Contains public sector information licensed under the Open Justice Licence v1.0.
England and Wales Court of Appeal (Civil Division)
(Aug 24, 2021)
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[2021] EWCA Civ 1279
Case Information
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FibroGen Inc v. Akebia Therapeutics Inc
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Factual and Procedural Background
This appeal concerns six patents owned by Company A and exclusively licensed to Company B, relating to the use of HIF-PH inhibitors for treating anaemia. Company B obtained the first marketing authorisation for a HIF-PH inhibitor product in Japan in 2019, based on Company A's and Company B's roxadustat product, anticipated to achieve significant sales.
Company C and Company D jointly developed a rival HIF-PH inhibitor, vadadustat, in clinical trials for anaemia. The litigation began with Company C and Company D seeking revocation of Company A's patents. Company B brought a quia timet infringement claim against Company C and Company D, alleging that a future launch of vadadustat would infringe the patents. Company A was joined as defendant in that claim. For convenience, Company A and Company B are collectively referred to as Company A, and Company C and Company D as Company C.
The patents form two families: Family A, based on application WO 03/053997 ("WO 997"), includes three UK patents with earliest priority date 6 December 2001; Family B, based on WO 2004/108121 ("WO 121"), includes three UK patents with validity assessed as at 29 April 2004. The Family A patents primarily relate to treatment of anaemia associated with chronic kidney disease (CKD), while Family B patents relate to anaemia of chronic disease (ACD).
Company C challenged Family A patents on grounds of inventive step and insufficiency, particularly alleging lack of plausibility and undue burden due to excessive claim breadth. The inventive step challenge focused on obviousness over prior art called Epstein. Insufficiency was also alleged based on uncertainty regarding claims requiring a compound to be a "structural mimetic of 2-oxoglutarate".
Infringement issues for Family A involved whether vadadustat fell within the claim scope and whether it infringed by equivalence. For Family B, the inventive step challenge was based on WO 997, and insufficiency challenges mirrored those for Family A. Company A also pursued a quia timet infringement claim for Family B, contending that Company C intended to market vadadustat infringing those patents.
The trial involved extensive expert evidence in nephrology, medicinal chemistry, and clinical practice. The trial judge found Family A patents not obvious over Epstein but invalid for insufficiency due to lack of plausibility and undue burden, and uncertainty insufficiency succeeded. Vadadustat was found to infringe the wide Family A claims on normal construction but not by equivalence. Family B patents were found obvious over WO 997 and insufficient for the same reasons. No threat of infringement of Family B patents was found.
On appeal, Company A challenges the insufficiency findings for both patent families (except for single compound claims), the obviousness finding against Family B, and Company C challenges the finding that vadadustat falls within Formula I. The appeal proceeds with permission of the court below.
Legal Issues Presented
- Whether the Family A patents are invalid for insufficiency due to lack of plausibility and undue burden, and uncertainty, particularly regarding claims combining structural and functional features.
- Whether the Family B patents are invalid for obviousness over WO 997.
- Whether vadadustat infringes the Family A patents and falls within the chemical scope of Formula I.
- Interpretation and application of the law concerning sufficiency of disclosure as it relates to claims with combined structural and functional features.
- Whether the claims are conceptually uncertain due to ambiguous claim language such as "structural mimetic of 2-oxoglutarate".
Arguments of the Parties
The opinion does not contain a detailed account of the parties' legal arguments.
Table of Precedents Cited
| Precedent | Rule or Principle Cited For | Application by the Court |
|---|---|---|
| Regeneron v Genentech [2020] UKSC 27 | Two-stage insufficiency test: plausibility and undue burden; reasonable prediction; application to claims with broad structural and functional features. | The court applied the two-stage test, emphasizing that claims must be plausible and capable of being performed without undue burden. The court disagreed with the trial judge's narrow interpretation requiring identification of substantially all compounds. |
| Idenix v Gilead [2016] EWCA Civ 1089 | Insufficiency based on lack of plausibility; claims to Markush classes require reasonable prediction of efficacy. | The court distinguished this case as not involving double functional features and rejected the trial judge's reliance on Idenix to require the patent to demonstrate plausibility across all compounds. |
| Dipeptidyl-Peptidase-Inhibitoren (BGH X ZB 8/12, 2013) | Claims with broad functional language are not insufficient if the skilled person can identify compounds without undue burden; functional features can cover unknown compounds. | The court agreed with the BGH that the trial judge's requirement that the skilled person identify substantially all compounds was too strict and that claims with functional features need only enable identification of compounds without undue burden. |
| Unwired Planet v Huawei [2016] EWHC 576 (Pat) | Distinction between ambiguity and conceptual uncertainty in patent claims; conceptual uncertainty can invalidate a claim. | The court applied this framework to assess whether the term "structural mimetic of 2-oxoglutarate" was conceptually uncertain and found it was, due to lack of clear test to determine the feature. |
| Actavis v ICOS [2019] UKSC 15 | Principles on inventive step, obviousness, expectation of success, and stepwise analysis. | The court applied the principles rejecting improper stepwise analysis and confirmed that expectation of success is relevant but does not require manifest certainty of outcome. |
| Warner Lambert v Generics [2018] UKSC 56 | Plausibility requirement in sufficiency of disclosure. | The court cited this in support of the plausibility stage of the insufficiency analysis. |
| Biogen Inc. v Medeva plc [1997] RPC 1 | Principle of general application for claims in general terms; reasonable prediction of efficacy. | The court relied on this to explain that claims in general terms are valid if a principle of general application is disclosed, allowing reasonable prediction of efficacy across the claim scope. |
| Generics v Lundbeck [2009] UKHL 12 | Claims must be judged by their terms, not by partial technical contributions. | The court held that validity must be assessed by reference to the claims themselves, rejecting attempts to limit technical contribution by reference to partial inventive step findings. |
