JP2009544680A - ポリサッカライドによるタンパク質のn末端誘導体化 - Google Patents
ポリサッカライドによるタンパク質のn末端誘導体化 Download PDFInfo
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- JP2009544680A JP2009544680A JP2009521342A JP2009521342A JP2009544680A JP 2009544680 A JP2009544680 A JP 2009544680A JP 2009521342 A JP2009521342 A JP 2009521342A JP 2009521342 A JP2009521342 A JP 2009521342A JP 2009544680 A JP2009544680 A JP 2009544680A
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- Prior art keywords
- protein
- sialic acid
- polysaccharide
- buffer
- composition
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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/505—Erythropoietin [EPO]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/53—Colony-stimulating factor [CSF]
- C07K14/535—Granulocyte CSF; Granulocyte-macrophage CSF
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
- C12N9/22—Ribonucleases [RNase]; Deoxyribonucleases [DNase]
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y301/00—Hydrolases acting on ester bonds (3.1)
- C12Y301/21—Endodeoxyribonucleases producing 5'-phosphomonoesters (3.1.21)
- C12Y301/21001—Deoxyribonuclease I (3.1.21.1)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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Families Citing this family (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005016974A1 (en) * | 2003-08-12 | 2005-02-24 | Lipoxen Technologies Limited | Sialic acid derivatives for protein derivatisation and conjugation |
| ES2294535T3 (es) | 2003-08-12 | 2008-04-01 | Lipoxen Technologies Limited | Derivados del acido polisialico. |
| KR101400105B1 (ko) | 2006-07-25 | 2014-06-19 | 리폭센 테크놀로지즈 리미티드 | N-말단 폴리시알화 |
| BRPI0720282B8 (pt) | 2006-12-15 | 2021-05-25 | Baxalta GmbH | construção proteica, composição farmacêutica, e, kit |
| DK2115010T3 (da) | 2007-02-28 | 2012-02-06 | Lipoxen Technologies Ltd | Mindskelse af endotoksin i polysialinsyrer |
| US8742079B2 (en) | 2007-08-20 | 2014-06-03 | Protalix Ltd. | Saccharide-containing protein conjugates and uses thereof |
| RU2391354C1 (ru) * | 2008-10-15 | 2010-06-10 | Учреждение Российской академии наук Институт биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова РАН, Российская Федерация, от имени которой выступает Федеральное агентство по науке и инновациям | Комплекс биологически активного рекомбинантного белка с полисиаловой кислотой |
| MX2011004195A (es) * | 2008-10-20 | 2011-09-27 | Usv Ltd | Un proceso mejorado para la pegilacion de proteinas. |
| WO2010051335A1 (en) * | 2008-10-31 | 2010-05-06 | Amgen Inc. | Materials and methods relating to stem cell mobilization by multi-pegylated granulocyte colony stimulating factor |
| US8846103B2 (en) | 2009-01-28 | 2014-09-30 | Smartcells, Inc. | Exogenously triggered controlled release materials and uses thereof |
| MX2011007930A (es) | 2009-01-28 | 2011-09-06 | Smartcells Inc | Conjugados de insulina cristalina. |
| AU2010208305A1 (en) | 2009-01-28 | 2011-09-08 | Smartcells, Inc. | Synthetic conjugates and uses thereof |
| BRPI1007457A2 (pt) | 2009-01-28 | 2015-08-25 | Smartcells Inc | Conjungado, formulação de liberação prolongada, e, sistema de distribuição de bomba. |
| JP2012520879A (ja) | 2009-03-20 | 2012-09-10 | スマートセルズ・インコーポレイテツド | 末端官能基化コンジュゲートおよびその用途 |
| WO2010107520A1 (en) | 2009-03-20 | 2010-09-23 | Smartcells, Inc. | Soluble non-depot insulin conjugates and uses thereof |
| US8809501B2 (en) | 2009-07-27 | 2014-08-19 | Baxter International Inc. | Nucleophilic catalysts for oxime linkage |
