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US4629694A Expired / Lapsed US ⏱️ 0.0 years remaining

Detecting and distinguishing between plasminogen activators

Assignee: Cornell Research Foundation Inc
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Filing: 1983-07-12
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Granted: 1986-12-16
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Expires: 2003-07-12
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Abstract

Abstract This invention relates to a method for determining fibrinolytic activation in human blood and to a method to distinguish between tissue (e.g. vascular) plasminogen activator and urokinase-like plasminogen activator contributions to fibrinolytic activation. Broadly, the method of the invention relates to detecting the level of plasmin-plasmin inhibitor complexes in blood plasma samples before and after clotting thereof; a greater increase in the complex level in the clotted sample as compared to non-clotted samples indicating the presence of circulating tissue plasminogen activator, with substantially identical levels of increase of complex in both the clotted and unclotted samples indicating the sole presence of urokinase-type plasminogen activator in the sample.

Inventors

  • 👤 Peter C. Harpel

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-07 13:16
CPC Classifications
C; C12; C12Q; C12Q1/00; C12Q1/56; G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/86; G01N2333/00; G01N2333/81; G01N2333/90; G01N2333/914; G01N2333/948; G01N2333/968; G01N2333/972; G01N2333/9723; Y; Y10; Y10S; Y10S435/00; Y10S435/971

Claims Analysis

Total Claims: 10
Claim 1
Independent Claim 125 words
A method of determining plasminogen activator induced fibrinolytic activity in human blood which comprises: (a) providing plasma samples from freshly drawn blood comprising a first sample which is unclotted and a second sample which has been clotted; (b) determining the level of plasmin-naturally occurring plasmin inhibitor complex in both the unclotted and clotted samples first proximate the time of establishment of the samples and again after a time delay sufficient to allow plasminogen activator present in the sample to convert a significant portion of the plasminogen present in the samples to plasmin; and (c) comparing the levels of the plasmin-naturally occurring plasmin inhibitor complex in both the unclotted and clotted plasma samples to identify tissue-type plasminogen activator or urokinase-type plasminogen activator contributions to fibrinolytic activity.
Claim 2
Independent Claim 125 words
A method of determining plasminogen activator induced fibrinolytic activity in human blood which comprises: (a) providing plasma samples from freshly drawn blood comprising a first sample which is unclotted and a second sample which has been clotted; (b) determining the level of plasmin-naturally occurring plasmin inhibitor complex in both the unclotted and clotted samples first proximate the time of establishment of the samples and again after a time delay sufficient to allow plasminogen activator present in the sample to convert a significant portion of the plasminogen present in the samples to plasmin; and (c) comparing the levels of the plasmin-naturally occurring plasmin inhibitor complex in both the unclotted and clotted plasma samples to identify tissue-type plasminogen activator or urokinase-type plasminogen activator contributions to fibrinolytic activity.
Claim 3
Dependent Claim 33 words
The method as in claim 1 wherein the clotted and unclotted, plasma samples are provided and the first complex determination made within about thirty minutes from the time that the blood is extracted.
Claim 4
Independent Claim 40 words
The method as in claims 1 or 2 where the fibrinolytic activity is tissue-type plasminogen activator induced and the activity is indicated by a significantly greater increase in complex levels in the clotted sample as compared to the unclotted sample.
Claim 5
Independent Claim 39 words
A method as in claims 1 or 2 where the fibrinolytic activity is urokinase-like plasminogen activator induced and the activity is indicated by a substantially identical level of increase in the clotted sample as compared to the unclotted sample.
Claim 6
Dependent Claim 63 words
The method as in claim 1 wherein the level of complex in the samples is determined by a method which comprises: (a) forming an insoluble immobilized immunocaptured naturally occurring plasmin inhibitor-plasmin complex comprising plasmin, naturally occurring plasmin inhibitor and plasmin inhibitor antibody or an inhibitor reactive fragment thereof, and (b) detecting the plasmin or plasmin inhibitor-plasmin complex in the insoluble immobilized immunocaptured complex.
Claim 7
Dependent Claim 30 words
The method of claim 5 wherein immobilized naturally occurring plasmin inhibitor-plasmin complex is affixed to a solid or semisolid matrix by means of the inhibitor antibody or active fragment thereof.
Claim 8
Dependent Claim 49 words
The method of claim 5 or 6 wherein: (a) the plasma samples are contacted with a complex reactive solid or semisolid matrix have affixed thereon inhibitor antibody or an inhibitor reactive fragment thereof to immunocapture complex from the plasma samples. (b) analytically determining the quantity of the captured complex.
Claim 9
Dependent Claim 17 words
The method of claim 7 wherein the inhibitor is α 2 plasmin inhibitor or α 2 macroglobulin.
Claim 10
Dependent Claim 29 words
The method of claim 1, 2, 5 or 6 wherein the human blood sample is drawn after venous occlusion sufficient to stimulate tissue-type plasminogen activator activity in said blood.

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1989-12-15 1990-06-16 1990-12-16 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1993-12-15 1994-06-16 1994-12-16 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1997-12-15 1998-06-16 1998-12-16 $7700.00 Window Closed / Lapsed

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