FI109810B - Förfarande för enzymatisk spaltning av rekombinanta proteiner med användning av IgA-proteiner - Google Patents
Förfarande för enzymatisk spaltning av rekombinanta proteiner med användning av IgA-proteiner Download PDFInfo
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- C07K14/53—Colony-stimulating factor [CSF]
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- C07K—PEPTIDES
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Claims (36)
1. Förfarande för enzymatisk spjälkning av sammansmälta 25 proteiner och utvinning av önskvärda partier av dessa sam- t ,'· mansmälta proteiner, kännetecknat av att man :* (1) med gentekniska medel modifierar en övergängsregion *; väri tvä partier av det sammansmälta proteinet är förbundna ,· med varandra, sälunda att i denna övergängsregion bildas 3 0 ätminstone ett IgA-proteas-igenkänningsställe med aminosy- rasekvensen Y-Pro ! X-Pro, väri X kan utgöras av en godtyck- , . lig aminosyra och Y kan utgöras av en eller flera godtyck- » * · liga aminosyror, ·;· (2) spjälkar det i steg (1) bildade sammansmälta proteinet ; ; : 35 medelst IgA-proteas i den med ! betecknade positionen i igenkänningsstället och (3) utvinner efter spjälkningen ett eller flera önskvärda ;;; partier av det sammansmälta proteinet, varvid det samman- 4i 109810 smälta proteinet ej innehäller nägra polypeptidpartier, som kodas av nägot genavsnitt hos en gen för en IgA-proteas-fö-relöpare, som omfattar de naturliga IgA-proteas-igenkän-ningsställena. 5
2. Förfarande enligt patentkrav 1, kannetecknat av att man ästadkommer modifieringen av övergängsregionen hos ett sam-mansmält protein genom inneslutning av nukleotidsekvenser, som kodar ett IgA-proteas-igenkänningsställe eller en del 10 därav, varvid nukleotidsekvenserna inlägges före och/eller efter ett eller flera DNA-avsnitt, som kodar önskvärda par-tier av det sammansmälta proteinet.
3. Förfarande enligt patentkrav 1 eller 2, kännetecknat av 15 att man modifierar ett sammansmält protein, som ursprung- ligen ej uppvisar nägot naturligt IgA-igenkänningsställe.
4. Förfarande enligt nägot föregäende patentkrav, känne-tecknat av att man modifierar övergängsregionen hos ett 20 sammansmält protein, som förutom ett önskvärt parti ocksä innehäller ett eller flera bärarpartier.
5. Förfarande enligt patentkrav 4, kännetecknat av att bä-rarpartiet hos det sammansmälta proteinet innehäller ett . 25 parti av β-galaktosidas. »
6. Förfarande enligt patentkrav 4, kännetecknat av att bä- ! rarpartiet hos det sammansmälta proteinet innehäller flera laddade aminosyror och/eller ett protein eller en polypep-30 tid som binds med hög affinitet vid specifika substanser.
