KR20050047031A - 면역글로불린 Fc 영역을 캐리어로 포함하는 약제학적조성물 - Google Patents
면역글로불린 Fc 영역을 캐리어로 포함하는 약제학적조성물 Download PDFInfo
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- KR20050047031A KR20050047031A KR1020040092781A KR20040092781A KR20050047031A KR 20050047031 A KR20050047031 A KR 20050047031A KR 1020040092781 A KR1020040092781 A KR 1020040092781A KR 20040092781 A KR20040092781 A KR 20040092781A KR 20050047031 A KR20050047031 A KR 20050047031A
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- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Abstract
Description
이론치(kDa) | 측정치(kDa) | |
IFNα-PEG-Fc(실시예 1) | 75.4 | 75.9 |
hGH-PEG-Fc(실시예 3) | 78.4 | 78.6 |
G-CSF-PEG-Fc(실시예 4) | 75.3 | 75.9 |
17S-G-CSF 유도체-PEG-Fc(실시예 4) | 75.0 | 75.9 |
EPO-PEG-Fc(실시예 5) | 91.4 | 91.0 |
이론치(kDa) | 측정치(kDa) | |
IFNα-PEG-DG Fc (실시예 11) | 72.8 | 73.0 |
IFNα-PEG-재조합 AG Fc 유도체(I) (실시예 13) | 72.3 | 72.2 |
IFNα-PEG-재조합 AG Fc 유도체(II) (실시예 13) | 46.8 | 46.6 |
천연형IFNα | IFNα-40K PEG(비교예 1) | IFNα-PEG-알부민(비교예 2) | IFNα-PEG-Fc(실시예 1) | IFNα-PEG-DG Fc(실시예 11) | IFNα-PEG-재조합 AG Fc 유도체(I)(실시예 13) | IFNα-PEG-재조합 AG Fc 유도체(II)(실시예 13) | |
Tmax(hr) | 1.0 | 30 | 12 | 30 | 48 | 24 | 24 |
T1/2(hr) | 1.7 | 35.8 | 17.1 | 90.4 | 71.0 | 61.2 | 31.2 |
MRT(hr) | 2.1 | 71.5 | 32.5 | 150.1 | 120.6 | 111.0 | 58.8 |
천연형 hGH | hGH-40K PEG(비교예 1) | hGH-PEG-알부민 (비교예 2) | hGH-PEG-Fc (실시예 3) | |
Tmax(hr) | 1.0 | 12 | 12 | 12 |
T1/2(hr) | 1.1 | 7.7 | 5.9 | 11.8 |
MRT(hr) | 2.1 | 18.2 | 13.0 | 18.8 |
천연형 G-CSF | G-CSF-40K PEG(비교예 1) | G-CSF-PEG-알부민(비교예 2) | G-CSF-PEG-Fc(실시예 4) | |
Tmax(hr) | 2.0 | 12 | 12 | 12 |
T1/2(hr) | 2.8 | 4.8 | 5.2 | 6.9 |
MRT(hr) | 5.2 | 24.5 | 25.0 | 32.6 |
17S-G-CSF 유도체 | 17S-G-CSF-40K PEG (비교예 1) | 17S-G-CSF-PEG-알부민 (비교예 2) | 17S-G-CSF-PEG-Fc(실시예 4) | |
Tmax(hr) | 2.0 | 24 | 24 | 24 |
T1/2(hr) | 2.9 | 4.3 | 6.4 | 7.0 |
MRT(hr) | 5.8 | 24.4 | 25.1 | 33.2 |
천연형 EPO | 고 당쇄화 EPO | EPO-PEG-Fc(실시예 5) | EPO-PEG-재조합 AG Fc 유도체 (실시예 13) | |
Tmax(hr) | 6.0 | 12 | 30 | 48 |
T1/2(hr) | 9.4 | 18.4 | 61.5 | 87.9 |
MRT(hr) | 21.7 | 26.8 | 117.6 | 141.6 |
농도(ng/㎖) | 비활성(IU/㎎) | 천연형 IFNα에 대한 상대적 활성(%) | |
천연형 IFNα | 100 | 4.24E+08 | 100 |
IFNα-40K PEG | 100 | 2.04E+07 | 4.8 |
IFNα-PEG-알부민 | 100 | 2.21E+07 | 5.2 |
IFNα-PEG-Fc | 100 | 1.19E+08 | 28.1 |
IFNα-PEG-DG Fc | 100 | 1.09E+08 | 25.7 |
