NO321382B1 - Nye rensete og isolerte neurotrofiske proteiner, nukleinsyresekvensen som koder for disse proteiner, ny vektor og vertscelle som inneholder nevnte vektor, en fremgangsmate for fremstilling av nevnte proteiner, en innretning for a behandle nerveskade, en farmasoytisk sammensetning samt anvendelse av nevnte proteiner. - Google Patents
Nye rensete og isolerte neurotrofiske proteiner, nukleinsyresekvensen som koder for disse proteiner, ny vektor og vertscelle som inneholder nevnte vektor, en fremgangsmate for fremstilling av nevnte proteiner, en innretning for a behandle nerveskade, en farmasoytisk sammensetning samt anvendelse av nevnte proteiner. Download PDFInfo
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- NO321382B1 NO321382B1 NO19940922A NO940922A NO321382B1 NO 321382 B1 NO321382 B1 NO 321382B1 NO 19940922 A NO19940922 A NO 19940922A NO 940922 A NO940922 A NO 940922A NO 321382 B1 NO321382 B1 NO 321382B1
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Classifications
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0085—Brain, e.g. brain implants; Spinal cord
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, ***e
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/808—Materials and products related to genetic engineering or hybrid or fused cell technology, e.g. hybridoma, monoclonal products
- Y10S530/809—Fused cells, e.g. hybridoma
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/827—Proteins from mammals or birds
- Y10S530/839—Nerves; brain
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
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- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- General Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biophysics (AREA)
- Psychology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Engineering & Computer Science (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Gastroenterology & Hepatology (AREA)
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- Psychiatry (AREA)
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- Microbiology (AREA)
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- Hospice & Palliative Care (AREA)
- Plant Pathology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Compounds Of Unknown Constitution (AREA)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
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US76468591A | 1991-09-20 | 1991-09-20 | |
US77410991A | 1991-10-08 | 1991-10-08 | |
US78842391A | 1991-11-06 | 1991-11-06 | |
US85541392A | 1992-03-19 | 1992-03-19 | |
PCT/US1992/007888 WO1993006116A1 (en) | 1991-09-20 | 1992-09-17 | Glial derived neurotrophic factor |
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NO940922D0 NO940922D0 (no) | 1994-03-15 |
NO940922L NO940922L (no) | 1994-05-19 |
NO321382B1 true NO321382B1 (no) | 2006-05-02 |
Family
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Application Number | Title | Priority Date | Filing Date |
