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.)
Filing date
Publication date
Priority claimed from US06/256,204external-prioritypatent/US6610830B1/en
Application filed by F. Hoffmann-La Roche Ag, Gennetech Inc.filedCriticalF. Hoffmann-La Roche Ag
Priority claimed from YU162281Aexternal-prioritypatent/YU47700B/en
Publication of SI8111622ApublicationCriticalpatent/SI8111622A/en
Publication of SI8111622BpublicationCriticalpatent/SI8111622B/en
Preparation Of Compounds By Using Micro-Organisms
(AREA)
Claims (59)
61 PATENTNI ZAHTEVKI 1. Postopek za pridobivanje mikroorganizmov, ki so sposobni za proizvodnjo polipeptidov z aminokislinsko sekvenco zrelega humanega levkocitnega interferona brez predhodne sekvence, označen s tem, da mikroorganizem z eksprimirajočim vektorjem, ki se da replicirati in ki vsebuje DNK-sekvenco, ki kodira zreli humani levkocitni interferon brez predhodne sekvence, transformiramo in gojimo na sam po sebi znan način.A process for the production of microorganisms capable of producing polypeptides with the amino acid sequence of a mature human leukocyte interferon without a prior sequence, characterized in that the microorganism has a DNA-replicating expression vector comprising a DNA sequence. mature human leukocyte interferon without prior sequence is transformed and cultured in a manner known per se.2. Postopek po zahtevku 1, označen s tem, da transformacijo izvedemo s plazmidom.Process according to Claim 1, characterized in that the transformation is carried out with a plasmid.3. Postopek po zahtevku 1 ali 2, označen s tem, da uporabimo eksprimirajoči vektor, ki vsebuje DNK-sekvenco, ki kodira zreli humani levkocitni interferon A (LeIF A) brez predhodne sekvence.Method according to claim 1 or 2, characterized in that an expression vector comprising a DNA sequence encoding mature human leukocyte interferon A (LeIF A) without a prior sequence is used.4. Postopek po zahtevku 1 ali 2, označen s tem, da uporabimo eksprimirajoči vektor, ki vsebuje DNK-sekvenco, ki kodira zreli humani levkocitni interferon B (LeIF B) brez predhodne sekvence.Method according to claim 1 or 2, characterized in that an expression vector comprising a DNA sequence encoding mature human leukocyte interferon B (LeIF B) without a prior sequence is used.5. Postopek po zahtevku 1 ali 2, označen s tem, da uporabimo eksprimirajoči vektor, ki vsebuje DNK-sekvenco, ki kodira zreli humani levkocitni interferon C (LeIF C) brez predhodne sekvence.The method of claim 1 or 2, characterized in that an expression vector comprising a DNA sequence encoding mature human leukocyte interferon C (LeIF C) without a prior sequence is used.6. Postopek po zahtevku 1 ali 2, označen s tem, da uporabimo eksprimirajoči vektor, ki vsebuje DNK-sekvenco, ki kodira zreli humani levkocitni interferon D (LeIF D) brez predhodne sekvence.Method according to claim 1 or 2, characterized in that an expression vector comprising a DNA sequence encoding mature human leukocyte interferon D (LeIF D) without a prior sequence is used.7. Postopek po zahtevku 1 ali 2, označen s tem, da uporabimo eksprimirajoči vektor, ki vsebuje DNK-sekvenco, ki kodira zreli humani levkocitni interferon F (LeIF F) brez predhodne sekvence. 62The method of claim 1 or 2, characterized in that an expression vector comprising a DNA sequence encoding mature human leukocyte interferon F (LeIF F) without a prior sequence is used. 628. Postopek po zahtevku 1 ali 2, označen s tem, da uporabimo eksprimirajoči vektor, ki vsebuje DNK-sekvenco, ki kodira zreli humani levkocitni interferon H (LeIF H) brez predhodne sekvence.A method according to claim 1 or 2, characterized in that an expression vector comprising a DNA sequence encoding mature human leukocyte interferon H (LeIF H) without a prior sequence is used.9. Postopek po zahtevku 1 ali 2, označen s tem, da uporabimo eksprimirajoči vektor, ki vsebuje DNK-sekvenco, ki kodira zreli humani levkocitni interferon I (LeIF I) brez predhodne sekvence.The method of claim 1 or 2, characterized in that an expression vector comprising a DNA sequence encoding mature human leukocyte interferon I (LeIF I) without a prior sequence is used.10. Postopek po zahtevku 1 ali 2, označen s tem, da uporabimo eksprimirajoči