CA2663352A1 - Albumin fusion proteins - Google Patents
Albumin fusion proteins Download PDFInfo
- Publication number
- CA2663352A1 CA2663352A1 CA002663352A CA2663352A CA2663352A1 CA 2663352 A1 CA2663352 A1 CA 2663352A1 CA 002663352 A CA002663352 A CA 002663352A CA 2663352 A CA2663352 A CA 2663352A CA 2663352 A1 CA2663352 A1 CA 2663352A1
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- dose
- albumin
- albumin fusion
- fusion protein
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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| US60/960,039 | 2007-09-12 | ||
| PCT/US2007/019841 WO2008033413A2 (en) | 2006-09-14 | 2007-09-13 | Albumin fusion proteins |
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| US7906118B2 (en) | 2005-04-06 | 2011-03-15 | Ibc Pharmaceuticals, Inc. | Modular method to prepare tetrameric cytokines with improved pharmacokinetics by the dock-and-lock (DNL) technology |
| EP1631496B1 (en) | 2003-04-28 | 2014-02-26 | Medical Instill Technologies, Inc. | Container with valve assembly for filling and dispensing substances, and apparatus and method for filling |
| US8652484B2 (en) | 2004-02-13 | 2014-02-18 | Immunomedics, Inc. | Delivery system for cytotoxic drugs by bispecific antibody pretargeting |
| US8491914B2 (en) | 2004-02-13 | 2013-07-23 | Ibc Pharmaceuticals, Inc. | Dock-and-lock (DNL) complexes for delivery of interference RNA |
| US9481878B2 (en) | 2004-02-13 | 2016-11-01 | Immunomedics, Inc. | Compositions and methods of use of immunotoxins comprising ranpirnase (Rap) show potent cytotoxic activity |
| US8435539B2 (en) | 2004-02-13 | 2013-05-07 | Immunomedics, Inc. | Delivery system for cytotoxic drugs by bispecific antibody pretargeting |
| US8003111B2 (en) | 2005-04-06 | 2011-08-23 | Ibc Pharmaceuticals, Inc. | Dimeric alpha interferon pegylated site-specifically shows enhanced and prolonged efficacy in vivo |
| US8551480B2 (en) | 2004-02-13 | 2013-10-08 | Immunomedics, Inc. | Compositions and methods of use of immunotoxins comprising ranpirnase (Rap) show potent cytotoxic activity |
| US8034352B2 (en) | 2005-04-06 | 2011-10-11 | Ibc Pharmaceuticals, Inc. | Tetrameric cytokines with improved biological activity |
| US7901680B2 (en) | 2005-10-19 | 2011-03-08 | Ibc Pharmaceuticals, Inc. | Dock-and-lock (DNL) vaccines for cancer therapy |
| US8562988B2 (en) | 2005-10-19 | 2013-10-22 | Ibc Pharmaceuticals, Inc. | Strategies for improved cancer vaccines |
| US8481041B2 (en) | 2005-04-06 | 2013-07-09 | Ibc Pharmaceuticals, Inc. | Dock-and-lock (DNL) constructs for human immunodeficiency virus (HIV) therapy |
| US8349332B2 (en) | 2005-04-06 | 2013-01-08 | Ibc Pharmaceuticals, Inc. | Multiple signaling pathways induced by hexavalent, monospecific and bispecific antibodies for enhanced toxicity to B-cell lymphomas and other diseases |
| US9931413B2 (en) | 2005-04-06 | 2018-04-03 | Ibc Pharmaceuticals, Inc. | Tetrameric cytokines with improved biological activity |
| US8475794B2 (en) | 2005-04-06 | 2013-07-02 | Ibc Pharmaceuticals, Inc. | Combination therapy with anti-CD74 antibodies provides enhanced toxicity to malignancies, Autoimmune disease and other diseases |
