A second bite at the cherry
Second medical use claims have a long-standing history in European Patent Office (EPO) case law. As is well known, the first ever decision of the EPO’s Enlarged Board of Appeal confirmed the patentability of second medical use claims when written in the so-called Swiss-type format. The Enlarged Board in that 1984 decision, G5/83, held that protection was available for “specified new and inventive therapeutic application[s]”. In the years that followed the technical boards of appeal controversially discussed what exactly was meant by the “specified therapeutic applications” referred to by the Enlarged Board.
This controversy culminated in the landmark decision T1020/03, handed down in 2004. In that decision, Technical Board 3.3.4 discussed various earlier rulings that had imposed certain restrictions on the meaning of the required “specified new and inventive therapeutic application” (requiring, eg, the identification of at least the active agent, the disease to be treated or the patient group—see T4/98).
Board 3.3.4 argued that such restrictions were irreconcilable with the ruling of G5/83, meaning that second medical use claims should be patentable irrespective of the detail in which the claimed therapeutic use was specified. The discussion was finally settled in a further decision of the Enlarged Board of Appeal which endorsed the position taken in T1020/03.
As the ruling of G5/83 had meanwhile been codified in article 54(5) of the European Patent Convention (EPC) 2000—which establishes the patentability of a known substance or composition for “any specific use” in a therapeutic method of treatment, provided that this use is novel and inventive—the Enlarged Board dealt with the meaning of the term “any specific use” recited in this new legal provision. In its decision G2/08 of February 19, 2010, it came to the conclusion that the term “any specific use” in article 54(5) of the EPC 2000, which essentially corresponds to the “specified application” referred to in G5/83, cannot be construed to be limited to new indications.
Rather, it may also mean, for example, new and inventive dosage regimens. Apart from dosage regimens, the Enlarged Board also acknowledged that the case law at that point had already established, inter alia, that a new patient group mentioned in a second medical use claim could likewise give rise to patentable subject matter, even if the active agent and the disease were identically disclosed in the prior art.
A complex situation
The situation becomes more complex if the active agent is the same, the disease to be treated is the same, and a new patient group is not addressed in the claims, but a new mode of action has been found by the applicant.
One of the first decisions in this category is T290/86, where the competent board decided that the use of lanthanum salts in the removal of plaque for avoiding tooth decay was novel over a prior art document that disclosed the use of such salts for depressing the solubility of tooth enamel in organic acids present in saliva, despite also being for the purpose of inhibiting tooth decay. In the board’s view, these were two technical effects in the sense of G5/83 that could be clearly held distinct.
In the same technical field, the board in T542/96 found that the feature “providing an improved remineralising effect” established novelty over a prior art dentifrice containing the same combination of compounds which was disclosed for the avoidance of caries. Specifically, it was held that the terms “tooth decay” and “caries” identify different and not necessarily overlapping situations. Remineralisation was also achievable for teeth that were not affected by caries.
In later decisions, the boards posed the question of whether the new technical effect would lead to a “new clinical situation” or would open up “new areas of therapeutic treatment”. Thus, in T1127/05, the board had to decide whether a claim relating to the use of integrin ανß3 antagonists for inhibiting angiogenesis should be considered novel. The prior art disclosed the same compounds in the inhibition of angiogenesis.
However, the prior art compounds were characterised as being antagonists of the αvß5 integrins. Since the pathways involving the different integrins and the angiogenesis mediated were associated with different diseases, the board acknowledged novelty, emphasising that the claimed antagonists open up new areas of therapeutic treatment.
The board did not, however, require the claim under consideration to recite any specific diseases associated with ανß3‑mediated angiogenesis, and so to be actually limited to the treatment of such specific diseases.
The further decision T1955/09 dealt with the problem of whether a newly found antibiotic activity of certain peptides could confer novelty to a second medical use claim. The peptides were already known to inhibit the activity of toxins produced by bacteria and fungi.
The board found that the technical feature of killing bacteria and fungi expressed in the claim amounted to a new technical effect. The known technical effect was considered to be a direct effect on the toxins, whereas the new technical effect was held to be an indirect effect on the toxins, namely the killing of bacteria or fungi producing the toxins. This led to a new clinical situation where the physician could target the infection itself rather than merely combating the toxins.
A similar situation was dealt with by the board in T1642/06. The claimed invention referred to the use of a sigma receptor antagonist in the treatment of cancer. The claim was further characterised by the feature that the antagonist inhibits neovascularisation of the cancer by inhibiting proliferation and/or survival of normal endothelial cells. The prior art disclosed the use of the same compounds for the same disease.
“Such a ‘new clinical situation’ may be present, for example, if the newly discovered technical effect makes the claimed therapeutic treatment particularly advantageous under certain clinical circumstances.”
However, the compounds were described to act via the induction of tumour cell cycle arrest and/or apoptosis. The board considered the prior art effect to be a direct one on the cancer cells, whereas the claimed inhibition of neovascularisation was considered an indirect effect on the cancer cells. Again, this created a new clinical situation because the clinician could decide to target the supporting vasculature instead of the tumour cells themselves.
The board decided along the same line in T836/01. The prior art taught that IL-6 can be used to combat cancer by the activation of the immune system. This was considered to be an indirect effect. In contrast, the claimed invention related to the use of IL-6 for inhibiting tumour cell growth and influencing terminal differentiation of cancer cells, ie, a direct effect. A new clinical situation arose, inter alia, since the newly discovered technical effect could be used to treat a new subgroup of patients. This subgroup was, however, not mentioned in the main claim under consideration.
