JP5583005B2 - 血管新生を増大させるための組成物および方法 - Google Patents
血管新生を増大させるための組成物および方法 Download PDFInfo
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| JP4571776B2 (ja) * | 2002-11-05 | 2010-10-27 | Jx日鉱日石エネルギー株式会社 | 潤滑油組成物 |
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Family Cites Families (104)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4352883A (en) | 1979-03-28 | 1982-10-05 | Damon Corporation | Encapsulation of biological material |
| US4353888A (en) | 1980-12-23 | 1982-10-12 | Sefton Michael V | Encapsulation of live animal cells |
| US4407957A (en) | 1981-03-13 | 1983-10-04 | Damon Corporation | Reversible microencapsulation of a core material |
| US5525464A (en) | 1987-04-01 | 1996-06-11 | Hyseq, Inc. | Method of sequencing by hybridization of oligonucleotide probes |
| US4883666A (en) | 1987-04-29 | 1989-11-28 | Massachusetts Institute Of Technology | Controlled drug delivery system for treatment of neural disorders |
| US5283187A (en) | 1987-11-17 | 1994-02-01 | Brown University Research Foundation | Cell culture-containing tubular capsule produced by co-extrusion |
| US5158881A (en) | 1987-11-17 | 1992-10-27 | Brown University Research Foundation | Method and system for encapsulating cells in a tubular extrudate in separate cell compartments |
| DE3829766A1 (de) | 1988-09-01 | 1990-03-22 | Akzo Gmbh | Verfahren zur herstellung von membranen |
| DE3829752A1 (de) | 1988-09-01 | 1990-03-22 | Akzo Gmbh | Integrale asymmetrische polyaethersulfonmembran, verfahren zur herstellung und verwendung zur ultrafiltration und mikrofiltration |
| US5800992A (en) | 1989-06-07 | 1998-09-01 | Fodor; Stephen P.A. | Method of detecting nucleic acids |
| US5143854A (en) | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
| US5194596A (en) | 1989-07-27 | 1993-03-16 | California Biotechnology Inc. | Production of vascular endothelial cell growth factor |
| US5350836A (en) | 1989-10-12 | 1994-09-27 | Ohio University | Growth hormone antagonists |
| GB8927546D0 (en) | 1989-12-06 | 1990-02-07 | Ciba Geigy | Process for the production of biologically active tgf-beta |
| US5084350A (en) | 1990-02-16 | 1992-01-28 | The Royal Institution For The Advance Of Learning (Mcgill University) | Method for encapsulating biologically active material including cells |
| US5618531A (en) | 1990-10-19 | 1997-04-08 | New York University | Method for increasing the viability of cells which are administered to the brain or spinal cord |
| ATE156344T1 (de) | 1991-04-25 | 1997-08-15 | Univ Brown Res Found | Implantierbare, biokompatible immunisolator- trägersubstanz zum abgeben ausgesuchter, therapeutischer produkte |
| DE69230613T2 (de) | 1991-07-02 | 2000-12-28 | Inhale Inc | Verfahren und vorrichtung zum abgeben von medikamenten in aerosolform |
| AU679167B2 (en) | 1991-09-20 | 1997-06-26 | Amgen, Inc. | Glial derived neurotrophic factor |
| US5939524A (en) | 1991-12-09 | 1999-08-17 | The Scripps Research Institute | Platelet GPIII P1A1 and P1A2 epitopes, their preparation and use |
| US5414135A (en) | 1991-12-30 | 1995-05-09 | Sterling Winthrop Inc. | Vinyl sulfone coupling of polyoxyalkylenes to proteins |
| US5785049A (en) | 1994-09-21 | 1998-07-28 | Inhale Therapeutic Systems | Method and apparatus for dispersion of dry powder medicaments |
