T 1057/22 related to a patent for the use of a rather unappetizing sounding fish oil and juice emulsion ("fish juice") to treat cancer. This Kat confesses that her interest in this case was primarily piqued by the oddness of the subject matter. Fish juice to treat cancer seems a rather unpromising starting point for demonstrating sufficiency. It is thus all the more surprising that the limited data provided in the patent was found to sufficiently support a relatively broad second medical use claim. The claims maintained on appeal were not even limited to a specific type of juice. The case therefore once again confirms that relatively low bar for sufficiency at the EPO. However, the low evidence standard for supporting a therapeutic use in Europe can be a double-edged sword, given that it can also be used to justify the relevance of highly speculative prior art disclosures of therapeutic uses. The decision in T 1057/22 thus raises the question of whether we have the correct evidence standard for therapeutic use.
Case Background: Fish juice
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Fish juice anyone? |
The examples in the patent provided data purporting to show the effects of fish oil/juice emulsions on the growth of cancer cell lines, as compared to fish oil without fruit juice. The data was also purported to demonstrate the effect of the fish juice in reducing tumour growth in a mouse cancer model, as compared to drinking water. The juice in the examples was a mixture of apple, pear, pomegranate, aronia and passionfruit juice, corresponding to the commercial product. However, the description indicated that the juice may be selected from a list of 24 different fruit and vegetable juices. In fact, according to the general disclosure, "[a]ny juice suitable for stabilizing the oxidation of the fish oil may, however, be used."
Sufficiency: A lack of plausibility requires substantiated doubt supported by verifiable facts
The patent was opposed by the rival nutritional supplement company, Nutricia. The Opponent argued on appeal that the claim was not sufficiently disclosed because it did not plausibly demonstrate that the combination of fish oil with all types of juice would have the claimed therapeutic effect (see also IPKat: Plausibility demystified). The Opponent also pointed out that the examples used compositions comprising not only the fish oil and juices, but also milk and vitamins, that may be contributing to the effect on cancer cells. As such, the Opponent argued, there were serious doubts that a skilled person would be able to carry out the invention over the whole claimed range.
The sufficiency bar in Europe can often seem surprisingly low. For a medical use claim, in vitro and mouse data data may be enough to satisfy the requirement (IPKat). The key question for sufficiency of a second medical use claim is whether there is a lack of substantiated doubt with respect to the claimed therapeutic use (IPKat). In the present case, the Board of Appeal dismissed the insufficiency objection, noting the "ample guidance" in the application as filed over the choice of juice. The description indicated that juices from fruits or berries having a high level of antioxidants could be used, and provided an accompanying "comprehensive list of suited juices" (r. 3.2.3).
The Board of Appeal also dismissed the argument that the evidence provided in the examples was undermined by the other potentially anti-cancer agents included in the compositions: "In the board's view, the respondent's converse conclusion is an unsubstantiated assertion" (r.3.2.5) The Board of Appeal thus concluded that there was "no evidence on file to support the [...] allegation that choosing any of these explicitly proposed juices might fail to achieve the claimed therapeutic effects."
The Board of Appeal found that the claims were therefore sufficiently disclosed. The Board of Appeal also found the claims inventive, based on the lack of any suggestion in the prior art that Nutrifriend 1100 may be used to treat, specifically, pancreatic cancer and neurological cancer. The Board of Appeal therefore also dismissed the Opponent's inventive step attack and remitted the case back to the Opposition Division with the order to maintain the patent on the basis of the claims according to auxiliary request.
Final thoughts
Those unfamiliar with the patent system may be surprised that a monopoly for use in a new indication of a known composition may be awarded solely on the basis of sparse pre-clinical data, especially when the known composition is so broadly defined. However, the relatively low sufficiency bar in Europe for second medical use inventions can be a double-edged sword for patentees. The low evidence standard for sufficiency is mirrored by the difficulty of overcoming novelty and inventive step objections based on speculative prior art disclosures of a therapeutic use. The evidence standard required for a second medical use claim is also light years away from the evidence standard required for regulatory approval, namely the requirement for a pivotal phase 3 clinical trial costing potentially hundreds of million of dollars. It is furthermore widely accepted that, in contrast to other technical fields, drug discovery is becoming only slower and more expensive over time, so called Eroom's law (the opposite of Moore's law). Given the raison d'etre of the patent system is to promote innovation, do we therefore need a reset of what it means for a therapeutic use to be disclosed?
It is notable that, in the present case, the commercial value of the patent is highly questionable, given that it seems highly unlikely that fish juice will ever be approved as a pharmaceutical for the treatment of pancreatic or neurological cancer. On the contrary, some experts advise cancer patients to avoid fish supplements, citing evidence they fish oils may counteract chemotherapy. The fishy evidence in T 1057/22 raises the question of whether we are rewarding the right kind of innovation.
