• 응용통계연구
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• 제24권3호
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• pp.495-503
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• 2011

When a patent of an innovative (brand-name) small-molecule drug expires, generic copies of the innovative drug may be marketed if their therapeutic equivalence to the innovative drug has been shown. The small-molecule drugs are considered therapeutically equivalent and can be used interchangeably if two drugs are shown to be pharmaceutically equivalent with identical active substance and bioequivalent with comparable pharmacokinetics in a crossover clinical trial. However, the therapeutic equivalence paradigm cannot be applied to biosimilars since the active ingredients of biosimilars are huge molecules with complex and heterogeneous structures, and these molecules are difficult to replicate in every detail. The European Medicine Agency(EMEA) has introduced a regulatory biosimilar pathway which mandates clinical trials to show therapeutic equivalence. In this paper, we discuss statistical considerations in the design and analysis of biosimilar cancer clinical trials.

• Toxicological Research
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• 제32권1호
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• pp.9-14
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• 2016

The National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) provides validation support for US Federal agencies and the US Tox21 interagency consortium, an interagency collaboration that is using high throughput screening (HTS) and other advanced approaches to better understand and predict chemical hazards to humans and the environment. The use of HTS data from assays relevant to the estrogen receptor signaling data pathway is used as an example of how HTS data can be combined with computational modeling to meet the needs of US agencies. As brief summary of US efforts in the areas of biologics testing, acute toxicity, and skin sensitization will also be provided.

• Communications for Statistical Applications and Methods
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• 제22권4호
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• pp.389-399
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• 2015

It is important not to overcalculate sample sizes for clinical trials due to economic, ethical, and scientific reasons. Kang and Kim (2014) investigated the accuracy of a well-known sample size calculation formula based on the approximate power for continuous endpoints in equivalence trials, which has been widely used for Development of Biosimilar Products. They concluded that this formula is overly conservative and that sample size should be calculated based on an exact power. This paper extends these results to binary endpoints for three popular metrics: the risk difference, the log of the relative risk, and the log of the odds ratio. We conclude that the sample size formulae based on the approximate power for binary endpoints in equivalence trials are overly conservative. In many cases, sample sizes to achieve 80% power based on approximate powers have 90% exact power. We propose that sample size should be computed numerically based on the exact power.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.173.1-173.1
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• 2003

One of attractive target for Rheumatoid Arthritis (RA) therapy is the cytokine, tumor necrosis factor-alpha (TNF-$\alpha$), which has been shown to be overproduced in the joint of RA patients. The clinical success of anti- TNFR biologics has validated TNF-$\alpha$ as a drug discovery target. Thus, inhibiting of formation of TNF-$\alpha$ has been emerged to an intriguing approach for RA therapy. TNF-$\alpha$ is processed from its membrane bound precursor by the metalloprotease TNF-$\alpha$ converting enzyme (TACE), Here, biological evaluation, mode of action of natural TACE inhibitor, Gelastatin hydroxamate, are addressed. (omitted)

• BMB Reports
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• 제55권1호
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• pp.11-19
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• 2022

The coronavirus disease 2019 (COVID-19) is an ongoing global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe COVID-19 exhibit hyper-inflammatory responses characterized by excessive activation of myeloid cells, including monocytes, macrophages, and neutrophils, and a plethora of pro-inflammatory cytokines and chemokines. Accumulating evidence also indicates that hyper-inflammation is a driving factor for severe progression of the disease, which has prompted the development of anti-inflammatory therapies for the treatment of patients with COVID-19. Corticosteroids, IL-6R inhibitors, and JAK inhibitors have demonstrated promising results in treating patients with severe disease. In addition, diverse forms of exosomes that exert anti-inflammatory functions have been tested experimentally for the treatment of COVID-19. Here, we briefly describe the immunological mechanisms of the hyper-inflammatory responses in patients with severe COVID-19. We also summarize current anti-inflammatory therapies for the treatment of severe COVID-19 and novel exosome-based therapeutics that are in experimental stages.

• Tuberculosis and Respiratory Diseases
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• 제87권1호
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• pp.12-21
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• 2024

The management of severe asthma presents a significant challenge in asthma treatment. Over the past few decades, remarkable progress has been made in developing new treatments for severe asthma, primarily in the form of biological agents. These advances have been made possible through a deeper understanding of the underlying pathogenesis of asthma. Most biological agents focus on targeting specific inflammatory pathways known as type 2 inflammation. However, recent developments have introduced a new agent targeting upstream alarmin signaling pathways. This opens up new possibilities, and it is anticipated that additional therapeutic agents targeting various pathways will be developed in the future. Despite this recent progress, the mainstay of asthma treatment has long been inhalers. As a result, the guidelines for the appropriate use of biological agents are not yet firmly established. In this review, we aim to emphasize the current state of biological therapy for severe asthma and provide insights into its future prospects.

