Sandoz Ltd v Bristol-Myers Squibb Holdings Ireland Unlimited Company

JurisdictionEngland & Wales
JudgeMr Justice Meade
Judgment Date07 April 2022
Neutral Citation[2022] EWHC 822 (Pat)
Docket NumberCase Nos: HP-2020-000042 and HP-2021-000003
CourtChancery Division (Patents Court)

[2022] EWHC 822 (Pat)

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, EC4

Before:

Mr Justice Meade

Case Nos: HP-2020-000042 and HP-2021-000003

Between:
Sandoz Limited
Claimant/Pt 20 Defendant in HP-2020-000042
Teva Pharmaceutical Industries Limited
Claimant in HP-2020-000003
and
Bristol-Myers Squibb Holdings Ireland Unlimited Company
Defendant/Pt 20 Claimant in HP-2020-000042 & HP-2021-000003

and

Teva UK Limited
Part 20 Defendant in HP-2021-000003

Michael Tappin QC, Stuart Baran and Alice Hart (instructed by Bristows LLP) for Sandoz

Justin Turner QC and Thomas Lunt (instructed by Pinsent Masons LLP) for Teva

Iain Purvis QC and Anna Edwards-Stuart (instructed by Hogan Lovells International LLP and Wilmer Cutler Pickering Hale and Dorr LLP) for Bristol-myers Squibb

Hearing dates: 31 January, 1–4 and 9–10 February 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.

Introduction

3

The issues

4

The witnesses and the skilled team

4

Some irrelevant matters

5

Applicable legal principles – plausibility

6

T 939/92 Agrevo/Triazoles

6

Warner-Lambert v Generics [2018] UKSC 56

10

Fibrogen v Akebia [2021] EWCA Civ 1279

17

Identifying what it means to “work”

25

T 0016/18 Sumitomo

27

No requirement to file data

28

No particular level of activity required

28

Agreed common general knowledge

28

Disputed common general knowledge

29

Was a nanomolar K i/IC 50 necessary for therapy?

29

Selectivity

30

Predictability of in vitro and in vivo characteristics from structure alone

31

Binding pockets of factor Xa; their relevance to inhibitor design

32

Specific series of compounds

33

The teaching of '652

36

The claims of the Patent

44

Proposed amended claims

45

Evidence and arguments on plausibility

46

Plausibility of factor Xa binding

46

The teaching on page 170

47

3g quantity of apixaban

47

The compounds synthesised; apixaban as a “typical” one

48

Structural analysis

51

P1 4-methoxyphenyl

53

The lactam at the P4 position

54

The rigidified core

54

Dr Redshaw's evidence

55

The differences in aggregate

55

Conclusion on the structure case

55

Plausibility of factor Xa binding – overall assessment

55

Plausibility of therapy

56

Selectivity

56

Clear and easy tests

56

Non-therapeutic uses

57

Standard or reference compounds

57

Diagnostic assays

58

Anti-coagulants

58

Lead compounds

58

Conclusion on non-therapeutic uses

59

Obviousness over '131

59

Obviousness of compound per se claims: Teva's point

60

The proposed amendments

61

Added matter

62

Clarity

62

Conclusions

62

Mr Justice Meade

INTRODUCTION

1

This is the trial of two actions in which the Claimants, respectively Sandoz Limited (“Sandoz”) and Teva Pharmaceutical Industries Limited (“Teva”) seek the revocation of European Patent (UK) 1 427 415 B1 (“the Patent”) in the name of Bristol-Myers Squibb Holdings Ireland Unlimited Company (“BMS”). The priority date is 21 September 2001.

2

The claims of the Patent relate to a compound called apixaban, sold by BMS under the name ELIQUIS and which is used for thromboembolic disorders.

3

There is also a corresponding SPC (SPC/GB11/042) but nothing separate turns on that: it is invalid if the Patent is invalid.

4

BMS has counterclaimed for infringement. Infringement is admitted by Sandoz and Teva in the event that the Patent is valid. So in substance this was a patent revocation trial.

