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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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 |
| US7220717B2 (en) | 1997-08-14 | 2007-05-22 | Yeda Research And Development Company Ltd. | 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 |
| AU766190B2 (en) | 1998-10-16 | 2003-10-09 | Biogen Idec Ma Inc. | Interferon-beta fusion proteins and uses |
| EA004789B9 (ru) * | 1998-10-16 | 2017-05-31 | Байоджен, Инк. | Полимерные конъюгаты бета-1а-интерферона и их использование |
| 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 |
| CA2369595C (en) * | 1999-04-23 | 2010-10-05 | Alza Corporation | Conjugate having a cleavable linkage for use in a liposome |
| 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 |
| US7144574B2 (en) | 1999-08-27 | 2006-12-05 | Maxygen Aps | Interferon β variants and conjugates |
| TR200101086A3 (xx) * | 1999-10-15 | 2001-08-21 | ||
| ATE522563T1 (de) * | 1999-12-24 | 2011-09-15 | Kyowa Hakko Kirin Co Ltd | Verzweigte polyalkylenglykole |
| AR027509A1 (es) | 2000-01-10 | 2003-04-02 | Maxygen Aps | Conjugados g-csf |
| CA2397347C (en) | 2000-02-11 | 2011-07-12 | Maxygen Aps | Factor vii or viia-like molecules |
| DE60236796D1 (de) | 2001-01-30 | 2010-08-05 | Kyowa Hakko Kirin Co Ltd | Verzweigte polyalkylenglykole |
| EP1234583A1 (en) * | 2001-02-23 | 2002-08-28 | F. Hoffmann-La Roche Ag | PEG-conjugates of HGF-NK4 |
| IL156059A0 (en) | 2001-02-27 | 2003-12-23 | Maxygen Aps | NEW INTERFERON beta-LIKE MOLECULES |
| KR100961859B1 (ko) | 2001-07-11 | 2010-06-09 | 맥시겐 홀딩스 엘티디 | 지-씨에스에프 접합체 |
| BRPI0306993B8 (pt) | 2002-01-18 | 2021-05-25 | Biogen Idec Inc | polímero de polialquilenoglicol ativado; composição; e uso de um composto na produção de um medicamento para o tratamento de esclerose múltipla ou infecção viral suscetível |
| 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 |
| CN102319437B (zh) * | 2002-12-26 | 2017-10-13 | 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 |
| JP2006519170A (ja) * | 2002-12-26 | 2006-08-24 | マウンテン ビュー ファーマシューティカルズ，インコーポレイテッド | サイトカイン、ケモカイン、増殖因子、ポリペプチドホルモン、およびレセプター結合活性が保存されたそのアンタゴニストのポリマー結合体 |
| EP1608745B1 (en) | 2003-03-20 | 2009-05-13 | 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 |
| NZ548255A (en) * | 2004-02-02 | 2010-10-29 | Ambrx Inc | Modified human interferon polypeptides and their uses |
| AU2008201682B2 (en) * | 2004-02-02 | 2011-02-24 | Ambrx, Inc. | Modified human interferon polypeptides and their uses |
| EP1586334A1 (en) * | 2004-04-15 | 2005-10-19 | TRASTEC scpa | G-CSF conjugates with peg |
| AU2005244448B2 (en) | 2004-05-17 | 2011-03-17 | Ares Trading S.A. | Hydrogel interferon formulations |
| CA2567309A1 (en) | 2004-06-01 | 2005-12-15 | Ares Trading S.A. | Method of stabilizing proteins |
| EA010979B1 (ru) | 2004-06-01 | 2008-12-30 | Арес Трейдинг С.А. | Стабилизированные жидкие препаративные формы интерферона |
| 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 |
| KR20070090023A (ko) | 2004-12-22 | 2007-09-04 | 암브룩스, 인코포레이티드 | 변형 인간 성장 호르몬 |
| BRPI0518661A2 (pt) | 2004-12-22 | 2008-12-02 | Ambrx Inc | mÉtodos para expressço e purificaÇço do hormânio do crescimento humano recombinante |
| BRPI0519170A8 (pt) | 2004-12-22 | 2018-05-08 | Ambrx Inc | formulações de hormônio de crescimento humano que compreendem um aminoácido não naturalmente codificado |
| 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 |
| 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 |
| 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 |
| EP1933860A2 (en) | 2005-09-01 | 2008-06-25 | Ares Trading S.A. | Treatment of optic neuritis |
| 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 |
| US7632492B2 (en) * | 2006-05-02 | 2009-12-15 | Allozyne, Inc. | Modified human interferon-β polypeptides |
| AU2007253264A1 (en) | 2006-05-24 | 2007-11-29 | Novo Nordisk Health Care Ag | Factor IX analogues having prolonged in vivo half life |
