CA2703943A1 - Albumin fusion proteins - Google Patents
Albumin fusion proteins Download PDFInfo
- Publication number
- CA2703943A1 CA2703943A1 CA2703943A CA2703943A CA2703943A1 CA 2703943 A1 CA2703943 A1 CA 2703943A1 CA 2703943 A CA2703943 A CA 2703943A CA 2703943 A CA2703943 A CA 2703943A CA 2703943 A1 CA2703943 A1 CA 2703943A1
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- CA
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- Prior art keywords
- albumin
- fusion protein
- albumin fusion
- fragment
- seq
- Prior art date
- 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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Landscapes
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Applications Claiming Priority (3)
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| US11/932,823 US20080194481A1 (en) | 2001-12-21 | 2007-10-31 | Albumin Fusion Proteins |
| US11/932,823 | 2007-10-31 | ||
| PCT/US2008/012306 WO2009058322A1 (en) | 2007-10-31 | 2008-10-30 | Albumin fusion proteins |
Publications (1)
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| CA2703943A1 true CA2703943A1 (en) | 2009-05-07 |
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| CA2405550A1 (en) | 2000-04-12 | 2001-10-25 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| AU2002364586A1 (en) | 2001-12-21 | 2003-07-30 | Delta Biotechnology Limited | Albumin fusion proteins |
| CA2484556A1 (en) | 2001-12-21 | 2003-07-24 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| 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 |
| HUE055861T2 (hu) | 2004-04-21 | 2021-12-28 | Alexion Pharma Inc | Csontbejuttató konjugátumok és azok alkalmazási módszere fehérjék csonthoz kötéséhez |
| EP2013113B1 (en) * | 2006-04-24 | 2018-03-21 | Medical Instill Technologies, Inc. | Needle penetrable and resealable lyophilization device and related method |
| EP2046367A4 (en) * | 2006-06-07 | 2009-11-11 | Human Genome Sciences Inc | ALBUM INFUSION PROTEINS |
| NZ590469A (en) * | 2008-07-18 | 2012-08-31 | Novozymes Adenium Biotech As | Treatment of rheumatoid arthritis with human beta defensins (1-4) |
| CA2750727A1 (en) * | 2008-07-18 | 2010-01-21 | Novozymes Adenium Biotech A/S | Treatment of inflammatory bowel diseases with mammal beta defensins |
| AU2009272680A1 (en) * | 2008-07-18 | 2010-01-21 | Novozymes Adenium Biotech A/S | Treatment of inflammatory diseases with mammal beta defensins |
| BR112012004094A2 (pt) | 2009-08-24 | 2016-03-08 | Amunix Operating Inc | composições de fator vii de coagulação e métodos para fazer e usar as mesmas |
| EP2826489A1 (en) | 2009-12-08 | 2015-01-21 | Teva Pharmaceutical Industries, Ltd. | BChE albumin fusions for the treatment of cocaine abuse |
| AU2011218294A1 (en) | 2010-02-16 | 2012-08-30 | Medimmune, Llc | HSA-related compositions and methods of use |
| CA2823066A1 (en) | 2010-12-27 | 2012-07-05 | Alexion Pharma International Sarl | Compositions comprising natriuretic peptides and methods of use thereof |
| US9045564B2 (en) | 2011-02-15 | 2015-06-02 | Medimmune, Llc | HSA-related compositions and methods of use |
| CN103379915A (zh) * | 2011-02-15 | 2013-10-30 | 米迪缪尼有限公司 | Hsa相关组合物及使用方法 |
| WO2012115772A2 (en) | 2011-02-25 | 2012-08-30 | Medtronic, Inc. | Therapy for kidney disease and/or heart failure |
