Fishy evidence: Do we have the right sufficiency standard for therapeutic use? (T 1057/22)

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

Fish juice anyone? 

The patent in T 1057/22 claimed the second medical use of a fish oil and juice emulsion to treat cancer  (EP2991507). On appeal, the claims were limited in an auxiliary request to the treatment of pancreatic or neurological cancer. The claim covered the therapeutic use of the patentee's (SmartFish) health-food product. The product is marketed as Nutrifriend, a "fresh and tasty oral nutritional supplement". The marketing information also assures us that the product is "smooth and creamy" and that there is "no rancid fish taste". A pilot clinical study (NCT02515032) found that the fish juice may counteract nutritional deficit and muscle wasting from chemotherapy (cachexia) in lung cancer patients (Laviano et al.). However, there is no clinical evidence that Nutrifriend can treat or prevent cancer.  

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)