TWI666219B - 使用免疫球蛋白片段之位點專一性ｇｌｐ－２接合物 - Google Patents
使用免疫球蛋白片段之位點專一性ｇｌｐ－２接合物 Download PDFInfo
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- TWI666219B TWI666219B TW101150930A TW101150930A TWI666219B TW I666219 B TWI666219 B TW I666219B TW 101150930 A TW101150930 A TW 101150930A TW 101150930 A TW101150930 A TW 101150930A TW I666219 B TWI666219 B TW I666219B
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
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- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
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- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
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- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
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- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
Landscapes
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- General Chemical & Material Sciences (AREA)
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- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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| ??10-2011-0147684 | 2011-12-30 | ||
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| KR20130049671A (ko) | 2011-11-04 | 2013-05-14 | 한미사이언스 주식회사 | 생리활성 폴리펩타이드 결합체 제조 방법 |
| AR090281A1 (es) | 2012-03-08 | 2014-10-29 | Hanmi Science Co Ltd | Proceso mejorado para la preparacion de un complejo polipeptidico fisiologicamente activo |
| US9949927B2 (en) | 2012-04-10 | 2018-04-24 | The Regents Of The University Of California | Bis-polymer lipid-peptide conjugates and nanoparticles thereof |
| WO2015042252A1 (en) * | 2013-09-19 | 2015-03-26 | The Regents Of The University Of California | Methods of treatment using bis-polymer lipid-peptide conjugates and nanoparticles thereof |
| WO2015056713A1 (ja) * | 2013-10-15 | 2015-04-23 | 国立大学法人東京大学 | ｃ－Ｍｅｔタンパク質アゴニスト |
| AU2014364589B2 (en) | 2013-12-18 | 2020-02-27 | The California Institute For Biomedical Research | Modified therapeutic agents, stapled peptide lipid conjugates, and compositions thereof |
| DK3127923T3 (da) * | 2014-03-31 | 2021-11-22 | Hanmi Pharm Ind Co Ltd | Fremgangsmåde til forbedring af oppløselighed af protein og peptid ved hjælp af immunoglobulin-fc-fragment-binding |
| KR101825048B1 (ko) * | 2014-12-31 | 2018-02-05 | 주식회사 제넥신 | GLP 및 면역글로불린 하이브리드 Fc 융합 폴리펩타이드 및 이의 용도 |
| TW202444744A (zh) | 2016-07-11 | 2024-11-16 | 以色列商歐科生物製品有限公司 | 長效型凝血因子及其生產方法 |
| CN107987170B (zh) * | 2016-10-27 | 2018-12-18 | 浙江道尔生物科技有限公司 | 一种用于治疗肠道疾病的融合蛋白 |
| WO2018157131A1 (en) | 2017-02-27 | 2018-08-30 | Urigen N.A. | Treatment of lower urinary tract epithelium with glucagon like peptide 2 |
| KR102174436B1 (ko) * | 2017-08-17 | 2020-11-04 | 주식회사 엘지화학 | 불용성 안료 화합물의 정성분석방법 |
| JP7249492B2 (ja) * | 2017-08-22 | 2023-03-31 | タケダ ファーマシューティカルズ ユーエスエー インコーポレイテッド | Ｇｌｐ－２融合ポリペプチドならびに消化管の状態を処置および予防するための使用 |
| CA3084326A1 (en) * | 2017-09-28 | 2019-04-04 | Jaehyuk Choi | Long-acting conjugates of glp-2 derivatives |
| KR102825098B1 (ko) * | 2017-11-06 | 2025-06-26 | 다케다 야쿠힌 고교 가부시키가이샤 | 수술전, 수술동안 또는 수술후 투여용 glp-2 유사체 및 펩티바디 |
| US20210355187A1 (en) * | 2018-10-24 | 2021-11-18 | Shire-Nps Pharmaceuticals, Inc. | Glp-2 fusion polypeptides and uses for treating and preventing gastrointestinal conditions |
| WO2020165900A1 (en) * | 2019-02-11 | 2020-08-20 | Opko Biologics Ltd. | Long-acting glp-2 analogs |
| US20220257722A1 (en) * | 2019-03-28 | 2022-08-18 | United States Government As Represented By The Department Of Veterans Affairs | Compositions and methods of treating and preventing systemic complications of acute illness |
| WO2021133087A1 (ko) * | 2019-12-24 | 2021-07-01 | 한미약품 주식회사 | Glp-2 또는 이의 결합체를 포함하는 골 대사성 질환에 대한 예방 또는 치료용 약학적 조성물 |
| CA3173353A1 (en) * | 2020-04-03 | 2021-10-07 | Jin Bong Lee | Pharmaceutical composition for preventing or treating mucositis induced by radiotherapy, chemotherapy, or combination thereof, comprising glp-2 derivatives or long-acting conjugate of same |
| US20230285584A1 (en) * | 2020-05-22 | 2023-09-14 | Hanmi Pharm. Co., Ltd. | Liquid formulation of long-acting conjugate of glp-2 |
| CN111560062A (zh) * | 2020-05-26 | 2020-08-21 | 成都圣诺生物制药有限公司 | 一种Elisiglutide的制备方法 |
