JP2008536479A - ジスルフィド架橋を有するタンパク質の発現法 - Google Patents
ジスルフィド架橋を有するタンパク質の発現法 Download PDFInfo
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- JP2008536479A JP2008536479A JP2007556197A JP2007556197A JP2008536479A JP 2008536479 A JP2008536479 A JP 2008536479A JP 2007556197 A JP2007556197 A JP 2007556197A JP 2007556197 A JP2007556197 A JP 2007556197A JP 2008536479 A JP2008536479 A JP 2008536479A
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- disintegrin
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| JP2019526253A (ja) * | 2016-08-25 | 2019-09-19 | ネクスゼン バイオテクノロジーズ インコーポレイテッドＮｅｘｇｅｎ Ｂｉｏｔｅｃｈｎｏｌｏｇｉｅｓ， Ｉｎｃ． | 皮膚細胞の増殖効果が増大したサソリ毒融合タンパク質及びそれを有効成分として含有するシワ改善、皮膚弾力の増大及びアンチエイジング化粧料組成物 |
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| EP2029156A4 (en) * | 2006-05-01 | 2010-07-21 | Univ Southern California | COMBINATION THERAPY FOR CANCER TREATMENT |
| US7943728B2 (en) * | 2006-12-26 | 2011-05-17 | National Cheng Kung University | Disintegrin variants and their use in treating osteoporosis-induced bone loss and angiogenesis-related diseases |
| US8802394B2 (en) | 2008-11-13 | 2014-08-12 | Radu O. Minea | Method of expressing proteins with disulfide bridges with enhanced yields and activity |
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| US20130045244A1 (en) * | 2010-02-11 | 2013-02-21 | University Of Southern California | Modified adam disintegrin domain polypeptides and uses thereof |
| CN102154336A (zh) * | 2011-01-25 | 2011-08-17 | 国家海洋局第三海洋研究所 | 嗜酸硫化芽孢杆菌硫氧还蛋白还原酶基因及其重组蛋白 |
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| CN105039377A (zh) * | 2015-08-24 | 2015-11-11 | 武汉真福医药股份有限公司 | 溶栓酶基因qk-02的表达方法及专用表达载体和工程菌 |
| CN108472330A (zh) * | 2015-11-13 | 2018-08-31 | 南加利福尼亚大学 | 作为近距离放射治疗剂的放射性标记的去整合素 |
| US10258567B1 (en) | 2016-11-17 | 2019-04-16 | Grace Procurements Llc | Vaginal probiotic products and related processes |
| CN107384934A (zh) * | 2017-08-18 | 2017-11-24 | 安徽安科生物工程（集团）股份有限公司 | 重组人干扰素α2b的制备方法 |
| US11169583B2 (en) * | 2018-08-07 | 2021-11-09 | Western Digital Technologies, Inc. | Methods and apparatus for mitigating temperature increases in a solid state device (SSD) |
| CA3114395A1 (en) * | 2018-09-25 | 2020-04-02 | Absci, Llc | Protein purification methods |
| CA3117992A1 (en) | 2018-11-08 | 2020-05-14 | Sutro Biopharma, Inc. | E coli strains having an oxidative cytoplasm |
| US12351850B2 (en) | 2020-04-30 | 2025-07-08 | Sutro Biopharma, Inc. | Methods of producing full-length antibodies using E. coli |
| CN114107353B (zh) * | 2021-10-29 | 2024-07-23 | 成都佩德生物医药有限公司 | 一种高效表达多肽毒素的质粒及其制备方法与应用 |
| EP4361172A3 (en) | 2022-10-27 | 2024-05-29 | Science4Beauty Sp. z o.o. | Expression vector for recombinant u-conotoxin tiiia or tiiialamut expression in e.coli |
| CN117756949B (zh) * | 2024-02-21 | 2024-10-15 | 中国人民解放军军事科学院军事医学研究院 | 一种正痘病毒属融合抗原及应用 |
| CN120118913B (zh) * | 2025-05-14 | 2025-09-02 | 中国科学院苏州纳米技术与纳米仿生研究所 | 一种编码人防御素的核酸分子及制备人防御素方法和应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000245467A (ja) * | 1999-02-26 | 2000-09-12 | Agency Of Ind Science & Technol | Ｓｐａｒｃ融合タンパク質およびその製造方法 |
