The paper addresses the issue of patenting inventions for new therapeutic uses in the light of the legal framework provided by the European Patent Convention and the case law of the EPO Technical Boards of Appeal. The patenting of new uses of a known compound is, especially in the pharmaceutical field, an essential lever to promote innovation. In recent years, the EPO has adopted an increasingly “accommodating” attitude towards this type of findings, clarifying that the new therapeutic application is not to be confined to the treatment of a new ailment, different from the one cured by the previous use of the compound, but may well target the very same technical problem (i.e. the cure of the same disease). Thus, protection (in the form of new therapeutic use inventions) has been granted to findings aimed at modifying the form of administration of the drug or its dosage, at changing the functioning of the drug at a physiological or cellular level, or even validating the use of the therapeutic treatment for a new class of patients with different characteristics. Given this new expansionist drift of protection, however, many knots remain to be unravelled. In particular, a clarification would be needed with regard to the perimeter of exclusivity attributed to inventions of new therapeutic use, which should be considered as product inventions limited to the specific field of use, but whose structure is generally identical to that of other inventions that insist on the same molecular composition.

Keywords: chemical and pharmaceutical inventions – patents – therapeutic interventions – essentials patents – patent protection

Sommario/Summary:

Introduction. - 1. Origin of the problem: second use patents in the chemical field. - 2. The codification of protection of “first” use inventions in the medical field … - 3. … and its drawbacks for the pharmaceutical industry. - 4. The protection of second medical use inventions through “Swiss-type use claims”. - 5. The expansionist trend of second medical use inventions. What does “further” use expressly mean? - a) Transposition of the therapeutical effects on a new class of patients. - b) Different way of functioning of the medicament at a physiological or at a cellular level. - c) Alteration of the original form of administration. - d) Different dosage regimen: the last bastion to conquer. - 6. The amendments of the EPC 2000 and the new frontiers of second use patents. - 6.1. The meaning of “any specific use” within the context of novelty of the invention and the patentability of new dosage regimens. - 6.2. The meaning of “any specific use” and the scope of protection of further medical use inventions. - Conclusion. - NOTE

Introduction.

It is very well known today that innovation in the twenty-first century tends to exhibit a cumulative and incremental feature. Technological progress often proceeds through small steps instead of major breakthroughs, giving birth to inventions which often do not lead to the introduction of entirely new pro­ducts, but rather provide ameliorated features of existing ones, for example improving the technical performances of a certain production process or elimi­nating a side effect of a product (ex. a medicinal one). The incremental nature of innovation has significant repercussions and implications from the perspective of patent law. And in fact sequential innovation, flourishing on the trail of previous ones, normally produces a flow of what patent lawyers and academics refer to as “derivative” or “follow-on” inventions [1]: meaning technical solutions whose conception has been possible thanks to the implementation of a teaching (often a portion of it) embedded in a previous invention (hence, in most of the cases, already subject to patent protection) [2]. Under the taxonomy of “derivative inventions” academics and courts have with time developed several sets of sub-categories, each with different features, according to the type and degree of intensity of the “borrowing” from the previous patented teaching. Whereas “improvement inventions” probably represent the most well-known category of derivative inventions [3], scholars have framed the notion of “combination inventions” and “translation inventions” to describe scenarios where the inventive result comes from the combined use of two or more technical teachings – sometimes simply some technical features – already contained in two or more previously patented inventions [4] or where the technical contribution of the invention consists in the transposition of a known inventive concept to a different technical field where it will achieve a different technical effect [5]. Hence, the peculiarity of this latter sub-group of derivative invention is given by the fact that the claimed (derivative) invention is identical, in its structural features [6], to the one claimed in a previous patent, but its transposition to a different field makes it capable of solving a distinct technical problem [7]. Another kind of derivative inventions which has recently gained relevance [...]

