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20 April 2021BiotechnologyThomas Moga

The curious case of Wuhan’s Institute of Virology and remdesivir

The Patent Law of the People’s Republic of China first went into effect on April 1, 1985. It has been amended three times with a fourth amendment scheduled to take effect on June 1, 2021.

The Chinese patent system includes an invention patent, similar to the utility patent of the US. The invention patent application is substantively examined by patent examiners to determine if the invention is novel, inventive, and has “practical applicability”.

The author found that personal interviews with Chinese patent examiners can be effective in advancing prosecution because many examination problems are the result of translation confusion.

Another type of patent in China, the utility model patent, has the same requirements although it is not ordinarily subjected to substantive examination prior to grant. The US has no parallel type of patent.

The last three and a half decades witnessed the development of China’s patent system from one providing only the most basic protection to a modern and generally comprehensive approach to protecting a range of inventions, utility models, and designs.  The fourth amendment provides further improvement to this system by introducing several new and expanded aspects to patent protection, some of which are directed to biotechnology. It is these improvements in particular which help to set the stage for better pharmaceutical protection in China. But many of the changes related to the protection of drugs may be tested given unexpected developments, such as the curious case involving Gilead, remdesivir, and Wuhan’s Institute of Virology.

Amendments to the patent law

The fourth amendment to the Patent Law leaves most features related to the patenting of biotechnology intact. For example, the prohibition on the patenting of methods for the diagnosis or the treatment of diseases (article 25) remains unchanged.

Also unchanged is the requirement that an applicant must disclose the “direct source and the origin” of genetic resources if the application is based on genetic material (article 26).

The amended Patent Law includes several important changes. Some of these are directed to increased statutory damages and increased damages for willful infringement while others are directed to patent term compensation, patent term extension, and the highly anticipated (and long overdue) system of patent linkage.

More changes

Several other important amendments appear in the amended Patent Law, such as provisions for patent term compensation. According to the amended article 42, when four years have passed from the invention patent application date and three years have passed from the date on which the request for substantive examination was filed when the patent is granted, the patent administrative organ under the State Council shall, upon the patentee’s request, provide compensation for the duration of the patent right for unreasonable delay in the process of granting, unless the unreasonable delay was caused by the applicant.

Another important amendment to the Patent Law relates to patent term extension for pharmaceutical patent applications. Again, according to amended article 42, in order to compensate for the time taken for the review and approval for the marketing of new drugs, the patent administrative organ under the State Council shall, upon the request of the patentee, provide compensation for the duration of the patent right for new drug-related invention approved for marketing in China. The compensation period shall not exceed five years, and the total effective duration of the patent right shall not exceed 14 years after the new drug is approved for marketing.

Patent linkage

In the US, pharmaceutical patenting requires two agencies to coordinate efforts—the patent granting authority (the US Patent and Trademark Office) and the drug approval and oversight authority (the US Food and Drug Administration).

Introduced in the US in the Drug Price Competition and Patent Term Restoration Act of 1984 (the Hatch-Waxman Act), patent linkage associates (or “links”) marketing approval of generic drugs to the term of the patented pharmaceutical.

China’s introduction of a patent linkage system attempts to fulfil its obligation under the 2020 US-China “Phase One” trade agreement.

Drug marketing

The amended Patent Law introduces new article 76, which provides that during the review and approval for drug marketing, where the applicant for a drug marketing licence and a related patentee or person of interest have disputes over the patent rights related to the drug applying for registration, the concerned parties may appeal to the People’s Court and request it to determine whether the technical solutions related to the drug applying for registration fall within the scope of protection of a patent for drug of others.

This article also provides that the applicant for drug marketing approval and the patentee or the person of interest may ask for administrative adjudication of the patent administrative organ under the State Council regarding the dispute over patent rights related to the drug applying for registration.

The drug regulatory administration under the State Council, in conjunction with the patent administrative organ under the State Council, shall formulate specific measures for resolution of disputes over patent rights during the handover period of reviewing and approval for a drug marketing licence and the drug marketing licence application stage, which shall be implemented after the approval of the State Council.

“Recent patent application activity of China’s Wuhan Institute of Virology provides some insight into the state of the pharmaceutical industry in China.”