| Mobil/Friction Reducing Additive G2/88 (EPO) | Novelty and inherency principles for second medical use claims. | The court considered but did not decide on the application of this line of cases, noting it was not necessary for the appeal decision. |
| Hallen v Brabantia [1991] RPC 195 | Unexpected beneficial effects and their role in inventive step. | The court applied the principle that unexpected beneficial effects do not confer inventive step if they would be discovered by obvious steps. |
| Mentor v Hollister [1991] FSR 577 | Reasonable trial and error and undue burden in sufficiency. | Cited to explain that reasonable experimentation is permissible and does not cause insufficiency unless it imposes an undue burden. |
| Rockwater v Technip [2004] RPC 46 | Skilled person and reading of prior art and cited documents. | Discussed in the context of whether the skilled person is deemed to read all cited documents with interest; the court found it fact-dependent. |
| Brugger v Medicaid [1996] RPC 635 | Obviousness of alternative uses; one obvious way forward does not exclude others. | The court applied this principle to reject the argument that obviousness of one use excludes obviousness of another. |
| General Tire v Firestone [1972] RPC 457 | Principle of inevitable result in novelty. | Referenced in rejecting an argument that the claims lacked novelty by inevitable result; court found no such finding was made. |
| Technograph v Mills & Rockley [1972] RPC 346 | Warning against stepwise analysis in obviousness. | The court held no improper stepwise analysis occurred as the steps taken by the skilled person were ascertainable without hindsight. |
Court's Reasoning and Analysis
The court began by examining the claims of Family A patents, focusing on claim construction and the application of sufficiency law to claims combining structural and functional features. It rejected the trial judge's construction that the claims implicitly promised that substantially all compounds covered by the broad structural definitions would have the claimed therapeutic efficacy. Instead, the court held that the claims are limited to compounds satisfying both structural features and step one functional features (e.g., HIF-PH inhibition and increasing endogenous erythropoietin), which are testable by appropriate assays.
The court emphasized a three-step approach to reasonable prediction (plausibility): (1) identify what compounds fall within the claim scope (both structural and functional features), (2) determine what it means for the invention to work (therapeutic efficacy), and (3) assess whether it is possible to make a reasonable prediction that substantially all such compounds will work.
Applying this, the court found it plausible that compounds satisfying both structural and functional features would be effective to treat CKD anaemia. The presence of inactive compounds within the structural class that do not satisfy the functional features is irrelevant, as they do not fall within the claim scope.
Regarding undue burden, the court rejected the trial judge's approach that the skilled person must identify substantially all compounds within the claim without undue burden. Instead, the test requires that the skilled person can identify some additional useful compounds beyond those named in the patent, and can work substantially anywhere within the claim scope without undue burden. The court found that although identifying further compounds would require routine, iterative structure-activity relationship (SAR) analysis involving substantial work, this would not constitute an undue burden.
The court also addressed the uncertainty insufficiency concerning the term "structural mimetic of 2-oxoglutarate". It found that the skilled person would construe this as referring to compounds having the capacity to competitively inhibit the target enzyme with respect to 2-oxoglutarate. While there may be a fuzzy boundary regarding potency thresholds, this does not amount to conceptual uncertainty invalidating the claims.
On the Family B patents, the court accepted the trial judge's finding that the claims were obvious over WO 997. WO 997 disclosed the use of the compounds for treating ACD and related conditions, including effects on iron transport and utilization, which formed the basis for the Family B claims. The court rejected arguments that the technical contribution included an unexpected beneficial effect on iron metabolism beyond that disclosed. Even if such a benefit existed, the skilled team would have discovered it by obvious steps, negating inventive step.
The court rejected the argument that the claims required a particular mode of action (e.g., overcoming reticuloendothelial block) as that was not a claim feature. The claims were construed broadly to cover treatment of functional iron deficiency regardless of mechanism.
Regarding infringement, the court upheld the finding that vadadustat falls within Formula I. The dispute concerned whether a chlorine substituent on an aryl group was covered by the claim language allowing substitution by halogens. The court agreed with the patentee that the "Permitted Aryl Language" applies broadly to all aryl groups in the relevant section of the claim, covering the chlorine substituent in vadadustat.
The court concluded by allowing the appeal on sufficiency grounds for Family A patents, thereby validating EP 823 and finding infringement by vadadustat for treatment of CKD anaemia. It dismissed the appeal on obviousness grounds for Family B patents, leaving them invalid. The respondent's notice challenging infringement was dismissed.
Holding and Implications
The Court of Appeal ALLOWED the appeal concerning the sufficiency of the Family A patents (notably EP 823), thereby restoring their validity and confirming infringement by vadadustat in the treatment of CKD anaemia.
The Court DISMISSED the appeal against the obviousness finding for the Family B patents, maintaining their invalidity on that ground.
The Court DISMISSED the respondent's notice challenging the conclusion that vadadustat falls within Formula I.
The decision clarifies the application of sufficiency law to claims combining structural and functional features, emphasizing a nuanced approach to plausibility and undue burden that does not require the skilled person to identify substantially all compounds within a claim. It also affirms that conceptual uncertainty requires inability to determine claim scope rather than mere difficulty or fuzzy boundaries.
The ruling has direct consequences for the parties: Company A's Family A patent EP 823 is valid and infringed, while Family B patents remain invalid due to obviousness. No new precedent was established beyond the application and clarification of existing principles in the context of complex pharmaceutical claims.
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