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NO19940922A NO321382B1 (no) | 1991-09-20 | 1994-03-15 | Nye rensete og isolerte neurotrofiske proteiner, nukleinsyresekvensen som koder for disse proteiner, ny vektor og vertscelle som inneholder nevnte vektor, en fremgangsmate for fremstilling av nevnte proteiner, en innretning for a behandle nerveskade, en farmasoytisk sammensetning samt anvendelse av nevnte proteiner. |
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US (7) | US7226758B1 (hu) |
EP (2) | EP0610254B1 (hu) |
KR (1) | KR100242093B1 (hu) |
AT (1) | ATE275197T1 (hu) |
AU (2) | AU679167B2 (hu) |
CA (1) | CA2119463C (hu) |
DE (1) | DE69233407T2 (hu) |
DK (1) | DK0610254T3 (hu) |
ES (1) | ES2225819T3 (hu) |
FI (1) | FI117556B (hu) |
GE (1) | GEP20002243B (hu) |
HK (2) | HK1017816A1 (hu) |
HU (2) | HU220795B1 (hu) |
IL (5) | IL103223A (hu) |
MX (1) | MX9205293A (hu) |
NO (1) | NO321382B1 (hu) |
NZ (1) | NZ244392A (hu) |
PT (1) | PT100879B (hu) |
SG (1) | SG48145A1 (hu) |
TW (1) | TW401422B (hu) |
WO (1) | WO1993006116A1 (hu) |
Families Citing this family (142)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5981165A (en) * | 1991-07-08 | 1999-11-09 | Neurospheres Holdings Ltd. | In vitro induction of dopaminergic cells |
WO1995006662A1 (en) * | 1993-09-01 | 1995-03-09 | Start Technology Partnership | Neuron regulatory factor for promoting neuron survival |
WO1995017203A1 (en) * | 1993-12-22 | 1995-06-29 | The University Of Medicine And Dentistry Of New Jersey | Novel nucleic acid sequences isolated from glial cells |
US6472585B1 (en) | 1994-04-25 | 2002-10-29 | Genentech, Inc. | Cardiotrophin-1 defective mouse |
US5534615A (en) * | 1994-04-25 | 1996-07-09 | Genentech, Inc. | Cardiac hypertrophy factor and uses therefor |
CA2188017C (en) * | 1994-04-25 | 2010-09-28 | Joffre Baker | Cardiotrophin and uses therefor |
US7258983B2 (en) | 1994-04-25 | 2007-08-21 | Genentech, Inc. | Cardiotrophin-1 compositions and methods for the treatment of tumor |
US5853385A (en) * | 1994-08-26 | 1998-12-29 | Cytotherapeutics, Inc. | Encapsulated PC12 cell transplants for treatment of Parkinson's disease |
US5733875A (en) * | 1994-11-15 | 1998-03-31 | Amgen Inc. | Methods of using GDNF as a neuroprotective agent |
JP3093974B2 (ja) * | 1995-06-27 | 2000-10-03 | 住友ベークライト株式会社 | 神経細胞用培養液、その製造方法及びこれを用いる神経細胞の培養方法 |
US5739307A (en) * | 1995-08-28 | 1998-04-14 | Washington University | Polynucleotide encoding neurturin neurotrophic factor |
US6743628B1 (en) | 1995-08-28 | 2004-06-01 | Washington University | Method of cell culture using neurturin |
US5731284A (en) * | 1995-09-28 | 1998-03-24 | Amgen Inc. | Method for treating Alzheimer's disease using glial line-derived neurotrophic factor (GDNF) protein product |
US6184200B1 (en) * | 1995-09-28 | 2001-02-06 | Amgen Inc. | Truncated glial cell line-derived neurotrophic factor |
US5641750A (en) * | 1995-11-29 | 1997-06-24 | Amgen Inc. | Methods for treating photoreceptors using glial cell line-derived neurotrophic factor (GDNF) protein product |
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 |
US5905027A (en) * | 1995-12-27 | 1999-05-18 | Uab Research Foundation | Method of diagnosing and treating gliomas |
US5837681A (en) * | 1996-02-23 | 1998-11-17 | Amgen Inc. | Method for treating sensorineural hearing loss using glial cell line-derived neurotrophic factor (GDNF) protein product |
