Second medical use of a known compound is an important invention to the pharmaceutical industry. However, due to the strict standard of examination for pharmaceutical patents in China, a large number of second medical use patent applications were rejected by the CNIPA. Although a few second medical use applications survived from the examination and were granted as patents in China, they were frequently challenged and most of them were declared invalid in the end. There were sayings by the pharmaceutical industry that Viagra second medical use patent was probably the only one that survived patent challenge in China.

Nevertheless, in the past two years, the CNIPA seemed to gradually easing the examination standard for pharma patent applications. In particular, the second medical use patent owned by the University of Bordeaux survived from a round of patent challenge in 2020, and this decision was selected by the CNIPA as one of TOP 10 exemplary Invalidation Cases for 2020.

In this paper, we will discuss the inventiveness of this patent, especially the CNIPA’s attitude towards the motivation of those skilled in the art based on the prior art to arrive at the claimed second medical use.

==Inventiveness: Is There A Motivation to Arrive at Second Medical Use? ==

Claim 1 recites “Use of a beta blocker for the manufacture of a medicament for the treatment of infantile capillary hemangiomas (IH), wherein said beta blocker is propranolol or a pharmaceutical salt thereof.”

The Petitioner of this case submitted that Claim 1 would be obvious in light of the disclosure of Evidence A and Evidence B. Specifically, Evidence A disclosed that fading of IH in infants is related to the increase of apoptotic cells, and the author presumed that an apoptosis-inducing agent could possibly accelerate the fading of IH in infants. Evidence B disclosed that adult rats were exposed to a beta blocker (e.g., propranolol), and their capillary endothelial cells underwent cell apoptosis. As such, the petitioner argued that those skilled in the art, when combining Evidence A and B, would have motivation to use propranolol for inducing apoptosis to capillary endothelial cells and thus treat IH in infants.

However, the Re-examination Board noticed that Evidence A was directed to an observation for cell apoptosis in IH sample biopsy, and merely proposed a possible mechanism to regulate fading of IH. From the perspective of those skilled in the art, this proposal is not well grounded, and not sufficient to guide a skilled artisan to use an apoptosis-inducing agent for the treatment of IH in infants.

In addition, the Re-examination Board held that, from Evidence B alone, although it showed that blocking of capillary endothelial cells alone by the beta blocker would induce apoptosis, it also showed that a simultaneous blocking of capillary endothelial cells and fibroblasts by the beta blocker could protect the endothelial cells from apoptosis. Considering IH not only contains endothelial cells but also contains other cells like fibroblasts, pericytes, mast cells and macrophages, the in vivo result would be much more complicated. It would be impossible to predict whether propranolol would induce apoptosis or block apoptosis in such complicated in vivo situation like infantile capillary hemangiomas. Therefore, the Re-examination Board held that those skilled in the art can’t obviously arrive at Claim 1 in light of the disclosure of Evidence A and Evidence B.

==Our Advices==

This case was selected as an exemplary invalidation case of CNIPA (2020) because it clearly showed the change of attitude of the CNIPA Examination Division towards the inventiveness of pharmaceutical patent, especially towards the second medical use patent.

It was common that the Examiner preferred to cherry-pick the footprints from the prior art and mistakenly combine footprints and concluded that there were “suggestions” or “motivations” in the art. However, it is important to note that life science, chemistry, pharmaceutical and medical studies are experiment-based sciences. Although scholars often boldly propose or suggest some possible mechanisms of treatment and published their ideas in a research paper, however, if these proposals or ideas were largely untested or unpredictable at the time of filing, then the Examiner shall stand in the shoes of those skilled in the art, and objectively evaluate whether the state of art gave sufficient motivation for those skilled in the art to arrive at the claimed solution. If the disclosure of the prior art was prophetic or hypothetic, then the Examiner shall not rely too much on such prior art against the inventiveness of the patent application.

We believe the selection of this case as one of TOP 10 exemplary cases could encourage more innovations from the pharmaceutical industry. The decision and approaches of this case will be frequently used by our attorneys in their daily work for evaluating the inventiveness of pharmaceutical patent applications.

If there are any questions in relation to this topic or any other patent-related matters, please feel free to contact Haoyu ZHOU (Elliot) for more discussion at patent@foundin.cn.