Federal Court dismisses Sanofi's appeal and orders that Amgen's Repatha patent applications proceed to grant, offering key lessons for other antibody patents approaching the end of their term.
The global patent litigation concerning Amgen's PCSK9 antibody patents has highlighted the divergent approach taken by major jurisdictions in assessing the validity of functionally defined antibody claims. In the US, Amgen's patent claims were ruled invalid by the Federal Circuit for lack of enablement.1 In corresponding European opposition proceedings, the claims of Amgen's patent were found to be enabled, but were subsequently invalidated by the Board of Appeal for lacking an inventive step.2
In 2022, a Delegate of the Commissioner of Patents in Australia ruled in Amgen's favour, finding that five of its patent applications are valid and should proceed to grant.3 A detailed discussion of this can be found in our previous article here. Sanofi appealed the decision to the Federal Court.
The Federal Court has dismissed Sanofi's appeal and ordered that Amgen's patent applications proceed to grant.4 The decision was made under the Patents Act 1990 prior to the introduction of amendments that raised the written description requirements, and so it is not directly applicable to patent applications that are subject to the current Patents Act 1990.
However, the decision holds important lessons for a number of other valuable antibody patents that are approaching the end of their term and that are still subject to the old Act - and that may be the target of litigation in coming years as biosimilars look to enter the market.
The opposed applications
The opposed applications stem from international patent application no. PCT/US2008/074097. The Australian national phase application has granted, and its term was extended under Australia's pharmaceutical patent term extension provisions.
Amgen filed several divisional applications, five of which were accepted and subsequently opposed by Sanofi in 2016. The opposed applications cover Amgen's cholesterol-lowering antibody, evolocumab (REPATHA), and potentially cover Sanofi's competitor antibody, alirocumab (PRAULENT).
Evolocumab targets PCSK9 and lowers low-density lipoprotein (LDL) cholesterol levels. Evolocumab was first approved by the Australian Therapeutic Goods Administration in 2015 for the treatment of hypercholesterolaemia. If granted, the opposed applications may also be eligible for an extension of term based on the regulatory approval of evolocumab.
The applicable law
The opposed applications are all subject to Patents Act 1990 as it existed prior to the introduction of the Intellectual Property Laws Amendment (Raising the Bar) Act 2012, which came into effect in 2013.
The so called "Raising the Bar" amendments were introduced by the Australian Parliament to align Australia's written description requirements with those of its major trading partners, particularly Europe and the US. Under the current Act, the requirements of support and sufficiency apply, meaning that, as in Europe, the claims must be commensurate with the technical contribution to the art, and the specification must enable a skilled person to perform the invention across the full scope of the claims without undue burden or further invention.
Under the "old" Act, however, the requirements of "full description" and "fair basis" apply. The standards set by full description and fair basis are much lower than those set by support and sufficiency, and challenging a patent on these grounds has been notoriously difficult (and more often than not, unsuccessful).
The claims
The claims of Amgen's patent applications were broadly grouped into three classes:
- epitope claims, which define an isolated monoclonal antibody by its ability to bind an epitope of PCSK9, the epitope comprising one or more nominated residues;
- residue claims, which define an isolated monoclonal antibody by its ability to bind one or more specific residues of PCSK9; and
- competition claims, which define an isolated monoclonal antibody by its ability to compete for binding with a structurally-defined antibody.
The claims also include functional language referring to the ability of the antibody to block or reduce binding of PCSK9 to the LDL receptor (LDLR).
Grounds of opposition
Sanofi summarised its opposition as follows:
- Failure to define the invention - The claims of the opposed applications fail to define the invention in that they pertain to any "isolated monoclonal antibody" having some claimed functional features only. The "blocking" function of an antibody, knowledge of the epitope or a residue or residues on an antigen to which an antibody binds, or reference to another antibody with which an antibody competes, does not define the structure of, or characterise the construction of, an antibody as claimed.
- Not a manner of manufacture - The claims of the opposed applications fail to define a manner of manufacture because they are for no more than a mere desideratum, namely, any monoclonal antibody providing particular functional outcomes.
- Lack of fair basis - The claims travel well beyond any invention described in the specification and omit essential features of that invention and are therefore not fairly based.
- Lack of clarity - The competition claims lack clarity because it is not clear whether "competes" means any degree of competition or some particular numerical degree of competition and, in any event, there is no workable standard to determine the exact boundaries of the claims. Various alternative competitive binding assays described in the specification can produce different results.
- Failure to describe the invention fully - The claims of the opposed applications are properly characterised as claims to a multiplicity of inventions, each a different antibody with a unique amino acid sequence and binding to a different epitope on PCSK9. The opposed applications are therefore insufficient because the person skilled in the art would need to engage in a research project in an attempt to produce one embodiment of each such invention.
- Lack of inventive step - The use of an antibody to inhibit PCSK9 had been postulated in well-known, peer-reviewed literature. LDLR residues in the PCSK9 and LDLR EGFa domain interface were known. It was "logical" that an antibody that blocks the binding of PCSK9 to LDLR (to any degree) would do so by binding to an epitope that included any one of the residues in the PCSK9/EGFa interface. It follows that the inventions do not involve any inventive step.