| HRP20160916T1 (hr) | 2009-07-27 | 2016-11-18 | Baxalta GmbH | Konjugati proteina za koagulaciju krvi |
| US9795683B2 (en) * | 2009-07-27 | 2017-10-24 | Lipoxen Technologies Limited | Glycopolysialylation of non-blood coagulation proteins |
| CN104530182A (zh) * | 2009-07-27 | 2015-04-22 | 利普森技术有限公司 | 非凝血蛋白的糖基多唾液酸化 |
| US8642737B2 (en) | 2010-07-26 | 2014-02-04 | Baxter International Inc. | Nucleophilic catalysts for oxime linkage |
| US9194011B2 (en) | 2009-11-17 | 2015-11-24 | Protalix Ltd. | Stabilized alpha-galactosidase and uses thereof |
| CN101787117B (zh) * | 2010-02-08 | 2012-05-23 | 江南大学 | 聚乙二醇-聚唾液酸嵌段共聚物的制备方法及应用 |
| MX2012013375A (es) * | 2010-05-17 | 2013-04-11 | Cebix Inc | Peptido c pegilado. |
| WO2011156242A2 (en) * | 2010-06-11 | 2011-12-15 | Lpath, Inc. | Improved anti-lysophospholipid antibody design using antibody structures |
| EP2598527A4 (en) | 2010-07-28 | 2014-01-08 | Smartcells Inc | RECOMBINANT EXPRESSED INSULIN POLYPEPTIDES AND APPLICATIONS THEREOF |
| US8933207B2 (en) | 2010-07-28 | 2015-01-13 | Smartcells, Inc. | Drug-ligand conjugates, synthesis thereof, and intermediates thereto |
| JP2013541500A (ja) | 2010-07-28 | 2013-11-14 | スマートセルズ・インコーポレイテツド | 組換えレクチン、結合部位修飾レクチンおよびそれらの用途 |
| AU2011356137A1 (en) | 2011-01-20 | 2013-08-15 | Protalix Ltd. | Nucleic acid construct for expression of alpha-galactosidase in plants and plant cells |
| EP2780030A4 (en) | 2011-11-17 | 2015-11-18 | Cebix Ab | PEGYLATED C-PEPTIDE |
| RU2676307C2 (ru) | 2013-10-04 | 2018-12-27 | Мерк Шарп И Доум Корп. | Чувствительные к глюкозе конъюгаты инсулина |
| WO2015130963A2 (en) | 2014-02-27 | 2015-09-03 | Xenetic Biosciences, Inc. | Compositions and methods for administering insulin or insulin-like protein to the brain |
| JP2019218265A (ja) * | 2016-09-14 | 2019-12-26 | 生化学工業株式会社 | ペプチドの血中滞留性を増強させる方法 |
| US20200179524A1 (en) * | 2017-04-25 | 2020-06-11 | Lipoxen Technologies Limited | Methods of treating multiple myeloma cancers expressing high levels of epo-receptor using psa-epo |
| WO2018197547A1 (en) | 2017-04-25 | 2018-11-01 | Lipoxen Technologies Limited | Methods of treating diseases related to net formation with parenteral administration of polysialylated dnase i |
| WO2020099513A1 (en) * | 2018-11-13 | 2020-05-22 | Lipoxen Technologies Limited | Glycopolysialylation of blinatumomab |
| KR20210151780A (ko) * | 2019-02-04 | 2021-12-14 | 제네틱 바이오사이언시스, 인코포레이티드 | 글리코폴리시알화된 치료 단백질 사용 방법 |
| MX2022000285A (es) | 2019-07-08 | 2022-02-03 | Gi Innovation Inc | Dimero de polipeptido con alto contenido de acido sialico, que comprende el dominio extracelular de la subunidad alfa del receptor fc de ige y composicion farmaceutica que comprende el mismo. |
| WO2022033480A1 (zh) * | 2020-08-11 | 2022-02-17 | 隆延生物科技(上海)有限公司 | 一种液体制剂及其应用 |
| CN114966021B (zh) * | 2022-05-19 | 2025-03-04 | 山东博科生物产业有限公司 | 一种稳定的脂蛋白相关磷脂酶a2测定试剂盒 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0733793A (ja) * | 1993-07-23 | 1995-02-03 | Snow Brand Milk Prod Co Ltd | シアル酸粉末 |
| JPH09506116A (ja) * | 1994-10-12 | 1997-06-17 | アムジエン・インコーポレーテツド | N末端化学修飾タンパク質組成物および方法 |
| JP2003533537A (ja) * | 2000-05-16 | 2003-11-11 | リポクセン テクノロジーズ リミテッド | タンパク質の誘導体化 |
| WO2005016973A1 (en) * | 2003-08-12 | 2005-02-24 | Lipoxen Technologies Limited | Polysialic acid derivatives |
| WO2005016974A1 (en) * | 2003-08-12 | 2005-02-24 | Lipoxen Technologies Limited | Sialic acid derivatives for protein derivatisation and conjugation |
| WO2006016168A2 (en) * | 2004-08-12 | 2006-02-16 | Lipoxen Technologies Limited | Sialic acid derivatives |