| JP2002528058A (ja) * | 1998-09-29 | 2002-09-03 | ザ・ユニバーシティー・オブ・サザン・カリフォルニア | コントートロスタチン（ｃｎ）、並びに転移及び他の症状の抑制におけるその使用方法 |
| JP2004500357A (ja) * | 1999-12-10 | 2004-01-08 | ザ・ユニバーシティー・オブ・サザン・カリフォルニア | コントートロスタチン（ｃｎ）並びに転移及びその他の症状の予防におけるその使用法 |
Family Cites Families (106)
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| US4610879A (en) | 1984-01-06 | 1986-09-09 | University Of Southern California | Fibrinolytic enzyme from snake vernom |
| US5066592A (en) | 1988-03-08 | 1991-11-19 | Temple University Of The Commonwealth System Of Higher Education | Trigramin - a platelet aggregation inhibiting polypeptide |
| US6133029A (en) | 1988-03-21 | 2000-10-17 | Chiron Corporation | Replication defective viral vectors for infecting human cells |
| US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| US5278324A (en) | 1990-08-28 | 1994-01-11 | Virginia Tech Intellectual Properties, Inc. | Water soluble derivatives of taxol |
| US5250683A (en) | 1991-09-23 | 1993-10-05 | Florida State University | Certain substituted taxanes and pharmaceutical compositions containing them |
| US5227400A (en) | 1991-09-23 | 1993-07-13 | Florida State University | Furyl and thienyl substituted taxanes and pharmaceutical compositions containing them |
| US5272171A (en) | 1992-02-13 | 1993-12-21 | Bristol-Myers Squibb Company | Phosphonooxy and carbonate derivatives of taxol |
| US5248796A (en) | 1992-06-18 | 1993-09-28 | Bristol-Myers Squibb Company | Taxol derivatives |
| US5254580A (en) | 1993-01-19 | 1993-10-19 | Bristol-Myers Squibb Company | 7,8-cyclopropataxanes |
| FR2705686B1 (fr) | 1993-05-28 | 1995-08-18 | Transgene Sa | Nouveaux adénovirus défectifs et lignées de complémentation correspondantes. |
| US6080569A (en) | 1993-06-24 | 2000-06-27 | Merck & Co., Inc. | Adenovirus vectors generated from helper viruses and helper-dependent vectors |
| US20030186884A1 (en) * | 2000-06-08 | 2003-10-02 | Markland Francis S. | Contortrostatin (CN) and methods for its use in preventing metastasis and other conditions |
| US6710030B1 (en) * | 1993-10-22 | 2004-03-23 | University Of Southern California | Contortrostain (CN) and methods for its use in preventing metastasis and other conditions |
| US5731288A (en) * | 1993-10-22 | 1998-03-24 | University Of Southern California | Compositions containing contortrostatin and methods for the use thereof |
| US7220724B2 (en) * | 1993-10-22 | 2007-05-22 | University Of Southern California | Contortrostatin CN and methods for its use in preventing metastasis and other conditions |
| US5814609A (en) * | 1993-10-22 | 1998-09-29 | University Of Southern California | Compositions containing a disintegrin and methods for its use in preventing metastasis and other conditions |
| US5658785A (en) | 1994-06-06 | 1997-08-19 | Children's Hospital, Inc. | Adeno-associated virus materials and methods |
| FR2725726B1 (fr) | 1994-10-17 | 1997-01-03 | Centre Nat Rech Scient | Vecteurs viraux et utilisation en therapie genique |
