Myoung Hee Lee

US Patent:

56372990, Jun 10, 1997

Filed:

Jun 5, 1995

Appl. No.:

8/461172

Inventors:

Jan McDonagh - Chestnut Hill MA
Myoung H. Lee - Brookline MA

Assignee:

Beth Israel Hospital - Boston MA

International Classification:

A61K 3848
A61K 3849
C12N 964
C12N 968

US Classification:

424 9463

Abstract:

This invention provides an improved method for enhancing the activity of thrombolytic agents, including t-PA, scu-PA, tcu-PA, streptokinase, acylated plasminogen-streptokinase activator complex (APSAC), mixtures of these, and other activators of plasminogen. The enhancement method comprises supplementation of plasma plasminogen levels with deglycosylated forms of glu- and lys-plasminogen. Deglycosylated plasminogen refers herein to glu- or lys-plasminogen 2 having a single oligosaccharide chain at Thr. sub. 345, plasminogens having a single oligosaccharide chain at Asn. sub. 288, and unglycosylated forms of plasminogen. The work described herein shows that a less glycosylated form of plasminogen (glu-plasminogen 2) has a higher affinity for fibrin clots than a more glycosylated plasminogen (glu-plasminogen 1). Based on this work, it is believed that glycosylation of plasminogen inhibits binding of plasminogen to fibrin clots, perhaps due to steric hindrance, and further, that deglycosylated forms of plasminogen may be more effective enhancers of scu-PA in thrombolytic therapy than fully glycosylated forms of plasminogen. Improved enhancement of the activity of thrombolytic agents allows the use of lower therapeutic doses and thus, is expected to relieve some of the bleeding and other side effects of thrombolytic therapy.

US Patent:

62970232, Oct 2, 2001

Filed:

Sep 2, 1994

Appl. No.:

8/300447

Inventors:

Jan McDonagh - Chestnut Hill MA
Myoung H. Lee - Brookline MA
Marcin J. Mankowski - Newton MA

Assignee:

Beth Israel Deaconess Medical Center, Inc. - Boston MA

International Classification:

C12Q 156

US Classification:

435 13

Abstract:

The invention is based upon the discovery that PAI-1 activity of a sample can be measured with sensitivity and correlation to in vivo activity without the use of standard curves. The assay determines the PAI-1 activity of a sample upon utilizing the second order rate equation for the reaction of PAI-1 and t-PA, as measured by their activities, in that sample.