Astellas v Teva & Sandoz
| Jurisdiction | England & Wales |
| Judge | Mr Justice Mellor |
| Judgment Date | 17 October 2023 |
| Neutral Citation | [2023] EWHC 2571 (Pat) |
| Court | Chancery Division (Patents Court) |
| Docket Number | Case No: HP-2021-000014 |
[2023] EWHC 2571 (Pat)
THE HON Mr Justice Mellor
Case No: HP-2021-000014
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
Thomas Mitcheson KC and Anna Edwards-Stewart (instructed by Hogan Lovells International LLP) for the Claimant
Charlotte May KC and Katherine Moggridge (instructed by Pinsent Masons LLP) for the Teva Defendants
Charlotte May KC and Joe Delaney (instructed by Pinsent Masons LLP) for the Sandoz Defendants
Hearing dates: 21 st–22 nd, 25 th–27 th, 29 th July 2022
APPROVED JUDGMENT
I direct that pursuant to CPR PD 39A para 6.1 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 circulation to the parties' representatives by email. It will also be released for publication on the National Archives and other websites. The date and time for hand-down is deemed to be Tuesday 17 th October 2023 at 10.30am.
THE HON Mr Justice Mellor
This Table of Contents is organised by topic and page number:
| INTRODUCTION | 5 |
| OVERVIEW OF THE ISSUES | 5 |
| THE EXPERTS | 7 |
| THE COMPOSITION OF THE SKILLED TEAM | 8 |
| Applicable principles | 8 |
| Analysis | 8 |
| COMMON GENERAL KNOWLEDGE | 10 |
| 1. An overview of the bladder and associated syndromes / conditions | 10 |
| 2. OAB | 10 |
| 3. OAB Treatments at the Priority Date | 11 |
| Antimuscarinics | 11 |
| 4. Issues for OAB Treatments | 13 |
| 5. OAB drugs in development at the Priority Date | 14 |
| 6. Benign prostatic hyperplasia (“BPH”) | 14 |
| 7. Tamsulosin hydrochloride | 14 |
| 8. Developing a Formulation | 15 |
| 9. The administration of drugs | 15 |
| 10. The gastro-intestinal tract (GI tract) | 16 |
| 11. Orally delivered drugs and their effect on the body | 18 |
| 12. Drug characteristics | 20 |
| 13. Excipient characteristics | 22 |
| 14. Immediate Release Formulations | 23 |
| 15. Modified Release | 23 |
| 16. Formulating extended-release drug products – overview | 24 |
| 17. Example MR formulations | 24 |
| 18. Food effects | 25 |
| 19. Causes of Food Effects | 26 |
| 20. Food effect studies | 26 |
| 21. Regulatory guidelines for food effects | 27 |
| 22. Pharmaceutical Development | 27 |
| DISPUTED CGK | 28 |
| The paddle speed used to test extended release formulations. | 28 |
| What the Skilled Team would have known about the guidance for conducting food effect studies set out in regulatory guidelines. | 28 |
| Whether accumulation would be a concern for a Skilled Team when considering development of an extended-release formulation. | 29 |
| THE PATENT | 30 |
| The central teaching | 32 |
| The Remaining Disclosure in the Patent | 39 |
| The Examples | 40 |
| The Claims | 42 |
| CONSTRUCTION | 43 |
| INSUFFICIENCY – EXCESSIVE CLAIM BREADTH | 47 |
| Applicable principles | 48 |
| Application to this case | 53 |
| The Defendants' case | 53 |
| Figure G | 54 |
| The Claimant's Response | 57 |
| Analysis | 57 |
| Professor Shakesheff's ‘mid-range’ theory | 61 |
| Astellas' ‘sweet-spot’ argument. | 64 |
| Conclusions | 64 |
| Uncertainty? | 66 |
| INVENTIVE STEP | 66 |
| Applicable principles | 66 |
| THE PRIOR ART | 69 |
| FIX | 70 |
| First, what Fix discloses to the Skilled Team | 70 |
| The rival contentions as to what Fix discloses | 77 |
| Second, what would the Skilled Team do, having considered Fix | 81 |
| Context and alternatives | 82 |
| Similarity to mirabegron | 86 |
| Solubility | 88 |
| Permeability | 91 |
| Third, the nature of the project which the Skilled Team is prepared to undertake | 93 |
| Fourth, whether the project would lead to a formulation which fell within claim 1 | 94 |
| Fifth, the Pozzoli analysis. | 95 |
| MICHEL — WITH OR WITHOUT CHAPPLE | 96 |
| ADDED MATTER | 98 |
| INFRINGEMENT — SANDOZ | 98 |
| INFRINGEMENT – TEVA'S REVISED PRODUCT | 102 |
| CONCLUSIONS | 102 |
Introduction
In this action the Claimant (Astellas) alleges that the generic mirabegron tablets proposed to be launched by the two sets of Defendants (Teva and Sandoz) infringe EP(UK) 2,345,410 (EP410 or the Patent). The Patent is entitled ‘Pharmaceutical composition for modified release’ and concerns a modified release pharmaceutical composition containing mirabegron (or a salt thereof) as an active ingredient. The Priority Date is 30 th September 2008.