US5929041A (en) * | 1996-02-23 | 1999-07-27 | Amgen Inc. | Method for preventing and treating sensorineural hearing loss and vestibular disorders using glial cell line-derived neurotrophic factor(GDNF) protein product |
PT888385E (pt) | 1996-03-14 | 2004-01-30 | Genentech Inc | Utilizacoes de gdnf e de receptores de gdnf |
US6716600B1 (en) | 1996-03-14 | 2004-04-06 | Washington University | Persephin and related growth factors |
US6232449B1 (en) | 1996-03-14 | 2001-05-15 | Washington University | Persephin and related growth factors |
US6222022B1 (en) | 1996-03-14 | 2001-04-24 | Washington University | Persephin and related growth factors |
US5741778A (en) * | 1996-03-19 | 1998-04-21 | Amgen Inc. | Method for treating Huntington's disease using glial cell line-derived neurotrophic factor (GDNF) protein product |
US6299895B1 (en) | 1997-03-24 | 2001-10-09 | Neurotech S.A. | Device and method for treating ophthalmic diseases |
US6455277B1 (en) * | 1996-04-22 | 2002-09-24 | Amgen Inc. | Polynucleotides encoding human glial cell line-derived neurotrophic factor receptor polypeptides |
US7138251B1 (en) | 1996-04-22 | 2006-11-21 | Amgen Inc. | Polynucleotides encoding a neurotrophic factor receptor |
AU2677797A (en) * | 1996-04-25 | 1997-11-12 | Genetic Therapy, Inc. | Viral vectors including polynucleotides encoding neurotrophic factors and uses therefor |
JP2000516457A (ja) * | 1996-07-29 | 2000-12-12 | バイオファーム ゲゼルシャフト ツア バイオテクノロジシェン エントヴィックルング ウント ツム フェルトリーブ フォン ファルマカ エムベーハー | ドパミン作動性ニューロンに対し生存促進活性を有するクロマフィン粒由来のegf様因子および膠細胞由来の神経栄養因子 |
ES2308800T3 (es) | 1997-01-08 | 2008-12-01 | Invitrogen Corporation | Metodos para la produccion de proteinas. |
US6025157A (en) * | 1997-02-18 | 2000-02-15 | Genentech, Inc. | Neurturin receptor |
US6777196B2 (en) | 1997-02-18 | 2004-08-17 | Genentech, Inc. | Neurturin receptor |
US6372453B1 (en) | 1997-02-18 | 2002-04-16 | Genetech, Inc. | Neurturin receptor |
US6042579A (en) * | 1997-04-30 | 2000-03-28 | Medtronic, Inc. | Techniques for treating neurodegenerative disorders by infusion of nerve growth factors into the brain |
US6043221A (en) * | 1997-07-30 | 2000-03-28 | Amgen Inc. | Method for preventing and treating hearing loss using a neuturin protein product |
SI1005358T1 (en) * | 1997-07-30 | 2003-06-30 | Amgen Inc. | Use of a neurturin protein product for preventing and treating hearing loss |
JP3761152B2 (ja) * | 1997-08-05 | 2006-03-29 | エフ.ホフマン−ラ ロシュ アーゲー | ヒトグリア細胞株由来神経栄養因子プロモーター、該プロモーターを含むベクター、および該プロモーターによる化合物のスクリーニング方法 |
US7026138B1 (en) | 1998-03-23 | 2006-04-11 | Genentech, Inc. | Polynucleotides encoding GFRα3 |
AU765070B2 (en) | 1998-03-23 | 2003-09-11 | Genentech Inc. | GFRalpha3 and its uses |
DE19816186A1 (de) * | 1998-04-14 | 1999-10-21 | Univ Muenchen L Maximilians | GDNF-kodierende DNA, Teile davon und GDNF-Varianten |
US6593133B1 (en) | 1998-07-06 | 2003-07-15 | Nsgene A/S | Neurotrophic factors |
US20020002269A1 (en) * | 1998-09-29 | 2002-01-03 | Jeffrey D. Milbrandt | Artemin, a neurotrophic factor |
US7060676B2 (en) * | 1999-12-20 | 2006-06-13 | Trustees Of Tufts College | T. cruzi-derived neurotrophic agents and methods of use therefor |
