Sufficiency of broad functional genus and first medical use claims in Europe (T 0424/21)

The Board of Appeal in T 0424/21 considered the sufficiency of a broad genus of antibodies and their use to treat any disease.  The breadth of the patent claims upheld on appeal may well be astonishing to US readers used to the onerous US sufficiency requirements. In contrast to the US, the decision from the EPO Boards of Appeal is a case study of how functional claim language that wouldn't pass muster in the US, can be used to great effect in Europe.  

Case background: Improved antibody function: 

The patent (EP2691417) related to modified antibodies having decreased effector function. Antibodies are made up of 2 parts, a target-binding region and a constant region. The target-binding region is highly variable between antibodies and gives the antibody its high specificity for its target. The constant region (Fc) is far less variable and controls the function of the antibody. The Fc region may, for example, allow the antibody to be recognised by Fc receptors (FcRs) on the surface of immune cells. Binding of an antibody to the FcRs on a cell can then activate the immune cell and direct antibody dependent cell killing (ADCC) of tissue cells infected with a virus or bacteria. 

Antibodies

For a monoclonal antibody directed to a specific disease target, antibody dependent cell killing mediated by the Fc can be an unwanted side effect. The patent in this case related to a modified antibody Fc region that had a reduced ability to activate antibody dependent cell killing. The granted claims related to a broad genus of antibodies, defined only by the specific mutations in the Fc region, and not limited to antibodies specific for particular disease targets. The claims also related broadly to the use of such an antibody as a medicament, without specifying any particular disease, in first medical use format, i.e. "The antibody or Fc fusion protein according to any one of claims 1-6 for use as a medicament."

Sufficiency for in vitro properties

On appeal, the Opponent argued that the antibodies specified by the claims were not sufficiently disclosed over the whole range claimed. The Opponent pointed out that, except for the triple mutation specified by claim 1, the claimed Fc regions were defined entirely by function, e.g. reduced antibody dependent cell killing (claim 2) or reduced binding to FcRs (claim 3). However, the examples in the specification only provided data for specific antibodies, an anti-CD20 and an anti-CD9 antibody. The Opponent therefore argued that the skilled person would not be able to obtain the claimed effects "for substantially all the Fc receptor variants falling within the scope of the claims".

The Board of Appeal dismissed the Opponent's argument with respect to each of the specific functional features. Critically for the Board of Appeal, the Opponent had "not provided any evidence that [the claimed effects] were restricted to the particular antibodies used in the examples". Therefore, "for the want of any serious doubts" over the applicability of the functional language across the claimed genus, the patent was found to enable the skilled person to obtain antibodies having the functional features of the claims (r. 33). 

Sufficiency of a first medical use

The Opponent also argued that the first medical use claims relating to the antibodies for use as a medicament (Article 54(4) EPC, Article 53(c) EPC) were also insufficiently disclosed. In this case, the specification did not provide any data demonstrating a treatment effect. The specification provided in vitro data showing the effect of the mutations when they were introduced into known therapeutic antibodies. For the Board of Appeal, it was plausible from this in vitro data that "the mutated antibodies [could] be used as a medicament [...] without the mutations in the Fc region impairing the therapeutic effect (r. 35). This position is in line with previous case law that in vitro data may support a claimed therapeutic effect (IPKat). 

The only question remaining for the Board of Appeal was therefore whether the claims should be limited to the particular therapies of the example antibodies, or if a claim directed to the use of the antibodies to treat any disease was justified. 

The Board of Appeal noted that the case law relating to the sufficiency of first medical use invention is relatively sparse. Previous cases have generally related to the question of sufficiency of first medical use cases in the context of an already known substance or composition. By contrast, in the present case, the product itself was novel (Case Law of the Boards of Appeal, II.C.7.2). However, the Board of Appeal noted that the same sufficiency standard should apply to first medical use cases regardless of whether the substance or composition is already known (r. 36). 

The Board of Appeal found that they could not "derive any requirement from the EPC whereby a patent would have to show that a compound is suitable for each and every disease in order for a first medical use to be sufficiency disclosed". Instead, the standard test for sufficiency at the EPO should be applied. At the EPO, a claimed invention may be rendered sufficient by just one example provided in the specification. The first medical use claim was therefore found sufficiently disclosed in view of the in vitro examples, and the ability of these examples to support a credible therapeutic effect. 

Final thoughts

This case is yet another reminder of the potential power of functional claim language in Europe. Used effectively, functional claim language can be used to obtain broad claims covering a whole class of molecules. The utility of functional language in Europe is in sharp contrast to the situation in the US, where the written description requirement curtails broad genus claiming based on functional definitions (IPKat). 

Readers familiar with UK court decisions relating to sufficiency and plausibility may find the approach taken by the EPO in this and similar cases surprising. In recent years, UK judges have made much of the sufficiency requirement that the claim is plausible over the whole scope of the claim (IPKat, IPKat). At the EPO, however, plausibility objections generally arise in considerations of inventive step instead of sufficiency. The EPO practice of considering plausibility as a component of inventive step has particular consequences for the applicability of post-filed data to a case, and this is the subject of the pending referral to the EBA (IPKat). 

In the present case, the Patentee importantly did not face a plausibility objection in inventive step. The problem to be solved in view of the prior art was identified by the Board of Appeal as being the provision of an antibody with reduced Fc effector function. In view of the in vitro data supporting the functional effects of the claimed Fc mutations, the Patentee thus did not face an objection that the problem had not been solved over the entire scope of the claim. Given that it is simpler to establish the plausibility of an easily measurable in vitro effect than it is to render plausible an expansive treatment effect, the nature of the objective technical problem to be solved is critical to the plausibility of a claimed invention at the EPO. 

Further reading

Patenting Biologic Therapeutics in the U.S. and Europe: More Than a Matter of Routine? (Landslide, Sep-Oct '22)

EPO Board of Appeal maintains functional epitope antibody genus claim (T 1964/18) (6 April 2022)

Strict US written description requirement applied to CAR-T-cell therapy (Juno v Kite) (9 Jan 2022)

Reasons for an EBA referral on plausibility, post-published evidence and problem-solution (21 Sep 2021)

When does pre-clinical data plausibly support a therapeutic effect? (T 966/18) (14 July 2021)

1.      Second medical use dosage regimen claim successfully traverses both insufficiency and "obvious-to-try" attacks (T 0799/16) (8 March 2021)