US and UK law of Patent Enablement – Clear Divergence: The Fibrogen and Amgen decisions

Introduction

On 15 December 2023, the pending appeal to the UK Supreme Court (“UKSC”) in the case of Fibrogen v Akebia was withdrawn. The UKSC had granted permission to appeal on 3 October 2022 from the decision of the Court of Appeal (“EWCA”) (Birss LJ leading) handed down in August 2021[1]. That decision was itself an appeal from the decision of Arnold LJ sitting as a judge in the High Court (Patents Court) (“EWHC”) dated 20 April 2020 [2].

The relevant claims were for a broad class of compounds, defined by structure and function, to be used for treating specified types of anaemia. Arnold LJ in the EWHC had held under a narrow approach that the claims were invalid for insufficiency as lacking plausibility and imposing an undue burden on the skilled addressee. The EWCA overturned this decision and laid down a three-part test combining structural and functional aspects of the claim in the assessment of insufficiency.

Then, on 18 May 2023 the US Supreme Court (“SCOTUS”) handed down its decision in Amgen v Sanofi [3] the most recent instalment of the global battle between Amgen and Sanofi over the cholesterol lowering drug Praluent. The Court upheld the decision of Federal Circuit Court of Appeals (“CAFC”) [4], finding two of Amgen’s patents (US 8829165 and US 8859741) were invalid for lack of enablement. The SCOTUS decision provides an interesting illustration of the narrow approach taken to enablement or sufficiency of disclosure on the other side of the Atlantic and provides a note of caution to patentees seeking functionally limited claims covering broad families of compounds.

In this discussion, we will contrast the current approaches to broad functionally limited claims in the US and UK.

Sufficiency of functional claims – the UK approach

FIBROGEN v AKEBIA

FibroGen v Akebia (“Fibrogen”) remains the leading case in the UK on the validity of broad functionally limited claims, such as those at issue in Amgen v Sanofi. Several other recent decisions in the UK have also considered sufficiency of disclosure in light of the Fibrogen decision [5]. In the case of Sandoz v BMS (concerning the drug apixiban) the EWCA decision (Arnold LJ) upheld the decision of Meade J at first instance, which found the BMS claim invalid on formal grounds of insufficiency in that the claim lacked plausibility [6]. Significantly, Meade J at first instance considered the EWCA decision in Fibrogen but observed that the context in Sandoz was quite different as the BMS invention was in identifying a single compound which, based on a known mechanism and known structural understanding, would treat a recognised kind of condition. As such, Meade J observed that there really was no useful analogy between the cases. On appeal, Arnold J likewise did not consider it necessary to apply Fibrogen.

Meade J subsequently highlighted the distinction between the Fibrogen and Sandoz lines of authority in his decision in Teva v Grunenthal [7], where he stated at [339] “the issue in Sandoz was about plausibility in respect of a single chemical compound rather than plausibility across the scope of a claim covering numerous possibilities; for the latter situation the key statement of the law is to be found in Fibrogen…”

In the UK, the requirement of enablement most closely aligns with that of sufficiency (although there is significant overlap with inventive step, where issues of plausibility are raised). The requirement for sufficient disclosure (and the closest equivalent of 35 U.S.C § 112) is found in s 72(1)(c) of the Patents Act 1977, which states a patent must “disclose the invention clearly enough and completely enough for it to be performed by a person skilled in the art”.

The EWCA in Fibrogen identified two requirements for a claim to a broad functionally limited class to be valid:

1. it must be possible for the skilled person, without undue burden, to identify some compounds beyond those named in the patent, which are within the claimed class; and
2. it must also be possible for the skilled person to work substantially anywhere within the whole claim. So, it must be possible for the skilled person, given any sensible compound within the structural class (or substantially any), to apply the tests without undue burden and work out if it is a claimed compound.

Importantly, the EWCA emphasised that it is not necessary for the skilled person to be able to identify a priori from the patent all (or substantially all) of the compounds which fall within the broadest scope of the claim for it to be valid. It must, however, be possible for the skilled person to make a reasonable prediction of whether the invention will work with any given compound within the claim. Importantly, what was meant by a “compound within the claim” was significantly narrowed. According to the EWCA, “compounds within the claim” were not merely those falling within the “staggeringly large” structural class but additionally, those that also had the functional characteristic of inhibiting the key enzyme (HIF-PH) [8]. Of this functionally narrowed class, the question for the skilled person was whether a reasonable prediction could be made that this narrower class would have the desired therapeutic effect – increasing Epo production/treating anaemia [9].

