100KDa protein from blood which binds to and inhibits the activity of plasminogen activators

• US 5,004,802 A
• Filed: 07/11/1986
• Issued: 04/02/1991
• Est. Priority Date: 07/12/1985
• Status: Expired due to Fees

• Current Assignee: Nederlandse Organisatie VOOR Toegepast-Natuurwetenschappelijk Onderzoektno Juliana Van Stolberglaan 148 2595 CL The Hague The Netherlands
• Original Assignee: Nederlandse Centrale Organisatie Voor Teegepast-Natturwentenschappelijk Orderzoel
• Inventors: Kluft, Cornelis
• Primary Examiner(s): Kepplinger, Esther L.
• Assistant Examiner(s): Kushan, Jeff P.
• Application Number:
  US06/884,418
• Time in Patent Office: 1,726 Days
• Field of Search: 530/380, 530/350, 530/395, 530/381, 530/412, 530/413, 530/417, 530/421, 424/101, 435/215, 435/216, 435/212, 435/217, 514/2, 514/8, 514/21
• US Class Current: 530/380
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/8132 Plasminogen activator inhibitors
• CPC Class Codes: Y10S 530/829 Blood

Abstract

A protein called PA binding protein has been isolated which binds specifically and reversibly to tissue plasminogen activator. The protein is characterized by a molecular mass of about 100,000 daltons, and electrophoretic mobility in agarose at pH 8.6 equal to that of plasma β-globulins and an isoelectric point of 6.5 to 7.0. The protein is thermostable up to at least 56° C. and is cleared from the circulation with a half life on the order of days.

Claims

1. A protein called plasminogen activator binding protein purified so as to be free from contamination with materials that interfere with the plasminogen activator binding activity of the protein, having at least the following properties;

(a) it has a molecular mass of about 100,000 daltons as determined by gel chromatography on ULTROGEL®

ACA 44;

(b) it has an electrophoretic mobility in agarose at pH 8.6 equal to that of plasma β

-globulins;

(c) it migrates to an isoelectric point of from 6.5 to 7.5;

(d) the protein binds specifically and reversibly to urokinase having a free active center;

(e) the protein binds specifically and reversibly to t-PA having a free active center and specific Kringle-2; and

(f) the protein is thermostable so that it remains its plasminogen activator binding activity when heated to up to at least 56°

C.