vektor, ki vsebuje DNK-sekvenco, ki kodira zreli humani levkocitni interferon J (LeIF J) brez predhodne sekvence.The method according to claim 1 or 2, characterized in that an expression vector comprising a DNA sequence encoding mature human leukocyte interferon J (LeIF J) without a prior sequence is used.11. Postopek po enem od zahtevkov 1 do 10, označen s tem, da kot izhodni organizem uporabimo bakterijo.Method according to one of Claims 1 to 10, characterized in that a bacterium is used as the starting organism.12. Postopek po zahtevku 11, označen s tem, da kot bakterijo uporabimo soj E.coli.Process according to Claim 11, characterized in that an E. coli strain is used as the bacterium.13. Postopek za pridobivanje polipeptidov z aminokislinsko sekvenco zrelega humanega levkocitnega interferona brez predhodne sekvence in brez glikozil-skupin, označen s tem, da kulturo mikroorganizma, ki je transformirana z vektorjem, ki se da replicirati in je sposoben za eksprimiranje takšnega peptida, dovedemo do eksprimiranja in izoliramo polipeptid.13. A method for producing polypeptides with the amino acid sequence of mature human leukocyte interferon without a prior sequence and without glycosyl groups, characterized in that the culture of the microorganism is transformed with a replicable vector capable of expressing such a peptide to expression and isolate the polypeptide.14. Postopek po zahtevku 13, označen s tem, da polipeptid vsebuje aminokislinsko sekvenco zrelega humanega levkocitnega interferona vezano na metionin.The method of claim 13, wherein the polypeptide comprises the amino acid sequence of a mature human leukocyte interferon bound to methionine.15. Postopek po zahtevku 13, označen s tem, da polipeptid vsebuje aminokislinsko sekvenco zrelega humanega levkocitnega interferona vezano na odcepljiv konjugans ali mikrobni signalni protein.The method of claim 13, wherein the polypeptide comprises the amino acid sequence of a mature human leukocyte interferon linked to a cleavable conjugate or microbial signaling protein.16. Postopek po enem izmed zahtevkov 13 do 15, označen s tem, da polipeptid vsebuje aminokislinsko parcialno sekvenco Cys-A]a-Trp-Glu-Val-Val-Arg-Ala-Glu-Ile-Met-Arg-Ser. 63Process according to one of Claims 13 to 15, characterized in that the polypeptide contains the amino acid partial sequence of Cys-A] a-Trp-Glu-Val-Val-Arg-Ala-Glu-Ile-Met-Arg-Ser. 6317. Postopek po enem izmed zahtevkov 13 do 15, označen s tem, da polipeptid na navedenem mestu aminokislinske sekvence vsebuje aminokisline navedene na Sliki 4 v vrsti "Ali".Method according to one of claims 13 to 15, characterized in that the polypeptide at said amino acid sequence site comprises the amino acids listed in Figure 4 in the " Or " series.18. Postopek po enem izmed zahtevkov 13 do 17, označen s tem, da je polipeptid v bistvu humani levkocitni interferon (LeIF) A, B, C, D, F, H, I ali J.Method according to one of claims 13 to 17, characterized in that the polypeptide is essentially human leukocyte interferon (LeIF) A, B, C, D, F, H, I or J.19. Postopek po zahtevku 13, za pridobivanje humanega levkocitnega interferona A (LeIF A).The method of claim 13, for producing human leukocyte interferon A (LeIF A).20. Postopek po zahtevku 13, za pridobivanje humanega levkocitnega interferona B (LeIF B).The method of claim 13, for producing human leukocyte interferon B (LeIF B).21. Postopek po zahtevku 13, za pridobivanje humanega levkocitnega interferona C (LeIF C).The method of claim 13, for producing human leukocyte interferon C (LeIF C).22. Postopek po zahtevku 13, za pridobivanje humanega levkocitnega interferona D (LeIF D).The method of claim 13, for producing human leukocyte interferon D (LeIF D).23. Postopek po zahtevku 13, za pridobivanje humanega levkocitnega interferona F (LeIF F).The method of claim 13, for producing human leukocyte interferon F (LeIF F).24. Postopek po zahtevku 13, za pridobivanje humanega levkocitnega interferona H (LeIF H).The method of claim 13, for producing human leukocyte interferon H (LeIF H).25. Postopek po zahtevku 13, za pridobivanje humanega levkocitnega interferona I (LeIF I).The method of claim 13, for producing human leukocyte interferon I (LeIF I).26. Postopek po zahtevku 13, za pridobivanje humanega levkocitnega interferona J (LeIF J).The method of claim 13, for producing human leukocyte interferon J (LeIF J).27. Postopek po enem izmed zahtevkov 13 do 26, označen s tem, da je mikroorganizem v bistvu bakterija.Method according to one of Claims 13 to 26, characterized in that the microorganism is essentially a bacterium.28. Postopek po zahtevku 27, označen s tem, da kot bakterijo uporabimo E.coli. 64Process according to Claim 27, characterized in that E. coli is used as the bacterium. 