BG64694B1 - Полиол - интерферон - бета конюгати - Google Patents
Полиол - интерферон - бета конюгати Download PDFInfo
- Publication number
- BG64694B1 BG64694B1 BG104871A BG10487100A BG64694B1 BG 64694 B1 BG64694 B1 BG 64694B1 BG 104871 A BG104871 A BG 104871A BG 10487100 A BG10487100 A BG 10487100A BG 64694 B1 BG64694 B1 BG 64694B1
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- BG
- Bulgaria
- Prior art keywords
- polyol
- peg
- ifn
- interferon
- thiol
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- 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
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Families Citing this family (82)
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| 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 |
| 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 |
| SG2008070138A (en) * | 1998-10-16 | 2017-08-30 | Biogen Ma Inc | Polymer conjugates of interferon beta- 1a and their uses |
| MXPA01010750A (es) * | 1999-04-23 | 2003-08-20 | Alza Corp | Conjugado que tiene un enlace dividible para utilizarse en un liposoma. |
| 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 |
| 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 |
| US7431921B2 (en) | 1999-08-27 | 2008-10-07 | Maxygen Aps | Interferon beta-like molecules |
| TR200101086A3 (es) * | 1999-10-15 | 2001-08-21 | ||
| AU2223401A (en) | 1999-12-24 | 2001-07-09 | Kyowa Hakko Kogyo Co. Ltd. | Branched polyalkylene glycols |
| CZ20022727A3 (cs) | 2000-01-10 | 2002-11-13 | Maxygen Holdings Ltd | Polypeptidový konjugát, způsob jeho výroby a farmaceutický prostředek |
| EP1982732A3 (en) | 2000-02-11 | 2011-06-08 | Bayer HealthCare LLC | Factor VII or VIIA-like conjugates |
| EP1400550B1 (en) * | 2001-01-30 | 2010-06-23 | Kyowa Hakko Kirin Co., Ltd. | Branched polyalkylene glycols |
| EP1234583A1 (en) | 2001-02-23 | 2002-08-28 | F. Hoffmann-La Roche Ag | PEG-conjugates of HGF-NK4 |
| PL367154A1 (en) | 2001-02-27 | 2005-02-21 | Maxygen Aps | New interferon beta-like molecules |
| BR0211071A (pt) | 2001-07-11 | 2004-12-21 | Maxygen Holdings Ltd | Conjugado polipeptìdico apresentando atividade de g-csf, método para preparar um conjugado de g-csf, composição, método para tratar um mamìfero sofrendo de um nìvel neutrofìlico insuficiente, e, uso do conjugado polipeptìdico |
| PT3025726T (pt) | 2002-01-18 | 2020-01-09 | Biogen Ma Inc | Compostos do polímero polialquileno e utilizações dos mesmos |
| 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 |
| WO2004020468A2 (en) * | 2002-08-28 | 2004-03-11 | 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 |
| US9125880B2 (en) * | 2002-12-26 | 2015-09-08 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates of interferon-beta with enhanced biological potency |
| KR101162908B1 (ko) * | 2002-12-26 | 2012-07-06 | 마운틴 뷰 파마슈티컬즈, 인크. | 수용체-결합 활성이 보존된, 사이토카인, 케모카인,성장인자, 폴리펩티드 호르몬 및 이들의 길항제의 중합체접합체 |
| ES2327044T3 (es) | 2003-03-20 | 2009-10-23 | Bayer Healthcare Llc | Variantes de fvii o fviia. |
| 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 |
| ES2428358T3 (es) | 2003-10-17 | 2013-11-07 | Novo Nordisk A/S | Terapia de combinación |
| AU2008201682B2 (en) * | 2004-02-02 | 2011-02-24 | Ambrx, Inc. | Modified human interferon polypeptides and their uses |
| SG135176A1 (en) | 2004-02-02 | 2007-09-28 | Ambrx Inc | Modified human four helical bundle polypeptides and their uses |
| EP1586334A1 (en) * | 2004-04-15 | 2005-10-19 | TRASTEC scpa | G-CSF conjugates with peg |