| CN107261119A (zh) * | 2011-02-28 | 2017-10-20 | 独立行政法人国立循环器病研究中心 | 恶性肿瘤转移抑制用药物 |
| DK2717898T3 (en) | 2011-06-10 | 2019-03-25 | Bioverativ Therapeutics Inc | COAGULATING COMPOUNDS AND PROCEDURES FOR USE THEREOF |
| US10400029B2 (en) | 2011-06-28 | 2019-09-03 | Inhibrx, Lp | Serpin fusion polypeptides and methods of use thereof |
| UA124083C2 (uk) | 2011-06-28 | 2021-07-21 | ІНГІБРЕКС, Інк. | Злитий серпіновий поліпептид і спосіб його застосування |
| US9217021B2 (en) | 2011-07-08 | 2015-12-22 | Defensin Therapeutics Aps | Oral treatment of inflammatory bowel disease |
| EP2750697A4 (en) | 2011-09-02 | 2015-03-25 | Medtronic Inc | CHIMERIC NATRIURETIC PEPTIDE COMPOSITIONS AND METHOD FOR THE PRODUCTION THEREOF |
| EA035323B1 (ru) | 2012-01-12 | 2020-05-28 | Биовератив Терапьютикс Инк. | Полипептиды химерного фактора viii и их применение |
| HRP20221531T1 (hr) | 2012-02-15 | 2023-02-17 | Bioverativ Therapeutics Inc. | Pripravci faktora viii i postupci dobivanja i korištenja istih |
| LT2822577T (lt) | 2012-02-15 | 2019-03-25 | Bioverativ Therapeutics Inc. | Rekombinantiniai faktoriaus viii baltymai |
| IN2014MN02089A (enExample) | 2012-03-20 | 2015-09-11 | Einstein Coll Med | |
| WO2013170636A1 (zh) * | 2012-05-18 | 2013-11-21 | 爱德迪安（北京）生物技术有限公司 | 用于糖尿病治疗的蛋白、蛋白缀合物及其应用 |
| US10052366B2 (en) | 2012-05-21 | 2018-08-21 | Alexion Pharmaceuticsl, Inc. | Compositions comprising alkaline phosphatase and/or natriuretic peptide and methods of use thereof |
| AU2013270683A1 (en) | 2012-06-08 | 2014-12-11 | Biogen Ma Inc. | Chimeric clotting factors |
| CA2875246A1 (en) | 2012-06-08 | 2013-12-12 | Biogen Idec Ma Inc. | Procoagulant compounds |
| US10138291B2 (en) | 2012-07-11 | 2018-11-27 | Bioverativ Therapeutics Inc. | Factor VIII complex with XTEN and von Willebrand Factor protein, and uses thereof |
| US9827250B2 (en) * | 2012-07-31 | 2017-11-28 | Johnson & Johnson Vision Care, Inc. | Lens incorporating myopia control optics and muscarinic agents |
| CA2888806A1 (en) | 2012-10-18 | 2014-04-24 | Biogen Idec Ma Inc. | Methods of using a fixed dose of a clotting factor |
| US10772940B1 (en) | 2012-12-11 | 2020-09-15 | University Of Kentucky Research Foundation | Cocaine hydrolase-FC fusion proteins for cocaine and methods for utilizing the same |
| WO2014113359A1 (en) * | 2013-01-15 | 2014-07-24 | Teva Pharmaceutical Industries Ltd. | Formulations of albu-bche, preparation and uses thereof |
| LT2956477T (lt) | 2013-02-15 | 2021-02-10 | Bioverativ Therapeutics Inc. | Optimizuotas faktoriaus viii genas |
| CN105007722A (zh) | 2013-02-16 | 2015-10-28 | 诺维信生物制药丹麦公司 | 药代动力学动物模型 |
| WO2014165093A2 (en) | 2013-03-13 | 2014-10-09 | Bristol-Myers Squibb Company | Fibronectin based scaffold domains linked to serum albumin or a moiety binding thereto |
| EA037906B1 (ru) | 2013-03-15 | 2021-06-04 | Биовератив Терапьютикс Инк. | Препараты полипептида фактора ix |
| WO2014210558A1 (en) | 2013-06-28 | 2014-12-31 | Biogen Idec Ma Inc. | Thrombin cleavable linker with xten and its uses thereof |
| US20160311885A1 (en) | 2013-08-14 | 2016-10-27 | Biogen Ma Inc. | Recombinant factor viii proteins |
| EP3033097B1 (en) | 2013-08-14 | 2021-03-10 | Bioverativ Therapeutics Inc. | Factor viii-xten fusions and uses thereof |
