NO329749B1 - Polyol-interferon-ß-konjugat, fremgangsmate for fremstilling derav, farmasoytisk blanding derav og anvendelse derav for fremstilling av medikamenter. - Google Patents
Polyol-interferon-ß-konjugat, fremgangsmate for fremstilling derav, farmasoytisk blanding derav og anvendelse derav for fremstilling av medikamenter. Download PDFInfo
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- NO329749B1 NO329749B1 NO20005337A NO20005337A NO329749B1 NO 329749 B1 NO329749 B1 NO 329749B1 NO 20005337 A NO20005337 A NO 20005337A NO 20005337 A NO20005337 A NO 20005337A NO 329749 B1 NO329749 B1 NO 329749B1
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- Prior art keywords
- polyol
- peg
- interferon
- ifn
- conjugate
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- A61K47/56—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
- A61K47/59—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
- 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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US8333998P | 1998-04-28 | 1998-04-28 | |
PCT/US1999/009161 WO1999055377A2 (en) | 1998-04-28 | 1999-04-28 | Polyol-ifn-beta conjugates |
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NO20005337L NO20005337L (no) | 2000-12-28 |
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NO20005337A NO329749B1 (no) | 1998-04-28 | 2000-10-23 | Polyol-interferon-ß-konjugat, fremgangsmate for fremstilling derav, farmasoytisk blanding derav og anvendelse derav for fremstilling av medikamenter. |
NO20100324A NO332224B1 (no) | 1998-04-28 | 2010-03-09 | Fremgangsmate for trinnvis festing av polyetylenglykol (PEG) andeler i serie til et polypeptid |
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NO20100324A NO332224B1 (no) | 1998-04-28 | 2010-03-09 | Fremgangsmate for trinnvis festing av polyetylenglykol (PEG) andeler i serie til et polypeptid |
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JP (2) | JP4574007B2 (ja) |
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CA (2) | CA2330451A1 (ja) |
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NO (2) | NO329749B1 (ja) |
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Families Citing this family (78)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5932462A (en) * | 1995-01-10 | 1999-08-03 | Shearwater Polymers, Inc. | Multiarmed, monofunctional, polymer for coupling to molecules and surfaces |
IL121860A0 (en) | 1997-08-14 | 1998-02-22 | Yeda Res & Dev | Interleukin-18 binding proteins their preparation and use |
US7704944B2 (en) | 1997-08-14 | 2010-04-27 | Yeda Research And Development Company Ltd. | Interleukin-18 binding proteins, their preparation and use for the treatment of sepsis |
US7220717B2 (en) | 1997-08-14 | 2007-05-22 | Yeda Research And Development Company Ltd. | Interleukin-18 binding proteins, their preparation and use |
ES2265693T3 (es) * | 1998-10-16 | 2007-02-16 | Biogen Idec Ma Inc. | Proteinas de fusion con interferon-beta y usos. |
ES2630278T3 (es) * | 1998-10-16 | 2017-08-21 | Biogen Ma Inc. | Conjugados poliméricos de interferón beta-1a y usos de los mismos |
US7303760B2 (en) * | 1999-04-23 | 2007-12-04 | Alza Corporation | Method for treating multi-drug resistant tumors |
US7238368B2 (en) * | 1999-04-23 | 2007-07-03 | Alza Corporation | Releasable linkage and compositions containing same |
CN1244376C (zh) * | 1999-04-23 | 2006-03-08 | 阿尔萨公司 | 可释放的键和含有该键的组合物 |
