"Medicine King" Xiu Meile's Patent Great Wall Attack and Defense

Humira (trade name Humira), or adalimumab (Adalimumab), is an anti-TNF-α drug developed by the world's top pharmaceutical giant AbbVie, which mainly treats rheumatoid arthritis, psoriasis and Crohn's disease. At present, Humira has obtained 14 indications worldwide. Since it was first approved by the FDA in 2002, Xiumile has accumulated nearly $100 billion in sales revenue, and to this day, it has set a new annual sales record for a single drug with a double-digit annual growth rate. Undoubtedly, it has been dubbed the title of "drug king. Global sales in 2017 reached $18.4 billion, of which $6 billion was contributed by markets outside the United States, mostly from Europe.

As the core patent US6090382(Human Antibodies That Bind Human TNF Alpha) in the United States has expired on December 31, 2016, and the patent in Europe has also expired on October 16, 2018 this week. Faced with such an attractive big cake, major biopharmaceutical companies around the world are speeding up the development of their own biosimilar drugs, and successively used the Inter Partes Review (IPR) to file a patent invalidation request against AbbVie, eyeing this huge market.

Impact of core patent expiration

In order to prevent other biosimilar companies from seizing the market after the expiration of the patent for Xiumile, AbbVie has applied for more than 70 patents in the United States, covering compounds, preparations, preparation processes, indications, usage methods, etc., building a "Great Wall" in the patent field, and there are multiple combined patents, whose expiration dates are generally between 2022 and 2034. Any company wants to copy Xiumile, either bypass the subsequent patent application or wait for the patent to expire, making it more difficult to develop Sumera's biosims.

Biosimilar drugs are surging.

Even if research and development is not easy, in the face of such a huge cake, the challenger is still one after another.

In addition to the launch of the world's first biosimilar Exemptia by Zydus-Cadilla in India in December 2014, many biosimilar biosimilars (biosimilar), imitation products (biosuperior) and follow-up products (follow-on-biologics) are under development.

In September 2016, the FDA approved Amgen's Xumila Biosimilar Amjevita (adalimumab-atto). In August 2017, the European Medicines Agency approved the Imraldi of Sumeria bio-similar drugs jointly produced by Samsung Bioepis and Biogen, which is also the second Sumeria bio-similar drug after the Amjevita of Amgen in the European market. According to the Financial Times, the big names preparing to enter the market include Amgen, Sandoz, Biogen and Samsung Bioepis, all of which have been approved by European regulators as replacements for Sumeria.

In fact, not only is the undercurrent surging in the international market, but also the imitation of Xiu Merit has already begun in China. According to statistics, there are 21 imitation manufacturers of Xiu Merit in China, pioneers such as Xinda Biology have advanced to the clinical stage, and both Xinda Biology and Baiaotai have reached the clinical stage 3, and the indications are ankylosing spondylitis.

patent attack and defense war

1. Patent Challenges

Xiumile's patent portfolio is undoubtedly one of the biggest obstacles for major biopharmaceutical companies to develop Xiumile generic drugs, so Xiumile has been repeatedly filed patent invalidation requests, these biosimilar companies launched a wave of attacks, but also later AbbVie launched a "patent dance" counterattack one of the reasons.

The first to launch a patent challenge against the drug Xumile was Amgen (Amgen). In June 2015, Amgen filed a patent invalidation request with the U.S. Patent and Trademark Office for the US8916157 and US8916158 of AbbVie's two Hemeile preparation patents on the grounds of lack of novelty and creativity. However, the U.S. Patent and Trademark Office found that Amgen did not prove the reasonable possibility of its claim and rejected the invalid request in January 2016. It is worth mentioning that due to the rejection of the patent invalidation request, the two patents involved in the case have undoubtedly become more valuable to AbbVie, which is why in the subsequent patent dance between the two parties, AbbVie will select the patent US8916157 to enter the scope of litigation-related patents covered by the first infringement lawsuit.