| CA2649810A1 (en) | 2006-05-24 | 2007-11-29 | Laboratoires Serono S.A. | Cladribine regimen for treating multiple sclerosis |
| 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 |
| CA2707840A1 (en) | 2007-08-20 | 2009-02-26 | Allozyne, Inc. | Amino acid substituted molecules |
| HRP20120483T1 (hr) * | 2007-12-20 | 2012-07-31 | Merck@Serono@SA | Formulacije peg interferona beta |
| NZ586947A (en) | 2008-02-08 | 2012-11-30 | 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 |
| US20100112660A1 (en) * | 2008-05-30 | 2010-05-06 | 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 |
| EP4450523A3 (en) | 2010-04-02 | 2025-03-12 | 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 |
| JP2013528374A (ja) | 2010-05-10 | 2013-07-11 | パーシード セラピューティクス リミテッド ライアビリティ カンパニー | Ｖｌａ４のポリペプチド阻害剤 |
| EP2593130A2 (en) | 2010-07-15 | 2013-05-22 | 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 |
| HK1199889A1 (en) | 2011-07-01 | 2015-07-24 | Bayer Intellectual Property Gmbh | Relaxin fusion polypeptides and uses thereof |
| EP2762489B1 (en) * | 2011-10-01 | 2018-03-28 | Glytech, Inc. | Glycosylated polypeptide and pharmaceutical composition containing same |
| PE20142451A1 (es) | 2012-02-27 | 2015-02-04 | Amunix Operating Inc | Composiciones de conjugados de xten y metodos para realizar las mismas |
| MX2014010209A (es) | 2012-02-29 | 2014-11-21 | Toray Industries | Agente inhibidor para acumulacion de fluido de la cavidad corporal. |
| 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 |
| 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 |
| WO2017030563A1 (en) | 2014-08-19 | 2017-02-23 | Biogen Ma Inc | Pegylation method |
| WO2016179007A1 (en) | 2015-05-01 | 2016-11-10 | Allysta Pharmaceuticals, Inc. | Adiponectin peptidomimetics for treating ocular disorders |
| CA2989637C (en) * | 2015-06-19 | 2023-01-10 | Eisai R&D Management Co., Ltd. | Cys80 conjugated immunoglobulins |
| NZ741552A (en) | 2015-11-09 | 2022-04-29 | Univ Colorado Regents | Compositions and methods for treatment of homocystinuria |
| EP3612214A4 (en) * | 2017-04-17 | 2021-01-20 | The Regents of the University of Colorado, A Body Corporate | ENZYME REPLACEMENT THERAPY OPTIMIZATION FOR THE TREATMENT OF HOMOCYSTINURIA |
| JP7495345B2 (ja) | 2017-11-24 | 2024-06-04 | 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 ハフツング | 進行型多発性硬化症の処置における使用のためのクラドリビン処方計画 |
| CA3125320A1 (en) | 2019-01-28 | 2020-08-06 | Toray Industries, Inc. | Polyethylene glycol-modified form of hepatocyte growth factor or active fragment thereof |
| BR112021012472A2 (pt) | 2019-01-28 | 2021-11-30 | Toray Industries | Forma modificada por polietileno glicol de um fator de crescimento de hepatócito ou um fragmento ativo do mesmo, e, medicamento |
| US20240226284A1 (en) | 2020-09-10 | 2024-07-11 | Merck Patent Gmbh | Novel treatment regimen for the treatment of autoimmune disorders |
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 |
| DE3676670D1 (de) * | 1985-06-26 | 1991-02-07 | Cetus Corp | Solubilisierung von proteinen fuer pharmazeutische zusammensetzungen mittels polymerkonjugierung. |
| 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 |
| 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 |
| NZ276943A (en) | 1993-11-10 | 1998-02-26 | Schering Corp Substituted For | Alpha-interferon conjugated to a non-antigenic polymer (preferably a polyalkylene oxide) and its preparation |
| CN1229385C (zh) | 1994-03-31 | 2005-11-30 | 安姆根有限公司 | 刺激巨核细胞生长和分化的组合物及方法 |
| NZ285664A (en) * | 1994-05-18 | 1998-07-28 | Inhale Therapeutic Syst | Dry powder interferon composition adapted for pulmonary delivery |
| 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 |
| AU751898B2 (en) * | 1997-07-14 | 2002-08-29 | Bolder Biotechnology, Inc. | Derivatives of growth hormone and related proteins |
| 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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1999
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2000
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2003
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