1. Origin of the problem: second use patents in the chemical field.

Second use inventions fall into the category of derivative inventions because they consist in the discovery of a new purpose or use of a product which has been already patented for a different employment [12]. In some way, they can be deemed as a new version of translation invention described above, where the inventor explores the technical teaching already protected by a patent trying to conceive further useful ways of employment of the invention in a different technical field or, in this case, even in the same one [13]. Comprehensibly translation inventions in industries like textiles and mechanics, the ones patent law was originally shaped for [14], did not proliferate. This is mainly due to the fact that in these sectors, the mode of employment of the (mechanical) product was (and still is) intrinsically linked to its structure, hence, automatically revealed by the inventor with the very same act of disclosing the invention and highlighting its advantages over the prior art in the solution of the prospected technical problem [15]. Moreover, because of this strin­gent link with its structural features, the mode of employment of a given mechanical invention tended to be (and generally is) just one [16]. Research in the chemical field challenged all the above assumptions. In chemical inventions, the technical features of the claims teach us what its constituent elements are and what is the chemical structure, but structure alone does not tell anything about what the chemical substance does [17] nor does it give us any suggestions about how it could be used or implemented [18]. Furthermore, experience in the field soon showed that chemical compounds and substances were often found to have several properties, hence were capable of multiple practical applications. The question therefore arose about what protection, if any, had to be granted to secondly conceived uses of a chemical compound already patented in light of a certain first property outlined by the inventor, given that there was indeed a widespread agreement at that time – much cherished by the EPO Chambers – that intended the concept of absolute (patent) protection for product inventions not simply to mean that protection would cover the product regardless of the way it had been manufactured, but also that protection would extend to each and every conceivable mode of employment of the claimed invention, even to the ones not envisioned by the [...]

2. The codification of protection of “first” use inventions in the medical field …

Patentability of pharmaceutical products has always been a rather thorny issue because the classical rationale of incentivising research and technical progress in the field throught the instrument of exclusive rights had to be balanced against a social public interest possibly higher in rank: namely, the protection of public health and the rights of individuals to (affordable) access to the best and more advanced medicaments and treatments [23]. With such difficult balancing of interests in mind, EPC framers introduced in Art. 52, 4° of the EPC 1973 a strict ban (still in force today) against patentability of therapeutic, diagnostic and surgical methods to be used in the human or animal body, on the ground that such subject matters could not be consi­dered inventions susceptible of industrial application pursuant to art. 52, 1° EPC [24]. The lack of exclusive rights on such methods indeed was meant to spur the dissemination of the most advanced medical techniques [25], while at the same time protecting physicians’freedom to choose the most appropriate treatment for their patients [26]. Within the delegations, however, some lamented the discriminatory nature of the ban, depriving only the medical sector from process claims, available for all other technical fields. For this reason, the signatories of the EPC contextually introduced, by way of an exception to the exception, the possibility to patent “products, in particular substances or compositions, for use in any of these methods” (art. 52, 4°, EPC 1973, last indent). This to make sure that products, such as medicaments, and substances used in medical treatments – for example vaccines – would not be touched by the exception and could benefit from patent protection [27]. Even this latter scenario, however, was not deemed entirely satisfactory. In such a framework, indeed, new compounds and substances, specifically conceived for a medical purpose, would receive protection as product inventions. No protection, however, seemed available for inventors whenever they would come up with a new and inventive medical application of a compound which was already known to the state of the art (think for example of a chemical substance previously patented in light of its hydrating properties, hence for cosmetic purposes, later found to also cure eczemas). Such cases, which were quite frequent in the industry, presented several hurdles to overcome. [...]

3. … and its drawbacks for the pharmaceutical industry.

The groundbreaking effects of the above provision in the EPC 1973 were limited as hinted above, only to first therapeutic uses – later discovered – of a chemical compound or substance known for its mode of employment in a different technical sector, leaving out of protection subsequently discovered medical applications of both first medical use inventions but also of substances and compositions patented as product inventions pursuant to a first therapeutical application. For its part, the jurisprudence of the EPO Technical Boards of the early eighties seemed to interpret the scope of protection of first therapeutic inventions very broadly, with the consequence of leaving little room for independent protection of further medical applications, which were all deemed to fall within the scope of protection of the first medical use invention [41]. In the well known decision Hoffman La Roche/Pyrrolidine derivatives, the Technical Board was confronted with the issue of how specific the claim towards the new therapeutic use should be, in order to overcome the hurdles set forth by the conjunct reading of Article 52(4) and Article 54(5) EPC 1973, and how such limitation should be interpreted, in terms of patent scope [42]. Interestingly, providing an interpretation that has later become established practice within the EPO jurisprudence [43], the Board concluded that despite a specific use in therapy is generally disclosed in the specification [44], this circumstance “[…] does not in itself call for a restriction of the purpose-limited product claim to that use” [45]. In the reasoning of the Technical Board, there would be no reason to discriminate, as far as the scope of protection is concerned, between an invention pertaining to a (structurally) new therapeutically active compound, whose protection would cover the whole field of therapy, notwithstanding the insertion in the specification of likely indications of use [46], and a therapeutically active compound whose structure was already known in the state of the art (although with relation to a different and non medical field). According to the Board, the principle of equal treatment, indeed, demanded that such broad protection be afforded also to first therapeutical use inventions which, for the first time, make a known compound – known in light of an application in a non medical field – available for therapy [47]. The consequence of [...]

