NO329525B1 - Fremgangsmate for fremstilling av et biologisk aktivt cytokin og et cDNA - Google Patents

Fremgangsmate for fremstilling av et biologisk aktivt cytokin og et cDNA Download PDF

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Publication number: NO329525B1
Authority: NO; Norway
Prior art keywords: proll; caspase; protease; human; cleavage site
Prior art date: 1999-04-13

Application number

NO20014966A

Other languages

English (en)

Norwegian (no)

Other versions

NO20014966L (no

NO20014966D0 (no

Inventor

Daniela Novick

Menachem Rubinstein

Bianling Liu

Pierre Graber

Original Assignee

Yeda Res & Dev

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.)

1999-04-13

Filing date

2001-10-12

Publication date

2010-11-01

2001-10-12 Application filed by Yeda Res & Dev filed Critical Yeda Res & Dev

2001-10-12 Publication of NO20014966D0 publication Critical patent/NO20014966D0/no

2001-12-11 Publication of NO20014966L publication Critical patent/NO20014966L/no

2010-11-01 Publication of NO329525B1 publication Critical patent/NO329525B1/no

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UPSFMJHZUCSEHU-JYGUBCOQSA-N n-[(2s,3r,4r,5s,6r)-2-[(2r,3s,4r,5r,6s)-5-acetamido-4-hydroxy-2-(hydroxymethyl)-6-(4-methyl-2-oxochromen-7-yl)oxyoxan-3-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide Chemical compound CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@H](O)[C@@H](NC(C)=O)[C@H](OC=2C=C3OC(=O)C=C(C)C3=CC=2)O[C@@H]1CO UPSFMJHZUCSEHU-JYGUBCOQSA-N 0.000 description 1
239000008188 pellet Substances 0.000 description 1
229920000024 polymyxin B Polymers 0.000 description 1
229960005266 polymyxin b Drugs 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
230000000861 pro-apoptotic effect Effects 0.000 description 1
230000005522 programmed cell death Effects 0.000 description 1
230000000770 proinflammatory effect Effects 0.000 description 1
230000002797 proteolythic effect Effects 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
238000012552 review Methods 0.000 description 1
238000013207 serial dilution Methods 0.000 description 1
239000002002 slurry Substances 0.000 description 1
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
210000000952 spleen Anatomy 0.000 description 1
239000012134 supernatant fraction Substances 0.000 description 1
238000012360 testing method Methods 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
230000009466 transformation Effects 0.000 description 1

Classifications

- 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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/52—Genes encoding for enzymes or proenzymes
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6472—Cysteine endopeptidases (3.4.22)
- C12N9/6475—Interleukin 1-beta convertase-like enzymes (3.4.22.10; 3.4.22.36; 3.4.22.63)
- 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/545—IL-1

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Health & Medical Sciences (AREA)
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Organic Chemistry (AREA)
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Molecular Biology (AREA)
Biochemistry (AREA)
General Health & Medical Sciences (AREA)
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Bioinformatics & Cheminformatics (AREA)
Medicinal Chemistry (AREA)
Wood Science & Technology (AREA)
Biophysics (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Gastroenterology & Hepatology (AREA)
Biotechnology (AREA)
Toxicology (AREA)
General Engineering & Computer Science (AREA)
Microbiology (AREA)
Physics & Mathematics (AREA)
Plant Pathology (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Enzymes And Modification Thereof (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)
Steroid Compounds (AREA)

NO20014966A 1999-04-13 2001-10-12 Fremgangsmate for fremstilling av et biologisk aktivt cytokin og et cDNA NO329525B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
IL12942799A IL129427A0 (en)	1999-04-13	1999-04-13	Preparation of biologically active molecules
PCT/IL2000/000220 WO2000061768A2 (en)	1999-04-13	2000-04-13	Preparation of biologically active molecules

Publications (3)

Publication Number	Publication Date
NO20014966D0 NO20014966D0 (no)	2001-10-12
NO20014966L NO20014966L (no)	2001-12-11
NO329525B1 true NO329525B1 (no)	2010-11-01

Family

ID=11072700

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20014966A NO329525B1 (no)	1999-04-13	2001-10-12	Fremgangsmate for fremstilling av et biologisk aktivt cytokin og et cDNA

Country Status (23)