| HUE057005T2 (hu) | 2013-09-25 | 2022-04-28 | Bioverativ Therapeutics Inc | Oszlopon történõ vírusinaktiváló eljárások |
| WO2015070014A1 (en) | 2013-11-08 | 2015-05-14 | Biogen Idec Ma Inc. | Procoagulant fusion compound |
| DK3091997T5 (da) | 2014-01-10 | 2024-10-14 | Bioverativ Therapeutics Inc | Kimære faktor viii-proteiner og anvendelser deraf |
| WO2015168284A1 (en) * | 2014-04-30 | 2015-11-05 | Teva Pharmaceutical Industries Ltd. | Albumin-bche in detoxification of neurotoxins |
| EP3160478A4 (en) | 2014-06-30 | 2018-05-16 | Bioverativ Therapeutics Inc. | Optimized factor ix gene |
| US10822596B2 (en) | 2014-07-11 | 2020-11-03 | Alexion Pharmaceuticals, Inc. | Compositions and methods for treating craniosynostosis |
| US9616114B1 (en) | 2014-09-18 | 2017-04-11 | David Gordon Bermudes | Modified bacteria having improved pharmacokinetics and tumor colonization enhancing antitumor activity |
| SG11201701803XA (en) | 2014-09-26 | 2017-04-27 | Bayer Pharma AG | Stabilized adrenomedullin derivatives and use thereof |
| EP3207130B1 (en) | 2014-10-14 | 2019-08-07 | Halozyme, Inc. | Compositions of adenosine deaminase-2 (ada2), variants thereof and methods of using same |
| 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 |
| CA2967851C (en) | 2014-12-05 | 2024-02-27 | Alexion Pharmaceuticals, Inc. | Treating seizure with recombinant alkaline phosphatase |
| US10603361B2 (en) | 2015-01-28 | 2020-03-31 | Alexion Pharmaceuticals, Inc. | Methods of treating a subject with an alkaline phosphatase deficiency |
| US10676723B2 (en) | 2015-05-11 | 2020-06-09 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| MX2018001497A (es) | 2015-08-03 | 2018-05-15 | Bioverativ Therapeutics Inc | Proteinas de fusion de factor ix y metodos para producirlas y usarlas. |
| RU2745528C2 (ru) | 2015-08-17 | 2021-03-26 | Алексион Фармасьютикалз, Инк. | Производство щелочных фосфатаз |
| US10016502B2 (en) * | 2015-08-29 | 2018-07-10 | Medrx Co., Ltd | Patch preparation containing an acid scavenger |
| WO2017058822A1 (en) | 2015-09-28 | 2017-04-06 | Alexion Pharmaceuticals, Inc. | Identifying effective dosage regimens for tissue non-specific alkaline phosphatase (tnsalp)-enzyme replacement therapy of hypophosphatasia |
| CN105254766B (zh) * | 2015-10-26 | 2018-10-16 | 中国航天员科研训练中心 | 机械生长因子MGF E domain肽在调控记忆相关基因和miRNA表达中的应用 |
| WO2017074466A1 (en) | 2015-10-30 | 2017-05-04 | Alexion Pharmaceuticals, Inc. | Methods for treating craniosynostosis in a patient |
| PL3411478T3 (pl) | 2016-02-01 | 2022-10-03 | Bioverativ Therapeutics Inc. | Geny zoptymalizowanego czynnika VIII |
| EP3426286A4 (en) | 2016-03-08 | 2019-12-04 | Alexion Pharmaceuticals, Inc. | PROCESS FOR TREATING HYPOPHOSPHATASIA IN CHILDREN |
| JP7613826B2 (ja) | 2016-04-01 | 2025-01-15 | アレクシオン ファーマシューティカルズ， インコーポレイテッド | アルカリホスファターゼによって筋力低下を治療すること |
| EP3436020A4 (en) | 2016-04-01 | 2019-12-25 | Alexion Pharmaceuticals, Inc. | METHOD FOR TREATING HYPOPHOSPHATASIE IN TEENS AND ADULTS |
| US10988744B2 (en) | 2016-06-06 | 2021-04-27 | Alexion Pharmaceuticals, Inc. | Method of producing alkaline phosphatase |
| EP3500289B1 (en) | 2016-08-18 | 2024-10-09 | Alexion Pharmaceuticals, Inc. | Asfotase alfa for use in treating tracheobronchomalacia |
| JP2020500306A (ja) | 2016-11-04 | 2020-01-09 | オーフス ウニベルシテット | 新生児Ｆｃ受容体の過剰発現により特徴づけられる腫瘍の同定と治療 |