| UA88300C2 (ru) | 2004-05-17 | 2009-10-12 | Эйрес Трейдинг С.А. | Гидрогелевые композиции, которые содержат интерферон |
| BRPI0510526A (pt) | 2004-06-01 | 2007-10-30 | Ares Trading Sa | formulações lìquidas estabilizadas de interferon |
| CA2567309A1 (en) | 2004-06-01 | 2005-12-15 | Ares Trading S.A. | Method of stabilizing proteins |
| TW200633718A (en) * | 2004-12-16 | 2006-10-01 | Applied Research Systems | Treatment of hepatitis c in the asian population |
| EP1827501B2 (en) | 2004-12-21 | 2013-11-20 | Nektar Therapeutics | Stabilized polymeric thiol reagents |
| WO2006073846A2 (en) | 2004-12-22 | 2006-07-13 | Ambrx, Inc. | Methods for expression and purification of recombinant human growth hormone |
| CN103690936A (zh) | 2004-12-22 | 2014-04-02 | Ambrx公司 | 经修饰的人类生长激素 |
| US7816320B2 (en) | 2004-12-22 | 2010-10-19 | Ambrx, Inc. | Formulations of human growth hormone comprising a non-naturally encoded amino acid at position 35 |
| EP1893632B1 (en) | 2005-06-17 | 2015-08-12 | Novo Nordisk Health Care AG | Selective reduction and derivatization of engineered factor vii proteins comprising at least one non-native cysteine |
| WO2007019331A2 (en) * | 2005-08-04 | 2007-02-15 | Nektar Therapeutics Al, Corporation | Conjugates of a g-csf moiety and a polymer |
| JP4944112B2 (ja) | 2005-08-26 | 2012-05-30 | アレス トレーディング ソシエテ アノニム | グリコシル化されたインターフェロンベータの調製方法 |
| AU2006286489B2 (en) | 2005-09-01 | 2012-08-09 | Ares Trading S.A. | Treatment of optic neuritis |
| US20070238656A1 (en) * | 2006-04-10 | 2007-10-11 | Eastman Kodak Company | Functionalized poly(ethylene glycol) |
| AU2007248680C1 (en) * | 2006-05-02 | 2014-01-23 | Allozyne, Inc. | Non-natural amino acid substituted polypeptides |
| US20080096819A1 (en) * | 2006-05-02 | 2008-04-24 | Allozyne, Inc. | Amino acid substituted molecules |
| RU2008145084A (ru) | 2006-05-24 | 2010-06-27 | Ново Нордиск Хелс Кеа Аг (Ch) | Аналоги фактора ix, имеющие пролонгированное время полужизни in vivo |
| AU2007253254B2 (en) | 2006-05-24 | 2013-01-17 | Merck Serono Sa | Cladribine regimen for treating multiple sclerosis |
| MX2009011870A (es) * | 2007-05-02 | 2009-11-12 | Ambrx Inc | Polipeptidos de interferon beta modificados y usos de los mismos. |
| CA2707840A1 (en) | 2007-08-20 | 2009-02-26 | Allozyne, Inc. | Amino acid substituted molecules |
| BRPI0821029A2 (pt) | 2007-12-20 | 2015-06-16 | Merck Serono Sa | Fomulações de peg-interferon-beta |
| NZ620606A (en) | 2008-02-08 | 2015-08-28 | 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. |
| EP2536753B1 (en) | 2010-02-16 | 2017-12-20 | Novo Nordisk A/S | Factor viii molecules with reduced vwf binding |
| ES2993140T3 (en) | 2010-04-02 | 2024-12-23 | Amunix Pharmaceuticals Inc | Binding fusion proteins, binding fusion protein-drug conjugates, xten-drug conjugates and methods of making and using same |
| 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 |
| EP2569331A1 (en) | 2010-05-10 | 2013-03-20 | Perseid Therapeutics LLC | Polypeptide inhibitors of vla4 |
| US20130183280A1 (en) | 2010-07-15 | 2013-07-18 | Novo Nordisk A/S | Stabilized factor viii variants |
| CN104788557A (zh) | 2010-09-15 | 2015-07-22 | 诺沃—诺迪斯克有限公司 | 具有减少的细胞摄取的因子viii变体 |
| EP2676675B1 (en) * | 2011-02-18 | 2019-04-10 | Stemdr Inc. | Composition containing inducer of sirt1 expression for preventing or treating sepsis or septic shock |
| MX2014000031A (es) | 2011-07-01 | 2014-07-09 | Bayer Ip Gmbh | Polipeptidos de fusion de relaxina y usos de los mismos. |
