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Cite as: [2015] EWHC 3370 (Pat), [2016] RPC 16

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		Neutral Citation Number: [2015] EWHC 3370 (Pat)
		Case Nos: HP-2014-000035, HP-2014-000021, HC-2014-001795

IN THE HIGH COURT OF JUSTICE
CHANCERY DIVISION
PATENTS COURT

Rolls Building
Fetter Lane, London, EC4A 1NLL

25 November 2015

B e f o r e :

THE HON MR JUSTICE ARNOLD
____________________

Between:

	GENERICS (UK) LIMITED trading as MYLAN	Claimant
	- and -
	WARNER-LAMBERT COMPANY LLC	Defendant

____________________

Michael Bloch QC and Kathryn Pickard (instructed by Taylor Wessing LLP) for Mylan
Adrian Speck QC and Isabel Jamal (instructed by Powell Gilbert LLP) for Actavis
Richard Miller QC, Tom Mitcheson QC and Miles Copeland (instructed by Allen & Overy LLP) for Warner-Lambert
Hearing date: 11 November 2015
____________________

HTML VERSION OF JUDGMENT
____________________

MR JUSTICE ARNOLD :

Contents

Topic	Para

Introduction	1-6
The law	7-25
General principles as to abusive re-litigation	7-8
Application to patent court	9-14
A rticle 138(3) EPC 2000	15-16
Central limitation	17-21
Foreign cases	22-25
Procedural history	26-108
The IASP definition of neuropathic pain	27-30
The Patent	31-32
The Lyrica marketing authorisation	33
Mylan and Actavis' claims for revocation	34-35
Warner-Lambert's application for central limitation	36-37
Warner-Lambert's infringement claim	38-39
The pleas of insufficiency	40-41
The pleas of independent validity	42
Pleas as to common general knowledge	43-48
Evidence in chief	49-56
Evidence in reply	57-64
Further evidence	65
Skeleton arguments	66-74
Opening speech	75-81
Cross-examination	82-92
Written closing submissions	93-99
Oral closing submissions	100-111
Assessment	112-148
Would a second trial be required?	114
Validity	115-133
Infringement	134-136
Is Warner-Lambert the victim of procedural unfairness on the part of Mylan and Actavis?	137-143
Would the amendment application delay the overall resolution of the dispute?	144-145
The wider public interest	146-147
Conclusion	148
Result	146

Introduction

On 10 September 2015 I handed down judgment following the trial of Mylan and Actavis' claims for revocation of the Patent, of Warner-Lambert's claim against Actavis for infringement of claims 1 and 3 of the Patent and of Actavis' claim against Pfizer for groundless threats: [2015] EWHC 2548 (Pat) ("Warner-Lambert V"). In that judgment I held that:

i) none of the claims of the Patent was obvious over any of the prior art relied upon by Mylan and Actavis;

ii) claims 1, 3, 4, 6, 13 and 14 of the Patent were invalid on the ground of insufficiency;

iii) even if claims 1 and 3 were valid, Actavis had not infringed those claims pursuant to section 60(1)(c) or section 60(2) of the Patents Act 1977; and

iv) Pfizer was liable for making groundless threats of patent infringement proceedings, albeit not in all the cases alleged by Actavis.

On 16 October 2015 I gave both Mylan and Actavis on the one hand and Warner-Lambert on the other hand permission to appeal against my decisions with respect to insufficiency, and I gave Warner-Lambert permission to appeal against my decision with respect to infringement under section 60(1)(c) (but not section 60(2)), subject to the qualification that I refused permission to appeal against my findings of fact. In view of certain submissions by counsel for Warner-Lambert during the hearing on 11 November 2015, I should make it clear that the permission to appeal which I granted to Warner-Lambert with respect to infringement was limited to claims 1 and 3 of the Patent, those being the only claims which were relied upon by Warner-Lambert at trial.

In the meantime, in case both appeals on validity are unsuccessful, on 1 October 2015 Warner-Lambert had made a conditional application to amend the Patent. The proposed amendments fall into two categories. The first category consists of simple deletion of claims which were held to be invalid. Those proposed amendments are, as I understand it, uncontroversial. The second category consists of an amendment which does not amount to a simple deletion, but on the contrary, amounts to a re-writing of one of the existing claims. The proposed amendment is to what was claim 3 of the Patent and, following deletion of old claim 1, will become new claim 2. For convenience I will continue to refer to it as claim 3. The amendment consists of adding to the end of the claim the words "caused by injury or infection of peripheral sensory nerves". The basis for that amendment is said to be the statement in [0006] of the Patent that "Neuropathic pain is caused by injury or infection of peripheral sensory nerves".

Mylan and Actavis both oppose the proposed re-writing amendment. It is Mylan and Actavis' contention that the application to make that amendment amounts to an abuse of the process of the court. In addition, it will be Mylan and Actavis' contention, if the application is allowed to proceed, that the amendment is not allowable on the grounds that it lacks clarity, adds subject matter and does not cure the invalidity of claim 3 (using the old numbering).

It is worth noting that Warner-Lambert evidently anticipated this objection, because the application was supported by a witness statement of Nicola Dagg of Warner-Lambert's solicitors running to 40 paragraphs which canvassed the procedural history of the proceedings at some length and concluded with the assertion that "there can be no prejudice to the Claimants by the making of the application at this stage".

On 16 October 2015 I directed a preliminary hearing of the issue as to whether the application amounts to an abuse of process.

The law

General principles as to abusive re-litigation

Abuse of the process of the court can take a number of forms. The form of abuse of process which is relevant here is that associated with the case of Henderson v Henderson (1843) 3 Hare 100. Although Henderson v Henderson itself was a case of cause of action estoppel, Sir James Wigram V-C's dicta in that case subsequently gave rise to a wider rule preventing re-litigation in circumstances not amounting to strict res judicata. This wider rule has come to be regarded as a manifestation of the court's power to prevent an abuse of its own process. The authorities on this wider rule were reviewed by Lord Bingham of Cornhill in Johnson v Gore Wood & Co [2002] 2 AC 1. Lord Bingham concluded in a frequently cited passage at 3l:

"But Henderson v Henderson abuse of process, as now understood, although separate and distinct from cause of action estoppel and issue estoppel, has much in common with them. The underlying public interest is the same: that there should be finality in litigation and that a party should not be twice vexed in the same matter. This public interest is reinforced by the current emphasis on efficiency and economy in the conduct of litigation, in the interests of the parties and the public as a whole. The bringing of a claim or the raising of a defence in later proceedings may, without more, amount to abuse if the court is satisfied (the onus being on the party alleging abuse) that the claim or defence should have been raised in the earlier proceedings if it was to be raised at all. I would not accept that it is necessary, before abuse may be found, to identify any additional element such as a collateral attack on a previous decision or some dishonesty, but where those elements are present the later proceedings will be much more obviously abusive, and there will rarely be a finding of abuse unless the later proceeding involves what the court regards as unjust harassment of a party. It is, however, wrong to hold that because a matter could have been raised in earlier proceedings it should have been, so as to render the raising of it in later proceedings necessarily abusive. That is to adopt too dogmatic an approach to what should in my opinion be a broad, merits-based judgment which takes account of the public and private interests involved and also takes account of all the facts of the case, focusing attention on the crucial question whether, in all the circumstances, a party is misusing or abusing the process of the court by seeking to raise before it the issue which could have been raised before. As one cannot comprehensively list all possible forms of abuse, so one cannot formulate any hard and fast rule to determine whether, on given facts, abuse is to be found or not. Thus while I would accept that lack of funds would not ordinarily excuse a failure to raise in earlier proceedings an issue which could and should have been raised then, I would not regard it as necessarily irrelevant, particularly if it appears that the lack of funds has been caused by the party against whom it is sought to claim. While the result may often be the same, it is in my view preferable to ask whether in all the circumstances a party's conduct is an abuse than to ask whether the conduct is an abuse and then, if it is, to ask whether the abuse is excused or justified by special circumstances. Properly applied, and whatever the legitimacy of its descent, the rule has in my view a valuable part to play in protecting the interests of justice."