Family Cites Families (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| DE2930542A1 (de) | 1979-07-27 | 1981-02-12 | Hoechst Ag | Neue insulinderivate und verfahren zu ihrer herstellung |
| US5308617A (en) * | 1988-08-10 | 1994-05-03 | Halzyme Ltd. | Protein heparin conjugates |
| US7217689B1 (en) * | 1989-10-13 | 2007-05-15 | Amgen Inc. | Glycosylation analogs of erythropoietin |
| AU646822B2 (en) * | 1989-10-13 | 1994-03-10 | Kirin-Amgen Inc. | Erythropoietin isoforms |
| US5846951A (en) | 1991-06-06 | 1998-12-08 | The School Of Pharmacy, University Of London | Pharmaceutical compositions |
| GB9112212D0 (en) | 1991-06-06 | 1991-07-24 | Gregoriadis Gregory | Pharmaceutical compositions |
| ES2115638T3 (es) | 1991-12-30 | 1998-07-01 | Akzo Nobel Nv | Composicion tiroactiva de liberacion controlada. |
| US20030053982A1 (en) * | 1994-09-26 | 2003-03-20 | Kinstler Olaf B. | N-terminally chemically modified protein compositions and methods |
| CA2299548C (en) * | 1997-08-05 | 2009-12-29 | Bioniche Inc. | Composition and method for regulating cell proliferation and cell death |
| AU2794199A (en) | 1998-02-26 | 1999-09-15 | Robertas Bunevicius | Thyroid hormone replacement using sustained release triiodothyronine |
| RU2141531C1 (ru) | 1999-05-26 | 1999-11-20 | Российское акционерное общество открытого типа "Биопрепарат" | Способ получения рекомбинантного инсулина человека |
| US6323311B1 (en) * | 1999-09-22 | 2001-11-27 | University Of Utah Research Foundation | Synthesis of insulin derivatives |
| DE60116758T2 (de) | 2000-05-18 | 2006-11-02 | Therics, Inc. | Einkapselung eines toxischen kerns in einen nicht-toxischen bereich in einer oralen darreichungsform |
| US7118737B2 (en) * | 2000-09-08 | 2006-10-10 | Amylin Pharmaceuticals, Inc. | Polymer-modified synthetic proteins |
| DE60137525D1 (de) * | 2000-10-16 | 2009-03-12 | Chugai Pharmaceutical Co Ltd | Peg-modifiziertes erythropoietin |
| JP4656814B2 (ja) | 2000-12-20 | 2011-03-23 | エフ.ホフマン−ラ ロシュ アーゲー | エリスロポエチンコンジュゲート |
| KR100401296B1 (ko) | 2000-12-27 | 2003-10-11 | 드림바이오젠 주식회사 | 수식물질에 의해 수식된 단백질 변이체 및 이것의 제조방법 |
| ES2411007T3 (es) | 2001-10-10 | 2013-07-04 | Novo Nordisk A/S | Remodelación y glicoconjugación de péptidos |
| US7125843B2 (en) * | 2001-10-19 | 2006-10-24 | Neose Technologies, Inc. | Glycoconjugates including more than one peptide |
| WO2003055526A2 (en) | 2001-12-21 | 2003-07-10 | Maxygen Aps | Erythropoietin conjugates |
| ITPD20010302A1 (it) | 2001-12-28 | 2003-06-28 | Bbs Riva Spa | Dispositivo idraulico per pompare e / p intercettare metallo allo stato fuso |
| US6763226B1 (en) | 2002-07-31 | 2004-07-13 | Computer Science Central, Inc. | Multifunctional world wide walkie talkie, a tri-frequency cellular-satellite wireless instant messenger computer and network for establishing global wireless volp quality of service (qos) communications, unified messaging, and video conferencing via the internet |
| EP1681303B1 (en) * | 2002-09-11 | 2013-09-04 | Fresenius Kabi Deutschland GmbH | HASylated polypeptides, especially HASylated erythropoietin |
| KR101045401B1 (ko) * | 2002-09-11 | 2011-06-30 | 프레제니우스 카비 도이치란트 게엠베하 | 하이드록시알킬 전분 유도체 |
| EP1400533A1 (en) * | 2002-09-11 | 2004-03-24 | Fresenius Kabi Deutschland GmbH | HASylated polypeptides, especially HASylated erythropoietin |
| CN1777440A (zh) | 2003-04-11 | 2006-05-24 | Pr药品有限公司 | 位点特异性蛋白质偶联物的制备方法 |
| WO2004101619A1 (ja) | 2003-05-15 | 2004-11-25 | Shionogi Co., Ltd. | 機能的糖ペプチドの合理的設計および合成 |
| US7074755B2 (en) | 2003-05-17 | 2006-07-11 | Centocor, Inc. | Erythropoietin conjugate compounds with extended half-lives |