| US9623115B2 (en) | 2005-04-06 | 2017-04-18 | Ibc Pharmaceuticals, Inc. | Dock-and-Lock (DNL) Complexes for Disease Therapy |
| US8158129B2 (en) | 2005-04-06 | 2012-04-17 | Ibc Pharmaceuticals, Inc. | Dimeric alpha interferon PEGylated site-specifically shows enhanced and prolonged efficacy in vivo |
| US7966746B2 (en) * | 2006-04-24 | 2011-06-28 | Medical Instill Technologies, LLC | Needle penetrable and laser resealable lyophilization method |
| CN102119175A (zh) * | 2008-04-10 | 2011-07-06 | Ibc药品公司 | 采用停靠与锁(dnl)技术制备具有增强的药物动力学的四聚细胞因子的模块方法 |
| CN102057054B (zh) * | 2008-04-11 | 2015-06-10 | 梅里麦克制药股份有限公司 | 人血清白蛋白接头以及其结合物 |
| US8927694B2 (en) | 2008-11-18 | 2015-01-06 | Merrimack Pharmaceuticals, Inc. | Human serum albumin linkers and conjugates thereof |
| US20110046060A1 (en) | 2009-08-24 | 2011-02-24 | Amunix Operating, Inc., | Coagulation factor IX compositions and methods of making and using same |
| EP2535057A2 (en) | 2010-02-09 | 2012-12-19 | Proyecto de Biomedicina Cima, S.L. | Compositions for the treatment of infectious and tumoural diseases |
| PT2717898T (pt) | 2011-06-10 | 2019-05-20 | Bioverativ Therapeutics Inc | Compostos pró-coagulantes e processos para a sua utilização |
| US8492386B2 (en) | 2011-10-21 | 2013-07-23 | Abbvie Inc. | Methods for treating HCV |
| AU2013201406B2 (en) | 2011-10-21 | 2014-10-02 | Abbvie Ireland Unlimited Company | Methods for treating HCV |
| US8466159B2 (en) | 2011-10-21 | 2013-06-18 | Abbvie Inc. | Methods for treating HCV |
| EP2583680A3 (en) | 2011-10-21 | 2013-06-12 | Abbvie Inc. | Mono (PSI-7977) or combination treatment of DAAs for use in treating HCV |
| US20140303074A1 (en) * | 2011-12-16 | 2014-10-09 | The J. David Gladstone Institutes | Compositions and Methods For Inhibiting Immunodeficiency Virus Transcription |
| HRP20191920T1 (hr) | 2012-01-12 | 2020-01-10 | Bioverativ Therapeutics Inc. | Kimerni polipeptidi faktora viii i njihova uporaba |
| CN119192402A (zh) | 2012-02-15 | 2024-12-27 | 比奥贝拉蒂治疗公司 | 因子viii组合物及其制备和使用方法 |
| WO2013123457A1 (en) | 2012-02-15 | 2013-08-22 | Biogen Idec Ma Inc. | Recombinant factor viii proteins |
| EP2863940A4 (en) | 2012-06-08 | 2016-08-10 | Biogen Ma Inc | Chimeric clotting factors |
| EP3693000B1 (en) | 2012-06-08 | 2022-03-02 | Bioverativ Therapeutics Inc. | Procoagulant compounds |
| PL2882450T3 (pl) | 2012-07-11 | 2020-06-29 | Bioverativ Therapeutics Inc. | Kompleks czynnika viii z xten i białkiem czynnika von willebranda oraz jego zastosowania |
| KR101520383B1 (ko) | 2012-08-02 | 2015-05-15 | 에이비온 주식회사 | Ｈｐｖ 감염과 관련된 암의 치료용 조성물 |
| KR101363575B1 (ko) * | 2012-08-07 | 2014-02-24 | 가천대학교 산학협력단 | 신부전증에 대한 신규 바이오마커 및 그의 용도 |
| KR101363576B1 (ko) * | 2012-08-07 | 2014-02-24 | 가천대학교 산학협력단 | 알츠하이머 질환에 대한 신규 바이오마커 및 그의 용도 |
| US20150202287A1 (en) | 2012-08-30 | 2015-07-23 | Merrimack Pharmaceuticals, Inc. | Combination therapies comprising anti-erbb3 agents |
| CA2888806A1 (en) | 2012-10-18 | 2014-04-24 | Biogen Idec Ma Inc. | Methods of using a fixed dose of a clotting factor |
| PL2956477T5 (pl) | 2013-02-15 | 2024-05-27 | Bioverativ Therapeutics Inc. | Zoptymalizowany gen czynnika viii |