IFNα-PEG-재조합AG Fc 유도체 | 100 | 9.58E+07 | 22.6 |
농도(ng/㎖) | 비활성* (U/㎎) | 천연형 HM-hGH에 대한 상대적 활성(%) | |
천연형 hGH | 100 | 2.71E+06 | 100 |
hGH(NIBSC 국제표준품) | 100 | 2.58E+06 | 95.2 |
hGH-40K PEG | 100 | 0.206E+06 | 7.6 |
hGH-PEG-알부민 | 100 | 0.141E+06 | 5.2 |
hGH-PEG-Fc | 100 | 0.76E+06 | 28.1 |
비활성*= 1/ED50×106(ED50: 최대 세포 성장의 50%를 나타내는 단백질양) |
ED50(IU/㎖) | G-CSF에 대한상대적 활성(%) | |
천연형 G-CSF(Filgrastim) | 0.30 | 100 |
17Ser-G-CSF | 0.26 | 115 |
G-CSF-20K PEG(Neulasta) | 1.20 | 25 |
17Ser-G-CSF-40K PEG | 10.0 | <10.0 |
17Ser-G-CSF-PEG-알부민 | 1.30 | 23.0 |
17Ser-G-CSF-PEG-Fc | 0.58 | 51.7 |
Claims (26)
- 면역글로불린 Fc 영역을 캐리어로 포함하는 약제학적 조성물
- 제1항에 있어서, 면역글로불린 Fc 영역이 비당쇄화됨을 특징으로 하는 약제학적 조성물.
- 제1항에 있어서, 면역글로불린 Fc 영역이 CH1, CH2, CH3 및 CH4 도메인으로 이루어진 그룹으로부터 1개 내지 4개 선택되는 도메인으로 이루어진 약제학적 조성물.
- 제3항에 있어서, 면역글로불린 Fc 영역이 힌지영역을 추가로 포함하는 약제학적 조성물.
- 제1항에 있어서, 면역글로불린 Fc 영역이 IgG, IgA, IgD, IgE, IgM, 이들의 조합(combination) 및 이들의 하이브리드(hybrid)의 Fc 영역으로 이루어진 군으로부터 선택되는 약제학적 조성물.
- 제5에 있어서, 면역글로불린 Fc 영역이 IgG1, IgG2, IgG3, IgG4, 이들의 조합 및 이들의 하이브리드의 Fc 영역으로 이루어진 군으로부터 선택되는 약제학적 조성물.
- 제6항에 있어서, 면역글로불린 Fc 영역이 IgG4 Fc 영역인 약제학적 조성물.
- 제7항에 있어서, 면역글로불린 Fc 영역이 인간 비당쇄화 IgG4 Fc 영역인 약제학적 조성물.
- 제1항에 있어서, 면역글로불린 Fc 영역과 결합되는 약물이 생리활성 폴리펩타이드인 약제학적 조성물.
- 제9항에 있어서, 생리활성 폴리펩타이드가 호르몬, 사이토카인, 효소, 항체, 성장인자, 전사조절인자, 혈액인자, 백신, 구조단백질, 리간드 단백질 및 수용체로 구성된 군으로부터 선택되는 약제학적 조성물.
- 제10항에 있어서, 생리활성 폴리펩타이드가 인간 성장 호르몬, 성장 호르몬 방출 호르몬, 성장 호르몬 방출 펩타이드, 인터페론류, 인터페론 수용체류, 콜로니 자극인자류, 글루카콘-유사 펩타이드류 (GLP-1등), 지프로테인 관련수용체 (G-protein-coupled receptor), 인터루킨류, 인터루킨 수용체류, 효소류, 인터루킨 결합 단백질류, 사이토카인 결합 단백질류, 마크로파지 활성인자, 마크로파지 펩타이드, B 세포인자, T 세포인자, 단백질 A, 알러지 억제인자, 세포 괴사 당단백질, 면역독소, 림포독소, 종양 괴사인자, 종양 억제인자, 전이 성장인자, 알파-1 안티트립신, 알부민, α-락트알부민, 아포리포단백질-E, 적혈구 생성인자, 고 당쇄화 적혈구 생성인자, 안지오포에이틴류, 헤모글로빈, 크롬빈, 트롬빈 수용체 활성 펩타이드, 트롬보모듈린, 혈액인자 Ⅶ, Ⅶa, Ⅷ, Ⅸ, 및 XIII, 플라즈미노젠 활성인자, 피브린-결합 펩타이드, 유로키나제, 스트렙토키나제, 히루딘, 단백질 C, C-반응성 단백질, 레닌 억제제, 콜라게나제 억제제, 수퍼옥사이드 디스뮤타제, 렙틴, 혈소판 유래 성장인자, 상피세포 성장인자, 표피세포 성장인자, 안지오스타틴, 안지오텐신, 골 형성 성장인자, 골 형성 촉진 단백질, 칼시토닌, 인슐린, 아트리오펩틴, 연골 유도인자, 엘카토닌, 결합조직 활성인자, 조직인자 경로 억제제, 여포 자극 호르몬, 황체 형성 호르몬, 황체 형성 호르몬 방출 호르몬, 신경 성장인자류, 부갑상선 호르몬, 릴랙신, 씨크레틴, 소마토메딘, 인슐린 유사 성장인자, 부신피질 호르몬, 글루카곤, 콜레시스토키닌, 췌장 폴리펩타이드, 가스트린 방출 펩타이드, 코티코트로핀 방출인자, 갑상선 자극호르몬, 오토탁신, 락토페린, 미오스타틴, 수용체류, 수용체 길항물질, 세포표면항원, 바이러스 유래 백신 항원, 단일클론 항체, 다중클론 항체 및 항체 단편류로 이루어진 군으로부터 선택되는 약제학적 조성물.
