Akebia Therapeutics Inc. v Fibrogen, Inc.
| Jurisdiction | England & Wales |
| Judge | Lord Justice Arnold |
| Judgment Date | 20 April 2020 |
| Neutral Citation | [2020] EWHC 866 (Pat) |
| Date | 20 April 2020 |
| Docket Number | Case Nos: HP-2018-0000036, IL-2019-000031 |
| Court | Chancery Division (Patents Court) |
[2020] EWHC 866 (Pat)
IN THE HIGH COURT OF JUSTICE
BUSINESS AND PROPERTY COURTS
INTELLECTUAL PROPERTY LIST (CHANCERY DIVISION)
PATENTS COURT
Rolls Building
Fetter Lane, London, EC4A 1NLL
Lord Justice Arnold
Case Nos: HP-2018-0000036, IL-2019-000031
Justin Turner QC, Thomas Mitcheson QC, Joe Delaney and Thomas Lunt (instructed by Carpmaels & Ransford LLP) for FibroGen
Justin Turner QC, Thomas Mitcheson QC, Kathryn Pickard and Michael Conway (instructed by Potter Clarkson LLP) for Astellas
Iain Purvis QC, Piers Acland QC and Anna Edwards-Stuart (instructed by Hogan Lovells International LLP) for Akebia and Otsuka
Hearing dates: 2–6, 9–12, 17–19 March 2020
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.
Contents
| Topic | Paragraphs |
| Introduction | 1–6 |
| The witnesses | 7–47 |
| Technical background | 48–106 |
| The Family A Patents | 107–153 |
| The claims of the Family A Patents: unconditionally amended | 154–163 |
| The claims of the Family A Patents: conditional amendments | 164 |
| The skilled team | 165–167 |
| Common general knowledge as at the Family A Priority Date | 168–203 |
| The documents cited in the Family A Patents | 204–258 |
| Construction of Family A claims | 259–303 |
| Obviousness of Family A over Epstein | 304–346 |
| Insufficiency of EP 823 and EP 301 | 348–405 |
| AgrEvo obviousness of EP 823 and EP 301 | 406 |
| Infringement of Family A by vadadustat | 407–462 |
| Amendment of EP 531 | 463 |
| The Family B Patents | 464–501 |
| The claims of the Family B Patents | 502–518 |
| The skilled team | 519 |
| Common general knowledge as at the Family A Priority Date | 520–543 |
| The documents cited in the Family B Patents | 544–548 |
| Construction of Family B claims | 549–553 |
| Obviousness of Family B over WO 997 | 554–574 |
| Insufficiency and AgrEvo obviousness of Family B | 575–578 |
| Infringement of Family B by vadadustat | 579–639 |
| Summary of principal conclusions | 640 |
Introduction
These proceedings were originally brought by Akebia Therapeutics Inc (“Akebia”) and Otsuka Pharmaceutical Co Ltd (“Otsuka”) seeking to revoke six patents (“the Patents”) belonging to FibroGen, Inc (“FibroGen”) in order to clear the way for their product vadadustat. Subsequently the exclusive licensee under the Patents, Astellas Pharma Inc (“Astellas”), brought a cross-claim for threatened infringement. For convenience, I shall refer to Akebia and Otsuka collectively as “the Defendants” and to FibroGen and Astellas collectively as “the Claimants”. There were also parallel proceedings involving two GlaxoSmithKline companies (“GSK”) and their product daprodustat which were to be tried together with these proceedings, but those proceedings were settled on the working day before trial.
The Patents concern the use of inhibitors (referred to as HIF-PHIs) of an enzyme called hypoxia inducible factor-prolyl hydroxylase (HIF-PH) for treating various types of anaemia and related conditions. Astellas obtained a marketing authorisation for the first oral HIF-PHI product, roxadustat, in Japan in September 2019, and intends to launch the product more widely, including in the UK. It hopes that the product will achieve blockbuster status by 2023. Vadadustat and daprodustat are HIF-PHI products which are both undergoing Phase III clinical trials at present.
The Patents have been grouped into two families of three patents, each deriving from a common international application, designated “Family A” and “Family B”:
| Family A | Family B |
| WO 03/053997 (“WO 997”) | WO 2004/108121 (“WO 121”) |
| EP (UK) No 1,463,823 (“EP 823”) | EP (UK) No 1,633,333 (“EP 333”) |
| EP (UK) No 2,289,531 (“EP 531”) | EP (UK) No 2,322,153 (“EP 153”) |
| EP (UK) No 2,298,301 (“EP 301”) | EP (UK) No 2,322,155 (“EP 155”) |
There is no challenge to the earliest claimed priority date of the Family A Patents, which is 6 December 2001. It is common ground that the validity of the Family B Patents should be assessed as at the second claimed priority date, which is 29 April 2004. I shall refer to these dates as “the Priority Dates”.
