CA2577755C - Neublastin variants - Google Patents
Neublastin variants Download PDFInfo
- Publication number
- CA2577755C CA2577755C CA2577755A CA2577755A CA2577755C CA 2577755 C CA2577755 C CA 2577755C CA 2577755 A CA2577755 A CA 2577755A CA 2577755 A CA2577755 A CA 2577755A CA 2577755 C CA2577755 C CA 2577755C
- Authority
- CA
- Canada
- Prior art keywords
- polypeptide
- arg
- neublastin
- seq
- ser
- 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.)
- Expired - Fee Related
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| US5824784A (en) | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
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| US5770577A (en) | 1994-11-14 | 1998-06-23 | Amgen Inc. | BDNF and NT-3 polypeptides selectively linked to polyethylene glycol |
| US5780014A (en) | 1995-04-14 | 1998-07-14 | Inhale Therapeutic Systems | Method and apparatus for pulmonary administration of dry powder alpha 1-antitrypsin |
| US5654007A (en) | 1995-06-07 | 1997-08-05 | Inhale Therapeutic Systems | Methods and system for processing dispersible fine powders |
| US5739307A (en) | 1995-08-28 | 1998-04-14 | Washington University | Polynucleotide encoding neurturin neurotrophic factor |
| US5733729A (en) | 1995-09-14 | 1998-03-31 | Affymetrix, Inc. | Computer-aided probability base calling for arrays of nucleic acid probes on chips |
| US5641749A (en) | 1995-11-29 | 1997-06-24 | Amgen Inc. | Method for treating retinal ganglion cell injury using glial cell line-derived neurothrophic factor (GDNF) protein product |
| US6063757A (en) | 1995-11-29 | 2000-05-16 | Urso; Richard G. | Wound treatment method with nerve growth factor |
| EP0943690B1 (en) | 1995-12-21 | 2006-11-29 | Ajinomoto Co., Inc. | Method for refolding human activin a |
| US6299895B1 (en) | 1997-03-24 | 2001-10-09 | Neurotech S.A. | Device and method for treating ophthalmic diseases |
| US6677135B1 (en) | 1996-05-08 | 2004-01-13 | Biogen, Inc. | Ret ligand (RetL) for stimulating neutral and renal growth |
| US5754524A (en) | 1996-08-30 | 1998-05-19 | Wark; Barry J. | Computerized method and system for analysis of an electrophoresis gel test |
| US6083725A (en) | 1996-09-13 | 2000-07-04 | Transkaryotic Therapies, Inc. | Tranfected human cells expressing human α-galactosidase A protein |
| JP2001501093A (ja) | 1996-09-26 | 2001-01-30 | メディカル リサーチ カウンシル | シャペロン断片 |
| KR100195886B1 (ko) | 1996-11-01 | 1999-06-15 | 김상조 | 당뇨병 치료용 의약조성물 |
| US6653098B1 (en) | 1998-02-23 | 2003-11-25 | G. D. Searle & Co. | Method of producing mouse and human endostatin |
| US20020055467A1 (en) | 1998-07-06 | 2002-05-09 | Johansen Teit E. | Novel neurotrophic factors |
| US6593133B1 (en) * | 1998-07-06 | 2003-07-15 | Nsgene A/S | Neurotrophic factors |
| PL209952B1 (pl) | 1998-07-14 | 2011-11-30 | Janssen Pharmaceutica Nv | Wyizolowana cząsteczka kwasu nukleinowego, wyizolowany ludzki neurotroficzny czynnik wzrostu, plazmid, wektor ekspresyjny, komórka gospodarza, zastosowania cząsteczki kwasu nukleinowego, zastosowania neurotroficznego czynnika wzrostu, kompozycje faramaceutyczne, przeciwciało oraz sposób wykrywania neurotroficznego czynnika wzrostu |
| US7067473B1 (en) | 1998-07-14 | 2006-06-27 | Janssen Pharmaceutica N.V. | Neurotrophic growth factor |
| JP2003524381A (ja) | 1998-09-22 | 2003-08-19 | ユニヴァーシティ オブ メリーランド,ボルチモア | システインノット成長因子ミュータント |
| US20020002269A1 (en) | 1998-09-29 | 2002-01-03 | Jeffrey D. Milbrandt | Artemin, a neurotrophic factor |
| US6361771B1 (en) | 1999-04-06 | 2002-03-26 | Neurotech S.A. | ARPE-19 as a platform cell line for encapsulated cell-based delivery |
