included the attachment of a notice recording, for example, that the generic product was not authorised, and was not to be used, for the treatment
of neuropathic pain: see Arnold J’s judgment, paras 526-527 and 586-589. That is a
very unpromising basis for any suggestion by Warner-Lambert that such a notice could or should have been given on the facts of this case, in order to avoid a
conclusion that the generic product Lecaent was “for” the patent-protected use of
countering neuropathic pain.
214. The delicate and difficult question is how far surrounding circumstances or general knowledge may be relevant, if in their light it is obvious or easily ascertainable that the process results in a product which, despite packaging and instructions making clear that it is for the non-patent-protected use, is destined for such use. For reasons already given, neither foreseeability nor subjective intention can be accepted as appropriate tests of liability.
215. The recent German authorities do not appear to give any direct answer to the question what a manufacturer is supposed to do, if it acquires the awareness of a “practice” of the sort mentioned in para 212 above. Dexmedetomidin (BeckRS 2018,
2410, para 44) says that it will be justified to hold it liable if “it still exploits this practice for itself by supplying its distributors”. If that means that it must stop
manufacturing and supplying any generic product, it involves an extreme solution which is too favourable to the patent-holder, since it excludes competition by the generic product even in patent-free areas of use. Another possibility is to read the German authorities as implying tacitly that the generic manufacturer should take (presumably, reasonable) steps to ensure that pharmacists and end users do not use
the generic product for patented use. That would equate with the Court of Appeal’s
approach in this case, which constructs a pre-condition to legitimate manufacture
and trade for which no basis, in my view, exists.216. There is however a further possibility, which appears to have the support of paras 351 and 353 of Kühnen’s work already cited, namely that, since a generic
manufacturer has no contractual relationship with and cannot give directions to a third party such as a doctor prescribing drugs, the most that can be expected of such a manufacturer is that it makes clear on the product that it is not for the patent- protected use. It would seem to me also appropriate under English law to hold a generic manufacturer responsible in similar circumstances, if it was not made clear, in one way or another, that the product resulting from its manufacturing process was for the non-patent-protected use. However, although the context was again somewhat different, I note here the rejection by Arnold J, in paras 443-447 of his
judgment, of Warner-Lambert’s submission that Actavis must be taken to have
foreseen the use of Lecaent for the treatment of neuropathic pain because of the
inclusion of warnings as to adverse effects if it was so used or because of “blue box”
wording to the effect that it might be prescribed to treat other conditions not listed
in the leaflet.217. Because context is all in the law, I also think that we should be careful about committing ourselves in obiter remarks in relation to other extreme cases not now before us. It may be going too far in favour of generic manufacturers to suggest as an absolute rule that a generic product, prepared, presented and put on the market, must always be viewed in isolation by reference only to its own packaging and instructions, and without regard to the realities or of the market for which it is prepared and into which it is being released. Take a situation where the circumstances make it obvious that a product, ostensibly limited in its permitted use by its packaging and instructions, was in fact destined for wider use; suppose that the manufacturer were to point out in separate studies, reports or advertisements that the composition resulting from its manufacturing process was pharmaceutically identical with that made by a manufacturer operating under a Swiss-form patent; or suppose a generic manufacturer were to produce and supply quantities of the pharmaceutical composition for a distributor in a context which only made sense if they were destined for the patent-protected use. Even then, the question could arise whether it was sufficient that this was obvious as between the generic manufacturer and its buyer or whether it would also have to be obvious more generally, and in particular to persons dealing in or using the composition down the chain in view of their potential exposure in the event of any infringement by the manufacturer. The wide and unqualified grasp of section 60(1)(c) (see para 205 above) might leave third parties with some exposure in a remote situation such as I am currently postulating.
218. I prefer to say no more, and to leave open, the position in this type of remote situation. Normally, a generic manufacturer, and it follows others such as doctors, pharmacists and end users, should be protected from infringement of a Swiss-form patent if the manufacturer ensures that the generic product resulting from its manufacturing process is produced, prepared and marketed with a clear limitation to patent-free uses. As Kühnen observes, a generic manufacturer cannot control the activities of doctors, pharmacists and end users, with which it is in no contractual relationship. The protection afforded by a Swiss-form patent, analysed as protecting a process in the way that English law analyses it, is valuable, but necessarily limited.
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