| WO2018102743A1 (en) | 2016-12-02 | 2018-06-07 | Bioverativ Therapeutics Inc. | Methods of treating hemophilic arthropathy using chimeric clotting factors |
| BR112019011198A2 (pt) | 2016-12-02 | 2019-12-17 | Bioverativ Therapeutics Inc | métodos de indução de tolerância imune a fatores de coagulação |
| US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| US11180535B1 (en) | 2016-12-07 | 2021-11-23 | David Gordon Bermudes | Saccharide binding, tumor penetration, and cytotoxic antitumor chimeric peptides from therapeutic bacteria |
| MA47163A (fr) | 2016-12-16 | 2019-11-06 | Biogen Ma Inc | Facteur 11 de différenciation de croissance activé protéolytiquement stabilisé |
| EA201991768A1 (ru) | 2017-01-31 | 2020-01-22 | Байоверетив Терапьютикс Инк. | Слитые белки на основе фактора ix и способы их получения и пути применения |
| 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 |
| CA3057502A1 (en) | 2017-03-31 | 2018-10-04 | Alexion Pharmaceuticals, Inc. | Methods for treating hypophosphatasia (hpp) in adults and adolescents |
| EP3628009A4 (en) * | 2017-05-19 | 2021-03-24 | The Regents of The University of Colorado, A Body Corporate | COMPOSITIONS AND PROCESSES FOR IMPROVING PERCEPTION |
| JP7374883B2 (ja) | 2017-08-09 | 2023-11-07 | 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 | 核酸分子およびその使用 |
| WO2019152692A1 (en) | 2018-02-01 | 2019-08-08 | Bioverativ Therapeutics, Inc. | Use of lentiviral vectors expressing factor viii |
| US11359000B2 (en) | 2018-03-28 | 2022-06-14 | Bristol-Myers Squibb Company | Interleukin-2/Interleukin-2 receptor alpha fusion proteins and methods of use |
| JP2021519590A (ja) | 2018-03-30 | 2021-08-12 | アレクシオン ファーマシューティカルズ， インコーポレイテッド | 糖タンパク質の製造 |
| RS66972B1 (sr) | 2018-05-18 | 2025-07-31 | Bioverativ Therapeutics Inc | Metode lečenja hemofilije a |
| KR20210027426A (ko) | 2018-07-03 | 2021-03-10 | 브리스톨-마이어스 스큅 컴퍼니 | Fgf21 제제 |
| CN119955796A (zh) | 2018-08-09 | 2025-05-09 | 比奥维拉迪维治疗股份有限公司 | 核酸分子及其用于非病毒基因疗法的用途 |
| JP2021534111A (ja) | 2018-08-10 | 2021-12-09 | アレクシオン ファーマシューティカルズ， インコーポレイテッド | アルカリホスファターゼを用いて神経線維腫症１型および関連状態を治療する方法 |
| BR112021010047A2 (pt) | 2018-12-06 | 2021-08-24 | Bioverativ Therapeutics Inc. | Uso de vetores lentivirais expressando o fator ix |
| EP3980059A1 (en) * | 2019-06-10 | 2022-04-13 | Infectious Disease Research Institute | Methods and compositions of astrovirus replicons |
| EP3986918A1 (en) | 2019-06-18 | 2022-04-27 | Bayer Aktiengesellschaft | Adrenomedullin-analogues for long-term stabilization and their use |
| CN115279896A (zh) | 2019-09-30 | 2022-11-01 | 比奥维拉迪维治疗股份有限公司 | 慢病毒载体配制品 |
| US12433938B2 (en) | 2019-12-09 | 2025-10-07 | Alexion Pharmaceuticals, Inc. | Alkaline phosphatase polypeptides and methods of use thereof |
| MX2023000156A (es) | 2020-06-24 | 2023-02-16 | Bioverativ Therapeutics Inc | Metodos para la eliminacion de factor viii libre de preparaciones de vectores lentivirales modificados para expresar dicha proteina. |
| CN112725305B (zh) * | 2021-01-13 | 2022-11-04 | 云南师范大学 | 热盐性敏感的菊粉酶突变体MutY119D及其制备方法 |
| AU2022218782A1 (en) | 2021-02-12 | 2023-08-17 | Alexion Pharmaceuticals, Inc. | Alkaline phosphatase polypeptides and methods of use thereof |
