Sanofi-Aventis Deutschland GmbH et al. v Amgen, Inc. (UPC, Central Division, Section Munich) – claim interpretation, priority claim and assessment of inventive step (non-obviousness)
See our earlier report here for the UPC headnotes.
On July 16, 2024, in one of the UPC’s first decisions on the merits based on a standalone revocation action by Sanofi-Aventis, the Central Division gives important guidelines on claim interpretation, the requirements for validly claiming a priority right, and particularly on the assessment of inventive step. A parallel decision regarding the same patent, EP 3 666 797 B1 (“patent-in-suit”) was issued by the same Division based on a counterclaim for revocation by Regeneron Pharmaceuticals, Inc. on the same day.
Facts of the case/technical background
The patent-in-suit relates to an antibody, or a fragment thereof, for use in reducing increased cholesterol levels in the blood and certain diseases associated with elevated serum cholesterol levels, such antibody binding to a certain part (“catalytic domain”) of a specific enzyme (PCSK9) and reducing the binding of PCSK9 to receptor protein LDLR. LDLR is expressed on the surface of liver cells and removes a certain type of cholesterol (Low density lipoprotein cholesterol, LDL-C, also referred to as “bad cholesterol”) from the blood (marginal no. 5.1 et seqq.).
According to the description of the patent-in-suit, experiments indicated that there was a relation between the levels of PCSK9 and LDLR in the body, for example, that adding PCSK9 to specific liver cells lowered the levels of cell surface LDLR. Against this background, according to the Central Division, the gist of the invention of the patent-in-suit was to target (in particular “inhibit”) PCSK9 by means of antibodies in order to regulate (increase) levels of LDLR and, thereby (reduce) LDL-cholesterol (cf. marginal no. 5.16).
Sanofi and Amgen both distribute cholesterol-lowering antibody drugs inhibiting PCSK9. On the same day that Sanofi filed their revocation action, Amgen brought an infringement action based on the patent-in-suit to the Munich Local Division of the UPC against Sanofi and Regeneron Pharmaceuticals, Inc., which is pending under number ACT_459916/2023. In those proceedings, Regeneron filed a counterclaim for revocation against the patent-in-suit (CC_586764/2023), which was decided on the same day.
In the revocation action, Sanofi requested that the patent-in-suit be fully revoked, arguing, in particular, that the subject matter of the patent-in-suit was not new (Art. 54 EPC) and lacked inventive step (Art. 56 EPC) over the prior art.
Decision by the Central Division
In summary, the patent-in-suit was fully revoked. While finding that the patent-in-suit validly claimed the priority of a prior US application and, thus, Sanofi’s novelty attacks were unsuccessful, the Court also decided that the subject-matter of the patent-in-suit did not involve an inventive step over the prior art document “Lagace”.
Claim interpretation and priority
The initial part of the decision regarding the merits of the case deals with claim interpretation, and in particular the interpretation of feature 3 of claim 1 of the patent-in-suit (“The monoclonal antibody or the antigen-binding fragment thereof binds to the catalytic domain of a PCSK9 protein of the amino acid sequence of SEQ ID NO: 1”; our emphasis). Following the Court of Appeal’s earlier decisions of February 26 (UPC_CoA_335/2023, NanoString ./. 10x Genomics) and of May 13 (UPC_CoA_1/2024, VusionGroup/Hanshow), the Central Division points to Art. 69 EPC as the starting point for any claim interpretation and stresses the relevance of the description and the drawings. In addition to that, the well-known concept that a patent may define terms independently and, thus, constitutes its “own lexicon” is confirmed (marginal no.s 6.3 et seqq.).
