US4507283A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Pharmacologically active compounds
Assignee: Beecham Group PLC
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Filing: 1983-04-05
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Granted: 1985-03-26
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Expires: 2003-04-05
Abstract
Abstract A derivative of streptokinase-human plasminogen activator complex, in which the active catalytic site essential for fibrinolytic activity is blocked by a 2- or 4-aminobenzoyl group, is useful in treating venous thrombosis. The blocking group is removable by hydrolysis such that the first order rate is in the range 0.7×10 -5 sec -1 to 2.5×10 -5 sec -1 in isotonic aqueous media at pH 7.4 at 37° C.
Inventors
- 👤 Richard A. G. Smith
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-26 21:17
CPC Classifications
C; C12; C12N; C12N9/00; C12N9/14; C12N9/48; C12N9/50; C12N9/64; C12N9/6421; C12N9/6424; C12N9/6456; C12N9/6459; A; A61; A61P; A61P7/00; A61P7/02; C07; C07K; C07K14/00; C07K14/195; C07K14/315; C07K14/3153; C12N9/96; C12Y; C12Y304/00; C12Y304/21; C12Y304/21069; A61K; A61K38/00
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
79 words
A derivative of streptokinase-human plasminogen activator complex in which the active catalytic site essential for fibrinolytic activity is blocked by a 2- or 4-aminobenzoyl group which is optionally substituted in the aromatic ring by an electron donating moiety, the group being removable by hydrolysis such that the first order rate constant for hydrolysis of the derivative is in the range 0.7×10 -5 sec -1 to 2.5×10 -5 sec -1 in isotonic aqueous media at pH 7.4 at 37° C.
Claim 2
Dependent Claim
79 words
A derivative of streptokinase-human plasminogen activator complex in which the active catalytic site essential for fibrinolytic activity is blocked by a 2- or 4-aminobenzoyl group which is optionally substituted in the aromatic ring by an electron donating moiety, the group being removable by hydrolysis such that the first order rate constant for hydrolysis of the derivative is in the range 0.7×10 -5 sec -1 to 2.5×10 -5 sec -1 in isotonic aqueous media at pH 7.4 at 37° C.
Claim 3
Dependent Claim
25 words
A derivative according to claim 1, in which the first order rate constant is from 1×10 -5 sec -1 to 2×10 -5 sec -1 .
Claim 4
Dependent Claim
26 words
A derivative according to claim 1, in which the aminobenzoyl group is substituted by a C 1-6 alkyl, C 1-6 alkoxy or C 1-6 alkenyl group.
Claim 5
Dependent Claim
29 words
A derivative according to claim 1, selected from 4-aminobenzoyl streptokinase plasminogen activator complex, 2-aminobenzoyl streptokinase plasminogen activator complex, 4-amino-3-methylbenzoyl streptokinase plasminogen activator complex, or 2-amino-3-methylbenzoyl streptokinase plasminogen activator complex.
Claim 6
Dependent Claim
58 words
A process for preparing a derivative according to claim 1, which comprises reacting streptokinase plasminogen activator complex with a blocking agent of the formula in which A is a locating group which locates the agent in the catalytic site, and B is a 2- or 4-aminobenzoyl group optionally substituted in the aromatic ring by an electron donating moiety.
Claim 7
Dependent Claim
17 words
A process according to claim 5, in which the group A is a 4-amidinophenyl or 4-acetamidinophenyl group.
Claim 8
Dependent Claim
103 words
A pharmaceutical composition useful for treating venous thrombosis in humans which comprises a therapeutically effective amount of a derivative of streptokinase-human plasminogen activator complex in which the active catalytic site essential for fibrinolytic activity is blocked by a 2- or 4-aminobenzoyl group which is optionally substituted in the aromatic ring by an electron donating moiety, the group being removable by hydrolysis such that the first order rate constant for hydrolysis of the derivative is in the range 0.7×10 -5 sec -1 to 2.5×10 -5 sec -1 in isotonic aqueous media at pH 7.4 at 37° C., in combination with a pharmaceutically acceptable carrier.