By resolving patent disputes between the innovator and generic drug companies early, time can be saved in the rollout of generic drugs when patent terms end. Article 75 completes the dispute resolution process that began with the third amendment to the Patent Law in which a US-style Bolar exemption was introduced. According to this provision, neither use of the patent for purposes of scientific research and experimentation nor the offer of information needed in the administrative approval to manufacture, use and import patented drugs or patented medical equipment and specially manufacture and import patented drugs or patented medical equipment for him is deemed patent infringement.  This provision protects generic drug makers from liability as patent infringers. While not entirely parallel with the US system, China’s amended Patent Law provides a clearer way forward for generic drug manufacturers by providing a basic patent linkage system.

Patent protection and the Wuhan Institute of Virology

Whether incentivised by the anticipated changes to China’s Patent Law or not, recent patent application activity of China’s Wuhan Institute of Virology provides some insight into the state of the pharmaceutical industry in China.

China’s first COVID-19 vaccine patent application was filed on March 18, 2020. While ordinarily taking two or three years, the application process proceeded at an astonishing rate most likely due to its being a “sensitive” and thus exceptional case, resulting in a patent grant on August 11, 2020.

Enter the Wuhan Institute of Virology and Gilead Science’s patented antiviral pharmaceutical, remdesivir. This drug functions by preventing an RNA-based virus from reproducing by interfering with replication of its spiral genome. It was first developed by Gilead in response to the Ebola virus with limited success. However, remdesivir proved effective in the treatment of many coronaviruses.

Gilead Sciences obtained two patents for remdesivir—US patent nos. 9,724,360 and 9,949,994, each titled “Methods for Treating Filoviridae Virus Infections”. Secondary patent filings in China include application nos. 107074902 and 110636884. In June 2020, Gilead was granted US patent 10,695,361 for “Methods for Treating Arenaviridae and Coronaviridae Virus Infections”. Several foreign counterparts to this application were filed, including pending Chinese application number 108348526.

While no reference is made in the ‘361 patent to COVID-19 as it was filed before the outbreak, in vitro and animal studies already proved remdesivir’s value in treatment of coronaviruses.

The preamble of claim 1 of the ‘361 patent specifies “a method for treating a Coronaviridae infection in a human in need thereof” while dependent claim 19 is directed to “the method of claim 1 wherein the Coronaviridae infection is caused by a Coronaviridae virus selected from SARS, MERS…”

After the outbreak of COVID-19 in China, Gilead shipped samples of remdesivir to Chinese hospitals to determine its effectiveness as a treatment for COVID-19. Studies of these samples of remdesivir by the Institute of Virology demonstrated that by combining remdesivir with chloroquine, a very old treatment for malaria, an effective treatment against COVID-19 was obtained. The institute then had a Chinese invention patent application prepared and filed with China’s patent office.

The institute’s patent application remains pending but Gilead’s work may stand in the way. For example, Gilead’s ‘361 patent, filed in 2015, disclosed a treatment method for a coronavirus infection. It also disclosed use against SARS and MERS. The immunomodulatory effects of chloroquine are known.

Thus, an argument can be made that it would have been obvious either to use remdesivir alone in the treatment of COVID-19, or to use it in combination with chloroquine. The institute may successfully counter obviousness by showing unexpected results against COVID-19 through the use of COVID-19 alone or combined with chloroquine.

Yet even if the institute succeeds in obtaining patent protection, it will not be able to use remdesivir (once Gilead’s Chinese patents are issued) in its treatment method unless a licence is first obtained from Gilead. The final chapter in this story has yet to be written.

Thomas Moga is a senior counsel at Dykema. He can be contacted at:  tmoga@dykema.com


More on this story

Americas
28 May 2020   The PrEP4All campaign has argued that the US government should own joint patent rights for remdesivir, the Gilead Sciences antiviral which is the only drug approved anywhere for treating COVID-19.
Asia
21 July 2020   Police in Mumbai and Hyderabad have arrested 14 people on suspicion of distributing black market remdesivir at five times its retail price.

More on this story

Americas
28 May 2020   The PrEP4All campaign has argued that the US government should own joint patent rights for remdesivir, the Gilead Sciences antiviral which is the only drug approved anywhere for treating COVID-19.
Asia
21 July 2020   Police in Mumbai and Hyderabad have arrested 14 people on suspicion of distributing black market remdesivir at five times its retail price.