4. The protection of second medical use inventions through “Swiss-type use claims”.

The loophole in the provisions of the EPC has been closed by the EBoA in seven parallel decision – the most famous being the EISAI decision – where it admitted protection of second medical use inventions claimed throughout so called “Swiss-type use claim” [52]. The latter was a new claiming format recently adopted at that time by the Swiss Federal Intellectual Property Office, in a statement of practice regarding use claims in general [53] and it was specifically meant to allow the patenting of inventions consisting in the use of a (known) substance or composition for the manufacture of a medicament for a specified (new) therapeutic application [54]. In other word, a peculiar form of process invention [55]. According to the EBoA, whilst a claim directed to the mere “use” of a substance for the treatment of the human or animal body by therapy had to be regarded “[…] as confined to the step of treament”, hence not patentable, the “Swiss-type use claim” did not conflict with the prohibition contained in art. 52(4) EPC 1973 (today 53(c) EPC2000), as the invention was not conceived as a pure method claim, but as a manufacturing process claim [56], where products obtained thereby were meant to be employed according to a new and inventive therapeutic application [57]. As far as novelty was concerned, the EBOA recurred to analogic reasoning and declared that like in the case of first medical uses of known chemical compounds – where novelty for the medicament forming the subject-matter of the claim was derived from the discovery, for the first time, of a medical application, regardless of the circumstance that the structural composition of the compound was known – also in the case of subsequent medical uses it seemed reasonable to derive novelty from the further pharmaceutical use of the known substance, notwithstanding the fact that a pharmaceutical implementation of the substance was already known [58]. Obviously, the EISAI decision and the introduction by the EBoA of a new claiming format to protect second medical use inventions were not spared cricitisms for going against the spirit of the EPC [59] and for an overly broad construction of the novelty requirement, stretching its contours way to far [60]. Abo­ve all, the fictional construction of such claiming format, depicted as a process claim where the process itself was – in [...]

5. The expansionist trend of second medical use inventions. What does “further” use expressly mean?

The term second use patent in the medical field has been initially intended, at least by scholars, as referring to an invention consisting in a second mode of employment of a known product, patented in light of a first medical use, in a way to treat [73] a different ailment than the one targeted by the first patent [74]. This case, indeed, was surely the most straightforward to address, given that the novelty of the invention – deriving from the new and specifically claimed use – would lay in the possibility of treating an illness not previously treated by means of the known substance as patented: hence, the invention solved a new technical problem [75]. In the aftermath of EISAI, however, the jurisprudence of the Technical Boards implemented the new Swiss type of claim format to second medical use invention very broadly, stretching the boundaries of patentable subject matter way beyond the requirement of a new different disease to be treated.

a) Transposition of the therapeutical effects on a new class of patients.

