The Pregabalin Trial: Generics (UK) Ltd v Warner-Lambert Company LLC
According to drugs.com, pregabalin is an anti-epileptic drug which works by slowing down impulses in the brain that cause seizures. A European patent for the drug was granted to Warner-Lambert Co, LLC ("Warner-Lambert")(now a subsidiary of Pfizer Inc.) under EP number 0 641 330. That patent expired on 17 May 2013 but was extended by a supplementary protection certificate ("SPC") until 17 May 2018. That SPC was allowed to lapse on 14 Oct 2013 and Warner-Lambert's data exclusivity in respect of the data used to obtain the marketing authorisation for prehabalin expired on 8 July 2014. Since then anybody has been free to make, import or sell pregabalin for treating epilepsy and generalized anxiety disorder in the United Kingdom and several companies including some of the parties to these proceedings have done just that.
Drugs.com notes that pregabalin also affects chemicals in the brain that send pain signals across the nervous system. It can therefore be used to control seizures and treat fibromyalgia as well as pain caused by nerve damage in patients with diabetes, herpes or neuropathic pain associated with spinal cord injury. A patent for those uses entitled "Isobuytlgaba and its derivatives for the treatment of pain" was granted to Warner Lambert LLC under EP number 0 934 061 on 28 May 2013.
The generics drugs manufacturers Generics (UK) Ltd trading as Mylan ("Mylan") and Actavis Group PTC EHF ("Actavis") applied for revocation of Warner Lambert's pain relief patent on 24 June and 12 Sept 2014 respectively. The grounds upon which they seek revocation are obviousness and insufficiency. Mr Justice Birss ordered those two applications to be heard together.
On 8 Dec 2014 Warner-Lambert sued Actavis for infringement of its pain relief patent on the ground that it had supplied pregabalin for pain relief which it was entitled to make, import and sell only for epilepsy and general anxiety disorder treatment. Warner-Lambert applied for a complicated interim injunction to inhibit the prescription of Activis's generic pregabalin tablets in the NHS. The application came on before Mr Justice Arnold in January of this year. The judge refused the relief on the ground that there was no serious issue to be tried and that in any case the balance of convenience favoured Actavis but ordered the infringement action to be tried with the revocation proceedings (see Warner-Lambert Company, LLC v Actavis Group Ptc EHF  EWHC 72 (Pat) and my case note Swiss Style Claims: Warner Lambert v Actavis 28 Jan 2015).
After that hearing there were a number of other interlocutory applications which Mr Justice Arnold summarized at paragraph 5 of his judgment in the trial of those various claims:
"I dismissed the application for an interim injunction for the reasons given in my judgment dated 21 January 2015  EWHC 72 (Pat) ("Warner-Lambert I"). Subsequently I dismissed an application by Actavis to strike out, alternatively for summary judgment dismissing, Warner-Lambert's claim for infringement under section 60(1)(c) of the Patents Act 1977 for the reasons given in my first judgment dated 6 February 2015  EWHC 223 (Pat) ("Warner-Lambert II"), but acceded to Actavis' application to strike out the claim for infringement under section 60 (2) for the reasons given in my second judgment dated 6 February 2015  EWHC 249 (Pat) ("Warner-Lambert III"). On 26 February 2015 I made an order, largely by consent, requiring the National Health Service Commissioning Board ("NHS England") to issue guidance to Clinical Commissioning Groups ("CCGs") in England and to the NHS Business Services Authority ("BSA") for transmission to NHS pharmacy contractors for the reasons given in my judgment dated 2 March 2015  EWHC 485 (Pat) ("Warner-Lambert IV"). On 28 May 2015 the Court of Appeal dismissed an appeal by Warner-Lambert against Warner-Lambert I and allowed an appeal by Warner-Lambert against Warner-Lambert III for the reasons given in the judgment of Floyd LJ delivered on that date  EWCA Civ 556 ("Warner-Lambert CA")."There have also been a number of case management hearings in which the Secretary of State for Health has been permitted to intervene in the infringement claim. Actavis has counterclaimed against Warner-Lambert for groundless threats.
The revocation applications together with Warner-Lambert's infringement claim and Actavis's threats action came on for trial before Mr Justice Arnold on 29 June 2015. His Lordship delivered judgment on most of those issues on 10 Sept 2015. The case reference is Generics (UK) Ltd v Warner-Lambert Company LLC  EWHC 2548 (Pat) (10 Sept 2015).