After Amjin, in November 2015, Coherus filed a review procedure against AbbVie: first, it filed a request for invalidation of the patent US8889135, on the grounds that the ingestion dose claimed by the patent was common knowledge in the field; Then in December of the same year, it filed a request for invalidation of the other two patent US9017680 and US9073987 involving rheumatoid arthritis indications. At the same time, boehringer-Ingelheim Corporation (BI) has also proposed a bilateral review procedure for the patent US8889135 on the grounds that claims 1 to 5 of the patent do not involve an inventive step. Different from Amjin's rejection, the U.S. Patent and Trademark Office believed that Coherus and BI proved its claim reasonable and could be reviewed. Therefore, on May 24, 2016, the Patent Office decided to review the above-mentioned patents involved. On July 6, 2016, the U.S. Patent and Trademark Office's Patent Trial and Appeal Board (PTAB) of the U.S. Patent and Trademark Office, after multi-party intellectual property review, the five "135 patents" challenges filed by BI and Coherus against Xiumile were decided in support. AbbVie stated in an email that he would appeal to PTAB against the result of the patent judgment. In fact, this is what AbbVie has to do, because the "135 patent" covers the frequency of treatment of Sumeira. And a number of key information such as dosage used, this patent is a city that must be captured for competitors who develop Sumeira bio-similar drugs.

Previously, in order to prevent other biosimilar companies from seizing the market after the expiration of the patent, AbbVie specially applied for two patents for injection methods for rheumatoid arthritis and psoriasis, and extended the patent time to 2022 and 2023 respectively. Samsung Bioepis, a biopharmaceutical company owned by Samsung, and its European commercialization partner Biogen filed a patent invalidation lawsuit against it.

2. Patent Dance

The U.S. "Biologics Price Competition and Innovation Act" (BPCIA) has formulated a system to resolve patent disputes between original research drug companies and generic drug companies. The system is called "patent dance". Its procedures can be roughly divided into three parts, namely, information exchange procedures, patent scope negotiation and litigation, and pre-market notification.

The information exchange procedure refers to that after the generic drug company submits the drug review to the FDA, it needs to provide the original research drug company's complete copy of the application documents and manufacturing process and other relevant information. After receiving the information, the original research drug company determines which patents the generic drug company has infringed and submits the patent list of infringing patents to the other party. After receiving the list, the generic drug company can also submit the patent list that it considers reasonable, the parties then entered into a patent scope negotiation session with the aim of defining the scope of litigation-related patents covered by the first infringement lawsuit.

After Amjin's biosimilar ABP100 passed FDA review, on August 4, 2016, AbbVie filed a patent infringement lawsuit against Amjin, accusing the generic ABP100 of infringing a number of patent rights of Xiumile, and Xiumile's "patent dance" kicked off.

Amnesty Company disclosed relevant information to AbbVie Company first, and then AbbVie listed 61 infringed patents from more than 100 patents related to drug Xiumile according to the materials. Both parties selected 6 patents from the list, of which 2 patents were selected by both parties at the same time, so the first infringement lawsuit involved 10 patents. From the perspective of the selected patents, almost all the patents selected by Amjin are preparation process patents. According to speculation, one reason is that Amjin itself is an expert in biopharmaceuticals and has greater confidence in the field of drug preparation process. The other reason is that it is easier to circumvent the design of the preparation process patents; while the patents selected by AbbVie cover a wide range, including preparations, preparation processes, usage methods, etc, obviously, AbbVie's strategy is to protect Humilo in all its aspects, and as mentioned above, AbbVie also chose the patent US8916157 involved in the two-party review process that Amjin first filed to increase his chances of winning.

At present, in the U.S. market, AbbVie has successively reached settlement agreements with Amgen, Samsung Bioepis and Mylan, and the biosimilars developed by the latter three are allowed to land in the United States as early as January 31, June 30 and July 31, 2023, respectively.

Conclusion

Unlike generic chemical drugs, exact imitation of biotech drugs is almost impossible, so we often use the term "biosimilar" instead of "generic" for biotech drugs. It can be considered that even if Xiumile is "imitated", it is difficult to be "copied", because I am afraid no drug can win more than 10 indications as easily as Xiumile. In addition, although the core compound patents of Xiumile have lost protection in the United States and Europe, it is still shaded by more than 70 other patents, preventing the research and development process of competitors, even if the patent challenges of generic pharmaceutical companies pass, generic drug applications have been successfully reviewed by the FDA, and there are still dozens of remaining patents waiting to be challenged. In the long litigation tug-of-war, Xiumile can continue to enjoy the throne of drug king and ensure that the champion will not be left behind. Based on this, AbbVie's Chairman and CEO Richard A. Gonzalez optimistically stated that Xiumile will usher in its sales peak in 2022. As for whether it can be achieved, we will wait and see.