US4285932A
Expired / Lapsed
US
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Enzyme derivatives for use in the treatment of venous thrombosis
Assignee: Roberts Laboratories Inc
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Filing: 1979-08-20
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Granted: 1981-08-25
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Expires: 1999-08-20
Abstract
Abstract A pharmaceutical composition which comprises a pharmaceutically acceptable carrier together with an in vivo fibrinolytic enzyme as defined herein wherein the catalytic site essential for fibrinolytic activity is blocked by a group which is removable by hydrolysis at a rate such that the pseudo-first order rate constant for hydrolysis is in the range 10 -6 sec -1 to 10 -3 sec -1 in isotonic aqueous media at pH 7.4 at 37° C.; is useful in the treatment of venous thrombosis.
Inventors
- 👤 Richard A. G. Smith
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 18:41
CPC Classifications
C; C12; C12N; C12N9/00; C12N9/14; C12N9/48; C12N9/50; C12N9/64; C12N9/6421; C12N9/6424; C12N9/6435; A; A61; A61P; A61P7/00; A61P7/02; C07; C07D; C07D307/00; C07D307/02; C07D307/34; C07D307/38; C07D307/54; C07K; C07K14/00; C07K14/195; C07K14/315; C07K14/3153; C12N9/6456; C12N9/6462; C12N9/96; C12Y; C12Y304/00; C12Y304/21; C12Y304/21007; C12Y304/21073; A61K; A61K38/00
Claims Analysis
Total Claims: 33
Claim 1
Independent Claim
77 words
A pharmaceutical composition for treatment of Venous thrombosis which comprises a pharmaceutically acceptable carrier together with an in vivo fibrinolytic enzyme as defined herein wherein the catalytic site essential for fibrinolytic activity is blocked by a group which is removable by hydrolysis at a rate such that the pseudo-first order rate constant for hydrolysis is in the range 10 -6 sec -1 to 10 -3 sec -1 in isotonic aqueous media at pH 7.4 at 37° C.
Claim 2
Dependent Claim
77 words
A pharmaceutical composition for treatment of Venous thrombosis which comprises a pharmaceutically acceptable carrier together with an in vivo fibrinolytic enzyme as defined herein wherein the catalytic site essential for fibrinolytic activity is blocked by a group which is removable by hydrolysis at a rate such that the pseudo-first order rate constant for hydrolysis is in the range 10 -6 sec -1 to 10 -3 sec -1 in isotonic aqueous media at pH 7.4 at 37° C.
Claim 3
Dependent Claim
44 words
A pharmaceutical composition for the prophylactic or therapeutic treatment of venous thrombosis comprising a pharmaceutically acceptable carrier together with an in vivo fibrinolytic enzyme which can be reversibly deactivated and a blocking acyl group removable by hydrolysis at a rate defined by claim 1.
Claim 4
Dependent Claim
20 words
A pharmaceutical composition according to claim 2, wherein the enzyme is urokinase, streptokinase-plasminogen activator complex, vascular activator and mammalian plasmins.
Claim 5
Dependent Claim
13 words
A composition as claimed in claim 1 wherein the enzyme is human plasmin.
Claim 6
Dependent Claim
15 words
A composition as claimed in claim 1 wherein the enzyme is streptokinase/human plasminogen activator complex.
Claim 7
Dependent Claim
21 words
A composition as claimed in claim 1 wherein the enzyme is a mixture of human plasmin and streptokinase/human plasminogen activator complex.
Claim 8
Dependent Claim
19 words
A composition as claimed in claim 1 wherein the group which is removable by hydrolysis is an acyl group.
Claim 9
Dependent Claim
21 words
A composition as claimed in claim 7 wherein the acyl group is a benzoyl, substituted benzoyl, acryloyl or substituted acryloyl group.
Claim 10
Dependent Claim
47 words
A composition as claimed in claim 7 wherein the acyl group is a benzoyl group or a substituted benzoyl group having one or more meta and/or para substituents wherein the sum of the Hammett σ m and σ p values is in the range +0.1 to -1.1.
Claim 11
Dependent Claim
31 words
A composition as claimed in claim 9 wherein the acyl group is benzoyl, optionally substituted with halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkanoyloxy, C 1-6 alkanoylamino or p-guanidino.
Claim 12
Dependent Claim
26 words
A composition as claimed in claim 8 wherein the acyl group is acryloyl, optionally substituted with C 1-6 alkyl, furyl, phenyl, or C 1-6 alkyl phenyl.