7. Förfarande enligt nägot av föregäende patentkrav, kän- : netecknat av att X betecknar Ser, Thr eller Ala. , 35 8. Förfarande enligt patentkrav 7, kännetecknat av att X betecknar Ser eller Thr. 42 109810
9. Förfarande enligt nägot av föregäende patentkrav, kanne-tecknat av att Y avslutas av sekvensen Pro, Pro-Ala, Arg-Pro, Pro-Arg-Pro, Ala-Pro-Arg-Pro eller Pro-Ala-Pro-Arg-Pro. 5
10. Förfarande enligt patentkrav 9, kännetecknat av att IgA-proteas-igenkänningsstället uppvisar aminosyrasekvensen a) Pro-Ala-Pro1Ser-Pro, 10 b) Pro-Pro!Ser-Pro, c) Pro-Arg-Pro-Pro ’ Ala-Pro, d) Pro-Pro ! Thr-Pro, e) Ala-Pro-Arg-Pro-Pro ' Thr-Pro eller f) Pro-Ala-Pro-Arg-Pro-Pro!Thr-Pro 15
11. Förfarande enligt nägot av föregäende patentkrav, kännetecknat av att man (1) transformerar en cell med ett rekombinant DNA och/eller en rekombinant vektor, varvid nämnda DNA respektive vektor 2. innehäller minst en kopia av en gen som kodar ett samman-smält protein som innehäller ätminstone ett IgA-proteas-igenkänningsställe i en övergängsregion, (2) odlar den transformerade cellen i ett lämpligt medium, (3) bringar genen som kodar det sammansmälta proteinet att • 25 uttryckas i den transformerade cellen, , (4) spjälkar det sammansmälta proteinet med IgA-proteas och •it (5) isolerar ett eller flera önskvärda partier av det sam- 1 mansmälta proteinet. ’· 30 12. Förfarande enligt patentkrav 11, kännetecknat av att Ϊ · det sammansmälta proteinet spjälkas i mediet efter cellupp-slutning och/eller efter avskiljande av cellulära proteiner ’·· med ett IgA-proteas. 35 13. Förfarande enligt nägot av föregäende patentkrav, kän- ► » netecknat av att man använder för spjälkning av det samman-'/ smälta proteinet ett IgA-proteas, som härstammar frän patois gena bakteriearter av släktet Neisseria speciellt Neisseria • I » « 109810 gonorrhoeae och Neisseria meningitidis eller av släktet Haemophilus, speciellt Haemophilus influenzae och Haemophilus aegypticus, eller ett protein som härletts ur lik-nande IgA-proteas genom modifiering. 5
14. Förfarande enligt patentkrav 13, kännetecknat av att man använder ett IgA-proteas för spjälkningen av det sam-mansmälta proteinet, som utvunnits fran en överproduceran-de, icke-patogen bakteriestam. 10
15. Förfarande enligt patentkrav 13 eller 14, käxmetecknat av att man använder IgA-proteaset i immobiliserad form för spjälkningen av det sammansmälta proteinet. 15 16. Förfarande enligt nägot av patentkraven 11-15, känne- tecknat av att man spjälkar ett saxnmansmält protein, som föreligger i löslig, olöslig, membranassocierad eller cell-bunden form. 20 17. Förfarande enligt patentkrav 16, kännetecknat av att man spjälkar ett sammansmält protein som föreligger säsom en olöslig utfällningskropp.
18. Förfarande enligt nägot av föregäende patentkrav, kän-25 netecknat av att man för framställning av rekombinanta pro- teiner frän prokaryota celler utan N-terminal metioningrupp spjälkar ett sammansmält protein med sekvensen Met-Y- • t Pro 1 X-Pro-A, väri A betecknar en godtycklig aminosyra och » Y betecknar en eller flera godtyckliga aminosyror och A be-30 tecknar en godtycklig aminosyrasekvens, med ett IgA-pro- teas, varvid ett protein respektive en peptid med amino-syrasekvensen X-Pro-A erhälles säsom spjälkningsprodukt. ! » » » ( · t »
19. Förfarande enligt patentkrav 18, kännetecknat av att ,·, 35 det önskvärda partiet av det sammansmälta proteinet börjar i · !.* med aminosyrasekvensen X-Pro. ' I I » I 44 109810
20. Förfarande enligt patentkrav 18, kännetecknat av att man efter spjälkning med IgA-proteaset behandlar det önsk-värda partiet av det sammansmälta proteinet i ytterligare ett steg med ett dipeptidyl-aminopeptidas och avspjälkar pä 5 detta sätt den N-terminala sekvensen X-Pro.
21. Förfarande enligt patentkrav 20, kännetecknat av att man för avspjälkning av den N-terminala sekvensen X-Pro an-vänder ett X-Pro-dipeptidyl-aminopeptidas. 10
22. Förfarande enligt nagot av föregäende patentkrav, kännetecknat av att X-Pro-A betecknar human granulocyt-koloni-stimulerande faktor (G-CSF) eller ett derivat därav. 15 23. Förfarande enligt patentkrav 22, kännetecknat av att X- Pro-A är en rekombinant-G-CSF som härstammar frän prokaryo-ter eller ett rekombinant-G-CSF-derivat, som inte har N-terminal metioninrest, och att G-CSF eller G-CSF-derivatet är väsentligen fritt frän G-CSF som härstammar frän proka-20 ryoter och har en N-terminal metioninrest.
