- Polymorphs are commercially important. Typically, medically active molecules can exist in different solid-state forms (crystal forms) which can have different properties, such as one polymorph having better storage stability (hence, the differences are typically not in the basic medical activity). A patent on a polymorph can be used effectively to extend the patent term because for regulatory reasons, generic companies can not easily use a different polymorph (e.g. “pharmaceutical polymorphs provide an excellent way for a company to further protect a small molecule drug in order to recoup the billions of dollars that go into research and development, thereby enabling further research and development” (link, emphasis added).
- The big obstacle to getting a patent for a polymorph is as of yet T 777/08 (Atorvastatin) holding that as of 1995, screening for polymorphism was routine in the art such that “in the absence of any unexpected property, the mere provision of a crystalline form of a known pharmaceutically active compound cannot be regarded as involving an inventive step”.
- The present Board: “The fact that the skilled person is taught in the prior art to investigate polymorphs in order to isolate the crystalline form having the most desirable properties is in itself not necessarily sufficient to consider a specific polymorphic form having a certain desired property obvious”.
- The present Board: “The board acknowledges that, in view of their disclosures, D4, D5 and D7 teach the investigation of polymorphs in order to isolate the crystalline form having the most desirable properties. This in itself is not sufficient to deny inventive step, however. Only if the prior art contains a clear pointer that it is the claimed subject-matter that solves this problem or where it at least creates a reasonable expectation that a suggested investigation will be successful, can inventive step be denied. In this case, however, there is no clear pointer in any of D4, D5 or D7 that it is the specific crystalline Form I as defined in claim 1 that is the most stable form. ”
- The present Board: “the decision in T 777/08 is concerned with the arbitrary selection of any crystalline form and considers it obvious that any arbitrary crystalline form has better filterability and drying characteristics than the corresponding amorphous form. This is entirely different from the present case. The present case is NOT about the selection of any crystalline form but about the selection of one specific crystalline form, namely Form I of bosutinib monohydrate. Furthermore, the selection of this specific crystalline form is not arbitrary, but rather this form has unexpected properties, namely an improved stability when compared with the other crystalline forms in D1, D2 and D3.”
- I note that in T 777/08, the “solution as defined in claim 3 of the main request and claim 1 of the auxiliary request relates to a specific polymorph of atorvastatin” namely “form IV of crystalline atorvastatin hydrate”. The technical effect was " shorter filtration and drying times for form IV compared to the amorphous form". In T 777/08, “the appellant further argued that the presence of an inventive step was supported by the fact that a specific polymorph was being claimed rather than crystalline forms in general. The board does not deny that there may be other options for solving the problem posed []. However, an arbitrary selection from a group of equally suitable candidates cannot be viewed as involving an inventive step”.
EPO T 1684/16 - link
4.3 Inventive step in view of D1, D2 or D3 as the closest prior art
4.3.1 As set out above, the compound in claim 1 of the first auxiliary request is a specific crystalline form of bosutinib monohydrate ("Form I"). The patent aims to provide methods for preparing this form and pharmaceutical compositions containing this form for the treatment of pancreatic and prostate cancer (paragraph [0001] of the patent).
4.3.2 Closest prior art
D1, D2 and D3 disclose solid/crystalline forms of bosutinib.
In accordance with the parties' submissions, any of D1, D2 and D3 may be regarded as the closest prior art.
In D1, D2 and D3, the products are described as a "light pink solid" having a melting point of 116-120°C in D1 (example 1), a solid having a melting point of 125-128°C in D2 (example 50) and a crystalline solid in D3 (example 45). There is no indication that the crystalline form is obtained in D1 and D2, and no indication of the specific nature of the crystalline form obtained in D3. The distinguishing feature is thus the specific crystalline form of bosutinib monohydrate ("Form I"), as defined in claim 1.