Country	Link
US (1)	US7098002B1 (de)
EP (1)	EP1169460B1 (de)
JP (1)	JP4822587B2 (de)
KR (1)	KR100682185B1 (de)
CN (1)	CN1324140C (de)
AR (1)	AR023468A1 (de)
AT (1)	ATE326536T1 (de)
AU (1)	AU781342B2 (de)
BR (1)	BR0009782A (de)
CA (1)	CA2368994C (de)
DE (1)	DE60028022T2 (de)
DK (1)	DK1169460T3 (de)
EA (1)	EA006825B1 (de)
EE (1)	EE05591B1 (de)
ES (1)	ES2259287T3 (de)
IL (3)	IL129427A0 (de)
MX (1)	MXPA01010487A (de)
NO (1)	NO329525B1 (de)
PT (1)	PT1169460E (de)
SI (1)	SI1169460T1 (de)
UA (1)	UA73940C2 (de)
WO (1)	WO2000061768A2 (de)
ZA (1)	ZA200108364B (de)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2001029232A2 (en) *	1999-10-20	2001-04-26	Scios Inc.	Functional cloning of genes encoding proteins/enzymes involved in proteolytic cleavage
US7273722B2 (en) *	2000-11-29	2007-09-25	Allergan, Inc.	Neurotoxins with enhanced target specificity
WO2002101049A2 (en)	2001-03-08	2002-12-19	Ares Trading S.A.	Interleukin-18 mutants, their production and use
IL142246A0 (en) *	2001-03-26	2002-03-10	Applied Research Systems	Method and kit for quantitation of polypeptides
CA2475177A1 (en)	2002-02-11	2003-08-21	Zymogenetics, Inc.	Materials and methods for preparing dimeric growth factors
ATE374825T1 (de) *	2003-02-21	2007-10-15	Biotecnol Sa	Verwendung von caspasen zur herstellung von reifen rekombinanten fusionsproteinen
CA2534629C (en) *	2003-08-06	2016-01-19	University Of Maryland Biotechnology Institute	Engineered proteases for affinity purification and processing of fusion proteins
CA2545024A1 (en) *	2003-11-24	2005-06-02	Novo Nordisk A/S	Fusion proteins and methods of cleavage of such proteins
ATE517914T1 (de)	2004-03-08	2011-08-15	Zymogenetics Inc	Dimere fusionsproteine und materialien und verfahren zu deren herstellung
ATE518882T1 (de)	2005-09-19	2011-08-15	Allergan Inc	Mit clostridientoxin aktivierbare clostridientoxine
JP5093783B2 (ja) *	2006-04-20	2012-12-12	クリングルファーマ株式会社	Ｈｇｆ前駆体蛋白質改変体及びその活性型蛋白質
DE102007008596B4 (de) *	2007-02-15	2010-09-02	Friedrich-Schiller-Universität Jena	Biologisch wirksame Moleküle auf Grundlage von PNA und siRNA, Verfahren zu deren zellspezifischen Aktivierung sowie Applikationskit zur Verabreichung
US20090304719A1 (en)	2007-08-22	2009-12-10	Patrick Daugherty	Activatable binding polypeptides and methods of identification and use thereof
WO2009044988A1 (en) *	2007-10-01	2009-04-09	Korea Research Institute Of Bioscience And Biotechnology	Method for large scale preparation of procaspases, which can be artificially activated, in e. coli expression system and their activation
DE102009043743B4 (de)	2009-03-13	2016-10-13	Friedrich-Schiller-Universität Jena	Zellspezifisch wirksame Moleküle auf Grundlage von siRNA sowie Applikationskits zu deren Herstellung und Verwendung
RU2636046C2 (ru)	2009-01-12	2017-11-17	Сайтомкс Терапьютикс, Инк	Композиции модифицированных антител, способы их получения и применения
AU2010215761B2 (en)	2009-02-23	2017-04-06	Cytomx Therapeutics, Inc	Proproteins and methods of use thereof
CN103923897B (zh) *	2013-01-11	2016-06-01	中国人民解放军军事医学科学院生物工程研究所	caspase重组酶原及其编码基因与应用
CN103388001B (zh) *	2013-07-16	2016-01-20	中国人民解放军第四军医大学	一种含凝血酶切割位点gst膜型表达载体及转染阳性细胞的方法
RU2711322C1 (ru)	2013-12-20	2020-01-16	Ф. Хоффманн-Ля Рош Аг	Улучшенные способы получения рекомбинантного полипептида
BR112017020690A2 (pt)	2015-03-30	2018-06-26	Greenlight Biosciences Inc	produção livre de células de ácido ribonucleico
HUE057952T2 (hu)	2015-06-24	2022-06-28	Hoffmann La Roche	Anti-transzferrin receptor antitestek testreszabott affinitással
TWI873952B (zh)	2015-10-02	2025-02-21	瑞士商赫孚孟拉羅股份公司	雙特異性抗‐人類cd20/人類轉鐵蛋白受體抗體及使用方法
AR106189A1 (es)	2015-10-02	2017-12-20	Hoffmann La Roche	ANTICUERPOS BIESPECÍFICOS CONTRA EL A-b HUMANO Y EL RECEPTOR DE TRANSFERRINA HUMANO Y MÉTODOS DE USO
CA3020312A1 (en)	2016-04-06	2017-10-12	Greenlight Biosciences, Inc.	Cell-free production of ribonucleic acid
KR102894284B1 (ko)	2017-10-11	2025-12-03	그린라이트 바이오사이언시스, 아이엔씨.	뉴클레오시드 트리포스페이트 및 리보핵산 생산을 위한 방법 및 조성물
KR20200080749A (ko) *	2018-12-27	2020-07-07	주식회사 폴루스	N-말단의 메티오닌이 절단된 목적 단백질 발현용 유전자 발현 카세트 및 이를 이용하여 n-말단의 메티오닌이 절단된 목적 단백질을 생산하는 방법
AU2020327671A1 (en) *	2019-08-13	2022-03-03	King's College London	Immunoresponsive cells armoured with spatiotemporally restricted activity of cytokines of the IL-1 superfamily