| WO2005003149A1 (en) | 2003-07-03 | 2005-01-13 | Cipla Limited | Process for the preparation of finasteride form i |
| CA2534652C (en) | 2003-08-05 | 2013-12-10 | Dematic Corp. | Motorized roller transverse drive |
| CA2948114C (en) | 2003-08-06 | 2019-02-26 | Che-Hung Robert Lee | Polysaccharide-protein conjugate vaccines |
| MXPA06001358A (es) | 2003-08-08 | 2006-05-15 | Fresenius Kabi Gmbh | Conjugados de hidroxialquil almidon y g-csf. |
| KR20060120141A (ko) * | 2003-11-24 | 2006-11-24 | 네오스 테크놀로지스, 인크. | 글리코페질화 에리트로포이에틴 |
| US7956032B2 (en) * | 2003-12-03 | 2011-06-07 | Novo Nordisk A/S | Glycopegylated granulocyte colony stimulating factor |
| AU2004296855B2 (en) | 2003-12-03 | 2011-01-06 | Ratiopharm Gmbh | Glycopegylated Granulocyte Colony Stimulating Factor |
| CN101659704A (zh) * | 2004-03-11 | 2010-03-03 | 弗雷泽纽斯卡比德国有限公司 | 通过还原氨基化制备的羟烷基淀粉和蛋白质的偶联物 |
| FR2868071B1 (fr) * | 2004-03-26 | 2006-06-09 | Biomerieux Sa | Reactifs de marquage, procedes de synthese de tels reactifs et procedes de detection de molecules biologiques |
| DE102004030392A1 (de) | 2004-06-23 | 2006-01-19 | Endress + Hauser Flowtec Ag, Reinach | Meßwandler vom Vibrationstyp |
| WO2006014148A2 (fr) | 2004-08-04 | 2006-02-09 | Sergey Alexandrovich Orlov | Procede permettant d'organiser un processus de jeu a action intermittente |
| GB2416993A (en) | 2004-08-11 | 2006-02-15 | Dinesh Verma | Opthalmic prosthesis |
| US8652334B2 (en) | 2004-08-12 | 2014-02-18 | Lipoxen Technologies Limited | Fractionation of charged polysaccharide |
| WO2006074467A2 (en) | 2005-01-10 | 2006-07-13 | Neose Technologies, Inc. | Glycopegylated granulocyte colony stimulating factor |
| TWI376234B (en) * | 2005-02-01 | 2012-11-11 | Msd Oss Bv | Conjugates of a polypeptide and an oligosaccharide |
| US8217154B2 (en) | 2005-02-23 | 2012-07-10 | Lipoxen Technologies Limited | Activated sialic acid derivatives for protein derivatisation and conjugation |
| JP3989936B2 (ja) * | 2005-04-07 | 2007-10-10 | 進 須永 | 抗腫瘍剤及び新規dnアーゼ |
| US20070099820A1 (en) | 2005-10-19 | 2007-05-03 | Smartcells, Inc. | Polymer-drug conjugates |
| KR101400105B1 (ko) * | 2006-07-25 | 2014-06-19 | 리폭센 테크놀로지즈 리미티드 | N-말단 폴리시알화 |
| CN102470144A (zh) | 2009-07-16 | 2012-05-23 | 花王株式会社 | 进食后血中胰岛素浓度上升抑制剂 |
| US9006400B2 (en) | 2011-09-26 | 2015-04-14 | Novartis Ag | Fibroblast growth factor-21-Fc fusion proteins |
-
2007
- 2007-07-25 KR KR1020097003805A patent/KR101400105B1/ko not_active Expired - Fee Related
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Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0733793A (ja) * | 1993-07-23 | 1995-02-03 | Snow Brand Milk Prod Co Ltd | シアル酸粉末 |
| JPH09506116A (ja) * | 1994-10-12 | 1997-06-17 | アムジエン・インコーポレーテツド | N末端化学修飾タンパク質組成物および方法 |
| JP2003533537A (ja) * | 2000-05-16 | 2003-11-11 | リポクセン テクノロジーズ リミテッド | タンパク質の誘導体化 |
| WO2005016973A1 (en) * | 2003-08-12 | 2005-02-24 | Lipoxen Technologies Limited | Polysialic acid derivatives |
| WO2005016974A1 (en) * | 2003-08-12 | 2005-02-24 | Lipoxen Technologies Limited | Sialic acid derivatives for protein derivatisation and conjugation |
| JP2007501889A (ja) * | 2003-08-12 | 2007-02-01 | リポクセン テクノロジーズ リミテッド | タンパク質の誘導体化及び結合のためのシアル酸誘導体 |
| WO2006016168A2 (en) * | 2004-08-12 | 2006-02-16 | Lipoxen Technologies Limited | Sialic acid derivatives |
Non-Patent Citations (2)
| Title |
|---|
| JPN6011051325; Biochim. Biophys. Acta. vol.1622, 2003, p.42-9 * |
| JPN6011051329; Int. J. Pharm. vol.300, 2005, p.125-30 * |
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