| CN119823285B (zh) * | 2025-01-09 | 2025-08-19 | 石家庄市农林科学研究院 | 一种貉α干扰素和β防御素融合蛋白及其编码基因和应用 |
Family Cites Families (69)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US5514567A (en) * | 1979-01-30 | 1996-05-07 | Juridical Foundation, Japanese Foundation For Cancer Research | DNA and recombinant plasmid |
| US5326859A (en) * | 1979-10-30 | 1994-07-05 | Juridical Foundation, Japanese Foundation For Cancer Research | DNA and recombinant plasmid |
| US4530901A (en) * | 1980-01-08 | 1985-07-23 | Biogen N.V. | Recombinant DNA molecules and their use in producing human interferon-like polypeptides |
| US4456748A (en) * | 1981-02-23 | 1984-06-26 | Genentech, Inc. | Hybrid human leukocyte interferons |
| WO1983002461A1 (en) * | 1982-01-19 | 1983-07-21 | Cetus Corp | Multiclass hybrid interferons |
| US4966843A (en) * | 1982-11-01 | 1990-10-30 | Cetus Corporation | Expression of interferon genes in Chinese hamster ovary cells |
| JPS60136596A (ja) * | 1983-12-26 | 1985-07-20 | Suntory Ltd | ペプチド及びこれを有効成分とする利尿剤 |
| US4716217A (en) * | 1984-08-31 | 1987-12-29 | University Patents, Inc. | Hybrid lymphoblastoid-leukocyte human interferons |
| US4734491A (en) * | 1984-08-31 | 1988-03-29 | University Patents, Inc. | DNA sequences encoding hybrid lymphoblastoid-leukocyte human interferons |
| EP0216846B2 (en) | 1985-04-01 | 1995-04-26 | Celltech Limited | Transformed myeloma cell-line and a process for the expression of a gene coding for a eukaryotic polypeptide employing same |
| GB8510219D0 (en) | 1985-04-22 | 1985-05-30 | Bass Plc | Isolation of fermentation products |
| US4980286A (en) | 1985-07-05 | 1990-12-25 | Whitehead Institute For Biomedical Research | In vivo introduction and expression of foreign genetic material in epithelial cells |
| JPS6296086A (ja) | 1985-10-21 | 1987-05-02 | Agency Of Ind Science & Technol | 複合プラスミド |
| GB8601597D0 (en) | 1986-01-23 | 1986-02-26 | Wilson R H | Nucleotide sequences |
| US5002764A (en) * | 1986-08-12 | 1991-03-26 | Schering Corporation | Treatment of actinic keratoses with alpha2 interferon |
| US5489425A (en) | 1987-06-24 | 1996-02-06 | The Dow Chemical Company | Functionalized polyamine chelants |
| US4994560A (en) | 1987-06-24 | 1991-02-19 | The Dow Chemical Company | Functionalized polyamine chelants and radioactive rhodium complexes thereof for conjugation to antibodies |
| GB8717430D0 (en) | 1987-07-23 | 1987-08-26 | Celltech Ltd | Recombinant dna product |
| GB8725529D0 (en) | 1987-10-30 | 1987-12-02 | Delta Biotechnology Ltd | Polypeptides |
| JPH01215289A (ja) | 1988-02-22 | 1989-08-29 | Toa Nenryo Kogyo Kk | 遺伝子組換えによる正常ヒト血清アルブミンａの製造方法 |
| GB8809129D0 (en) | 1988-04-18 | 1988-05-18 | Celltech Ltd | Recombinant dna methods vectors and host cells |
| DE353450T1 (de) | 1988-06-24 | 1990-09-06 | The Dow Chemical Co., Midland, Mich. | Macrocyclische bifunktionelle chelatbildner, komplexe davon und ihre konjugierten antikoerper. |
| CN1033030C (zh) | 1988-06-24 | 1996-10-16 | 唐化学原料公司 | 大环双官能螯合剂及其配合物和抗体共轭物的制备方法 |
| US5756065A (en) | 1988-06-24 | 1998-05-26 | The Dow Chemical Company | Macrocyclic tetraazacyclododecane conjugates and their use as diagnostic and therapeutic agents |
| US5274119A (en) | 1988-07-01 | 1993-12-28 | The Dow Chemical Company | Vicinal diols |
| DE68925893T2 (de) | 1988-07-23 | 1996-08-08 | Delta Biotechnology Ltd | Sekretorische leader-sequenzen |