It will be convenient to describe the disclosure of the Patents by reference to the two international applications listed above (“the Applications”), in particular because WO 997, which was published on 3 July 2003, is relied upon by the Defendants as prior art against the Family B Patents. Nevertheless, caution is required, because there are some small, but nevertheless potentially significant, textual differences between the Applications and the respective Patents. I shall return to this point below.
The Defendants contend that the Family A Patents are obvious over A.C.R. Epstein et al, “C. elegans EGL-9 and Mammalian Homologs Define a Family of Dioxygenases that Regulate HIF by Prolyl Hydroxylation”, Cell, 107, 43–54 (5 October 2001) (“Epstein”), that the Family B Patents are obvious over WO 997 and that all the Patents are insufficient. The Defendants also dispute that they threaten to infringe any of the Patents. Furthermore, FibroGen has applied to amend the Patents both unconditionally and conditionally. Most of the amendment applications are unopposed save on the ground that they do not cure the alleged invalidity of the Patents, but one is. The result is a case of considerable complexity, as indicated by the fact that the parties' written closing submissions run to 434 paragraphs (Claimants) and 537 paragraphs (Defendants), and cross-refer to further material in their respective opening skeleton arguments.
The witnesses
Each side called two principal expert witnesses, a nephrologist and a medicinal chemist. Helpfully, each pair of experts was called back-to-back. Less helpfully, the medicinal chemists were called before the nephrologists. The logical order would have been the other way around. This is a problem which I have encountered before. I appreciate that the availability of experts can make scheduling their testimony in the logical order difficult, but I would urge legal teams to do their utmost to try to ensure that this is done.
The Defendants also called a second medicinal chemist, Prof Fishwick. Originally, Prof Fishwick's evidence was directed solely to the number of compounds covered by Formula (I) in what was then claim 19 of EP 823 as proposed to be amended (now claim 19A). It was justifiable for the Defendants to wish to call a second expert for that discrete and limited purpose, particularly given that claim 19 of EP 823 was asserted by the Claimants against the Defendants, but not against GSK. As part of that exercise, however, Prof Fishwick interpreted Formula (I). The Defendants' main medicinal chemist, Prof Ward also interpreted Formula (I), and at that stage appeared to reach the same conclusion. No objection to this was raised by the Claimants prior to the trial, even though the Claimants did (successfully) raise an objection to a different instance of duplication of expert evidence by the Defendants (and GSK) at the pre-trial review. Shortly before the trial, both Prof Ward and Prof Fishwick served supplementary reports acknowledging errors in documents prepared by the Defendants' solicitors which they had exhibited illustrating their interpretation; but at that stage it became clear that they were interpreting Formula (I) differently. Although the Claimants did object to this after the trial had commenced, given that no objection had been raised previously, I permitted the Defendants to call Prof Fishwick not merely to give evidence as to his calculations, but also as to the interpretation of the claim. (The admissibility of the latter evidence is a separate point, to which I will return below.) Sensibly, counsel kept their cross-examination of all three medicinal chemistry experts on this issue brief.
In addition to the experts referred to above, each side called an additional nephrologist to address questions of current and future clinical practice in the United Kingdom which are relevant to the issue of infringement. I will refer to these witnesses as “the clinical practice experts”. Again, it was justifiable for the parties to call additional experts to address these questions, because (for differing reasons) their principal nephrology experts were unable to do so. Without objection from the Defendants, counsel for the Claimants also cross-examined the Defendants' clinical practice expert on some questions of common general knowledge at the Priority Dates.
Expert evidence in patent cases
Before turning to consider the experts individually, it is once again necessary for me to address some general questions concerning expert evidence in patent cases. The Patents Court depends on the assistance it receives from expert witnesses, many of whom are scientists of considerable distinction in their own fields. Particularly in complex cases such as this, preparing expert reports and giving oral evidence can be an arduous task in terms of the time, effort and concentration involved. It is vital that the task of the experts is not made more difficult by the lawyers than it needs to be.
I considered the preparation of expert reports in a passage in MedImmune Ltd v Novartis Pharmaceuticals UK Ltd [2011] EWHC 1669 (Pat) at [99]–[114] which is frequently cited, not least in experts' reports. The key point I made in that passage is that “the lawyers who instruct expert witnesses bear a heavy responsibility for...
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