| WO2022159555A1 (en) * | 2021-01-20 | 2022-07-28 | The Trustees Of Columbia University In The City Of New York | Methods for treating graft-versus-host disease using glp-2 agonists and analogues thereof |
| AU2022289610A1 (en) | 2021-06-09 | 2024-01-25 | The Scripps Research Institute | Long-acting dual gip/glp-1 peptide conjugates and methods of use |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101646451A (zh) * | 2007-01-05 | 2010-02-10 | 韩美药品工业株式会社 | 使用免疫球蛋白片段的促胰岛素缀合物 |
| WO2010107256A2 (en) * | 2009-03-20 | 2010-09-23 | Hanmi Pharm. Co., Ltd. | Method for preparing a site-specific physiologically active polypeptide conjugate |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US6096871A (en) | 1995-04-14 | 2000-08-01 | Genentech, Inc. | Polypeptides altered to contain an epitope from the Fc region of an IgG molecule for increased half-life |
| WO1997034631A1 (en) | 1996-03-18 | 1997-09-25 | Board Of Regents, The University Of Texas System | Immunoglobin-like domains with increased half lives |
| US6924264B1 (en) | 1999-04-30 | 2005-08-02 | Amylin Pharmaceuticals, Inc. | Modified exendins and exendin agonists |
| US6756480B2 (en) | 2000-04-27 | 2004-06-29 | Amgen Inc. | Modulators of receptors for parathyroid hormone and parathyroid hormone-related protein |
| DK1355942T3 (da) | 2000-12-07 | 2008-11-17 | Lilly Co Eli | GLP-1-fusionsproteiner |
| WO2002066511A2 (en) * | 2001-02-16 | 2002-08-29 | Conjuchem Inc. | Long lasting glucagon-like peptide 2 (glp-2) for the treatment of gastrointestinal diseases and disorders |
| CN1705681A (zh) * | 2002-10-14 | 2005-12-07 | 诺沃挪第克公司 | Glp－2化合物、制剂及其用途 |
| US20070060512A1 (en) | 2003-03-04 | 2007-03-15 | Homayoun Sadeghi | Dipeptidyl-peptidase protected protein |
| BRPI0406606A (pt) * | 2003-11-13 | 2005-12-06 | Hanmi Pharm Ind Co Ltd | Composição farmacêutica compreendendo uma região fc de imunoglobulina como um veìculo |
| DK1704234T3 (da) | 2003-11-21 | 2012-05-07 | Nps Pharma Inc | Fremstilling af glucagon-lignende peptid 2 og analoger |
| WO2006076471A2 (en) | 2005-01-12 | 2006-07-20 | Nobex Corporation | Bnp conjugates and methods of use |
| CN101171262B (zh) | 2005-05-04 | 2012-06-27 | 西兰制药公司 | 胰高血糖素样肽-2(glp-2)类似物 |
| WO2007067828A2 (en) | 2005-10-24 | 2007-06-14 | Centocor, Inc. | Glp-2 mimetibodies, polypeptides, compositions, methods and uses |
| CA2755133A1 (en) * | 2009-03-20 | 2010-09-23 | Amgen Inc. | Selective and potent peptide inhibitors of kv1.3 |
| KR101746686B1 (ko) | 2010-10-26 | 2017-06-15 | 한미사이언스 주식회사 | 면역글로불린 단편을 이용한 글루카곤 유사 펩타이드―２（ｇｌｐ―２）약물 결합체 |
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2011
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2012
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- 2012-12-28 TW TW101150930A patent/TWI666219B/zh active
- 2012-12-28 US US14/369,436 patent/US9504757B2/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101646451A (zh) * | 2007-01-05 | 2010-02-10 | 韩美药品工业株式会社 | 使用免疫球蛋白片段的促胰岛素缀合物 |
| WO2010107256A2 (en) * | 2009-03-20 | 2010-09-23 | Hanmi Pharm. Co., Ltd. | Method for preparing a site-specific physiologically active polypeptide conjugate |
Non-Patent Citations (2)
| Title |
|---|
| Drucker DJ, "Glucagon-Like Peptide 2", The Journal of Clinical Endocrinology & Metabolism, Volume 86, Issue 4, p1759-1764, 2001 * |
| Roberts MJ et al., "Chemistry for peptide and protein PEGylation", Advanced Drug Delivery Reviews Volume 54, Issue 4, Pages 459-476, 2002/06/17 * |
Also Published As
| Publication number | Publication date |
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| ES2725805T3 (es) | 2019-09-27 |
| KR20130078634A (ko) | 2013-07-10 |
| CN109810198B (zh) | 2023-06-06 |
| CN109810198A (zh) | 2019-05-28 |
| EP2797621A4 (en) | 2015-09-02 |
| KR101895047B1 (ko) | 2018-09-06 |
| AR089506A1 (es) | 2014-08-27 |
| EP2797621A1 (en) | 2014-11-05 |
| TW201333032A (zh) | 2013-08-16 |
| WO2013100704A1 (en) | 2013-07-04 |
| JP6131490B2 (ja) | 2017-05-24 |
| EP2797621B1 (en) | 2019-03-06 |
| US20140377290A1 (en) | 2014-12-25 |
| US9504757B2 (en) | 2016-11-29 |
| CN104144697A (zh) | 2014-11-12 |
| JP2015503554A (ja) | 2015-02-02 |
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