CN103965347B - 经修饰干扰素β多肽和其用途 - Google Patents
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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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JP2010525821A (ja) * | 2007-05-02 | 2010-07-29 | アンブルックス,インコーポレイテッド | 修飾IFNβポリペプチドおよびこれらの使用 |
EP2231856A4 (en) | 2007-12-11 | 2011-05-18 | Scripps Research Inst | IN VIVO EXPRESSION OF NON-NATURAL AMINO ACIDS IN THE METHYLOTROPHIC YEAST PICHIA PASTORIS |
CN102307905B (zh) * | 2008-12-10 | 2015-11-25 | 斯克利普斯研究院 | 利用化学反应性非天然氨基酸产生载体-肽偶联物 |
US9238878B2 (en) | 2009-02-17 | 2016-01-19 | Redwood Bioscience, Inc. | Aldehyde-tagged protein-based drug carriers and methods of use |
GB0908393D0 (en) * | 2009-05-15 | 2009-06-24 | Almac Sciences Scotland Ltd | Labelling method |
JPWO2011024887A1 (ja) * | 2009-08-26 | 2013-01-31 | 国立大学法人 岡山大学 | 環状ペプチドを含む結合体およびその作製方法 |
AR080993A1 (es) * | 2010-04-02 | 2012-05-30 | Hanmi Holdings Co Ltd | Formulacion de accion prolongada de interferon beta donde se usa un fragmento de inmunoglobulina |
EP3572091B1 (en) | 2010-08-17 | 2023-12-13 | Ambrx, Inc. | Modified relaxin polypeptides and their uses |
US9567386B2 (en) | 2010-08-17 | 2017-02-14 | Ambrx, Inc. | Therapeutic uses of modified relaxin polypeptides |
CN101942026B (zh) * | 2010-10-14 | 2014-08-27 | 成都正能生物技术有限责任公司 | 长效干扰素融合蛋白及其用途 |
EP2663647A4 (en) | 2011-01-14 | 2015-08-19 | Redwood Bioscience Inc | POLYPEPTIDE IMMUNOGLOBULINS WITH ALDEHYDIC MARKING AND THEIR USE METHOD |
KR101838919B1 (ko) * | 2015-03-03 | 2018-03-15 | 에이비온 주식회사 | 인간 인터페론-베타 변이체가 접합된 면역사이토카인 및 이의 제조방법 |
EP3875477A1 (en) | 2015-04-17 | 2021-09-08 | Alpine Immune Sciences, Inc. | Immunomodulatory proteins with tunable affinities |
CN104761645A (zh) * | 2015-04-30 | 2015-07-08 | 山东禹王制药有限公司 | α干扰素融合蛋白制剂及应用 |
RU2614264C2 (ru) * | 2015-06-19 | 2017-03-24 | Федеральное государственное бюджетное учреждение "Государственный научный центр Институт иммунологии" Федерального медико-биологического агентства России | Оптимизированный ген, кодирующий рекомбинантный белок - аналог интерферона бета человека |
AU2017257504A1 (en) | 2016-04-26 | 2018-10-25 | R.P. Scherer Technologies, Llc | Antibody conjugates and methods of making and using the same |
US10513537B2 (en) | 2016-05-11 | 2019-12-24 | Ge Healthcare Bioprocess R&D Ab | Separation matrix |
US10730908B2 (en) | 2016-05-11 | 2020-08-04 | Ge Healthcare Bioprocess R&D Ab | Separation method |
US10703774B2 (en) | 2016-09-30 | 2020-07-07 | Ge Healthcare Bioprocess R&D Ab | Separation method |
US11753438B2 (en) | 2016-05-11 | 2023-09-12 | Cytiva Bioprocess R&D Ab | Method of cleaning and/or sanitizing a separation matrix |
EP3454887B1 (en) * | 2016-05-13 | 2021-01-20 | Orionis Biosciences BV | Targeted mutant interferon-beta and uses thereof |
US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
SG10201912034UA (en) | 2017-02-08 | 2020-02-27 | Bristol Myers Squibb Co | Modified relaxin polypeptides comprising a pharmacokinetic enhancer and uses thereof |
WO2019073315A1 (en) | 2017-10-09 | 2019-04-18 | Mansour Poorebrahim | ANALOGUE PEPTIDE OF INTERFERON-BETA |
KR20210009982A (ko) * | 2019-07-18 | 2021-01-27 | 에이비온 주식회사 | 2당화된 인터페론-베타 단백질의 정제 방법 |
KR102593710B1 (ko) * | 2020-04-29 | 2023-10-25 | 에이비온 주식회사 | 이중 돌연변이를 가지는 인간 인터페론-베타 변이체 및 인간 인터페론-베타 변이체의 안정성을 향상시키는 방법 |
WO2023288226A2 (en) * | 2021-07-12 | 2023-01-19 | Nektar Therapeutics | Polymer engineered forms of interferon-gamma and methods of use |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1852732A (zh) * | 2002-12-26 | 2006-10-25 | 山景医药公司 | 具有增强的生物学效用的干扰素-β的聚合物缀合物 |
Family Cites Families (316)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3773919A (en) * | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
US4289872A (en) * | 1979-04-06 | 1981-09-15 | Allied Corporation | Macromolecular highly branched homogeneous compound based on lysine units |
US6410697B1 (en) | 1979-04-20 | 2002-06-25 | Schering Corporation | Process for purifying human leukocyte interferon |
US5554513A (en) * | 1979-11-21 | 1996-09-10 | Yeda Research & Development Co. Ltd. | Production of recombinant human interferon-beta2 |
IE57069B1 (en) | 1980-04-03 | 1992-04-22 | Biogen Inc | Dna sequences,recombinant dna molecules and processes for producing human fibroblast interferon |
US6610830B1 (en) | 1980-07-01 | 2003-08-26 | Hoffman-La Roche Inc. | Microbial production of mature human leukocyte interferons |
US4414150A (en) * | 1980-11-10 | 1983-11-08 | Genentech, Inc. | Hybrid human leukocyte interferons |
US4456748A (en) * | 1981-02-23 | 1984-06-26 | Genentech, Inc. | Hybrid human leukocyte interferons |
FR2504010B1 (fr) * | 1981-04-15 | 1985-10-25 | Sanofi Sa | Medicaments anticancereux contenant la chaine a de la ricine associee a un anticorps antimelanome et procede pour leur preparation |
US4551433A (en) * | 1981-05-18 | 1985-11-05 | Genentech, Inc. | Microbial hybrid promoters |
JPS57206622A (en) * | 1981-06-10 | 1982-12-18 | Ajinomoto Co Inc | Blood substitute |
US4485045A (en) * | 1981-07-06 | 1984-11-27 | Research Corporation | Synthetic phosphatidyl cholines useful in forming liposomes |
US4614651A (en) * | 1981-07-12 | 1986-09-30 | Damon Biotech, Inc. | Interferon epsilon |
NZ201705A (en) | 1981-08-31 | 1986-03-14 | Genentech Inc | Recombinant dna method for production of hepatitis b surface antigen in yeast |
US4678751A (en) * | 1981-09-25 | 1987-07-07 | Genentech, Inc. | Hybrid human leukocyte interferons |
US5096705A (en) * | 1981-10-19 | 1992-03-17 | Genentech, Inc. | Human immune interferon |
AU561343B2 (en) * | 1981-10-19 | 1987-05-07 | Genentech Inc. | Human immune interferon by recombinant dna |
US4672108A (en) * | 1981-12-07 | 1987-06-09 | Hoffmann-La Roche Inc. | Crystalline human leukocyte interferon |
JPS58110600A (ja) | 1981-12-25 | 1983-07-01 | Kyowa Hakko Kogyo Co Ltd | ヒトβ型インタ−フエロン遺伝子を含む組みかえ体プラスミド |