Image credit: Midjourney
Further reading
- Lost in translation: Are animal models predictive of a treatment effect? (Jan 2019)
- When does pre-clinical data plausibly support a therapeutic effect? (T 966/18) (July 2021)
- Sufficiency of broad functional genus and first medical use claims in Europe (T 0424/21) (Oct 2022)
- Plausibility demystified - a review of EPO case law before G 2/21 (Feb 2023)
- UK divergence from the EPO on plausibility (Sandoz v BMS), Part 1: Is the "plausibility" test the same for both sufficiency and inventive step? (July 2023)
- G 2/21 does not permit armchair inventing (T 0258/21) (Oct 2023)
- Inventive step of treating a subpopulation of patients in view of prior art reporting a positive phase 3 clinical trial (T 1437/21) (March 2024)
![Fishy evidence: Do we have the right sufficiency standard for therapeutic use? (T 1057/22)](https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgxYQVrT8XANrkZw-xe7wEGYEdTb60ruPKfKy3WT-jncs5jTjHha1WQ-4p12zeo4cf3wB32tEHH89bA2172o4U5Eir7ek9LexsXV0mWkTtDDfsWgbX_Lt_hOFy7Ql2z_97lXzFhFNvdpFAMbSULeZb22G60vJUrmCeedZd0n0dH0l3xdKq26Hwp/s72-c/Picture1.png)
The questions is asked whether we need a reset of what it means for a therapeutic use to be disclosed? This case cannot be used as evidence to support a problem with the sufficiency requirement for a medical use. Just because the poster believes the invention is fishy is not a just reason. Yes, it may appear unlikely that there would be a proven clinical benefit if a trial is conducted. Yes, there is no commercial benefit from a therapeutic patent for a "nutritional supplement" absent clinical data. More importantly, there should be no promotion of the supplement for any remote anticancer benefit absent marketing approval. This would be unlawful though there are many methods marketers can use to avoid illegality.
ReplyDeleteSo why is this not a case that should lead us to write to our MP's? Simply, because there is credible data in the patent that an anti-cancer effect is achieved both in vitro (cancer cell lines) and in vivo (murine model) using the claimed substance. Issues over breadth of scope are legal technicalities that are case-specific and are irrelevant to the broader question of what data is required to justify support.
As commented, clinical trial data is not the relevant standard. That is the standard for marketing approval. For the patent system to support pharmaceutical innovation, it is also an unworkable standard. There are many who believe it is the right standard; the ignorant.
The data provided in the patent is the same data used to support patents for unapproved pharmaceuticals; those the poster would not find fishy. Such unapproved pharmaceuticals may have a more realistic chance of success than the fish oil in the minds of the "pharma-informed", but they are themselves at high risk of failure. Indeed, composition of matter patents cover may trillions of compounds that have a cat-in-hell's chance of success.
The in vitro and in vivo tests of the patent are reasonable experiments to conduct to determine whether a compound has any potential benefit for further evaluation. Whether such tests are reasonably predictive for the supplement of the patent is something that expert evidence would shed further light on. The opposition was a little weak, and maybe the patent is undeserved, but the patentee's case was the stronger.
The final comment on whether the right kind of innovation is being rewarded is indicative of the objection to this patent being possibly based on a non-objective analysis.
Rose reports that the Opponent failed to meet its burden of proof and convince the tribunal that the data was insufficient to establish plausibility. Indeed, in TKIP's judgement, the data was, all along, "credible". Rose discusses the obviousness issue and then asks whether a "reset" of the sufficiency standard is needed in Europe but it seems to me that if one is needed it is in the USA rather than in Europe.
ReplyDeleteBut then again, if the obviousness enquiry under the EPC were to be as grotesque as in the USA, one could understand the EPO resorting more often to Art 83 EPC to prevent unpatentable matter making it through to grant. As it is, at the EPO, obvious subject matter can be refused without much ado. And that's the more important thing, isn't it?
The interaction between plausibility and evidential burden of an opponent remains complex. The question is does the opponent simply have to show the data in the patent is weak or does it have to provide actual evidence (data) of lack of efficacy of the therapeutic agent? Here the board decided they needed evidence. See quote from decision below:
ReplyDelete"3.2.4 Moreover, there is no evidence on file to support the respondent's allegation that choosing any of these explicitly proposed juices might fail to achieve the claimed therapeutic effects. The respondent has not submitted any such evidence, for example, in the form of experimental data. In this context, the board disagrees with the statement given in the decision under appeal that a skilled person would not know which juice to choose. As outlined above, the board is of the opinion that a skilled person is provided with ample guidance as to suitable juices to be used."
If the opponent doesn't file evidence on sufficiency/enablement, they risk the board deciding against them essentially due to a 'lack of effort'. Boards do not like laziness on the part of any of the parties in front of them, and decisions often reflect that. Here the opponent took the risk and lost