초록 ▼

연구목표
○ 사이토카인, 효소치료제, 항체의약품의 글리칸 변이체와 오리지널 당단백질 각각에 대하여 체내 안정성 및 효능, 조직분포 특성, 활성, 인체유래세포 안전성을 분석·평가하고, 기존 당단백질과 비교함으로써 글리칸 구조와 당단백질 성능 간의 관계를 규명함
○ 글리칸 구조 변형에 따라 바이오의약품의 체내 효능·안전성이 향상된 글리칸 의약품 3종 이상을 선별하고 최적화 기술 기반을 확립함

연구개발성과
○ 글리칸 변이 EPO의 약물동력학적 지표 분석을 통해 오리지널 EPO(aranesp)보다 반감기가

연구목표
○ 사이토카인, 효소치료제, 항체의약품의 글리칸 변이체와 오리지널 당단백질 각각에 대하여 체내 안정성 및 효능, 조직분포 특성, 활성, 인체유래세포 안전성을 분석·평가하고, 기존 당단백질과 비교함으로써 글리칸 구조와 당단백질 성능 간의 관계를 규명함
○ 글리칸 구조 변형에 따라 바이오의약품의 체내 효능·안전성이 향상된 글리칸 의약품 3종 이상을 선별하고 최적화 기술 기반을 확립함

연구개발성과
○ 글리칸 변이 EPO의 약물동력학적 지표 분석을 통해 오리지널 EPO(aranesp)보다 반감기가 늘어난 글리칸 변이 EPO 2종을 선별하였으며, 글리칸 변이 EPO 효능 평가 동물 모델(신성빈혈)을 구축함
○ 효소치료제 (α-Galactosidase, β-Glucocerebrosidase) 활성 평가법(효소-기질 평가법, LC/MS/MS 지질 정량법)을 구축하고 고셔병 마우스 모델에 적용하여 효소치료제의 조직분포를 확인함
○ CTLA4-Ig의 유효성 평가를 위한 관절염 동물 모델을 구축하여 염증 억제 효능을 평가하고, 항체활성 평가법을 구축함

(출처 : 보고서 요약서 3p)

Abstract ▼

□ Purpose & Contents
Purpose
○ For quality improvement of biopharmaceuticals, the in vivo stability, efficacy, tissue distribution, bioactivity and safety for human-derived cells related to immunogenicity will be analyzed and evaluated for each of variants obtained through the glycan structur

□ Purpose & Contents
Purpose
○ For quality improvement of biopharmaceuticals, the in vivo stability, efficacy, tissue distribution, bioactivity and safety for human-derived cells related to immunogenicity will be analyzed and evaluated for each of variants obtained through the glycan structure modifications of various types of biopharmaceuticals such as cytokine, enzyme and antibody, and these data will be compared to those from each of the original biopharmaceuticals.
○ Also, in order to optimize the efficacy and safety of each variant of glycan structure modifications, at least 3 forms of variants will be selected and the related techniques or methodology will be established for each of the biopharmaceuticals tested.
Contents
○ In vivo stability evaluation
＊ Perform the comparative pharmacokinetic study of glycan structure modified cytokines (EPO and GM-CSF) and enzymes (α-galactosidase and β-glucocerebrosidase) using rats
＊ Select efficiency improved glycan structure variants through comparative stability analysis of each variants
○ Evaluation of efficacy, bioactivity and tissue distribution
＊ Perform the efficacy evaluation of glycan structure modified cytokines by establishing efficacy test model of cytokines, EPO and GM-CSF
＊ Select efficiency improved glycan structure variants through comparing cytokine variants, EPO and GM-CSF, with the original biopharmaceuticals
＊ Test the bioactivity of glycan structure modified enzymes through establishing the bioactivity test model of enzymes, α-galactosidase, β-glucocerebrosidase, and confirm the in vivo tissue distribution of those enzymes concurrently
＊ Select the glycan structure that can improve the tissue distribution of enzymes, α-galactosidase, β-glucocerebrosidase
＊ Establish the antibody evaluation system of IgG and CTLA4-Ig by using ADCC and CDC test system
＊ Confirm the quality improved glycan structure by comparing antibody efficacy of IgG and CTLA4-Ig with original biopharmaceuticals
○ Evaluation of immunogenicity and safety
＊ Establish the test methodology to evaluate the immunogenicity of glycan structure variants (cytokines, enzymes and antibodies)
＊ Confirm the safer glycan structure by comparing the immunogenicity of glycan variants with the original biopharmaceuticals

□ Results
○ In vivo stability evaluation
＊ Perform the comparative pharmacokinetic study of glycan structure modified cytokine EPO and using rats
○ Evaluation of efficacy, bioactivity and tissue distribution
＊ Perform the efficacy evaluation of glycan structure modified cytokines by establishing efficacy test model of cytokine EPO
＊ Establish the efficacy test model of α-galactosidase, β-glucocerebrosidase
＊ Establish the antibody evaluation system of IgG and CTLA4-Ig by using ADCC and CDC test system
○ Evaluation of immunogenicity and safety
＊ Establish the test methodology to evaluate the immunogenicity of glycan structure variants

□ Expected Contribution
○ Capable to propose the efficacy evaluation guideline or prediction method for biosimilars or biobetters through the precision analysis of glycoprotein biopharmaceuticals efficacy improvement and bioactivity of glycan structure by establishing the efficacy optimization skills of biopharmaceuticals with glycan structure modifications
○ Expectable to analyze the therapeutical method for diseases with unknown causes and to acquire the therapeutic techniques by understanding the glycan structure and action mechanism
○ Capable to secure the source technology for controling and evaluating glycoprotein following the tendency of increasing patent application for glycoprotein biopharmaceuticals globally

(출처 : SUMMARY 5p)

목차 Contents

• 표지 ... 1
• 제 출 문 ... 2
• 보고서 요약서 ... 3
• 요 약 문 ... 4
• SUMMARY ... 5
• 목차 ... 6
• 제1장. 연구개발과제의 개요 ... 7
• 1. 연구개발 목적 ... 7
• 2. 연구개발의 필요성 ... 7
• 3. 연구개발 범위 ... 8
• 제2장. 국내외 기술 개발 현황 ... 10
• 1. 세계적 수준 ... 10
• 2. 국내 수준 ... 10
• 3. 국내외 연구현황 ... 11
• 제3장. 연구 수행 내용 및 성과 ... 13
• 1. 연차별 연구개발의 목표 및 내용 ... 13
• 2. 연차별 성과 ... 14
• 제4장. 목표 달성도 및 관련 분야 기여도 ... 35
• 1. 목표 달성도 ... 35
• 2. 관련 분야 기여도 ... 35
• 제5장. 연구개발성과의 활용계획 ... 39
• 제6장. 연구 과정에서 수집한 해외 과학기술 정보 ... 40
• 제7장. 연구개발성과의 보안등급 ... 40
• 제8장. 국가과학기술종합정보시스템에 등록한 연구시설·장비 현황 ... 40
• 제9장. 연구개발과제 수행에 따른 연구실 등의 안전 조치 이행 실적 ... 40
• 제10장. 연구개발과제의 대표적 연구 실적 ... 40
• 제11장. 기타 사항 ... 41
• 제12장. 참고 문헌 ... 41
• 끝페이지 ... 41