| FR2649991B2 (fr) | 1988-08-05 | 1994-03-04 | Rhone Poulenc Sante | Utilisation de derives stables du plasmide pkd1 pour l'expression et la secretion de proteines heterologues dans les levures du genre kluyveromyces |
| US5696239A (en) | 1988-10-31 | 1997-12-09 | The Dow Chemical Company | Conjugates possessing ortho ligating functionality and complexes thereof |
| US5342604A (en) | 1988-10-31 | 1994-08-30 | The Dow Chemical Company | Complexes possessing ortho ligating functionality |
| US5808003A (en) | 1989-05-26 | 1998-09-15 | Perimmune Holdings, Inc. | Polyaminocarboxylate chelators |
| US5073627A (en) | 1989-08-22 | 1991-12-17 | Immunex Corporation | Fusion proteins comprising GM-CSF and IL-3 |
| GB8924021D0 (en) | 1989-10-25 | 1989-12-13 | Celltech Ltd | Recombinant dna method and vectors for the use therein |
| US5173408A (en) | 1989-11-13 | 1992-12-22 | Lange Louis George Iii | Mammalian pancreatic cholesterol esterase |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| JPH07108232B2 (ja) | 1990-10-09 | 1995-11-22 | エム・ディ・リサーチ株式会社 | ペプチド又は蛋白質の製造方法 |
| ATE254179T1 (de) * | 1990-11-29 | 2003-11-15 | Agronomique Inst Nat Rech | Neue type-i-interferon varianten, ihre verfahren zur herstellung, und ihre verwendungen |
| US5641670A (en) | 1991-11-05 | 1997-06-24 | Transkaryotic Therapies, Inc. | Protein production and protein delivery |
| US6270989B1 (en) | 1991-11-05 | 2001-08-07 | Transkaryotic Therapies, Inc. | Protein production and delivery |
| US5540923A (en) * | 1991-12-06 | 1996-07-30 | Landsforeningen Til Kraeftens Bekaemplse | Interferon proteins |
| US5428139A (en) | 1991-12-10 | 1995-06-27 | The Dow Chemical Company | Bicyclopolyazamacrocyclophosphonic acid complexes for use as radiopharmaceuticals |
| FR2686899B1 (fr) * | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
| US5505931A (en) | 1993-03-04 | 1996-04-09 | The Dow Chemical Company | Acid cleavable compounds, their preparation and use as bifunctional acid-labile crosslinking agents |
| ES2153385T5 (es) | 1992-07-31 | 2008-09-01 | Genentech, Inc. | Composicion acuosa a base de hormona del crecimiento humana. |
| TW402639B (en) | 1992-12-03 | 2000-08-21 | Transkaryotic Therapies Inc | Protein production and protein delivery |
| US5932780A (en) | 1994-02-28 | 1999-08-03 | Yissum Research Development Company Of Hebrew University Of Jerusalem | Transgenic non-human animal assay system for anti-cholinesterase substances |
| GB9404270D0 (en) | 1994-03-05 | 1994-04-20 | Delta Biotechnology Ltd | Yeast strains and modified albumins |
| US5695750A (en) * | 1994-11-25 | 1997-12-09 | The United States Of America As Represented By The Secretary Of The Army | Compositions for use to deactivate organophosphates |
| US5480640A (en) * | 1995-05-02 | 1996-01-02 | Schering Corporation | Alpha interferon for treating prostate cancer |
| US6001625A (en) * | 1995-05-19 | 1999-12-14 | The United States Of America As Represented By The Secretary Of The Army | Site-directed mutagenesis of esterases |
| GB9526733D0 (en) | 1995-12-30 | 1996-02-28 | Delta Biotechnology Ltd | Fusion proteins |
| JP2000506865A (ja) * | 1996-03-14 | 2000-06-06 | ジ イミューン リスポンス コーポレイション | インターフェロンをコードする遺伝子の標的を定めた送達 |
