FI106029B - Föbättrad aktivering av rekombinant DNA proteiner - Google Patents

Föbättrad aktivering av rekombinant DNA proteiner Download PDF

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Publication number
FI106029B
FI106029B FI920742A FI920742A FI106029B FI 106029 B FI106029 B FI 106029B FI 920742 A FI920742 A FI 920742A FI 920742 A FI920742 A FI 920742A FI 106029 B FI106029 B FI 106029B
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FI
Finland
Prior art keywords
pro
seq
arg
met
lys
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FI920742A
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English (en)
Finnish (fi)
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FI920742A0 (fi
FI920742A (fi
Inventor
Carola Dony
Dorothea Ambrosius
Rainer Rudolph
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Roche Diagnostics Gmbh
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Application filed by Roche Diagnostics Gmbh filed Critical Roche Diagnostics Gmbh
Publication of FI920742A0 publication Critical patent/FI920742A0/fi
Publication of FI920742A publication Critical patent/FI920742A/fi
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Publication of FI106029B publication Critical patent/FI106029B/sv

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • 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
    • C07K14/53—Colony-stimulating factor [CSF]
    • C07K14/535—Granulocyte CSF; Granulocyte-macrophage CSF
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/06—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents
    • C07K1/08—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents using activating agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
    • C07K1/113—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure
    • C07K1/1136—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure by reversible modification of the secondary, tertiary or quarternary structure, e.g. using denaturating or stabilising agents
    • 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
    • C12N15/62—DNA sequences coding for fusion proteins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • General Engineering & Computer Science (AREA)
  • Analytical Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • Immunology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Adhesives Or Adhesive Processes (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Adhesive Tapes (AREA)
  • Dental Preparations (AREA)
  • Manufacture Of Macromolecular Shaped Articles (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Claims (12)