Applying these principles to the case at hand, feature 3 is interpreted by the Court as follows: The „catalytic domain“ is understood to be the “region consisting of amino acid residues 123 to 419” (marginal no. 6.12), based on the wording of the claim and the description of the patent-in-suit, and the term „binding“ is interpreted to require that “the antibody must bind to at least one amino acid residue that lies within the catalytic domain” (marginal no.s 6.17 et seq.). In addition, considering feature 4 in particular, the “binding” of the antibody pursuant to feature 3 must allow the realization of feature 4 to occur, i.e. preventing or reducing the binding of PCSK9 to LDLR, without being “limited to any particular degree of reduction of the binding of PCSK9 to LDLR” (marginal no.s 6.23 et seqq.).
With regard to priority, the Central Division states that “the same invention” in accordance with Art. 87 EPC is present, if the skilled person can “directly and unambiguously” derive the subject-matter of the claim from the previous application (marginal no. 7.6). This is in line with the standard applied by the EPO. In the present case, the Central Division finds that a binding to the “catalytic domain” is already “directly and unambiguously” shown in the priority application US20080010630P (“P3”), and, as a consequence, that the patent-in-suit can validly claim the priority date of P3 (marginal no.s 7.7 et seqq.). As a consequence, documents C1 and C2, having a later priority date, were not part of the prior art and could not be considered when assessing novelty (marginal no. 7.14).
Inventive step or non-obviousness – legal framework
In contrast to the standard for priority (cf. above), the Court does not apply the EPO’s “problem-solution approach” to assess inventiveness, which would require to first identify the closest prior art: The Central Division states that it was not necessary to identify the “most promising”, i.e. closest, starting point and instead (merely) requires a “realistic starting point” (marginal no. 8.6). According to the Court’s definition, “a starting point is realistic if its teaching would have been of interest to a skilled person who, at the priority date of the patent at issue, was seeking to develop a similar product or method to that disclosed in the prior art which thus has a similar underlying problem as the claimed invention”. This is relevant because the EPO had identified a different document (“Graham”) as the closest prior art during examination.
Starting from this “realistic” point, the Court then asks whether it was “obvious” for the skilled person to arrive at the technical solution of the patent-in-suit, in view of the underlying problem. This requires that such person would be “motivated (…) to consider the claimed solution and to implement it as a next step (…) in developing the prior art” – particular difficulties with associated next steps may be relevant, meaning that it would not have been obvious to take such steps (marginal no. 8.8). Notably, the last sentence of headnote 4 of the decision (“The decisive question that has to be answered is whether the claimed solution is non-obvious”; our emphasis) appears to put this test on its head, shifting the burden of presentation from the claimant to the patentee.
Another important point included in this decision is the concept of “reasonable expectation of success”, which is primarily relevant for inventions in biochemistry and pharmaceutics. According to this concept, a “reasonable expectation of success” may indicate, or even be required, for a finding of lack of inventive step (cf. headnote 4, and marginal no.s 8.56 et seqq.). Notably, this concept is introduced in the subsequent section assessing inventive step (cf. below).
Concluding the section on the legal framework, the Court states that “a technical effect or advantage achieved by the claimed subject matter compared to the prior art may be an indication for inventive step”, but also that “a feature that is selected in an arbitrary way out of several possibilities cannot generally contribute to inventive step” (marginal no. 8.10).
Inventive step or non-obviousness – application
In the following section (marginal no.s 8.11 et seqq.), prior art document C3 (“Lagace”) is described and analyzed in detail, with a particular focus on the last sentence of the final paragraph of the “Discussion” section, which reads as follows: “If PCSK9 functions as a secreted factor as suggested by the current data, then additional approaches to neutralize its activity, including the development of antibodies to block its interaction with the LDLR or inhibitors to block its action in plasma, can be explored for the treatment of hypercholesterolemia” (underlined by the Court).