The EWCA applied a three-part test to determine if a reasonable prediction could be made that the claim would work with a given compound:

1. identify what it is which falls within the scope of the claimed class (which may be defined by both structural and (step one) functional characteristics);
2. determine what it means to say that the invention works (i.e. what is the promised (step two) effect);
3. on the basis of (1) and (2) answer the question whether it is possible to make a reasonable prediction that the invention will work with substantially everything falling within the scope of the claim.

The EWCA therefore decided in a broad approach that patent claims for broad classes of compounds were not necessarily invalid for insufficiency even if they covered a potentially enormous number of compounds. Similarly, the test for undue burden was not the cumulative burden of identifying and testing for efficacy all the compounds covered by the structural formula and/or the functional requirements of the claim. The EWCA decision was highly encouraging to patent owners in the life sciences field, marking as it did a sea-change in the UK approach to insufficiency/undue burden and plausibility/reasonable expectation.

Following the withdrawal of the appeal to the UKSC, the three-part test laid down by the EWCA stands as settled law for the indefinite future, with no further cases considering this issue on the horizon.

Enablement of functionally defined genus claims – the US approach

AMGEN V SANOFI

Background

Both Amgen and Sanofi market monoclonal antibody drugs for the treatment of high cholesterol. Both drugs work by inhibiting a protein called PCSK9, which reduces the body’s ability to remove low density lipoprotein (“LDL”) cholesterol from the bloodstream. Both Amgen and Sanofi developed and patented specific antibodies which target PCSK9 and commercialised them under the brand names Repatha and Praluent respectively. Subsequently, Amgen also obtained two patents (US 8,829,165, “US165” and US 8,859,741, “US741”), which broadly claimed all antibodies which bind to specific amino acid residues on PCSK9 and block binding to LDL receptors.

Starting in 2014, US165 and US741 became the subject of litigation in various jurisdictions [10], with Amgen asserting infringement by Sanofi’s Praluent product. After protracted proceedings the US District Court found in 2019 that both patents were invalid for lack of enablement. This decision was upheld on appeal to the CAFC in February 2021. Amgen appealed this decision to the SCOTUS, which unanimously upheld the decision of the CAFC in May 2023.

Enablement

The enablement requirement in US patent law is found in section 112 of the Patent Act (35 U.S.C § 112) which requires a patent specification to include “a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art… to make and use the same.” In the recent decision, the SCOTUS started by emphasising that this requirement is central to the patent ‘bargain’ by ensuring the public has the full benefit of the invention following expiry of the patent. The key question is, of course, what level of disclosure is required to enable a skilled person to make and use the invention and perhaps more importantly, how to match the level of disclosure to the breadth of the claims.

Although the technology at issue has changed hugely over time, the Court noted that US caselaw back to the 19th century consistently emphasises that the “specification must enable the full scope of the invention as defined by its claims. The more one claims, the more one must enable.” This does not necessarily mean that a patent will be invalid either because it only provides limited examples or requires a “reasonable amount of experimentation” to implement. It is possible for broad claims to be enabled by one (or a few) examples where “some general quality… running through the class that gives it a peculiar fitness for the particular purpose.” is disclosed. However, the Court noted numerous examples where patents which claimed a broad class of materials, limited with reference to a particular function, were found to lack enablement because the disclosure did not match the breadth of the claim.

In the case of US165 and US741, the patents claimed a class of antibodies identified by a twofold functional requirement (1) that it binds to particular amino acid residues on PCSK9 and (2) that it blocks the binding of PCSK9 to LDL receptors. To support these claims, the patents contained details of 26 exemplary antibodies, identified by their amino acid sequences (including evolocumab, the active ingredient in Repatha). Sanofi conceded that the patents were enabled with respect to those 26 antibodies, but the Court noted the claims extended far beyond, to an entire class of antibodies (at least one million) which could bind to a particular region on PCSK9 and have the desired effect.

Beyond the 26 examples provided, Amgen argued the patents were sufficiently enabled, despite the breadth of the claims, because they described two methods for identifying antibodies within the claims – referred to as the “roadmap” and “conservative substitution”. The SCOTUS disagreed, concluding that the “roadmap” was little more than a trial-and-error process of preparing a large number of antibodies and screening them for binding to PCSK9. Similarly, the “conservative substitution” approach required substitutions to be…