US7431921B2 (en) | 2000-04-14 | 2008-10-07 | Maxygen Aps | Interferon beta-like molecules |
US6531122B1 (en) | 1999-08-27 | 2003-03-11 | Maxygen Aps | Interferon-β variants and conjugates |
US7144574B2 (en) | 1999-08-27 | 2006-12-05 | Maxygen Aps | Interferon β variants and conjugates |
TR200101086A3 (ja) * | 1999-10-15 | 2001-08-21 | ||
JP4593048B2 (ja) | 1999-12-24 | 2010-12-08 | 協和発酵キリン株式会社 | 分岐型ポリアルキレングリコール類 |
ES2327606T3 (es) | 2000-01-10 | 2009-11-02 | Maxygen Holdings Ltd | Conjugados de g-csf. |
DE60138364D1 (de) | 2000-02-11 | 2009-05-28 | Bayer Healthcare Llc | Gerinnungsfaktor vii oder viia konjugate |
CA2436623C (en) | 2001-01-30 | 2011-08-02 | Kyowa Hakko Kogyo Co., Ltd. | Branched polyalkylene glycols |
EP1234583A1 (en) | 2001-02-23 | 2002-08-28 | F. Hoffmann-La Roche Ag | PEG-conjugates of HGF-NK4 |
YU48703A (sh) | 2001-02-27 | 2006-05-25 | Maxygen Aps | Novi interferonu beta-slični molekuli |
NZ530545A (en) | 2001-07-11 | 2006-10-27 | Maxygen Holdings Ltd | Specific conjugates comprising a polypeptide exhibiting G-CSF activity and a non-polypeptide moiety |
EA009783B1 (ru) | 2002-01-18 | 2008-04-28 | Байоджен Айдек Ма Инк. | Полиалкиленгликоль с остатком для конъюгации биологически активного соединения |
TWI334785B (en) | 2002-06-03 | 2010-12-21 | Serono Lab | Use of recombinant ifn-β1a and pharmaceutical composition comprising recombinant ifn-β1a for the treatment of hcv infection in patients of asian race |
AU2003254641A1 (en) * | 2002-08-28 | 2004-03-19 | Maxygen Aps | Interferon beta-like molecules for treatment of cancer |
US8129330B2 (en) * | 2002-09-30 | 2012-03-06 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof |
PL219741B1 (pl) | 2002-12-26 | 2015-07-31 | Mountain View Pharmaceuticals | Sposób zwiększania antyproliferacyjnego potencjału nieglikozylowanego interferonu-beta-1b in vitro, koniugat wytworzony tym sposobem i jego zastosowanie oraz kompozycja farmaceutyczna zawierająca koniugat i jej zastosowanie |
TWI364295B (en) | 2002-12-26 | 2012-05-21 | Mountain View Pharmaceuticals | Polymer conjugates of cytokines, chemokines, growth factors, polypeptide hormones and antagonists thereof with preserved receptor-binding activity |
AU2004221761B2 (en) | 2003-03-20 | 2010-01-07 | Bayer Healthcare Llc | FVII or FVIIa variants |
TWI272948B (en) | 2003-05-01 | 2007-02-11 | Ares Trading Sa | HSA-free stabilized interferon liquid formulations |
GB0316294D0 (en) | 2003-07-11 | 2003-08-13 | Polytherics Ltd | Conjugated biological molecules and their preparation |
EP2641611A3 (en) | 2003-10-17 | 2013-12-18 | Novo Nordisk A/S | Combination therapy |
AU2008201682B2 (en) * | 2004-02-02 | 2011-02-24 | Ambrx, Inc. | Modified human interferon polypeptides and their uses |
AU2005319099B2 (en) | 2004-02-02 | 2010-09-16 | Ambrx, Inc. | Modified human growth hormone |
AU2005211362B2 (en) | 2004-02-02 | 2008-03-13 | Ambrx, Inc. | Modified human interferon polypeptides and their uses |
EP1586334A1 (en) * | 2004-04-15 | 2005-10-19 | TRASTEC scpa | G-CSF conjugates with peg |
JP2007538048A (ja) | 2004-05-17 | 2007-12-27 | アレス トレーディング ソシエテ アノニム | ヒドロゲル・インターフェロン製剤 |
WO2005117948A1 (en) | 2004-06-01 | 2005-12-15 | Ares Trading S.A. | Method of stabilizing proteins |
US7731948B2 (en) | 2004-06-01 | 2010-06-08 | Ares Trading S.A. | Stabilized interferon liquid formulations |
