NO308308B1 - Produksjon av biologisk aktive, rekombinante medlemmer av NGF/BDNF-familien til neurotrofiske proteiner - Google Patents
Produksjon av biologisk aktive, rekombinante medlemmer av NGF/BDNF-familien til neurotrofiske proteiner Download PDFInfo
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- NO308308B1 NO308308B1 NO911303A NO911303A NO308308B1 NO 308308 B1 NO308308 B1 NO 308308B1 NO 911303 A NO911303 A NO 911303A NO 911303 A NO911303 A NO 911303A NO 308308 B1 NO308308 B1 NO 308308B1
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- 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
-
- 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
- C07K14/48—Nerve growth factor [NGF]
-
- 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
- C07K14/50—Fibroblast growth factor [FGF]
- C07K14/503—Fibroblast growth factor [FGF] basic FGF [bFGF]
-
- C—CHEMISTRY; METALLURGY
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/70—Vectors or expression systems specially adapted for E. coli
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/8215—Microorganisms
- Y10S435/822—Microorganisms using bacteria or actinomycetales
- Y10S435/848—Escherichia
- Y10S435/849—Escherichia coli
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Hospice & Palliative Care (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Psychiatry (AREA)
- Pharmacology & Pharmacy (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines Containing Plant Substances (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US50544190A | 1990-04-06 | 1990-04-06 | |
US54775090A | 1990-07-02 | 1990-07-02 | |
US07/594,126 US5235043A (en) | 1990-04-06 | 1990-10-09 | Production of biologically active, recombinant members of the ngf/bdnf family of neurotrophic proteins |
Publications (3)
Publication Number | Publication Date |
---|---|
NO911303D0 NO911303D0 (no) | 1991-04-03 |
NO911303L NO911303L (no) | 1991-10-07 |
NO308308B1 true NO308308B1 (no) | 2000-08-28 |
Family
ID=27414291
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO911303A NO308308B1 (no) | 1990-04-06 | 1991-04-03 | Produksjon av biologisk aktive, rekombinante medlemmer av NGF/BDNF-familien til neurotrofiske proteiner |
Country Status (17)
Country | Link |
---|---|
US (1) | US5235043A (ja) |
EP (1) | EP0450386B1 (ja) |
JP (1) | JP2521851B2 (ja) |
KR (1) | KR910018545A (ja) |
AT (1) | ATE183232T1 (ja) |
AU (1) | AU651339B2 (ja) |
CA (1) | CA2038669C (ja) |
DE (1) | DE69131514T2 (ja) |
DK (1) | DK0450386T3 (ja) |
ES (1) | ES2140379T3 (ja) |
FI (1) | FI108146B (ja) |
GR (1) | GR3031632T3 (ja) |
IE (1) | IE910827A1 (ja) |
IL (1) | IL97602A (ja) |
NO (1) | NO308308B1 (ja) |
NZ (1) | NZ237544A (ja) |
TW (1) | TW206258B (ja) |
Families Citing this family (54)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5229500A (en) * | 1989-08-30 | 1993-07-20 | Regeneron Pharmaceuticals, Inc. | Brain derived neurotrophic factor |
US5180820A (en) * | 1989-08-30 | 1993-01-19 | Barde Yves Alain | Brain-derived neurotrophic factor |
US5606031A (en) * | 1990-04-06 | 1997-02-25 | Lile; Jack | Production and purification of biologically active recombinant neurotrophic protein in bacteria |
US5986070A (en) * | 1990-04-06 | 1999-11-16 | Amgen Inc. | Production of biologically active NGF proteins |
ES2119779T3 (es) * | 1990-09-05 | 1998-10-16 | Southern Cross Biotech Pty Ltd | Solubilizacion de proteinas en formas activas. |
US5530109A (en) * | 1991-04-10 | 1996-06-25 | Ludwig Institute For Cancer Research | DNA encoding glial mitogenic factors |
NZ243084A (en) * | 1991-06-12 | 1995-08-28 | Regeneron Pharma | Production and recovery of recombinant neurotrophins, genes for a modified lamb signal sequence, fusion genes and plasmids |