| US5641665A (en) | 1994-11-28 | 1997-06-24 | Vical Incorporated | Plasmids suitable for IL-2 expression |
| US6040295A (en) | 1995-01-13 | 2000-03-21 | Genemedicine, Inc. | Formulated nucleic acid compositions and methods of administering the same for gene therapy |
| ATE204329T1 (de) | 1995-05-22 | 2001-09-15 | Us Gov Health & Human Serv | Retrovirale vektoren aus gefluegel-sarcom- leukoseviren ermoeglichen den transfer von genen in saeugetierzellen und ihre therapeutischen anwendungen |
| AU5253998A (en) | 1996-11-13 | 1998-06-03 | Board Of Regents, The University Of Texas System | Diminishing viral gene expression by promoter replacement |
| US6660758B1 (en) | 1996-12-13 | 2003-12-09 | The Scripps Research Institute | Epothilone analogs |
| US6380394B1 (en) | 1996-12-13 | 2002-04-30 | The Scripps Research Institute | Epothilone analogs |
| US6441186B1 (en) | 1996-12-13 | 2002-08-27 | The Scripps Research Institute | Epothilone analogs |
| US6034072A (en) | 1997-02-10 | 2000-03-07 | Genemedicine, Inc. | IL-2 gene expression and delivery systems and uses |
| DE19713213A1 (de) | 1997-03-28 | 1998-10-01 | Ruebben Alexander Dr Med | Metallstent zur verlängerten Offenhaltung von Hohlorganen |
| AUPO742497A0 (en) * | 1997-06-18 | 1997-07-10 | N.J. Phillips Pty. Limited | An applicator |
| US6605599B1 (en) | 1997-07-08 | 2003-08-12 | Bristol-Myers Squibb Company | Epothilone derivatives |
| AU9340998A (en) | 1997-08-09 | 1999-03-01 | Schering Aktiengesellschaft | New epothilone derivatives, method for producing same and their pharmaceutical use |
| US6365749B1 (en) | 1997-12-04 | 2002-04-02 | Bristol-Myers Squibb Company | Process for the preparation of ring-opened epothilone intermediates which are useful for the preparation of epothilone analogs |
| US6498257B1 (en) | 1998-04-21 | 2002-12-24 | Bristol-Myers Squibb Company | 2,3-olefinic epothilone derivatives |
| US6399638B1 (en) | 1998-04-21 | 2002-06-04 | Bristol-Myers Squibb Company | 12,13-modified epothilone derivatives |
| DE19820599A1 (de) | 1998-05-08 | 1999-11-11 | Biotechnolog Forschung Gmbh | Epothilonderivate, Verfahren zu deren Herstellung und deren Verwendung |
| DE19826988A1 (de) | 1998-06-18 | 1999-12-23 | Biotechnolog Forschung Gmbh | Epothilon-Nebenkomponenten |
| DE19848306A1 (de) | 1998-10-14 | 2000-04-20 | Schering Ag | Verfahren zur Herstellung von Epothilon B und Derivaten sowie Zwischenprodukte für dieses Verfahren |
| US6440944B2 (en) | 1998-10-16 | 2002-08-27 | Genvec, Inc. | Methods of administering adenoviral vectors |
| EP1135470A2 (en) | 1998-11-20 | 2001-09-26 | Kosan Biosciences, Inc. | Recombinant methods and materials for producing epothilone and epothilone derivatives |
| EP1140944B1 (en) | 1998-12-22 | 2003-08-27 | Novartis AG | Epothilone derivatives and their use as antitumor agents |
| US6780620B1 (en) | 1998-12-23 | 2004-08-24 | Bristol-Myers Squibb Company | Microbial transformation method for the preparation of an epothilone |