| EP0961832A4 (en) | 1996-09-18 | 2003-02-26 | Human Genome Sciences Inc | HUMAN TUMOR NECROSIS FACTOR-TYPE RECEPTOR GENES |
| CA2405550A1 (en) * | 2000-04-12 | 2001-10-25 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| DK1355942T3 (da) * | 2000-12-07 | 2008-11-17 | Lilly Co Eli | GLP-1-fusionsproteiner |
| US7070973B2 (en) * | 2000-12-26 | 2006-07-04 | Board Of Regents Of The University Of Nebraska | Butyrylcholinesterase variants and methods of use |
| CA2433057A1 (en) * | 2000-12-26 | 2002-08-22 | Applied Molecular Evolution, Inc. | Butyrylcholinesterase polypeptide variants with increased catalytic efficiency and methods of use |
| US7049121B2 (en) * | 2001-12-20 | 2006-05-23 | Applied Molecular Evolution | Butyrylcholinesterase variant polypeptides with increased catalytic efficiency and methods of use |
| US6989261B2 (en) * | 2001-12-20 | 2006-01-24 | Eli Lilly And Company | Butyrylcholinesterase variant polypeptides with increased catalytic efficiency and methods of use |
| US20060253913A1 (en) * | 2001-12-21 | 2006-11-09 | Yue-Jin Huang | Production of hSA-linked butyrylcholinesterases in transgenic mammals |
| CA2484556A1 (en) | 2001-12-21 | 2003-07-24 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| AU2002364586A1 (en) * | 2001-12-21 | 2003-07-30 | Delta Biotechnology Limited | Albumin fusion proteins |
| AU2002353374A1 (en) * | 2001-12-21 | 2003-07-09 | Nexia Biotechnologies, Inc. | Production of butyrylcholinesterases in transgenic mammals |
| CA2513213C (en) * | 2003-01-22 | 2013-07-30 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| SI1729795T1 (sl) | 2004-02-09 | 2016-04-29 | Human Genome Sciences, Inc. | Albuminski fuzijski proteini |
| US20060051859A1 (en) * | 2004-09-09 | 2006-03-09 | Yan Fu | Long acting human interferon analogs |
| KR20080071119A (ko) | 2005-08-12 | 2008-08-01 | 휴먼 게놈 사이언시즈, 인코포레이티드 | 알부민 융합 단백질 |
| US8008257B2 (en) * | 2005-10-20 | 2011-08-30 | University Of Ottawa Heart Institute | ANF fusion proteins |
| EP2046367A4 (en) * | 2006-06-07 | 2009-11-11 | Human Genome Sciences Inc | ALBUM INFUSION PROTEINS |
-
2007
- 2007-10-31 US US11/932,823 patent/US20080194481A1/en not_active Abandoned
-
2008
- 2008-10-30 CA CA2703943A patent/CA2703943A1/en not_active Abandoned
- 2008-10-30 WO PCT/US2008/012306 patent/WO2009058322A1/en not_active Ceased
- 2008-10-30 JP JP2010532056A patent/JP2011501959A/ja active Pending
- 2008-10-30 AU AU2008319332A patent/AU2008319332B2/en active Active
- 2008-10-30 EP EP08843705A patent/EP2211888A4/en not_active Withdrawn
-
2010
- 2010-04-06 IL IL204839A patent/IL204839A0/en unknown
- 2010-06-03 US US12/793,658 patent/US8287859B2/en not_active Expired - Lifetime
-
2013
- 2013-11-11 JP JP2013233069A patent/JP5856131B2/ja active Active
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| EP2211888A1 (en) | 2010-08-04 |
| IL204839A0 (en) | 2010-11-30 |
| AU2008319332B2 (en) | 2014-05-08 |
| JP2011501959A (ja) | 2011-01-20 |
| JP2014079245A (ja) | 2014-05-08 |
| EP2211888A4 (en) | 2010-11-17 |
| JP5856131B2 (ja) | 2016-02-09 |
| US8287859B2 (en) | 2012-10-16 |
| US20080194481A1 (en) | 2008-08-14 |
| WO2009058322A1 (en) | 2009-05-07 |
| AU2008319332A1 (en) | 2009-05-07 |
| US20110002888A1 (en) | 2011-01-06 |
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