US5389529A (en) * | 1991-06-12 | 1995-02-14 | Regeneron Pharmaceuticals, Inc. | Modified lamβ signal sequence and processes for producing recombinant neurotrophins |
DE4139000A1 (de) * | 1991-11-27 | 1993-06-03 | Boehringer Mannheim Gmbh | Verfahren zur gentechnologischen herstellung von biologisch aktivem ss-ngf |
US5488099A (en) * | 1992-03-06 | 1996-01-30 | Persson, Deceased; Hakan B. | Multifunctional chimeric neurotrophic factors |
US5328837A (en) * | 1992-05-18 | 1994-07-12 | Genentech, Inc. | Hepatocyte growth factor protease domain variants |
US5316921A (en) * | 1992-05-18 | 1994-05-31 | Genentech, Inc. | Single-chain hepatocyte growth factor variants |
DK0642580T3 (da) * | 1992-05-18 | 2002-12-23 | Genentech Inc | Hepactocytvækstfaktorvarianter |
EP0573904B1 (en) * | 1992-06-08 | 2001-09-26 | Takeda Chemical Industries, Ltd. | Therapeutic agent for neutropenia |
US5364645A (en) * | 1992-10-30 | 1994-11-15 | The Regents Of The University Of California | Method of controlling microorganisms by pulsed ultraviolet laser radiation |
EP0632008B1 (en) * | 1993-06-01 | 1998-02-04 | Ono Pharmaceutical Co., Ltd. | Pentanoic acid derivatives |
ATE175677T1 (de) * | 1993-10-18 | 1999-01-15 | Regeneron Pharma | Heterodimere der wachstumsfaktoren |
US5470719A (en) * | 1994-03-18 | 1995-11-28 | Meng; Shi-Yuan | Modified OmpA signal sequence for enhanced secretion of polypeptides |
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 |
US5607711A (en) * | 1995-11-01 | 1997-03-04 | The Regents Of The University Of California | Method of controlling insects and mites with pulsed ultraviolet light |
US5859311A (en) * | 1995-11-27 | 1999-01-12 | University Of Kentucky Research Foundation | Transgenic mice which overexpress neurotrophin-3 (NT-3) and methods of use |
US7015316B1 (en) | 1996-03-14 | 2006-03-21 | Washington University | Polynucleotides encoding human persephin and related growth factors |
US6222022B1 (en) | 1996-03-14 | 2001-04-24 | Washington University | Persephin and related growth factors |
NZ329482A (en) | 1996-03-14 | 2000-05-26 | Univ Washington | A growth factor persephin related to the GDNF/neurturin family of growth factors Methods of treating conditions related to persephin deficiency detecting gene alterations and identifying other members of the family are included |
EP0904355B1 (de) * | 1996-06-11 | 2004-03-03 | Boehringer Mannheim Gmbh | Verfahren zur aktivierung von denaturiertem protein |
US5910435A (en) * | 1996-07-25 | 1999-06-08 | Wisconsin Alumni Research Foundation | Method of folding proteins with synthetic dithiol catalysts |
HU222666B1 (hu) | 1996-11-15 | 2003-09-29 | Genentech, Inc. | Eljárás neuorotrofinok tisztítására |
US6042579A (en) * | 1997-04-30 | 2000-03-28 | Medtronic, Inc. | Techniques for treating neurodegenerative disorders by infusion of nerve growth factors into the brain |
ES2297889T3 (es) | 1997-07-14 | 2008-05-01 | Bolder Biotechnology, Inc. | Derivados de hormona de crecimiento y proteinas relacionadas. |
US7495087B2 (en) | 1997-07-14 | 2009-02-24 | Bolder Biotechnology, Inc. | Cysteine muteins in the C-D loop of human interleukin-11 |
EP0994188B1 (de) * | 1998-10-09 | 2004-01-07 | Scil proteins GmbH | Verfahren zur Gewinnung von aktivem Beta-NGF |
ATE406907T1 (de) * | 1998-10-28 | 2008-09-15 | Cornell Res Foundation Inc | Methoden zur regulierung der angiogenese und vaskuläre integrität mittels trk rezeptor liganden bdnf, nt-3 und nt-4 |
US6329136B1 (en) | 1998-10-30 | 2001-12-11 | The Regents Of The University Of California | Method for laser inactivation of infectious agents |
BR122013003013B8 (pt) * | 1999-01-14 | 2021-07-06 | Bolder Biotechnology Inc | proteína isolada monopeguilada do hormônio do crescimento e método para sua obtenção |
