The prior art disclosure only provided data for the use of substance B alone, and the combination with substance A was an arbitrary selection from a list of around forty alternatives. The Board of Appeal nonetheless found the claim at issue to lack novelty, and may have been influenced by the accompanying data in the patent, which only showed the utility of substance A in a combination therapy. In view of this, it appears that the Board of Appeal applied a lenient standard for enablement when assessing the prior art.

The patent at issue: sufficiency

Claim 1 of the main request was in the form of a second medical use claim directed to tauroursodeoxycholic acid (TUDCA) for use in the treatment of amyotrophic lateral sclerosis (ALS): “1. Tauroursodeoxycholic acid (TUDCA) or a pharmaceutically acceptable salt thereof for use in the treatment of a neurodegenerative disorder in a mammal, characterized in that said neurodegenerative disorder is amyotrophic lateral sclerosis.”

Notably, the claim encompassed the use of TUDCA as a monotherapy to treat ALS. However, the data in the patent only showed efficacy in ALS patients for the combination therapy of TUDCA + riluzole + vitamin E.

At first instance, despite the absence of any data regarding the monotherapy, the Opposition Division decided that claim 1 was sufficiently disclosed, because the opponent had not provided any verifiable evidence that TUDCA would not have “at least to some extent” a therapeutic activity in the treatment of ALS.

On appeal, sufficiency of disclosure was not considered further by the Board of Appeal. It appears that this was due to the opponent’s failure to maintain this ground in its reply to the appeal. However, although not explicitly mentioned, the Board of Appeal may nonetheless have considered it necessary to apply the same sufficiency standard to the prior art patent application, which was an important factor regarding novelty.

The prior art patent application: novelty

A novelty objection was raised over D8, which was a patent application relating to compositions comprising low doses of diazoxide for use in the treatment of a mammal afflicted with ALS: “1. Diazoxide or a pharmaceutically acceptable salt thereof for use as a medicament at a daily dose of from 0.15 mg/m2/day to 13.00 mg/m2/day expressed as mg/m2/day of diazoxide free base in the treatment of a mammal afflicted with amyotrophic lateral sclerosis (ALS).”

D8 included an example showing that low doses of diazoxide improve survival in a mouse model for AML. The Board of Appeal further noted that the utility of diazoxide in treatment of ALS described in D8 had “not been disproved”.

The decisive parts of D8 were claims 8 and 9, which disclosed the combined administration of diazoxide and one or more therapeutic agents useful in the treatment of ALS. Claim 9 of D8 disclosed TUDCA in a list of around forty therapeutic agents, allegedly “useful in the treatment of ALS”: “9. Diazoxide or a pharmaceutically acceptable salt thereof for use according to claim 8, wherein the medicament comprises diazoxide and one or more additional therapeutic agents useful in the treatment of amyotrophic lateral sclerosis selected from CK-2017357, olesoxime (TRO19622), arimoclomol, riluzole, tretionin and pioglitazone HC1, AVP-923, memantine, talampanel, tauroursodeoxycholic acid (TUDCA), thalidomide, olanzapine, KNS-760704, lithium carbonate, NP001, ONO-2506PO, tamoxifen, creatine monohydrate, coenzyme Q10, YAM80, sodium phenylbutyrate, pyrimethamine, R(+)pramipexole dihydrochloride monohydrate, vitamin E, minocycline, topiramate, gabapentin, AEOL-10150, stem cell injections, SB-509, autologous bone marrow-derived stem cells, ceftriaxone, E0302 (mecobalamin), MCI-186, glatiramer acetate, insulin-like growth factor-1 (IGF-I), ISIS 333611, sNN0029, GSK1223249, brain-derived neurotrophic factor (BDNF) and anti-CD40L antibody.”

Based on established case law that a single selection from a list cannot confer novelty, the Board of Appeal held that a composition comprising diazoxide and TUDCA for use in the treatment of a mammal afflicted with ALS was derivable directly and unambiguously from D8.

Importantly, the Board of Appeal went on to decide that this was also an enabling disclosure. It held that, even if D8 did not provide any in vitro or in vivo experiments with regard to the efficacy of TUDCA in the treatment of ALS, D8 however provided an enabling disclosure for a combination treatment based on diazoxide and TUDCA. Crucially, the Board of Appeal emphasised that the efficacy of diazoxide is supported by experimental data and “had not been disproven”.

In accordance with established case law, the Board of Appeal held that the discovery of a new property of a particular ingredient of a known composition (TUDCA in the composition comprising diazoxide and TUDCA, used for a known and identical general purpose, that is, the treatment of a mammal afflicted with ALS) cannot confer novelty. Novelty can only be recognised if this new property is applied in a new use.

Therefore, claim 1 of the main request was found to lack novelty over D8.

A successful novelty-sufficiency squeeze?

The Board of Appeal appeared to take a strict approach to novelty in this case. In view of the data in the patent, which related to a combination treatment with TUDCA + riluzole + vitamin E, it appears that the Board of Appeal erred on denying novelty in view of a different combination, which was disclosed in the prior art. In different circumstances (for example, if the patent had clearly enabled a monotherapy with TUDCA), it is possible the Board of Appeal would have come to a different conclusion.

For example, the selection of TUDCA from claim 9 of D8 appears to be an arbitrary selection from a very long list. A single selection from a list does not usually confer novelty. However, in the context of a medical use claim in which the successful treatment of the disease is a limiting feature of the claim, it appears arguable whether each and every one of the combinations disclosed could be considered to be an enabling disclosure.

In addition, second medical use claims are formulated based on the wording of Article 54(5) of the European Patent Convention (EPC), which distinguishes between the use of a “substance” or “composition”. In D8 the claims only referred to TUDCA in the context of a composition, without any evidence that TUDCA was an active agent in the treatment of ALS. However, the claim at issue referred to a substance (that is, TUDCA or a pharmaceutically acceptable salt thereof), and therefore arguably includes the technical feature that this substance is an active agent in the treatment of ALS. Other boards may have considered this enough to render the claim novel.

In this case it was relatively straightforward for the patentee to render claim 1 novel over D8, such that this attack was not fatal. It appears that no inventive step objection was raised by the opponent starting from D8 and the Board of Appeal did not consider this. It is not clear how the Board of Appeal would have dealt with an inventive step attack starting from the same disclosure.

This case is a reminder that even when considering individual grounds of opposition, a Board of Appeal may nevertheless take into account other grounds. In this case, although sufficiency was not at issue the Board of Appeal appears to have taken this into account, and applied a lenient standard for enablement when assessing the prior art. It appears that this may therefore be considered an example of a successful novelty-sufficiency squeeze in the context of a second medical use claim.

Useful links

• EP3016654, European Patent Register: dycip.com/ep301665
• EP2422787, European Patent Register: dycip.com/ep2422787