| EP0679088B1 (en) | 1992-09-29 | 2002-07-10 | Inhale Therapeutic Systems | Pulmonary delivery of active fragments of parathyroid hormone |
| US5349056A (en) | 1992-10-09 | 1994-09-20 | Regeneron Pharmaceuticals | Modified ciliary neurotrophic factors |
| US6472178B1 (en) | 1998-02-27 | 2002-10-29 | Regeneron Pharmaceuticals, Inc. | Nucleic acids encoding a modified ciliary neurotrophic factor and method of making thereof |
| CA2092271C (en) | 1993-03-09 | 2009-10-13 | Eddie Reed | Use of g-csf for treating taxol side-effects |
| SG48813A1 (en) | 1993-08-12 | 1998-05-18 | Cytotherapeutics Inc | Improved composition and methods for the delivery of biologically active molecules using genetically altered cells contained in biocompatible immunoisolatory capsules |
| DE4339605A1 (de) | 1993-11-20 | 1995-05-24 | Beiersdorf Ag | Desodorierende Wirkstoffkombinationen auf der Basis von alpha, omega-Alkandicarbonsäuren und Fettsäurepartialglyceriden |
| US5834029A (en) | 1994-07-20 | 1998-11-10 | Cytotherapeutics, Inc. | Nerve guidance channel containing bioartificial three-dimensional hydrogel extracellular matrix derivatized with cell adhesive peptide fragment |
| US5824784A (en) | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
| US5795716A (en) | 1994-10-21 | 1998-08-18 | Chee; Mark S. | Computer-aided visualization and analysis system for sequence evaluation |
| 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 |
| US6184200B1 (en) | 1995-09-28 | 2001-02-06 | Amgen Inc. | Truncated glial cell line-derived neurotrophic factor |
| US6063757A (en) * | 1995-11-29 | 2000-05-16 | Urso; Richard G. | Wound treatment method with nerve growth factor |
| AU1121997A (en) | 1995-11-29 | 1997-06-19 | Amgen, Inc. | Method for treating sensory neuropathy using glial cell line-derived neurotrophic factor (gdnf) protein product |
| 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 |
| DE69636739T2 (de) | 1995-12-21 | 2007-10-18 | Ajinomoto Co., Inc. | Verfahren zur rückfaltung von menschlichem activin a |
| US6299895B1 (en) | 1997-03-24 | 2001-10-09 | Neurotech S.A. | Device and method for treating ophthalmic diseases |
| US6878544B2 (en) | 1996-04-19 | 2005-04-12 | Neurotech Sa | Retinal cell lines with extended life-span and their applications |
| 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 |
| WO2000073348A2 (en) | 1999-06-02 | 2000-12-07 | Genentech, Inc. | Methods and compositions for inhibiting neoplastic cell growth |
| WO1998032869A1 (en) | 1997-01-29 | 1998-07-30 | Neurosearch A/S | Expression vectors and methods for in vivo expression of therapeutic polypeptides |
| ES2297889T3 (es) | 1997-07-14 | 2008-05-01 | Bolder Biotechnology, Inc. | Derivados de hormona de crecimiento y proteinas relacionadas. |
| GB9718908D0 (en) | 1997-09-05 | 1997-11-12 | Rowett Research Services Limit | Proteins |
| US20020192209A1 (en) | 1997-09-17 | 2002-12-19 | Genentech, Inc. | Methods and compositions for inhibiting neoplastic cell growth |
| WO1999049039A2 (en) | 1998-03-23 | 1999-09-30 | Genentech, Inc. | GFRα3 AND ITS USES |
| US6653098B1 (en) | 1998-02-23 | 2003-11-25 | G. D. Searle & Co. | Method of producing mouse and human endostatin |
| US6593133B1 (en) | 1998-07-06 | 2003-07-15 | Nsgene A/S | Neurotrophic factors |
| US20020055467A1 (en) | 1998-07-06 | 2002-05-09 | Johansen Teit E. | Novel neurotrophic factors |