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5824297A (en) *	1990-06-25	1998-10-20	Oncogene Science, Inc.	Tissue-derived tumor growth inhibitors, methods of preparation and uses thereof
AU659412B2 (en) *	1990-06-25	1995-05-18	Osi Pharmaceuticals, Inc.	Tissue-derived tumor growth inhibitors
DE69229252T2 (de) *	1991-08-16	1999-12-16	Merck & Co., Inc.	DNS, welche das Interleukin-1B-Vorläufer-Converting-Enzym kodiert
AU683834B2 (en) *	1991-12-31	1997-11-27	Zymogenetics Inc.	Methods for producing thrombin
JPH06125784A (ja) *	1992-01-17	1994-05-10	Takeda Chem Ind Ltd	モノクローナル抗体，ハイブリドーマ，その製造法および用途
US6303369B1 (en) *	1993-09-30	2001-10-16	Carl Spana	Protein expression system
EP0870028A1 (de)	1995-12-29	1998-10-14	Incyte Pharmaceuticals, Inc.	Nukleinsäuren, die für interferon gamma-induzierenden faktor kodieren
JP4059941B2 (ja) *	1996-08-26	2008-03-12	社団法人芝蘭会	Ｒｈｏ標的タンパク質ｐ１４０ｍＤｉａ
AT405516B (de) *	1997-02-27	1999-09-27	Immuno Ag	Faktor x-analoge mit modifizierter proteasespaltstelle
JPH10327872A (ja) *	1997-05-30	1998-12-15	Otsuka Pharmaceut Co Ltd	Ｂｃｌ−２相互作用蛋白遺伝子ｂｉｓ
EP1013763B1 (de) *	1997-08-07	2011-02-02	Toray Industries, Inc.	Methode zur herstellung von canine interleukin 18

1999
- 1999-04-13 IL IL12942799A patent/IL129427A0/xx unknown
2000
- 2000-04-12 AR ARP000101692A patent/AR023468A1/es not_active Application Discontinuation
- 2000-04-13 MX MXPA01010487A patent/MXPA01010487A/es active IP Right Grant
- 2000-04-13 DE DE60028022T patent/DE60028022T2/de not_active Expired - Lifetime
- 2000-04-13 BR BR0009782-9A patent/BR0009782A/pt active Search and Examination
- 2000-04-13 CA CA002368994A patent/CA2368994C/en not_active Expired - Fee Related
- 2000-04-13 ES ES00919108T patent/ES2259287T3/es not_active Expired - Lifetime
- 2000-04-13 JP JP2000611691A patent/JP4822587B2/ja not_active Expired - Fee Related
- 2000-04-13 PT PT00919108T patent/PT1169460E/pt unknown
- 2000-04-13 KR KR1020017012973A patent/KR100682185B1/ko not_active Expired - Fee Related
- 2000-04-13 AT AT00919108T patent/ATE326536T1/de active
- 2000-04-13 DK DK00919108T patent/DK1169460T3/da active
- 2000-04-13 EP EP00919108A patent/EP1169460B1/de not_active Expired - Lifetime
- 2000-04-13 SI SI200030860T patent/SI1169460T1/sl unknown
- 2000-04-13 IL IL14584200A patent/IL145842A0/xx active IP Right Grant
- 2000-04-13 WO PCT/IL2000/000220 patent/WO2000061768A2/en not_active Ceased
- 2000-04-13 CN CNB008080577A patent/CN1324140C/zh not_active Expired - Fee Related
- 2000-04-13 EE EEP200100530A patent/EE05591B1/xx not_active IP Right Cessation
- 2000-04-13 AU AU39851/00A patent/AU781342B2/en not_active Ceased
- 2000-04-13 UA UA2001117751A patent/UA73940C2/uk unknown
- 2000-04-13 US US09/958,914 patent/US7098002B1/en not_active Expired - Fee Related
- 2000-04-13 EA EA200101078A patent/EA006825B1/ru not_active IP Right Cessation
2001
- 2001-10-10 IL IL145842A patent/IL145842A/en not_active IP Right Cessation
- 2001-10-11 ZA ZA200108364A patent/ZA200108364B/en unknown
- 2001-10-12 NO NO20014966A patent/NO329525B1/no not_active IP Right Cessation