The Court finds that the person skilled in the art, starting from this „explicit suggestion” in Lagace (marginal no. 8.80), would have developed antibodies binding to PCSK9 as a treatment for hypercholesterolemia. The Court states that PCSK9 was a (genetically) “validated target for lowering LDL levels in the blood” (marginal no.s 8.32 et seqq.) and that the skilled person learnt from Lagace “that PCSK9 functions extracellularly in vivo” (marginal no.s 8.36 et seqq.). This is important because antibodies are large protein molecules which can generally only be applied outside of cells (marginal no. 8.36). Both aspects were disputed by the Defendant, arguing that neither the extracellular pathway of PCSK9 nor the details of the interaction between PCSK9 and LDLR, were known at the priority date.
However, the Central Division cannot conclude “that the skilled person at the relevant date would have serious doubts about whether PCSK9 indeed acts (at least also) extracellularly in vivo as taught by Lagace, at least not doubts that were of such a nature that these would have dissuaded the skilled person from pursuing an antibody approach to block the interaction between PCSK9 and LDLR as suggested by Lagace” (marginal no. 8.50). As indicated by the last sentence of headnote 4 (cf. above), it appears that the Court does not review whether it was obvious to arrive at the invention of the patent-in-suit, but instead asks for reasons why the patented solution was non-obvious (i.e. inventive) from the skilled person’s perspective.
The Court then addresses the aspect of “reasonable expectation of success”, finding that “the uncertainties raised by the Defendant would not have prevented the skilled person from taking the obvious next step, i.e. developing PCSK9/LDLR inhibiting antibodies (…) due to insufficient prospects of success” and leaving open the question whether such requirement had to be applied at all (marginal no.s 8.56 et seqq.). The Court continues by stating that “the absence of a reasonable expectation of success (or more in general: non-obviousness) does not follow from the mere fact that other ways of solving the underlying problem are also suggested in the prior art and/or (would) have been pursued by others” – in this regard, again, the Court does not ask the claimant to provide reasons why the invention of the patent-in-suit was obvious, i.e. why the person skilled in the art would have chosen a specific way within a number of alternative ways, but requires the patentee to show why choosing the patented way was based on an inventive step.
The Court also finds that the skilled person “would arrive at antibodies falling under the claim” applying known methods (marginal no.s 8.66 et seqq.), and, finally, that the requirement that the claimed antibody “binds to the catalytic domain” in feature 3 was arbitrary and that there was no “apparent causal technical connection between the feature “binds to the catalytic domain” and the reduction of the binding of PCSK9/LDRL and, ultimately, the therapeutic effect claimed”, so that this feature could not contribute to inventive step and, therefore, must be ignored (marginal no.s 8.76 et seqq.).
As a consequence, the Central Division fully revokes the patent-in-suit, also finding that the Auxiliary Requests made by the Defendant did not remedy the granted claims’ lack of inventive step. In accordance with Art. 69 UPCA and Rule 118.5 RoP, the Defendant is ordered to bear the legal costs incurred by the Claimants to a maximum amount of 1.375 mio. EUR, which ceiling was agreed upon by the Parties.
Take aways:
In summary, the present decision provides important guidelines, in particular with regard to the assessment of inventive step in revocation proceedings. The reasoning is very well written, with respect to the structure and detail of the findings as well as the application of the legal principles to the present case and the discussion of both sides’ arguments.
Notably, on the substance, this decision appears to establish high hurdles regarding the validity of patents, particularly in the fields of biochemistry and pharmaceutics, in that it quite quickly establishes a motivation for the skilled person to take the next step(s) of developing antibodies for a certain target based on a cautiously worded sentence in a science paper (“If PCSK9 functions as a secreted factor as suggested by the current data, then additional approaches to neutralize its activity, including the development of antibodies to block its interaction with the LDLR or inhibitors to block its action in plasma, can be explored for the treatment of hypercholesterolemia”; emphasis added) and then requires the patentee to give reasons why the patented solution was nevertheless non-obvious for the skilled person.
It will be interesting to see if Amgen appeals this decision and, if so, whether or to what extent the Court of Appeals will uphold the Central Division’s principles and findings, for example with respect to the EPA’s problem-solution approach.