The Patent in Suit
European patent number 0 934 061 was granted "for the use of an analog of gamma-aminobutyric acid (GABA) in pain therapy, as the compound exhibits analgesic/antihyperalgesic action." It was summarized as
"a method of using a compound identified below in the treatment of pain, especially for treatment of chronic pain disorders. Such disorders include, but are not limited to, inflammatory pain, postoperative pain, osteoarthritis, pain associated with metastatic cancer, trigeminal neuralgia, acute herpetic and postherpetic neuralgia, diabetic neuropathy, causalgia, brachial plexus avulsion, occipital neuralgia, reflex sympathetic dystrophy, fibromyalgia, gout, phantom limb pain, burn pain, and other forms of neuralgic, neuropathic, and idiopathic pain syndromes."Claim 1 was for the
"Use of [pregabalin] or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical composition for treating pain."The subsequent claims were for such use in the treatment of different types of pain.
Swiss Style Claims
In my previous case note I wrote:
"The use of pregabalin for the treatment of pain is an example of a "Swiss style claim". In G 5/83 the Enlarged Board of Appeal of the European Patent Office held that a patent could be granted for a second or subsequent medical use if a specification claimed the use of a known substance that was already used for the treatment of one condition in the manufacture of a medicament for the treatment of another condition. Since the revision of the European Patent Convention by the Act revising the European Patent Convention of 29 Nov 2000 it has ceased to be necessary to draft claims for second and subsequent medical use in this way because art 54 (5) of the Convention now permits second and subsequent medical uses of known substances."Between paragraphs  and  of his judgment Mr Justice Arnold explained the policy for formulating patent claims in this way:
" It has increasingly been recognised over the past 30 years or so that it is important to find new uses for existing medicines. Existing medicines have the advantage that they are known compounds which have been shown to have acceptable safety profiles, and therefore need much less testing from that perspective. Experience shows that a compound which has therapeutic benefit in one application not infrequently turns out to have therapeutic benefit in another application (sometimes more than one other application) which may be quite different to the first application. Thus there is significant potential and value in finding such second (and third, etc.) medical uses. Discovering such second medical uses requires difficult and expensive research, however. How is such research to be funded? The answer which has been provided by the European patent system is to grant patents for second (and subsequent) medical uses of known compounds. The monopoly thus conferred on the inventor who finds the second medical use provides the return on the investment required to fund the research.As I indicated in my previous note it is no longer necessary to draft patents in this form because the European Patent Convention has been revised. The judge made clear at paragraph  that it should not be assumed that anything he said in his judgment about Swiss form claims necessarily applies to claims in the new form.
 There are two significant obstacles to the grant of patents for second medical uses under the European patent system: first, the compounds themselves are not new, which is a fundamental requirement for patentability of a product; and secondly, methods of treatment of the human (or animal) body by therapy are not patentable, in order to protect doctors from claims for patent infringement. The European patent system has attempted to overcome these obstacles in two ways.
 The first way was through a piece of judicial lawmaking which fudged some of the difficult issues. This involved the use of claims in Swiss form i.e. "use of substance X for the preparation of a medicament (or pharmaceutical composition) for treating indication Y" (a purpose-limited process claim): see G 05/83 Eisai/Second medical indication  OJ EPO 64."
Referring to Windsurfing International Inc v Tabur Marine (Great Britain) Ltd  RPC 59 and Pozzoli v BDMO SA  BusLR D117,  EWCA Civ 588,  FSR 37 Mr Justice Arnold directed himself as follows:
"(1) (a) Identify the notional 'person skilled in the art';The Skilled Addressee
(b) Identify the relevant common general knowledge of that person;
(2) Identify the inventive concept of the claim in question or if that cannot readily be done, construe it;
(3) Identify what, if any, differences exist between the matter cited as forming part of the 'state of the art' and the inventive concept of the claim or the claim as construed;
(4) Viewed without any knowledge of the alleged invention as claimed, do those differences constitute steps which would have been obvious to the person skilled in the art or do they require any degree of invention?"