6429. Postopek za pridobivanje replikabilnega vektorja, ki je sposoben, da v mikroorganizmu povzroči eksprimiranje polipeptida z aminokislinsko sekvenco zrelega humanega levkocitnega interferona, označen s tem, da se prva DNK-sekvenca, ki kodira omenjeni polipeptid, operativno veže z drugo DNK-sekvenco, ki vsebuje za eksprimiranje potrebne kodone.29. A method of obtaining a replicable vector capable of inducing in a microorganism the expression of a polypeptide with the amino acid sequence of a mature human leukocyte interferon, characterized in that the first DNA sequence encoding said polypeptide is operably linked to a second DNA sequence containing the codons required to express.30. Postopek po zahtevku 29, označen s tem, da druga DNK-sekvenca povzroči eksprimiranje v bakteriji.The method of claim 29, wherein the second DNA sequence causes expression in a bacterium.31. Postopek po zahtevku 30, označen s tem, da kot bakterijo uporabimo E.coli.Process according to Claim 30, characterized in that E. coli is used as the bacterium.32. Postopek po enem izmed zahtevkov 29 do 31, označen s tem, da polipeptid vsebuje aminokislinsko sekvenco zrelega humanega levkocitnega interferona vezano na metionin.Method according to one of claims 29 to 31, characterized in that the polypeptide comprises the amino acid sequence of a mature human leukocyte interferon bound to methionine.33. Postopek po enem izmed zahtevkov 29 do 31, označen s tem, da polipeptid vsebuje aminokislinsko sekvenco zrelega humanega levkocitnega interferona vezano na odcepljiv konjugans ali mikrobni signalni protein.Method according to one of claims 29 to 31, characterized in that the polypeptide comprises the amino acid sequence of a mature human leukocyte interferon linked to a cleavable conjugate or a microbial signaling protein.34. Postopek po enem izmed zahtevkov 29 do 31, označen s tem, da polipeptid vsebuje aminokislinsko parcialno sekvenco Cys-Ala-Trp-G]u-Val-Val-Arg-AJa-Glu-Ile-Met-Arg-Ser.Process according to one of Claims 29 to 31, characterized in that the polypeptide comprises the amino acid partial sequence of Cys-Ala-Trp-G-u-Val-Val-Arg-AJa-Glu-Ile-Met-Arg-Ser.35. Postopek po enem izmed zahtevkov 29 do 31, označen s tem, da polipeptid na navedenem mestu aminokislinske sekvence vsebuje aminokisline navedene na Sliki 4 v vrsti "AH".Method according to one of claims 29 to 31, characterized in that the polypeptide at said amino acid sequence site contains the amino acids listed in Figure 4 in the " AH " series.36. Postopek po enem izmed zahtevkov 29 do 31, označen s tem, da je polipeptid v bistvu humani levkocitni interferon (LeIF) A, B, C, D, F, U, I ali J.Method according to one of claims 29 to 31, characterized in that the polypeptide is essentially human leukocyte interferon (LeIF) A, B, C, D, F, U, I or J.37. Postopek po enem izmed zahtevkov 29 do 31, označen s tem, da se eksprimira humani levkocitni interferon A (LeIF A).Method according to one of Claims 29 to 31, characterized in that human leukocyte interferon A (LeIF A) is expressed.38. Postopek po enem izmed zahtevkov 29 do 31, označen s tem, da se eksprimira humani levkocitni interferon B (LeIF B). 65Method according to one of Claims 29 to 31, characterized in that human leukocyte interferon B (LeIF B) is expressed. 