• 생명과학회지
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• 제22권6호
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• pp.703-712
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• 2012

AAV는 매우 안전하고 효율적인 유전자전달방법으로 인정되어 왔다. 그러나, AAV가 가진 생물의약품으로서 단점은 효율적이고 재현성 높은 생산법이 취약하고, 또한 다양한 혈청형을 간단한 한 가지 공통적 방법으로 신뢰성 있게 정량하는 방법이 개발되어야 하는 것이다. 따라서, 본 연구에서는 AAV2와 아데노바이러스를 동시에 감염하는 종래의 생산법에 의한 효율성과 새로운 생산법, 즉 AAV2 감염 후 pHelper 플라스미드를 transfection 하는 방법을 통한 생산효율성을 비교하였고, HEK293과 293T를 생산세포주로 하여 시간에 따른 생산효율성도 분석하였다. 그 결과 AAV2와 pHelper DNA를 포함한 새로운 생산법은 기존의 방법에 비해 10배 이상 높은 생산효율성을 보였고, 293T에서 AAV2를 10 MOI로 감염한 후 5일째에 가장 높은 생산효율성을 보였는데, 생산세포 한 개 당 $1.61{\times}10^5$ virus genomes (v.g.)을 생산하는 결과였다. 따라서 이 생산조건을 다른 혈청형 생산에 적용한 결과, 모든 혈청형에서 생산세포주 한 개 당 $10^5$ v.g. 이상을 생산하는 효율성을 보였다. 한편, 다양한 AAV 혈청형을 한 가지 공통적인 방법으로 정량하기 위해 the universal PCR 프라이머를 제작하였고, 그것을 이용하여 신뢰성 높고 10개 분자까지도 증폭이 가능한 결과를 모든 혈청형에서 얻었다. 그러므로 이 한 쌍의 정량용 the universal 프라이머는 임상시험용 아데노바이러스벡터에 존재하는 AAV오염을 검출하는 것에도 사용 가능하다.

• 약학회지
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• 제55권4호
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• pp.284-288
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• 2011

The test method for biologics of lot release system is based on 'Test procedure and specification for biological products,' generally, thimerosal content is measured by chemical analysis using O.D. In this study, the comparative analysis was carried out using the gold amalgamation method for thimerosal content was compared to the existing methods, which are described above. The gold amalgamation method, which uses atomic absorption spectrophotometry, was meets all the method validation acceptance criteria. It is considered to be proper as the assay and identification test for thimerosal. In this study, the comparative analysis was performed three times. As a result, gold amalgamation method is more convenient and easy to perform as this assay doesn't have pre-treatment procedure. Also this assay showed good precision and reproducibility compared to the conventional method. Therefore, it is appropriate to alternate the assay method of thimerosal from the conventional chemical analysis to gold amalgamation method to improve the credibility of lot release system and the quality control of biologics, by standardizing test method.

• 대한수의학회지
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• 제58권3호
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• pp.167-170
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• 2018

Two 12-month-old cattle with anthelmintics containing trichlorfon the day before death presented to the Animal and Plant Quarantine Agency for diagnosis. In necropsy, they revealed enlargement of the spleens, redness of mucosa and serosa in stomachs and intestines, and friable kidneys. Histopathologically, hemorrhages in the spleens, omasums, abomasums, and intestines as well as renal tubular necrosis were observed. Trichlorfon was detected at above the lethal dose in the ruminal contents. Based on these findings, we diagnosed this case as death caused by trichlorfon poisoning.

• Macromolecular Research
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• 제11권6호
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• pp.451-457
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• 2003

Anion-substituted poly(vinyl alcohol) (PVA) membranes, carboxymethylated PVA (C-PVA), and sulfonated PVA (S-PVA) were prepared and the effects of these substitutions on the plasma protein adsorption were studied by one- and two-dimensional gel electrophoresis and immunoblotting. When Cuprophane was used as a negative control, the amount of total proteins bound to samples decreased in the order Cuprophane > PVA > C-PVA > S-PVA, which we attribute to the effects of the surface characteristics of the samples, such as their surface tensions and electrostatic properties, on the adsorption of proteins to the surfaces of the materials. The results revealed that albumin was the most abundant protein in all the samples. The proportion of adsorbed fibrinogen to S-PVA exceeded those of PVA and C-PVA, whereas S-PVA exhibited the lowest IgG adsorption affinity among the samples we studied.