- 제11항에 있어서, 생리활성 폴리펩타이드가 인간 성장 호르몬, 콜로니 자극 인자, 인터페론-알파, 인간 적혈구 생성인자 및 Fab' 항체 단편으로 이루어진 군으로부터 선택되는 약제학적 조성물.
- 제1항에 있어서, 면역글로불린 Fc 영역이 펩타이드성 또는 비펩타이드성 링커를 매개로 약물과 결합되는 약제학적 조성물.
- 면역글로불린 Fc 영역을 캐리어로 포함함으로써 약물의 생체 내 지속성을 증가시키는 방법.
- 제14항에 있어서, 면역글로불린 Fc 영역이 비당쇄화됨을 특징으로 하는 방법.
- 제14항에 있어서, 면역글로불린 Fc 영역이 CH1, CH2, CH3 및 CH4 도메인으로 이루어진 그룹으로부터 1개 내지 4개 선택되는 도메인으로 이루어진 방법.
- 제16항에 있어서, 면역글로불린 Fc 영역이 힌지영역을 추가로 포함하는 방법.
- 제14항에 있어서, 면역글로불린 Fc 영역이 IgG, IgA, IgD, IgE, IgM, 이들의 조합(combination) 및 이들의 하이브리드(hybrid)의 Fc 영역으로 이루어진 군으로부터 선택되는 방법.
- 제18항에 있어서, 면역글로불린 Fc 영역이 IgG1, IgG2, IgG3, IgG4, 이들의 조합 및 이들의 하이브리드의 Fc 영역으로 이루어진 군으로부터 선택되는 방법.
- 제19항에 있어서, 면역글로불린 Fc 영역이 IgG4 Fc 영역인 방법.
- 제20항에 있어서, 면역글로불린 Fc 영역이 인간 비당쇄화 IgG4 Fc 영역인 방법.
- 제14항에 있어서, 면역글로불린 Fc 영역과 결합되는 약물이 생리활성 폴리펩타이드인 방법.
- 제22항에 있어서, 생리활성 폴리펩타이드가 호르몬, 사이토카인, 효소, 항체, 성장인자, 전사조절인자, 혈액인자, 백신, 구조단백질, 리간드 단백질 및 수용체로 구성된 군으로부터 선택되는 방법.
