Claims
- 1. A staphylokinase derivative comprising an amino acid sequence which differs from SEQ ID NO:10 due to substitution of one or more amino acids therein with cysteine thus reducing the clearance from plasma in patients, and further wherein the staphylokinase derivative has a fibrinolytic or fibrinogenolytic property.
- 2. The staphylokinase derivative of claim 1, in which the substitution further results in dimerization, increased specific activity, reduced clearance and/or increased thrombolytic potency of the derivative.
- 3. The staphylokinase derivatives as claimed in claim 1, in which amino acid K109 has been replaced by a cysteine.
- 4. A dimeric staphylokinase derivative comprising a peptide having essentially the amino acid sequence depicted in FIG. 1 (SEQ ID NO: 10) in which amino acid K109 has been replaced by a cysteine.
- 5. A pharmaceutical composition comprising at least one of the staphylokinase derivatives as claimed in claim 2 together with a suitable excipient.
Priority Claims (1)
Number |
Date |
Country |
Kind |
95200023 |
Jan 1995 |
EP |
|
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation-in-part of U.S. patent application Ser. No. 08/784,971, filed Jan. 16, 1997, now U.S. Pat. No. 5,951,980 which is a continuation-in-part of U.S. patent application Ser. No. 08/499,092, filed Jul. 6, 1995, now abandoned which is a continuation-in-part of U.S. patent application Ser. No. 08/371,505, filed Jan. 11, 1995, now U.S. Pat. No. 5,695,754, issued Dec. 9, 1997.
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Sako et al. |
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Aug 1994 |
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Dec 1995 |
A |
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Dec 1997 |
A |
Foreign Referenced Citations (1)
Number |
Date |
Country |
0721982 |
Jul 1996 |
EP |
Non-Patent Literature Citations (11)
Entry |
Silewce et al. (1995) J. Biol. Chem. 270 : 27192-27198.* |
Regenmortel (1986) TIBS 11 : 36-39.* |
Bowie et al. (1990) Science 247 : 1307-1310.* |
Collen, D. et al; Thrombolytic properties of poorly immunogenic variants of recombinant staphylokinase; p. 30 (Jun. 1998). |
Collen, D. et al; “Recombinant staphylokinase variants with altered immunoreactivity III: Species variability of antibody binding patterns” pp. 455-463 (Jan. 1997). |
Collen, D. et al: “Recombinant staphylokinase variants with altered immunoreactivity I: Construction and characterization” p. 197-206 (Jul. 15, 1996). |
Collen, D. et al: “Recombinant staphylokinase variants with altered immunoreactivity IV: Identification of variats with reduced antibody induction but intact potency” pp. 463-472 (Jan. 21, 1997). |
Collen et al. “Primary structure and gene structure of staphylokinase.” Fibrinolysis 6: 226-231 (1992). |
Collen et al. “Comparative thrombolytic and immunogenic properties of staphylokinase and streptokinase.” Fibrinolysis 6: 232-242 (1992). |
Collen “Coronary thrombolysis with recombinant staphylokinase in patients with evolving myocardial infarction.” Circulation 87: 1850-1853 (1993). |
Collen et al. “Comparative immunogenicity and thrombolytic properties toward arterial and venous thrombi of streptokinase and recombinant staphylokinase in baboons.” Circulation 87: 996-1006 (1993). |
Continuation in Parts (3)
|
Number |
Date |
Country |
Parent |
08/784971 |
Jan 1997 |
US |
Child |
09/020018 |
|
US |
Parent |
08/499092 |
Jul 1995 |
US |
Child |
08/784971 |
|
US |
Parent |
08/371505 |
Jan 1995 |
US |
Child |
08/499092 |
|
US |