Claims
- 1. A non-glycosylated tissue plasminogen activator represented by the following amino acid sequence (I) as its primary structure: ##STR9## X is -Lys- and Y is -TyrSerGlnProGlnPheArgIle- or -TyrSerGlnProGlnPheAspIle-.
- 2. The non-glycosylated tissue plasminogen activator of claim 1, in which R is Ser-, X is -Lys- and Y is -TyrSerGlnProGlnPheAspIle-.
- 3. The non-glycosylated plasminogen activator of claim 1, in which R is Ser-, X is -Lys- and Y is TyrSerGlnProGlnPheArgIle.
- 4. A isolated DNA encoding amino acid sequence (I) as defined in claim 1.
- 5. An expression vector of DNA encoding amino acid sequence (I) as defined in claim 1 wherein the sequence is expressed in Escherichia coli.
- 6. An Escherichia coli transformed with an expression vector of DNA sequence encoding amino acid sequence (I) as defined in claim 1.
- 7. A process for the production of tissue plasminogen a activator of claim 1 which comprises, culturing an Escherichia coli TRANSFORMED with an expression vector of DNA encoding an amino acid sequence (I) as defined in claim 1 in a nutrient medium, and recovering the resultant t-PA from the cultured broth.
- 8. A pharmaceutical composition comprising tissue plasminogen activator of claim 1 and pharmaceutically acceptable carrier(s).
- 9. A tissue plasminogen activator expressed by a recombinant microorganism, lacking finger, growth factor and kringle 1 domains which further lacks glycosylation.
- 10. A process for the production of the tissue plasminogen activator of claim 9 which comprises,
- culturing Escherichia coli transformed with an expression vector of DNA encoding the tissue plasminogen activator of claim 9 in a nutrient medium, and
- recovering the resultant tissue plasminogen activator from the cultured broth.
- 11. A pharmaceutical composition comprising the tissue plasminogen activator of claim 9 and a pharmaceutically acceptable carrier.
- 12. A tissue plasminogen activator expressed by a recombinant microorganism, lacking finger, growth factor and kringle 1 domains which further lacks glycosylation, in which arginine residue at 275 position of native human tissue plasminogen activator is replaced by another amino acid residue.
- 13. A process for the production of the tissue plasminogen activator of claim 12 which comprises,
- culturing Escherichia coli transformed with an expression vector of DNA encoding the tissue plasminogen activator of claim 12 in a nutrient medium, and
- recovering the resultant tissue plasminogen activator from the cultured broth.
- 14. A pharmaceutical composition comprising the tissue plasminogen activator of claim 12 and pharmaceutically acceptable carrier.
- 15. The tissue plasminogen activator of claim 12 in which an arginine residue at 275 position of native human tissue plasminogen activator is replaced by an aspartic acid residue.
- 16. A process for the production of the tissue plasminogen activator of claim 15 which comprises,
- culturing Escherichia coli transformed with an expression vector of DNA encoding the tissue plasminogen activator of claim 15 in a nutrient medium, and
- recovering the resultant tissue plasminogen activator from the cultured broth.
- 17. A pharmaceutical composition comprising the tissue plasminogen activator of claim 15 and a pharmaceutically acceptable carrier.
Priority Claims (3)
Number |
Date |
Country |
Kind |
8718298 |
Aug 1987 |
GBX |
|
8725052 |
Oct 1987 |
GBX |
|
8726683 |
Nov 1987 |
GBX |
|
Parent Case Info
This application is a continuation of application Ser. No. 08/238,796, filed on May 6, 1994, now abandoned; which is a continuation of Ser. No. 08/131,672, filed Oct. 5, 1993, abandoned; which is a continuation of Ser. No. 07/991,714, filed Dec. 16, 1992, abandoned; which is a continuation of Ser. No. 07/879,736, filed May 6, 1992, abandoned; which is a continuation of Ser. No. 07/711,410 filed Jun. 5, 1991, abandoned; which is a continuation of Ser. No. 07/227,149 filed Aug. 2, 1988, abandoned.
Foreign Referenced Citations (1)
Number |
Date |
Country |
0093619 |
Nov 1983 |
EPX |
Continuations (6)
|
Number |
Date |
Country |
Parent |
238796 |
May 1994 |
|
Parent |
131672 |
Oct 1993 |
|
Parent |
991714 |
Dec 1992 |
|
Parent |
879736 |
May 1992 |
|
Parent |
711410 |
Jun 1991 |
|
Parent |
227149 |
Aug 1988 |
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