In earlier actions Teva and Sandoz sought revocation of another Astellas patent EP(UK) 1,559,427 B1 (EP427) and Supplementary Protection Certificate SPC/GB13/035 (which relies on EP427 as its basic patent) which protect a remedy for use in the treatment of Overactive Bladder (OAB) syndrome comprising mirabegron or a salt thereof as an active ingredient. Meade J. heard the trial of the EP427 case in March 2022 and found that patent to be valid and infringed: see [2022] EWHC 1316 (Pat). At the date of the trial, Teva and Sandoz had obtained permission to appeal but both Teva and Sandoz were injuncted from launching their generic mirabegron products. Their appeal was later dismissed: see [2023] EWCA Civ 880.
Overview of the issues
So far as infringement is concerned, Teva does not contest that its original product (‘the Original Teva Product’) infringes EP410, but it has brought a claim for a declaration of non-infringement in respect of its New Teva Product. There was insufficient time to prepare that issue for determination at this trial and the parties agreed it should be determined later, if that is necessary. Sandoz does not admit infringement.
Teva and Sandoz each counterclaim for revocation of the Patent on the grounds of obviousness, insufficiency and added matter. By the conclusion of the PTR, Teva and Sandoz had aligned their validity attacks, and added a further added matter attack based on some of the evidence to be led by Astellas (specifically some evidence of Professor Shakesheff). For obviousness the Defendants rely on three prior art citations:
i) “ Controlled-Release Oral Delivery Systems”, Joseph A. Fix et al., ACS Symposium Series, American Chemical Society: Washington DC, 2000; 752;14–24 ( Fix);
ii) “The Pharmacokinetic Profile of Tamsulosin Oral Controlled Absorption System (OCAS®)”, Michel, M., European Urology Supplements Volume 4, Issue 2 (2005) 15–24 ( Michel);
iii) “The Oral Controlled Absorption System (OCAS®): The Evolution of Tamsulosin for the Treatment of Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia (LUTS/BPH)”, Chapple, C., European Urology Supplements Volume 4, Issue 7 (2005) 20–22 ( Chapple) when read with Michel.
Two insufficiency allegations were pleaded and pursued by the Defendants. The main attack was excessive claim breadth. The subsidiary attack was ambiguity or uncertainty, although this seemed to have died away by the time of written closings, only to be resurrected in the final minutes of the trial if the drug release measure in [0010] was in vivo, a point I consider below.
On the main attack, the Defendants say it is not plausible that the invention of the Patent works (in the sense of reducing the food effect) with substantially all products falling within the scope of at least claim 1. Accordingly, they say the claim scope exceeds the technical contribution such that the claims of the Patent are invalid. The Defendants also say the Patent is AgrEvo-obvious in that it is lacking in any relevant technical contribution.
Astellas defends the revocation claim and on 17 June 2022 applied to amend the Patent unconditionally. Astellas also advances 3 conditional amendments to the Patent as fall-back positions. All the amendments are opposed on the grounds that they do not cure the invalidity of the Patent. The Defendants' initial position was that the proposed amendments made the added matter position worse not better.
Those are the headline issues, however the issues which took up the most time at trial were first, insufficiency, second, obviousness and third, some disputes as to whether the Skilled Team included a pharmacokineticist and related CGK issues. As I relate in more detail below, the insufficiency arguments continued to develop throughout. Those arguments turn on how the Patent was understood at the Priority Date by the Skilled Team. For that reason, it is necessary to analyse and understand the Patent in some detail.
The experts
The parties called a total of five expert witnesses in the following disciplines:
i) Formulator: Professor Shakesheff (for Astellas) and Professor Craig (for Teva & Sandoz);
ii) Clinician: Professor Drake (for Astellas) and Dr Morley (for Teva & Sandoz);
iii) Pharmacokineticist: Dr Blakey (for Teva & Sandoz). Astellas did not call a separate PK expert but addressed the PK aspects of the case via Professor Shakesheff.
The evidence from the clinicians was short and not really controversial at all. Both Professor Drake and Dr Morley gave their evidence clearly and both assisted the Court.
Dr Blakey was a guarded witness and sometimes he had to be pressed to provide the answer. Astellas cited two examples. First, where he was initially reluctant to accept that if the skilled team was told that a drug formulation had continuous drug release for four hours or more, they would assume that it was being...
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