In May 2015, the Israeli Patent and Trademark Office (IL PTO) issued new working guidelines relating to the examination of patent applications claiming crystal and salt forms of known compounds. The guidelines reflect a significantly more restrictive approach than previously enunciated by the IL PTO regarding the patentability of polymorph and salt patents. Specifically, according to the guidelines:
- Novel crystal and salt forms of known compounds are prima facie obvious unless a “substantial advantage” is demonstrated over the prior art. The guidelines state that a “high level of proof” is required to rebut a showing of prima facie obviousness.
- A skilled person would appreciate that most pharmaceutical compositions can crystallize in more than one crystal form which will have different properties such as stability, solubility, hygroscopicity, etc. Thereupon, it would be obvious to try to crystallize known compounds with a reasonable expectation of success. In other words, according to the IL PTO, screening does not require any type of “creative sophistication”. Similarly, claims to a process for making crystalline or amorphous compounds will only be found to be inventive if the claimed process recites “special” or “unique” reaction conditions or parameters.
- Not every advantage over the prior art will be sufficient to establish inventive step. An advantage will only be regarded as a “substantial advantage” satisfying inventive step when the benefits are not recognized and well-known in the art.
- Claims to new crystal forms must include the highest intensity X-ray powder diffraction (XRPD) peaks which conclusively characterize the crystal form (such as eight, ten, etc. of the highest intensity peaks). Claiming the crystal form with a small number of peaks will be considered to be insufficient to distinguish the claimed crystal form from other forms. There is no indication yet from the IL PTO regarding the “minimum” number of peaks to be recited in a claim. For example, a “small” number of peaks (such as 2-4) could be granted if it is established that these peaks conclusively characterize the crystal form.
- Claims to processes for making a crystal form must identify the solvent and recite the specific process parameters such as solvent ratios, temperature, heating or cooling rate, etc.
- The following lack inventive step:
- A polymorph obtained spontaneously due to conversion from another crystal form.
- Obtaining a single crystal form using several crystallization procedures that utilize several solvent systems (there is no inventive step because of the high likelihood that a skilled person would have obtained the claimed form).
- When crystallization attempts lead to several new forms having satisfactory properties (there is no inventive step because several polymorphs were found to be suitable).
Interestingly, the guidelines presume that research for novel salts and crystal forms to be nothing more than a routine exercise. The guidelines make no reference to the complexity of the research, the lack of predictability as to which forms can be made and their respective properties or provide any flexibility for any serendipity that might be involved. Instead, the guidelines raise the threshold for patentability for novel salt and crystal forms to be higher than that for other types of inventions. Thus, it appears that novel salts and crystal forms will be subject to an automatic “obvious to try” test. Moreover, the guidelines raise doubts whether only “exotic” advantages, which are ordinarily not found will be sufficient to establish patentability.
As mentioned previously, the guidelines are overly restrictive and inconsistent with Israeli case law. There is no basis in Israeli case law for applying a different, more stringent patentability requirement to salt and polymorph patents. In fact, the “obvious to try” test sometimes used by the IL PTO has not been accepted by the Israeli Courts. Moreover, the Supreme Court of Israel has recognized the difficulties involved in the development of a new salt form amenable to pharmaceutical formulation and stated that the development of a novel salt entails a genuine and substantive research program.
Please continue to watch the BRIC Wall Blog for further postings on the patentability of crystal and salt forms.
This post was written by Lisa Mueller and Liad Whatstein of Liad Whatstein & Co.