Korean pharmaceutical companies are struggling to develop new drugs out of natural products, as the Nagoya Protocol recently took effect. The protocol enhances each nation’s rights to biological resources that go into food, medicine, and cosmetics.
Natural product-derived drugs refer to medicines developed with acting ingredients extracted from animals, plants, and minerals. The World Health Organization forecasts that the market of national product-extracted medication will grow to 400 trillion won ($354.1 billion) by 2023.
Many Korean pharmaceutical companies have also entered the natural product-based drugs market.
Dong-A ST enjoyed popularity with its gastritis therapy Stillen, which used Artemisia herb as its main ingredient. Now, the drugmaker is working on investigational treatments including DA-9803 (Mori fructus, Poria) and DA-9801 (Dioscorea nipponica Makino, Dioscoreae Rhiozoma).
The Korean firm licensed out the technology for DA-9803, built a local cultivation facility and secured a stable supply chain of the ingredient in preparation for commercialization.
Yungjin Pharm is developing YPL-001, extracted from a plant named “Veronica rotunda var. subintegra,” to treat chronic obstructive pulmonary disease (COPD).
Natural product-derived drugs already available in the market include GC Pharma’s Shinbaro, SK Chemicals’ Joins, Ahngook Pharm’s Synatura, and Korea PMG Pharm’s Layla.
According to IQVIA data, Layla sold 16.1 billion won, Stillen, 9.3 billion won, and Shinbaro, 6.3 billion won in 2017.
Since the Nagoya Protocol took effect in August, however, each country’s rights to biological resources have been reinforced.
Under the Nagoya Protocol, users of genetic resources in medicines and cosmetics should share profits from those generic resources with the source providers.
If drugmakers want to produce drugs and functional foods using genetic resources including natural materials, they must negotiate with companies to pay royalty within limits set by the government of each country. As Korea is a user of generic resources, not a holder, it is expected to pay 60-70 billion won royalties per year.
The ratification of the Nagoya Protocol not only creates the issue of royalty payment but that of patent registration as well.
|Yoon Ju-byeong, the principal researcher at the biological research team at Dongwha Pharm, speaks about how to develop biological drugs by utilizing overseas biomaterials and supporting new materials, at a forum in Seoul on Tuesday.|
Yoon Ju-byeong, the principal researcher at the biological research team at Dongwha Pharm, voiced difficulties in patent-related issues when developing natural product-derived medicines.
His comments came at a forum on how to develop biological drugs by utilizing overseas biomaterials and supporting new materials, jointly organized by the Korea Pharmaceutical and Bio-Pharma Manufacturers Association (KPBMA) and the National Institute of Biological Resources (NIBR) on Tuesday.
Dongwha Pharm is working on a new drug using Justicia procumbens, commonly known as Water Willow, according to Yoon.
Although water willow is not on the list of Korean Pharmacopoeia (KP) or Korean Herbal Pharmacopeia (KHP), the Ministry of Food and Drug Safety designated its leaves as “a possible part of food material with a certain effect.”
The habitat of Justicia procumbens includes Korea, Japan, China, India, and Southeast Asia.
Dongwha collected and analyzed the plant from 16 regions, including China, and found that they satisfied with the ministry’s guidelines (Pearson’s product moment correlation coefficient). The company derived a new drug candidate DW2008S from the plant and confirmed that the experimental drug was effective in allergic diseases and airway constriction in animal tests.
However, the Korean Intellectual Property Office (KIPO) refused to approve the company’s application for a patent on DW2008S' efficacy in allergic diseases.
The KIPO cited the existing asthma-treating effect of Justicia transquebariensis L., a plant within the same genus of Justicia procumbens, as the reason for refusal. Plants under the same genus have similar biosynthetic pathways and pharmacological effects, the KIPO said. Thus, the KIPO could not recognize Justicia procumbens’ novelty, it said.
Dongwha had to purchase 19 plants that could be bred out of Justicia plants through a foreign plant export bank to analyze the compositional structure and effectiveness of all plant extracts, Yoon said. The company had to prove that Justicia procumbens had a superior efficacy than the other plants under the same genus, he said.
Dongwha’s case shows that many variables come into play in developing natural product-derived drugs, besides the royalty issue, under the Nagoya Protocol.
“Before the Nagoya Protocol took effect, we used to focus on the plantation sites and production volume of the ingredients for national product-derived drugs,” a pharmaceutical source said. “After the ratification of the protocol, we are finding out royalties and legal issues on the registration and management of genetic resources. We need a clearer guideline and preparation.”
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