US4973479A (en) * | 1982-01-15 | 1990-11-27 | Cetus Corporation | Interferon-α61 |
US5098703A (en) * | 1982-01-15 | 1992-03-24 | Cetus Corporation | Interferon-alpha 76 |
US4975276A (en) * | 1982-01-15 | 1990-12-04 | Cetus Corporation | Interferon-alpha 54 |
EP0098876A1 (en) * | 1982-01-19 | 1984-01-25 | Cetus Corporation | Multiclass hybrid interferons |
EP0088046B1 (de) * | 1982-02-17 | 1987-12-09 | Ciba-Geigy Ag | Lipide in wässriger Phase |
US4671958A (en) * | 1982-03-09 | 1987-06-09 | Cytogen Corporation | Antibody conjugates for the delivery of compounds to target sites |
US6936694B1 (en) * | 1982-05-06 | 2005-08-30 | Intermune, Inc. | Manufacture and expression of large structural genes |
DE3218121A1 (de) | 1982-05-14 | 1983-11-17 | Leskovar, Peter, Dr.-Ing., 8000 München | Arzneimittel zur tumorbehandlung |
US4462940A (en) * | 1982-09-23 | 1984-07-31 | Cetus Corporation | Process for the recovery of human β-interferon-like polypeptides |
US5702699A (en) | 1982-09-23 | 1997-12-30 | Cetus Corporation | Process for the recovery of lipophilic proteins |
US4588585A (en) * | 1982-10-19 | 1986-05-13 | Cetus Corporation | Human recombinant cysteine depleted interferon-β muteins |
US4966843A (en) | 1982-11-01 | 1990-10-30 | Cetus Corporation | Expression of interferon genes in Chinese hamster ovary cells |
US4511502A (en) * | 1982-12-22 | 1985-04-16 | Genentech, Inc. | Purification and activity assurance of precipitated heterologous proteins |
US4512922A (en) * | 1982-12-22 | 1985-04-23 | Genentech, Inc. | Purification and activity assurance of precipitated heterologous proteins |
US4511503A (en) * | 1982-12-22 | 1985-04-16 | Genentech, Inc. | Purification and activity assurance of precipitated heterologous proteins |
US4820352A (en) * | 1983-01-10 | 1989-04-11 | Bausch & Lomb Incorporated | Cleaning and conditioning solutions for contact lenses and methods of use |
US5089398A (en) * | 1983-02-22 | 1992-02-18 | Chiron Corporation | Enhanced yeast transcription employing hybrid GAPDH promoter region constructs |
US4876197A (en) * | 1983-02-22 | 1989-10-24 | Chiron Corporation | Eukaryotic regulatable transcription |
US4518584A (en) * | 1983-04-15 | 1985-05-21 | Cetus Corporation | Human recombinant interleukin-2 muteins |
US4755465A (en) * | 1983-04-25 | 1988-07-05 | Genentech, Inc. | Secretion of correctly processed human growth hormone in E. coli and Pseudomonas |
US4859600A (en) * | 1983-04-25 | 1989-08-22 | Genentech, Inc. | Recombinant procaryotic cell containing correctly processed human growth hormone |
US4544545A (en) * | 1983-06-20 | 1985-10-01 | Trustees University Of Massachusetts | Liposomes containing modified cholesterol for organ targeting |
GB8317880D0 (en) * | 1983-07-01 | 1983-08-03 | Searle & Co | Structure and synthesis of interferons |
US4689406A (en) * | 1983-08-10 | 1987-08-25 | Amgen | Enhancement of microbial expression of polypeptides |
US4681930A (en) | 1983-09-20 | 1987-07-21 | Hoffmann-La Roche Inc. | Immune interferon and a method for its extraction and purification |
EP0142641B1 (de) * | 1983-09-26 | 1991-01-16 | Udo Dr. Ehrenfeld | Mittel und Erzeugnis für die Diagnose und Therapie von Tumoren sowie zur Behandlung von Schwächen der zelligen und humoralen Immunabwehr |
US4855238A (en) | 1983-12-16 | 1989-08-08 | Genentech, Inc. | Recombinant gamma interferons having enhanced stability and methods therefor |
US4880734A (en) * | 1984-05-11 | 1989-11-14 | Chiron Corporation | Eukaryotic regulatable transcription |
GB8412564D0 (en) * | 1984-05-17 | 1984-06-20 | Searle & Co | Structure and properties |
CA1302320C (en) * | 1984-06-11 | 1992-06-02 | Hideo Niwa | Expression of human cromosomal interferon-_ in animal cells |
JPS6156199A (ja) * | 1984-08-27 | 1986-03-20 | Shionogi & Co Ltd | 新規ヒトインタ−フエロンα類 |
US5120832A (en) * | 1984-08-27 | 1992-06-09 | Genentech, Inc. | Distinct family of human leukocyte interferons |
US4542225A (en) * | 1984-08-29 | 1985-09-17 | Dana-Farber Cancer Institute, Inc. | Acid-cleavable compound |
US4675483A (en) * | 1984-09-10 | 1987-06-23 | Siemens Aktiengesellschaft | Contact arrangement for vacuum switches |
US4738921A (en) * | 1984-09-27 | 1988-04-19 | Eli Lilly And Company | Derivative of the tryptophan operon for expression of fused gene products |
US4659839A (en) * | 1984-10-10 | 1987-04-21 | Mallinckrodt, Inc. | Coupling agents for radiolabeled antibody fragments |
US4837148A (en) * | 1984-10-30 | 1989-06-06 | Phillips Petroleum Company | Autonomous replication sequences for yeast strains of the genus pichia |
US4959314A (en) * | 1984-11-09 | 1990-09-25 | Cetus Corporation | Cysteine-depleted muteins of biologically active proteins |
US4885166A (en) * | 1985-06-11 | 1989-12-05 | Ciba-Geigy Corporation | Hybrid interferons |
DE3675588D1 (de) * | 1985-06-19 | 1990-12-20 | Ajinomoto Kk | Haemoglobin, das an ein poly(alkenylenoxid) gebunden ist. |
US4917888A (en) * | 1985-06-26 | 1990-04-17 | Cetus Corporation | Solubilization of immunotoxins for pharmaceutical compositions using polymer conjugation |
US4766106A (en) * | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
US4810643A (en) | 1985-08-23 | 1989-03-07 | Kirin- Amgen Inc. | Production of pluripotent granulocyte colony-stimulating factor |
US6004548A (en) | 1985-08-23 | 1999-12-21 | Amgen, Inc. | Analogs of pluripotent granulocyte colony-stimulating factor |
US4680338A (en) * | 1985-10-17 | 1987-07-14 | Immunomedics, Inc. | Bifunctional linker |
AU6543286A (en) | 1985-10-25 | 1987-05-19 | Zymogenetics Inc. | Method of using bar1 for secreting foreign proteins |
US4699784A (en) * | 1986-02-25 | 1987-10-13 | Center For Molecular Medicine & Immunology | Tumoricidal methotrexate-antibody conjugate |
EP0260350B1 (en) | 1986-09-05 | 1992-02-12 | Cetus Oncology Corporation | Oxidation-resistant interferon-beta muteins and their production; formulations containing such muteins |