| MXPA01010692A (es) | 1999-04-22 | 2004-09-06 | Univ Zuerich | Matrices de proteina modificadas para ingenieria de tejidos o liberacion controlada. |
| DE60002496T2 (de) | 1999-10-29 | 2004-03-25 | Biopharm Gesellschaft Zur Biotechnologischen Entwicklung Von Pharmaka Mbh | Verwendung von gdnf für behandlung von hornhautdefekten |
| CA2327208A1 (en) | 2000-11-30 | 2002-05-30 | The Government Of The United States Of America | Methods of increasing distribution of therapeutic agents |
| AU2002232785B2 (en) | 2000-12-22 | 2006-05-18 | Genentech, Inc. | Use of artemin, a member of the GDNF ligand family for preparing a neuroprotective medicament |
| US7442370B2 (en) | 2001-02-01 | 2008-10-28 | Biogen Idec Ma Inc. | Polymer conjugates of mutated neublastin |
| JP4259868B2 (ja) * | 2001-02-01 | 2009-04-30 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | ニューブラスチンのポリマー結合体および同様の使用方法。 |
| US7276580B2 (en) | 2001-03-12 | 2007-10-02 | Biogen Idec Ma Inc. | Neurotrophic factors |
| ES2374971T3 (es) * | 2001-03-28 | 2012-02-23 | Biogen Idec Ma Inc. | Uso de polipéptidos de neublastina para el tratamiento del dolor neuropático. |
| US20040077543A1 (en) | 2001-03-28 | 2004-04-22 | Sah Dinah W. Y. | Treatment using neublastin polypeptides |
| ES2382899T3 (es) | 2001-04-24 | 2012-06-14 | Purdue Research Foundation | Método y composiciones para tratar lesiones en tejido nervioso de mamífero |
| US20030125521A1 (en) | 2001-06-20 | 2003-07-03 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of disorders involving angiogenesis |
| US20040028613A1 (en) | 2001-06-25 | 2004-02-12 | Nastech Pharmaceutical Company Inc | Dopamine agonist formulations for enhanced central nervous system delivery |
| US7129085B2 (en) | 2001-10-11 | 2006-10-31 | Bristol-Myers Squibb Company | Polynucleotides encoding a human leucine-rich repeat domain containing protein, HLLRCR-1 |
| GB0205022D0 (en) | 2002-03-04 | 2002-04-17 | Univ Cambridge Tech | Materials and methods for the treatment of cns damage |
| JP4310608B2 (ja) | 2002-04-25 | 2009-08-12 | 東洋紡績株式会社 | Hsp70ファミリータンパク質基質結合ドメインフラグメントの利用方法 |
| EP1897552B1 (en) | 2003-04-18 | 2009-06-17 | Biogen Idec MA Inc. | Polymer-conjugated glycosylated neublastin |
| AU2004245175C1 (en) | 2003-06-10 | 2010-03-18 | Biogen Ma Inc. | Improved secretion of neublastin |
| US7598059B2 (en) | 2003-10-02 | 2009-10-06 | Biogen Idec Ma Inc. | Neublastin expression constructs |
| US20050180957A1 (en) | 2004-01-16 | 2005-08-18 | Scharp David W. | Method of using fibrin-bound angiogenic factors to stimulate vascularization of transplant site of encapsulated cells |
| CN101031645B (zh) | 2004-06-23 | 2011-06-08 | 组织基因股份有限公司 | 神经再生 |
| US7598356B2 (en) | 2004-07-08 | 2009-10-06 | Board of Regents of the University of Nebraska by and on behalf of the University of Nebraska Medical Center | Method for purifying a protein of the cystine-knot superfamily |
| CN101043899B (zh) | 2004-08-19 | 2011-03-30 | 比奥根艾迪克Ma公司 | 重折叠转化型生长因子beta家族蛋白 |
| DK1786454T3 (da) | 2004-08-19 | 2010-09-06 | Biogen Idec Inc | Neublastinvarianter |
| WO2007042040A2 (en) | 2005-10-11 | 2007-04-19 | Ns Gene A/S | TREATMENT OF RETINOPATHIES USING GFRα3 AGONISTS |
| TWI501774B (zh) | 2006-02-27 | 2015-10-01 | Biogen Idec Inc | 神經性病症之治療 |
| US20100056440A1 (en) | 2006-03-01 | 2010-03-04 | Biogen Idec Ma Inc. | Compositions and methods for administering gdnf ligand family proteins |
| SI2019683T2 (sl) | 2006-04-25 | 2022-10-28 | The Regents Of The University Of California | Dajanje rastnih faktorjev za zdravljenje motenj CŽS |
| TWI445544B (zh) | 2007-05-01 | 2014-07-21 | Biogen Idec Inc | 增進血管形成之組合物及方法 |
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