Teva Pharmaceutical Industries Ltd v Astellas Pharma Inc.
| Jurisdiction | England & Wales |
| Judge | Mr Justice Meade |
| Judgment Date | 01 June 2022 |
| Neutral Citation | [2022] EWHC 1316 (Pat) |
| Court | Chancery Division (Patents Court) |
| Docket Number | Case Nos: HP-2020-000046 and HP-2021-000005 |
and
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[2022] EWHC 1316 (Pat)
Mr Justice Meade
Case Nos: HP-2020-000046 and HP-2021-000005
IN THE HIGH COURT OF JUSTICE
BUSINESS AND PROPERTY COURTS OF ENGLAND AND WALES
INTELLECTUAL PROPERTY LIST (ChD)
PATENTS COURT
Rolls Building
Fetter Lane
London, EC4A 1NL
Justin Turner QC and Stuart Baran for Teva (instructed by Pinsent Masons LLP), Justin Turner QC and Joe Delaney for Sandoz (instructed by Pinsent Masons LLP)
Roger Wyand QC and Anna Edwards-Stuart (instructed by Hogan Lovells International LLP) for Astellas
Hearing dates: 15, 17, 18, 21 and 24 March 2022
I direct that no official shorthand note shall be taken of this Judgment and that copies of this version as handed down may be treated as authentic. This Judgment was handed down remotely by email circulation to the parties' representatives and release to the National Archives. Deemed date for hand-down: 1st June 2022.
| Introduction | 3 |
| The issues | 3 |
| The witnesses | 4 |
| The law — obviousness | 6 |
| Basic principles | 6 |
| Brugger v. Medicaid | 6 |
| Inhale v Quadrant | 7 |
| Conor v. Angiotech | 7 |
| Relying on problems not solved | 8 |
| The skilled team — the law | 9 |
| The skilled team — assessment | 10 |
| Agreed common general knowledge | 11 |
| Bladder Physiology | 12 |
| Storage phase | 13 |
| Voiding phase | 14 |
| Treatment Of Overactive Bladder Syndrome/Its Constituent Symptoms | 15 |
| Methods Of Investigating New Therapies | 15 |
| In vitro methods: | 15 |
| In vivo methods: | 16 |
| β3 adrenoceptors | 17 |
| Disputed common general knowledge | 18 |
| The β3 adrenoreceptor in detrusor function and β3-AR agonists | 18 |
| CIR/SWOT | 24 |
| Other therapeutic approaches | 25 |
| The teaching of the Patent | 28 |
| The claims of the Patent | 29 |
| Obviousness over '288 | 30 |
| Teaching of '288 | 30 |
| Which compounds are disclosed as having been tested and for what? | 34 |
| Obviousness discussion | 35 |
| Pozzoli steps 1 and 2 | 35 |
| Pozzoli step 3 | 35 |
| Pozzoli step 4 | 35 |
| The parties' key points | 35 |
| Key cross-examination relied on | 37 |
| Urine retention | 40 |
| Assessment | 40 |
| The insufficiency squeeze | 42 |
| Conclusions | 43 |
INTRODUCTION
In these two actions Teva Pharmaceutical Industries Limited (“Teva”) and Sandoz AG (“Sandoz”) seek the revocation of European Patent (UK) 1 559 427 B1 (“the Patent”) in the name of Astellas Pharma Inc. (“Astellas”). The priority date, unchallenged by the start of trial, is 7 November 2002.
The Patent protects the compound mirabegron, which is sold by Astellas under the name Betmiga. It is a treatment for overactive bladder (“OAB”). It is a β3 adrenoreceptor agonist (for short, I will in general refer to “β3-AR agonist” or “β3-AR agonism” in this judgment, although not when citing or quoting other documents).
There is also a corresponding SPC (SPC/GB13/035). The only attack on its validity is that the Patent is invalid so I need say no more about it separately.
Astellas has counterclaimed for infringement. Infringement is admitted by Teva and Sandoz (and in each case another group company the subject of a Part 20 claim, on whose identity nothing turns) in the event that the Patent is valid. So in substance this was a patent revocation trial.
Teva and Sandoz have distinct teams of solicitors at the same firm (owing to Sandoz's team moving during the litigation). They use the same leading Counsel, but different junior Counsel. Mr Turner QC undertook all the oral advocacy for Teva and Sandoz, to whom I will refer collectively as “the Claimants”.
THE ISSUES
By the start of the trial, the issues were very limited:
i) A number of disputes over the skilled team.
ii) Some issues over common general knowledge (“CGK”).
iii) Obviousness over a single piece of prior art, Australian Patent Application AU 199889288 B2 (“'288”) published on 6 May 1999.
iv) Insufficiency, run as a squeeze against obviousness.