| US6596875B2 (en) | 2000-02-07 | 2003-07-22 | James David White | Method for synthesizing epothilones and epothilone analogs |
| WO2000047584A2 (de) | 1999-02-11 | 2000-08-17 | Schering Aktiengesellschaft | Epothilon-derivate, verfahren zu deren herstellung und ihre pharmazeutische verwendung |
| US6406722B1 (en) | 1999-02-18 | 2002-06-18 | Robert G. Gallaher | Method of treating viral infections and lesions with taxane compounds |
| CZ20012951A3 (cs) | 1999-02-18 | 2001-11-14 | Schering Aktiengesellschaft | 16-Halogensubstituované deriváty epothilonu, způsoby jejich výroby a jejich farmaceutické pouľití |
| US6387664B1 (en) * | 1999-02-26 | 2002-05-14 | Secretary Of Agency Of Industrial Science And Technology | Sparc fusion protein and method for producing the same |
| AU772750C (en) | 1999-04-30 | 2005-02-24 | Schering Aktiengesellschaft | 6-alkenyl-, 6-alkinyl- and 6-epoxy-epothilone derivatives, process for their production, and their use in pharmaceutical preparations |
| US6878699B1 (en) | 1999-05-21 | 2005-04-12 | University Of Hawaii | Taccalonolide microtubule stabilizing agents |
| US20050042275A1 (en) | 1999-08-04 | 2005-02-24 | Jean-Claude Sonntag | Epothilone compositions |
| US6294374B1 (en) | 1999-10-08 | 2001-09-25 | The Scripps Research Institute | Use of catalytic antibodies for synthesizing epothilone |
| US6518421B1 (en) | 2000-03-20 | 2003-02-11 | Bristol-Myers Squibb Company | Process for the preparation of epothilone analogs |
| US6593115B2 (en) | 2000-03-24 | 2003-07-15 | Bristol-Myers Squibb Co. | Preparation of epothilone intermediates |
| TWI310684B (en) | 2000-03-27 | 2009-06-11 | Bristol Myers Squibb Co | Synergistic pharmaceutical kits for treating cancer |
| DE10020517A1 (de) | 2000-04-19 | 2001-10-25 | Schering Ag | Neue Epothilon-Derivate, Verfahren zu deren Herstellung und ihre pharmazeutische Verwendung |
| US6489314B1 (en) | 2001-04-03 | 2002-12-03 | Kosan Biosciences, Inc. | Epothilone derivatives and methods for making and using the same |
| US6998256B2 (en) | 2000-04-28 | 2006-02-14 | Kosan Biosciences, Inc. | Methods of obtaining epothilone D using crystallization and /or by the culture of cells in the presence of methyl oleate |
| US6589968B2 (en) | 2001-02-13 | 2003-07-08 | Kosan Biosciences, Inc. | Epothilone compounds and methods for making and using the same |
| AU2001266583A1 (en) | 2000-05-26 | 2001-12-11 | Kosan Biosciences, Inc. | Epothilone derivatives and methods for making and using the same |
| US6638742B1 (en) | 2000-07-07 | 2003-10-28 | University Of Portland | Methods for obtaining taxanes |
| UA75365C2 (en) | 2000-08-16 | 2006-04-17 | Bristol Myers Squibb Co | Epothilone analog polymorph modifications, a method for obtaining thereof (variants), a pharmaceutical composition based thereon |
| DE50111753D1 (de) | 2000-10-16 | 2007-02-08 | R & D Biopharmaceuticals | Epothilon-synthesebausteine i: unsymmetrisch substituierte acyloine und acyloinderivate, verfahren zu deren herstellung sowie deren verwendung zur herstellung von epothilonen und epothilonderivaten |