5

Sandoz and Teva are separately represented but have made common cause, submitting joint skeleton arguments and sharing expert witnesses, and with their Counsel splitting the oral advocacy at trial. They have run the same arguments with one exception, an obviousness attack made by Teva alone. I will refer to Sandoz and Teva together as “the Claimants”.

6

Apixaban's use in therapy depends on its activity as a factor Xa inhibitor. It is not in dispute that in fact apixaban has proven to be a potent factor Xa inhibitor and a useful therapeutic, but the central attack on the Patent is that it did not make plausible that apixaban would have any useful factor Xa inhibitory activity, or be useful in therapy, or for any other purpose.

7

It was common ground that the issue of plausibility should be tested by reference to the application for the Patent, published as WO 2003/026652 A1 (“' 652”), because if plausibility had to be based on something that was only in the Patent and not in '652, there would be added matter. On that basis, an added matter squeeze fell away.

8

BMS has also applied to amend the Patent's claims.

9

There has been related litigation in Canada, where BMS has been successful. But BMS did not submit that it could rely on the result there in this litigation and from what I have seen a very different legal standard applies there. Dr Camp, BMS's medicinal chemistry expert, was involved in the Canadian litigation and that forms part of the background to his evidence in this case.

THE ISSUES

10

The issues were:

10.1 Some issues over common general knowledge (“CGK”). Much more was agreed than was in dispute.

10.2 Lack of plausibility. Lack of plausibility is not a ground for revocation in itself and it was run both as Agrevo obviousness and insufficiency. Neither side said it made a difference which head applies, and I agree in the light of the case law to which I refer below, in particular Warner-Lambert and Fibrogen. So I will just refer to lack of plausibility.

10.3 Obviousness over WO 00/39131 “Nitrogen Containing Heterobicycles as Factor Xa Inhibitors” (“'131”). This was not a “classical” obviousness attack: the Claimants do not say it was positively obvious to get to apixaban specifically from '131. Rather, they said that '131 contains very similar teaching to '652 about broad classes of compounds that include apixaban, and that there is no technical contribution in '652 over what '131 discloses.

10.4 (Teva only) That claims 1–6 exceed the technical contribution of the Patent and that in particular the claims to products per se are invalid even if some usefulness were to be plausible.

10.5 Allowability of the amendments, where the points were:

10.5.1 Whether the amendments were capable of curing any invalidity.

10.5.2 Lack of clarity.

10.5.3 Added matter.

THE WITNESSES AND THE SKILLED TEAM

11

The parties each called three experts. They were in:

11.1 Medicinal chemistry;

11.2 “The coagulation cascade”, which refers to the pharmacology/biochemistry of relevance;

11.3 Pharmacokinetics or DMPK (“drug metabolism and pharmacokinetics”).

12

Permission for the third of those, DMPK, was pressed for by BMS at the directions stage because it intended to argue that there was a contribution in relation to pharmacokinetics in '652. That argument collapsed with the oral evidence and I think the Claimants were right all along that the Patent is nothing to do with DMPK issues. There was no material dispute over the skilled team by the end of trial in any event: it would be a drug design/development team comprising (i) a medicinal chemist and (ii) a biochemist or pharmacologist, who would have relevant experience in industry. I have paid some minimal attention to evidence from the DMPK witnesses below, but it could easily have been given by one of the other experts and does not change my view on the skilled team.

13

There was no fact evidence.

14

The Claimants' experts were:

14.1 Dr Sally Redshaw (medicinal chemistry);

14.2 Dr Robert Leadley (pharmacology/biochemistry);

14.3 Prof Kevin Read (DMPK).

15

BMS's experts were:

15.1 Dr Nicholas Camp (medicinal chemistry);

15.2 Prof James Morrissey (pharmacology/biochemistry);

15.3 Dr David Taft (DMPK).

16

The only witness of whom personal criticism was made was Dr Taft. The Claimants submitted that his evidence was not credible, to such an extent that he must have been insincere in his defence of it. I reject any personal criticism of Dr Taft. The position he supported was indeed extreme and if it had not been given up on by BMS I would have rejected it, but I think he honestly believed it.