1. Förfarande för att aktivera rekombinant-DNA-tekniska protei-ner som är i ätminstone delvis inaktiv form, känneteck-n a t av att med användning av i och för sig kända upplösnings-och/eller renatureringstekniker aktiveras ett protein vars N- 10 och/eller C-terminal innefattar extra hjälpsekvenser med en längd pä 2-50 aminosyror, varvid hjälpsekvensernas relativa hyd-rofobitet har ett negativt talvärde beräknat som summan av de relativa hydrofobiteterna hos de enskilda aminosyrorna som visas i tabell 1. 15
2. Förfarande enligt patentkrav 1, kännetecknat av att i hjälpsekvenserna är förhällandet mellan relativ hydrofobi-tet och antalet aminosyror -2,0 kcal/mol eller lägre. 20
3. Förfarande enligt nägot av föregäende patentkrav, k ä n n e - tecknat av att hjälpsekvenserna är anslutna tili N-termi-nalen av proteinet som skall aktiveras.
• · ·.**: 4. Förfarande enligt nägot av föregäende patentkrav, k ä n n e- ♦ #2f? tecknat av att hjälpsekvenserna är anslutna till C-termi-nalen av proteinet som skall aktiveras. « • · · « · • · »·1
: 5. Förfarande enligt nägot av föregäende patentkrav, k ä n n e - • · tecknat av att hjälpsekvenserna innehäller minst tvä ami- ♦ · · • $0 nosyror valda bland glutamin, aspartat, lycin, arginin och pro- lin. « « • t • « € 1 “ ♦ < 1 « « ««1'
6. Förfarande enligt patentkrav 5, kännetecknat av att hjälpsekvenserna innehäller minst tvä glutamatrester. 4 3151: • « · • · · • · • · · « • · • · • 1 1 22 106029
7. Förfarande enligt patentkrav 5 eller 6, känneteck-n a t av att hjälpsekvenserna innehäller direkt efter varandra tvä med samma förtecken laddade aminosyror valda bland glutamat, aspartat, lycin och arginin. 5
8. Förfarande enligt patentkrav 7, kännetecknat av att hjälpsekvenserna innehäller tvä glutamatrester direkt efter varandra. 10
9. Förfarande enligt nägot av föregäende patentkrav, kanne - tecknat av att proteinerna sorti skall aktiveras innefattar en spjälkningspunkt pä fogpunkten mellan hjälpsekvensen och det önskade proteinet. 15
10. Förfarande enligt patentkrav 9, kännetecknat av att spjälkningspunkten är spjälkningspunkten för IgA-proteas.
11. Förfarande enligt nägot av föregäende patentkrav, kännetecknat av att N-terminalen hos proteinet sora skall akti- 20 veras har en hjälpsekvens med nägon av följande sekvenser: Met-Glu (SEQ ID NO: 1) Met-Thr-Pro-Leu-Pro-Arg-Pro-Pro (SEQ ID NO: 2) Met-Thr-Pro-Leu-His-His-Pro-Arg-Pro-Pro (SEQ ID NO: 3) .^5 Met-Thr-Pro-Leu-Lys-Lys-Pro-Arg-Pro-Pro (SEQ ID NO: 4) « · Met-Thr-Pro-Leu-Glu-Glu-Gly-Pro-Arg-Pro-Pro (SEQ ID NO: 5) :·. Met-Thr- Pro-Leu-Glu-Glu-Gly-Thr- Pro-Leu- Pro-Arg- Pro- Pro • · · (SEQ ID NO: 6) Met-Thr-Pro-Leu-Glu-Glu-Gin-Pro-Pro (SEQ ID NO: 7) • · · 0* Met - Lys - Ala - Lys - Arg - Phe - Lys - Lys - His - Pro - Arg - Pro - Pro :·: ! (SEQ ID NO: 8) Met-Thr-Pro-Leu-Glu-Glu-Gly-Ile-Glu-Gly-Arg (SEQ ID NO: 9) • · · Met-Thr-Pro-Leu-Lys-Ala-Lys-Arg-Phe-Lys-Lys-His-Pro-Arg-Pro-Pro •‘j (SEQ ID NO: 10) £5 I « <
12. Förfarande enligt nägot av föregäende patentkrav, k ä n n e- f * < * tecknat av att proteinet som skall aktiveras är en faktor «a · • *.· (G-CSF) som stimulerar granulocytkolonier eller dess derivat. « « « a · • · • · »
FI920742A 1991-02-21 1992-02-20 Föbättrad aktivering av rekombinant DNA proteiner FI106029B (sv)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE4105480A DE4105480A1 (de) 1991-02-21 1991-02-21 Verbesserte aktivierung von rekombinanten proteinen
DE4105480 1991-02-21

Publications (3)

Publication Number Publication Date
FI920742A0 FI920742A0 (fi) 1992-02-20
FI920742A FI920742A (fi) 1992-08-22
FI106029B true FI106029B (sv) 2000-11-15

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ID=6425597

Family Applications (1)

Application Number Title Priority Date Filing Date
FI920742A FI106029B (sv) 1991-02-21 1992-02-20 Föbättrad aktivering av rekombinant DNA proteiner

Country Status (20)