| US20040038324A1 (en) | 2000-11-22 | 2004-02-26 | Atadja Peter Wisdom. | Epothilone resistant cell lines |
| RU2292904C2 (ru) | 2001-01-09 | 2007-02-10 | Мерк Патент Гмбх | Комбинированная терапия, использующая ингибиторы рецептора тирозинкиназы и ингибиторы ангиогенезиса |
| EP1353668B1 (en) | 2001-01-25 | 2008-03-19 | Bristol-Myers Squibb Company | Processes for the preparation of pharmaceutical preparations containing epothilone analogues for the treatment of cancer |
| CN1489466A (zh) | 2001-01-25 | 2004-04-14 | ����˹�ж�-����˹˹������˾ | 包含埃博霉素类似物的非肠道制剂 |
| US20030004338A1 (en) | 2001-02-01 | 2003-01-02 | Li Wen Sen | Process for the preparation of epothilone analogs |
| US6893859B2 (en) | 2001-02-13 | 2005-05-17 | Kosan Biosciences, Inc. | Epothilone derivatives and methods for making and using the same |
| CN1610549A (zh) | 2001-02-20 | 2005-04-27 | 布里斯托尔-迈尔斯斯奎布公司 | 用于治疗难治肿瘤的埃坡霉素衍生物 |
| MXPA03007394A (es) | 2001-02-20 | 2003-12-04 | Bristol Myers Squibb Co | Tratamiento de tumores refractarios mediante uso de derivados de epotilona. |
| DE60232719D1 (de) | 2001-02-27 | 2009-08-06 | Novartis Ag | Kombination enthaltend einen inhibitor der signaltransduktion und ein epothilonderivat |
| CA2440555A1 (en) | 2001-03-14 | 2002-09-19 | Bristol-Myers Squibb Company | Combination of epothilone analogs and chemotherapeutic agents for the treatment of proliferative diseases |
| WO2002074042A2 (en) | 2001-03-19 | 2002-09-26 | Novartis Ag | Combinations comprising an antidiarrheal agent and an epothilone or an epothilone derivative |
| US6906188B2 (en) | 2001-04-30 | 2005-06-14 | State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of Oregon State University | Method for synthesizing epothilones and epothilone analogs |
| US20030023082A1 (en) | 2001-05-15 | 2003-01-30 | Gary Ashley | Epothilone derivatives and methods for making and using the same |
| JP2004532888A (ja) | 2001-06-01 | 2004-10-28 | ブリストル−マイヤーズ スクイブ カンパニー | エポチロン誘導体 |
| DE10138347A1 (de) | 2001-08-03 | 2003-02-27 | Schering Ag | Geschützte 3,5-Dihydroxy-2,2-dimethyl-valeronitrile für die Synthese von Epothilonen- und Derivaten und Verfahren zur Herstellung |
| CN100536841C (zh) | 2001-08-23 | 2009-09-09 | 诺瓦提斯公司 | 环丙基和环丁基埃坡霉素类似物 |
| US20030186334A1 (en) | 2001-09-12 | 2003-10-02 | Temple University - Of The Commonwealth System Of Higher Education | KTS-disintegrins |
| WO2003029195A1 (en) | 2001-09-28 | 2003-04-10 | Sumika Fine Chemicals Co., Ltd. | Intermediates for epothilone derivative and process for producing these |
| WO2003042217A2 (en) | 2001-11-15 | 2003-05-22 | Kosan Biosciences, Inc. | Method for making epothilone compounds by bioconversion with microorganisms |
| TW200408407A (en) | 2001-11-30 | 2004-06-01 | Dana Farber Cancer Inst Inc | Methods and compositions for modulating the immune system and uses thereof |
| DE10164592A1 (de) | 2001-12-21 | 2003-07-03 | Schering Ag | C1-C6-Epothilon-Fragmente und Verfahren für die Herstellung von C1-C6-Fragmenten von Epothilonen und deren Derivaten |
