Patenting polymorphs: EPO Board of Appeal provides guidance on inventive step (T 325/16)
Whether a new polymorph of a known pharmaceutical compound is considered inventive, and therefore patentable, is a hotly contested question at the European Patent Office (EPO).
The Board of Appeal at the EPO has provided further guidance in the decision of T 325/16. The full decision can be found here.
Solid matter can be divided into two primary categories – amorphous, and crystalline.
Crystalline solids demonstrate regular, repeating patterns in the arrangement of atoms, ions or molecules of which they are comprised, whereas amorphous solids do not. Where two crystalline solids comprise the same atoms, ions or molecules but vary in the way in which those atoms, ions or molecules repeat, they are termed “polymorphs”.
In a pharmaceutical context, polymorphs are important because properties such as the stability and solubility of an active pharmaceutical ingredient can vary markedly from one polymorph to the next. Where these properties are beneficial, polymorphs can be granted patent protection – thereby providing a mechanism to further extend the patent protection afforded to new pharmaceutical compounds.
The patent contested in T 325/16 (EP2431376) disclosed three polymorphs of known anti-tumour agent radgocitabine (“types I, II, and III” radgocitabine). Types I and II radgocitabine were linked to an enhanced stability to degradation so were claimed, along with methods for their production.
During opposition, the patent was revoked for lack of an inventive step. On appeal, the patentee (appellant) requested the decision of the opposition division be overturned. The appeal is interesting for its discussion of inventive step.
Submissions (Inventive Step)
The appellant’s inventive step submissions were based on T 1684/16. Here, the contested patent claimed a new polymorph of a known pharmaceutical showing enhanced stability relative to the closest prior art compound, a crystalline solid. The Board formulated the objective technical problem as the provision of a more stable form of the known pharmaceutical and found that because the inherent unpredictability of polymorphism screening meant that there could be no reasonable expectation that one polymorph would be more stable than the next, the claims involved an inventive step.
In the present case, the appellant argued that the claimed radgocitabine polymorphs demonstrated an enhanced stability over the closest prior art disclosing a crystalline form of radgocitabine, and that the objective technical problem could be seen in the provision of an anti-tumour agent containing a crystalline form of radgocitabine with a higher stability. In light of the finding of T 1684/16 that such the search for more stable polymorphs is inherently unpredictable, the appellant argued that the claims must involve an inventive step.
The respondent’s inventive step submissions were based on T 777/08. Here, the contested patent claimed a new polymorph of a known pharmaceutical showing only enhanced filterability and drying characteristics relative to the closest prior art compound, an amorphous solid. The Board formulated the objective technical problem as the provision of a product having improved filterability and drying characteristics and found that since most crystalline polymorphs would possess improved filterability and drying characteristics when compared to the amorphous form, the skilled person would have a clear expectation of success in solving the objective technical problem upon undertaking routine polymorphism screening. That polymorphs would exhibit enhanced stability relative to the amorphous form was also considered to be expected by the skilled person. The Board in T 777/08 therefore found that the claims amounted to an arbitrary selection of a specific polymorph from a group of equally suitable candidates, which did not involve an inventive step.
In the present case, the respondent argued that the appellant failed to prove that the claimed radgocitabine polymorphs were more stable than amorphous radgocitabine, let alone the crystalline form disclosed by the prior art. The respondent’s objective technical problem was therefore formulated less ambitiously as the provision of an alternative crystalline form of radgocitabine. Based on this line of reasoning, the respondent argued that the polymorphs were merely “equally suitable” in the context of T 777/08. The respondent further argued that even if the claimed polymorphs could be associated with an enhanced stability, T 777/08 also taught that the skilled person would have a clear expectation of success in providing radgocitabine polymorphs with enhanced stability. The respondent argued that the claims could not involve an inventive step.
Decision (Inventive Step)
The Board found that the appellant had successfully demonstrated that the claimed polymorphs exhibited enhanced stability to degradation when compared to the closest prior art compound, a crystalline form of radgocitabine. The clear expectation of success of T 777/08 upon which the respondent relied was therefore found not to be applicable, since this line of reasoning was true only for where the starting point of the search for a more stable polymorph was an amorphous solid.
The Board therefore formulated the objective technical problem as the provision of an anti-tumour agent containing a crystalline form of radgocitabine with a higher stability.
In deciding whether the skilled person would arrive at the claimed solution to this objective technical problem without the exercise of an inventive step, the Board firstly acknowledged that the prior art did indeed suggest screening for the most stable polymorph. The Board also acknowledged that the closest prior art disclosed experimental conditions for the preparation of radgocitabine polymorphs identical to those employed in the contested patent.
However, these facts alone were found not to preclude inventive step. Rather, the Board found that because there could be no reasonable expectation that one polymorph would be more stable than the next (cf. T 1684/16), for inventive step to be denied the prior art must contain a clear pointer that the claimed radgocitabine polymorphs would be more stable than other crystalline forms of radgocitabine.
Since no such pointers were discovered, the Board found the claims to involve an inventive step.
T 325/16 is useful to applicants for polymorph patents in Europe. It sets out that yes, polymorphism screening is a part of the routine of the person skilled in the art. However, that polymorphism screening is routine should not preclude inventive step so long as the specifically claimed polymorphs are linked to a technical advantage that is not explicitly suggested by the prior art.
This article is for informational purposes only and does not constitute legal advice. Please, therefore, get in touch with your usual Forresters Attorney if you need further advice.