It was common ground that the "person skilled in the art" in this case would be a team consisting of a neuroscientist and a clinician. The neuroscientist would be a pre-clinical researcher with an interest in developing new analgesics and knowledge of various animal models of pain. He or she would typically have a master's degree or doctorate in neuroscience, pharmacology or neurophysiology or a related biological field and would be familiar with the molecular physiology of pain and analgesia. The clinician would specialize in the treatment of pain. The judge decided he or she could be a rheumatologist, neurologist or anaesthetist. The members of the team would work together and be led by the neuroscientist.
Common General Knowledge
Mr Justice Arnold referred to his review of the law on "common general knowledge" between paragraphs  and  of his judgment in KCI Licensing Inc and Others v Smith & Nephew Plc and Others  Bus LR D27,  EWHC 1487 (Pat),  FSR 31 which had been approved by the Court of Appeal on appeal (see KCI Licensing Inc and Others v Smith & Nephew Plc and Others (2011) 117 BMLR 81,  FSR 8,  EWCA Civ 1260. The learned judge added the following points between paragraphs  and :
 First, in some cases the party attacking the patent seeks to build up the common general knowledge in order to bolster its case on its obviousness. In other cases the patentee seeks to build up the common general knowledge in order to bolster its case on sufficiency. In the present case both sides sought to build up different aspects of the common general knowledge for their respective purposes. As is common ground, whichever party seeks to establish that something is common general knowledge and whatever that party's purpose in doing so, the burden lies on the party seeking to establish the common general knowledge and the test to be applied is the same.Between paragraphs  and  the judge reviewed the evidence and concluded at paragraph  that it was common general knowledge that:
 Secondly, in some cases the breadth of the claims is such that they cover two (or more) different fields and hence are addressed to persons skilled in both those fields. The fields may be different aspects of the same art or, in an extreme case, different arts altogether. In such circumstances it is legitimate to consider the question of obviousness from the perspective of each addressee, and hence in the light of that addressee's common general knowledge, although this does not mean that there cannot be invention in marrying two different arts: see Inhale Therapeutic Systems Inc v Quadrant Healthcare plc  RPC 21 at - (Laddie J). Counsel for Mylan and Actavis accepted that, at least on the facts of the present case, the same approach should be applied to sufficiency i.e. it is enough if the invention can be performed by one of the addressees using that addressee's common general knowledge.
 Thirdly, an issue arises in this case as to whether common general knowledge has a territorial dimension. What if a matter was known to persons skilled in the art in the USA, but not to persons skilled in the art in the UK? In Teva UK Ltd v Merck & Co Inc  EWHC 2952 (Pat),  FSR 17 Floyd J (as he then was) said:
'101. A question arises as to whether it is sufficient to establish that a particular fact was known in the United Kingdom, or whether it is necessary to establish, where the art is an international one, that it was known more widely. The question does arise here. Counsel for Warner-Lambert submitted that matter relied on as being common general knowledge must be shown to be common general knowledge in the UK, but counsel for Mylan and Actavis disputed that this was necessary. Although I only received limited argument on the point, it seems to me that, at minimum, it must be shown that the matter in question was common general knowledge in the UK. The reason for this is that, whether one is concerned with the validity of a European Patent (UK), or a UK patent, one is concerned with a right in respect of the UK. It is true that the prior art may have been published anywhere in the world, but I do not think that alters the need for the skilled team to consider that art as if they were located in the UK. I do not think it matters that a fact was common general knowledge in (say) China, if it was not common general knowledge here. The position may be different if all the persons skilled in a particular art in the UK are acquainted with the position in China, but no point of that kind arises here. I do not consider that this approach is contrary to Article 27(1) of TRIPS, which provides that "patents shall be available and patent rights enjoyable with discrimination as to the place of invention", as counsel for Mylan and Actavis submitted.
102. Mr Thorley maintained that the relevant common general knowledge was that in this country. Mr Birss was content to accept that proposition, whilst pointing out that where the art was an international one, it is relevant on the facts to take account of evidence that individuals abroad had not heard of it. Neither side showed any enthusiasm for arguing that common general knowledge had to be more extensive than the United Kingdom.
103. I am content to proceed on this legal basis, as I did not hear detailed argument on the point. It would seem to me to be an odd result if a patent for the United Kingdom could survive if it was obvious in the light of the common general knowledge in this country. A more difficult question may arise if a fact is only common general knowledge abroad. But that does not arise here.'