US4894330A (en) | 1986-12-23 | 1990-01-16 | Cetus Corporation | Purification of recombinant beta-interferon incorporating RP-HPLC |
US5186933A (en) | 1986-12-30 | 1993-02-16 | Baylor College Of Medicine | Synthesis and immunogenicity of rotavirus genes using a baculovirus expression system |
US4908432A (en) * | 1987-01-09 | 1990-03-13 | New York University | Novel polypeptide having gamma-interferon activity |
JPH02502876A (ja) | 1987-03-16 | 1990-09-13 | アメリカン バイオジェネティック サイエンシズ インク | ワクチンと生物学的殺虫剤における組換えバクロウイルス閉塞体 |
DE3712564A1 (de) | 1987-04-14 | 1988-11-24 | Bioferon Biochem Substanz | Verfahren zur konstruktion einer animalen zellinie fuer die herstellung von humanem interferon-beta |
US5229490A (en) * | 1987-05-06 | 1993-07-20 | The Rockefeller University | Multiple antigen peptide system |
AU2136788A (en) | 1987-07-24 | 1989-03-01 | Cetus Corporation | Production of ricin toxins in a baculovirus-insect cell expression system |
AU2251488A (en) | 1987-07-24 | 1989-03-01 | Cetus Corporation | Production of biologically active forms of csf using a baculovirus (acnpv)-insect cell expression system |
US5080891A (en) * | 1987-08-03 | 1992-01-14 | Ddi Pharmaceuticals, Inc. | Conjugates of superoxide dismutase coupled to high molecular weight polyalkylene glycols |
US4929555A (en) * | 1987-10-19 | 1990-05-29 | Phillips Petroleum Company | Pichia transformation |
GB8725529D0 (en) | 1987-10-30 | 1987-12-02 | Delta Biotechnology Ltd | Polypeptides |
US4904584A (en) * | 1987-12-23 | 1990-02-27 | Genetics Institute, Inc. | Site-specific homogeneous modification of polypeptides |
CA1340772C (en) | 1987-12-30 | 1999-09-28 | Patricia Tekamp-Olson | Expression and secretion of heterologous protiens in yeast employing truncated alpha-factor leader sequences |
US5674706A (en) | 1988-05-06 | 1997-10-07 | Chiron Corporation | High level expression of proteins in yeast |
CA1324969C (en) | 1988-05-06 | 1993-12-07 | Jeffrey R. Shuster | High level expression of proteins in yeast |
FR2631974B1 (fr) * | 1988-05-31 | 1992-12-11 | Agronomique Inst Nat Rech | Baculovirus modifie, son procede de preparation et son application en tant que vecteur d'expression de genes |
AU4197389A (en) | 1988-08-05 | 1990-03-05 | Mount Sinai School Of Medicine Of The City University Of New York, The | In vivo infection of live insects with a recombinant baculovirus |
GB8819453D0 (en) | 1988-08-16 | 1988-09-21 | Roy P | Production of bluetongue virus non-structural proteins using baculovirus expression vector |
NZ230425A (en) | 1988-09-02 | 1992-07-28 | Molecular Eng Ass | Production of paramyxovirus fusion (f) protein using recombinant baculovirus expression vector |
US5218092A (en) * | 1988-09-29 | 1993-06-08 | Kyowa Hakko Kogyo Co., Ltd. | Modified granulocyte-colony stimulating factor polypeptide with added carbohydrate chains |
US5997856A (en) | 1988-10-05 | 1999-12-07 | Chiron Corporation | Method and compositions for solubilization and stabilization of polypeptides, especially proteins |
US6780613B1 (en) | 1988-10-28 | 2004-08-24 | Genentech, Inc. | Growth hormone variants |
WO1990004788A1 (en) | 1988-10-28 | 1990-05-03 | Genentech, Inc. | Method for identifying active domains and amino acid residues in polypeptides and hormone variants |
EP0446299A4 (en) | 1988-11-18 | 1992-05-13 | The Regents Of The University Of California | Method for site-specifically incorporating unnatural amino acids into proteins |
US5047335A (en) | 1988-12-21 | 1991-09-10 | The Regents Of The University Of Calif. | Process for controlling intracellular glycosylation of proteins |
EP0401384B1 (en) | 1988-12-22 | 1996-03-13 | Kirin-Amgen, Inc. | Chemically modified granulocyte colony stimulating factor |
US4902502A (en) * | 1989-01-23 | 1990-02-20 | Cetus Corporation | Preparation of a polymer/interleukin-2 conjugate |
AU5187190A (en) | 1989-02-23 | 1990-09-26 | University Of Ottawa | Improved baculovirus expression system capable of producing foreign gene proteins at high levels |
WO1990010277A1 (en) | 1989-02-24 | 1990-09-07 | Cell Analysis Systems, Inc. | Method and apparatus for determining a proliferation index of a cell sample |
US6372206B1 (en) | 1989-03-02 | 2002-04-16 | University Of Florida | Orally-administered interferon-TAU compositions and methods |
US5705363A (en) | 1989-03-02 | 1998-01-06 | The Women's Research Institute | Recombinant production of human interferon τ polypeptides and nucleic acids |
US5122614A (en) * | 1989-04-19 | 1992-06-16 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
US5324844A (en) * | 1989-04-19 | 1994-06-28 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
ATE300519T1 (de) | 1989-04-19 | 2005-08-15 | Enzon Inc | Verfahren zum herstellen von modifizierten polypeptiden die eine polypeptid und ein polyalkylenoxid enthalten |
ATE92107T1 (de) | 1989-04-29 | 1993-08-15 | Delta Biotechnology Ltd | N-terminale fragmente von menschliches serumalbumin enthaltenden fusionsproteinen. |
US5766883A (en) | 1989-04-29 | 1998-06-16 | Delta Biotechnology Limited | Polypeptides |
WO1990014428A1 (en) | 1989-05-17 | 1990-11-29 | University Of Georgia Research Foundation, Inc. | Improved baculovirus expression vectors |
FR2649120B1 (fr) | 1989-06-30 | 1994-01-28 | Cayla | Nouvelle souche et ses mutants de champignons filamenteux, procede de production de proteines recombinantes a l'aide de ladite souche et souches et proteines obtenues selon ce procede |
IL91562A0 (en) | 1989-09-07 | 1990-04-29 | Yeda Res & Dev | Interferon-gamma receptor fragment and its production |
US5889151A (en) | 1989-10-20 | 1999-03-30 | Societe Leb-Tech | Purified human alpha interferon receptor |
US5312808A (en) | 1989-11-22 | 1994-05-17 | Enzon, Inc. | Fractionation of polyalkylene oxide-conjugated hemoglobin solutions |
US5162601A (en) * | 1989-11-22 | 1992-11-10 | The Upjohn Company | Plant potyvirus expression vector with a gene for protease |
