FI105202B - Förfarande för framställning av aktiverbara fibrinolytiska och antikombotiska plasminogenanaloga - Google Patents
Förfarande för framställning av aktiverbara fibrinolytiska och antikombotiska plasminogenanaloga Download PDFInfo
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- FI105202B FI105202B FI922610A FI922610A FI105202B FI 105202 B FI105202 B FI 105202B FI 922610 A FI922610 A FI 922610A FI 922610 A FI922610 A FI 922610A FI 105202 B FI105202 B FI 105202B
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- plasminogen
- factor
- thrombin
- protein
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- 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
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6435—Plasmin (3.4.21.7), i.e. fibrinolysin
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/315—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Streptococcus (G), e.g. Enterococci
- C07K14/3153—Streptokinase
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- C07K14/815—Protease inhibitors from leeches, e.g. hirudin, eglin
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- C12N15/09—Recombinant DNA-technology
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- C12N15/62—DNA sequences coding for fusion proteins
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- 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
- C12N15/625—DNA sequences coding for fusion proteins containing a sequence coding for a signal sequence
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- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
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- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
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- 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
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6456—Plasminogen activators
- C12N9/6459—Plasminogen activators t-plasminogen activator (3.4.21.68), i.e. tPA
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- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21007—Plasmin (3.4.21.7), i.e. fibrinolysin
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- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21069—Protein C activated (3.4.21.69)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/001—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination
- C12N2830/002—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination inducible enhancer/promoter combination, e.g. hypoxia, iron, transcription factor
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- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/70—Vector systems having a special element relevant for transcription from fungi
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- C12N2840/00—Vectors comprising a special translation-regulating system
- C12N2840/10—Vectors comprising a special translation-regulating system regulates levels of translation
- C12N2840/107—Vectors comprising a special translation-regulating system regulates levels of translation inhibiting translational read-through
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Claims (6)
1. Förfarande för framställning av en plasminogenanalog som kan aktiveras med blodkoaguleringsenzym för att fa plasminaktivitet, kännetecknat av att värdcellen transfekteras eller transformeras med en expressionsvektor innehallande en DNA-5 sekvens som kodar nämnda plasminogenanalog, cellen odlas pä ett lämpligt växt-substrat under forhällanden som möjliggör expression av plasminogenanalogen och plasminogenanalogen atervinns ur odlingssubstratet, och att blodkoaguleringsenzy-met är kallikrein, faktor Xlla, XIa, IXa, Vila, Xa, trombin (faktor Ila) eller aktiverat protein C. 10
2. Förfarande enligt patentkrav 1, kännetecknat av att plasminogenanalogen in- nehaller en brytpunktssekvens a) P4-P3-Gly-Arg, i vilken P4 är en hydrofob rest och P3 en sur rest, b) P4-P3-Pro-Arg-Pl'-P2', i vilken saväl P4 som P3 är sinsemellan oberoende en hydrofob rest och säväl ΡΓ som P2' är oberoende en icke-sur rest, c) P2-Arg-Pl', i vilken den ena av restema P2 och ΡΓ är glycin och den andra vilken 15 som heist aminosyrarest och d) Gly-Pro-Arg.
3. Förfarande enligt patentkrav 1 eller 2, kännetecknat av att analogen innehäller en eller flera andra modifikationer (jämfört med en glu-plasminogen av vild typ), vilka kan vara en eller flera additioner, deletioner eller substitutioner.
4. Syntetisk eller rekombinant DNA-nukleinsyra, kännetecknad av att den kodar 20 en plasminogenanalog som kan aktiveras med ett blodkoaguleringsenzym för att er- hälla plasminaktivitet, varvid enzymet är kallikrein, faktor Xlla, XIa, IXa, Vila, Xa, trombin (faktor Ha) eller aktiverat protein C. •
5. Vektor, kännetecknad av att den innehäller en första nukleinsyra som kodar en plasminogenanalog enligt patentkrav 4 eller är associerad tili en kloningspunkt 25 som är funktionellt forbunden med en andra nukleinsyrasekvens som innehäller en stark promotor- och enhancersekvens som härletts frän mänskligt cytomegalovirus, en tredje nukleinsyrasekvens som kodar en polyadenyliseringssekvens som härletts ;; frän SV40, och en fjärde nukleinsyrasekvens som kodar ett valbart gpt-tecken som uttrycks ur SV40-promotom och som dessutom har en SV40-polyadenyliserings-30 signal vid 3’-änden av en valbar teckensekvens.