24. Förfarande enligt patentkrav 23, kännetecknat av att G-CSF eller G-CSF-derivatet är under 0,1 % kontaminerat med andra proteiner. 25 ·. 25. Förfarande enligt patentkrav 23 eller 24, kännetecknat av att G-CSF eller G-CSF-derivatet är under 10~3 % kontami-.! nerat med andra proteiner och kvantitativt fritt frän G-CSF med N-terminal metioninrest. 30
26. Sammansmält protein som innehäller flera polypeptidpar-tier, kännetecknat av att det uppvisar i minst en över-gängsregion mellan ifrägavarande polypeptidpartier ett el-' '· ler flera med gentekniska medel infört IgA-proteas-igen- 35 känningsställen med aminosyrasekvensen Y-Pro'' X-Pro, väri X i · betecknar en godtycklig aminosyra, företrädesvis Ser, Thr t 1’ eller Ala, och Y kan vara en eller flera godtyckliga amino- ;,· syror, varvid det sammansmälta proteinet ej innehäller näg- * - i · « 109810 ra polypeptidpartier, som kodas av nagot genavsnitt hos en gen för en IgA-proteas-förelöpare, som omfattar de natur-liga IgA-proteas-igenkänningsställena.
27. Sammansmält protein enligt patentkrav 26, kännetecknat av att det uppvisar aminosyrasekvensen Met-Y-Pro ! X-Pro-A, väri X och Y har ovan angiven betydelse och A betecknar en godtycklig aminosyrasekvens.
28. Sammansmält protein enligt patentkrav 26 eller 27, kän netecknat av att Y innehäller sekvensen Pro, Pro-Ala, Pro-Arg-Pro, Ala-Pro-Arg-Pro eller Pro-Ala-Pro-Arg-Pro i sin ände.
29. Sammansmält protein enligt nagot av patentkraven 26-28, kännetecknat av att aminosyrasekvensen X-Pro-A betecknar en human granulocyt-koloni-stimulerande faktor (G-CSF) eller ett derivat därav.
30. Rekombinant DNA, kännetecknat av att det kodar ett sam mansmält protein enligt nagot av patentkraven 26-29.
31. Rekombinant vektor, kännetecknad av att den innehäller en eller flera kopior av ett rekombinant DNA enligt patent- 25 krav 30. t t *
32. Rekombinant vektor enligt patentkrav 31, kännetecknad ! av att nämnda rekombinanta DNA star under kontroll av en ', inducerbar expressionssignal. 30 : t
33. Rekombinant vektor enligt patentkrav 31 eller 32, kännetecknad av att den utgöres av en prokaryot vektor. : 34. Rekombinant vektor enligt nagot av patentkraven 30-32, 35 kännetecknad av att den utgörs av en plasmid. * · • » • » t » i I > » » 46 1 0 9 8 1 0
35. Cell, kannetecknad av att den är transformerad med ett DNA enligt patentkrav 30 eller en vektor enligt patentkrav 31-34.
