• Asian Journal of Innovation and Policy
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• v.8 no.2
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• pp.180-207
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• 2019

This article explores the historical evolutionary process of the biopharmaceutical industry of Korea, and how intentional and unintentional policy interventions have triggered the creation of the industry's system dynamics and paved the way for the generation of a few global leading products, including biosimilar, as well as next-generation therapeutics of gene and cell. The policies cover the simple technology transfer of API synthesis to overcome the endemic parasitic disease, new substance patent adoption and new drug development consortia, human resource development, various national initiatives influenced by the Human Genome Project, and venture promotion schemes. The scope and implementation tools under these policies have been aligned and refined to transform traditional fine chemical-based pharmaceuticals, to stimulate large companies' participation and to create technology-based venture companies in the biopharma business of Korea.

• Journal of Life Science
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• v.21 no.11
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• pp.1652-1657
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• 2011

The production of blood cells is regulated by more than 20 different growth factors, called hematopoitic growth factors. These factors have been produced in prokaryotic and mammalian systems for their clinical use. Glranulocyte-Colony Stimulating Factor (G-CSF) is an important therapeutic factor for cancer patients as well as patients with congenital conditions. These patients do not have enough neutrophils and have a high risk of infection. Two groups of recombinant G-CSF have been used to specially treat cancer patients after chemotherapy because chemotherapy induces neutropenia, a major side effect of chemotherapy drugs. Here, structural and biological characteristics of G-CSF are presented. In addition, the relationship between chemotherapy and neutropenia, which is a severe reduction of neutrophils in the blood, and clinical application of G-CSF is discussed. Recombinant G-CSFs are grouped in two forms. Non-glycosylated G-CSF, filgrastim, is produced in Escherichia coli and glycosylated G-CSF, lenograstim, is produced in Chinese hamster ovary cells. Differences in structure and biological activity are compared and challenges for biosimilar production are also highlighted.

• Journal of Life Science
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• v.30 no.11
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• pp.1012-1020
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• 2020

Remicade is a therapeutic biosimilar natural antibody in which the mouse variable domain has been linked to the human constant domain. It is a chimeric monoclonal antibody specific to tumor necrosis factor-alpha (TNF-α) and has been developed for the treatment of rheumatoid arthritis. To investigate the biological activity of the Remicade antibody, we carried out a bioinformatics study using a protein data bank to characterize the TNF-α antigen binding mechanism of the Remicade natural antibody. Because the production of the Remicade antibody is often limited by genetic instability of the natural antibody-producing cell, we generated a Remicade single-chain variable domain fragment antibody (Remicade) in which a heavy chain variable domain (VH) is joined with a light chain variable domain (VL) by a polypeptide linker. Furthermore, Remicade was fused to a leucine zipper (RemicadeScZip) for higher production and higher antigen-binding activity than Remicade. The Remicade and Remicade ScZip were expressed in Escherichia coli and purified by a Ni⁺-NTA-agarose column. As expected, the purified proteins had migrated as 28.80 kDa and 33.96 kDa in sodium dodecyl sulfate-polyacrylamide electrophoresis. The TNF-α antigen binding activity of Remicade was not observed by ELISA and western blot. In contrast, RemicadeScZip showed antigen-binding activity. Additional bio-layer interferometry analysis confirmed the antigen-binding activity of RemicadeScZip, suggesting that the leucine zipper stabilized the folding of RemicadeScZip in a denatured condition and improved the TNF-α antigenbinding activity.

• Journal of Korea Multimedia Society
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• v.18 no.9
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• pp.1105-1117
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• 2015

During the last decade, the business infrastructure has become digital with increased interconnections among products, processes, and services. Across many firms spanning different industries and sectors, digital technologies are fundanmentally transforming business stratiges, business processes, firm capabilities, productes and services, and key interfirm relationships in extended business networks. With the emergence of smartphones, the paradigm of the ICT industry is rapidly changing as the line between global and local markets are being blurred. In the changing global environment, although some game companies are accelerating the improvement of their global competitiveness and cases of successes of venture enterprises by developing biosimilar technology are being discovered, majority of ICT companies are focusing on limited marketing activities to get subcontracts or projects from large companies. Thus the aim of this study is to find out how digital ecosystems evolve and how business models and strategies have changed of individual companies according to the evolution of the digital ecosystems.

• Journal of Information Technology Services
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• v.15 no.1
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• pp.1-18
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• 2016

Recently, in the bio-field success stories of ventures through a biosimilar technology is being excavated. but the growth of ICT industry has been stagnant since reaching a boom in the dissemination of early high-speed internet in 2000s. The purpose of this study is to explore the factors of change of business model and business strategy of ICT ventures and SMEs with the evolution of the digital ecosystem, and to drive the factors to be competitive on the global value chain. The researcher selected an entreprenuership, market-innovation orientation, technology-innovation orientation, and Administration-innovation orientation as internal factors influencing the global competence and healthiness of the ecosystem as external factors. The researcher applied samples of 94 ICT Venture and SMEs to a research model, and adopted 5 hypotheses. The researcher believes that only a few hypotheses were adopted because it takes time for overall innovation orientation of ICT Venture and SMEs to result in the real global competence as the their innovation orientation is still on the level of domestic market. And the researcher also thinks that only healthiness of the ecosystem affected management performances because the companies' performances of the last 3 years were so weak that the correlation between innovation orientation of each company and the performances were not big enough.