 Fourthly, as is established by the authorities discussed in KCI, in order to acquire the status of common general knowledge, a matter must be generally known and generally regarded as a good basis for further action by the bulk of those engaged in the art in question. What amounts to being "generally regarded as a good basis for further action" is a context-dependent question. Thus a scientific theory does not have to have been generally accepted as correct if it is regarded as a reasonable working hypothesis by the bulk of those skilled in art. Furthermore, a theory may be regarded as a good basis for some forms of action (such as experiments in vitro or in animal models) even if not for others (such as administration to humans). See Intervet UK Ltd v Merial  EWHC 294 (Pat) at  and Novartis AG v Focus Pharmaceuticals Ltd  EWHC 1068 (Pat) at -"
- Neuropathic pain was characterized by secondary hyperalgesia and allodynia, in the sense that these symptoms were present in the large majority of patients, but a significant minority did not display these symptoms.
- Secondary hyperalgesia and allodynia involved central augmentation. In some cases this would be central sensitisation, but not in all cases.
The judge identified the inventive concept by construing the claims in accordance with the principles set out in Kirin-Amgen Inc v Hoechst Marion Roussel Ltd  RPC 9,  UKHL 46,  1 All ER 667, (2005) 28(7) IPD 28049,  RPC 169 and summarized by Lord Justice Jacob at paragraph  of his judgment in Virgin Atlantic Airways Ltd v Premium Aircraft Interiors UK Ltd  EWCA Civ 1062,  RPC 8:
"(i) The first overarching principle is that contained in Article 69 of the European Patent Convention.The judge reminded himself that Swiss style claims are process claims rather than product claims and that they are directed to manufacturers of medicaments or pharmaceutical compositions.
(ii) Article 69 says that the extent of protection is determined by the claims. It goes on to say that the description and drawings shall be used to interpret the claims. In short the claims are to be construed in context.
(iii) It follows that the claims are to be construed purposively - the inventor's purpose being ascertained from the description and drawings.
(iv) It further follows that the claims must not be construed as if they stood alone - the drawings and description only being used to resolve any ambiguity. Purpose is vital to the construction of claims.
(v) When ascertaining the inventor's purpose, it must be remembered that he may have several purposes depending on the level of generality of his invention. Typically, for instance, an inventor may have one, generally more than one, specific embodiment as well as a generalised concept. But there is no presumption that the patentee necessarily intended the widest possible meaning consistent with his purpose be given to the words that he used: purpose and meaning are different.
(vi) Thus purpose is not the be-all and end-all. One is still at the end of the day concerned with the meaning of the language used. Hence the other extreme of the Protocol - a mere guideline - is also ruled out by Article 69 itself. It is the terms of the claims which delineate the patentee's territory.
(vii) It follows that if the patentee has included what is obviously a deliberate limitation in his claims, it must have a meaning. One cannot disregard obviously intentional elements.
(viii) It also follows that where a patentee has used a word or phrase which, acontextually, might have a particular meaning (narrow or wide) it does not necessarily have that meaning in context.
(ix) It further follows that there is no general 'doctrine of equivalents.'
(x) On the other hand purposive construction can lead to the conclusion that a technically trivial or minor difference between an element of a claim and the corresponding element of the alleged infringement nonetheless falls within the meaning of the element when read purposively. This is not because there is a doctrine of equivalents: it is because that is the fair way to read the claim in context.
(xi) Finally purposive construction leads one to eschew the kind of meticulous verbal analysis which lawyers are too often tempted by their training to indulge."
Conclusion on obviousness
Having construed the claims Mr Justice Arnold compared the inventive concept as contained in those claims with the prior art relied upon by and Mylan and Actavus and considered whether they constituted steps that would have been obvious to the neuroscientist and clinician mentioned above having regard to common general knowledge. His Lordship concluded at paragraph  that they did not.
S.14 (3) of the Patents Act 1977 requires a specification to
"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."If it does not to do so, any patent that may have been grated for the invention may revoked under s.72 (1) (d). Revocation on that ground is known as "insufficiency." In Eli Lilly & Company v Human Genome Sciences Inc. (2008) 31(10) IPD 31066, (2009) 105 BMLR 27,  EWHC 1903 (Pat),  RPC 29 Mr Justice Kitchin (as he then was) had said at paragraph  of his judgment:
"The specification must disclose the invention clearly and completely enough for it to be performed by a person skilled in the art. The key elements of this requirement which bear on the present case are these:Having already construed the claims and identified the skilled addressee and the common general knowledge Mr Justice Arnold considered whether the specification was sufficient to allow the invention to be performed over the whole scope of the claim without undue influence. He concluded at paragraph 358 that some but not all the claims were invalid for insufficiency. The invalid claims were 1, 3, 4, 6, 13 and 14.