17

As to the other witnesses, points of detail were made about their approach and about their specific experiences. I will deal with those where they arise and to the extent I think them important, which they generally were not. My assessment of these specific points takes place against the backdrop of my more general view that the witnesses were well qualified and gave their evidence fairly and honestly.

18

A basic divergence between the parties was that the factor Xa knowledge was spread differently among their witnesses. For the Claimants, the factor Xa knowledge was possessed by Dr Leadley, with Dr Redshaw having no previous experience in relation to it. For BMS, Dr Camp had a lot of contemporaneous involvement relevant to factor Xa inhibition and Prof Morrissey had none of any significance. Although this probably meant that the Claimants' witnesses together represented the notional skilled team better, in that medicinal chemists often have no direct experience of the specific target of a given project, I did not think it mattered.

SOME IRRELEVANT MATTERS

19

Both sides raised matters which I think are irrelevant and which I will mention now so as to dismiss them.

20

For its part, BMS emphasised that apixaban has proved to be a...

To continue reading

Request your trial
5 cases
  • Bristol Myers Squibb Holdings Ireland Unlimited v Norton (Waterford) Ltd T/A Teva Pharmaceuticals Ireland
    • Ireland
    • High Court
    • 8 December 2023
    ...EWCA Civ. 1610. Regeneron Pharmaceuticals v. Genentech Inc [2013] EWCA Civ. 93. Sandoz Ltd v. BMS Holdings Ireland Unlimited Co. [2022] EWHC 822 (Pat.). Sussex Peerage Case (1844) 11 Cl & F 85. National Justice Compania Naviera SA v. Prudential Assurance Co Ltd. (The Ikarian Reefer) (No. ......
  • Sandoz Ltd v Bristol-Myers Squibb Holdings Ireland Unlimited Company
    • United Kingdom
    • Court of Appeal (Civil Division)
    • 4 May 2023
    ...COURT OF JUSTICE, BUSINESS AND PROPERTY COURTS OF ENGLAND AND WALES, INTELLECTUAL PROPERTY LIST (ChD), PATENTS COURT Mr Justice Meade [2022] EWHC 822 (Pat) Royal Courts of Justice Strand, London, WC2A 2LL Daniel Alexander KC and Anna Edwards-Stuart (instructed by Hogan Lovells International......
  • Bristol-Myers Squibb Holdings Ireland v Norton (Waterford) Ltd T/A Teva Pharmaceuticals Ireland
    • Ireland
    • High Court
    • 17 February 2023
    ...Limited successfully prevailed in revocation proceedings before the High Court of England and Wales in relation to the Patent. ( [2022] EWHC 822 (Pat), per Meade J.; the ‘UK Judgment’.) BMS has recently been granted leave to appeal to the Court of Appeal. (For the reasons set out in paragr......
  • Gilead Sciences Inc. (a company registered in the US State of Delaware) v Nucana Plc
    • United Kingdom
    • Chancery Division (Patents Court)
    • 21 March 2023
    ...dispute about the applicable law. I summarised the relevant principles and key cases recently in Sandoz & Teva v. Bristol-Myers Squibb [2022] EWHC 822 (“ Sandoz”). There, I referred to the three-step test from Fibrogen v. Akebia [2021] EWCA Civ 1279 at [53]: i) First, what falls within the......
  • Request a trial to view additional results
1 firm's commentaries
  • Blockbuster Blood Thinning Patent Revoked
    • United Kingdom
    • Mondaq UK
    • 27 April 2022
    ...to the compound Apixaban (ELIQUIS) for lack of plausibility (Sandoz Limited, Teva Pharmaceuticals v Bristol-Myers Squibb Holdings [2022] EWHC 822 (Pat). Apixaban (Eliquis) is used for thromboembolic disorders and is one of BMS biggest The invalidity action against EP'415 for "Lactam-contain......

VLEX uses login cookies to provide you with a better browsing experience. If you click on 'Accept' or continue browsing this site we consider that you accept our cookie policy. ACCEPT