• Mass Spectrometry Letters
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• v.6 no.3
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• pp.53-58
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• 2015

Recombinant erythropoietins (EPOs) are an important class of biotherapeutics that stimulate red blood cell production. The quality, safety, and potency of EPO variants are determined largely by their glycosylation, which makes up nearly half their mass. Thus, detailed glycomic analyses are important to assess biotherapeutic quality and establish the equivalency of biosimilar EPOs now coming to market. High-resolution mass spectrometry (MS) has recently emerged as the premier tool for glycan analysis in EPOs. Using the accurate mass measurements provided by high-resolution MS, the compositions of even large, complex glycans can easily be determined. When combined with a nano-LC separation, differentiation of structural isomers also becomes a possibility. These components, together, provide a comprehensive picture of biotherapeutic glycosylation. In this review, we provide an overview of MS-based analytical platform for glycomic characterization of EPO biotherapeutics and biosimilars.

• Mass Spectrometry Letters
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• v.12 no.3
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• pp.85-92
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• 2021

The therapeutic antibody drug market has experienced explosive growth as mAbs become the main therapeutic modality for a variety of diseases. Characterization of glycosylation that directly affects the efficacy and safety of therapeutic monoclonal antibodies (mAbs) is critical for therapeutics development, bioprocess system optimization, lot release, and comparability evaluation. The LC/MS approach has been widely used to structurally characterize mAbs, and recently attempts have been made to obtain comprehensive information on the primary structure and post-translational modifications (PTMs) of mAbs through intact protein analysis. In this study, we performed state-of-the-art LC/MS based intact protein analysis to readily identify and characterize glycoforms of various mAbs. Different glycoforms of mAbs produced in different expression cell lines including CHO, SP2/0 and HEK cells were monitored and compared. In addition, the comparability of protein molecular weight, glycoform pattern, and relative abundances of glycoforms between the commercialized trastuzumab biosimilar and the original product was determined in detail using the given platform. Intact mAb analysis allowed us to gain insight into the overall mAb structure, including the complexity and diversity of glycosylation. Furthermore, our analytical platform with high reproducibility is expected to be widely used for biopharmaceutical characterization required at all stages of drug development and manufacturing.

• Journal of Pharmaceutical Investigation
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• v.40 no.1
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• pp.15-21
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• 2010

Sibutramine is an orally administered centrally-acting antiobesity agent and inhibits both noradrenaline(norephinephirine) and serotonin(5-HT) reuptake. These effects are contributed by its active metabolites, M1 and M2. However, as the free base form of sibutramine is an oil form in room temperature, it had the problem of handling and stability. Thus, this drug should be used in the form of acid salt form in the pharmaceutical application. Unfortunately, anhydrous sibutramine hydrochloride is highly hygroscopic and unstable. In order to solve the hygroscopicity of the anhydrous salt form, another sibutramine acid salt form must be developed as a hydrate form. In this study. to overcome these problems, various of sibutramine acid salt forms were prepared with the pharmaceutically available salts such as maleate, esylate, mandelate, camsylate, besylate, salicylate, tartrate, isethionate and malate forms, and their physicochemical properties were investigated. Sibutramine malate was selected for excellent solubility and stability among the listed salt forms above. Its pharmacokinetic parameters were evaluated in rats comparing with sibutramine HCl, resulting in similar parameters. In vitro dissolution study of sibutramine malate-loaded capsule was performed comparison with commercial product ($Reductil^{(R)}$) in pH 1.2, pH 4.0, pH 6.8 and water medium. Our results indicated that there were no significant differences in their dissolution profiles were similar in all tested medium. Thus, sibutramine malate-loaded capsule should be a potential candiate due to its excellent solubility, good stability and biosimilar absorption.

• The Korean Society of Law and Medicine
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• v.21 no.1
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• pp.223-259
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• 2020

With COVID-19 spreading rapidly around the world, research and development issues on treatments and vaccines for the virus are of high interest. Among them, Remdesivir was the first to show noticeable therapeutic effects and began clinical trials, with each country authorizing the use of the drug through emergency approval. However, Gilead Co., Ltd., the developer of Remdesivir, received a lot of criticism from civic groups for submitting the application for the marketing authorization as an orphan drug. This is because when a new drug got a marketing authorization as an orphan drug could be granted an exclusive status for seven year. The long-term exclusive status of an orphan drug comes from the policy purpose of motivating pharmaceutical companies to develop treatment opportunities for patients suffering from rare diseases, which was not appropriate to apply to infectious disease treatments. This paper provides a review of the problems and improvement directions of the domestic system through comparative legal consideration against the United States, Europe and Japan for the statutes which give exclusive status to medicines. The domestic system has a fundamental problem that it does not have explicit provisions in the statute in the manner of granting exclusive status, and that it uses the review system to give it exclusive status indirectly. In addition, in the case of orphan drugs, the "Rare Diseases Management Act" and the "Regulations on Examination of Items Permission and Reporting of Drugs" provide overlapping review periods, and despite the relatively long monopoly period, there seems to be no check clause to recover exclusive status in the event of a change in circumstances. Given that biopharmaceuticals are difficult to obtain patents, the lack of such provisions is a pity of domestic legislation, although granting exclusive rights may be a great motivation to induce drug development. In the United States, given that the first biosimilar also has a one-year monopoly period, it can be interpreted that domestic legislation is quite strictly limited to granting exclusive status to biopharmaceuticals. The need for improvement of the domestic system will be recognized in that it could undermine local pharmaceutical companies' willingness to develop biopharmaceuticals in the future, and in that it is also necessary to harmonize international regulations. Taking advantage of the emergence of COVID-19 as an opportunity, we look again at the problems of the domestic system that grants exclusive rights to medicines and hope that an overall revision of the relevant legislation will be made to establish a unified legal basis.