Lord Millett added at 59-60:

"It is one thing to refuse to allow a party to relitigate a question which has already been decided; it is quite another to deny him the opportunity of litigating for the first time a question which has not previously been adjudicated upon. This latter (though not the former) is prima facie a denial of the citizen's right of access to the court conferred by the common law and guaranteed by article 6 of the Convention for the Protection of Human Rights and Fundamental Freedoms (1953). While, therefore, the doctrine of res judicata in all its branches may properly be regarded as a rule of substantive law, applicable in all save exceptional circumstances, the doctrine now under consideration can be no more than a procedural rule based on the need to protect the process of the court from abuse and the defendant from oppression. In Brisbane City Council for AG for Queensland [1979] AC 411, 425 Lord Wilberforce, giving the advice of the Judicial Committee of the Privy Council, explained that the true basis of the rule in Henderson v Henderson 3 Hare 100 is abuse of process and observed that it 'ought only to be applied when the facts are such as to amount to an abuse: otherwise there is a danger of a party being shut out from bringing forward a genuine subject of litigation'. There is, therefore, only one question to be considered in the present case: whether it was oppressive or otherwise an abuse of the process of the court for Mr Johnson to bring his own proceedings against the firm when he could have brought them as part of or at the same time as the company's action. This question must be determined as at the time when Mr Johnson brought the present proceedings and in the light of everything that had then happened. There is, of course, no doubt that Mr Johnson could have brought his action as part of or at the same time as the company's action. But it does not at all follow that he should have done so or that his failure to do so renders the present action oppressive to the firm or an abuse of the process of the court. As May LJ observed in Manson v Vooght [1999] BPIR 376, 387, it may in a particular case be sensible to advance claims separately. In so far as the so-called rule in Henderson v Henderson suggests that there is a presumption against the bringing of successive actions, I consider that it is a distortion of the true position. The burden should always rest upon the defendant to establish that it is oppressive or an abuse of process for him to be subjected to the second action"

Application to patent cases

Most patents contain one or more independent claims together with subsidiary claims with additional features. As progressively more features are included in the subsidiary claims, so the scope of the monopoly narrows. In this way the subsidiary claims provide the patentee with a series of fall-back positions in case the independent valid is held to be invalid. It is not uncommon for there to be a considerable number of subsidiary claims. For that reason, it is the invariable practice of the Patents Court to require the patentee to specify which claims it will contend to be independently valid (i.e. which claims it will contend are valid even if the main claim is invalid) well in advance of trial.

In addition to the fall-back positions provided by the subsidiary claims, it is open to the patentee to apply to amend the claims pursuant to section 75 of the Patents Act 1977. Such an application may be unconditional or conditional upon a finding of invalidity. (There was a period when the courts did not permit patentees to make conditional applications, but this has been permitted for about ten years now.) Where the application is conditional, it can provide the patentee with yet further fall-back positions. When made before trial, such application will normally be directed to be heard at trial. If it is only made shortly before trial, the court may direct that the application be advertised (and any opposition from third parties as a result of advertisement determined) following trial if necessary. This procedure enables the validity of the proposed amended claims to be determined at the same trial as the granted claims.

As a result of the procedures described above, it frequently happens that, following trial, the court finds that some claims (whether as originally granted or as proposed to be amended) are valid and some are invalid. In those circumstances the court will not normally revoke the patent, but instead will direct the patent to be amended to delete the invalid claims (as well as allowing any amendments which have been applied for and found allowable). Normally there can be no objection to such an amendment.

In some cases, however, the patentee makes an application after judgment not simply to delete claims which have been held invalid, but rather to make what are contended to be validating amendments to some or all of the claims. Typically this will involve re-writing the claims by inserting additional features from the description. This may happen either where the court has held that all of the existing claims are invalid or where the court has held that some of the claims are invalid and the patentee wishes to make a validating amendment to some or all of the latter. The present case is an instance of the latter scenario.

Where such an application is made, it is common for the other party to object that the application should not be permitted to proceed because it will require a second trial of the validity of the proposed amended claims and thus amounts to an abuse of process on Henderson v Henderson grounds. The principles to be applied in determining whether such an objection should be upheld were considered by the Court of Appeal in a trio of cases in each of which the leading judgment was given by Jacob LJ, namely Nikken Kosakusho Works v Pioneer Trading Co [2005] EWCA Civ 906, [2006] FSR 4, Vector Corp v Glatt Air Techniques Ltd [2007] EWCA Civ 805, [2008] RPC 10 and Nokia GmbH v IPCom GmbH [2011] EWCA Civ 6, [201l] FSR 15.

The principles were stated by Jacob LJ in the last of these cases as follows:

"100. I described the position for such a type [of amendment application] in Nikken [2006] FSR 4:

'[11] Class (c) involves something different, a proposed claim which was not under attack and could not have been under attack prior to trial. If the court is to allow such a claim to be propounded after trial, there is almost bound to be a further battle which would arise in the proposed amendment proceedings. That battle will be over whether or not the proposed amended claim is valid. I say "almost bound" because I can just conceive a case where the point was covered by the main litigation in some way or other.'

I should have added that a further battle may also arise about the allowability of the amendments. ...

101. In Nikken I then went on to say that an exercise of discretion to allow two trials would be improper for three reasons which I can summarise here:

(a) It would breach the general procedural rule laid down as long ago as 1843 in Henderson v Henderson (1843) 3 Hare 100, that a party should normally not be allowed to advance in a second proceeding matter he could have advanced in the first.

(b) That rule had been applied in patent cases by this Court in Windsurfing International Inc v Tabur Marine (Great Britain) Ltd [1985] R.P.C. 59, CA and Aldous [L.]J. in Lubrizol Corp v Esso Petroleum Co Ltd (No. 5) [1998] R.P.C. 727, CA. I said Aldous [L.]J had epitomised the position when he said, at p.790:

'I believe it is a fundamental principle of patent litigation that a party must bring before the court the issues that he seeks to have resolved, so as to enable the court to conclude the litigation between the parties.'

(c) The general court rules were 'dead against' allowing amendment proceedings requiring a second trial after a first trial had determined the patent was invalid. I put it this way:

'[19] … The whole code is governed by the overriding objective contained in Part 1.1.1. 1.1.2 specifies some examples of cases of dealing with a case justly. 2(b) is "saving expense". Plainly a second trial would cause increased expense. 2(d) is ensuring that it is "dealt with expeditiously and fairly". Having two bites of the cherry is doing neither of those things.

[20] The rules descend into more detail. Under the court's duty to manage cases, 1.4 requires the court actively to manage cases and 1.4.2 says that active case management includes "identifying the issues at an early stage and dealing with as many aspects of the case as it can on the same occasion".'

102. Moreover I considered that a case involving the validity of a patent concerned not merely the private rights of the parties but also the public interest and the court was "particularly entitled to have regard to that".

103. I also said that:

'[25] In the real world patentees, faced with a real problem about the construction of their claims, ought to face up to them early and decide whether they need an amendment or might need an amendment. That is one of the purposes of the rule, to make people face up to their cases at an early stage, not at a late stage.'

That of course also applies to the validity of the claims.