Claim 9
Dependent Claim
103 words
A pharmaceutical composition useful for treating venous thrombosis in humans which comprises a therapeutically effective amount of a derivative of streptokinase-human plasminogen activator complex in which the active catalytic site essential for fibrinolytic activity is blocked by a 2- or 4-aminobenzoyl group which is optionally substituted in the aromatic ring by an electron donating moiety, the group being removable by hydrolysis such that the first order rate constant for hydrolysis of the derivative is in the range 0.7×10 -5 sec -1 to 2.5×10 -5 sec -1 in isotonic aqueous media at pH 7.4 at 37° C., in combination with a pharmaceutically acceptable carrier.
Claim 10
Dependent Claim
25 words
A composition according to claim 7 in which the first order rate constant is from 1×10 -5 sec -1 to 2×10 -5 sec -1 .
Claim 11
Dependent Claim
26 words
A composition according to claim 7 in which the aminobenzoyl group is substituted by a C 1-6 alkyl, C 1-6 alkoxy or C 1-6 alkenyl group.
Claim 12
Dependent Claim
33 words
A composition according to claim 7 wherein the derivative is selected from 4-aminobenzoyl streptokinase plasminogen activator complex, 2-aminobenzoyl streptokinase plasminogen activator complex, 4-amino-3-methylbenzoyl streptokinase plasminogen activator complex, or 2-amino-3-methylbenzoyl streptokinase plasminogen activator complex.
Claim 13
Dependent Claim
10 words
A composition according to claim 7 in intravenous administration form.
Claim 14
Independent Claim
108 words
A method for treating venous thrombosis in humans which comprises administering to a human in need thereof a therapeutically effective amount of a derivative of streptokinase-human plasminogen activator complex in which the active catalytic site essential for fibrinolytic activity is blocked by a 2- or 4-aminobenzoyl group which is optionally substituted in the aromatic ring by an electron donating moiety, the group being removable by hydrolysis such that the first order rate constant for hydrolysis of the derivative is in the range 0.7×10 -5 sec -1 to 2.5×10 -5 sec -1 in isotonic aqueous media at pH 7.4 at 37° C., in combination with a pharmaceutically acceptable carrier.
Claim 15
Independent Claim
108 words
A method for treating venous thrombosis in humans which comprises administering to a human in need thereof a therapeutically effective amount of a derivative of streptokinase-human plasminogen activator complex in which the active catalytic site essential for fibrinolytic activity is blocked by a 2- or 4-aminobenzoyl group which is optionally substituted in the aromatic ring by an electron donating moiety, the group being removable by hydrolysis such that the first order rate constant for hydrolysis of the derivative is in the range 0.7×10 -5 sec -1 to 2.5×10 -5 sec -1 in isotonic aqueous media at pH 7.4 at 37° C., in combination with a pharmaceutically acceptable carrier.
Claim 16
Dependent Claim
25 words
A method according to claim 12 in which the first order rate constant is from 1×10 -5 sec -1 to 2×10 -5 sec -1 .
Claim 17
Dependent Claim
26 words
A method according to claim 12 in which the aminobenzoyl group is substituted by a C 1-6 alkyl, C 1-6 alkoxy or C 1-6 alkenyl group.
Claim 18
Dependent Claim
33 words
A method according to claim 12 wherein the derivative is selected from 4-aminobenzoyl streptokinase plasminogen activator complex, 2-aminobenzoyl streptokinase plasminogen activator complex, 4-amino-3-methylbenzoyl streptokinase plasminogen activator complex, or 2-amino-3-methylbenzoyl streptokinase plasminogen activator complex.
Claim 19
Dependent Claim
11 words
A method according to claim 12 wherein the administration is intravenous.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1988-03-25 | 1988-09-24 | 1989-03-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1992-03-25 | 1992-09-24 | 1993-03-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1996-03-25 | 1996-09-24 | 1997-03-26 | $7700.00 | Window Closed / Lapsed |