However, the limited scope of the issues was arrived at only very shortly before trial, and I need to say a little about the issues that were dropped, since it is necessary in order to understand some of the evidence and the roles of the respective experts.
Up until the day before the trial, and including in the Claimants' opening, there was an attack on priority entitlement. In the event that priority was lost, certain other prior art citations were raised, some for novelty only.
After skeletons were submitted, the Claimants dropped their priority attack, and all of the prior art except '288.
Teva had also run a citation referred to as '111, which was a European application related to '288; '111 contains more examples than '288. A practical consequence of this was that much of Astellas' evidence was written by reference to '111 rather than '288. The Claimants avoided that problem by their experts not dealing with '111, but regrettably they did not tell Astellas before experts' reports. So when reading Astellas' experts' reports one has to have in mind that references to '111 can and generally should be read also as relating to '288.
I also record at this stage that '288 and '111 arise from a common PCT application, WO 99/20607 (“607”), which is referred to in the Patent at [0004]. The evidence refers to '607 in places, but '607 is in Japanese and the parties treated '111 as being materially the same as '607.
THE WITNESSES
The parties each called two experts, a clinician and a pharmacologist. There was no fact evidence.
The Claimants' experts were:
i) Prof Paul Abrams (clinician);
ii) Dr Thomas Argentieri (pharmacologist).
Astellas' experts were:
i) Dr Ian Mills (clinician);
ii) Dr Gordon McMurray (pharmacologist).
Dr Argentieri gave evidence by video platform from the US, which required splitting his evidence across two days to allow afternoon sittings, because of the time difference. I do not think this adversely impacted him or my ability to assess his evidence; a brief sound problem was cured during a break. All the other evidence and all the oral argument was live in Court. I am grateful, as ever, to the Court staff, the IT providers and the shorthand writers.
There was a noticeable difference between the sides' respective expert teams in relation to the clinicians. Prof Abrams has had a distinguished career as a urology consultant in the NHS. Dr Mills on the other hand qualified as a medical doctor but since then has mainly worked in industry as a pharmaceutical clinician (including in particular at Pfizer). His professional accreditations make him the equivalent of a consultant in the NHS, but he has had much less patient-contact experience than Prof Abrams.
Both Prof Abrams and Dr Mills were well able to explain clinical matters of relevance to the case, but there was little dispute over the “pure” clinical picture. That and the fact that Prof Abrams' written evidence was largely directed to issues arising on the priority attack meant that he spent little time in the witness box. Dr Mills was questioned for considerably longer, and that was because his perspective as a pharmaceutical clinician meant that his views overlapped with those of the pharmacologist more than those of Prof Abrams did. None of this is a criticism of either of them, but it feeds into a point about the skilled team, to which I return below.
In closing written submissions the Claimants said that while they made “no particular criticisms of any of the expert witnesses”, Dr Mills and “perhaps to a lesser extent” Dr McMurray held on to unsustainable positions “but not sufficiently to colour the overall value of their evidence”. They gave certain examples thereafter and I will touch on these where relevant, but there was nothing in them to lead me to doubt my overall impression that both gave their evidence, for which I am grateful, fairly and honestly. They were also both good explainers.
The Claimants also said in closing written submissions that Astellas' experts “gave the appearance (we can say only appearance) of having been overly lawyered”. I do not think they gave any such appearance and anyway since the Claimants stopped short of saying that the witnesses in fact were “overly lawyered” I cannot see where the point would go.
No criticism was made of Prof Abrams, who was a good, clear, knowledgeable witness and entirely fair. His role in the case was fairly limited, for the reasons explained above.
Counsel for Astellas criticised Dr Argentieri on several fronts:
i) That he approached '288 on the basis that the skilled pharmacologist had already decided to pursue β3-AR agonists and that the relevant question was, leaving aside all other patents and molecules, “would it be unreasonable to synthesise all six compounds [in '288] and test them”;
ii) That he conceived of the skilled addressee as being “smarter than everyone else”;
iii) That he produced an incomplete list of the therapeutic pathways that were under consideration for OAB at the priority date;
iv) That he said '288 contained “data” when it in fact did not in the relevant respects.
The first two of these are not criticisms of Dr Argentieri's independence or integrity, but rather go to whether he was asking himself the right question. I think there was some force in them and I deal with them where they arise but they do not lead me to conclude that he was not doing his best to give complete and honest evidence.
In relation to the third point I note that Dr Argentieri provided the list from memory and directed only to...
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Astellas v Teva & Sandoz
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