Country Link
US (1) US5578710A (sv)
EP (1) EP0500108B1 (sv)
JP (1) JP2528232B2 (sv)
KR (1) KR950014493B1 (sv)
AT (1) ATE144284T1 (sv)
AU (1) AU641081B2 (sv)
CA (1) CA2061569C (sv)
CZ (1) CZ282744B6 (sv)
DE (2) DE4105480A1 (sv)
DK (1) DK0500108T3 (sv)
ES (1) ES2093122T3 (sv)
FI (1) FI106029B (sv)
GR (1) GR3021395T3 (sv)
HU (1) HU214881B (sv)
IE (1) IE920276A1 (sv)
IL (1) IL101024A (sv)
MX (1) MX9200709A (sv)
NO (1) NO300329B1 (sv)
NZ (1) NZ241570A (sv)
ZA (1) ZA921230B (sv)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5718893A (en) * 1984-04-15 1998-02-17 Foster; Preston F. Use of G-CSF to reduce acute rejection
US5581476A (en) 1993-01-28 1996-12-03 Amgen Inc. Computer-based methods and articles of manufacture for preparing G-CSF analogs
SE9301057L (sv) * 1993-03-30 1994-10-01 Pharmacia Ab Beredning med kontrollerad frisättning
US5536495A (en) * 1994-04-15 1996-07-16 Foster; Preston F. Use of G-CSF to reduce acute rejection
US20030053982A1 (en) 1994-09-26 2003-03-20 Kinstler Olaf B. N-terminally chemically modified protein compositions and methods
US5824784A (en) 1994-10-12 1998-10-20 Amgen Inc. N-terminally chemically modified protein compositions and methods
US6245740B1 (en) 1998-12-23 2001-06-12 Amgen Inc. Polyol:oil suspensions for the sustained release of proteins
JP2004524005A (ja) 2000-09-08 2004-08-12 マサチューセッツ　インスティテュート　オブ　テクノロジー Ｇ−ｃｓｆアナログ組成物および方法
CA2438652A1 (en) 2001-02-19 2002-09-06 Merck Patent Gesellschaft Mit Beschraenkter Haftung Method for identification of t-cell epitopes and use for preparing molecules with reeduced immunogenicity
EP1425304B9 (en) 2001-07-11 2010-09-08 Maxygen, Inc. G-csf conjugates
KR100508358B1 (ko) 2002-03-20 2005-08-17 주식회사 바이오폴리메드 생체적합성 고분자가 시스테인 잔기에 화학양론적으로 결합된 ｇ-ｃｓｆ의 제조 방법
US7666627B2 (en) * 2002-08-08 2010-02-23 Targetex Kft. Folded recombinant catalytic fragments of multidomain serine proteases, preparation and uses thereof
US7695723B2 (en) 2002-12-31 2010-04-13 Sygnis Bioscience Gmbh & Co. Kg Methods of treating neurological conditions with hematopoietic growth factors
US7785601B2 (en) 2002-12-31 2010-08-31 Sygnis Bioscience Gmbh & Co. Kg Methods of treating neurological conditions with hematopoietic growth factors
US7220407B2 (en) 2003-10-27 2007-05-22 Amgen Inc. G-CSF therapy as an adjunct to reperfusion therapy in the treatment of acute myocardial infarction
WO2006055260A2 (en) 2004-11-05 2006-05-26 Northwestern University Use of scf and g-csf in the treatment of cerebral ischemia and neurological disorders
BRPI0611221A2 (pt) 2005-06-01 2010-08-24 Maxygen Holdings Ltd polipeptÍdeos de g-csf peguilados e mÉtodos de produÇço dos mesmos
WO2008014252A2 (en) * 2006-07-24 2008-01-31 Tetralogic Pharmaceuticals Corporation Iap inhibitors
WO2009023566A2 (en) 2007-08-09 2009-02-19 Genzyme Corporation Method of treating autoimmune disease with mesenchymal stem cells
US8758761B2 (en) 2007-09-30 2014-06-24 University Of Florida Research Foundation, Inc. Combination therapies for treating type 1 diabetes
US8283372B2 (en) 2009-07-02 2012-10-09 Tetralogic Pharmaceuticals Corp. 2-(1H-indol-3-ylmethyl)-pyrrolidine dimer as a SMAC mimetic
KR101857825B1 (ko) 2010-03-04 2018-05-14 피페넥스 인크. 변성 없이 가용성 재조합 인터페론 단백질을 제조하는 방법
NZ601759A (en) 2010-03-17 2013-07-26 Biogenerix Gmbh Method for obtaining biologically active recombinant human g-csf
WO2011123570A2 (en) 2010-04-01 2011-10-06 Pfenex Inc. Methods for g-csf production in a pseudomonas host cell
MX2015000683A (es) * 2012-08-02 2015-04-10 Hoffmann La Roche Metodo para producir moleculas monomericas y multimericas y uso de las mismas.