US5219564A (en) * | 1990-07-06 | 1993-06-15 | Enzon, Inc. | Poly(alkylene oxide) amino acid copolymers and drug carriers and charged copolymers based thereon |
FR2664905B1 (fr) * | 1990-07-18 | 1994-08-12 | Agronomique Inst Nat Rech | Baculovirus modifie, son procede d'obtention, et vecteurs d'expression obtenus a partir dudit baculovirus. |
WO1992001800A1 (en) | 1990-07-20 | 1992-02-06 | Chiron Corporation | Method for integrative transformation of yeast using dispersed repetitive elements |
EP0541721A4 (en) | 1990-08-02 | 1993-12-29 | Chiron Corporation | Expression of human cmv glycoprotein-h using the baculovirus-insect cell expression system |
WO1992004363A1 (en) * | 1990-09-04 | 1992-03-19 | The Salk Institute Biotechnology/Industrial Associates, Inc. | Production of insulin-like growth factor-1 in methylotrophic yeast cells |
EP0513332A4 (en) | 1990-11-14 | 1993-03-17 | Cargill, Incorporated | Conjugates of poly(vinylsaccharide) with proteins for the stabilization of proteins |
US5252714A (en) * | 1990-11-28 | 1993-10-12 | The University Of Alabama In Huntsville | Preparation and use of polyethylene glycol propionaldehyde |
ATE164395T1 (de) | 1990-12-03 | 1998-04-15 | Genentech Inc | Verfahren zur anreicherung von proteinvarianten mit geänderten bindungseigenschaften |
US5231178A (en) * | 1991-01-16 | 1993-07-27 | The Salk Institute Biotechnology/Industrial Associates, Inc. | Method for the purification of intact, correctly-folded insulin-like growth factor-1 |
EP0576589A4 (en) | 1991-03-18 | 1994-07-27 | Enzon Inc | Hydrazine containing conjugates of polypeptides and glycopolypeptides with polymers |
AU1651992A (en) | 1991-03-19 | 1992-10-21 | United States of America, as represented by the Secretary, U.S. Department of Commerce, The | Expression of influenza nucleoprotein antigens in baculovirus |
US5595732A (en) * | 1991-03-25 | 1997-01-21 | Hoffmann-La Roche Inc. | Polyethylene-protein conjugates |
US6013433A (en) | 1991-04-26 | 2000-01-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Baculovirus expression vectors and recombinant antigens for detecting type-specific antibodies to herpes simplex virus |
US5281698A (en) * | 1991-07-23 | 1994-01-25 | Cetus Oncology Corporation | Preparation of an activated polymer ester for protein conjugation |
US5290686A (en) * | 1991-07-31 | 1994-03-01 | The United States Of America As Represented By The Department Of Health And Human Services | Expression of influenza a M2 protein in baculovirus |
DE4128319A1 (de) | 1991-08-27 | 1993-03-04 | Bioferon Biochem Substanz | Neues rekombinantes human-ifn-beta, verfahren zu dessen herstellung und dieses enthaltende pharmazeutische zubereitungen |
US5540923A (en) * | 1991-12-06 | 1996-07-30 | Landsforeningen Til Kraeftens Bekaemplse | Interferon proteins |
IT1260468B (it) | 1992-01-29 | 1996-04-09 | Metodo per mantenere l'attivita' di enzimi proteolitici modificati con polietilenglicole | |
FR2686899B1 (fr) | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
JPH07505915A (ja) | 1992-04-14 | 1995-06-29 | コーネル リサーチ ファウンデーション、インコーポレーテッド | 樹枝状巨大分子およびその製造法 |
US5516657A (en) * | 1992-05-11 | 1996-05-14 | Cambridge Biotech Corporation | Baculovirus vectors for expression of secretory and membrane-bound proteins |
ZA933926B (en) * | 1992-06-17 | 1994-01-03 | Amgen Inc | Polyoxymethylene-oxyethylene copolymers in conjuction with blomolecules |
WO1994004193A1 (en) | 1992-08-21 | 1994-03-03 | Enzon, Inc. | Novel attachment of polyalkylene oxides to bio-effecting substances |
US5382657A (en) | 1992-08-26 | 1995-01-17 | Hoffmann-La Roche Inc. | Peg-interferon conjugates |
US5298643A (en) | 1992-12-22 | 1994-03-29 | Enzon, Inc. | Aryl imidate activated polyalkylene oxides |
AU6029594A (en) | 1993-01-15 | 1994-08-15 | Enzon, Inc. | Factor viii - polymeric conjugates |
US5349001A (en) | 1993-01-19 | 1994-09-20 | Enzon, Inc. | Cyclic imide thione activated polyalkylene oxides |
US5321095A (en) | 1993-02-02 | 1994-06-14 | Enzon, Inc. | Azlactone activated polyalkylene oxides |
US5532142A (en) * | 1993-02-12 | 1996-07-02 | Board Of Regents, The University Of Texas System | Method of isolation and purification of fusion polypeptides |
IL104734A0 (en) * | 1993-02-15 | 1993-06-10 | Univ Bar Ilan | Bioactive conjugates of cellulose with amino compounds |
US5441734A (en) | 1993-02-25 | 1995-08-15 | Schering Corporation | Metal-interferon-alpha crystals |
EP0626448A3 (de) | 1993-05-26 | 1998-01-14 | BOEHRINGER INGELHEIM INTERNATIONAL GmbH | Verfahren zur Herstellung und Reinigung von alpha-Interferon |
WO1994028024A1 (en) | 1993-06-01 | 1994-12-08 | Enzon, Inc. | Carbohydrate-modified polymer conjugates with erythropoietic activity |
WO1994029344A1 (en) | 1993-06-11 | 1994-12-22 | Pestka Biomedical Laboratories, Inc. | Super proteins including interferons and interleukins |
WO1995000162A1 (en) | 1993-06-21 | 1995-01-05 | Enzon, Inc. | Site specific synthesis of conjugated peptides |
GB9317618D0 (en) | 1993-08-24 | 1993-10-06 | Royal Free Hosp School Med | Polymer modifications |
US5762939A (en) | 1993-09-13 | 1998-06-09 | Mg-Pmc, Llc | Method for producing influenza hemagglutinin multivalent vaccines using baculovirus |
US5919455A (en) | 1993-10-27 | 1999-07-06 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
US5643575A (en) | 1993-10-27 | 1997-07-01 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
US5491076A (en) | 1993-11-01 | 1996-02-13 | The Texas A&M University System | Expression of foreign genes using a replicating polyprotein producing virus vector |
US5605792A (en) | 1993-11-04 | 1997-02-25 | The Ohio State University Research Foundation | Infectious bursal disease virus VP2 fusion protein expressed by baculovirus, use as diagnostic |
US5951974A (en) | 1993-11-10 | 1999-09-14 | Enzon, Inc. | Interferon polymer conjugates |
EP0730470B1 (en) | 1993-11-10 | 2002-03-27 | Enzon, Inc. | Improved interferon polymer conjugates |