6539. Postopek po enem izmed zahtevkov 29 do 31, označen s tem, da se eksprimira humani levkocitni interferon C (LeIF C).Method according to one of Claims 29 to 31, characterized in that human leukocyte interferon C (LeIF C) is expressed.40. Postopek po enem izmed zahtevkov 29 do 31, označen s tem, da se eksprimira humani levkocitni interferon D (LeIF D).Method according to one of Claims 29 to 31, characterized in that human leukocyte interferon D (LeIF D) is expressed.41. Postopek po enem izmed zahtevkov 29 do 31, označen s tem, da se eksprimira humani levkocitni interferon F (LeIF F).Method according to one of Claims 29 to 31, characterized in that human leukocyte interferon F (LeIF F) is expressed.42. Postopek po enem izmed zahtevkov 29 do 31, označen s tem, da se eksprimira humani levkocitni interferon H (LeIF H).Method according to one of Claims 29 to 31, characterized in that human leukocyte interferon H (LeIF H) is expressed.43. Postopek po enem izmed zahtevkov 29 do 31, označen s tem, da se eksprimira humani levkocitni interferon I (LeIF I).Method according to one of Claims 29 to 31, characterized in that human leukocyte interferon I (LeIF I) is expressed.44. Postopek po enem izmed zahtevkov 29 do 31, označen s tem, da se eksprimira humani levkocitni interferon J (LeIF J).Method according to one of Claims 29 to 31, characterized in that human leukocyte interferon J (LeIF J) is expressed.45. Polipeptid, označen s tem, da vsebuje aminokislinsko sekvenco zrelega humanega levkocitnega interferona, kije ne spremlja nobena predhodna sekvenca.45. A polypeptide comprising the amino acid sequence of a mature human leukocyte interferon that is not accompanied by any prior sequence.46. Polipeptid po zahtevku 45, ki ga ne spremlja pridruženo glikoziranje.The polypeptide of claim 45, which is not accompanied by associated glycosylation.47. Polipeptid, označen s tem, da vsebuje aminokislinsko sekvenco zrelega humanega levkocitnega interferona in aminokislino metionin vezano na N-terminus običajne prve aminokisline omenjenega interferona.47. A polypeptide comprising the amino acid sequence of a mature human leukocyte interferon and the amino acid methionine linked to the N-terminus of a conventional first amino acid of said interferon.48. Polipeptid, označen s tem, da vsebuje aminokislinsko sekvenco zrelega humanega levkocitnega interferona in razdelilni konjugiran ali mikrobni signalni protein, vezan na N-terminus običajne prve aminokisline omenjenega interferona.A polypeptide comprising the amino acid sequence of a mature human leukocyte interferon and a dividing conjugate or microbial signaling protein bound to the N-terminus of a conventional first amino acid of said interferon.49. Polipeptid po kateremkoli izmed zahtevkov 45 do 47, označen s tem, da aminokislinska sekvenca omenjenega interferona vsebuje parcialno sekvenco Cys-Ala-Trp-Glu-Val-Val-Arg-Ala-Glu-Ile-Met-Arg-Ser. 6 6A polypeptide according to any one of claims 45 to 47, wherein the amino acid sequence of said interferon comprises the partial sequence of Cys-Ala-Trp-Glu-Val-Val-Arg-Ala-Glu-Ile-Met-Arg-Ser. 6 650. Polipeptid, po kateremkoli izmed zahtevkov 45 do 47, označen s tem, da sekvenca omenjenega interferona vsebuje aminokisline specificirane in locirane, kot je prikazano v vrsti "AH" na Sliki 4.The polypeptide of any one of claims 45 to 47, wherein the sequence of said interferon comprises amino acids specified and located as shown in the " AH " in Figure 4.51. Polipeptid po kateremkoli izmed zahtevkov 45 do 47, ki je izbran iz skupine, ki je sestavljena iz humanega levkocitnega interferona (LeIF) A, B, C, D, F, H, I in J.A polypeptide according to any one of claims 45 to 47, selected from the group consisting of human leukocyte interferon (LeIF) A, B, C, D, F, H, I and J.52. Humani levkocitni interferon A (LeIF A).52. Human leukocyte interferon A (LeIF A).53. Humani levkocitni interferon B (LeIF B).53. Human leukocyte interferon B (LeIF B).54. Humani levkocitni interferon C (LeIF C).54. Human leukocyte interferon C (LeIF C).55. Humani levkocitni interferon D (LeIF D).55. Human leukocyte interferon D (LeIF D).56. Humani levkocitni interferon F (LeIF F).56. Human leukocyte interferon F (LeIF F).57. Humani levkocitni interferon H (LeIF H).57. Human leukocyte interferon H (LeIF H).58. Humani levkocitni interferon I (LeIF I).58. Human leukocyte interferon I (LeIF I).59. Humani levkocitni interferon J (LeIF J). Za: F.HOFFMANN-LA ROCHE AG in GENETECH, INC.59. Human leukocyte interferon J (LeIF J). For: F.HOFFMANN-LA ROCHE AG and GENETECH, INC.
SI8111622A1980-07-011981-06-30Process for obtaining interferon
SI8111622B
(en)