Patentability of polymorphs
In chemistry, polymorphism relates to the ability of a solid material to exist in more than one form or crystal structure. Polymorphs are considered crucial in the development of new pharmaceutical products, since the different crystalline forms of a drug may have different physicochemical properties that can influence the quality, safety and efficacy of the final drug product.
Although Decision 486, which establishes the common IP regime for Colombia, Bolivia, Ecuador and Peru, does not specifically exclude polymorphs from patentability, the Colombian PTO (SIC) has usually set very high standards regarding the compliance with the clarity and inventive step requirements, resulting in many patent applications directed to polymorphs being rejected.
One of the most common objections raised by Colombian examiners regarding polymorph patent applications is the lack of clarity of claims. According to the SIC´s Guidelines for patent examination, a polymorph must be characterized in a claim by its physicochemical parameters, such as:
1. Single crystal x-ray diffraction pattern (SCXRD). If a claim characterizes the polymorph through this pattern, no additional data will be required.
2. X-ray powder diffraction (XRPD) pattern, which must have at least 20 characteristic peaks measured between 5°, 2θ and 90°, 2θ. X-ray analysis is the preferred technique to characterize a polymorph.
3. Raman and IR spectroscopy.
4. 13C-NMR spectroscopy.
5. Methods of thermal analysis: TGA, DTA and DSC.
Even if claims are clearly drafted as described above, many patent applications referred to polymorphs are rejected by the SIC due to lack of inventive step. The Colombian PTO requires demonstration that the new polymorph unexpectedly solves a technical problem in the prior art (for example enhanced pharmaceutical efficacy), usually by the submission of comparative data.
In 2009 the Andean Court ruled in favor of the patentability of an application referred to a new polymorphic form of atorvastatin calcium (Form III) that had been previously rejected by the SIC due to lack of inventive step. The Court decision stated that it was non-obvious to a person skilled in the art.
However, the above Court decision was not adopted by the SIC and the high standards regarding the compliance with the inventive step requirement have been generally very subjective, so the decisions on polymorph patent applications have varied considerably from application to application.
Recently, the SIC has granted a patent to Novartis AG related to a polymorph of a compound useful for the treatment of respiratory diseases. Hopefully this reflects a more favorable approach of the SIC to the analysis of polymorph patent applications that are properly characterized and show surprising effects.