- 제23항에 있어서, 생리활성 폴리펩타이드가 인간 성장 호르몬, 성장 호르몬 방출 호르몬, 성장 호르몬 방출 펩타이드, 인터페론류, 인터페론 수용체류, 콜로니 자극인자류, 글루카콘-유사 펩타이드류 (GLP-1등), 지프로테인 관련수용체 (G-protein-coupled receptor), 인터루킨류, 인터루킨 수용체류, 효소류, 인터루킨 결합 단백질류, 사이토카인 결합 단백질류, 마크로파지 활성인자, 마크로파지 펩타이드, B 세포인자, T 세포인자, 단백질 A, 알러지 억제인자, 세포 괴사 당단백질, 면역독소, 림포독소, 종양 괴사인자, 종양 억제인자, 전이 성장인자, 알파-1 안티트립신, 알부민, α-락트알부민, 아포리포단백질-E, 적혈구 생성인자, 고 당쇄화 적혈구 생성인자, 안지오포에이틴류, 헤모글로빈, 트롬빈, 트롬빈 수용체 활성 펩타이드, 트롬보모듈린, 혈액인자 Ⅶ, Ⅶa, Ⅷ, Ⅸ, 및 XIII, 플라즈미노젠 활성인자, 피브린-결합 펩타이드, 유로키나제, 스트렙토키나제, 히루딘, 단백질 C, C-반응성 단백질, 레닌 억제제, 콜라게나제 억제제, 수퍼옥사이드 디스뮤타제, 렙틴, 혈소판 유래 성장인자, 상피세포 성장인자, 표피세포 성장인자, 안지오스타틴, 안지오텐신, 골 형성 성장인자, 골 형성 촉진 단백질, 칼시토닌, 인슐린, 아트리오펩틴, 연골 유도인자, 엘카토닌, 결합조직 활성인자, 조직인자 경로 억제제, 여포 자극 호르몬, 황체 형성 호르몬, 황체 형성 호르몬 방출 호르몬, 신경 성장인자류, 부갑상선 호르몬, 릴랙신, 씨크레틴, 소마토메딘, 인슐린 유사 성장인자, 부신피질 호르몬, 글루카곤, 콜레시스토키닌, 췌장 폴리펩타이드, 가스트린 방출 펩타이드, 코티코트로핀 방출인자, 갑상선 자극호르몬, 오토탁신, 락토페린, 미오스타틴, 수용체류, 수용체 길항물질, 세포표면항원, 바이러스 유래 백신 항원, 단일클론 항체, 다중클론 항체 및 항체 단편류로 이루어진 군으로부터 선택되는 방법.
- 제24항에 있어서, 생리활성 폴리펩타이드가 인간 성장 호르몬, 콜로니 자극 인자, 인터페론-알파, 인간 적혈구 생성인자 및 Fab' 항체 단편으로 이루어진 군으로부터 선택되는 방법.
- 제14항에 있어서, 면역글로불린 Fc 영역이 펩타이드성 또는 비펩타이드성 링커를 매개로 약물과 결합되는 방법.
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Application Number | Priority Date | Filing Date | Title |
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KR20030080299 | 2003-11-13 | ||
KR1020030080299 | 2003-11-13 |
Publications (2)
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KR20050047031A true KR20050047031A (ko) | 2005-05-19 |
KR100775343B1 KR100775343B1 (ko) | 2007-11-08 |
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Family Applications (5)
Application Number | Title | Priority Date | Filing Date |
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KR1020040092782A KR100725315B1 (ko) | 2003-11-13 | 2004-11-13 | 면역글로불린 단편을 이용한 단백질 결합체 및 그의제조방법 |
KR1020040092781A KR100775343B1 (ko) | 2003-11-13 | 2004-11-13 | 면역글로불린 Fc 영역을 캐리어로 포함하는 약제학적조성물 |
KR1020040092783A KR100725314B1 (ko) | 2003-11-13 | 2004-11-13 | 면역글로불린 불변영역의 대량 생산 방법 |
KR1020040092780A KR20050047030A (ko) | 2003-11-13 | 2004-11-13 | 약물의 캐리어로서 유용한 IgG Fc 단편 및 그의제조방법 |
KR1020060036697A KR20060054252A (ko) | 2003-11-13 | 2006-04-24 | 약물의 캐리어로서 유용한 IgG Fc 단편 및 그의제조방법 |
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KR1020040092780A KR20050047030A (ko) | 2003-11-13 | 2004-11-13 | 약물의 캐리어로서 유용한 IgG Fc 단편 및 그의제조방법 |
KR1020060036697A KR20060054252A (ko) | 2003-11-13 | 2006-04-24 | 약물의 캐리어로서 유용한 IgG Fc 단편 및 그의제조방법 |
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KR (5) | KR100725315B1 (ko) |
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AU (2) | AU2004282985B8 (ko) |
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ES (6) | ES2454666T3 (ko) |
HK (2) | HK1149570A1 (ko) |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8263084B2 (en) | 2003-11-13 | 2012-09-11 | Hanmi Science Co., Ltd | Pharmaceutical composition for treating obesity-related disease comprising insulinotropic peptide conjugate |
US8476230B2 (en) | 2007-01-05 | 2013-07-02 | Hanmi Science Co., Ltd | Insulinotropic complex using an immunoglobulin fragment |
WO2009069983A3 (en) * | 2007-11-29 | 2009-08-20 | Hanmi Pharmaceutical Co Ltd | A pharmaceutical composition for treating obesity-related disease comprising insulinotropic peptide conjugate |
KR20180071241A (ko) * | 2013-07-12 | 2018-06-27 | 한미약품 주식회사 | FcRn 결합력이 유지되는 면역글로불린 Fc 결합체 |
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