| WO2014144549A1 (en) | 2013-03-15 | 2014-09-18 | Biogen Idec Ma Inc. | Factor ix polypeptide formulations |
| AU2014302100B2 (en) | 2013-06-28 | 2020-02-13 | Bioverativ Therapeutics Inc. | Thrombin cleavable linker with XTEN and its uses thereof |
| WO2015023891A2 (en) | 2013-08-14 | 2015-02-19 | Biogen Idec Ma Inc. | Factor viii-xten fusions and uses thereof |
| WO2015048330A2 (en) | 2013-09-25 | 2015-04-02 | Biogen Idec Ma Inc. | On-column viral inactivation methods |
| US10584147B2 (en) | 2013-11-08 | 2020-03-10 | Biovertiv Therapeutics Inc. | Procoagulant fusion compound |
| FI4176894T3 (fi) | 2014-01-10 | 2024-05-29 | Bioverativ Therapeutics Inc | Kimeerisiä tekijä viii -proteiineja ja niiden käyttötarkoituksia |
| WO2016004113A1 (en) | 2014-06-30 | 2016-01-07 | Biogen Ma Inc. | Optimized factor ix gene |
| KR102122463B1 (ko) | 2014-10-14 | 2020-06-15 | 할로자임, 아이엔씨 | 아데노신 디아미네이즈-2(ada2)의 조성물, 이의 변이체 및 이를 사용하는 방법 |
| MA40835A (fr) | 2014-10-23 | 2017-08-29 | Biogen Ma Inc | Anticorps anti-gpiib/iiia et leurs utilisations |
| MA40861A (fr) | 2014-10-31 | 2017-09-05 | Biogen Ma Inc | Anticorps anti-glycoprotéines iib/iiia |
| CA2994547A1 (en) | 2015-08-03 | 2017-02-09 | Bioverativ Therapeutics Inc. | Factor ix fusion proteins and methods of making and using same |
| RU2614141C1 (ru) * | 2015-12-28 | 2017-03-23 | федеральное государственное бюджетное образовательное учреждение высшего образования "Тюменский государственный медицинский университет" Министерства здравоохранения Российской Федерации (ФГБОУ ВО Тюменский ГМУ Минздрава России) | Способ прогнозирования парафарингиального абсцесса при остром паратонзиллите |
| PT3411478T (pt) | 2016-02-01 | 2022-09-13 | Bioverativ Therapeutics Inc | Genes do fator viii otimizados |
| WO2017189978A1 (en) | 2016-04-28 | 2017-11-02 | Emory University | Alkyne containing nucleotide and nucleoside therapeutic compositions and uses related thereto |
| BR112019011198A2 (pt) | 2016-12-02 | 2019-12-17 | Bioverativ Therapeutics Inc | métodos de indução de tolerância imune a fatores de coagulação |
| US12161696B2 (en) | 2016-12-02 | 2024-12-10 | Bioverativ Therapeutics Inc. | Methods of treating hemophilic arthropathy using chimeric clotting factors |
| WO2018112362A1 (en) | 2016-12-16 | 2018-06-21 | Biogen Ma Inc. | Stabilized proteolytically activated growth differentiation factor 11 |
| CR20190389A (es) | 2017-01-31 | 2019-11-26 | Bioverativ Therapeutics Inc | Proteínas de fusión del factor ix y procedimientos de preparación y utilización de las mismas |
| US10767164B2 (en) | 2017-03-30 | 2020-09-08 | The Research Foundation For The State University Of New York | Microenvironments for self-assembly of islet organoids from stem cells differentiation |
| WO2019032898A1 (en) | 2017-08-09 | 2019-02-14 | Bioverativ Therapeutics Inc. | NUCLEIC ACID MOLECULES AND USES THEREOF |
| JP2021512126A (ja) | 2018-02-01 | 2021-05-13 | バイオベラティブ セラピューティクス インコーポレイテッド | 第ｖｉｉｉ因子を発現するレンチウイルスベクターの使用 |
| JP7460609B2 (ja) | 2018-05-14 | 2024-04-02 | ウェアウルフ セラピューティクス， インコーポレイテッド | 活性化可能なインターロイキン－２ポリペプチド及びその使用方法 |