US20040014082A1 (en) * | 2000-08-11 | 2004-01-22 | Invitrogen Corporation | Highly homogeneous molecular markers for electrophoresis |
US6426065B1 (en) * | 2000-11-07 | 2002-07-30 | Clairol Incorporated | Use of tris(hydroxymethyl)aminomethane in cold permanent waving processes |
US7442370B2 (en) | 2001-02-01 | 2008-10-28 | Biogen Idec Ma Inc. | Polymer conjugates of mutated neublastin |
US7276580B2 (en) | 2001-03-12 | 2007-10-02 | Biogen Idec Ma Inc. | Neurotrophic factors |
AU2002250203B2 (en) | 2001-03-28 | 2006-08-10 | Biogen Ma Inc. | Use of neublastin polypeptides for treating neuropathic pain |
US20030050273A1 (en) * | 2001-08-29 | 2003-03-13 | Keiya Ozawa | Compositions and methods for treating neurodegenerative diseases |
US7828728B2 (en) * | 2003-07-25 | 2010-11-09 | Dexcom, Inc. | Analyte sensor |
US8364229B2 (en) * | 2003-07-25 | 2013-01-29 | Dexcom, Inc. | Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise |
US7613491B2 (en) | 2002-05-22 | 2009-11-03 | Dexcom, Inc. | Silicone based membranes for use in implantable glucose sensors |
US7497827B2 (en) | 2004-07-13 | 2009-03-03 | Dexcom, Inc. | Transcutaneous analyte sensor |
US20030228295A1 (en) * | 2002-04-25 | 2003-12-11 | Svendsen Clive N. | Use of human neural stem cells secreting GDNF for treatment of parkinson's and other neurodegenerative diseases |
US20060088899A1 (en) * | 2002-05-31 | 2006-04-27 | Alvarez Vernon L | Combination chemotherapy with chlorotoxin |
US7528112B2 (en) | 2002-11-15 | 2009-05-05 | Drexel University | Small survival-promoting/immunomodulatory peptide for treatment of brain damage, neurodegenerative disorders, and inflammatory disorders |
US7388079B2 (en) * | 2002-11-27 | 2008-06-17 | The Regents Of The University Of California | Delivery of pharmaceutical agents via the human insulin receptor |
KR20060002745A (ko) * | 2003-01-13 | 2006-01-09 | 마헨드라 에스 라오 | 치료적 생성물의 전달을 위한 증식성 줄기세포 및전구세포에서의 후보 분자의 지속적 발현 |
US20050048041A1 (en) * | 2003-01-13 | 2005-03-03 | Rao Mahendra S. | Persistent expression of candidate molecule in proliferating stem and progenitor cells for delivery of therapeutic products |
US8946151B2 (en) | 2003-02-24 | 2015-02-03 | Northern Bristol N.H.S. Trust Frenchay Hospital | Method of treating Parkinson's disease in humans by convection-enhanced infusion of glial cell-line derived neurotrophic factor to the putamen |
US20040209810A1 (en) * | 2003-02-24 | 2004-10-21 | Gill Steven S. | Method of treating Parkinson's disease in humans by intraputaminal infusion of glial cell-line derived neurotrophic factor |
EP2322205A1 (en) | 2003-04-18 | 2011-05-18 | Biogen Idec MA Inc. | Polymer-conjugated glycosylated neublastin |
US7875293B2 (en) * | 2003-05-21 | 2011-01-25 | Dexcom, Inc. | Biointerface membranes incorporating bioactive agents |
CN100475846C (zh) | 2003-06-10 | 2009-04-08 | Ns基因公司 | 增加的神经胚素分泌 |
EP1648298A4 (en) * | 2003-07-25 | 2010-01-13 | Dexcom Inc | OXYGEN-IMPROVED MEMBRANE SYSTEMS FOR IMPLANTABLE DEVICES |
US9763609B2 (en) | 2003-07-25 | 2017-09-19 | Dexcom, Inc. | Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise |
US7591801B2 (en) | 2004-02-26 | 2009-09-22 | Dexcom, Inc. | Integrated delivery device for continuous glucose sensor |