Claim 13
Dependent Claim
77 words
A derivative of an in vivo fibrinolytic enzyme as defined herein wherein the catalytic site essential for fibrinolytic activity is blocked by a group which is removable by hydrolysis such that the pseudo-first order rate constant for hydrolysis of the derivative is in the range 10 -6 sec -1 to 10 -3 sec -1 in isotonic aqueous media at pH 7.4 at 37° C. with the exception of: (1) p-guanidinobenzoyl human plasmin, (2) p-guanidinobenzoyl streptokinase-plasminogen activator complex.
Claim 14
Dependent Claim
77 words
A derivative of an in vivo fibrinolytic enzyme as defined herein wherein the catalytic site essential for fibrinolytic activity is blocked by a group which is removable by hydrolysis such that the pseudo-first order rate constant for hydrolysis of the derivative is in the range 10 -6 sec -1 to 10 -3 sec -1 in isotonic aqueous media at pH 7.4 at 37° C. with the exception of: (1) p-guanidinobenzoyl human plasmin, (2) p-guanidinobenzoyl streptokinase-plasminogen activator complex.
Claim 15
Dependent Claim
13 words
A derivative as claimed in claim 12 wherein the enzyme is human plasmin.
Claim 16
Dependent Claim
15 words
A derivative as claimed in claim 12 wherein the enzyme is streptokinase/human plasminogen activator complex.
Claim 17
Dependent Claim
21 words
A derivative as claimed in claim 12 wherein the enzyme is a mixture of human plasmin and streptokinase/human plasminogen activator complex.
Claim 18
Dependent Claim
20 words
A derivative as claimed in claim 12 to wherein the group which is removable by hydrolysis is an acyl group.
Claim 19
Dependent Claim
21 words
A derivative as claimed in claim 16 wherein the acyl group is a benzoyl, substituted benzoyl, acryloyl or substituted acryloyl group.
Claim 20
Dependent Claim
47 words
A derivative as claimed in claim 19 wherein the acyl group is a benzoyl group or a substituted benzoyl group having one or more meta and/or para substituents wherein the sum of the Hammett σ m or σ p values is in the range +0.1 to -1.1.
Claim 21
Dependent Claim
31 words
A derivative as claimed in claim 18 wherein the acyl group is benzoyl, optionally substituted with halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkanoyloxy, C 1-6 alkanoylamino or p-guanidino.
Claim 22
Dependent Claim
26 words
A derivative as claimed in claim 17 wherein the acyl group is acryloyl, optionally substituted with C 1-6 alkyl, furyl, phenyl, or C 1-6 alkyl phenyl.
Claim 23
Dependent Claim
3 words
p-Anisoyl human plasmin.
Claim 24
Dependent Claim
3 words
p-Anisoyl human plasmin.
Claim 25
Dependent Claim
6 words
p-Anisoyl streptokinase human plasminogen activator complex.
Claim 26
Dependent Claim
6 words
p-Anisoyl streptokinase human plasminogen activator complex.
Claim 27
Dependent Claim
13 words
A mixture of p-anisoyl human plasmin and p-anisoyl streptokinase human plasminogen activator complex.
Claim 28
Dependent Claim
13 words
A mixture of p-anisoyl human plasmin and p-anisoyl streptokinase human plasminogen activator complex.
Claim 29
Dependent Claim
78 words
A process for preparing a derivative of an in vivo fibrinolytic enzyme as claimed in claim 12 which process comprises reacting an in vivo fibrinolytic enzyme as defined herein with a blocking agent: AB wherein A is a group which is selective for the catalytic site essential for fibrinolytic activity and which is capable of transfering from the group B to the catalytic site and B is a group which facilitates the attachment of A to the enzyme.
Claim 30
Dependent Claim
14 words
A process as claimed in claim 24 wherein the agent AB is p-nitrophenyl p-guanidinobenzoate.
Claim 31
Dependent Claim
55 words
A process for preparing a derivative as claimed in claim 11 which process comprises reacting an in vivo fibrinolytic enzyme with a compound: EF wherein E is a locating group which is selective for the catalytic site and F is a group which is capable of transfering from the locating group to the active site.
Claim 32
Dependent Claim
16 words
A process as claimed in claim 26 wherein E is a benzoyl or substituted benzoyl group.
Claim 33
Dependent Claim
13 words
A process as claimed in claim 26 wherein E is p-amidinophenyl, or p-acetamidinophenyl.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1984-08-24 | 1985-02-23 | 1985-08-25 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1988-08-24 | 1989-02-23 | 1989-08-25 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1992-08-24 | 1993-02-23 | 1993-08-25 | $7700.00 | Window Closed / Lapsed |