(i) the first step is to identify the invention and that is to be done by reading and construing the claims;
(ii) in the case of a product claim that means making or otherwise obtaining the product;
(iii) in the case of a process claim, it means working the process;
(iv) sufficiency of the disclosure must be assessed on the basis of the specification as a whole including the description and the claims;
(v) the disclosure is aimed at the skilled person who may use his common general knowledge to supplement the information contained in the specification;
(vi) the specification must be sufficient to allow the invention to be performed over the whole scope of the claim;
(vii) the specification must be sufficient to allow the invention to be so performed without undue burden."
Having decided that claims 1 and 3 were invalid for insufficiency it was not strictly necessary for the judge to decide whether those claims had been infringed. Warner-Lambert's case was that pregabalin that had lawfully been manufactured by Actavis for the treatment of epilepsy and generalized anxiety disorder had been supplied for pain relief.
Warner-Lambert relied on s.60 (1) (c) and (2) of the Patents Act 1977.
As to the claim under 60 (1) (c) Mr Justice Arnold held that in a Swiss style claim it is necessary to prove intention on the part of the manufacturer that the medicament or pharmaceutical composition should be used for the new therapeutic use. As there was no evidence that Actavis intended its products to be used to treat pain unless and until claims 1 and 3 of the Patent were held invalid the claim failed on that head. In Warner-Lambert Company, LLC v Actavis Group Ptc EHF and others  EWCA Civ 556 Lord Justice Floyd had said at paragraph  of his judgment that s.60 (1) (c) would be infringed if a generics manufacturer knew or could foresee that his products would be used for the new use. Even applying that test Actavis would not have infringed claims 1 and 3.
As for the claim under s.60 (2) there was no act of manufacture by any party downstream from Actavis, nor even the prospect of such an act. The claim under that head failed too.
The judge agreed to declare that neither Actavis nor any of its wholesalers, nor any doctors. patients or intermediaries had infringed Warner-Lambert's patent.
Shortly before Actavis was due to launch its generic pregabalin Warner-Lambert wrote to the Department of Health, NICE, superintendent pharmacists and others indicating that the prescription of that product for pain relief would infringe its patent. The judge held that some of those letters were unjustifiable threats within the meaning of s.70 (1) of the Patents Act 1977.
At paragraph  of his judgment, Mr Justice Arnold concluded that:
"i) none of the claims of the Patent is obvious over any of the prior art relied upon by Mylan and Actavis;Epilogue
ii) claims 1, 3, 4, 6, 13 and 14 of the Patent are invalid on the ground of insufficiency;
iii) even if claims 1 and 3 are valid, Actavis have not infringed those claims pursuant to section 60(1)(c) or section 60(2); and
iv) Pfizer is liable for making groundless threats of patent infringement proceedings, albeit not in all the cases alleged by Actavis."
At paragraph  the judge said:
"I have now lived with this case for nine months. During that time, I have heard and determined the applications which led to the Warner-Lambert I, II, III and IV judgments, I have heard and determined a number of other case management applications, I have heard the trial and I have written this judgment. During that time, I have reflected repeatedly and at length on the issues raised by this litigation. At the end of that period of reflection, I remain more convinced than ever that the best solution to the problem of protecting the monopoly conferred by a second medical use patent while allowing lawful generic competition for non-patented indications of the substance in question is to separate the patented market for the substance from the non-patented market by ensuring that prescribers write prescriptions for the patented indication by reference to the patentee's brand name and write prescriptions for non-patented indications by reference to the generic name of the substance (the INN)."He urged patentees who want their second medical use patents to be enforced to provide NHS England with all the information and assistance it requires to enable it to issue appropriate guidance as and when required. He urged generic companies who want their interests in obtaining untroubled access to lawful markets protected to cooperate with NHS England as well. "In short," he added "what is needed is a system for dealing with these situations."
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