| TW200303202A (en) | 2002-02-15 | 2003-09-01 | Bristol Myers Squibb Co | Method of preparation of 21-amino epothilone derivatives |
| AU2003212457A1 (en) | 2002-03-01 | 2003-09-16 | University Of Notre Dame | Derivatives of epothilone b and d and synthesis thereof |
| WO2003077903A1 (en) | 2002-03-12 | 2003-09-25 | Bristol-Myers Squibb Company | C12-cyano epothilone derivatives |
| DK1483251T3 (da) | 2002-03-12 | 2010-04-12 | Bristol Myers Squibb Co | C3-cyano-epothilon-derivater |
| RU2358730C2 (ru) | 2002-05-01 | 2009-06-20 | Новартис Аг | Производное эпотилона для лечения гепатомы и других раковых заболеваний |
| TW200400191A (en) | 2002-05-15 | 2004-01-01 | Bristol Myers Squibb Co | Pharmaceutical compositions and methods of using C-21 modified epothilone derivatives |
| JP2006514681A (ja) | 2002-05-20 | 2006-05-11 | コーザン バイオサイエンシス インコーポレイテッド | エポチロンｄの投与方法 |
| US7799561B2 (en) | 2002-06-12 | 2010-09-21 | Sigma-Aldrich, Co. | Affinity peptides and method for purification of recombinant proteins |
| US7008936B2 (en) | 2002-06-14 | 2006-03-07 | Bristol-Myers Squibb Company | Combination of epothilone analogs and chemotherapeutic agents for the treatment of proliferative diseases |
| CN100439374C (zh) | 2002-08-02 | 2008-12-03 | 诺瓦提斯公司 | 埃坡霉素衍生物 |
| US7053201B2 (en) | 2002-08-30 | 2006-05-30 | National Defense Medical Center | Nucleic acid molecules and polypeptides related to h-ADAM7 |
| BRPI0314133A8 (pt) | 2002-09-23 | 2017-09-19 | Bristol Myers Squibb Co | Processo para isolamento de epotilona b, métodos para cultivo de microorganismo que produza epotilona a ou b e para purifiação de apotilona |
| GB0230024D0 (en) | 2002-12-23 | 2003-01-29 | Novartis Ag | Organic compounds |
| JP2004217535A (ja) | 2003-01-10 | 2004-08-05 | Nec Soft Ltd | 蛋白質ｔｒｉｍｅｓｔａｔｉｎの結晶化、構造座標の決定、構造座標の使用 |
| US7763430B2 (en) * | 2003-04-22 | 2010-07-27 | Baxter International Inc. | Diagnostic assay for anti-von Willebrand Factor cleaving protease (ADAMTS13) antibodies |
| PL1664033T3 (pl) | 2003-09-25 | 2008-04-30 | Tapestry Pharmaceuticals Inc | Analogi 9,10-alfa, alfa-OH-taksanu i sposoby ich wytwarzania |
| US7960513B2 (en) | 2004-12-17 | 2011-06-14 | Monash University | Antibody against a human ADAM protease |
| JP2008536479A (ja) | 2005-02-11 | 2008-09-11 | ユニバーシティ オブ サザン カリフォルニア | ジスルフィド架橋を有するタンパク質の発現法 |
| US9265933B2 (en) | 2005-09-08 | 2016-02-23 | Massachusetts Eye And Ear Infirmary | Cochlear implants containing biological cells and uses thereof |
| EP2029156A4 (en) * | 2006-05-01 | 2010-07-21 | Univ Southern California | COMBINATION THERAPY FOR CANCER TREATMENT |
| US8852290B2 (en) | 2007-03-02 | 2014-10-07 | Doheny Eye Institute | Biocompatible implants and methods of making and attaching the same |
| US8802394B2 (en) | 2008-11-13 | 2014-08-12 | Radu O. Minea | Method of expressing proteins with disulfide bridges with enhanced yields and activity |