In DUPHAR/Pigs II the Board granted protection, in the form of a second medical use invention, to the therapeutical application of a vaccine, which was already known to be effective in the treatment of a certain class of animal (i.e. sero-negative pigs), with regard to a new and different class of animals (i.e. sero-positive pigs) [76]. The Board clearly recognized that, different from the circumstances in EISAI, the alleged second medical indication in this case was not aimed at curing a different ailment. The question, therefore, concerned whether the newly discovered efficacy of a vaccine (to immunize against a known illness but) in relation to a different class of animals (than the ones it had already been proven useful for) could be considered a new therapeutic application, from which novelty could be inferred in accordance with the principles of the Enlarged Board’s Decision [77]. The question was positively answe­red by the Board, explaining that “[…] a new use is not only valuable in cases where a novel area of therapeutic use, i.e. a novel medical indication, is provided but also in those cases where a novel class of animals, which previously did not respond to a medicament, is cured or protected against a disease (italics added)” [78], and therefore concluding that “[…] the question whether a new therapeutic use is in accordance with the decision GR 05/83 should not be answered exclusively on the basis of the ailment to be cured but also on the basis of the subject (in the present case the new group of pigs) to be treated” [79].

b) Different way of functioning of the medicament at a physiological or at a cellular level.

Another peculiar case concerned circumstances where the further medical application was recognized in the different way of functioning of the medicament at a physiological or at a cellular level [80]. In ICI/Cleaning Plaque, for example, the invention under scrutiny regarded a treatment of the human body with the same active substance (i.e. lanthanum salts), for the same therapeutic purpose (i.e. prevention of tooth decay), of a previously granted (and expired) patent [81]. The Board considered that while the therapeutic purpose could seem the same, the prior art document disclosed the use of lanthanum salts in dental compositions for the purpose of depressing the solubility of tooth enamel in organic acids, thus strengthening the enamel so as to inhibit tooth decay. Quite differently, the claimed invention was aimed at improving the removal of plaque from teeth by using compositions including lanthanum salts in a way to inhibit tooth decay, which would be caused by the presence of the plaque. Thus, according to the Board the claimed invention brought up a novel and different technical effect which represented a further novel therapeutical application pursuant to EISAI [82].

c) Alteration of the original form of administration.

From there, the expansionist trend of the Technical Boards went on to broaden patentable subject matter in a way to further extend protection to inventions amounting to an alteration of the original form of administration of a certain pharmaceutical substance [83]. In HCG/SERONO the invention regarded the use of human chorionic gonadotrophin (HCG) for the manufacture of a medicament aimed at treating male sexual disorders [84]. The invention was once again claimed pursuant to the Swiss type format, the alleged novelty and inventiveness of the technical contribution lying in the subcutaneous form of administration. Protection had been initially denied in light of a prior art do­cument showing the use of the same substance to treat the same ailment via intramuscular injection. By contrast, on appeal The Board acknowledged that the question to be decided regarded precisely “whether a difference in the mode of administration of a medicament can be treated as a new therapeutic use” [85] and took the view that “mode of administration may be a critical factor in a medical treatment, and no reason can be seen for any a priori bar to relying on this difference when distinguishing over the prior art. Rather patentability must be treated as depending only on whether this modification is in fact novel and inventive” [86]. In a similar fashion, in Trigonelline/MAI the Technical Board granted protection to a second medical use invention consisting in the use of trigonelline (substance extracted from fenugreek seeds) for the production of capsules (for peroral administration) for reviving, stimulating and enhancing hair growth in living creatures, whereas the prior art contained plenty of anticipating documents, in particular one disclosing the use of fenugreek seeds in a compound (containing ten plant substances) administered in topical form (i.e. as a lotion to be put on the sculp) to treat hair loss and stimulate hair growth [87].

d) Different dosage regimen: the last bastion to conquer.