104. Both Laws L.J. and Waller L.J. delivered short, but emphatic concurring judgments. Laws L.J. said:

'[33] I agree. I wish only to underline my firm support for the view, which is a major and emphatic theme of my Lord, Jacob L.J.'s judgment, that the result of this appeal is driven by the principle of the general law given by Henderson and clothed with renewed vigour by the overriding objective of the CPR, that in any given litigation the parties are required to bring forward their whole case. It provides [the report says "provokes"] certainty and [the report says "of"] economy and minimises expense, and it applies as powerfully in this area of the law as any other.'

And Waller LJ:

'[34] In one sense the question is whether there should be some special rule in patent cases. In any other litigation it would be unfair to allow a party to amend his case post judgment so as to allow an opportunity to succeed after a further trial, however small. The question is whether there is something special about patent litigation. The authorities do not support the proposition that there is something special. Indeed, those authorities cited both by the judge and by my Lord go to the opposite effect. Those are reinforced, as I would see it, by the new CPR. I am relieved to find the position to be so.'

…

108. I do not think there is anything inconsistent between [the speeches of Lord Bingham and Lord Millett in Johnson v Gore Wood] and Nikken. I accept entirely that the true test is one of abuse of process – procedural fairness - and that the burden lies on the party objecting to the second action to show this. However where a party fails to advance a case he could have advanced much earlier and does so without any real justification, he is abusing the process and the other party is therefore entitled to object. It is not normally procedurally fair to subject the other side to successive cases when you could readily have put them all in one go.

109. There are exceptions, depending on the facts (such as the facts of Gore-Wood). …"

Article 138(3) EPC 2000

Counsel for Warner-Lambert pointed out that Article 138 of the European Patent Convention was amended in 2000 (with effect from 13 December 2007) to introduce paragraph (3) which provides:

"In proceedings before the competent court or authority relating to the validity of the European patent, the proprietor of the patent shall have the right to limit the patent by amending the claims. The patent as thus limited shall form the basis for the proceedings."

In my view this does not affect the principles stated by Jacob LJ in Nokia for two reasons. The first is that the purpose of this provision was simply to ensure that all EPC Contracting States allowed post-grant amendment, in particular by way of defence of invalidity proceedings. Unlike some EPC Contracting States, the United Kingdom already provided for this in section 75 of the 1977 Act and in its procedural rules. Article 138(3) is not concerned with procedural fairness in litigation. Secondly, Jacob LJ considered Article 138 in Nokia at [125]-[130], and held that it did not detract from the principles he had set out earlier in his judgment.

Central limitation

The EPC 2000 also introduced Articles 105a-105c, which provide a procedure whereby the claims of a European Patent can be centrally limited in all the designated Contracting States by a single application to the European Patent Office.

In my view these provisions do not affect the principles stated by Jacob LJ in Nokia either, for three reasons. First, these provisions are not concerned with procedural fairness in litigation in Contracting States either. Secondly, Jacob LJ considered these provisions in Nokia at [94] and held that they were not relevant. Thirdly, the effect of an application for central limitation on pending English proceedings was considered by the Court of Appeal in Samsung Electronics Co Ltd v Apple Retail UK Ltd [2014] EWCA Civ 250, [2015] RPC 3. Kitchin LJ made it clear at [51]-[52] that it would not be an abuse of the process for a patentee to make a central limitation application, even if it would be an abuse for the patentee to apply to make the same amendment under section 75, following the trial in English proceedings.

As I understand Kitchin LJ's reasoning, this is because central limitation is a separate and fundamentally different procedure to amendment under section 75. An application under section 75 is made to the court, may be conditional, only applies to the UK designation, takes place in the context of infringement and/or revocation proceedings and is subject to the discretion of the court. An application for central limitation is made to the EPO, must be unconditional, applies to all designated Contracting States, is independent of any litigation in any of those States and cannot be refused on discretionary grounds.

As Kitchin LJ pointed out at [54], where an application is made under section 75, the English courts retain the power to control their own proceedings and to prevent activities which would amount to an abuse of their process. Where an application is made for a central limitation, the process is that of the EPO, and hence any question of preventing an abuse of that process would be a matter for the EPO.

As Kitchin LJ also made clear at [55]-[58], however, the fact that the application for a central limitation is not an abuse of the process of the EPO does not answer the distinct question of whether an attempt by the patentee to rely upon the centrally limited claims in the English proceedings would be an abuse of the process of the English court. The answer to that question will depend on all the circumstances.

Foreign cases

Counsel for Warner-Lambert referred in his submissions to the decisions of the Hoge Raad (Supreme Court of the Netherlands) in Boston Scientific Scimed Inc v Medinol Ltd (6 March 2009) and of the Bordeaux Cour d'Appel in SAS Eparco v SARL Ouest Environment ELRL (11 June 2012). In my judgment neither of these judgments is of assistance in the present case. This is for two reasons. The first is both were concerned with the impact of limitations to the patent in suit upon pending appeals in national proceedings (the situation which confronted the Court of Appeal in Samsung v Apple). In Boston Scientific the patent had been centrally limited in the EPO, while in Eparco it appears that the patent was limited in the French Intellectual Property Office. Where a patent is limited pending appeal, the issue which arises is as to the impact of the limitation on the appeal.

Secondly, and more fundamentally, any assessment of abuse of process must depend upon the procedural rules applicable in the relevant jurisdiction, which will reflect the procedural philosophy applicable in that jurisdiction. But the EPC Contracting States differ not merely in their procedural rules, but also in their procedural philosophies. Thus there are different conceptions of procedural economy. The traditional English conception is that it requires the first instance court to adjudicate upon all essential points in dispute, certainly all points that require findings of fact or evaluation. In that way, if there is an appeal, the Court of Appeal is in a position to deal with any issues of law that may then arise and dispose of the case without either a re-hearing or remitting it to the first instance court. By contrast, there are many civil law jurisdictions where the view is taken that the correct approach to procedural economy is for the first instance court only to decide the issues which are sufficient to enable that court to dispose of the case, and to leave other issues undecided.

These differing views as to procedural economy are related to the different views which are taken as to the scope of an appeal, including new arguments and new evidence. In England and Wales, appeal is by way of review only. The question is whether the first instance court was wrong in reaching its decision. New arguments will generally only be admitted if they concern the existing issues, can be determined on the findings of fact made below and can be determined without prejudicing the opposing party. New evidence is rarely admitted. By contrast, in some other legal systems, appeals (at least to the second instance) are by way of re-hearing in the full sense, and new arguments and new evidence are more freely admitted. Furthermore, in those systems issues may be decided for the first time on appeal, or if further evidence is required cases may be remitted to the first instance.

If you have a system where your approach to procedural economy is that the first instance court can decide one point, if that is sufficient for it to dispose of the case, and then you have a complete re-hearing in the Court of Appeal with the Court of Appeal able to receive new arguments and new evidence and to decide issues for the first time or remit them back to the first instance, that inevitably means that your view on abuse of process will be rather different than if you have a system whereby the first instance court decides all points and the appellate court is engaged only in a review.

Procedural history

Both sides rely on the procedural history which led to Warner-Lambert V, but they advance completely different interpretations of that history. Accordingly, it is necessary for me to set it out in detail. Before doing so, I need to correct an error in Warner-Lambert V.

The IASP definition of neuropathic pain

The second edition of the IASP Classification of Chronic Pain published in 1994 defined "neuropathic pain" as:

"Pain initiated or caused by a primary lesion or dysfunction in the nervous system.