Sanofi was unsuccessful on each ground, as summarised below.
Failure to define the invention
Sanofi's principal attack on the opposed applications was based on what it says is the failure of the claims to define the invention. In particular, Sanofi submitted that each of the relevant claims did not sufficiently define the structure of a monoclonal antibody ("MAb") either by reference to its amino acid sequence or otherwise. Rather, the claims were limited by a result to be achieved.
Sanofi submitted that the claims did not permit others to know whether a MAb that they proposed to make was either inside or outside the claims in advance of making it. Sanofi's argument was not that the method of testing whether a MAb fell within the scope of a claim is unclear or ambiguous, but instead that defining the MAb by reference to results obtained through testing after generation is impermissible.
Justice Nicholas found Sanofi's argument to be contrary to authority.5 What is essential, His Honour said, is that a person skilled in the art is able to determine whether a particular MAb is within or outside the claims.6 In that regard, the functional limitations in the claims were not shown to be insufficient to characterise the construction of the relevant MAbs so as to enable the skilled person to determine whether any particular MAb falls within the scope of the claims. Consequently, this ground of opposition failed.
Manner of manufacture
Sanofi submitted that it is not possible to identify the structure of any putative "isolated monoclonal antibody" within the claims of the applications. It submitted that the substance of the invention as claimed is not a MAb and is instead no more than an abstract idea or a "mere desideratum" of any antibody that has the desired functional outcome.
Nicholas J did not accept these arguments, finding that the claimed antibodies are a product made through human action beginning with the immunisation of transgenic mice with PCSK9 followed by the creation of hybridomas.7
Fair basis
Prior to its amendment by the Raising the Bar Act, section 40(3) of the Patents Act 1990 required the claims of a patent to be "fairly based on the matter described in the specification". Section 40(3) now requires that the claims be "supported by matter disclosed in the specification". Establishing "support" requires that the technical contribution to the art disclosed by the specification justify the breadth of the claim.8
Fair basis, on the other hand, is not concerned with the technical contribution to the art or the inventive merit of the invention. Fair basis requires that the body of the specification contain "a real and reasonably clear disclosure" of what is claimed.9
Sanofi submitted that none of the claims of the opposed applications are fairly based because the claimed invention is different from the invention described in the respective specifications. Sanofi's submissions proceeded on the basis that the specifications disclose the invention as "at best three isolated monoclonal antibodies (21B12, 31H4 and, perhaps, 16F12)".10
Epitope and residue claims
Sanofi submitted that the specification does not describe "any single antibody (or even any combination of antibodies) that binds to all of the claimed residues, or even a significant subset thereof". Generally, Sanofi's submissions on this point took issue with the relevant claims including certain residues, where no specific (i.e., generated and tested) antibody has been identified in the specifications as binding to that residue.
Nicholas J did not accept these submissions, finding that the epitope and residue claims can be fairly based, even if the specification does not state that the residues within those claims are part of structural or functional epitopes. It is enough that the specification explains that antibodies which interact with, or block, the residues identified in the examples of specification will be useful in the inhibition of PCSK9 binding to LDLR. It is not necessary for the specification to provide scientific proof of the relationship between core and boundary residues and the functional and structural epitopes of any antibody.11
Sanofi's argument largely relied on the proposition that the claims cover many more antibodies than the true invention, which it said should be understood to be 21B12 and 31H4 (and perhaps 16F12). However, His Honour found that the specification does not need to exemplify every antibody the subject of the claims in order for the claims to be fairly based. Nor does the specification require the skilled person to engage in impermissible extrapolation. The disclosures in the specification demonstrate that the reference antibodies exemplify the invention, but do not limit it.12
Sanofi's comparison between the exemplified antibodies and the potential total number of antibodies falling within the class (i.e., "hundreds, if not thousands or many more") did not assist it once it was accepted that the invention described is not limited to 21B12, 31H4 and 16F12. His Honour observed that this kind of analysis might well be relevant to the support requirement now found in the Patents Act 1990, but it has no role to play in assessing fair basis.13
His Honour also found there was no basis for Sanofi's argument that the claims omit essential elements, namely core residues in certain interaction interfaces. A claim which lacks fair basis because it omits a particular element is one that, by that omission, becomes a claim to a fundamentally different invention. That was not found to be the case here.14
Competition claims
With regard to the competition claims, Sanofi argued that the "suggestion that an applicant invented both the invention described in the specification, together with anything that may be later demonstrated to compete with that thing at a later point in time, must be wrong as a matter of principle".
Sanofi also submitted that if the competition claims are understood to include those antibodies which compete to any degree, then the competing antibodies "are not described in the Applications by reference to any degree of competition".
Sanofi did not point to any particular statement in the specification that teaches against the invention being antibodies that compete with 21B12 and 31H4. The submissions instead took issue with the breadth of the monopoly falling within the competition claims, and repeated some of the arguments previously considered.
