On May 10, 2022, the CNIPA approved and disclosed a patent case: "Pangolin coronavirus xCOV and its application and the application of drugs against coronavirus infection" (Publication No. CN113046327B, hereinafter referred to as Patent No. 327), there is only one approved claim: the use of cepharanthine in the preparation of a drug for the treatment of SARS-COV-2 virus infectious disease. With the news that the patent of cepharanthine (the alkaloid derived from the genus Seraphine)’s medical use against COVID-19 virus is approved released, and it is pointed out in the news that "the article in Science magazine confirms this conclusion: the researchers compare cepharanthine with 25 other candidate compounds together for study, and the results showed that the EC50 of cepharanthine against the new coronavirus ... is much lower than other candidate drugs". Though the relevant clinical trials have not yet been carried out, it has driven the stock price of cepharanthine concept stocks in the mainland Chinese stock market to skyrocket.

However, the content of the approved claims of Patent No. 327 is actually hard to correspond to its patent name. In terms of the patent specification content, it can be seen from the background technology and relevant paragraphs of the invention content of Patent No. 327 that the main purpose of Patent No. 327 is to provide a safe model that can screen anti-SARS-COV-2 virus drugs without infecting humans, which uses the xCOV pangolin coronavirus similar to the complete genome sequence of SARS-COV-2 and 92.5% originated with Portein S of SARS-COV-2 virus. The embodiment example of Patent No. 327 records: “To research whether the receptor of the cells infected by xCOV pangolin coronavirus is ACE2”, “To screen potential anti-SARS-COV-2 virus drugs from the marketed drug library with xCOV pangolin coronavirus”, “To conform xCOV pangolin coronavirus replication in cells with real-time quantitative PCR”, “half of the maximum effective concentration (EC50) of cepharanthine to xCOV pangolin coronavirus”, “half of the cytotoxic concentration of cepharanthine to the test cells (CC50)”, and “the results of the experiment in which the xCOV pangolin virus that does not infect humans is used to stimulate SARS-COV-2 virus testing the antiviral effect of cepharanthine against virus, including the selectivity index of cepharanthine, the time point of virus action, and RNASeq compared with drugs leading to tested cells’ death. However, only a related test of cepharanthine against SARS-COV-2 virus is not involved in the Instruction No. 327.

Even though the xCOV pangolin coronavirus is similar to the SARS-COV-2 virus and has some homology, they are still not totally identical. The applicant used a self-established model to speculate on the effect of cepharanthine against SARS-COV-2 virus instead of a scientific method commonly used by those skilled in the art to confirm the efficacy. For example, Science in the magazine issued after the patent No. 327 is filed, the SARS-COV-2 virus was directly used as the test object. Moreover, the applicant did not provide further experimental results in the description to confirm that the xCOV pangolin coronavirus can indeed represent the SARS-COV-2 virus, and can be used to verify that cepharanthine can indeed resist the SARS-COV-2 virus. Just speculation without recording the relevant test methods and results may make it impossible for those skilled in the art who know all the common technical knowledge in the technical field of the invention "before the filing date" to obtain or summarize the technical solution claimed by the claim “the use of cepharanthine in the preparation of drugs for the treatment of SARS-COV-2 virus infectious diseases” from the contents disclosed in the description, which does not conform to Article 26, paragraph 4 of the Patent Law of the Chinese Mainland. The specification shall be based on description, clearly and concisely limiting the scope. In addition, in accordance with the Chapter 2 of Part II, Description and Claims of the Guidelines for Patent Examination, “The specification provides a specific technical solution but without experimental data, and the solution must be confirmed by relying on experimental results. For example, for the invention of a new use of a known compound, in general, experimental data need to be given in the description to confirm its stated use and effect, otherwise it will not be able to achieve the request.” Since the description does not provide the experimental data of the new use of the known compound-cepharanthine in anti-SARS-COV-2 virus, the description of Patent No. 327 may also be considered to be incompatible with the requirements that can be realized, but not in compliance with Article 26, paragraph 3, of the Patent Law.

Based on the examination process of Patent No. 327, although the examiner did not make any comments on the non-compliance with the requirements for realization of Patent No. 327, it did issue an examination opinion stating that "according to the description of the description, the novel coronavirus xCOV isolated in this application has the highest homology to SARS-COV-2, and it’s safe for humans, thereby the applicant believed that xCOV can be used to screen and evaluate the active ingredients anti-SARS-COV-2 virus... However, even if they have high homology, there are still certain differences between the two, not only in the sequence structure of the protein S and genome, but also in the host range, etc., thus the they belong to two different viruses taxonomically. Moreover, the application has no further verification on that drugs having a therapeutic effect on pangolin coronavirus xCOV have similar therapeutic effects on SARS-COV-2 and similar EC50 and CC50, etc. Therefore, based on the fully disclosed content of the description, it is hard for those skilled in the art to predict that pangolin coronavirus xCOV can be used for screening and evaluating the active ingredients anti-SARS-COV-2 virus, the claim is deemed to not meet the supporting requirements.

Although the applicant has persuaded the examiner that based on the fully disclosed content of the description, those skilled in the art can predict that pangolin coronavirus xCOV can be used to screen and evaluate the active ingredients against SARS-COV-2 virus, the applicant has successfully overcome the rejection for the supporting requirements, making Patent No. 327 approved. However, in order to reduce the risk of receiving a refusal opinion or avoid possible invalidation challenges after the patent is approved, when the pharmacological test commonly used by those skilled in the art is not used in a patent application which instead wants to establish a new model to replace the original one, it is recommended that the applicant provide comparative experimental data in the description submitted at the time of application to verify the representativeness of the new model, and specifically state that those skilled in the art can indeed predict the feasibility of the newly established model based on the fully disclosed content of the description.

From Tai E International Patent & Law Office

June 2022