Note: See also Neurogenic Pain and Central Pain. Peripheral neuropathic pain occurs when the lesion or dysfunction affects the peripheral nervous system. Central pain may be retained as the term when the lesion or dysfunction affects the central nervous system."

Consistently with the note, "central pain" was defined as:

"Pain initiated or caused by a primary lesion or dysfunction in the central nervous system".

If the definition of "neuropathic pain" quoted above is compared with the version of the definition set out in Warner-Lambert V at [50], it can be seen that the latter wrongly includes the words "peripheral or central" before the words "nervous system". (Less importantly, the latter also substitutes the word "of" for the word "in".)

This error stems from paragraph 4.7 of Dr Scadding's first report, which quoted the definition with the extraneous words. By contrast, paragraph 41 of Prof Wood's first report and paragraph 48 of Prof Woolf's report quoted the definition correctly. Furthermore, the correct definition was put to Prof Clauw in cross-examination by counsel for Mylan. I regret that I did not spot this when writing the judgment. Astonishingly, the error does not appear to have been noticed by any of the parties until Warner-Lambert drew it to my attention after a draft of this judgment was circulated to the parties as a result of statements made in the draft.

The correct version of IASP definition does not distinguish between the peripheral nervous system and the central nervous system. Accordingly, and as is confirmed by the note, the definition embraces both peripheral neuropathic pain and central (neuropathic) pain. I therefore do not consider that this error affects my reasoning with respect to insufficiency in Warner-Lambert V.

The Patent

The specification states at [0006]

"The instant invention is a method of using (S)-3-(aminomethyl)-5-methylhexanoic acid or a pharmaceutically acceptable salt thereof as an analgesic in the treatment of pain as listed above. Pain such as inflammatory pain, neuropathic pain, cancer pain, postoperative pain, and idiopathic pain which is pain of unknown origin, for example, phantom limb pain are included especially. Neuropathic pain is caused by injury or infection of peripheral sensory nerves. It includes, but is not limited to pain from peripheral nerve trauma, herpes virus infection, diabetes mellitus, causalgia, plexus avulsion, neuroma, limb amputation, and vasculitis. Neuropathic pain is also caused by nerve damage from chronic alcoholism, human immunodeficiency virus infection, hypothyroidism, uremia, or vitamin deficiencies. Neuropathic pain includes, but is not limited to pain caused by nerve injury such as, for example, the pain diabetics suffer from."

There is no use in the specification of the expressions "peripheral neuropathic pain" or "central neuropathic pain".

As explained in more detail in Warner-Lambert V at [98]-[110] and [344], the Patent presents data from three animal models (the rat paw formalin model, the carrageenin model and the post-operative pain model) which were recognised models for inflammatory pain, but none of which was a recognised model for neuropathic pain. The specification expressly states that the data presented show that pregabalin is effective in the treatment of inflammatory pain. By contrast, the specification does not claim that the data presented show that pregabalin is effective in the treatment of neuropathic pain. The specification expressly mentions two recognised models of neuropathic pain (the CCI and spinal nerve ligation models), but presents no data from such models. There is no mention in the specification of central sensitisation. Indeed, there is no suggestion in the specification that there is any unifying characteristic or principle which enables a prediction to be made in respect of conditions other than inflammatory pain.

The Lyrica marketing authorisation

Pfizer markets Lyrica under licence from Warner-Lambert under the trade mark Lyrica. Pfizer has a marketing authorisation for Lyrica in respect of "peripheral and central neuropathic pain" as well as epilepsy and general anxiety disorder ("GAD"). Thus Warner-Lambert will have been aware at all material times that there was a distinction between peripheral neuropathic pain and central neuropathic pain.

Mylan and Actavis' claims for revocation

Mylan commenced its claim for revocation of the Patent on 24 June 2014. Actavis commenced their claim for revocation of the Patent on 12 September 2014. Both Mylan and Actavis launched their claims in order to clear the way for launching full label generic pregabalin products (i.e. ones authorised for neuropathic pain as well as epilepsy and GAD).

On 16 September 2014 Birss J ordered an expedited trial of Mylan's claim, to commence on 29 June 2015. Mylan's claim was expedited on the basis of the commercial significance of the pregabalin market and the need for legal certainty as regards the scope of Warner-Lambert's rights. On 3 November 2014 Birss J ordered Actavis' claim to be tried together with Mylan's claim.

Warner-Lambert's application for central limitation

On 22 September 2014 Warner-Lambert applied to the EPO centrally to limit the claims of the Patent to the use of pregabalin (as opposed to a broader class of compounds). It is obvious that the purpose of the application was to address part of the insufficiency case raised by Mylan and Actavis. The application was successful and the amendments were made on 21 January 2015.

As a result, claim 1 was limited to use of pregabalin for the preparation of a pharmaceutical composition for treating pain. Claim 3 was limited to "neuropathic pain"; claim 4 to "cancer pain"; claim 6 to "phantom limb pain"; claim 10 to "trigeminal neuralgia pain"; claim 11 to "acute herpetic and post-herpetic pain"; claim 12 to "causalgia pain"; and claim 14 to "fibromyalgia pain".

Warner-Lambert's infringement claim

On 8 December 2014 Warner-Lambert commenced a claim for infringement of the Patent against Actavis, and applied for an interim injunction, in respect of Actavis' intended launch of a skinny label generic pregabalin product for the treatment of epilepsy and GAD under the trade mark Lecaent. I heard the application for an interim injunction on 13-15 January 2015. On the first day of the hearing I directed that the trial of the infringement claim should be expedited so as to be heard immediately after the trial of the claims for revocation.

The only claims of the Patent which were relied upon by Warner-Lambert for the purposes of its infringement claim against Actavis were claims 1 and 3.

The plea of insufficiency

After Warner-Lambert had limited the claims of the Patent centrally to claim only the use of pregabalin, Mylan and Actavis amended their Grounds of Invalidity so that their plea of insufficiency read as follows:

"The specification of the Patent does not disclose the invention claimed in each and every claim thereof clearly enough and completely enough for them to be performed by a person skilled in the art.

PARTICULARS

(a) The biological results presented in the specification are confined to the use of (S)-3- (aminomethyl)-5-methylhexanoic acid and 3-aminomethyl-5-methylhexanoic acid in a limited number of animal tests (hereinafter the "Animal Tests"). The person skilled in the art could not, from such results and/or his common general knowledge, make a reasonable prediction (nor does the specification make it plausible) that:

…

(i)~~(iii)~~ the compound of claim 1 would be effective in treating any types of pain referred to in paragraph [0003] or as claimed in any claim other than those for which the Animal Tests provide a plausible model.

(b) Further or alternatively, it would require undue effort on the part of the skilled person to identify:

…

(i)~~(iii)~~ whether the compounds of claim 13 was~~were~~ in fact effective in treating any (and if so which) types of pain referred to in paragraph [0003] or as claimed in any claim other than those for which the Animal Tests provide a plausible model.

(c) Further or alternatively, claim 1~~-3 include~~ is to the manufacture of a medicament using a compounds which areis only effective in treating certain types of pain. Without prejudice to the generality of the foregoing, the Second Claimant will rely on the fact that (S)-3- (aminomethyl)-5-methylhexanoic acid is ineffective in established acute postoperative pain.

(d) In the premises, the monopoly claimed in each and every claim of the Patent exceeds the technical contribution (if any) made by the patentee."

Warner-Lambert now complains that this pleading was unparticularised, but at the time it did not serve a request for further information in respect of it. In any event, I agree with Mylan and Actavis that it was clear from the pleading that it was being alleged that the claims were implausible in relation to any types of pain for which the three animal models used to generate the data presented in the Patent were not a plausible proxy.

