The Supreme Court of Korea recently rendered decisions regarding the inventiveness standards for selection inventions and crystalline form inventions, addressing criticism that the inventiveness standards for these inventions were too strict.
Previously, with regard to the inventiveness requirement of a selection invention that fell within a broader or generic concept disclosed in the prior art, the Supreme Court had ruled that the selection invention should exhibit an effect qualitatively different from, or quantitatively remarkable over, that of the prior art.
Similarly, the court previously held that, in the absence of special circumstances, a novel crystalline form invention of a known compound would meet the inventiveness standard only when the crystalline form invention exhibited an effect qualitatively different from, or quantitatively remarkable over, that of the known compound.
In 2021, however, the Supreme Court departed from the previous approach in upholding the inventiveness of a selection invention. The court held that to determine the inventiveness of a selection invention, the difficulty to conceive the selection invention should first be examined, and if difficulty cannot be shown, the inventiveness of the selection invention may then be assessed based on the existence of a remarkable effect of the selection invention (Supreme Court Case No. 2019 Hu 10609 rendered on April 8 2021).
Furthermore, the Supreme Court recently upheld the inventiveness of a specific crystalline form invention without requiring corroboration of the presence of a remarkable effect of the crystalline form invention (Supreme Court Case No. 2018 Hu 10923 rendered on March 31 2022).
The court found that it was not obvious to conclude, in view of the ordinary level of skill as of the filing date, that a person skilled in the art would have easily conceived such a crystalline form exhibiting certain beneficial effects from the teachings of a prior art reference that disclosed a compound with the same chemical structure but failed to specify its crystalline form.
Selection invention case
Background
The patent at issue related to novel lactam-containing compounds and derivatives thereof useful as inhibitors of factor Xa, and was based on the discovery that certain compounds with a lactam ring were useful as inhibitors of factor Xa and exhibited superior pharmacokinetic properties. Specifically, claim 1 of the subject patent was directed to a particular compound with the lactam ring (apixaban).
Meanwhile, the prior art reference disclosed nitrogen-containing heterobicyclic compounds useful as inhibitors of factor Xa, and specifically disclosed 66 core structures for the nitrogen-containing heterobicyclic compounds. As the prior art reference defined such compounds by a Markush grouping of various substituents applicable to the 66 core structures, an enormous number of compounds could theoretically be covered by the prior art reference, depending on the selection of a core structure and the combination of substituents applicable thereto.
In invalidation trials against the subject patent lodged by several generic companies, the Korean Intellectual Property Office Trial Board rendered a decision invalidating the subject patent for lack of inventiveness over the prior art reference.
In an appeal against the decision, the Patent Court again denied the inventiveness of the subject patent because the specification failed to describe any effect that was qualitatively different from, or quantitatively remarkable over, that of the prior art reference, and such effect had not been corroborated.
The Supreme Court decision
On appeal, however, the Supreme Court reversed the decision of the Patent Court. In doing so, the Supreme Court first indicated that difficulty to conceive an invention, which is generally considered in determining inventiveness, should equally be considered first when determining the inventiveness of a selection invention, like the one of the subject patent directed to specific species falling within the scope theoretically covered by the Markush formula provided in the prior art reference, but not specifically disclosed therein.
In particular, the court stated that difficulty to conceive the subject invention shall be determined in light of:
The number of compounds theoretically included in the scope of the 66 core structures and the substituents applicable thereto defined by the Markush formula of the prior art reference;
The existence of a motivation, suggestion, or reason for the selection of the specific compounds or substituents; and
Structural similarity between the patented compounds and those specifically disclosed in the prior art reference.
Based on the above reasoning, the Supreme Court noted that the lactam ring in claim 1 of the subject patent needed to be attached to the core structure at a particular position. However, there was no teaching or suggestion pointing to the lactam ring in a preferred embodiment of the prior art reference, and no compound that had a similar structure to the claimed compounds of the subject patent or contained a lactam ring at a correct position was among those specifically listed therein.
In addition, the Supreme Court noted that the subject invention had an improved inhibiting activity and selectivity for factor Xa when compared with known inhibitors of factor Xa, exhibited improved pharmacokinetic effects, and showed improved effects for combination with other therapeutic agents in light of the disclosures given in the specification of the subject patent and experimental data submitted during prosecution.
