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“Lazertinib's meticulous patent strategy which only the patent attorneys can see”

26 Dec 2022
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Completion of patent portfolio by technology transfer step: Genosco → Yuhan Corporation → Janssen

 

In Jan. 2021, lazertinib (LeclazaTM) was conditionally approved, obtaining the glorious title of the 31st new drug in Korea. This is a big event in the history of new drug development in Korea, which has been rather long for a while since tegoprazan (K-capTM) of HK inno.N (formerly CJ Healthcare) was approved. I would like to evaluate it as the first milestone established by the brilliant lineup consisting of Genosco/Oscotech- Yuhan Corporation- Janssen (J&J).


Lazertinib is attracting attention as a rising star in the non-small cell lung cancer (NSCLC) market, where IRESSA, TARCEVA, and TAGRISO stand out firmly, by setting EGFR (Epidermal Growth Factor Receptor) T790M mutations as therapeutic targets (3rd generation) with a tyrosine kinase inhibitor (TKI).


As a patent attorney working in the healthcare field, I could not hold down a desire to delve into the patents related to lazertinib. In particular, as a development progressed and licensing deals were made twice, I was very curious about which patents were applied when.


Substance patent by Genosco/Oscotech


The substance invention of lazertinib was tracked. It confirmed that after the US provisional application (US 62/063,394) was made on Oct. 13, 2014, the US regular application (US 14/881,930) and PCT application (PCT/KR2015/010784) were completed on Oct. 13, 2015 (independent claims among the claims of the US regular application and the PCT application are established in Markush type to cover 145 aminopyrimidine derivatives (indicated in a red circle)).



Considering the fact that technology transfer between Genosco/Oscotech and Yuhan Corporation became effective on July 29, 2015 (based on the information disclosed by Oscotech), it is presumed that the provisional application was made by Genosco/Oscotech (Oct. 13, 2014), and the regular application was made by Yuhan Corporation (Oct. 13, 2015). What is surprising here is that the technology transfer was completed about 7 months after the provisional application by Genosco/Oscotech. Considering the fact that it takes quite a lot of physical time to prepare the term sheet, perform due diligence, and negotiate the actual contract terms, etc., the technology transfer was completed at a very surprising speed. This is presumably because significant potency data have already been accumulated before and after the provisional application (comparative experiments with afatinib and erlotinib are disclosed in the specification of regular application as follows).



Subsequent patents handed over to Yuhan Corporation


The necessity of life cycle management (LCM) was discussed in the editorial dated Jan. 2020 (see, Hit News, Humira with different portfolios in the US vs. European patents, what are the results?) It is mentioned once again that there are follow-up patents for LCM or evergreening as follows: ▲ use invention for pharmaceutical following indication expansion or drug repositioning ▲ use invention for pharmaceutical for a new patient group ▲ use invention for pharmaceutical limited to method and dosage of administration ▲ salt invention ▲ crystalline form/solvate/co-crystal inventions, ▲ formulation (composition) invention, ▲ manufacturing method invention, etc.


Yuhan Corporation, which received the technology transfer of lazertinib, also did not neglect LCM. It seems that they started working on a follow-up patents after licensing-in in 2015 and looking into the possibility of development or success. Specifically, a total of four inventions were filed at three-month intervals in 2018, including one invention of salt (mesylate)/crystalline form (KR 10-2018-0044850) in April 2018, two inventions of manufacturing method in July 2018 (KR 10-2018-0086376 and KR 10-2018-0086377), and one invention of formulation (composition invention) (KR 10-2018-0124171) in October 2018, and then succeeded in licensing-out to Janssen (J&J) in November. 2018.


Total contract size of L/O was about KRW 1.4 trillion (USD 1.255 billion), of which lazertinib substance invention took up the most part, but there is no doubt that four subsequent patents helped to increase the value of technology by even a little.


Through the above successful L/O of lazertinib and additional L/O of other pipelines, Yuhan Corporation has become synonymous with open-innovation, and proposed a new business model (BM) for new drug development for domestic pharmaceutical companies.


Janssen finalizes subsequent patents based on clinical data


Janssen, which had the EGFR/c-MET dual antibody, amivantamab (JNJ61186372), needed a pipeline that could supplement this, and it seems that lazertinib was selected as a partner for its combined use. Since the end of 2018, a single clinical trial of lazertinib and a combined clinical trial of lazertinib + amivantamab have been conducted, and follow-up patents based on the clinical data derived therefrom have been confirmed.


Specifically, in May 2020, a patent for method and dosage of administration for lazertinib alone (US 15/931,626) was filed as a joint application between Janssen and Yuhan Corporation, and a patent for combined administration of lazertinib and amivantamab (US 15/931,726) ) was filed exclusively by Janssen.


In summary, it is understood that 1) Genosco/Oscotech/Yuhan Corporation applied for substance invention and laid the foundation, 2) Yuhan Corporation applied for salt/crystalline form invention, manufacturing method invention, formulation (composition) invention, etc. to increase the value, and 3) in the clinical phase, Yuhan Corporation/Janssen completed their patent portfolios. The case of lazertinib will bring us one step closer to a patent strategy for successful protection of low molecular weight synthetic drugs.


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