A very controversial case within the patentability of second medical use invention has regarded the case of new dosage regimens. The early approach of the EPO Chambers in this instance seemed to be very much influenced by the German jurisprudence where the Supreme Court denied protection on the ground that administration regimen constituted an abstract medical activity, therefore not patentable pursuant to the equivalent German provision of art. 52(4) EPC 1973 [88]. In PROCTER & GAMBLE/Gastrointestinal compositions, the Board denied protection to an invention consisting in the use of a combination of two known substances for the manufacture of a known medicament for treating or preventing gastrointestinal disorders, where the only distinguishing technical feature amounted to the slightly different prescribed regimen for the treatment [89]. While the ultimate decision of the issue was greatly facilitated by the presence of anticipating prior art [90], the Board took great care in explaining that “[…] determination of the best individual treatment schedule, in particular the prescribing and modification of drug regimens used for administering a particular medicament, so as to comply with the specific needs of a patient, appear to be in the first place part of the typical activities and duties of the doctor in attendance in exercising his professional skills of curing, preventing or alleviating the symptoms of suffering and illness. These are, however, typical non-commercial and non-industrial medical activities which Article 52(4) EPC 1973 intends to free from restraint” [91]. Similar conclusions were achieved in Thiazide diuretics/EURO-CELTI­QUE, regarding the administration of a known medicament (i.e. thiazide diuretics) in a particular prescribed dosage regimen for the (known) treatment of hypertension (without simultaneously causing effective diuresis) [92]. Here once again the Board expressed the view that protection could not be granted when novelty exclusively hinged upon activities which were non-commercial and non-industrial: i.e. medical activities, which the EPC framers intended to remain free and unconstrained [93]. While this view was defended for a while by the Technical Boards in seve­ral other decisions [94], it didn’t take long for the reasons and needs of the phar­maceutical industries to break this wall and convince the EPO of their soundness. In [...]

6. The amendments of the EPC 2000 and the new frontiers of second use patents.

Given the increased importance of second use inventions in the medical field [101], when times were ripe for a revision, EPC signatory Countries decided to put to rest once for all the praetorian law [102] created by the EBoA in EISAI by introducing clear-cut amendments to the Convention, which would eliminate any legal uncertainties regarding the patentability of further medical uses [103]. With specific regard to second medical use inventions in particular Art. 54 was substantively amended so that its new version, contained in the so cal­led EPC 2000, embedded a new 5th prong (the existing one becoming the 4Th of the same article) specifically meant to extend patent protection to any further medical use of a known substance or composition (already patented in light of a first medical application). In the wording of the new prong, patent protection will not be excluded for any known substance or composition for “[…] any specific use in a method referred to in Article 53(c) EPC 2000, provided that such use is not comprised in the state of the art” [104]. While the aim of such amendment was claimed to be the granting of a form protection equivalent to that offered by Swiss-type of claims [105], in a way to set aside such claiming format and bring clarity and certainty in the field, it seems none of such goals were achieved. It is worth pointing out that the enactment of the EPC 2000, which happened to enter into force only in 2007, did not mark the end of Swiss-type of claims. In lack of an express elimination of the latter, the EPO divisions keeped releasing titles of protection drafted in such claiming format until the EBoA in ABBOTT RESPIRATORY/Dosage Regime sanctioned its express abolition in 2010 (to be effective in early 2011) [106]. This means that up to 2031 at least (as the grant of a CPC could prolong duration of other five years) Swiss-type of claim inventions will coexist with the new purpose-bound product protection format introduced by the EPC 2000, which renders clarification on any like difference in scope of protection even more compelling.

6.1. The meaning of “any specific use” within the context of novelty of the invention and the patentability of new dosage regimens.

The perimeter of the new Art. 54(5) EPC 2000 was deeply explored by the Enlarged Board of Appeal following the remittal by the Technical Board in KOS LIFE SCIENCES INC/Dosage regimen [107]. The invention claimed the use of nicotinic acid for the manufacture of a sustained release medicament for use in the treatment of hyperlipidaemia by oral administration. Whereas the use of nicotinic acid in the treatment of hyperlipidemiae was known at the time of filing, as shown by prior art documents, the patentee argued that (second medical use invention’s) novelty stemmed from claim 1 expressly indicating a different dosage regimen (i.e. “once per day prior to sleep”). The Examining division, however, refused protection on the basis that the specific drug administration regimen constituted a medical activity excluded from patentability (by Art. 52(4) EPC 1973) and therefore could not be considered a further medical indication from which novelty could be inferred [108]. Confronted with the issue, the Board of Appeal deemed that the points of law at issue deserved clarity and remitted the case before the EBoA precisely asking whether, from a joint reading of new Art. 53(c) and Art. 54(5) EPC 2000, protection could be granted to a second use of the medicament providing a new and inventive treat­ment by therapy of a certain illness when the very same medicament was already known to be useful for that specific illness. Secondly, assuming a positive answer to the first question, the Technical Board asked whether patentability could be possible even in istances where the only novel feature of the treatment was a new and inventive dosage regime [109]. The EBoA started its analysis by examining at length the new EPC provisions, as modified by the EPC 2000 [110], especially concentrating on the new prong of Article 54 EPC introducing protection for further medical use inventions. Following the same line of reasoning of the TBA in GENETECH [111], the EBoA asserted that Article 54(5) EPC did not define any degree of distinctiveness the new use must possess in order to qualify for protection [112], and that limiting patentability of further medical use inventions only to cases of inventions aimed at treating a different illness than the one targeted by a previous patent (regardless whether first or second use patent) would amount to an arbitrary reading of the provision, at odds with the good faith principle stated in [...]