| US7067473B1 (en) | 1998-07-14 | 2006-06-27 | Janssen Pharmaceutica N.V. | Neurotrophic growth factor |
| HK1045528B (zh) | 1998-07-14 | 2006-10-27 | 詹森药业有限公司 | 神经营养生长因子 |
| CA2343313A1 (en) | 1998-09-14 | 2000-03-23 | Lars Ostergaard Pedersen | A method of producing a functional immunoglobulin superfamily protein |
| EP1115866A1 (en) | 1998-09-22 | 2001-07-18 | University of Maryland at Baltimore | Cystine knot growth factor mutants |
| US6284540B1 (en) | 1998-09-29 | 2001-09-04 | Washington University | Artemin, a novel neurotrophic factor |
| WO2000034475A2 (en) | 1998-12-09 | 2000-06-15 | Amgen Inc. | Grnf4, a gdnf-related neurotrophic factor |
| PT1626058E (pt) | 1999-03-08 | 2008-02-15 | Genentech Inc | Composições e métodos para o diagnóstico de tumores |
| 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. |
| PT1223966E (pt) | 1999-10-29 | 2003-09-30 | Biopharm Ges Biotechn Entwickl | Utilizacao do gdnf para tratamento de defeitos na cornea |
| US6866851B1 (en) | 1999-12-28 | 2005-03-15 | Washington University | GFRα1-RET specific agonists and methods therefor |
| WO2001076639A2 (en) | 2000-04-06 | 2001-10-18 | Pharmacia Corporation | Chemically-modified myelopoietin conjugates |
| IL152804A0 (en) | 2000-05-16 | 2003-06-24 | Bolder Biotechnology Inc | Methods for refolding proteins containing free cysteine residues |
| JP2001329126A (ja) | 2000-05-22 | 2001-11-27 | Bridgestone Corp | 硬化性組成物 |
| CA2327208A1 (en) | 2000-11-30 | 2002-05-30 | The Government Of The United States Of America | Methods of increasing distribution of therapeutic agents |
| IL140110A0 (en) | 2000-12-05 | 2002-02-10 | Applied Research Systems | Improvement of homogeneity and secretion of recombinant proteins in mammalian systems |
| NZ526610A (en) | 2000-12-22 | 2009-08-28 | Genentech Inc | New use of artemin, a member of the GDNF ligand family |
| US7442370B2 (en) | 2001-02-01 | 2008-10-28 | Biogen Idec Ma Inc. | Polymer conjugates of mutated neublastin |
| DK1355936T3 (da) * | 2001-02-01 | 2007-10-29 | Biogen Idec Inc | Polymerkonjugater af neublastin og fremgangsmåder til anvendelse af samme |
| US7276580B2 (en) | 2001-03-12 | 2007-10-02 | Biogen Idec Ma Inc. | Neurotrophic factors |
| US20040077543A1 (en) | 2001-03-28 | 2004-04-22 | Sah Dinah W. Y. | Treatment using neublastin polypeptides |
| CN1525866B (zh) | 2001-03-28 | 2013-05-29 | 比奥根艾迪克Ma公司 | 神经胚活素多肽的治疗作用 |
| EP1389121B1 (en) | 2001-04-24 | 2012-02-22 | Purdue Research Foundation | Method and compositions for treating mammalian nerve tissue injuries |
| US7164007B2 (en) * | 2001-06-20 | 2007-01-16 | Genentech, Inc. | Anti-PR020044 antibodies |
| 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 |
| EP1314739A1 (en) | 2001-11-22 | 2003-05-28 | Bayer Ag | Process for renaturation of recombinant, disulfide containing proteins at high protein concentrations in the presence of amines |
| 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 |
| DE10229175A1 (de) | 2002-06-28 | 2004-01-15 | Valeo Klimasysteme Gmbh | Zylinderklappe mit strukturierter rauher Oberfläche |
| WO2004094592A2 (en) | 2003-04-18 | 2004-11-04 | Biogen Idec Ma Inc. | Polymer-conjugated glycosylated neublastin |
| NZ544263A (en) | 2003-06-10 | 2009-04-30 | Nsgene As | Improved secretion of neublastin |
