Following the highly anticipated Supreme Court decision in Warner-Lambert v Generics in relation to plausibility at the end of last year, the UK High Court has recently applied the new plausibility test for the first time in Eli Lilly v Genentech Inc.1 Eli Lilly sought revocation of a Genentech patent concerning an antibody which specifically binds to the IL-17A/F heterodimer in the treatment of rheumatoid arthritis and psoriasis, on the basis of novelty, obviousness and insufficiency (lack of plausibility).
Mr Justice Arnold held certain claims in Genentech’s patent, those concerning treatment of rheumatoid arthritis, to be novel, but obvious in light of the prior art. Other claims in relation to the treatment of psoriasis were found to be insufficient for lack of plausibility.
Genentech Inc. is the proprietor of EP (UK) No 1 641 822 (“the Patent”) titled “IL-17A/F heterologous peptides and therapeutic uses thereof’. Whilst Genentech does not market a product covered by the Patent, Eli Lilly markets an antibody called ixekizumab sold under the trade name ‘Taltz’ for treatment of moderate to severe plaque psoriasis and psoriatic arthritis for adults.
The Patent specification states that the invention “relates to identifying novel secreted polypeptides of the interleukin-17 (IL-17) family which have been shown to be related to immune-mediated and inflammatory disease.” Interleukins are immune-modulating agents and also referred to as cytokines. The Patent provides an overview of the IL-17 family of cytokines which are implicated in immune related diseases. The Patent further describes IL-17A and IL-17F members of the IL-17 family and discusses the identification of a new human cytokine that is comprised of a heterodimer consisting of IL-17A and IL-17F (IL-17A/F) stating that molecules which inhibit IL-17A/F activity would be expected to have practical utility when an inhibition of the immune response is desired. The claims of the Patent cover an isolated antibody which specifically binds to the IL-17A/F heterodimer in the treatment of rheumatoid arthritis or psoriasis. Psoriasis and rheumatoid arthritis are included in a long list of examples of immune-related and inflammatory diseases in the specification of the Patent.
Eli Lilly filed a revocation action alleging that the claims of the Patent are invalid on grounds of lack of novelty, obviousness and insufficiency. They also sought a declaration that dealings in ixekizumab does not infringe the Patent.
Ixekizumab was developed as an antibody against IL-17A for treatment of rheumatoid arthritis and asthma. Eli Lilly then later obtained a marketing authorisation for ixekizumab for the treatment of psoriasis.
Obviousness and Anticipation
Mr Justice Arnold dismissed Eli Lilly’s claims that the Patent was anticipated but held that some claims of the Patent were obvious over a US patent which disclosed recombinant production of a heterodimer between IL-17F and IL-17A. He also held that other claims were obvious as far as they were directed to rheumatoid arthritis.
Lack of Plausibility
Mr Justice Arnold considered the seven propositions made by Lord Sumption in Warner-Lambert in relation to plausibility:
- The proposition that the product is efficacious for treatment must be plausible.
- A mere possibility or bare assertion is not enough.
- The therapeutic effect may be made plausible by the patent showing that it was worth trying for a reason.
- There is no need to prove that the product works, but there must be something indicating a reasonable prospect that it works.
- This reasonable prospect must be based on a direct effect on a metabolic mechanism specifically involved in the disease, this mechanism being either known from prior art or demonstrated in the patent per se.
- This can be achieved by the inclusion of experimental data or other reasoning based on the properties of the product.
- This plausibility has to be apparent from the disclosure of the patent itself (including common general knowledge).
Based on the evidence, Mr Justice Arnold held that the skilled person would not regard it as plausible that and anti-IL-17A/F antibody would have a discernible therapeutic effect on psoriasis. The Patent contained no experimental data on the role or effect of IL-17A/F in psoriasis, nor any discussion of the role or effect of IL-17 A/F in psoriasis. Pointing away from the idea that it would work, the Patent showed that IL-17A/F is an order of magnitude less potent than the homodimer IL-17 A/A. Important in his finding was that the Patent specification claimed efficacy against a broad list of conditions in relation to which the skilled person would not think it plausible that the antibody would be efficacious in relation to them all, and there was not specific singling out of psoriasis. Therefore, he found that Genentech’s claim of an efficacy against psoriasis not to have been plausibly disclosed by the Patent.
Given that it is now known that ixekizumab is known to bind to both IL-17A/A and Il-17A/F together with more recent research that shows that IL-17A/F plays a role in psoriasis, Mr Justice Arnold, applying the Supreme Court test for infringement from Actavis v Eli Lilly (pemetrexed), which takes into account equivalents, held that if the Patent claims were valid, that Eli Lilly would have infringed them.
This case shows court’s application of the principles established in Warner-Lambert in relation to plausibility. The dearth of experimental data or any other scientific reason as to why it would work made the Patent open to an attack of insufficiency for lack of plausibility. In his findings, Mr Justice Arnold did accept that whilst Warner-Lambert was concerned with a second medical use whereas this case concerned a first medical use of a previously unknown antibody. It remains to be seen whether Genetech will appeal the case.
The case highlights the dilemma faced by patentees as to when they ought to file an application. File too early and risk a finding of insufficiency (implausibility), file too late and increase chances of a finding of anticipation or obviousness. The findings of this case also gives an opportunity to new market entrants wishing to ‘clear the way’.