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"How to plan a patent strategy like Cabilly, which reigned over the antibody drug market"

26 Dec 2022
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Platform technology regaining attention with the revived Hanmi Pharmaceutical’s Efinopegdutide

 

When monitoring pharmaceutical-bio news, certain keywords ring in our ears. Looking back on the past, stem cells, biosimilar, immunotherapy, cell-gene therapy, exosome, microbiome, open innovation, etc. come to mind. Looking at the news these days, platforms seem to be popular.


Although we noticed the word “platform”, why platform technology is so important and how great it is will not be discussed. We believe that the market already knows. When developing or possessing a technology which can be called a platform, the role of patent attorneys is to present opinions on whether to apply for a patent or hide it as know-how, and further provide an opinion on the strategy to acquire a right related thereto when filing a patent application.


What on earth is platform technology?


What is platform technology referred in the pharmaceutical-bio industry? Citing the expression from Bae Jin-Gun, CEO of Baejin Bioscience, “base technology which can derive a large number of candidate substances by applying to existing drugs” can be referred to as platform technology. Let's take a look at the technologies which accords with this definition.


Efinopegdutide, which was exported to Janssen as a treatment for diabesity, was recently magnificently revived as a treatment for nonalcoholic fatty liver (NASH) with a technology transfer (worth USD 870 million) to Merck (MSD). For this, LAPSCOVERY, long-acting platform of Hanmi Pharmaceutical, was applied. Here, efinopegdutide is a product of LAPSCOVERY platform technology (the pipeline to which LAPSCOVERY is applied includes rolontis, efeglenatide, eflapegrastim, etc.).


Looking at other platform technologies of Korean companies, the following seems to be platform technologies which achieved technology transfer: ▲ Dual antibody platform, Grabody, from ABL Bio (technology transferred to Dong-A ST, Dt & SanoMedics, Trigger Therapeutics, Yuhan Corporation, TSD, etc.), ▲ long-acting protein platform, hyFc, from Genexine (technology transferred to Yuhan Corporation, NeoImmuneTech [affiliate company], etc.), ▲ human hyaluronidase SC formulation platform, ALT-B4, from Alteogen (technology transferred to two global pharmaceutical companies), ▲ ADC linker platform, ConjuAll, from Lego ChemBio (technology transferred to Takeda, FOSUN, Iksuda, etc.), ▲ CRISPR/Cas9 platform from ToolGen (technology transferred to Keygen, Thermo Fisher, Monsanto, Optipharm, Orient Bio, NGene, MK Biotech, nSAGE, etc.)


Looking at the platform technologies of overseas companies, the followings come to our mind: ▲ PD-1 original technology from BMS-Ono Pharm (royalty settled in a lawsuit with MSD), ▲ CAR-T cell therapy original technology from BMS-Juno Therapeutics (won in a patent infringement lawsuit claiming the compensation of USD 752 million against Gilead-Kite Pharma; Gilead’s appealing in under way) ▲ ADC platform from Daiichi Sankyo (technology transferred to AstraZeneca 2 times) ▲ VHL-based PROTAC original technology from Arvinas, ▲ CRBN-based PROTAC original technology from C4 therapeutics.


As such, the platform technology itself can be transferred (representatively Legochem Bio, Alteogen, Daiichi Sankyo) based on expandability or generality, or the technology to the pipeline to which the platform technology is applied (representatively, Hanmi Pharmaceutical, Genexine) can be transferred. On the other hand, if a patent for an original technology, which can be seen as a platform like PD-1 or CAR-T, is infringed, there may be filed lawsuits with an astronomical amount. The reason why there is no lawsuit against PROTAC technology is presumed to be due to the fact that Arvinas' pipeline, which is the most advanced, remains in phase 1 clinical trial, and if multiple products are launched, tolls for E3 ligase patents including VHL and CRBN may have to be paid.


Should it be disclosed as a patent? Or be hidden as know-how?


The basic principle of the patent system is to be granted an exclusive right of patent right in return for disclosing one's technology to the public. That is to say, the patent system can be strongly protected by laws, but the contents of technology must be opened in return. In the end, the fact that the contents of technology must be exposed to competitors can be a factor which makes people hesitant to apply for a patent.


On the other hand, know-how is to hide the technology without disclosing it to the outside by filing for a patent, so it can be permanently preserved as one's own technology as long as it is kept secret (e.g., coke manufacturing process of Coca-Cola). However, if the technology is leaked or if the technology can be easily imitated by competitors, the life of know-how will stop then and there.


Meanwhile, the Cabilly patent is the most famous platform patent in the field of therapeutic antibodies. This patent, which derived from the name of the inventor, Shmuel Cabilly, was jointly owned by Genentech and the City of Hope Hospital. Since the first application was filed in 1983 (Cabilly I patent), subsequent patents (Cabilly I and II patents) utilizing the unique continuation application system of the U.S. have reigned the antibody drug market until 2018.


This patent acquired a right to general method for manufacturing recombinant antibodies, which can be mentioned in a textbook of molecular biology, according to which DNA sequences in heavy and light chain antibody variable regions are transformed into host cells and then expressed to produce recombinant antibodies. Because it was practically impossible to avoid this patent in manufacturing antibody drugs, in order to launch blockbuster-class antibody drugs such as Humira on the market, it was necessary to pay royalties for the Cabilly patent. In 2018 alone when the patent lastly existed, it is estimated that Roche (acquired by Genentech in 2009) and City of Hope Hospital, two owners of Cabilly patents, have collected nearly USD 1 billion in royalties.


If in a situation where there should occur infringements like the above-mentioned Cabilly patent, it should naturally be protected as a patent in order to collect royalties.


However, if the patent is registered with a hole through which a competitor can easily escape, even if a patent right is obtained, it is only a good-for-nothing which loses its function as a platform patent. On the contrary, it may expose the core part of technology to competitors, so it may be desirable to keep it as know-how without applying for a patent if you are concerned about such a situation.


As described above, the decision of whether to disclose the platform technology by filing a patent application or hide it as know-how is not to made in a uniform manner. After comprehensively considering various factors like the nature of technology and the maturity of market, etc., it is necessary to work out a detailed strategy which strategically distinguishes between the areas to be patented and the areas to be kept as know-how.


Do you want to get the platform technology patented?


Platform technology entitles a right to the basic technology with generality in the applicable field, but it is actually impossible to prove all specific development forms through experiments. Therefore, a patent specification is prepared and filed only with representative experimental results. From this, there is a high possibility of an extremely difficult tug-of-war with examiners of the Korean Intellectual Property Office over whether a patent right for the entire platform technology can be granted.


It is difficult to say that the examination guidelines for the description requirements of bioscience patents are well established by country. This is because the issue of deciding how far a platform patent should be acknowledged is intricately intertwined with complicated issues as to what extent the reproducible range of a person skilled in the art should be acknowledged from the experimental contents in light of the changing level of biotechnology, how far the exclusive right should be allowed compared to the contribution of inventor, etc.


Therefore, it is recommended to first carefully review the examination cases accumulated in each country and then determine the scope of experimental contents to be described in the specification. It is also a good way to make the most of the system guaranteed by the Patent Act, such as properly reflecting the contents of papers announced at the time of filing in the specification or using the preferential examination system to receive examination results before the disclosure of application and then consider re-application, etc.


If the application is filed as a platform technology but the rights are registered with limitation, there may occur a tragic incident which opens the possibility of evasion by third parties as a result. Therefore, it is desirable to consider a good patent strategy in advance rather than rushing to apply for a platform patent.

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