The plea of independent validity

On 28 November 2014 Warner-Lambert notified Mylan and Actavis that it intended to contend that claims 1, 3-7, 9, 11, 13 and 14 were independently valid. It follows that Warner-Lambert must have given thought to its fall-back positions in the event that claim 3 was found invalid.

Pleas as to common general knowledge

On 12 December 2014 Mylan and Actavis served a statement of the common general knowledge. Paragraph 8 was in the following terms:

"Neuropathic pain is caused by trauma- or disease-evoked damage affecting the peripheral nerves, posterior (sensory) spinal nerve roots, sensory transmission pathways in the spinal cord and brain stem, or the major sensory regions of the brain, collectively known as the somatosensory pathway or system."

On 27 January 2015 Warner-Lambert served a reply statement which took the form of an amended version of the Mylan and Actavis statement. Among the amendments were the following to paragraph 8 (re-renumbered as 14):

"The causes of many types of neuropathic pain are not well-understood or defined. Neuropathic pain may be is caused by trauma-or disease evoked damage or alterations affecting the peripheral nerves (which can include damage to or changes in nociceptors) posterior (sensory) spinal nerve roots, sensory transmission pathways in the spinal cord and brain stem, or the major sensory regions of the brain, collectively known as the somatosensory pathway or system."

The key difference between these versions for present purposes is that Mylan and Actavis' version clearly covers both peripheral and central neuropathic pain, whereas Warner-Lambert's version appears to be limited to peripheral neuropathic pain.

Warner-Lambert's version of the statement also included a section headed "Central sensitisation" which stated at paragraph 5 that "the phenomenon of central sensitisation has long been recognised clinically in nociceptive, inflammatory and neuropathic pain conditions". It also referred at paragraph 32 to the late phase of the rat paw formalin model being "linked to central sensitisation" and at paragraph 33 to the carrageenin model providing "some information about central sensitisation".

Mylan and Actavis accept that it was apparent to them from Warner-Lambert's version of the statement that central sensitisation was the basis on which Warner-Lambert would seek to rebut the allegation of insufficiency. They nevertheless say, and I accept, that it was not apparent to them how Warner-Lambert would seek to do so prior to service of the evidence in chief.

Although there was some correspondence about the statement of common general knowledge, no agreement was reached on the points of difference.

Evidence in chief

On 17 April 2015 the parties exchanged evidence in chief.

In support of Mylan and Actavis' insufficiency case, Dr Scadding expressed the opinion in his report that none of claims 1, 3, 6, 10, 11, 12 and 14 were supported by the data in the Patent from the three animal models. Dr Scadding accepted that claims 2, 5, 7, 8 and 9 were supported by the data. As for claim 4 (cancer pain), his view was that it was supported in so far as the pain was nociceptive, but not in so far as the pain was neuropathic. Prof Wood gave evidence in his report to similar effect.

As is common ground, the main focus of the insufficiency attack in this evidence centred around the distinction between neuropathic pain and inflammatory pain. To this end, large portions of the first report of Prof Wood was given over to evidence that central sensitisation was only recognised as a minor feature of inflammatory pain, and not neuropathic pain at all, and to the suggestion that the data in the Patent only supported claims to those pain types which were inflammatory in nature.

Warner-Lambert points out, correctly, that neither Prof Wood nor Dr Scadding distinguished between peripheral neuropathic pain and central neuropathic pain in their reports when commenting on the plausibility of the claims in question. Mylan and Actavis reply, equally correctly, that they had no particular need to do so, since Mylan and Actavis interpreted claim 3 as covering all forms of neuropathic pain and no claim was being advanced by Warner-Lambert which was limited to peripheral (or central) neuropathic pain.

More importantly, perhaps, Warner-Lambert points out that both Prof Wood and Dr Scadding specifically noted the absence of any data from the CCI and ligation models to support the claims in question. Warner-Lambert says that, since these models are models of peripheral nerve damage, Warner-Lambert understandably did not appreciate that it would be said that phantom limb pain was a central pain that had nothing to do with peripheral neuropathic pain.

It should be noted, however, that Dr Scadding's report not only (as explained above) misquoted the IASP definition of neuropathic pain in a way which made it clear that it covered both peripheral and central neuropathic pain, but also specifically distinguished between peripheral and central neuropathic pain (at paragraph 4.9). In addition, Dr Scadding introduced (at paragraph 4.22) an anatomical classification of causes of neuropathic pain in Appendix 1 to the report. This divided the conditions into five groups: "Peripheral Nerve", which included causalgia, amputation and plexus cancer invasion; "Dorsal Root Ganglion & Spinal Root", which included trigeminal neuralgia; "Spinal Cord", which included multiple sclerosis and tumour; "Brainstem", which also included multiple sclerosis; and "Brain" which included ischaemic and haemorrhagic stroke, tumour and phantom limb pain. Furthermore, Dr Scadding referred to the statement in the Patent at [0006] that neuropathic pain is caused by injury or infection of peripheral sensory nerves, and expressly made the point that "CNS damage could also result in neuropathic pain" (at paragraph 6.6). Dr Scadding also expressed the opinion that fibromyalgia was not considered to be a neuropathic pain in 1996 (at paragraph 6.5).

In support of Warner-Lambert's case as to the sufficiency of the claims, Prof Woolf expressed the opinion in his report that the three animal models were "models of central sensitisation" and as such were appropriate models for any pain types which included central sensitisation as a component, which included all the claimed pain types. In particular, he said that some conditions contained elements of both neuropathic pain and inflammatory pain and that central sensitisation was common to both (at paragraphs 45-46). He did not explicitly address the differences between paragraph 8 of Mylan and Actavis' statement of the common general knowledge and Warner-Lambert's version, however. Indeed, he quoted the IASP definition of neuropathic pain without commenting on the fact that it embraced both peripheral and central neuropathic pain.

Prof Clauw's report acknowledged that certain types of pain, including phantom limb pain, are primarily due to central causes, but expressed the view that all the specific pain conditions in the claims would be understood as having a central sensitisation component. He did not explicitly address the differences between paragraph 8 of Mylan and Actavis' statement of the common general knowledge and Warner-Lambert's version either. Moreover, he described neuropathic pain as resulting from "damage to elements of the nervous system (e.g. due to diabetes, alcohol intake, chemotherapy drugs, strokes) or entrapment of nerves …" (at paragraph 35). This description appears to embrace central as well as peripheral neuropathic pain, but obscures the distinction between the two. Prof Clauw also said that phantom limb pain was a form of neuropathic pain.

Evidence in reply

On 22 May 2015 the parties exchanged evidence in reply.

As is common ground, it continued to be Mylan and Actavis' primary case, supported by Prof Wood and Dr Scadding, that the data in the Patent did not make the treatment of neuropathic pain of any kind plausible.

Nevertheless, Dr Scadding did state in paragraph 7.4 of his second report (emphasis added):

"Professor Clauw goes on to say that the various pain conditions listed in claims 2 to 14 and in paragraph [0003] of the Patent would have been recognised by the Skilled Clinician as possessing a central sensitisation component. Again I disagree. In the case of 'idiopathic pain syndromes' the Skilled Clinician would struggle to associate these syndromes with any particular mechanism, let alone central sensitisation. In the case of peripheral neuropathic pain, the position was, at best, unknown (see paragraph 4.2 above). As for neuropathic pain caused by lesions in the central nervous system, it would not occur to the Skilled Clinician that these possessed a central sensitisation component. For example ischaemic and haemorrhagic stroke are relatively common causes of central pain, as is multiple sclerosis (MS). MS typically affects the spinal cord in multiple sites (although it frequently also affects the brain stem, cerebellum, and cerebral hemispheres). Other types of neuropathic pain where the primary cause is a lesion in the central nervous system and which the Skilled Clinician would not expect to possess a central sensitisation component are listed in Appendix 1 to my First Report under the headings Spinal Cord, Brainstem and Brain."