US9135402B2 (en) | 2007-12-17 | 2015-09-15 | Dexcom, Inc. | Systems and methods for processing sensor data |
US7920906B2 (en) | 2005-03-10 | 2011-04-05 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
US20050049196A1 (en) * | 2003-08-29 | 2005-03-03 | Michael Hutchinson | Indirect delivery of growth factors into the central nervous system |
WO2005023861A2 (en) * | 2003-09-05 | 2005-03-17 | Licentia, Ltd. | Gdnf-related neuropeptides |
US7598059B2 (en) | 2003-10-02 | 2009-10-06 | Biogen Idec Ma Inc. | Neublastin expression constructs |
CN1897977A (zh) * | 2003-10-20 | 2007-01-17 | Ns基因公司 | 帕金森氏病的体内基因治疗 |
US9247900B2 (en) | 2004-07-13 | 2016-02-02 | Dexcom, Inc. | Analyte sensor |
US8093205B2 (en) | 2003-12-01 | 2012-01-10 | Medtronic, Inc. | Method for treating a stroke by implanting a first therapy delivery element in the CNS and a second therapy delivery element in a damaged tissue of the CNS to promote neurogenesis |
US20050123526A1 (en) * | 2003-12-01 | 2005-06-09 | Medtronic Inc. | Administration of growth factors for neurogenesis and gliagenesis |
US7364592B2 (en) * | 2004-02-12 | 2008-04-29 | Dexcom, Inc. | Biointerface membrane with macro-and micro-architecture |
WO2009048462A1 (en) | 2007-10-09 | 2009-04-16 | Dexcom, Inc. | Integrated insulin delivery system with continuous glucose sensor |
US20050208090A1 (en) * | 2004-03-18 | 2005-09-22 | Medtronic, Inc. | Methods and systems for treatment of neurological diseases of the central nervous system |
GB2414934A (en) * | 2004-06-11 | 2005-12-14 | Gill Steven Streatfield | Treatment of Parkinson's disease with GDNF |
CA2568150A1 (en) * | 2004-06-21 | 2006-01-05 | Medtronic, Inc. | Medical systems and methods for delivering compositions to cells |
ATE474586T1 (de) | 2004-08-19 | 2010-08-15 | Biogen Idec Inc | Neublastin-varianten |
KR101241551B1 (ko) | 2004-08-19 | 2013-03-11 | 바이오겐 아이덱 엠에이 인코포레이티드 | 전환 성장 인자 베타 패밀리 단백질의 리폴딩 |
US8133178B2 (en) | 2006-02-22 | 2012-03-13 | Dexcom, Inc. | Analyte sensor |
WO2007019860A2 (en) * | 2005-08-16 | 2007-02-22 | Copenhagen University | Gdnf derived peptides |
US8053569B2 (en) * | 2005-10-07 | 2011-11-08 | Armagen Technologies, Inc. | Nucleic acids encoding and methods of producing fusion proteins |
US8124095B2 (en) * | 2005-10-07 | 2012-02-28 | Armagen Technologies, Inc. | Fusion proteins for delivery of erythropoietin to the CNS |
US8741260B2 (en) * | 2005-10-07 | 2014-06-03 | Armagen Technologies, Inc. | Fusion proteins for delivery of GDNF to the CNS |
WO2007048413A1 (en) * | 2005-10-28 | 2007-05-03 | Nsgene A/S | IMPLANTABLE BIOCOMPATIBLE IMMtTNOISOLATORY VEHICLE FOR DELIVERY OF GDNF |
EP1969003B8 (en) | 2005-12-14 | 2010-11-10 | Hermo Pharma Ltd. | Uses of a NEUROTROPHIC FACTOR PROTEIN |
TWI501774B (zh) | 2006-02-27 | 2015-10-01 | Biogen Idec Inc | 神經性病症之治療 |
DK2019683T4 (da) | 2006-04-25 | 2022-08-29 | Univ California | Indgivelse af vækstfaktorer til behandling af CNS-lidelser |
US20070259031A1 (en) * | 2006-04-26 | 2007-11-08 | The Regents Of The University Of California | Compositions and methods for convection enhanced delivery of high molecular weight neurotherapeutics |