36. Cell enligt patentkrav 35, kännetecknad av att den ut- göres av en prokaryot cell. » > ♦ < · > · * » * I * « ·
5. I i t ! * I •
Applications Claiming Priority (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4003149 | 1990-02-03 | ||
| DE4003149 | 1990-02-03 | ||
| DE4015921 | 1990-05-17 | ||
| DE4015922A DE4015922A1 (de) | 1990-05-17 | 1990-05-17 | Verfahren zur enzymatischen prozessierung von proteinen unter verwendung von iga-proteasen (igase) |
| DE4015921 | 1990-05-17 | ||
| DE4015922 | 1990-05-17 | ||
| DE4039415A DE4039415A1 (de) | 1990-02-03 | 1990-12-10 | Verfahren zur herstellung rekombinanter proteine ohne n-terminalen methioninrest |
| DE4039415 | 1990-12-10 | ||
| EP9100192 | 1991-02-01 | ||
| PCT/EP1991/000192 WO1991011520A1 (de) | 1990-02-03 | 1991-02-01 | VERFAHREN ZUR ENZYMATISCHEN SPALTUNG REKOMBINANTER PROTEINE UNTER VERWENDUNG VON IgA-PROTEASEN |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI923463A FI923463A (fi) | 1992-07-31 |
| FI923463A0 FI923463A0 (fi) | 1992-07-31 |
| FI109810B true FI109810B (sv) | 2002-10-15 |
Family
ID=27434868
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI923463A FI109810B (sv) | 1990-02-03 | 1992-07-31 | Förfarande för enzymatisk spaltning av rekombinanta proteiner med användning av IgA-proteiner |
Country Status (19)
| Country | Link |
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| US (1) | US5427927A (sv) |
| EP (2) | EP0513073B1 (sv) |
| JP (2) | JPH0789952B2 (sv) |
| KR (1) | KR960011919B1 (sv) |
| AT (2) | ATE219518T1 (sv) |
| AU (1) | AU638309B2 (sv) |
| CA (1) | CA2074943C (sv) |
| CZ (1) | CZ284774B6 (sv) |
| DK (1) | DK0513073T3 (sv) |
| ES (2) | ES2177536T3 (sv) |
| FI (1) | FI109810B (sv) |
| HU (1) | HU217103B (sv) |
| IE (1) | IE64938B1 (sv) |
| IL (1) | IL97119A0 (sv) |
| LV (1) | LV10309B (sv) |
| NO (1) | NO311142B1 (sv) |
| NZ (1) | NZ236819A (sv) |
| PT (1) | PT96658B (sv) |
| WO (1) | WO1991011520A1 (sv) |
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| WO1996009395A2 (de) * | 1994-09-21 | 1996-03-28 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Arzneimittel zur prophylaxe und behandlung von und diagnostika zur erkennung von autoimmunkrankheiten und viralen erkrankungen |
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-
1991
- 1991-01-18 NZ NZ236819A patent/NZ236819A/xx unknown
- 1991-01-31 IL IL97119A patent/IL97119A0/xx not_active IP Right Cessation
- 1991-02-01 HU HU9202511A patent/HU217103B/hu unknown
- 1991-02-01 KR KR1019920701858A patent/KR960011919B1/ko not_active IP Right Cessation
- 1991-02-01 CA CA002074943A patent/CA2074943C/en not_active Expired - Lifetime
- 1991-02-01 ES ES93121015T patent/ES2177536T3/es not_active Expired - Lifetime
- 1991-02-01 JP JP3503102A patent/JPH0789952B2/ja not_active Expired - Lifetime
- 1991-02-01 EP EP91902956A patent/EP0513073B1/de not_active Expired - Lifetime
- 1991-02-01 ES ES91902956T patent/ES2076521T3/es not_active Expired - Lifetime
- 1991-02-01 PT PT96658A patent/PT96658B/pt not_active IP Right Cessation
- 1991-02-01 EP EP93121015A patent/EP0602688B1/de not_active Expired - Lifetime
- 1991-02-01 WO PCT/EP1991/000192 patent/WO1991011520A1/de active IP Right Grant
- 1991-02-01 AT AT93121015T patent/ATE219518T1/de not_active IP Right Cessation
- 1991-02-01 AT AT91902956T patent/ATE124456T1/de not_active IP Right Cessation
- 1991-02-01 CZ CS91241A patent/CZ284774B6/cs not_active IP Right Cessation
- 1991-02-01 AU AU71496/91A patent/AU638309B2/en not_active Ceased
- 1991-02-01 US US07/917,034 patent/US5427927A/en not_active Expired - Lifetime
- 1991-02-01 IE IE35891A patent/IE64938B1/en not_active IP Right Cessation
- 1991-02-01 DK DK91902956.1T patent/DK0513073T3/da active
-
1992
- 1992-07-30 NO NO19923010A patent/NO311142B1/no unknown
- 1992-07-31 FI FI923463A patent/FI109810B/sv active
-
1993
- 1993-09-24 LV LVP-93-1094A patent/LV10309B/lv unknown
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1995
- 1995-01-04 JP JP7000120A patent/JP2766621B2/ja not_active Expired - Lifetime
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