TW200633718A (en) * | 2004-12-16 | 2006-10-01 | Applied Research Systems | Treatment of hepatitis c in the asian population |
US7851565B2 (en) | 2004-12-21 | 2010-12-14 | Nektar Therapeutics | Stabilized polymeric thiol reagents |
EP1836316A4 (en) | 2004-12-22 | 2009-07-22 | Ambrx Inc | PROCESS FOR EXPRESSION AND CLEANING OF RECOMBINANT HUMAN GROWTH HORMONE |
NZ555386A (en) | 2004-12-22 | 2011-01-28 | Ambrx Inc | Formulations of human growth hormone comprising a non-naturally encoded amino acid |
JP5335422B2 (ja) | 2005-06-17 | 2013-11-06 | ノボ ノルディスク ヘルス ケア アクチェンゲゼルシャフト | 少なくとも1つの非天然のシステインを含んでいる操作されたタンパク質の選択的な還元および誘導体化 |
JP2009503111A (ja) * | 2005-08-04 | 2009-01-29 | ネクター セラピューティックス エイエル,コーポレイション | G−csf部分および重合体の複合体 |
LT1917276T (lt) | 2005-08-26 | 2018-05-25 | Ares Trading S.A. | Glikozilinto interferono beta gavimo būdas |
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 |
US20070238656A1 (en) * | 2006-04-10 | 2007-10-11 | Eastman Kodak Company | Functionalized poly(ethylene glycol) |
US20080096819A1 (en) * | 2006-05-02 | 2008-04-24 | Allozyne, Inc. | Amino acid substituted molecules |
EP2395099A3 (en) * | 2006-05-02 | 2012-05-16 | Allozyne, Inc. | Amino acid substituted molecules |
MX2008014971A (es) | 2006-05-24 | 2008-12-05 | Serono Lab | Regimen de cladribine para tratar esclerosis multiple. |
EP2213733A3 (en) | 2006-05-24 | 2010-12-29 | Novo Nordisk Health Care AG | Factor IX analogues having prolonged in vivo half life |
WO2008137471A2 (en) * | 2007-05-02 | 2008-11-13 | Ambrx, Inc. | Modified interferon beta polypeptides and their uses |
CA2707840A1 (en) * | 2007-08-20 | 2009-02-26 | Allozyne, Inc. | Amino acid substituted molecules |
KR20100099298A (ko) | 2007-12-20 | 2010-09-10 | 메르크 세로노 에스. 에이. | Peg인터페론베타 제형 |
SG188143A1 (en) | 2008-02-08 | 2013-03-28 | Ambrx Inc | Modified leptin polypeptides and their uses |
CN101525381B (zh) * | 2008-03-04 | 2012-04-18 | 北京百川飞虹生物科技有限公司 | 一种重组复合干扰素及其表达载体的构建和表达 |
WO2009155102A2 (en) * | 2008-05-30 | 2009-12-23 | Barofold, Inc. | Method for derivatization of proteins using hydrostatic pressure |
US20110124614A1 (en) * | 2008-10-25 | 2011-05-26 | Halina Offner | Methods And Compositions For The Treatment of Autoimmune Disorders |
DE102009032179A1 (de) * | 2009-07-07 | 2011-01-13 | Biogenerix Ag | Verfahren zur Reinigung von Interferon beta |
ES2365343B1 (es) | 2009-11-19 | 2012-07-10 | Fundación Centro Nacional De Investigaciones Cardiovasculares Carlos Iii | Uso de cd98 como marcador de receptividad endometrial. |
WO2011101242A1 (en) | 2010-02-16 | 2011-08-25 | Novo Nordisk A/S | Factor viii molecules with reduced vwf binding |
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 |
WO2011143274A1 (en) | 2010-05-10 | 2011-11-17 | Perseid Therapeutics | Polypeptide inhibitors of vla4 |
EP2593130A2 (en) | 2010-07-15 | 2013-05-22 | Novo Nordisk A/S | Stabilized factor viii variants |
EP3466968A1 (en) | 2010-09-15 | 2019-04-10 | Stichting Sanquin Bloedvoorziening | Factor viii variants having a decreased cellular uptake |
JP2014506889A (ja) * | 2011-02-18 | 2014-03-20 | ステムディーアール インク. | Sirt1発現誘導物質を含む敗血症または敗血症性ショックの予防または治療用組成物 |
CA2840552A1 (en) | 2011-07-01 | 2013-01-10 | Bayer Intellectual Property Gmbh | Relaxin fusion polypeptides and uses thereof |
SG10201602076QA (en) * | 2011-10-01 | 2016-04-28 | Glytech Inc | Glycosylated polypeptide and pharmaceutical composition containing same |