US5446090A (en) | 1993-11-12 | 1995-08-29 | Shearwater Polymers, Inc. | Isolatable, water soluble, and hydrolytically stable active sulfones of poly(ethylene glycol) and related polymers for modification of surfaces and molecules |
FR2715664B1 (fr) | 1994-01-31 | 1996-04-12 | Proteine Performance Sa | Baculovirus recombinant et son utilisation pour la production d'anticorps monoclonaux. |
JP3090586B2 (ja) | 1994-03-15 | 2000-09-25 | 片倉工業株式会社 | システインプロテアーゼ遺伝子欠損バキュロウイルスおよびその製造法並びにこれを利用する有用タンパク質の製造法 |
US5545723A (en) | 1994-03-15 | 1996-08-13 | Biogen Inc. | Muteins of IFN-β |
US5473034A (en) * | 1994-03-18 | 1995-12-05 | Hyogo Prefectural Government | Method for producing protein-synthetic polymer conjugate and said conjugate produced thereby |
US5629384A (en) | 1994-05-17 | 1997-05-13 | Consiglio Nazionale Delle Ricerche | Polymers of N-acryloylmorpholine activated at one end and conjugates with bioactive materials and surfaces |
US5686110A (en) | 1994-06-02 | 1997-11-11 | Enzon, Inc. | Water soluble complex of an alkyl or olefinic end capped polyalkylene oxide and a water insoluble substance |
US5730990A (en) | 1994-06-24 | 1998-03-24 | Enzon, Inc. | Non-antigenic amine derived polymers and polymer conjugates |
US6403375B1 (en) | 1994-08-24 | 2002-06-11 | Boyce Thompson Institute For Plant Research, Inc. | Establishment of Trichoplusia ni cell lines in serum-free medium for recombinant protein and baculovirus production |
US5650234A (en) | 1994-09-09 | 1997-07-22 | Surface Engineering Technologies, Division Of Innerdyne, Inc. | Electrophilic polyethylene oxides for the modification of polysaccharides, polypeptides (proteins) and surfaces |
US5871986A (en) | 1994-09-23 | 1999-02-16 | The General Hospital Corporation | Use of a baculovirus to express and exogenous gene in a mammalian cell |
US5766582A (en) | 1994-10-11 | 1998-06-16 | Schering Corporation | Stable, aqueous alfa interferon solution formulations |
US5824784A (en) | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
CA2204726A1 (en) | 1994-11-09 | 1996-12-27 | Robin E. Offord | Functionalized polymers for site-specific attachment |
US5738846A (en) | 1994-11-10 | 1998-04-14 | Enzon, Inc. | Interferon polymer conjugates and process for preparing the same |
IL116085A (en) | 1994-12-16 | 1999-12-31 | Ortho Pharma Corp | Spray dried erythropoietin |
US5932462A (en) | 1995-01-10 | 1999-08-03 | Shearwater Polymers, Inc. | Multiarmed, monofunctional, polymer for coupling to molecules and surfaces |
WO1996025496A1 (en) | 1995-02-17 | 1996-08-22 | Instituut Voor Dierhouderij En Diergezondheid (Id-Dlo) | PRODUCTION OF BIOLOGICALLY ACTIVE RECOMBINANT BOVINE FOLLICLE STIMULATING HORMONE (REC bFSH) IN THE BACULOVIRUS EXPRESSION SYSTEM |
FR2732035B1 (fr) | 1995-03-23 | 1997-05-30 | Agronomique Inst Nat Rech | Procede de regulation de l'expression d'un gene dans un baculovirus, par un site de fixation d'un recepteur de l'acide retinoique, et vecteur pour la mise en oeuvre du dit procede |
US6184344B1 (en) | 1995-05-04 | 2001-02-06 | The Scripps Research Institute | Synthesis of proteins by native chemical ligation |
NZ308772A (en) | 1995-05-17 | 1999-04-29 | Du Pont | Recombinant baculovirus insecticides |
US5814485A (en) | 1995-06-06 | 1998-09-29 | Chiron Corporation | Production of interferon-β (IFN-β) in E. coli |
AU5893696A (en) | 1995-06-07 | 1996-12-30 | Novo Nordisk A/S | Modification of polypeptides |
US5672662A (en) | 1995-07-07 | 1997-09-30 | Shearwater Polymers, Inc. | Poly(ethylene glycol) and related polymers monosubstituted with propionic or butanoic acids and functional derivatives thereof for biotechnical applications |
US5840565A (en) | 1995-08-22 | 1998-11-24 | The Regents Of The University Of California | Methods for enhancing the production of viral vaccines in PKR-deficient cell culture |
US5908621A (en) | 1995-11-02 | 1999-06-01 | Schering Corporation | Polyethylene glycol modified interferon therapy |
WO1997026332A1 (en) | 1996-01-17 | 1997-07-24 | Schering Corporation | Baculovirus expression system for human interleukin 5 receptor and method of screening for interleukin 5 antagonists |
US5861279A (en) | 1996-01-17 | 1999-01-19 | Schering Corporation | Baculovirus expression system for human interleukin 5 receptor and method of screening for interleukin 5 antagonists |
US5747639A (en) | 1996-03-06 | 1998-05-05 | Amgen Boulder Inc. | Use of hydrophobic interaction chromatography to purify polyethylene glycols |
KR20000029673A (ko) | 1996-08-02 | 2000-05-25 | 오르토-맥네일 파마슈티칼, 인코퍼레이티드 | 단일의공유결합된n-말단수용성폴리머를갖는폴리펩티드 |
US5980948A (en) | 1996-08-16 | 1999-11-09 | Osteotech, Inc. | Polyetherester copolymers as drug delivery matrices |
US6214966B1 (en) | 1996-09-26 | 2001-04-10 | Shearwater Corporation | Soluble, degradable poly(ethylene glycol) derivatives for controllable release of bound molecules into solution |
AU5794598A (en) | 1996-12-13 | 1998-07-03 | Patricia Tekamp-Olson | Method for expression of heterologous proteins in yeast |
BR9606270A (pt) | 1996-12-18 | 1998-09-22 | Univ Minas Gerais | Processo para a produção da proteína do interferon beta-cis humano recombinante e proteína de interferon beta-cis humano recombinante |
ATE200030T1 (de) | 1997-01-29 | 2001-04-15 | Polymasc Pharmaceuticals Plc | Pegylationsverfahren |
GB9703406D0 (en) | 1997-02-19 | 1997-04-09 | Chiron Spa | Expression of heterologous proteins |
WO1998047089A1 (en) | 1997-04-11 | 1998-10-22 | California Institute Of Technology | Apparatus and method for automated protein design |
DE19717864C2 (de) | 1997-04-23 | 2001-05-17 | Fraunhofer Ges Forschung | Humanes rekombinantes Interferon-beta, Verfahren zu seiner Herstellung und seine Verwendung |
WO1998048837A1 (en) | 1997-04-30 | 1998-11-05 | Enzon, Inc. | Polyalkylene oxide-modified single chain polypeptides |
