FI112367B - Förfarande för framställing av polypeptidanaloger av ett baktericid/permeabilitet förbättrande protein eller biologiskt aktiva fragment därav eller ett hybridfusioprotein som innehåller detta och vidförfarandet användbara DNA-sekvenser, vektorer och värdceller - Google Patents

Förfarande för framställing av polypeptidanaloger av ett baktericid/permeabilitet förbättrande protein eller biologiskt aktiva fragment därav eller ett hybridfusioprotein som innehåller detta och vidförfarandet användbara DNA-sekvenser, vektorer och värdceller Download PDF

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FI112367B
FI112367B FI953658A FI953658A FI112367B FI 112367 B FI112367 B FI 112367B FI 953658 A FI953658 A FI 953658A FI 953658 A FI953658 A FI 953658A FI 112367 B FI112367 B FI 112367B
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rbpi
protein
dna
bpi
cells
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Arnold Horwitz
David Burke
Georgia Theofan
Manik Baltaian
Lynn Grinna
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Xoma Corp
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Claims (16)

1. Förfarande för framställning av polypeptid-analoger av ett baktericid/permeabilitet förbättrande pro- 5 tein eller biologiskt aktiva fragment därav, i vilka cy-steinresten i position 132 har ersatts med en olik aminosy-ra, kännetecknat av att det innehäller steg i vilka man odlar en värdcell som har stabilt transformerats 10 eller transfekterats med DNA som kodar för nämnda polypep-tidanalog av det baktericida/permeabilitet förbättrande proteinet eller det biologiskt aktiva fragmentet därav i ett lämpigt odlingsmedium och isolerar nämnda polypeptid eller polypeptidianalog 15 frän nämnda värdcell eller nämnda odlingsmedium.
2. Förfarande enligt patentkrav 1, kännetecknat av att aminosyran som ersätter nämnda cys-teinrest är en icke-polar aminosyra, som väljs bland en grupp som innehäller alanin och serin. 20
3. Förfarande enligt patentkrav 1, känne tecknat av att alanin ersätter cysteinresten i position 132. I
4. Förfarande enligt patentkrav 1, 2 eller 3 kännetecknat av att nämnda protein eller poly-*. 25 peptidanalog innehäller, förutom ersättningen av cysteinet i position 132, 176 - 199 originella aminoterminala ami- » nosyrarester av det baktericida/permeabilitet förbättrande proteinet.
, 5. Förfarande enligt patentkrav 4, k ä n n e - » ; 30 tecknat av att nämnda protein eller polypeptid- » analog innehäller 193 originella aminoterminala aminosyra-; : rester av det baktericida/permeabilitet förbättrande pro teinet. » » 69 Π 2ό6'/
6. DNA, kännetecknad av att den kodar för en polypeptidanalog av ett baktericid/permeabilitet förbättrande protein eller ett biologiskt aktivt fragment därav, i vilka cysteinresten i position 132 har ersatts 5 med en olik aminosyra.
7. DNA enligt patentkrav 6, kännetecknad av att den kodar för en leader-sekvens med längden av 31 aminosyror och 193 första N-terminala rester av det baktericida/permeabilitet förbättrande proteinet och att 10 den innehäller ett slutkodon efter kodonet som befinner sig omedelbart efter det leucinresten i position 193 kodande kodonet.
8. DNA enligt patentkrav 6, kännetecknad av att den kodar för en leader-sekvens med längden 15 av 31 aminosyror och 193 första N-terminala rester av det baktericida/permeabilitet förbättrande proteinet och att den innehäller ett slutkodon efter kodonet som befinner sig omedelbart efter det isoleucinresten i position 199 kodande kodonet.
9. Autonomt replikerande DNA-vektor, k ä n n e - tecknad av att den innehäller en DNA enligt patentkrav 6.
; | 10. Värdcell, kännetecknad av att den ", har stabilt transformerats eller transfekterats med en DNA 25 enligt patentkrav 6 sä att expressionen av nämnda polypeptidanalog i nämnda värdcell blir möjlig.
11. Eukaryotisk värdcell, kännetecknad av att den är enligt patentkrav 10.
12. Värdcell enligt patentkrav 11, k ä n n e - , I 30 tecknad av att dess ATCC-kodnummer väljs bland ;· gruppen som innehäller kodnumren ATCC CRL 11246 och ATCC HB 11247.
13. Förfarande för framställning av ett hybrid-fusionsprotein, som innehäller aminoterminalt en polypepti- 35 danalog som producerats genom ett förfarande enligt patent-* krav 1 och karboxyterminalt ätminstone en konstant domän av 70 11266) immunoglobulins tunga kedja eller en allelisk variant dä-rav, kännetecknat av att det innehäller steg i vilka man odlar en värdcell som har stabilt transformerats 5 eller transfekterats med en DNA som kodar ett hybrid-fusionsprotein som innehäller aminoterminalt en polypepti-danalog, som producerats genom ett förfarande enligt pa-tentkrav 1 ooh karboxyterminalt ätminstone en konstant do-män av immunoglobulins tunga kedja eller en allelisk va-10 riant därav i ett lämpligt odlingsmedium och isolerar nämnda hybridfusionsprotein fran nämnda värdcell eller nämnda odlingsmedium.
14. DNA, kännetecknad av att den kodar för ett hybridfusionsprotein, som innehäller aminoter- 15 minalt en polypeptidanalog, som producerats genom ett förfarande enligt patentkrav 1 och karboxyterminalt ätminstone en konstant domän av immunoglobulins tunga kedja eller en allelisk variant därav.
15. Autonomt replikerande DNA-vektor, k ä n n e -20 tecknad av att den innehäller en DNA enligt patentkrav 14 .
16. Värdcell, kännetecknad av att den ; | har stabilt transformerats eller transfekterats med en DNA : enligt patentkrav 14 sä att expressionen av nämnda fusions- 25 polypeptid i nämnda värdcell blir möjlig. 1
FI953658A 1993-02-02 1995-08-01 Förfarande för framställing av polypeptidanaloger av ett baktericid/permeabilitet förbättrande protein eller biologiskt aktiva fragment därav eller ett hybridfusioprotein som innehåller detta och vidförfarandet användbara DNA-sekvenser, vektorer och värdceller FI112367B (sv)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US08/013,801 US5420019A (en) 1993-02-02 1993-02-02 Stable bactericidal/permeability-increasing protein muteins
US1380193 1993-02-02
US9401235 1994-02-02
PCT/US1994/001235 WO1994018323A1 (en) 1993-02-02 1994-02-02 Stable bactericidal/permeability-increasing protein products and pharmaceutical compositions containing the same

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FI953658A0 FI953658A0 (sv) 1995-08-01
FI953658A FI953658A (sv) 1995-09-07
FI112367B true FI112367B (sv) 2003-11-28

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FI953658A FI112367B (sv) 1993-02-02 1995-08-01 Förfarande för framställing av polypeptidanaloger av ett baktericid/permeabilitet förbättrande protein eller biologiskt aktiva fragment därav eller ett hybridfusioprotein som innehåller detta och vidförfarandet användbara DNA-sekvenser, vektorer och värdceller
FI20031199A FI115633B (sv) 1993-02-02 2003-08-26 DNA som kodar ett stabilt baktericida/permeabilitetsförbättrande proteinfragment, vektor, värdcell och förfarande för framställning av dessa proteinfragment

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US (6) US5420019A (sv)
EP (3) EP0689592B1 (sv)
JP (4) JP4139867B2 (sv)
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AU (1) AU693089B2 (sv)
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