In the case underlying T1229/03, the use of an oestrogen compound in the treatment of neurodegenerative diseases was claimed. The board acknowledged that the feature “by protecting a population of nerve cells from death” conferred novelty despite the prior art describing the use of such compounds for promoting mechanisms for repairing nerve cells, which were considered distinct technical effects.
Similarly, in T509/04 the therapeutic effect of promoting normal muscle growth in juvenile patients suffering from cerebral palsy by administering botulinum toxin was considered to confer novelty to the claimed invention. The prior art had described the treatment of the same disease with the same compound, but merely disclosed an improvement in gait pattern and seated balance as well as decreased spasticity of injected muscles.
More decisions
Other board of appeal decisions dealt more critically with applicants’ claims that functional features defining new technical effects could establish novelty of second medical use claims. In one of the early cases decided, the board in T254/93 considered the claimed subject matter to be anticipated by the prior art. Here, the applicant claimed the use of a retinoid for avoiding corticosteroid-induced skin atrophies. The prior art, albeit only in an example, disclosed the combination of, inter alia, a corticosteroid and vitamin A in the treatment of dermatosis.
Since the patients did not develop skin atrophies, the board concluded that a physician being aware of this prior art teaching would continue treating patients suffering from dermatosis using this combination. Although the prior art did not specifically disclose that vitamin A prevented skin atrophies, the board found that the avoidance of skin atrophies was inextricably linked to the administration of corticosteroids, in order to confer the beneficial effects of the latter.
In this way, the skilled person would resort to pharmaceutical compositions that achieved this goal as disclosed in the prior art. What the claimed invention contributed to the art was the realisation that the retinoid was responsible for the avoidance of the adverse side-effects.
However, this knowledge was unsuitable to confer novelty to the claimed use because it merely amounted to an explanation of an effect, whereas the process of achieving the effect and the effect itself were already known in the prior art.
The competent board also denied novelty in the case T384/03. The applicant claimed the use of a carbonic anhydrase inhibitor in the treatment of glaucoma. Such uses were known in the art. According to the applicant, however, the prior art merely described the effect of lowering intraocular pressure (IOP) which it argued to be distinct from the claimed effect of increasing retinal and optic nerve head blood velocity (OBF).
The board nevertheless concluded that, upon administration of the drug, both technical effects acted in the same direction, namely the lowering of IOP and increase of OBF. Thus, whereas the effects could be considered distinct, they were not independent in the treatment of glaucoma.
A similar conclusion was reached by the board in T486/01. The patent claimed the use of IGF-1 in the treatment of central nervous system (CNS) injuries whereby the loss of glial cells or non-cholinergic neuronal cells should be reduced. The art taught that IGF-1 could be used in the treatment of Parkinson’s disease, for example. However, it also taught that different cells from the ones mentioned in the claim were affected.
The board did not see this as a decisive difference that could warrant the acknowledgement of novelty. It denied that the finding expressed in the claim would lead to a truly new therapeutic application that would, for example, allow the treatment of a new sub-group of patients (reference was made to T19/86 and T893/90). Nor was there any evidence that the treatment could be carried out selectively such that only the cells mentioned in the claim would be affected but not those disclosed in the prior art. The applicant’s finding could therefore only be considered as the “discovery of additional items of knowledge about further mechanisms of action underlying the known therapeutic application of IGF-1 in the treatment of CNS insults”.
In the case underlying T406/06, the applicant argued for novelty on the basis of the feature “for stimulating beta-cell proliferation to prevent or treat beta-cell depletion” in a second medical use claim that required the use of GLP-1 in the treatment of diabetes. In the prior art, GLP-1 was already used for treating diabetes. The applicant could not show that there were any other pathological conditions that were associated with beta-cell depletion.
For the board it was therefore clear that the therapeutic use conferred by the feature “for stimulating beta-cell proliferation to prevent or treat beta-cell depletion” was nothing else but the treatment of diabetes. According to the board, novelty cannot be acknowledged solely because the claim recites a new technical effect.
New clinical situation
In summary, if applicants wish to rely on new technical effects and particularly new modes of action recited in second medical use claims for establishing novelty over the prior art, it seems decisive that they can successfully argue that the claimed effects do not merely amount to an explanation of the previously known therapy, but rather can lead to a “new clinical situation”.
Arguably, such a new clinical situation may be present, for example, if the newly discovered technical effect makes the claimed therapeutic treatment particularly advantageous under certain clinical circumstances, so that the claimed treatment can be applied specifically and purposefully in such situations where the achievement of precisely this effect is desirable.
In particular, arguing that the new technical effect constitutes a direct effect (eg, on cancer cells or on a pathogen) as compared to an indirect effect disclosed in the prior art, or vice versa, is expected to help applicants’ cases. Similarly, claiming a neuroprotective effect in distinction from a neuroregenerative effect disclosed in the prior art, or vice versa, would likewise seem feasible.
Yet, although there is now a large body of EPO case law accepting second medical use claims that recite a novel technical effect, it will be interesting to see how the competent courts of the EPC contracting states dealing with patent infringement will assess cases arising from such patents. It also remains to be seen whether an omission of the claimed technical effect in third parties’ patient information leaflets might still win the patentee an infringement suit in a case such as the one underlying T509/04. So far, we are not aware of any decision taken by German courts dealing with such a situation.
However, in view of the case law of the EPO discussed above, we do consider it advisable to carefully contemplate the possibility of incorporating fallback lines specifying the mode of action of a therapeutic agent when drafting new patent applications for second medical use inventions.
Joachim Wachenfeld is a partner at Vossius & Partner. He can be contacted at: wachenfeld@vossiusandpartner.com
Oswin Ridderbusch is an attorney at Vossius & Partner. He can be contacted at: o.ridderbusch@vossiusandpartner.com