US5990237A (en) | 1997-05-21 | 1999-11-23 | Shearwater Polymers, Inc. | Poly(ethylene glycol) aldehyde hydrates and related polymers and applications in modifying amines |
US5965393A (en) | 1997-07-01 | 1999-10-12 | National Institute Of Immunology | Method for enhancing foreign gene expression in baculovirus expression vector system |
US7270809B2 (en) * | 1997-07-14 | 2007-09-18 | Bolder Biotechnology, Inc. | Cysteine variants of alpha interferon-2 |
AU751898B2 (en) | 1997-07-14 | 2002-08-29 | Bolder Biotechnology, Inc. | Derivatives of growth hormone and related proteins |
GB9715660D0 (en) | 1997-07-25 | 1997-10-01 | Zeneca Ltd | Proteins |
AU8688798A (en) | 1997-08-05 | 1999-03-01 | Chiron Corporation | Novel (pichia pastoris) gene sequences and methods for their use |
DE19735593C2 (de) | 1997-08-15 | 1999-08-26 | Hepavec Ag Fuer Gentherapie | Hüllprotein-modifizierter Baculovirus-Vektor für die Gentherapie |
US6090584A (en) | 1997-08-21 | 2000-07-18 | University Technologies International Inc. | Baculovirus artificial chromosomes and methods of use |
US5989868A (en) | 1997-09-12 | 1999-11-23 | The Board Of Regents Of The University Of Oklahoma | Fusion protein systems designed to increase soluble cytoplasmic expression of heterologous proteins in esherichia coli |
PT1015576E (pt) | 1997-09-16 | 2005-09-30 | Egea Biosciences Llc | Metodo para a sintese quimica completa e montagem de genes e de genomas |
WO1999016318A1 (en) | 1997-09-26 | 1999-04-08 | Uab Research Foundation | Reduced antigenic cells and uses therefor |
US6004573A (en) | 1997-10-03 | 1999-12-21 | Macromed, Inc. | Biodegradable low molecular weight triblock poly(lactide-co-glycolide) polyethylene glycol copolymers having reverse thermal gelation properties |
US6201072B1 (en) | 1997-10-03 | 2001-03-13 | Macromed, Inc. | Biodegradable low molecular weight triblock poly(lactide-co- glycolide) polyethylene glycol copolymers having reverse thermal gelation properties |
DE19748489A1 (de) | 1997-11-03 | 1999-05-06 | Roche Diagnostics Gmbh | Polyethylenglykol-derivatisierte Biomoleküle und deren Verwendung in heterogenen Nachweisverfahren |
US6448369B1 (en) | 1997-11-06 | 2002-09-10 | Shearwater Corporation | Heterobifunctional poly(ethylene glycol) derivatives and methods for their preparation |
JP2001526033A (ja) | 1997-12-08 | 2001-12-18 | ジェネンテク・インコーポレイテッド | ヒトインターフェロン−イプシロンというi型インターフェロン |
ZA9811070B (en) | 1997-12-08 | 2000-07-03 | Genentech Inc | Type I interferons. |
EP0924298A1 (en) | 1997-12-18 | 1999-06-23 | Stichting Instituut voor Dierhouderij en Diergezondheid (ID-DLO) | Protein expression in baculovirus vector expression systems |
US5985263A (en) | 1997-12-19 | 1999-11-16 | Enzon, Inc. | Substantially pure histidine-linked protein polymer conjugates |
US5981709A (en) | 1997-12-19 | 1999-11-09 | Enzon, Inc. | α-interferon-polymer-conjugates having enhanced biological activity and methods of preparing the same |
CN1292033A (zh) | 1998-03-04 | 2001-04-18 | 昂尼克斯药物公司 | 用于遗传物质高通量表达的杆状病毒表达系统和方法 |
WO1999045026A1 (en) | 1998-03-05 | 1999-09-10 | Chiron Corporation | Method for increasing the serum half-life of a biologically active molecule |
ATE268609T1 (de) | 1998-03-12 | 2004-06-15 | Nektar Therapeutics Al Corp | Polyethylenglycolderivate mit benachbarten reaktiven gruppen |
US6180096B1 (en) | 1998-03-26 | 2001-01-30 | Schering Corporation | Formulations for protection of peg-interferon alpha conjugates |
KR100264953B1 (ko) | 1998-04-03 | 2001-03-02 | 박현우 | 재조합 베큘로바이러스, 이의 제조방법 및 이를 포함하는 미생물 살충제 |
CN100335503C (zh) * | 1998-04-28 | 2007-09-05 | 应用研究系统Ars股份公司 | 多元醇干扰素β偶联物 |
CZ299460B6 (cs) | 1998-05-07 | 2008-08-06 | Shire Human Genetic Therapies, Inc. | DNA konstrukt, izolovaná molekula nukleové kyseliny, homologne rekombinantní bunka a její použití azpusob produkce G-CSF |
US6451986B1 (en) | 1998-06-22 | 2002-09-17 | Immunex Corporation | Site specific protein modification |
US6168932B1 (en) | 1998-07-13 | 2001-01-02 | Parker Hughes Institute | Recombinant DTctGMCSF fusion toxin in a baculovirus expression vector system |
US6472512B1 (en) | 1998-07-21 | 2002-10-29 | Human Genome Sciences, Inc. | Keratinocyte derived interferon |
US6245528B1 (en) | 1998-07-28 | 2001-06-12 | Academia Sinica | Latent baculovirus expression system |
US6368825B1 (en) | 1998-08-10 | 2002-04-09 | Academia Sinica | Baculovirus containing minimal CMV promoter |
ATE258946T1 (de) | 1998-08-28 | 2004-02-15 | Gryphon Sciences | Verfahren zur herstellung von polyamidketten von genauer länge und deren konjugate mit proteinen |
WO2000020032A1 (en) | 1998-10-06 | 2000-04-13 | Trustees Of Dartmouth College | RECOMBINANT CAT ALLERGEN, Fel dI, EXPRESSED IN BACULOVIRUS FOR DIAGNOSIS AND TREATMENT OF CAT ALLERGY |
US6420339B1 (en) | 1998-10-14 | 2002-07-16 | Amgen Inc. | Site-directed dual pegylation of proteins for improved bioactivity and biocompatibility |
US6403312B1 (en) | 1998-10-16 | 2002-06-11 | Xencor | Protein design automatic for protein libraries |
EA005005B1 (ru) | 1998-10-16 | 2004-10-28 | Байоджен, Инк. | ГИБРИДНЫЙ ПОЛИПЕПТИД β1α-ИНТЕРФЕРОНА ЧЕЛОВЕКА, ЕГО МУТАНТНЫЕ ФОРМЫ И ПРОИЗВОДНЫЕ И СОДЕРЖАЩАЯ ИХ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ |
ES2257884T3 (es) | 1998-10-16 | 2006-08-01 | Biogen Idec Ma Inc. | Conjugados de polimero e interferon beta-1a y sus usos. |
CA2348822A1 (en) | 1998-10-30 | 2000-05-11 | Novozymes A/S | Glycosylated proteins having reduced allergenicity |
US6451346B1 (en) | 1998-12-23 | 2002-09-17 | Amgen Inc | Biodegradable pH/thermosensitive hydrogels for sustained delivery of biologically active agents |
US6433144B1 (en) | 1999-01-12 | 2002-08-13 | Viragen, Inc. | Compositions of highly-purified natural mixtures of type I Interferon derived from leukocytes and methods |
US6350589B1 (en) | 1998-12-31 | 2002-02-26 | Viragen, Inc. | Compositions of highly-purified natural mixtures of type I interferon derived from leukocytes and methods |