| AU2012317325B2 (en) * | 2011-10-01 | 2016-10-06 | Glytech, Inc. | Glycosylated polypeptide and pharmaceutical composition containing same |
| CN107496932A (zh) | 2012-02-27 | 2017-12-22 | 阿穆尼克斯运营公司 | Xten缀合组合物和制造其的方法 |
| CA2865879A1 (en) | 2012-02-29 | 2013-09-06 | Toray Industries, Inc. | Inhibitory agent for body cavity fluid accumulation |
| WO2014157107A1 (ja) | 2013-03-29 | 2014-10-02 | 株式会社糖鎖工学研究所 | シアリル化糖鎖が付加されたポリペプチド |
| WO2016013697A1 (ko) * | 2014-07-24 | 2016-01-28 | 에이비온 주식회사 | 인터페론-베타 변이체의 폴리에틸렌글리콜 배합체 |
| WO2016013911A1 (ko) * | 2014-07-24 | 2016-01-28 | 에이비온 주식회사 | 페길화된 인터페론 -베타 변이체 |
| EP3183264B1 (en) | 2014-08-19 | 2020-07-29 | Biogen MA Inc. | Pegylation method |
| CA2981822C (en) | 2015-05-01 | 2023-04-11 | Allysta Pharmaceuticals, Inc. | Adiponectin peptidomimetics for treating ocular disorders |
| DK3310816T3 (da) * | 2015-06-19 | 2020-10-12 | Eisai R&D Man Co Ltd | Cys80-konjugerede immunoglobuliner |
| EP4487914A3 (en) | 2015-11-09 | 2025-03-26 | The Regents of the University of Colorado, A Body Corporate | Compositions and methods for treatment of homocystinuria |
| CN110753556A (zh) * | 2017-04-17 | 2020-02-04 | 科罗拉多州立大学董事会法人团体 | 治疗同型半胱氨酸尿症的酶替代疗法优化 |
| AU2018372007A1 (en) | 2017-11-24 | 2020-07-09 | Merck Patent Gmbh | Cladribine regimen for use intreating progressive forms of multiple sclerosis |
| CA3124682A1 (en) | 2019-01-28 | 2020-08-06 | Toray Industries, Inc. | Polyethylene glycol-modified form of hepatocyte growth factor or active fragment thereof |
| 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 |
| AU2021342333A1 (en) | 2020-09-10 | 2023-04-06 | Merck Patent Gmbh | Novel treatment regimen for the treatment of autoimmune disorders |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4766106A (en) | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| US5206344A (en) * | 1985-06-26 | 1993-04-27 | Cetus Oncology Corporation | Interleukin-2 muteins and polymer conjugation thereof |
| DE3676670D1 (de) * | 1985-06-26 | 1991-02-07 | Cetus Corp | Solubilisierung von proteinen fuer pharmazeutische zusammensetzungen mittels polymerkonjugierung. |
| US4917888A (en) | 1985-06-26 | 1990-04-17 | Cetus Corporation | Solubilization of immunotoxins for pharmaceutical compositions using polymer conjugation |
| 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 |
| CA2176229C (en) | 1993-11-10 | 2003-05-27 | Carl W. Gilbert | Improved interferon polymer conjugates |
| BR9506017A (pt) | 1994-03-31 | 1997-10-14 | Amagen Inc | Polipeptide poninculeotídeo isolado sequência de Dna e Cdna vetor de Dna célula hospedeira anticorpo composição farmacêutica derivado de Mgdf produto polípeptídeo Mgdf com grupos peg e preparação do mesmo e processo para produzir um polipeptídeo Mgdf humano e uma condição trombocitopênica para aumentar o número de megacarióticos maduroas e de plaquetas em um paciente necessitado dos mesmos e para fixar um polímero solúvel em água a um polipeptídeo Mgdf uma molècula de polietileno glicol a um polipeptideo Mgdf e poipeptideo glicol solúvel em água a um polipeptideo mgdf |
| EP0759939B1 (en) * | 1994-05-18 | 2005-07-20 | Nektar Therapeutics | 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 |
| DE69800640T2 (de) * | 1997-01-29 | 2001-07-05 | Polymasc Pharmaceuticals Plc, London | Pegylationsverfahren |
| DE69838552T2 (de) * | 1997-07-14 | 2008-05-21 | Bolder Biotechnology, Inc., Louisville | Derivate des wachstumshormons und verwandte proteine |
| 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 |
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