EP1872790A1 (en) | 2006-06-26 | 2008-01-02 | DeveloGen Aktiengesellschaft | New formulation for increasing bioavailability of neurturin |
AU2007285763B2 (en) | 2006-08-18 | 2011-12-15 | Armagen Technologies, Inc. | Agents for blood-brain barrier delivery |
KR100770440B1 (ko) * | 2006-08-29 | 2007-10-26 | 삼성전기주식회사 | 질화물 반도체 발광소자 |
US8637459B2 (en) | 2006-11-08 | 2014-01-28 | Emory University | Enhancing a population of insulin releasing cells using GFR-A1 agonists |
NZ580947A (en) | 2007-05-01 | 2012-05-25 | Biogen Idec Inc | Compositions and methods for increasing vascularization |
US20090011040A1 (en) * | 2007-05-02 | 2009-01-08 | Naash Muna I | Use of compacted nucleic acid nanoparticles in non-viral treatments of ocular diseases |
US20200037874A1 (en) | 2007-05-18 | 2020-02-06 | Dexcom, Inc. | Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise |
US20100210604A1 (en) * | 2007-06-13 | 2010-08-19 | Meythaler Jay M | Zwitterion solution for low-volume therapeutic delivery |
US20110021469A1 (en) | 2007-06-13 | 2011-01-27 | Meythaler Jay M | baclofen solution for low-volume therapeutic delivery |
US8974791B2 (en) * | 2007-07-27 | 2015-03-10 | Armagen Technologies, Inc. | Methods and compositions for increasing α-L-iduronidase activity in the CNS |
FI20070808A0 (fi) | 2007-10-25 | 2007-10-25 | Mart Saarma | GDNF:n silmukointivariantit ja niiden käytöt |
US8417312B2 (en) | 2007-10-25 | 2013-04-09 | Dexcom, Inc. | Systems and methods for processing sensor data |
US9839395B2 (en) | 2007-12-17 | 2017-12-12 | Dexcom, Inc. | Systems and methods for processing sensor data |
GB0803352D0 (en) | 2008-02-22 | 2008-04-02 | Ntnu Technology Transfer As | Oligopeptidic compounds and uses thereof |
WO2009121026A1 (en) | 2008-03-28 | 2009-10-01 | Dexcom, Inc. | Polymer membranes for continuous analyte sensors |
FI20080326A0 (fi) | 2008-04-30 | 2008-04-30 | Licentia Oy | Neurotroofinen tekijä MANF ja sen käytöt |
BRPI0912683A2 (pt) | 2008-05-15 | 2016-01-26 | Transmolecular Inc | tratamento de tumores metastáticos |
ES2658626T3 (es) | 2009-02-12 | 2018-03-12 | Curna, Inc. | Tratamiento de enfermedades relacionadas con el factor neurotrófico derivado de células gliales (GDNF) por inhibición de transcrito antisentido natural a GDNF |
JP5873003B2 (ja) | 2009-03-18 | 2016-03-01 | アーメイゲン・テクノロジーズ・インコーポレイテッドArmagen Technologies, Inc. | IgGデコイ受容体融合タンパク質の血液脳関門送達のための組成物および方法 |
WO2010144696A1 (en) | 2009-06-11 | 2010-12-16 | Burnham Institute For Medical Research | Directed differentiation of stem cells |
HUE044865T2 (hu) | 2009-10-09 | 2019-11-28 | Armagen Inc | Eljárások és készítmények a központi idegrendszerben iduronát-2-szulfatáz-aktivitás növelésére |
WO2011064437A2 (es) | 2009-11-26 | 2011-06-03 | Proyecto De Biomedicina Cima, S.L. | Vectores virales y procedimientos útiles en la preparación de gdnf |
AU2011213678B2 (en) | 2010-02-04 | 2015-01-29 | Eisai Inc. | Chlorotoxin polypeptides and conjugates and uses thereof |
CN106957356B (zh) | 2010-05-11 | 2021-05-25 | 弗雷德哈钦森癌症研究中心 | 氯毒素变体、缀合物及其使用方法 |
MX2013006216A (es) | 2010-12-02 | 2013-10-17 | Neurotech Usa Inc | Lineas celulares que secretan andamios de anticuerpos anti-angionicos y receptores solubles y sus usos. |