WO2013130684A1 (en) | 2012-02-27 | 2013-09-06 | Amunix Operating Inc. | Xten-folate conjugate compositions and methods of making same |
CN104136038A (zh) | 2012-02-29 | 2014-11-05 | 东丽株式会社 | 体腔积液抑制剂 |
CN104334574B (zh) | 2013-03-29 | 2020-01-14 | 株式会社糖锁工学研究所 | 附加唾液酸化糖链的多肽 |
US11759500B2 (en) | 2014-07-24 | 2023-09-19 | Abion Inc. | PEGylated interferon-beta variant |
WO2016013697A1 (ko) * | 2014-07-24 | 2016-01-28 | 에이비온 주식회사 | 인터페론-베타 변이체의 폴리에틸렌글리콜 배합체 |
MX2017002140A (es) | 2014-08-19 | 2017-08-21 | Biogen Ma Inc | Metodo de pegilacion. |
EP4014985A1 (en) | 2015-05-01 | 2022-06-22 | Allysta Pharmaceuticals, Inc. | Adiponectin peptidomimetics for treating ocular disorders |
MD3310816T2 (ro) * | 2015-06-19 | 2021-01-31 | Eisai R&D Man Co Ltd | Imunoglobuline conjugate Cys80 |
JP7146897B2 (ja) * | 2017-04-17 | 2022-10-04 | ザ リージェンツ オブ ザ ユニバーシティ オブ コロラド,ア ボディー コーポレイト | ホモシスチン尿症の治療のための酵素補充療法の最適化 |
WO2020158690A1 (ja) | 2019-01-28 | 2020-08-06 | 東レ株式会社 | 肝細胞増殖因子又はその活性断片のポリエチレングリコール修飾体 |
WO2020158691A1 (ja) | 2019-01-28 | 2020-08-06 | 東レ株式会社 | 肝細胞増殖因子又はその活性断片のポリエチレングリコール修飾体 |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
JP2524586B2 (ja) * | 1985-06-26 | 1996-08-14 | シタス コーポレイション | ポリマ−接合を利用する医薬組成物用蛋白質の可溶化 |
US5206344A (en) * | 1985-06-26 | 1993-04-27 | Cetus Oncology Corporation | Interleukin-2 muteins and polymer conjugation thereof |
US5208344A (en) * | 1987-07-31 | 1993-05-04 | American Home Products Corporation | Naphthalenepropionic acid derivatives as anti-inflammatory/antiallergic agents |
US5166322A (en) * | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
US5595732A (en) * | 1991-03-25 | 1997-01-21 | Hoffmann-La Roche Inc. | Polyethylene-protein conjugates |
US5382657A (en) | 1992-08-26 | 1995-01-17 | Hoffmann-La Roche Inc. | Peg-interferon conjugates |
PT730470E (pt) | 1993-11-10 | 2002-08-30 | Enzon Inc | Conjugados melhorados de interferao-polimero |
US5766581A (en) | 1994-03-31 | 1998-06-16 | Amgen Inc. | Method for treating mammals with monopegylated proteins that stimulates megakaryocyte growth and differentiation |
AU696387B2 (en) * | 1994-05-18 | 1998-09-10 | Inhale Therapeutic Systems, Inc. | Methods and compositions for the dry powder formulation of interferons |
US5824784A (en) * | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
US5932462A (en) | 1995-01-10 | 1999-08-03 | Shearwater Polymers, Inc. | Multiarmed, monofunctional, polymer for coupling to molecules and surfaces |
SE9503380D0 (sv) * | 1995-09-29 | 1995-09-29 | Pharmacia Ab | Protein derivatives |
TW517067B (en) * | 1996-05-31 | 2003-01-11 | Hoffmann La Roche | Interferon conjugates |
US5851984A (en) * | 1996-08-16 | 1998-12-22 | Genentech, Inc. | Method of enhancing proliferation or differentiation of hematopoietic stem cells using Wnt polypeptides |
KR0176625B1 (ko) | 1996-11-05 | 1999-04-01 | 삼성전자주식회사 | 적외선 물체검출장치 |
ATE200030T1 (de) * | 1997-01-29 | 2001-04-15 | Polymasc Pharmaceuticals Plc | Pegylationsverfahren |
NZ502375A (en) * | 1997-07-14 | 2001-11-30 | Bolder Biotechnology Inc | The addition of non-natural cysteine derivatives to cause the protein to act as antagonists of the GH family |
US6307024B1 (en) * | 1999-03-09 | 2001-10-23 | Zymogenetics, Inc. | Cytokine zalpha11 Ligand |
US6531122B1 (en) * | 1999-08-27 | 2003-03-11 | Maxygen Aps | Interferon-β variants and conjugates |
-
1999
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