US6703225B1 (en) | 1999-01-12 | 2004-03-09 | Sumitomo Pharmaceuticals Company, Limited | Interferon-α |
US6281211B1 (en) | 1999-02-04 | 2001-08-28 | Euro-Celtique S.A. | Substituted semicarbazides and the use thereof |
US6994986B2 (en) | 1999-03-17 | 2006-02-07 | The Board Of Trustees Of The Leland Stanford University | In vitro synthesis of polypeptides by optimizing amino acid metabolism |
JP4707237B2 (ja) | 1999-03-17 | 2011-06-22 | ザ ボード オブ トラスティーズ オブ ザ リーランド スタンフォード ジュニア ユニバーシティ | 外因性アミノ酸および新規atp再生システムを用いたインビトロ高分子生合成の方法 |
US6342216B1 (en) | 1999-03-17 | 2002-01-29 | The Board Of Regents, The University Of Texas System | Therapy of cancer by insect cells containing recombinant baculovirus encoding genes |
US6337191B1 (en) | 1999-03-22 | 2002-01-08 | The Board Of Trustees Of The Leland Stanford Junior University | Vitro protein synthesis using glycolytic intermediates as an energy source |
CA2370330C (en) | 1999-04-16 | 2009-01-20 | Wm. Marsh Rice University | Biodegradable poly(propylene fumarate) networks cross linked with poly(propylene fumarate)-diacrylate macromers |
US6514729B1 (en) | 1999-05-12 | 2003-02-04 | Xencor, Inc. | Recombinant interferon-beta muteins |
AU5144200A (en) | 1999-05-21 | 2000-12-12 | Greff, Richard J. | Novel high viscosity embolizing compositions |
JP2003525592A (ja) | 1999-06-22 | 2003-09-02 | ユニバシティ オブ メリーランド カレッジ パーク | インターフェロンタウ変異体及びその製法 |
US6261805B1 (en) | 1999-07-15 | 2001-07-17 | Boyce Thompson Institute For Plant Research, Inc. | Sialyiation of N-linked glycoproteins in the baculovirus expression vector system |
US7144574B2 (en) | 1999-08-27 | 2006-12-05 | Maxygen Aps | Interferon β variants and conjugates |
US6531122B1 (en) | 1999-08-27 | 2003-03-11 | Maxygen Aps | Interferon-β variants and conjugates |
US6485937B1 (en) | 1999-10-15 | 2002-11-26 | The Rockefeller University | System for rapid generation of recombinant baculovirus-based expression vectors for silkworm larvae |
US6348558B1 (en) | 1999-12-10 | 2002-02-19 | Shearwater Corporation | Hydrolytically degradable polymers and hydrogels made therefrom |
ES2321800T5 (es) | 1999-12-22 | 2017-02-17 | Nektar Therapeutics | Procedimiento de preparación de ésteres de 1-benzotriazolil carbonato de polímeros solubles en agua |
WO2001046291A1 (en) | 1999-12-22 | 2001-06-28 | Shearwater Corporation | Sterically hindered derivatives of water soluble polymers |
US6413507B1 (en) * | 1999-12-23 | 2002-07-02 | Shearwater Corporation | Hydrolytically degradable carbamate derivatives of poly (ethylene glycol) |
US6646110B2 (en) | 2000-01-10 | 2003-11-11 | Maxygen Holdings Ltd. | G-CSF polypeptides and conjugates |
US6602498B2 (en) | 2000-02-22 | 2003-08-05 | Shearwater Corporation | N-maleimidyl polymer derivatives |
AU780270B2 (en) | 2000-02-23 | 2005-03-10 | Association Francaise Contre Les Myopathies | Treatment of immune diseases |
AU2001257577A1 (en) | 2000-02-28 | 2001-09-03 | Shearwater Corporation | Water-soluble polymer conjugates of artelinic acid |
GB0012997D0 (en) | 2000-05-26 | 2000-07-19 | Eurogene Limited | Gene delivery |
US6586207B2 (en) | 2000-05-26 | 2003-07-01 | California Institute Of Technology | Overexpression of aminoacyl-tRNA synthetases for efficient production of engineered proteins containing amino acid analogues |
JP2002030098A (ja) | 2000-07-17 | 2002-01-29 | Institute Of Immunology Co Ltd | バキュロウィルスの発芽ウイルスからウイルスエンベロープを回収する方法 |
KR100396983B1 (ko) | 2000-07-29 | 2003-09-02 | 이강춘 | 고반응성의 가지 달린 고분자 유도체 및 고분자와 단백질또는 펩타이드의 접합체 |
JP2004508338A (ja) | 2000-09-08 | 2004-03-18 | グリフォン セラピューティクス,インコーポレーテッド | ポリマー修飾合成タンパク質 |
US7118737B2 (en) * | 2000-09-08 | 2006-10-10 | Amylin Pharmaceuticals, Inc. | Polymer-modified synthetic proteins |
US7544354B2 (en) | 2000-10-27 | 2009-06-09 | Novartis Vaccines And Diagnostics | Methods of protein purification and recovery |
PT1343518E (pt) | 2000-11-07 | 2009-08-03 | Novartis Vaccines & Diagnostic | Composições de interferão estabilizadas |
US6436386B1 (en) | 2000-11-14 | 2002-08-20 | Shearwater Corporation | Hydroxyapatite-targeting poly (ethylene glycol) and related polymers |
TW593427B (en) | 2000-12-18 | 2004-06-21 | Nektar Therapeutics Al Corp | Synthesis of high molecular weight non-peptidic polymer derivatives |
TWI246524B (en) | 2001-01-19 | 2006-01-01 | Shearwater Corp | Multi-arm block copolymers as drug delivery vehicles |
JP2004529633A (ja) | 2001-03-15 | 2004-09-30 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | 低減された免疫原性を有する修飾されたヒトインターフェロンベータ |
WO2002079415A2 (en) | 2001-03-30 | 2002-10-10 | Lexigen Pharmaceuticals Corp. | Reducing the immunogenicity of fusion proteins |
WO2002080959A1 (en) | 2001-04-03 | 2002-10-17 | Universitair Medisch Centrum Utrecht | Method of treatment of hypoxia/ischaemia blutflusswiderstand |
US6887462B2 (en) | 2001-04-09 | 2005-05-03 | Chiron Corporation | HSA-free formulations of interferon-beta |
MXPA03009566A (es) | 2001-04-19 | 2004-12-06 | Scripps Research Inst | Metodos y composicion para la produccion de pares trna-aminoaciltrna sintetasa ortogonales. |
US6566132B1 (en) | 2001-04-26 | 2003-05-20 | Isis Pharmaceuticals, Inc. | Antisense modulation of Interferon gamma receptor 1 expression |
GB0113657D0 (en) | 2001-06-05 | 2001-07-25 | Geneprot Inc | Improved native chemical ligation with three or more components |
US20040138412A1 (en) | 2001-09-07 | 2004-07-15 | Paolo Botti | Extended native chemical ligation |
US6908963B2 (en) | 2001-10-09 | 2005-06-21 | Nektar Therapeutics Al, Corporation | Thioester polymer derivatives and method of modifying the N-terminus of a polypeptide therewith |
JP4758608B2 (ja) | 2001-11-07 | 2011-08-31 | ネクター セラピューティックス | 分枝ポリマーおよびそれらの結合体 |
US7884182B2 (en) | 2001-11-14 | 2011-02-08 | Amylin Pharmaceuticals, Inc. | Chemical peptide ligation with three or more components |
JP5424521B2 (ja) * | 2001-12-21 | 2014-02-26 | ヒューマン ジノーム サイエンシーズ, インコーポレイテッド | アルブミン融合タンパク質 |