In my view this evidence was clearly drawing a distinction between peripheral neuropathic pain and central neuropathic pain, and equally clearly making the point that, even if the possession of a central sensitisation component (i.e. the unifying principle or characteristic relied upon by Warner-Lambert as supporting the breadth of the claims) could be regarded as a characteristic of peripheral neuropathic pain, it was not a characteristic of central neuropathic pain.

Warner-Lambert has adduced evidence on this application that Warner-Lambert and its advisors did not appreciate the significance of this evidence. That is a matter between Warner-Lambert and its advisors.

In any event, Prof Clauw responded in his second report to Dr Scadding's comments about neuropathic pain in the latter's first report, and specifically the way Dr Scadding had distinguished between peripheral and central neuropathic pain. In this context Prof Clauw stated (at paragraph 17):

"Secondly, although Dr Scadding acknowledges IASP's 1994 Classification of Chronic Pain in paragraph 4.7, he omits reference to the 'dysfunction' aspect of this definition in his characterisation of neuropathic pain in paragraph 4.9. The skilled team at the Priority Date would have understood that neuropathic pain could be caused by 'dysfunction' of the central nervous system rather than [i.e. as well as] a lesion, and the … IASP definition … therefore encompassed conditions such as fibromyalgia."

Prof Clauw went on to express the view that, although it was known that peripheral aspects contributed to neuropathic pain in many cases, central sensitisation often made a major contribution (at paragraphs 18-24).

It may be noted that Prof Clauw did not point out that Dr Scadding had misquoted the IASP definition. It appears that Prof Clauw did not regard the misquotation as significant, because the definition embraced pain caused by a lesion or dysfunction in the central nervous system as well as in the peripheral nervous system, that is to say, both peripheral and central neuropathic pain. It also appears that Prof Clauw had turned his mind to the way in which the claim could be supported in so far as it extended to central neuropathic pain.

As for Prof Woolf, his second report did not really address this issue, but it is noticeable that he did use the expression "peripheral neuropathic pain" in places (e.g. at paragraphs 28 and 46), thus implicitly distinguishing it from central neuropathic pain.

Further evidence

Between 22 May 2015 and trial, both sides served further expert reports. In particular, Warner-Lambert served a third report from Prof Woolf on 15 June 2015 in which he responded to a number of points made by Dr Scadding in the latter's second report, but not paragraph 7.4.

Skeleton arguments

The parties exchanged skeleton arguments for trial on 22 June 2015.

The distinction between peripheral neuropathic pain and central neuropathic pain was clearly raised in Mylan and Actavis' skeleton argument as part of their insufficiency argument on claim 3.

First, at paragraph 14(6) in the Introduction and Overview section, having set out a number of points to the effect that the claim to neuropathic pain was not supported by the specification or the common general knowledge, Mylan and Actavis added:

"In any event, important types of neuropathic pain such as pain from stroke and multiple sclerosis had no relationship to central sensitisation, since they do not involve any peripheral damage. So the claim is still too broad."

Secondly, when addressing the common general knowledge with respect to neuropathic pain, Mylan and Actavis quoted the IASP definition and went on at paragraph 42:

"The lesion or dysfunction can occur either in the PNS (referred to as peripheral neuropathic pain) or in the CNS (referred to simply as central pain). A table indicating the various causes of neuropathic pain (which is non-exhaustive) by reference to the relevant anatomical site is at Annex 1 to Dr Scadding's first report. ..."

Thirdly, in the section on construction, Mylan and Actavis said at paragraph 116:

"Sixth, the Skilled Clinician would recognise that some of the pain conditions listed in paragraph [0003] and claims 2-14 are unlikely to involve central sensitisation. Dr Scadding gives the example of central pain⁶¹."

Footnote 61 cited paragraph 7.4 of Dr Scadding's second report.

Finally, in the section on insufficiency, Mylan and Actavis said under the heading "Claim 3 is too broad even if the formalin test is as Warner-Lambert says" (emphasis added):

"132. Dr Scadding says that with respect to central pain (neuropathic pain where the primary cause is a lesion in the CNS such as stroke pain or multiple sclerosis), it would not occur to the Skilled Clinician that these possessed a central sensitisation component⁶⁷. This makes obvious sense because in such a situation there is no peripheral drive to cause the sensitisation. It follows that even if the specification makes it plausible that pregabalin would be effective in treating peripheral neuropathic pain (which the Claimants do not accept), claim 3 still exceeds the patentee's technical contribution.

133. We are unsure what Warner-Lambert's answer to this point is, but it seems likely that the point is a major part of the reason why Warner-Lambert (wrongly) says that claim 1 is implicitly limited to pain with a central sensitisation component."

Footnote 67 again cited paragraph 7.4 of Dr Scadding's second report.

Warner-Lambert points out that:

i) the table in Annex 1 to Dr Scadding's first report included 18 conditions in total;

ii) the only conditions specifically mentioned in the skeleton argument in this connection were stroke pain and multiple sclerosis;

iii) the reference to the absence of any peripheral drive to cause central sensitisation in cases of central neuropathic pain implied that the conditions relied on were not caused by damage or injury at the periphery.

I accept all of these points, but I would add that stroke pain and multiple sclerosis were clearly being put forward as non-limiting examples.

The issue was not addressed at all in Warner-Lambert's skeleton argument, which only addressed Mylan and Actavis' primary plausibility attack at paragraph 158:

"As we currently understand it the Claimants' case on insufficiency is that the common general knowledge ... was that the animal tests in the Patent are predictive only of those types of pain set out in paragraph [0003] and subsequently claimed which are inflammatory in nature and not those which are neuropathic in nature, such that the skilled team could not, from the results of those tests and/or common general knowledge make a reasonable prediction that pregabalin would work to treat neuropathic pain."

Nevertheless, there was no complaint by Warner-Lambert following the exchange of skeleton arguments that it had been taken by surprise by the distinction drawn by Mylan and Actavis between peripheral neuropathic pain and central neuropathic pain.

Opening speech

In his opening speech at trial on 29 June 2015 counsel for Actavis said (at page 5 line 22 – page 6 line 9):

"Within neuropathic pain my Lord will be hearing about different category types. You will be hearing about diabetic neuropathy, post herpetic neuropathy and so forth. In terms of broad categories you will also be hearing about central neuropathic pain, where the damage to the nerve system is in the central nervous system; and peripheral neuropathic pain where the damage is in the peripheral nervous system. There are also categories my Lord will have picked up where there is dispute whether as at the priority date they were regarded as neuropathic pain at all or not. So quite a complicated picture, my Lord. Those, I think, are the main categories to keep one's eye on in the evidence."

In this passage counsel for Acytavis was careful to distinguish between peripheral neuropathic pain and central neuropathic pain. He explained why this mattered in two later passages.

In the first he said (at page 27 line 15 to page 28 line 18).