For the foregoing reasons, the Supreme Court held that:
A person skilled in the art would have had to experiment with numerous combinations of selections through trial and error to arrive at the subject invention from the prior art reference;
The inventiveness of the subject invention over the prior art reference cannot be denied since it would not be obvious to conceive the subject invention from the prior art reference without the benefit of hindsight knowledge of the subject invention; and
The subject invention produced certain improved effects over the prior art.
Crystalline form invention case
Background
The prior art reference disclosed tylosin as a macrolide antibiotic for use in the treatment or prophylaxis of pasteurellosis of mammalian livestock or poultry.
The claimed invention of the subject application related to a novel crystalline form I of tylosin (‘Form I’) characterised by a particular powder X-ray diffraction spectrum. According to the specification of the subject application, the object of the invention was to provide Form I, which possessed greater stability at an ambient temperature, exhibited advantageous thermodynamic properties, and showed less water uptake than other solid-state forms of tylosin.
In addition to the disclosures in the specification, experimental data submitted during prosecution further showed, among the novel crystalline forms of tylosin (Forms I to IV) obtained, that Form I specifically was thermodynamically more stable and less hygroscopic than amorphous or other crystalline forms.
In response to the examiner’s final rejection for lack of inventiveness over the prior art reference, the applicant filed an appeal with the Trial Board. However, the board dismissed the appeal because the invention would have easily been conceived from the prior art reference and thus lacked inventiveness.
In an appeal against the decision, the Patent Court denied the inventiveness of the subject invention for the following reasons:
A person skilled in the art would have easily recognised the possibility that the tylosin compound disclosed in the prior art reference may exist in a variety of crystalline forms, and thus it would have been obvious for a skilled person to try to obtain, thermodynamically, the most stable crystalline form by way of investigating all tylosin polymorphs through crystallisation techniques known in the art;
Form I of the subject invention was merely the most stable crystalline form identified as a result of formulation processes routinely carried out in the relevant technical field; and
The superior physical stability and low hygroscopicity of Form I were not recognised as qualitatively different or quantitatively remarkable effects that would have been unexpected by a person skilled in the art.
The Supreme Court decision
On appeal, however, the Supreme Court reversed the Patent Court decision. In doing so, the Supreme Court first clarified that although polymorph screening is routinely performed to investigate whether a pharmaceutical compound has various crystalline forms in the course of formulation design of the compound, such routine practice cannot be the sole basis to deny a determination of difficulty to conceive a crystalline form invention.
In this regard, the Supreme Court set forth the standard for determining the inventiveness of a crystalline form invention by examining whether a person skilled in the art would have easily conceived the crystalline form invention from prior art based on consideration of various factors, including:
Whether polymorphism of a compound disclosed in the prior art was known or predictable;
Whether the prior art provided a teaching, suggestion, or motivation that would have led to the specific crystalline form of the claimed invention;
Whether the specific crystalline form of the claimed invention was a polymorph that would have been identified through routine polymorph screening of a compound disclosed in the prior art; and
Whether the specific crystalline form of the claimed invention exhibited beneficial effects unexpected from the prior art.
Under such standard, the Supreme Court noted that the prior art reference failed to specify whether the solid compound of tylosin disclosed therein had a crystalline form or an amorphous form. It was not known at the time of the filing date of the subject application whether tylosin had a variety of crystalline forms, and the starting materials and specific parameters for the crystallisation process (such as solvent, temperature, and time) employed in deriving the tylosin compound disclosed in the prior art reference and Form I of the subject invention were different.
As such, the Supreme Court found that it was not clear whether a person skilled in the art would have easily conceived Form I from the prior art reference by way of making appropriate adjustments to the parameters of the crystallisation process or performing routine polymorph screening.
Furthermore, the Supreme Court indicated that it was difficult to conclude that the effects of Form I could be expected from the prior art reference in view of the fact that the specification of the subject application provided concrete experimental results showing superior thermodynamic stability and low hygroscopicity of Form I, whereas the prior art reference described no experimental results comparable to the effects of Form I.
Significance of the decisions
The Supreme Court’s relaxation of the inventiveness standard for particular types of inventions such as selection inventions and crystalline form inventions is considered more consistent with the practices of other major foreign countries.
Owing to these pro-patent Supreme Court decisions, a decrease in the invalidation rate of patents for selection inventions and crystalline form inventions and an increase in the allowability of patent applications pertaining to such inventions is expected. The approach adopted by the Supreme Court is a promising sign for patentees in Korea, especially those in the pharmaceutical industry.
