In a recent opinion generally affirming the patentability of new crystalline forms, the Patent Trial and Appeals Board (PTAB) reversed an examiner’s decision rejecting claims to a crystalline form of eliglustat hemitartrate salt based on an obvious to try rationale. Ex Parte Liu et al., 2021 Pat. App. LEXIS 5753 (P.T.A.B. September 27, 2021). The patent application was owned by Genzyme Corporation. The claim at issue read:
A hemitartrate salt of [eliglustat] wherein the salt is in a crystalline form, the crystalline form characterized by at least two major X-ray powder diffraction peaks at 2θ angles selected from the group consisting of 5.1°, 6.6°, 10.7°, 11.0°, 15.9°, and 21.7°, wherein the specified 2θ angle means the specified value ±0.2°, and the X-ray powder diffraction diagram is obtained by using Cu Kα radiation.
The prior art reference (“McEachern”) disclosed eliglustat and a method for synthesizing the free base of eliglustat. McEachern also disclosed that eliglustat could form various salts, including the hemitartrate salt. McEachern did not disclose a method of synthesizing the hemitartrate salt, or that the salt would exist in a crystalline form, as opposed to an amorphous form.
Nevertheless, the Examiner argued that McEachern anticipated the claimed crystalline form of eliglustat and rendered the crystalline form obvious. As for obviousness, the Examiner argued:
a skilled artisan would have been highly motivated to use various well-known crystallization solvents to form the product in order to improve the solubility, stability, or hygroscopicity of eliglustat, because Brittain teaches that the crystalline structure of a compound exerts "a profound effect" on its solid-state properties.
and
a skilled artisan would have had a reasonable expectation of success in arriving at any one of the preparation processes disclosed in the instant specification, which would inherently result in the claimed crystalline form of eliglustat hemitartrate, because "crystallization optimization was so commonplace that automated screening techniques," such as the highthroughput ("HT") crystallization methodologies described in Morissette, were utilized in the art to screen "hundreds or thousands of crystallization conditions in parallel."
The PTAB summed up the Examiner’s position as follows:
the crux of the obviousness rejection appears to be that it would have been obvious to try to crystallize eliglustat hemitartrate and that, given the knowledge in the prior art regarding parameters affecting crystallization and the capability of high throughput crystallization methodologies to screen large numbers of crystallization conditions to identify optimal crystalline forms for, e.g., pharmaceutical ingredients, … a skilled artisan would have had a reasonable expectation of hitting upon the conditions for formation of the claimed crystalline form of eliglustat tartrate.
The PTAB equated the Examiner's argument to an "obvious to try" rejection, explaining,
The above rationale would appear to render obvious any crystalline form of a useful compound.
Quoting Federal Circuit precedent from In re Kubin, 561 F.3d 1351, 1359 (Fed. Cir. 2009) and In re O'Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988)), the PTAB rejected the Examiner's argument, holding:
it would be error to equate "obvious to try" with "obviousness under § 103," where what would have been "obvious to try" would have been to vary all parameters or try each of numerous possible choices until one possibly arrived at a successful result, where the prior art gave either no indication of which parameters were critical or no direction as to which of many possible choices is likely to be successful.
Key takeaways:
Despite technological advances in polymorph screening, patents for new crystalline forms remain largely patentable as long as they are not inherently disclosed in the prior art. This case was particularly notable because the patent applicant admitted that eliglustat hemitartrate itself was anticipated by the prior art, and did not offer any proof that eliglustat existed in more than one crystalline form. The scope of the claim also was notable requiring for infringement only two XRPD peaks chosen from a listing of six.