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4532207A (en) * 1982-03-19 1985-07-30 G. D. Searle & Co. Process for the preparation of polypeptides utilizing a charged amino acid polymer and exopeptidase
DK55685A (da) * 1985-02-07 1986-08-08 Nordisk Gentofte Enzym eller enzymkompleks med proteolytisk aktivitet
US4530787A (en) * 1984-03-28 1985-07-23 Cetus Corporation Controlled oxidation of microbially produced cysteine-containing proteins
US5082775A (en) * 1984-05-11 1992-01-21 Berlex Laboratories, Inc. Efficient process for isolating insoluble heterologous protein using non-ionic detergents
US4948729A (en) * 1985-03-25 1990-08-14 Cetus Corporation Production of soluble recombinant proteins
US4783415A (en) * 1985-03-28 1988-11-08 Meiji Seika Kabushiki Kaisha Gene coding for signal peptides and utilization thereof
US5087564A (en) * 1985-06-20 1992-02-11 Monsanto Company Release of recombinant peptides from polypeptides using V8 endopeptidase
DE3636903A1 (de) * 1985-12-21 1987-07-02 Hoechst Ag Fusionsproteine mit eukaryotischem ballastanteil
JPH0618781B2 (ja) * 1986-10-18 1994-03-16 中外製薬株式会社 感染症治療剤
US5013653A (en) * 1987-03-20 1991-05-07 Creative Biomolecules, Inc. Product and process for introduction of a hinge region into a fusion protein to facilitate cleavage
AU605291B2 (en) * 1987-03-20 1991-01-10 Micromet Ag Process for the purification of recombinant polypeptides
JPH03503596A (ja) * 1987-06-24 1991-08-15 ノボ・ノルディスク　エー／エス 蛋白質若しくはポリペプチドの調製方法、該ポリペプチドをコードするｄｎａ配列、該ｄｎａ配列およびポリペプチドを有する微生物および該ポリペプチドの薬学的製剤としての利用
DE3835350A1 (de) * 1988-10-17 1990-04-19 Boehringer Mannheim Gmbh Aktivierung von gentechnologisch hergestellten, in prokaryonten exprimierten antikoerpern
ZA901719B (en) * 1989-03-19 1991-01-30 Akzo Nv Hog cholera virus vaccine and diagnostics
US5191063A (en) * 1989-05-02 1993-03-02 University Of Medicine And Dentistry Of New Jersey Production of biologically active polypeptides by treatment with an exogenous peptide sequence
US5115102A (en) * 1989-07-21 1992-05-19 Monsanto Company Variant proteins and polypeptides possessing enhanced affinity for immobilized-metal affinity matrices
JPH06500084A (ja) * 1990-08-20 1994-01-06 ノボ　ノルディスク　アクティーゼルスカブ 生物学的に活性な化合物、その製造方法及びその利用

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Publication number Publication date
NO920671D0 (no) 1992-02-20
HU214881B (hu) 1998-07-28
CA2061569C (en) 2000-10-24
US5578710A (en) 1996-11-26
FI920742A0 (fi) 1992-02-20
IE920276A1 (en) 1992-08-26
EP0500108A3 (en) 1993-04-07
NZ241570A (en) 1994-09-27
ES2093122T3 (es) 1996-12-16
ATE144284T1 (de) 1996-11-15
DE59207351D1 (de) 1996-11-21
HUT68021A (en) 1995-04-04
MX9200709A (es) 1992-09-01
CA2061569A1 (en) 1992-08-22
JPH05244977A (ja) 1993-09-24
EP0500108A2 (de) 1992-08-26
IL101024A (en) 1996-06-18
FI920742A (fi) 1992-08-22
AU1094892A (en) 1992-08-27
EP0500108B1 (de) 1996-10-16
GR3021395T3 (en) 1997-01-31
DE4105480A1 (de) 1992-08-27
CZ282744B6 (cs) 1997-09-17
ZA921230B (en) 1992-11-25
DK0500108T3 (da) 1997-03-24
JP2528232B2 (ja) 1996-08-28
NO920671L (no) 1992-08-24
AU641081B2 (en) 1993-09-09
KR950014493B1 (ko) 1995-12-02
IL101024A0 (en) 1992-11-15
NO300329B1 (no) 1997-05-12
CS49992A3 (en) 1992-09-16
HU9200548D0 (en) 1992-04-28
KR920016464A (ko) 1992-09-24

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