US20020049303A1 (en) * | 1999-06-28 | 2002-04-25 | Tang Jordan J. N. | Catalytically active recombinant memapsin and methods of use thereof |
US6545127B1 (en) * | 1999-06-28 | 2003-04-08 | Oklahoma Medical Research Foundation | Catalytically active recombinant memapsin and methods of use thereof |
EP1206578A2 (en) | 1999-08-11 | 2002-05-22 | Whitehead Institute For Biomedical Research | Bdnf polymorphism and association with bipolar disorder |
US7223406B2 (en) * | 2000-07-21 | 2007-05-29 | The Regents Of The University Of California | Methods and compositions for preventing and treating male erectile dysfunction and female sexual arousal disorder |
AU2001278981A1 (en) * | 2000-07-21 | 2002-02-05 | Tom F Lue | Prevention and treatment of sexual arousal disorders |
US20040121947A1 (en) * | 2000-12-28 | 2004-06-24 | Oklahoma Medical Research Foundation | Compounds which inhibit beta-secretase activity and methods of use thereof |
US20030232365A1 (en) * | 2001-02-15 | 2003-12-18 | Whitehead Institute For Biomedical Research | BDNF polymorphisms and association with bipolar disorder |
EP1233075A3 (en) * | 2001-02-15 | 2003-01-08 | Whitehead Institute For Biomedical Research | BDNF polymorphism and association with bipolar disorder |
AU2002359301B2 (en) * | 2001-10-23 | 2008-07-03 | Comentis, Inc. | Beta-secretase inhibitors and methods of use |
US20060234944A1 (en) * | 2001-10-23 | 2006-10-19 | Oklahoma Medical Reseach Foundation | Beta-secretase inhibitors and methods of use |
US20030219696A1 (en) * | 2002-05-23 | 2003-11-27 | Moreland Gerald W. | Method and apparatus for preventing backflow in dental saliva evacuators |
JP2005305107A (ja) * | 2004-03-25 | 2005-11-04 | Sei Matsuoka | 価値的情報値の測定装置およびこれを使用した測定方法 |
AU2006279896A1 (en) * | 2005-08-10 | 2007-02-22 | Oklahoma Medical Research Foundation | Truncated memapsin 2 for use for treating Alzheimer's disease |
WO2008002572A2 (en) * | 2006-06-27 | 2008-01-03 | The Government Of The United States Of America As Represented By The Secretary Of Health And Human Services | Method for measuring mature brain derived neurotrophic factor |
IT1394596B1 (it) * | 2008-09-30 | 2012-07-05 | Fond Parco Tecnologico Padano | Produzione di ngf in pianta. |
EP2594295A1 (en) | 2011-11-16 | 2013-05-22 | Servicio Andaluz De Salud | Nerve implants based on a compacted biomaterial containing cells |
GB201804641D0 (en) * | 2018-03-22 | 2018-05-09 | Inivata Ltd | Methods of sequencing nucleic acids and error correction of sequence reads |
IT202000032423A1 (it) | 2020-12-24 | 2022-06-24 | Univ Degli Studi Di Trieste | Metodo per la produzione di forme processate proteoliticamente di fattori trofici o fattori di crescita |
EP4413993A1 (en) * | 2023-02-10 | 2024-08-14 | Dompe' Farmaceutici S.P.A. | Method of obtaining recombinant human brain-derived neurotrophic factor |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4511502A (en) * | 1982-12-22 | 1985-04-16 | Genentech, Inc. | Purification and activity assurance of precipitated heterologous proteins |
US4599197A (en) * | 1982-12-22 | 1986-07-08 | Genentech, Inc. | Purification and activity assurance of precipitated heterologous proteins |
US4511503A (en) * | 1982-12-22 | 1985-04-16 | Genentech, Inc. | Purification and activity assurance of precipitated heterologous proteins |
US4512922A (en) * | 1982-12-22 | 1985-04-23 | Genentech, Inc. | Purification and activity assurance of precipitated heterologous proteins |
