A new mode of administration is a new specific medical use (but not necessarily inventive) (T 0295/22)

The Board of Appeal decision in T 0295/22 tackles the question of whether a new mode of administration of a drug should be considered a new medical use. The Board of Appeal concludes that the current EPO Guidelines for Examination are wrong on this point, and that mode of administration may be considered a specific new medical use. However, the decision also found that the unexpected effects of the new mode of administration were alone not enough to establish inventive step in view of, what the Board of Appeal considered, clear motivation in the prior art towards the claimed solution.

Legal background: Medical use claiming and unexpected effects

In Europe, whilst methods of treatment are excluded from patentability under Article 53(c) EPC, it is possible to patent substances or compositions for use in a method of treatment under Articles 54(4) and (5) EPC (i.e. medical use). Under the EPC 1973, medical use claims were only permitted in Swiss-type style, i.e. in the format "Use of compound X for the manufacture of a medicament for treating disease Y" (G 5/83). The current Article 54(5) EPC 2000 format for medical use claiming instead directly claims "Compound X for use in treating disease Y".  

First medical use claims under Articles 54(4) EPC provide broad protection for any medical use of a known substance. To allow patents on subsequent medical uses while avoiding double patenting, Articles 54(5) EPC requires second/further medical uses to be "specific". G 2/08 clarified this specificity requirement should be interpreted minimally, i.e. it only needs to be more specific than first medical use protection, and isn't confined to particular medical indications. 

Obvious-to-try? 

For inventive step, the same legal principles apply to a medical use claims as for any invention, including the case law on unexpected technical effects. An effect which is unexpected can be regarded as an indication of an inventive step, but certain preconditions must be met. Particularly, if arriving at the claimed subject matter would have been "obvious to try" by a skilled person, with a reasonable expectation of success, the presence of an unexpected bonus effect may not be sufficient to establish inventiveness. 

Case Background: A new mode of administration

The patent at issue in this case (EP2962690, Amgen) related to the compound apremilast, which is marketed as Otezla for treating inflammatory diseases. The claims specified stereomerically pure apremilast comprising greater than 80% of the (+) enantiomer and less than 20% of the (-) enantiomer, for use as a medicament administered orally. Claim 1 did not specify the indication or dose of apremilast. 

The problem purportedly solved by the invention related to the challenge associated with oral administration of PDE4 inhibitors. The therapeutic use of PDE4 inhibitors faces two key issues, the potential cardiovascular side effects following systemic delivery due to a lack of selectivity for PDE4 and concomitant PDE3 inhibition, and the propensity of PDE4 inhibitors to induce emesis (vomiting). The patent presented experimental results indicating that stereomerically pure apremilast could overcome these challenges.

The patent was opposed by multiple parties including Teva, who argued that the claims lacked inventive step. The Opposition Division maintained the patent based on an auxiliary request, and both the Patentee and Opponents appealed.

Modes of administration are limiting features of medical use claims

A key question for the Board of Appeal in this case was how to interpret the oral administration feature in the claims. The EPO Guidelines for Examination indicate, with reference to T 51/93, that in a claim which only defines the mode of delivery but no specific therapeutic effect, the definition of the mode of delivery is merely illustrative and not a restrictive technical feature capable of establishing novelty (EPO Guidelines for Examination, G-VI 6.1.2). In other words, according to the Guidelines, if the only new feature of a compound's medical use is the method of administration, the claim lacks novelty over any disclosure of the previous medical use of the compound (regardless of indication or mode of administration). 

However, in the present case, the Board of Appeal rejected the Guideline's interpretation of T 51/93 that modes of delivery are to be understood as merely illustrative in second medical use claims. The Board of Appeal noted that T 51/93 made an important distinction between claim formats. For Swiss-type claims, T 51/93 recognised mode of administration as a characterising feature without requiring a specific medical condition. However, for "Process for making X for use Y" claims, T 51/93  found that medical purpose merely illustrated potential use without characterising the claimed subject matter. However, both of these claim formats are different to Article 54(5) EPC 2000 second medical use claims. 

In construing EPC 2000 second medical use claims, the Board of Appeal cited G 2/08, which found that the Article 54(5) EPC specificity requirement should only be contrasted against first medical use claims' broad protection, rather than requiring specific medical indications. Applying this principle, the Board of Appeal reasoned that Article 54(5) EPC "is to be construed merely by contrast to the generic broad protection conferred by the first claimed medical application of a substance or composition" (r. 4.1). The oral administration feature of the claim was therefore considered a characterising technical feature of the claims, without the need to further limit the claim to any particular indication or dose. The claims were therefore found novel in view of the new administration method. 

Assessment of inventive step

The closest prior art identified by the Board of Appeal disclosed apremilast with optical purity >95% as a PDE4 inhibitor useful for treating inflammatory diseases. The Board of Appeal found that the only difference between the claimed subject matter and the closest prior art was the oral administration feature discussed above. 

The Patentee argued that the application as filed demonstrated unexpected advantages for oral administration, including high PDE4 selectivity, favourable therapeutic index versus emesis, and improved solubility. However, the Board of Appeal held that whilst these effects may have been unexpected, they did not overcome the strong motivation to try oral administration:

"Taking account of this jurisprudence the Board considers that in the present case the reasonable expectation that orally administered apremilast allows for safe and well-tolerated effective treatment prevails over any unforeseen level of the PDE4 selectivity [...] having regard to the compelling motivation to administer PDE4 inhibitors by the oral route." (r. 4.5.2)

The Board of Appeal cited decisions including T 970/00 and T 1356/21 to support its reasoning that unexpected effects alone cannot establish inventive step where there was an obvious path to the invention. Critically, the Board of Appeal characterised the case as a "one-way street" situation where practical alternatives (i.e. other modes of administration) were limited.

The patent was thus ultimately revoked for lack of inventive step.

Final thoughts

The decision in this case contradicts the current Guidelines for Examination with respect to modes of administration as a specific use in second medical use claims. It will be interesting to see whether other Boards of Appeal follow suit. 

However, even if the novelty hurdle is overcome, the decision in T 0295/22 is also tells us that relying on mode of administration as your inventive hook is a challenging strategy. In this case, the Patentee failed to convince the Board of Appeal that oral administration resulted in an unexpected technical effect. Given that there are relatively few modes of administration available, and oral administration is one of the most commonly used, the lack of convincing reasons why oral administration would not have been "obvious to try" was ultimately the patents downfall. 

Further reading

• The criteria for the novelty and inventive step of pharmaceutical selection inventions (T 1356/21) (Dec 2023)
• Make no bones about it: The "credibility test" has no place in the novelty assessment of second medical use claims (T 0558/20) (Aug 2023)
• Second medical use dosage regimen claim successfully traverses both insufficiency and "obvious-to-try" attacks (T 0799/16) (March 2021)