6.2. The meaning of “any specific use” and the scope of protection of further medical use inventions.

So what is the purpose of the introduction of the wording “any specific use” as opposed to the more generic “for use” (in a method referred to in Article 53(c) [115]) of the fourth prong of Art. 54 EPC? There is widespread consensus that such wording is meant to grant limited protection to the product clai­med in the invention (i.e. the substance or composition), whose scope is therefore limited to the specific function or purpose of the product, as specified in the patent, in the “for the use in the treatment of …” part of the claim [116]. This interpretation, which is in line with the intentions of the framers of the Revision, has been embraced also by the EPO Chambers that have agreed on the circumstance that the only appropriate way to interpret the wording “any specific use” within such provision is to refer it to the scope of protection, which is limited to the specific claimed use, as opposed “[…] to the generic broad protection conferred by the first claimed medical application of a substance of composition, which is in principle not confined to a particular indication” [117]. And indeed, while the latter could just vaguely claim some sort of medical use, being the substance known for its previous application in a different (non-medical) sector, second medical use inventions must demonstrate their departure from the first-use invention, hence they needed to claim a specific use within a method referred to in Article 53(c) EPC2000 [118]. Pursuant to the jurisprudence of the EPO Technical boards there would seem to be a hierarchy, therefore, in patent breadth – hence, strength – in the medical field, where (structurally) new compound or substances patented for the first time for a medical application would receive the strongest protection [119]: what we could call “absolute and across-sectors” product protection. Second in rank, there would be first medical use inventions. In this case, indeed, according to the EPO jurisprudence, protection would extend to all unforeseen medical uses of the compound and would not be anyhow limited in scope to the first therapeutical method of employment as described in the patent [120]. In this latter case, therefore, it would be more appropriate to talk about “sector-bound” product protection (or “absolute purpose-bound” protection). Eventually, subsequent [...]

Conclusion.

In the past decades, the EPO Chambers have gradually stretched the boun­daries of patentable subject matter in the medical field in a way to encompass each and every sliver of inventive activity, including at the very last also dosage regimens. From the perspective of pharmaceutical industries, second medical use inventions in all their forms (from those identifying a specific sub-class of patients to be treated to new dosage regimens) cover precious technical advances, whose conception has often requested enormous costs [132], hence deserve to be rewarded with an exclusive right. Scholars however have sometimes perceived some of these titles of protection as “weak” patents, often obtained and then employed to fence off rival companies and to avoid the competitive pressure coming from equivalent products, once patent protection is expired [133]. But beyond the issue of the strategic implementation of patents, which was beyond the topic of this paper, several inconsistencies can be spotted in the EPO approach. From a systematic point of view, while it may sound plausible to grant absolute protection to the inventor of a new compound patented for a medical application, the above hierarchy in patent strength between structurally new compound first patented for a therapeutical application, first medical use inventions and second medical use inventions does not persuade the reader. As vividly explained by several authors, the balancing of interests intrinsic in all patent laws between private interest of the firm to reap, with an exclusive right, the fruit of its investments in research, and public interest of society towards the advancement of science and technological progress, demands that patent protection be limited to the technical contribution invented [134], disclo­sed and claimed by the patentee [135]. As applied to the chemical field in gene­ral, such principle requires for protection be tailored to both the specific structure and the method of use of the compound [136]. Because in chemistry, structure and function of the invention are two ingredients bearing exactly the same relevance in the achievement of the desired technical contribution, protection of chemical inventions (especially in the medical field) should always be intended to be purpose-bound, no matter whether the compound is structurally new or not, or whether the compound was or not known to the medical field. Given this assumption, the [...]

NOTE