| WO2010093976A1 (en) | 2009-02-12 | 2010-08-19 | University Of Southern California | Bioadhesive patch for sutureless closure of soft tissue |
| US20130045244A1 (en) | 2010-02-11 | 2013-02-21 | University Of Southern California | Modified adam disintegrin domain polypeptides and uses thereof |
-
2006
- 2006-02-09 JP JP2007556197A patent/JP2008536479A/ja active Pending
- 2006-02-09 EP EP06849695A patent/EP1856255A4/en not_active Withdrawn
- 2006-02-09 US US11/351,311 patent/US7754850B2/en not_active Expired - Fee Related
- 2006-02-09 EP EP13157149.9A patent/EP2634252B1/en not_active Not-in-force
- 2006-02-09 CN CNA2006800117606A patent/CN101535492A/zh active Pending
- 2006-02-09 WO PCT/US2006/004413 patent/WO2007086879A2/en not_active Ceased
- 2006-02-09 CA CA002597647A patent/CA2597647A1/en not_active Abandoned
- 2006-02-09 AU AU2006336468A patent/AU2006336468B2/en not_active Ceased
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- 2010-07-06 US US12/831,226 patent/US8110542B2/en not_active Expired - Fee Related
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002528058A (ja) * | 1998-09-29 | 2002-09-03 | ザ・ユニバーシティー・オブ・サザン・カリフォルニア | コントートロスタチン（ｃｎ）、並びに転移及び他の症状の抑制におけるその使用方法 |
| JP2000245467A (ja) * | 1999-02-26 | 2000-09-12 | Agency Of Ind Science & Technol | Ｓｐａｒｃ融合タンパク質およびその製造方法 |
| JP2004500357A (ja) * | 1999-12-10 | 2004-01-08 | ザ・ユニバーシティー・オブ・サザン・カリフォルニア | コントートロスタチン（ｃｎ）並びに転移及びその他の症状の予防におけるその使用法 |
Non-Patent Citations (8)
| Title |
|---|
| JPN6011063282; Ｊ．Ｂｉｏｌ．Ｃｈｅｍ．，Ｖｏｌ．２７４，Ｎｏ．５３（１９９９）ｐ．３７８０９-３７８１４ * |
| JPN6011063283; Ａｒｃｈ．Ｂｉｏｃｈｅｍ．Ｂｉｏｐｈｙｓ．，Ｖｏｌ．３６９，Ｎｏ．２（１９９９）ｐ．２９５-３０１ * |
| JPN6011063284; Ｐａｔｈｏｐｈｙｓｉｏｌ．Ｈａｅｍｏｓｔ．Ｔｈｒｏｍｂ．，Ｖｏｌ．３４，Ｎｏ．４-５（２００５）ｐ．１７７-１８３ * |
| JPN6011063285; Ｊ．Ｂｉｏｌ．Ｃｈｅｍ．，Ｖｏｌ．２７０，Ｎｏ．４３（１９９５）ｐ．２５３２８-２５３３１ * |
| JPN6011063286; Ｐｒｏｔｅｉｎ Ｅｘｐｒ．Ｐｕｒｉｆ．，Ｖｏｌ．３５，Ｎｏ．２（２００４）ｐ．３４４-３５２ * |
| JPN6011063287; Ｍｉｃｒｏｂｉｏｌ．Ｒｅｖ．，Ｖｏｌ．６０，Ｎｏ．３（１９９６）ｐ．５１２-５３８ * |
| JPN6011063288; Ｐｒｏｔｅｉｎ Ｅｘｐｒ．Ｐｕｒｉｆ．，Ｖｏｌ．３８，Ｎｏ．１（２００４）ｐ．５１-６０ * |
| JPN6011063289; Ｊ．Ｇｅｎ．Ｖｉｒｏｌ．，Ｖｏｌ．７３，Ｐｔ．４（１９９２）ｐ．７７５-７８３ * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019526253A (ja) * | 2016-08-25 | 2019-09-19 | ネクスゼン バイオテクノロジーズ インコーポレイテッドＮｅｘｇｅｎ Ｂｉｏｔｅｃｈｎｏｌｏｇｉｅｓ， Ｉｎｃ． | 皮膚細胞の増殖効果が増大したサソリ毒融合タンパク質及びそれを有効成分として含有するシワ改善、皮膚弾力の増大及びアンチエイジング化粧料組成物 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1856255A4 (en) | 2010-01-27 |
| EP1856255A2 (en) | 2007-11-21 |
| EP2634252A3 (en) | 2013-11-13 |
| AU2006336468B2 (en) | 2012-04-12 |
| US8110542B2 (en) | 2012-02-07 |
| US7754850B2 (en) | 2010-07-13 |
| CA2597647A1 (en) | 2007-08-02 |
| AU2006336468A1 (en) | 2007-08-02 |
| EP2634252A2 (en) | 2013-09-04 |
| US20130345399A1 (en) | 2013-12-26 |
| US20060246541A1 (en) | 2006-11-02 |
| EP2634252B1 (en) | 2018-12-19 |
| WO2007086879A3 (en) | 2009-06-11 |
| US8338365B2 (en) | 2012-12-25 |
| US8685668B2 (en) | 2014-04-01 |
| US20120301453A1 (en) | 2012-11-29 |
| WO2007086879A2 (en) | 2007-08-02 |
| AU2006336468A2 (en) | 2010-04-29 |
| CN101535492A (zh) | 2009-09-16 |
| US20110097388A1 (en) | 2011-04-28 |
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