CA2111110A1 - Production and recovery of recombinant neurotrophins - Google Patents

Production and recovery of recombinant neurotrophins

Info

Publication number: CA2111110A1
Authority: CA; Canada
Prior art keywords: neurotrophin; seq; biologically active; sequence; recombinant
Prior art date: 1991-06-12
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

Application number

CA002111110A

Other languages

English (en)

French (fr)

Inventor

Nikos Panayotatos

James P. Fandl

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Regeneron Pharmaceuticals Inc

Original Assignee

Individual

Priority date (The priority date 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 date listed.)

1991-06-12

Filing date

1992-06-11

Publication date

1992-12-23

1991-11-21 Priority claimed from US07/796,106 external-priority patent/US5389529A/en

1992-06-11 Application filed by Individual filed Critical Individual

1992-12-23 Publication of CA2111110A1 publication Critical patent/CA2111110A1/en

Status Abandoned legal-status Critical Current

Links

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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/24—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
- C07K14/245—Escherichia (G)
- 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
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Engineering & Computer Science (AREA)
Zoology (AREA)
Biochemistry (AREA)
Biophysics (AREA)
General Health & Medical Sciences (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Bioinformatics & Cheminformatics (AREA)
Gastroenterology & Hepatology (AREA)
Wood Science & Technology (AREA)
Medicinal Chemistry (AREA)
Biomedical Technology (AREA)
Biotechnology (AREA)
General Engineering & Computer Science (AREA)
Toxicology (AREA)
Plant Pathology (AREA)
Microbiology (AREA)
Physics & Mathematics (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)
Peptides Or Proteins (AREA)

CA002111110A 1991-06-12 1992-06-11 Production and recovery of recombinant neurotrophins Abandoned CA2111110A1 (en)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US71518591A	1991-06-12	1991-06-12
US715,185		1991-06-12
US796,106		1991-11-21
US07/796,106 US5389529A (en)	1991-06-12	1991-11-21	Modified lamβ signal sequence and processes for producing recombinant neurotrophins

Publications (1)

Publication Number	Publication Date
CA2111110A1 true CA2111110A1 (en)	1992-12-23

Family

ID=27109290

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002111110A Abandoned CA2111110A1 (en)	1991-06-12	1992-06-11	Production and recovery of recombinant neurotrophins

Country Status (9)

Country	Link
EP (1)	EP0590059A4 (pt)
JP (1)	JPH06508036A (pt)
AU (1)	AU2238792A (pt)
CA (1)	CA2111110A1 (pt)
IE (1)	IE921888A1 (pt)
IL (1)	IL102170A0 (pt)
NZ (1)	NZ243084A (pt)
PT (1)	PT100580A (pt)
WO (1)	WO1992022665A1 (pt)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5169764A (en) *	1990-08-08	1992-12-08	Regeneron Pharmaceuticals, Inc.	Multitrophic and multifunctional chimeric neurotrophic factors, and nucleic acids and plasmids encoding the chimeras
WO1992005254A1 (en) *	1990-09-25	1992-04-02	Genentech, Inc.	Novel neurothrophic factor
AU1254295A (en) *	1993-12-17	1995-07-03	Perkin-Elmer Corporation, The	Uncharged polymers for separation of biomolecules by capillary electrophoresis
US6472585B1 (en)	1994-04-25	2002-10-29	Genentech, Inc.	Cardiotrophin-1 defective mouse
US7258983B2 (en)	1994-04-25	2007-08-21	Genentech, Inc.	Cardiotrophin-1 compositions and methods for the treatment of tumor
CA2188017C (en) *	1994-04-25	2010-09-28	Joffre Baker	Cardiotrophin and uses therefor
US5534615A (en) *	1994-04-25	1996-07-09	Genentech, Inc.	Cardiac hypertrophy factor and uses therefor
FR2729972B1 (fr) *	1995-01-31	1997-04-18	Sanofi Sa	Procede d'extraction de proteines periplasmiques de microorganismes procaryotes en presence d'arginine
BR9713055A (pt) *	1996-11-15	2000-04-04	Genentech Inc	Processo para isolar uma neurotrofina humana recombinante, composição de neurotrofina e processo para purificar uma neurotrofina
DE19944870A1 (de) *	1999-09-18	2001-03-29	Aventis Pharma Gmbh	Signalsequenzen zur Herstellung von Leu-Hirudin über Sekretion durch E. coli in das Kulturmedium