Also Published As

Publication number	Publication date
NO20014966L (no)	2001-12-11
CN1353761A (zh)	2002-06-12
EP1169460A2 (de)	2002-01-09
EE200100530A (et)	2002-12-16
NO20014966D0 (no)	2001-10-12
DE60028022T2 (de)	2006-09-28
AU781342B2 (en)	2005-05-19
WO2000061768A3 (en)	2001-02-08
EA006825B1 (ru)	2006-04-28
IL145842A0 (en)	2002-07-25
CN1324140C (zh)	2007-07-04
EP1169460B1 (de)	2006-05-17
DE60028022D1 (de)	2006-06-22
ES2259287T3 (es)	2006-10-01
BR0009782A (pt)	2002-01-08
IL129427A0 (en)	2000-02-17
EE05591B1 (et)	2012-10-15
DK1169460T3 (da)	2006-09-18
KR20020007365A (ko)	2002-01-26
AR023468A1 (es)	2002-09-04
JP4822587B2 (ja)	2011-11-24
MXPA01010487A (es)	2002-05-06
CA2368994A1 (en)	2000-10-19
CA2368994C (en)	2010-03-09
ATE326536T1 (de)	2006-06-15
PT1169460E (pt)	2006-07-31
JP2002541813A (ja)	2002-12-10
SI1169460T1 (sl)	2006-08-31
WO2000061768A2 (en)	2000-10-19
HK1044351A1 (en)	2002-10-18
IL145842A (en)	2008-06-05
UA73940C2 (uk)	2005-10-17
US7098002B1 (en)	2006-08-29
AU3985100A (en)	2000-11-14
KR100682185B1 (ko)	2007-02-12
ZA200108364B (en)	2002-10-11
EA200101078A1 (ru)	2002-04-25

Legal Events

Date	Code	Title	Description
2016-11-28	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
NO329525B1 (no)	2010-11-01	Fremgangsmate for fremstilling av et biologisk aktivt cytokin og et cDNA
EP3423078A2 (de)	2019-01-09	T-zell-modulierende multimere polypeptide und verfahren zur verwendung davon
KR20130059404A (ko)	2013-06-05	원핵생물 발현 구축물
KR101026526B1 (ko)	2011-04-01	대장균에서 외래단백질을 분비 생산하는 방법
AU2002222454A1 (en)	2002-08-22	Improvement of homogeneity and secretion of recombinant proteins in mammalian systems
EP1339855A2 (de)	2003-09-03	Verbesserung der homogenität und sekretion von rekombinanten proteinen in säugetiersystemen
CN108192905A (zh)	2018-06-22	一种表达盒、表达载体、宿主菌及制备无标签重组人il37成熟肽的方法
AU2001280442B2 (en)	2005-10-27	Method for preparing a physiologically active il-18 polypeptide
AU2001280442A1 (en)	2002-03-21	Method for preparing a physiologically active IL-18 polypeptide
WO1997023639A1 (en)	1997-07-03	Process for producing biologically active fused proteins
JP3251592B2 (ja)	2002-01-28	Ｉｌ―１６活性を有するプロセスされたポリペプチド、それらの製法、及びそれらの使用
KR100899173B1 (ko)	2009-05-26	인간 유래 조직형 플라스미노겐 활성화 인자의 대량발현용 재조합 유전자 및 그 단백질의 재구성 방법
WO2025066945A1 (zh)	2025-04-03	人重组白细胞介素-7的表达纯化方法
ZA200209955B (en)	2004-04-08	Method for preparing a physiologically-18-polypeptide.
HK1044351B (en)	2007-11-02	Preparation of biologically active molecules
HK1055138B (en)	2010-02-26	Method for preparing a physiologically active il-18 polypeptide