| EP3794022A1 (en) | 2018-05-14 | 2021-03-24 | Werewolf Therapeutics, Inc. | Activatable cytokine polypeptides and methods of use thereof |
| TW202015723A (zh) | 2018-05-18 | 2020-05-01 | 美商百歐維拉提夫治療公司 | 治療ａ型血友病的方法 |
| CN112601517A (zh) | 2018-07-03 | 2021-04-02 | 百时美施贵宝公司 | Fgf-21配制品 |
| SG11202101157VA (en) | 2018-08-09 | 2021-03-30 | Bioverativ Therapeutics Inc | Nucleic acid molecules and uses thereof for non-viral gene therapy |
| SG11202105880TA (en) | 2018-12-06 | 2021-07-29 | Bioverativ Therapeutics Inc | Use of lentiviral vectors expressing factor ix |
| US12465640B2 (en) | 2019-02-25 | 2025-11-11 | The University Of Chicago | Methods and compositions for treating inflammatory and autoimmune conditions with ECM-affinity peptides linked to anti-inflammatory agents |
| JP7754723B2 (ja) | 2019-05-14 | 2025-10-15 | ウェアウルフ セラピューティクス， インコーポレイテッド | 分離部分及びその使用方法 |
| WO2021067389A1 (en) | 2019-09-30 | 2021-04-08 | Bioverativ Therapeutics Inc. | Lentiviral vector formulations |
| BR112022009110A2 (pt) | 2019-11-14 | 2022-07-26 | Werewolf Therapeutics Inc | Polipeptídeos de citocina ativáveis e métodos de uso destes |
| US20250288542A1 (en) * | 2020-10-01 | 2025-09-18 | The Regents Of The University Of California | Methods and compositions to treat and prevent viral infections and acute respiratory distress syndrome |
| JP2024056667A (ja) * | 2022-10-11 | 2024-04-23 | Ｊｃｒファーマ株式会社 | 血清アルブミンと生理活性を有する蛋白質との融合蛋白質 |
Family Cites Families (2)
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| AU2005211725B2 (en) * | 2004-02-09 | 2010-07-15 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| BRPI0614761A2 (pt) * | 2005-08-12 | 2009-05-19 | Human Genome Sciences Inc | proteìnas de fusão de albumina |
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2007
- 2007-09-13 KR KR1020097007639A patent/KR20090064453A/ko not_active Withdrawn
- 2007-09-13 JP JP2009528277A patent/JP2010503396A/ja not_active Withdrawn
- 2007-09-13 WO PCT/US2007/019841 patent/WO2008033413A2/en not_active Ceased
- 2007-09-13 US US12/440,913 patent/US20100254944A1/en not_active Abandoned
- 2007-09-13 BR BRPI0716744A patent/BRPI0716744A2/pt not_active IP Right Cessation
- 2007-09-13 EP EP07838108A patent/EP2068905A4/en not_active Withdrawn
- 2007-09-13 MX MX2009002816A patent/MX2009002816A/es not_active Application Discontinuation
- 2007-09-13 AU AU2007294805A patent/AU2007294805A1/en not_active Abandoned
- 2007-09-13 CA CA002663352A patent/CA2663352A1/en not_active Abandoned
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2009
- 2009-03-12 IL IL197580A patent/IL197580A0/en unknown
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| WO2008033413A3 (en) | 2008-12-04 |
| AU2007294805A1 (en) | 2008-03-20 |
| US20100254944A1 (en) | 2010-10-07 |
| KR20090064453A (ko) | 2009-06-18 |
| EP2068905A4 (en) | 2009-12-30 |
| JP2010503396A (ja) | 2010-02-04 |
| BRPI0716744A2 (pt) | 2016-10-04 |
| MX2009002816A (es) | 2009-05-28 |
| IL197580A0 (en) | 2011-08-01 |
| EP2068905A2 (en) | 2009-06-17 |
| WO2008033413A2 (en) | 2008-03-20 |
| AU2007294805A2 (en) | 2009-05-28 |
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