DK161152C (da) * | 1983-03-03 | 1991-11-11 | Genentech Inc | Polypeptid med egenskaber som human beta-nervevaekstfaktor og fremgangsmaade til fremstilling deraf, dna-isolat omfattende en sekvens som koder for polypeptidet, replicerbar udtrykkelsesvektor for dna-sekvensen, rekombinant vaertscelle transformeret med vektoren, farmaceutisk praeparat indeholdende polypeptidet og fremg. der omfatter anvendelsen af polypeptidet til fremst. af et farmaceutisk praeparat |
US4766205A (en) * | 1985-11-13 | 1988-08-23 | Beatrice Companies, Inc. | Method for isolation of recombinant polypeptides in biologically active forms |
US4929700A (en) * | 1987-04-16 | 1990-05-29 | Cetus Corporation | Production of purified, biologically active, bacterially produced recombinant human CSF-1 |
IT1219874B (it) * | 1988-03-18 | 1990-05-24 | Fidia Farmaceutici | Utilizzazione del fattore di crescita nervoso umano e sue composizioni farmaceutiche |
US6709837B1 (en) * | 1989-03-10 | 2004-03-23 | Takeda Chemical Industries, Inc. | Polypeptide and production thereof |
US5180820A (en) * | 1989-08-30 | 1993-01-19 | Barde Yves Alain | Brain-derived neurotrophic factor |
GR1000980B (el) * | 1989-08-30 | 1993-03-31 | Max Planck Gesellschaft | Νευροτροφινη-3,ενας νεος neυροτροφικος παραγοντας που σχετιζεται με τον παραγοντα αναπτυξης νευρων και τον νευροτροφικο παραγοντα που προερχεται απο τον εγκεφαλο. |
US5229500A (en) * | 1989-08-30 | 1993-07-20 | Regeneron Pharmaceuticals, Inc. | Brain derived neurotrophic factor |
JPH05161493A (ja) * | 1989-08-30 | 1993-06-29 | Max Planck Ges Foerderung Wissenschaft Ev | ニューロトロフィン―3 |
-
1990
- 1990-10-09 US US07/594,126 patent/US5235043A/en not_active Expired - Lifetime
-
1991
- 1991-03-12 IE IE082791A patent/IE910827A1/en not_active IP Right Cessation
- 1991-03-18 DK DK91104171T patent/DK0450386T3/da active
- 1991-03-18 EP EP91104171A patent/EP0450386B1/en not_active Expired - Lifetime
- 1991-03-18 DE DE69131514T patent/DE69131514T2/de not_active Expired - Lifetime
- 1991-03-18 ES ES91104171T patent/ES2140379T3/es not_active Expired - Lifetime
- 1991-03-18 AT AT91104171T patent/ATE183232T1/de not_active IP Right Cessation
- 1991-03-19 IL IL9760291A patent/IL97602A/xx not_active IP Right Cessation
- 1991-03-20 CA CA002038669A patent/CA2038669C/en not_active Expired - Lifetime
- 1991-03-22 NZ NZ237544A patent/NZ237544A/xx unknown
- 1991-04-03 NO NO911303A patent/NO308308B1/no not_active IP Right Cessation
- 1991-04-05 FI FI911643A patent/FI108146B/fi active
- 1991-04-05 AU AU74130/91A patent/AU651339B2/en not_active Ceased
- 1991-04-06 JP JP3073389A patent/JP2521851B2/ja not_active Expired - Lifetime
- 1991-04-06 KR KR1019910005514A patent/KR910018545A/ko not_active Application Discontinuation
- 1991-04-08 TW TW080102624A patent/TW206258B/zh not_active IP Right Cessation
-
1999
- 1999-10-21 GR GR990402673T patent/GR3031632T3/el unknown
Also Published As
Publication number | Publication date |
---|---|
CA2038669C (en) | 2004-06-29 |
ES2140379T3 (es) | 2000-03-01 |
JPH06319549A (ja) | 1994-11-22 |
ATE183232T1 (de) | 1999-08-15 |
CA2038669A1 (en) | 1991-10-07 |
IE910827A1 (en) | 1991-10-09 |
DE69131514T2 (de) | 2000-05-04 |
IL97602A (en) | 2005-08-31 |
AU651339B2 (en) | 1994-07-21 |
KR910018545A (ko) | 1991-11-30 |
NZ237544A (en) | 1993-07-27 |
FI108146B (fi) | 2001-11-30 |
EP0450386A3 (en) | 1992-09-09 |
JP2521851B2 (ja) | 1996-08-07 |
NO911303L (no) | 1991-10-07 |
DE69131514D1 (de) | 1999-09-16 |
FI911643A0 (fi) | 1991-04-05 |
EP0450386B1 (en) | 1999-08-11 |
DK0450386T3 (da) | 2000-03-06 |
NO911303D0 (no) | 1991-04-03 |
GR3031632T3 (en) | 2000-01-31 |
FI911643A (fi) | 1991-10-07 |
TW206258B (ja) | 1993-05-21 |
IL97602A0 (en) | 1992-06-21 |
AU7413091A (en) | 1991-11-14 |
US5235043A (en) | 1993-08-10 |
EP0450386A2 (en) | 1991-10-09 |
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Legal Events
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MK1K | Patent expired |