In recent years, disputes over innovative drug patents have continuedly happened. Recently, CNIPA issued an oral examination announcement stating that the patent of Alnylam Pharmaceuticals, Inc. with the application number "2013800639305" and the invention name "PCSK9 iRNA composition and its method of application" was sued for invalidation. It is showed in the announcement that the requester is Li Caihui who is in charge of intellectual property rights of Juntuo Biotech, a subsidiary of Junshi Biotech.

In relation to the progress of this patent case, a Novartis pharmaceutical concerned said that there is no more information to disclose now, all-up progress is based on official information. Junshi Biotech did not give any further reply on the progress of the case.

In recent years, the "patent challenge" disputes over innovative drugs between generic pharmaceutical companies and original pharmaceutical companies have gradually increased, especially the patent dispute between CSPC Pharmaceutical Co., ltd and Roche, Huadong Medicine and Novo Nordisk arousing widespread concern in the industry. At present, as the term of the core patent of the original drug is close to expiration, the generic drug will use the Bolar exception in the patent law to find a way to launch it as soon as possible, and the original pharmaceutical company may prevent it from being launched on the grounds of infringing other patents. Before and after the launch of generic drugs, there was a concentrated outbreak.

In accordance with the Annual Report on Cardiovascular Health and Diseases in China (2021), in recent years, the blood lipid level and the prevalence of dyslipidemia in the Chinese population have shown an upward trend, and the overall prevalence of dyslipidemia in adults is as high as 40.4%. Dyslipidemia, especially elevated levels of low-density lipoprotein cholesterol (LDL-C) is the most paramount independent risk factor for atherosclerotic cardiovascular disease (ASCVD), so the reduction of LDL-C levels can significantly reduce the incidence of ASCVD and Danger of death. At the present stage, the awareness rate, treatment rate and control rate of dyslipidemia in Chinese adults are all at a low level. The current status of lipid-lowering treatment rate and success rate of ASCVD high-risk/very-high-risk groups is of real concern, there are still large clinic demand for lipid-lowering treatment not being met. It is not hard to see that behind Junshi Biotech's patent invalidation request against Novartis Inclisiran is more of a competition for the market share.

Nowadays, there are 3 PCSK9 inhibitors on the market worldwide, namely Evolocumab from Amgen/Astellas, Alirocumab from Regeneron/Sanofi and Inclisiran from Novartis. Many local pharmaceutical companies have also invested in the research and development of this new drug, including Innovent Bio, Junshi Bio, Hengrui Medicine, Akeso Bio are in the clinical stage.

Based on Novartis' 2022 financial report, Inclisiran achieved revenue of US$112 million in 2022. In 2021, Inclisiran sales was just only $12 million. Novartis disclosed in its financial report that Inclisiran is expected to be approved for listing in China in the second half of this year.

As for Junshi Biotech, according to the company’s external reply on investor relations activities, now Junshi Biology’s siRNA drug research and development platform has been initially built with two cornerstones for the success of perfect siRNA drugs, namely drug delivery system, chemical structure modification.

Junshi Bio stated that the clinical trial application of JS401, an siRNA drug targeting ANGPTL3 messenger RNA, jointly developed by the company and its partner Runjia Shanghai, was accepted by the NMPA in February this year. JS401 is potentially the first siRNA drug for this target in China, and it is intended to be mainly used for the treatment of hyperlipidemia. Now there is only one monoclonal antibody drug Evkeeza targeting ANGPTL3 (Evinacumab-dgnb, produced by Regeneron Pharmaceuticals) approved for marketing worldwide, it is applied for the treatment of homozygous familial hypercholesterolemia (HoFH) in children aged 12 and above or in adults) patients, and there is no similar target siRNA drug approved for marketing in the world, which means is benefit for competition.

"SiRNA drug is the active research and development field deployed by the firm. At this stage, the company still focuses on liver targeting, and the company’s focus on indications at early stage are mainly liver targeting and metabolism. Afterwards, the company will further explore the possibility of targeting organs or targets other than the liver based on the existing platform.” said by Junshi Bio.

In recent years, the number of "patent challenge" cases similar to Junshi and Novartis has begun to increase, and the patent strategy of innovative drugs has become one of the more important topics for companies.

At the end of last year, the new generation of "anti-influenza magic drug" Mabaloxavir also triggered a patent dispute between the original pharmaceutical and the first generic drug company. In October 2022, the first generic drug in China, Mabaloxavir Tablets of CSPC Ouyi Pharmaceutical Co., Ltd, was approved for marketing. Soon afterward, Roche Pharmaceuticals issued a public statement on its official Weibo, saying that the "Mabaloxavir Tablets" of CSPC Ouyi Pharmaceuticals was suspected of infringing the patent of Roche Mabaloxavir Tablets.

In the announcement, Roche Pharmaceuticals clearly pointed out that "Ouyi Company's generic drug has been approved by the State Drug Administration does not mean that Ouyi Company can manufacture, sell or promise to sell its generic drug mabaloxavir for the purpose of production and operation. Otherwise, it will constitute an infringement of the above-mentioned patent. As for the Ouyi’s application for the listing of generic drugs, the patentee has filed a patent linkage lawsuit.”

In addition, the patent lawsuit between Novo Nordisk and Huadong Medicine was heard on February 23, 2023. The invalidation application for the core patent of semaglutide CN200680006674 submitted by Huadong Medicine was judged invalid for by the CNIPA on September 5, 2022. For this, Novo Nordisk, the original pharmaceutical company, mentioned in its 2022 financial report that the Chinese patent of the drug will expire in 2026, but it has been judged invalid by CNIPA. The company appeal to the Beijing Intellectual Property Court for this decision which will then enter the stage of intellectual property litigation.

In accordance with Paragraph 5 of Article 69 of the Patent Law of the People's Republic of China (amended in 2008), where to provide information required for administrative approval, manufacture, use, and import patented drugs or patented medical devices, and manufacture, import patented medicines or patented medical devices shall not be deemed as infringement of patent rights.

That is to say, during the patent period of the original drug, other manufacturers can apply for marketing approval for generic drugs, but cannot produce and sell them, otherwise it will be judged as infringement. In fact, after the new patent law implemented on June 1, 2021 established the Chinese drug patent linkage system, patent disputes were also under the centralized jurisdiction of the Beijing Intellectual Property Court, and it has become a major trend to use the system to balance the interests of enterprises. In 2022, "China's first drug patent linkage lawsuit" appeared.

The national patent law has also been constantly improved for the balance of interests, not only to ensure the interests of imported manufacturers, but also to allow drugs developed by local manufacturers to enter the market as soon as possible, so that generic drugs can enter the market when the drug patent reaches the protection period for price deflation of medicines.

From Sina Finance

April 12th, 2023