"There is one construction point that I should mention, my Lord. If you have the skeleton arguments, that is the best place to see this point; so, if you take Warner-Lambert's skeleton, at paragraph 115. We are on the issue here of what 'for treating pain' means in claim 1. … It is just simply about what the word 'pain' means. As we see here, Warner-Lambert say that because their experts explain that the pain types are characterised by hyperalgesia and/or allodynia, they would have been recognised as having a central sensitisation component. We understand it, therefore, to be Warner-Lambert's case that 'pain' in claim 1 means pain having or being associated with a central sensitisation component. We do not agree. Our submission is that 'pain' has its ordinary meaning of pain. But the reason this matters is that, as we see it, it is one of Warner-Lambert's ways to address the insufficiency case, because whilst we disagree with them about the content of their evidence on central sensitisation, the most they can get to, if everything else falls into place for them, is that the experimental models in the patent give you an expectation of being able to treat pain which has a central sensitisation component. Now, there are types of pain that do not have a central sensitisation component. So, we submit the claim is insufficient for that reason; and it is by trying to implicitly read it down in this way, that Warner-Lambert seeks to escape that, as we understand it."

In the second passage he said (at page 29 line 23 – page 30 line 7):

"We also invite my Lord to have in mind, during the insufficiency evidence and argument, that neuropathic pain splits into two categories: one is peripheral neuropathic pain, and the other is central neuropathic pain. There is no association, whatever evidence may come out on the central sensitisation generally, there is no association of central sensitisation with central neuropathic pain, such as pain caused by stroke or multiple sclerosis. So, they will be insufficient for that reason, too."

Warner-Lambert again points out that the only conditions specifically mentioned in this passage were stroke and multiple sclerosis. Again, however, they were clearly non-limiting examples.

Counsel for Warner-Lambert did not make an opening speech, but he did raise two "housekeeping" points. He did not say that Warner-Lambert had been taken by surprise by the distinction drawn by Mylan and Actavis between peripheral neuropathic pain and central neuropathic pain.

Cross-examination

Prof Wood was not asked during cross-examination about the difference between peripheral neuropathic pain and central neuropathic pain. Warner-Lambert says that this was because he had not given any evidence about it in his reports. But Prof Wood himself raised the question (at day 1 page 56 line 25 – page 57 line 20, emphasis added):

"Q. So, if we just run through this briefly, there is a point in paragraph 3, and you explained in your first report, at paragraph 28, that 'a role for peripheral sensory neurons in most types of neuropathic pain was well established at the priority date'. It is not central to the issues in the case, is it, to go into this aspect in much more detail; do you agree with that?

A. No. I think this is a critically important aspect of our discussion, because we are dealing with a lot of pains that derive from neuropathies, from death in the periphery. So, I think if we are going to start talking about central mechanisms, then this is not an area that we should completely ignore.

Q. All right, Professor. You disagree with the suggestion that pain [will] arise without the involvement of nociceptors?

A. Well, there are clearly cases, like thalamic pain after a stroke, where there is no peripheral nervous system involvement at all. What I said is, most types of neuropathic pain involve the peripheral nervous system; and I think that is accurate and true."

Stroke pain was, of course, one of the examples which Mylan and Actavis had highlighted in their skeleton argument. Nevertheless, the cross-examiner did not pursue the matter.

On the other hand, Prof Wood was cross-examined briefly on the subject of phantom limb pain (at day 1 page 88 line 23 – page 89 line 7).

Dr Scadding was asked some questions about the difference between peripheral neuropathic pain and central neuropathic pain by reference to both the IASP definition (although it was not pointed out to him that he had misquoted this) and his Appendix 1 (at day 3 page 441 line 13 – page 447 line 19). During the course of this cross-examination Dr Scadding made the points that "by then people were using the broader terminology of 'neuropathic pain' to include central pain" and "the [IASP] definition refers to the initiating event". Dr Scadding was not cross-examined specifically about paragraph 7.4 of his second report or about stroke pain or multiple sclerosis as examples of central neuropathic pain, however.

Instead, counsel for Warner-Lambert cross-examined Dr Scadding about the Patent as follows (at day 3 page 570 line 6 – page 571 line 5):

"Q. I understand. Turn, please, to paragraph [0006]. You will see the first sentence of paragraph 6 says: 'The instant invention is a method of using pregabalin as an analgesic in the treatment of pain as listed above.' You would understand that as a reference back to paragraph [0003], would you not?

A. Yes.

Q. Then there is a list of pain states given. Then there follows a reference to neuropathic pain, and what the patent says is: 'Neuropathic pain is caused by injury or infection of peripheral sensory nerves.' Do you see that?

A. Yes.

Q. In fact, you would understand that as a reference to peripheral neuropathic pain?

A. Yes.

Q. This reflects the discussion we were having earlier. There was some uncertainty about what neuropathic pain means as a matter of common general knowledge at the priority date, but the patent here defines what it means by 'neuropathic pain'?

A. Yes.

Q. And whilst some might suggest that the patent should really have used the term 'peripheral neuropathic pain', instead of 'neuropathic pain', it is pretty clear what is meant by the term as a result of paragraph [0006]?

A. Yes."

As discussed in Warner-Lambert V at [257]-[260], in closing submissions counsel for Warner-Lambert relied upon this passage of cross-examination in support of a construction of claim 3 which restricted to words "neuropathic pain" to peripheral neuropathic pain, despite not having foreshadowed this contention anywhere and not having put it to Prof Wood, but I did not accept that construction. (It should perhaps be added that Prof Woolf espoused this interpretation of claim 3 in cross-examination, as can be seen from day 8 page 828 line 25 – page 829 line 3.)

For present purposes, what matters is that this shows that counsel for Warner-Lambert appreciated that Warner-Lambert faced a problem with respect to the sufficiency of claim 3 if claim 3 was construed to cover central neuropathic pain, and that the way in which he sought to address that problem was by contending for a narrow construction of claim 3 which limited it to peripheral neuropathic pain. The principal basis for that construction was the sentence in [0006] which is now relied on as supporting the proposed amendment to claim 3.

Prof Woolf was cross-examined about the difference between peripheral neuropathic pain and central neuropathic pain by reference to the IASP definition, paragraph 7.4 of Dr Scadding's second report and Dr Scadding's Appendix 1, and in particular about multiple sclerosis, stroke pain, cancer pain and phantom limb pain (at day 4 page 595 line 20 – page 604 line 8). Prof Woolf accepted that the IASP definition included both peripheral neuropathic pain and central neuropathic pain. He also accepted that the skilled team would not expect the conditions listed in the Spinal Cord, Brainstem and Brain columns of Dr Scadding's Appendix 1 to possess a central sensitisation component (except, according to Prof Woolf, for trauma, phantom limb pain and tumour depending on its location), and specifically that it was unlikely that there was any periphery-driven central sensitisation in pain caused by ischaemic or haemorrhagic stroke. In relation to multiple sclerosis, he accepted that this could cause central neuropathic pain, but said that peripheral neuropathic pain (and in particular trigeminal neuralgia) was a surprisingly common feature in patients with multiple sclerosis.

Prof Woolf was also cross-examined about the Patent at [0006], and he accepted that there were forms of neuropathic pain which were not caused by injury or infection of peripheral nerves and indeed did not involve peripheral sensory nerves at all (at day 5 page 820 line 2 – page 821 line 7).

Prof Woolf was also cross-examined about the extent to which the data in the Patent enabled the skilled team to make a prediction of efficacy in respect of the claimed conditions (at page 822 line 14 – page 832 line 20), during the course of which he accepted it would be impossible for the skilled team to make any reasonable prediction that pregabalin would be effective for treating central neuropathic pain (at page 828 line 17 – page 829 line 15).

Prof Clauw was also cross-examined about the difference between peripheral neuropathic pain and central neuropathic pain by reference to the IASP definition and Dr Scadding's evidence (at day 6 page 970 line 14 – page 979 line 2). He was also cross-examined in some detail about fibromyalgia (at page 981 line 19 – page 996 line 20).