Family Cites Families (5)

* Cited by examiner, † Cited by third party
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
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
AU4803890A (en) *	1988-12-15	1990-07-10	Invitron Corporation	Use of basic amino acids to solubilize immunoglobulins
US5235043A (en) *	1990-04-06	1993-08-10	Synergen, Inc.	Production of biologically active, recombinant members of the ngf/bdnf family of neurotrophic proteins
WO1992005254A1 (en) *	1990-09-25	1992-04-02	Genentech, Inc.	Novel neurothrophic factor

1992
- 1992-06-09 PT PT100580A patent/PT100580A/pt not_active Application Discontinuation
- 1992-06-09 NZ NZ243084A patent/NZ243084A/en not_active IP Right Cessation
- 1992-06-11 IL IL102170A patent/IL102170A0/xx unknown
- 1992-06-11 JP JP5501050A patent/JPH06508036A/ja active Pending
- 1992-06-11 CA CA002111110A patent/CA2111110A1/en not_active Abandoned
- 1992-06-11 WO PCT/US1992/005006 patent/WO1992022665A1/en not_active Ceased
- 1992-06-11 EP EP92914222A patent/EP0590059A4/en not_active Withdrawn
- 1992-06-11 AU AU22387/92A patent/AU2238792A/en not_active Abandoned
- 1992-07-01 IE IE188892A patent/IE921888A1/en not_active Application Discontinuation

Also Published As

Publication number	Publication date
WO1992022665A1 (en)	1992-12-23
JPH06508036A (ja)	1994-09-14
IL102170A0 (en)	1993-01-14
NZ243084A (en)	1995-08-28
EP0590059A4 (en)	1995-09-06
IE921888A1 (en)	1992-12-16
PT100580A (pt)	1993-09-30
AU2238792A (en)	1993-01-12
EP0590059A1 (en)	1994-04-06

Publication	Publication Date	Title
US5389529A (en)	1995-02-14	Modified lamβ signal sequence and processes for producing recombinant neurotrophins
Masiakowski et al.	1991	Recombinant human and rat ciliary neurotrophic factors
DE69233008T2 (de)	2004-01-22	Fusionierung von Peptiden und Proteinen mit Thioredoxin und thioredoxin-ähnlichen Molekülen
US5100784A (en)	1992-03-31	Process for the preparation of mature human serum albumin
EP0772627B1 (en)	2004-09-01	Production of biologically active recombinant neurotrophic protein
EP0205475B2 (en)	2002-09-04	Recombinant methods for production of serine protease inhibitors and dna sequences useful for same
JPH1129598A (ja)	1999-02-02	精製した毛様体神経栄養因子
CN108912221A (zh)	2018-11-30	用于生产重组融合蛋白的辅助蛋白、编码基因、重组融合蛋白、重组表达载体及制备方法
JPH0753118B2 (ja)	1995-06-07	原核宿主生物によるジスルフィド架橋された蛋白質の分泌の際に天然蛋白質の立体配座の形成を向上させる方法
US20020090678A1 (en)	2002-07-11	Phage-dependent superproduction of biologically active protein and peptides
CA2111110A1 (en)	1992-12-23	Production and recovery of recombinant neurotrophins
WO1991018101A1 (en)	1991-11-28	Process for producing protein
JP2002527062A (ja)	2002-08-27	活性なβ−ＮＧＦを得るための方法
AU2001284914A1 (en)	2002-05-23	Phage-dependent Superproduction of Biologically Active Protein and Peptides
WO2007112677A1 (en)	2007-10-11	Method of preparing human parathyroid hormone 1-34
JP2001008697A (ja)	2001-01-16	Ｅ．コリでの非融合タンパク質の調製方法
US20050227920A1 (en)	2005-10-13	Methods for production of recombinant vascular endothelial cell growth inhibitor
EP0495398B1 (de)	1998-12-16	Verfahren zur Herstellung von rekombinanter IgA-protease.
EP1706494B1 (en)	2012-07-04	Method for production of recombinant growth hormone in form of hybrid protein
RU2143492C1 (ru)	1999-12-27	Рекомбинантная плазмида, кодирующая гибридный белок - предшественник инсулина человека (варианты), штамм бактерий e.coli - продуцент гибридного белка - предшественника инсулина человека (варианты), способ получения инсулина человека
Ghasemi et al.	2004	Using L-arabinose for production of human growth hormone in Escherichia coli, studying the processing of gIII:: hGH precursor
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