Yue Guan, 4 August 2022, first published by MIP

On April 26 2022, the 22nd World Intellectual Property Day, the China National Intellectual Property Administration (CNIPA) released the Top Ten Patent Reexamination and Invalidation Cases of 2021, including two patent invalidation cases involving compound patents over marketed drugs. The CNIPA upheld the validity of both patents, including the Macitentan compound patent ZL01820481.3 (the ‘patent’).

The CNIPA’s decisions are evidently pro drug patentees. The perspectives embodied in the examination decision may offer practitioners a glimpse into the examination of pharmaceutical compound patents.

Background

Macitentan is an endothelin receptor-targeting antagonist developed by Actelion Pharmaceuticals (the ‘patentee’) that can effectively delay the progression of pulmonary hypertension.

In the invalidity procedure, the patentee narrowed the claimed Markush-type compound into Macitentan and Compound 104, the chemical structures of which are shown below.

The description of the patent states the spectrogram data and IC50 values for endothelin receptors ETA and ETB of Compound 104 and the mere chemical structure of Macitentan in a table, without supplying any data. No specific preparation method for either compound is stated in the description.

Compound 104 Macitentan

The challenge

The petitioner challenged the patentability of Macitentan by contending that given that the description fails to incorporate the data delineating the chemical structure of Macitentan and the specific preparation method thereof, there is no way for a person skilled in the art to know how to prepare Macitentan based on the preparations of other compounds in the description. Neither could such a person ascertain the technical effects of Macitentan. Therefore, the disclosure of the description was insufficient.

On top of that, a person skilled in the art, by leveraging the closest prior art and common knowledge, could easily obtain Macitentan by way of simple isostere group substitution; thus, Macitentan did not possess inventiveness.

The findings

The CNIPA’s detailed analysis of the petitioner's grounds found that:

There is no technical obstacle as to the preparation of Macitentan based on related embodiments detailed in the description for a person skilled in the art; and

The chemical structures of Macitentan and Compound 104 are extremely similar, so it is reasonable to anticipate that they would achieve similar technical effects, as substantiated by the evidence. The description thus sufficiently discloses Macitentan. The effects achieved by Macitentan are almost equal to those of the closest prior art, and the technical problem solved is to provide a different compound with an antagonistic effect on ETA and ETB. However, in the context that the prior art has explicitly introduced technical paths different from the distinguishing features, it does not suffice to draw a conclusion that a person skilled in the art would be motivated to obtain Macitentan merely based on common knowledge on isosteres.

In analysing this invalidity case, the CNIPA underlined the following. In seeking the protection of specific compounds, a patentee is advised to incorporate in the description specific examples on the preparation method or technical effects. The description will be at risk of being deemed insufficiently disclosed if the compounds are merely listed in a table, because the approach would exceed the reasonable expectations of a person skilled in the art.

Besides, providing a technical solution featuring a different technical path but achieving similar effects to the prior art is a route to design around existing patents in the pharmaceutical field.

An uphill battle

Patentees must fight an uphill battle in patenting such inventions, in comparison with those with better technical effects. In assessing the inventiveness of Macitentan, the CNIPA factored in the holistic status of the R&D of the prior art, and the difficulty in selection of a technical path (or the introduction of distinguishing features) against the backdrop of the aforesaid R&D status of prior art.

This case sheds some light on the CNIPA’s methodology in assessing the inventiveness of pharmaceutical inventions with similar effects to prior art. It could also serve as a point of reference in terms of the drafting of compound patents, and the examination criteria regarding sufficient disclosure and inventiveness in invalidity procedures.