Written closing submissions

The distinction between peripheral neuropathic pain and central neuropathic pain was pursued by Mylan and Actavis in their written closing submissions.

In the section dealing with common general knowledge, Mylan and Actavis submitted at paragraph 48:

"Neuropathic pain is not limited to pain caused by damage to the peripheral nervous system but also includes pain caused by damage or dysfunction of the central nervous system⁵⁶. A wide variety of disease processes that affect the nervous system may cause neuropathic pain⁵⁷. Appendix 1 to Dr Scadding's first report lists these in an anatomical classification. Some of these pains have nothing to do with damage to the peripheral nerve (see e.g. the conditions listed under 'Spinal Cord', 'Brainstem' and 'Brain')⁵⁸. On that basis, central sensitisation cannot be a cause of these types of pain, as there is no damaged nerve to provide the repetitive C-fibre barrage required. When this point was put to Prof Woolf in cross-examination, he agreed that there was no evidence that central sensitisation contributed to central pain states (with the possible exceptions of trauma, phantom limb pain and, depending on location, tumour)⁵⁹."

Footnote 58 cited the passage in Prof Wood's oral evidence quoted in paragraph 79 above.

In the section dealing with the construction of claim 1, Mylan and Actavis submitted under the heading "No rationale for central sensitisation playing a role":

"142. Another example is central neuropathic pain or 'central pain', which is neuropathic pain caused by lesions in the CNS, and includes ischaemic and stroke pain,²¹⁹ Multiple Sclerosis²²⁰ and also phantom limb pain²²¹, in relation to which there is a specific claim (claim 6). Central sensitisation depends upon damage at the periphery setting up a continual C-fibre barrage to the dorsal horn. Such peripheral damage forms no part of the damage that causes central pain. It was common ground between the clinicians that central pain did not include a central sensitisation component – see Scadding 1 §7.4 and Clauw XX at T6/971/20-24 & 974/2-5. Also, Prof Woolf accepted that at least some categories of central pain would not have been understood by the skilled neuroscientist to contain a central sensitisation component – See his XX at T4/p.601/3-602/25. This is consistent with Prof Woolf's chapter in the Textbook of Pain ([M2/45]) in which he stated at p.110 that central pain may well be due to central inhibition (as opposed to central sensitisation as Prof Woolf defined the term at Woolf 1 §§59-61 – see Woolf XX T5/780/6-15).

143. Similarly, there is a specific claim (claim 14) to fibromyalgia. Dr Scadding's evidence was that fibromyalgia, was a poorly understood condition. Nevertheless, indications were that it involved damage to the central nervous system as opposed to any peripheral pathology²²² and he did not agree that central sensitisation was a recognised component²²³. Prof Clauw, whose specialist expertise was fibromyalgia, confirmed that at the Priority Date the prevailing view was that there was no peripheral damage or inflammation that was playing a causative role in fibromyalgia pain and therefore, it was unlikely that the Skilled Clinician would consider that central sensitisation in the italicised sense would be playing a role²²⁴."

Footnote 219 cited the evidence of Prof Woolf in cross-examination, footnote 220 paragraph 7.4 of Dr Scadding's second report and footnote 221 Annex 1 to Dr Scadding's first report.

In the section dealing with the construction of claim 3, Mylan and Actavis addressed Warner-Lambert's new case that "neuropathic pain" was to be construed as limited to peripheral neuropathic pain, and in particular the cross-examination of Dr Scadding on this topic. In this context Mylan and Actavis submitted at paragraph 150:

"However, that exercise was done without providing Dr Scadding with the relevant context. In particular, Dr Scadding should have been taken to the references in both paragraphs [0003] and [0006] to "phantom limb pain" and should also have been shown claim 6, which is a specific claim to phantom limb claim. Dr Scadding's unchallenged evidence was that phantom limb pain is a type of central neuropathic pain²³⁰. Further, Dr Scadding was not taken to the references to fibromyalgia (which Prof Clauw said was a type of neuropathic pain). On that basis, had Dr Scadding been properly shown the context, he would not have agreed that the Patentee meant only peripheral neuropathic pain when it referred to neuropathic pain."

Footnote 230 again cited Appendix 1 to Dr Scadding's first report.

In the section dealing with insufficiency, Mylan and Actavis submitted:

"172. Even if it was accepted that central sensitisation did play a role in some neuropathic pain conditions (e.g. where there had been damage to a peripheral nerve), there were many conditions in which it did not. For example, central neuropathic pain conditions; idiopathic pain conditions (where, by definition, the cause of the pain is unknown); fibromyalgia and related conditions. Therefore, the general claims i.e. claims 1, 3, 6 and 13, together with claim 14, are bad.

173. Even in those pain conditions where central sensitisation may have played a role at some point, e.g. painful diabetic neuropathy and post-herpetic neuralgia, the heterogeneity of symptoms amongst patients suggests that the role central sensitisation plays diminishes with time. As a result, even in specific diagnostic categories, no reasonable prediction can be made that pregabalin will be effective. Consequently, even the more specific claims, such as claim 11, fall."

Warner-Lambert addressed this issue in its written closing submissions at paragraph 170 as follows:

"The only relevance of this to the case appears to be if (a) the claims are to be characterised by reference to central sensitisation and (b) central neuropathic pain is included within claim 3 and (c) it is suggested that central neuropathic pain is not characterised by central sensitisation and is thus implausible. We reject that notion for the reasons given, but the construction of 'neuropathic pain' by reference to the patent specification agreed to by Dr Scadding avoids the problem altogether. On the broader clinical view of hyperalgesia/allodynia, Prof Clauw explained that central neuropathic pain was understood to have these components at the priority date in any event (T6/974_2-5)."

Warner-Lambert went on to address fibromyalgia (at paragraph 172), but did not specifically address stroke pain, multiple sclerosis or phantom limb pain in its written closing submissions.

Oral closing submissions

The distinction between peripheral neuropathic pain and central neuropathic pain was pursued by Mylan and Actavis in counsel's oral closing submissions which closely tracked their written submissions.

In his oral closing submissions counsel for Warner-Lambert, having addressed Warner-Lambert's construction of claim 3, then dealt with fibromyalgia (day 7 page 1154 line 14 – page 1155 line 13) and phantom limb pain (page 1155 line 14 – page 1156 line 2). In relation to the latter, he said that this was "a point which was not really flagged anywhere in the evidence, but which has appeared in my learned friend's closing". He then proceeded to rely upon the evidence Prof Woolf had given in cross-examination and concluded "we say that phantom limb pain does not give the claimants any purchase of any aspect of insufficiency". Thus, to the extent that any complaint was made by Warner-Lambert about Mylan and Actavis' reliance upon phantom limb pain, it was in the mildest of terms.

Judgment

The following points should be noted about my reasoning with respect to insufficiency in Warner-Lambert V.

First, I found that the common general knowledge understanding of neuropathic pain was in accordance with the IASP definition, and hence embraced both peripheral and central neuropathic pain ([50]-[51]).

Secondly, I rejected Warner-Lambert's narrow construction of claim 3. Instead, I construed claim 3 in accordance with the IASP definition as covering both peripheral neuropathic pain and central neuropathic pain ([257]-[261]).

Thirdly, I held that it was not plausible in the light of the specification and the common general knowledge of the skilled team that pregabalin would be efficacious for the treatment of central neuropathic pain, but it was plausible that it would be efficacious for the treatment of peripheral neuropathic pain ([347]-[351]).

Fourthly, I noted at [352] that:

"Given that claim 3 is not restricted to peripheral neuropathic pain (and there is no application to amend it so as to restrict it in that way), however, this conclusion does not save the validity of claim 3."