UA112981C2 (uk) | 2011-04-11 | 2016-11-25 | Елі Ліллі Енд Компані | Варіант людського gdnf |
EP4218570A3 (en) | 2011-08-26 | 2023-10-04 | DexCom, Inc. | Polymer membranes for continuous analyte sensors |
EP4338797A3 (en) | 2011-12-02 | 2024-06-12 | Armagen, Inc. | Methods and compositions for increasing arylsulfatase a activity in the cns |
US9788765B2 (en) | 2012-09-28 | 2017-10-17 | Dexcom, Inc. | Zwitterion surface modifications for continuous sensors |
JP2016505826A (ja) | 2012-12-10 | 2016-02-25 | フレッド ハッチンソン キャンサー リサーチ センター | スクリーニングの方法 |
EP2968462B1 (en) | 2013-03-15 | 2020-12-23 | The Jackson Laboratory | Methods for promoting wound healing and hair growth |
US9737250B2 (en) | 2013-03-15 | 2017-08-22 | Dexcom, Inc. | Membrane for continuous analyte sensors |
US11559580B1 (en) | 2013-09-17 | 2023-01-24 | Blaze Bioscience, Inc. | Tissue-homing peptide conjugates and methods of use thereof |
US10369329B2 (en) | 2014-01-30 | 2019-08-06 | Renishaw Plc | Neurosurgical apparatus and method |
CN106460062A (zh) | 2014-05-05 | 2017-02-22 | 美敦力公司 | 用于scd、crt、crt‑d或sca治疗识别和/或选择的方法和组合物 |
US10538589B2 (en) | 2015-01-14 | 2020-01-21 | Armagen Inc. | Methods and compositions for increasing N-acetylglucosaminidase (NAGLU) activity in the CNS using a fusion antibody comprising an anti-human insulin receptor antibody and NAGLU |
GB201506052D0 (en) | 2015-04-09 | 2015-05-27 | Renishaw Plc | Movement disorder |
CA2986769A1 (en) | 2015-05-27 | 2016-12-01 | Neurotech Usa, Inc. | Use of encapsulated cell therapy for treatment of ophthalmic disorders |
EP3397398B1 (en) | 2015-12-30 | 2023-11-08 | Dexcom, Inc. | Biointerface layer for analyte sensors |
US11912750B2 (en) | 2016-11-10 | 2024-02-27 | Keros Therapeutics, Inc. | GDNF fusion polypeptides and methods of use thereof |
CA3210177A1 (en) | 2021-03-19 | 2022-09-22 | Dexcom, Inc. | Drug releasing membrane for analyte sensor |
AU2022345089A1 (en) | 2021-09-15 | 2024-05-02 | Dexcom, Inc. | Bioactive releasing membrane for analyte sensor |
AU2022397707A1 (en) | 2021-11-29 | 2024-06-13 | Shanghai Regenelead Therapies Co., Ltd. | Aadc/gdnf polynucleotide, and use thereof in treating parkinson's disease |
WO2023150646A1 (en) | 2022-02-02 | 2023-08-10 | Dexcom, Inc. | Sensing systems and methods for diagnosing, staging, treating, and assessing risks of liver disease using monitored analyte data |
WO2023164584A1 (en) | 2022-02-23 | 2023-08-31 | Dexcom, Inc. | Sensing systems and methods for providing decision support around kidney health and/or diabetes |
CA3239095A1 (en) | 2022-06-01 | 2023-12-07 | Dexcom, Inc. | Systems and methods for monitoring, diagnosis, and decision support for diabetes in patients with kidney disease |
WO2024050126A2 (en) | 2022-09-02 | 2024-03-07 | Dexcom, Inc. | Continuous analyte sensor devices and methods |
US20240225490A1 (en) | 2022-12-30 | 2024-07-11 | Dexcom, Inc. | Sensing systems and methods for hybrid glucose and ketone monitoring |
Family Cites Families (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4518526A (en) * | 1982-12-22 | 1985-05-21 | Genentech, Inc. | Purification and activity assurance of precipitated heterologous proteins |