Finding in Amgen's favour, Nicholas J pointed to passages in the opposed applications which explicitly contemplated the preparation of antibodies which compete with 21B12 and 31H4.15 His Honour also noted that the nature of the examples suggests that the invention described in the specification is, in addition to antibodies which bind to particular residues or epitopes, a class of antibodies that compete with the reference antibodies or other antibodies described in the specification.
With regard to Sanofi's argument concerning the degree of competition required for an antibody to fall within the claims, His Honour found that there is nothing in the specification which would suggest that a claim to antibodies which compete could not be fairly based because it did not specify any particular percentage or degree of competition.
Inventive step
Sanofi's primary case was that the relevant claims lacked an inventive step based on the common general knowledge as it stood at the priority date. Sanofi submitted that this case was strongly supported by the evidence of expert witnesses and scientific articles published before the priority date.
His Honour accepted that the notional person skilled in the art (which was considered to be a team of skilled persons) would have considered the possibility of generating PCSK9 inhibiting monoclonal antibodies as a potential treatment for hypercholesterolemia and related cardiovascular diseases. However, the relevant question was whether the notional team would have been directly led to try to generate such antibodies as a matter of course in the expectation that they may well block or inhibit binding between PCSK9 and LDLR.
Having regard to the evidence, His Honour was not persuaded that the question should be answered in the affirmative.16 In particular, His Honour found that the pathway to the generation of anti-PCSK9 antibodies was not clear or straightforward and was the subject of considerable uncertainty relating to PCSK9's mechanism of action and whether it would even be possible to generate an antibody to PCSK9. His Honour was therefore not satisfied that the notional skilled team would have been directly led to try an anti-PCSK9 antibody in the expectation that it may well succeed.
Clarity
Sanofi argued that the competition claims lack clarity because they do not provide a workable standard suitable to the intended use by which the skilled person can determine whether an antibody competes for binding with either of the reference antibodies.17 His Honour did not agree, finding that "competes" as used in the specification and the competition claims can refer to any scenario in which a test antibody prevents or inhibits the reference antibody from binding to the common antigen, including by steric hindrance, conformational changes on the antigen or by other indirect means.18
His Honour noted that the specifications identify various types of assays that may be used to determine whether the test antibody competes with a reference antibody, but it does not require that they compete to any particular degree. If there is any competition between the test antibody and the reference antibody, the requirement of the claims will be met.19
His Honour was also not persuaded that the competition claims do not provide a workable standard due to a failure to identify a particular competition assay. In particular, His Honour was not satisfied that the use of different assays to determine whether two antibodies compete for binding to the same antigen would be likely to produce materially different results.20
Sufficiency
Section 40(2)(a) of the Patents Act 1990, pre-amendment by the Raising the Bart Act requires that a complete specification "describe the invention fully". In Kimberly-Clark Australia Pty Ltd v Arico Trading International Pty Ltd [2001] HCA 8, the High Court described the relevant question as follows at [25]:
...[W]ill the disclosure enable the addressee of the specification to produce something within each claim without new inventions or additions or prolonged study of matters presenting initial difficulty?
Sanofi accepted that if the invention in each claim of the opposed applications is properly characterised as a single invention, namely a class of monoclonal antibodies, then the claims are fully described. But, Sanofi argued, where a claim is in effect a claim to more than one invention, the specification must describe how to perform an embodiment of each invention within the claim. In that regard, Sanofi said that the claims of the opposed application are not claims to a class of antibodies, but are claims to a very large number of individual, monoclonal antibodies, each binding to its own particular epitope on PCSK9.
His Honour was not persuaded that the each of the claims was for a number of different inventions. Rather, His Honour concluded that each of the specifications describes a class of antibodies which bind either directly to certain nominated residues, or to epitopes containing certain nominated residues.21
Orders
The Court ordered that the decision of the Delegate of the Commissioner of Patents be affirmed and that Amgen's patent applications proceed to grant. The parties have been given until 21 May 2025 to apply for leave to appeal the decision.
Footnotes:
1 No. 20-1074, Fed. Cir. 2021.
2 T 0845/19.
3 Sanofi v Amgen Inc. [2022] APO 67.
4 Sanofi v Amgen Inc. (No 3) [2025] FCA 387 ('Sanofi v Amgen').
5 Sanofi v Amgen at [199].
6 Sanofi v Amgen at [218].
7 Sanofi v Amgen at [241].
8 ToolGen Incorporated v Fisher (No 2) [2023] FCA 794 at [391]-[396] following Merck Sharp & Dohme Corporation v Wyeth LLC (No 3) (2020) 155 IPR 1 at [546]-[547].
9 Lockwood Security Products Pty Limited v Doric Products Pty Ltd [2004] HCA 58 at [69].
10 Sanofi v Amgen at [265].
11 Sanofi v Amgen at [315].
12 Sanofi v Amgen at [317].
13 Sanofi v Amgen at [318].
14 Sanofi v Amgen at [322].
15 Sanofi v Amgen at [339].
16 Sanofi v Amgen at [426].
17 Sanofi v Amgen at [430].
18 Sanofi v Amgen at [433]-[434].
19 Sanofi v Amgen at [435].
20 Sanofi v Amgen at [454].
21 Sanofi v Amgen at [464].
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