US6716821B2 (en) | 2001-12-21 | 2004-04-06 | Immunogen Inc. | Cytotoxic agents bearing a reactive polyethylene glycol moiety, cytotoxic conjugates comprising polyethylene glycol linking groups, and methods of making and using the same |
ATE437946T1 (de) | 2002-02-15 | 2009-08-15 | Univ New York State Res Found | Ribozyme mit breiter trna-aminoacylierungswirkung |
KR20040104504A (ko) | 2002-03-12 | 2004-12-10 | 맥시겐 에이피에스 | 스트로크의 치료를 위한 인터페론 베타-유사 분자 |
DE60332725D1 (de) | 2002-05-30 | 2010-07-08 | Scripps Research Inst | Kupferkatalysierte ligierung von aziden und acetylenen |
WO2004002500A1 (en) | 2002-06-28 | 2004-01-08 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of treating autoimmune diseases with interferon-beta and il-2r antagonist |
WO2004017921A2 (en) | 2002-08-23 | 2004-03-04 | Zymogenetics, Inc. | Method for treating inflammatory bowel disease |
US20050054053A1 (en) | 2002-10-01 | 2005-03-10 | Xencor, Inc. | Interferon variants with improved properties |
EP1581631A4 (en) * | 2002-10-01 | 2007-09-05 | Xencor Inc | INTERFERON VARIANTS HAVING IMPROVED PROPERTIES |
KR20050072441A (ko) | 2002-10-16 | 2005-07-11 | 더 스크립스 리서치 인스티튜트 | 케토 아미노산의 단백질로의 부위 특이적 도입 |
ATE445709T1 (de) | 2002-10-16 | 2009-10-15 | Scripps Research Inst | Glycoproteinsynthese |
US7314613B2 (en) * | 2002-11-18 | 2008-01-01 | Maxygen, Inc. | Interferon-alpha polypeptides and conjugates |
EP1583816A4 (en) | 2002-12-22 | 2007-06-13 | Scripps Research Inst | PROTEIN NETWORKS |
MXPA05006944A (es) | 2002-12-26 | 2005-12-14 | Mountain View Pharmaceuticals | Conjugados polimericos de interferon-beta cion potencia biologica aumentada. |
JP2006518725A (ja) | 2003-02-25 | 2006-08-17 | アプライド リサーチ システムズ エーアールエス ホールディング ナームロゼ フェンノートシャップ | 脱髄疾患におけるリバビリンとインターフェロンベータの併用 |
WO2004094593A2 (en) | 2003-04-17 | 2004-11-04 | The Scripps Research Institute | Expanding the eukaryotic genetic code |
WO2005007870A2 (en) | 2003-07-07 | 2005-01-27 | The Scripps Research Institute | COMPOSITIONS OF ORTHOGONAL LEUCYL-tRNA AND AMINOACYL-tRNA SYNTHETASE PAIRS AND USES THEREOF |
WO2005019415A2 (en) | 2003-07-07 | 2005-03-03 | The Scripps Research Institute | Compositions of orthogonal lysyl-trna and aminoacyl-trna synthetase pairs and uses thereof |
US7527943B2 (en) | 2003-07-07 | 2009-05-05 | The Scripps Research Institute | Compositions of orthogonal glutamyl-tRNA and aminoacyl-tRNA synthetase pairs and uses thereof |
CN100408090C (zh) | 2003-07-11 | 2008-08-06 | 舍林股份公司 | 改良的重组人干扰素-β-1b多肽 |
ES2831379T3 (es) * | 2003-10-09 | 2021-06-08 | Ambrx Inc | Derivados poliméricos para la modificación selectiva de proteínas |
RS52218B (en) | 2003-12-11 | 2012-10-31 | Ares Trading S.A. | STABILIZED FLUID INTERFERON FORMULATIONS |
EP1718664A4 (en) | 2004-02-02 | 2008-08-13 | Ambrx Inc | MODIFIED HUMAN FOUR FIXED PROPELLANT (4HB) BEAM POLYPEPTIDES, AND USE THEREOF |
WO2005091944A2 (en) | 2004-03-17 | 2005-10-06 | Eli Lilly And Company | Glycol linked fgf-21 compounds |
ZA200609412B (en) | 2004-05-17 | 2008-07-30 | Ares Trading Sa | Hydrogel interferon formulations |
EP1765382A1 (en) | 2004-06-07 | 2007-03-28 | Nastech Pharmaceutical Company Inc. | Intranasal formulations of interferon beta free of stabilizers that are proteins or polypeptides |
US7670595B2 (en) | 2004-06-28 | 2010-03-02 | Merck Patent Gmbh | Fc-interferon-beta fusion proteins |
EP1786917A4 (en) * | 2004-07-26 | 2008-05-28 | Enzon Pharmaceuticals Inc | OPTIMIZED INTERFERON BETA-GEN |
KR100781666B1 (ko) | 2004-11-02 | 2007-12-03 | 신영기 | 인간 인터페론-베타 변이체 |
KR101330626B1 (ko) | 2004-11-10 | 2013-11-18 | 노바티스 백신즈 앤드 다이아그노스틱스 인코포레이티드 | 탈아미드화된 인터페론-베타 |
TW200633718A (en) | 2004-12-16 | 2006-10-01 | Applied Research Systems | Treatment of hepatitis c in the asian population |
CA2927595C (en) | 2004-12-22 | 2023-01-31 | Ambrx, Inc. | Compositions containing, methods involving, and uses of non-natural amino acids and polypeptides |
ATE541934T1 (de) | 2004-12-22 | 2012-02-15 | Ambrx Inc | Zusammensetzungen von aminoacyl-trna-synthetase und verwendungen davon |
CN101247821B (zh) | 2005-06-03 | 2013-01-23 | Ambrx公司 | 经改良人类干扰素分子和其用途 |
DK1937824T3 (da) | 2005-08-18 | 2013-04-02 | Ambrx Inc | Sammensætninger af tRNA og anvendelser deraf |
SG155183A1 (en) | 2005-08-26 | 2009-09-30 | Ares Trading Sa | Process for the preparation of glycosylated interferon beta |
JP2009507003A (ja) | 2005-09-01 | 2009-02-19 | アレス トレーディング ソシエテ アノニム | 視神経炎の治療 |
FI20051003A0 (fi) | 2005-10-07 | 2005-10-07 | Faron Pharmaceuticals Oy | Menetelmä iskemiareperfuusiovaurion tai monielinhäiriön hoitamiseksi tai estämiseksi |
JP2010525821A (ja) * | 2007-05-02 | 2010-07-29 | アンブルックス,インコーポレイテッド | 修飾IFNβポリペプチドおよびこれらの使用 |
-
2008
- 2008-04-30 JP JP2010506615A patent/JP2010525821A/ja active Pending
- 2008-04-30 EP EP08747233.8A patent/EP2076533B1/en active Active
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CN1852732A (zh) * | 2002-12-26 | 2006-10-25 | 山景医药公司 | 具有增强的生物学效用的干扰素-β的聚合物缀合物 |
CN1859925A (zh) * | 2002-12-26 | 2006-11-08 | 山景医药公司 | 具有保留的受体结合活性的细胞因子、趋化因子、生长因子、多肽激素及其拮抗剂的聚合物缀合物 |
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IL201791A0 (en) | 2010-06-16 |
AU2008247815B2 (en) | 2012-09-06 |
NZ580686A (en) | 2012-11-30 |
WO2008137471A3 (en) | 2008-12-31 |
US8114630B2 (en) | 2012-02-14 |
CA2685596A1 (en) | 2008-11-13 |
US8329869B2 (en) | 2012-12-11 |
EP2076533A4 (en) | 2010-05-19 |
AU2008247815A1 (en) | 2008-11-13 |
CN101675071B (zh) | 2014-06-18 |
WO2008137471A2 (en) | 2008-11-13 |
EP2076533A2 (en) | 2009-07-08 |
BRPI0810622A2 (pt) | 2020-10-13 |
JP2010525821A (ja) | 2010-07-29 |
US20120197006A1 (en) | 2012-08-02 |
EP2076533B1 (en) | 2014-10-08 |
IL201791A (en) | 2016-07-31 |
MX2009011870A (es) | 2009-11-12 |
KR20100019467A (ko) | 2010-02-18 |
CN101675071A (zh) | 2010-03-17 |
CN103965347A (zh) | 2014-08-06 |
US20090208454A1 (en) | 2009-08-20 |
HK1134822A1 (en) | 2010-05-14 |
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