DE3587022T2 (de) | 1984-02-17 | 1993-06-17 | Genentech Inc | Menschlicher transformationswachstumsfaktor und vorlaeufer oder fragment hiervon, zellen, dna, vektoren und verfahren zu ihrer herstellung, zusammensetzungen und produkte, die diese enthalten, sowie davon abgeleitete antikoerper und diagnostizierverfahren. |
US4886747A (en) | 1985-03-22 | 1989-12-12 | Genentech, Inc. | Nucleic acid encoding TGF-β and its uses |
US5284763A (en) | 1985-03-22 | 1994-02-08 | Genentech, Inc. | Nucleic acid encoding TGF-β and its uses |
US5374548A (en) | 1986-05-02 | 1994-12-20 | Genentech, Inc. | Methods and compositions for the attachment of proteins to liposomes using a glycophospholipid anchor |
US5089396A (en) | 1985-10-03 | 1992-02-18 | Genentech, Inc. | Nucleic acid encoding β chain prodomains of inhibin and method for synthesizing polypeptides using such nucleic acid |
US5427780A (en) | 1985-10-30 | 1995-06-27 | Biogen, Inc. | Composition comprising Mullerian inhibiting substance-like polypeptides |
EP0233838A3 (en) * | 1986-02-04 | 1990-01-31 | Incyte Pharmaceuticals, Inc. | Neurite-promoting factor and process for the manufacture thereof |
US5187076A (en) * | 1986-07-01 | 1993-02-16 | Genetics Institute, Inc. | DNA sequences encoding BMP-6 proteins |
US5106627A (en) | 1987-11-17 | 1992-04-21 | Brown University Research Foundation | Neurological therapy devices |
US5283187A (en) | 1987-11-17 | 1994-02-01 | Brown University Research Foundation | Cell culture-containing tubular capsule produced by co-extrusion |
US4892538A (en) | 1987-11-17 | 1990-01-09 | Brown University Research Foundation | In vivo delivery of neurotransmitters by implanted, encapsulated cells |
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 |
US5324819A (en) | 1988-04-08 | 1994-06-28 | Stryker Corporation | Osteogenic proteins |
US5011472A (en) | 1988-09-06 | 1991-04-30 | Brown University Research Foundation | Implantable delivery system for biological factors |
ATE124726T1 (de) * | 1988-11-04 | 1995-07-15 | Zuerich Erziehungsdirektion | Wachstumsregelfaktoren für neuriten. |
US5250414A (en) | 1988-11-04 | 1993-10-05 | Erziehungsdirektion Of The Canton Zurich | Diagnostic methods using neurite growth regulatory factors |
US5225538A (en) | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
US5017735A (en) | 1989-07-24 | 1991-05-21 | Catalytica, Inc. | Selective sorption of 2,6-diisopropylnaphthalene |
AU6174490A (en) | 1989-08-04 | 1991-03-11 | Board Of Regents, The University Of Texas System | Methods and compositions; purified preparation of neural progenitor regulatory factor |
US5215969A (en) | 1989-08-11 | 1993-06-01 | Hahnemann University | Dopaminergic neurotrophic factor for treatment of Parkinson's disease |
JPH04507251A (ja) | 1989-08-11 | 1992-12-17 | ハーネマン・ユニヴァーシティー | パーキンソン病治療用のドーパミン作動性神経栄養因子 |
WO1991010470A1 (en) | 1990-01-08 | 1991-07-25 | Brown University Research Foundation | Devices and methods for enhanced delivery of active factors |
US5270181A (en) | 1991-02-06 | 1993-12-14 | Genetics Institute, Inc. | Peptide and protein fusions to thioredoxin and thioredoxin-like molecules |
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