| US7598059B2 (en) | 2003-10-02 | 2009-10-06 | Biogen Idec Ma Inc. | Neublastin expression constructs |
| BRPI0415563A (pt) | 2003-10-20 | 2007-01-02 | Nsgene As | método para o tratamento do mal de parkinson, uso de um vetor viral, vetor de expressão viral, composição farmacêutica, célula hospedeira isolada, linhagem de células de empacotamento, mamìfero não humano quimérico, dispositivo de cultura celular implantável, cápsula biocompatìvel, método para tratamento de uma doença do sistema nervoso, célula de mamìfero, e, método para produzir neurturin ou um seu equivalente funcional |
| WO2005072764A2 (en) * | 2004-01-16 | 2005-08-11 | Novocell, Inc. | Fibrin-bound angiogenic factors to stimulate vascularization of transplant site of encapsulated cells |
| EP1784486B1 (en) | 2004-06-23 | 2011-10-05 | TissueGene, Inc. | Nerve regeneration |
| 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 |
| GB2416539A (en) * | 2004-07-24 | 2006-02-01 | Reckitt Benckiser | Liquid cleaning composition, catalyst therefor and methods of cleaning |
| DK1786454T3 (da) | 2004-08-19 | 2010-09-06 | Biogen Idec Inc | Neublastinvarianter |
| CA2577690C (en) | 2004-08-19 | 2013-08-06 | Biogen Idec Ma Inc. | Refolding transforming growth factor beta family proteins |
| US20060165667A1 (en) | 2004-12-03 | 2006-07-27 | Case Western Reserve University | Novel methods, compositions and devices for inducing neovascularization |
| US20080260702A1 (en) | 2005-10-11 | 2008-10-23 | Jesper Roland Jorgensen | Treatment of Retinopathies Using Gfra3 Agonists |
| TWI501774B (zh) | 2006-02-27 | 2015-10-01 | Biogen Idec Inc | 神經性病症之治療 |
| ES2450065T3 (es) | 2006-03-01 | 2014-03-21 | Biogen Idec Ma Inc. | Composiciones y métodos para la administración de proteínas de la familia de ligandos del GDNF |
| DK2019683T4 (da) | 2006-04-25 | 2022-08-29 | Univ California | Indgivelse af vækstfaktorer til behandling af CNS-lidelser |
| EP2142205B1 (en) | 2007-05-01 | 2014-04-02 | Biogen Idec MA Inc. | Neublastin peptides for use in increasing vascularisation in tissue with impaired blood flow |
| WO2009020964A2 (en) | 2007-08-08 | 2009-02-12 | Biogen Idec Ma Inc. | Anti-neublastin antibodies and uses thereof |
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2008
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- 2008-05-01 WO PCT/US2008/062265 patent/WO2008137574A1/en not_active Ceased
- 2008-05-01 ES ES08747382.3T patent/ES2476253T3/es active Active
- 2008-05-01 CA CA002685686A patent/CA2685686A1/en not_active Abandoned
- 2008-05-01 NZ NZ580947A patent/NZ580947A/en not_active IP Right Cessation
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| Publication number | Publication date |
|---|---|
| WO2008137574A1 (en) | 2008-11-13 |
| AU2008247637B2 (en) | 2013-12-05 |
| EP2142205B1 (en) | 2014-04-02 |
| JP2013216689A (ja) | 2013-10-24 |
| US20130237477A1 (en) | 2013-09-12 |
| EP2142205A1 (en) | 2010-01-13 |
| NZ580947A (en) | 2012-05-25 |
| US20100261654A1 (en) | 2010-10-14 |
| JP2010526093A (ja) | 2010-07-29 |
| ES2476253T3 (es) | 2014-07-14 |
| TW200914040A (en) | 2009-04-01 |
| AU2008247637A1 (en) | 2008-11-13 |
| TWI445544B (zh) | 2014-07-21 |
| US8329655B2 (en) | 2012-12-11 |
| EP2142205A4 (en) | 2011-09-07 |
| US9138461B2 (en) | 2015-09-22 |
| CA2685686A1 (en) | 2008-11-13 |
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