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“Microbiome, which is about to evolve into drugs, also starts to be involved in a patent lawsuit."

26 Dec 2022
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B. infantis strain involved in a patent infringement lawsuit against Abbott using HMO

 

Microbiome refers to a community of microorganisms. The fact that microbiome which plays a beneficial role exists in the human intestines has been known for a long time, and various types of probiotics are sold at the market in the form of health functional foods. Furthermore, as the correlation between a specific microbiome and various diseases including cancer, infectious disease, atopic dermatitis, intestinal disease, metabolic disease, and Alzheimer's disease has been identified one after another, the potential for development as a drug (pharmabiotic) is also rapidly rising. Taking into consideration the fact that investment by global pharmaceutical companies is very active and that several microbiome pipelines (B-244, LACTIN-V, Oxabact, Rebiotix, RBX-2660, SER-109, etc.) in the US are already in phase 3 clinical trials, it seems that the day is not far off when the microbiome will emerge as the next-generation biopharmaceutical leader.


In Korea, interest in the microbiome can be felt very hot recently. Chong Kun Dang Healthcare is hitting a jackpot in the market with Lactofit, and existing pharmaceutical companies as well as bio-ventures including Chunlab, Kobiolab, Genome & Company, Cellbiotech, and MD Healthcare are targeting the microbiome drug market.


As articles related to microbiome are coming out every day, and this editorial aims to look at the patent issues of microbiome from the perspective of a patent attorney.


Naturally, patent disputes exist for microorganism inventions as well.


Dr. David Mills and his team at UC Davis University have found that the B. infantis strain, a subspecies of bifidobacterium longum, plays a key role in restoring the microbiome in healthy intestines of newborn babies. In addition, a follow-up study revealed that B. infantis strains can grow well in the intestines of newborn babies only when human milk oligosaccharides (HMO) are ingested as prebiotics. Based on this, Davis Mills and others founded Evolve BioSystems, a microbiome biotech company, in 2012, and launched EVIVO®, a product containing B. infantis strain and HMO. This product was used as an ingredient to restore intestinal imbalance in newborn babies in hospital neonatal rooms. The patent for the above invention was registered in 2012 under the name of UC Davis University and licensed to Evolve BioSystems.


Meanwhile, Abbott has been selling Similac®, a powdered milk product, and recently announced the launch of Similac Probiotic Tri-Blend, a product containing B. infantis strain and HMO.


In response, Evolve BioSystems, along with patent holder UC Davis, filed a patent infringement lawsuit in August of this year, alleging that Abbott's product infringed the above patent right (Case: 1:19-cv-05859).


The course of this lawsuit remains to be seen, but the case of related patent disputes suggests that we need to prepare against patent issues beforehand in the upcoming microbiome drug era. It is essential to thoroughly examine whether it is possible to freely operate other companies' patents (freedom-to-operate) from the microbiome development stage.


Do you want your microorganism invention to be protected by a patent?


In the patent, “microorganism invention” is a broad concept inclusive of all inventions that use microorganisms directly or indirectly, including not only newly discovered microbial strains but also new uses, manufacturing methods, storage methods, and culture conditions (culture medium, prebiotics, etc.) of known strains. In the healthcare market, the microbiome is mainly being developed in the form of health functional foods and drugs, all of which can be protected by the above “microorganism invention”.


Specifically, if it is a novel microorganism, the microorganism itself can be protected as a substance invention, and a specific population of microorganisms can be protected by a composition invention (however, patent eligibility for natural products differs from country to country). In addition, if new indication is revealed with a known microorganism, it may be protected as a use invention for pharmaceutical. In addition to inventions on microorganisms themselves, specific combinations, uses, manufacturing methods, and culture conditions (or prebiotics) of known microorganisms can also be protected by patents. For example, a patent may be granted for prebiotics which create an environment in the intestines for a particular microbiome to grow favorably.


First, let's assume a case of discovering a novel microorganism and confirming its usefulness (e.g., beneficial function exerted in the intestine). Because the patent specification should be prepared to an extent that a person skilled in the art can easily understand and reproduce the invention, the applicable microorganism should be readily available. Therefore, collection, separation, purification, screening methods, etc. for the applicable microorganism should be described in detail as much as possible in the specification. However, due to the nature of microorganism invention, it is sometimes difficult to obtain microorganisms no matter how detailed the specification is described. Therefore, the patent system selects a microorganism depository institution and has a system to deposit microorganisms when applying for a patent (Article 7 of the Budapest Treaty and Article 2 of the Enforcement Decree of the Korean Patent Act).


The microorganism depository institution preserves the microorganisms for a long time while checking the survival of deposited microorganisms. Deposited microorganisms can be distributed to anyone for research purposes, and for commercial purposes, they can be distributed only if the patent holder's permission is obtained (Article 4 of Patent Act Enforcement Decree). Through the microbial deposit system, the patent holder can avoid the risk of patent being invalidated due to the difficulty in obtaining microorganisms, and third parties can use the microorganisms effectively without infringing the patent right, so it can be said that it is a reasonable system which compromises the balance between the two.


There are four institutions in Korea for depositing microorganisms as follows: the KRIBB Korean Collection for Type Cultures (KCTC) under the Korea Research Institute of Bioscience and Biotechnology, the Korea Agricultural Culture Collection (KACC) under the National Institute of Agricultural Sciences, the Korean Culture Center of Microorganisms (KCCM), the Korean Cell Line Research Foundation (KCLRF), and some of them are also available for international deposits in addition to domestic deposits. It would be desirable to make an international deposit for an invention which considers overseas application as well.


Now let’s consider a case where microorganisms are already known. If the same microorganism is known, the microorganism itself is not novel and cannot be patented (in this case, it will have to be made into rights as a use invention for pharmaceutical, etc.). However, a novelty is acknowledged if the subspecies or strain is novel even if it is allogenic species of a known microorganism. However, since the name of strain can be assigned arbitrarily by the researcher who has isolated and identified it, it is a dangerous idea to think that a novelty can be acknowledged only by the difference in the strain name. Even if a novelty is acknowledged in this way, the patent may be invalidated if a patent dispute arises and the identity of strain is confirmed. Therefore, in order to have a novelty of strain be acknowledged, it is necessary to comprehensively consider the morphological classification of strain, the sample collected, and the mycological properties, etc., and if the 16s rRNA sequence, which is a uniquely conserved sequence for each microorganism, is different from the existing strain, it is a strong basis for a novelty to be acknowledged.


In the meantime, if an allogenic strain is already known, there may arise a controversy on whether the inventive step may be acknowledged even for a novel strain. As long as there is no significant difference in mycological properties, it is necessary to prove the effect superior to the known strain through an experiment comparing the effect (pharmacological activity or intestinal safety, etc. in the case of microbiome) caused by the use of microorganisms under the same conditions as the known strain.


In the end, it will be possible to prepare a good specification by identifying the characteristics of the known microorganism closest to the invention and considering in which part the microorganism to be patented is differentiated.

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