6. Cell eller cellinje, kännetecknad av att den ffamställts genom att transformera eller transfektera en cell eller cellinje med en nukleinsyra enligt patentkrav 4 eller 1' en vektor enligt patentkrav 5.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB898927722A GB8927722D0 (en) | 1989-12-07 | 1989-12-07 | Proteins and nucleic acids |
GB8927722 | 1989-12-07 | ||
GB9001912 | 1990-12-07 | ||
PCT/GB1990/001912 WO1991009118A2 (en) | 1989-12-07 | 1990-12-07 | Activatable fibrinolytic and anti-thrombotic proteins |
Publications (3)
Publication Number | Publication Date |
---|---|
FI922610A FI922610A (fi) | 1992-06-05 |
FI922610A0 FI922610A0 (fi) | 1992-06-05 |
FI105202B true FI105202B (sv) | 2000-06-30 |
Family
ID=10667597
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
FI922609A FI922609A (fi) | 1989-12-07 | 1992-06-05 | Proteiner och nukleinsyror. |
FI922610A FI105202B (sv) | 1989-12-07 | 1992-06-05 | Förfarande för framställning av aktiverbara fibrinolytiska och antikombotiska plasminogenanaloga |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
FI922609A FI922609A (fi) | 1989-12-07 | 1992-06-05 | Proteiner och nukleinsyror. |
Country Status (21)
Country | Link |
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US (2) | US5637492A (sv) |
EP (2) | EP0504241A1 (sv) |
JP (2) | JPH05502374A (sv) |
KR (2) | KR920703818A (sv) |
AT (1) | ATE155812T1 (sv) |
AU (3) | AU644399B2 (sv) |
CA (2) | CA2069085C (sv) |
DE (1) | DE69031127T2 (sv) |
DK (1) | DK0502968T3 (sv) |
ES (1) | ES2106073T3 (sv) |
FI (2) | FI922609A (sv) |
GB (1) | GB8927722D0 (sv) |
GR (1) | GR3024990T3 (sv) |
HU (1) | HU211628A9 (sv) |
IE (2) | IE81046B1 (sv) |
IL (2) | IL96601A (sv) |
NO (2) | NO305562B1 (sv) |
NZ (2) | NZ236330A (sv) |
PT (2) | PT96103B (sv) |
WO (2) | WO1991009125A1 (sv) |
ZA (2) | ZA909853B (sv) |
Families Citing this family (59)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CU22277A1 (es) * | 1990-05-23 | 1995-01-31 | Cigb | Procedimiento para el aislamiento y expresion de un gen codificante para estreptoquinasa,secuencia nucleotidica obtenida,adn recombinantes y microorganismos transformados |
GB9222758D0 (en) * | 1992-10-29 | 1992-12-09 | British Bio Technology | Proteins and nucleic acids |
GB9216558D0 (en) * | 1992-08-04 | 1992-09-16 | British Bio Technology | Modified proteases |
GB2286190B (en) * | 1992-10-29 | 1996-05-01 | British Biotech Pharm | Thrombin activatable plasminogen derivatives |
DE4323754C1 (de) * | 1993-07-15 | 1994-12-01 | Gruenenthal Gmbh | Bifunktionelle Urokinasevarianten mit verbesserten fibrinolytischen Eigenschaften und thrombinhemmender Wirkung |
SG49862A1 (en) * | 1993-08-04 | 2002-03-19 | Ucp Gen Pharma Ag | High molecular weight desulphatohirudin |
ES2080657B1 (es) * | 1993-09-27 | 1996-11-01 | Britisch Bio Technology Limite | Proteasas modificadas. |
US5945403A (en) | 1997-05-30 | 1999-08-31 | The Children's Medical Center Corporation | Angiostatin fragments and method of use |
US5837682A (en) | 1996-03-08 | 1998-11-17 | The Children's Medical Center Corporation | Angiostatin fragments and method of use |
JP3880064B2 (ja) * | 1994-04-26 | 2007-02-14 | ザ チルドレンズ メディカル センター コーポレイション | アンジオスタチンおよび血管形成の抑制におけるその使用 |
GB9412131D0 (en) * | 1994-06-17 | 1994-08-10 | British Bio Technology | Thrombolytic composition |
DE4440892A1 (de) * | 1994-11-17 | 1996-05-23 | Gruenenthal Gmbh | Proteine mit fibrinolytischen und gerinnungshemmenden Eigenschaften |
DE4442665A1 (de) * | 1994-11-30 | 1996-06-05 | Gruenenthal Gmbh | Chimäre Proteine mit fibrinolytischen und thrombinhemmenden Eigenschaften |
US5854049A (en) * | 1995-06-09 | 1998-12-29 | President And Fellows Of Harvard College | Plasmin-resistant streptokinase |
US5736364A (en) * | 1995-12-04 | 1998-04-07 | Genentech, Inc. | Factor viia inhibitors |
US6461640B1 (en) | 1995-12-08 | 2002-10-08 | Board Of Regents, The University Of Texas System | Local delivery of fibrinolysis enhancing agents |
CA2262751A1 (en) * | 1996-08-02 | 1998-02-12 | Roche Diagnostics Gmbh | Plasminogen activator capable of being activated by thrombin |
DE69833755T2 (de) * | 1997-05-21 | 2006-12-28 | Biovation Ltd. | Verfahren zur herstellung von nicht-immunogenen proteinen |
PT947585E (pt) | 1998-03-19 | 2001-11-30 | Instrumentation Lab Spa | Metodo in vitro melhorado, kits e reagentes para a peaquisa de defeitos de coagulacao sanguinea |
WO2000010506A2 (en) | 1998-08-20 | 2000-03-02 | University Of Vermont And State Agriculture College | Angiogenesis inhibitors and uses thereof |
IN190822B (sv) * | 1998-12-24 | 2003-08-23 | Council Scient Ind Res | |
WO2001036351A2 (en) | 1999-11-19 | 2001-05-25 | Corvas International, Inc. | Plasminogen activator inhibitor antagonists related applications |
US20030211094A1 (en) | 2001-06-26 | 2003-11-13 | Nelsestuen Gary L. | High molecular weight derivatives of vitamin k-dependent polypeptides |
US6423826B1 (en) * | 2000-06-30 | 2002-07-23 | Regents Of The University Of Minnesota | High molecular weight derivatives of vitamin K-dependent polypeptides |
US7160540B2 (en) | 2000-06-30 | 2007-01-09 | Regents Of The University Of Minnesota | Methods for detecting activity of clottings factors |
JP2004508048A (ja) * | 2000-09-05 | 2004-03-18 | カロリンスカ イノベーションズ アクティーエボラーグ | 内皮細胞増殖阻害物質に関する材料と方法 |
DE10108212A1 (de) * | 2001-02-20 | 2002-08-22 | Aventis Pharma Gmbh | Fusionsprotein zur Sekretion von Wertprotein in bakterielle Überstände |
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