Massachusetts Institute of Technology

University of Iowa Research Foundation

Children's Medical Center Corporation

Ramnath Sasisekharan

Robert Samuel Langer

Charles L Cooney

Robert J Linhardt

Daniel L Lohse

Joseph J Zimmermann

Kelley Wilson Moremen

Marsha A Moses

Matthew A Nugent

Charles I Cooney

A single, reproducible scheme to simultaneously purify all three of the heparin lyases from F. heparinum to apparent homogeneity is disclosed herein. The kinetic properties of the heparin lyases have been determined as well as the conditions to optimize their activity and stability. Mono-clonal antibodies to the three heparinases are also described and are useful for detection, isolation and characterization of the heparinases.

Purification, composition and specificity of Heparinase I, II, and III from Flavobacterium heparinum

A purified heparinase I, II and III free of lyase activity and each having a molecular weight of 42,800 84,100, 70,800, respectively, are produced by culturing Flavobacterium heparinum. The kinetic properties of the heparinases have been determined as well as the conditions to optimize their activity and stability.

Purification of Heparinase I, II and III from Flavobacterium heparinum

The cloning of the heparinase gene from Flavobacterium Heparinum using the polymerase chain reaction is described. The Open Reading Frame (ORF) corresponded to 1152 base pairs encoding a precursor protein of MW 43,800 daltons. The amino acid sequence reveals a 20-residue leader peptide. The gene was expressed in two expression systems in E. coli.

Method for obtaining a modified heparinase gene

Heparinase gene from flavobacterium heparinum

A single, reproducible scheme to simultaneously purify all three of the heparin lyases from F. heparinum to apparent homogeneity is disclosed herein. The kinetic properties of the heparin lyases have been determined as well as the conditions to optimize their activity and stability. Monoclonal antibodies to the three heparinases are also described and are useful for detection, isolation and characterization of the heparinases.

Purification, composition and specificity of heparinase I, II, and III

Pharmaceutical compositions for delivering an effective dose to a desired site of a heparinase. These compositions are based on the discovery that heparinase alone can inhibit angiogenesis. The effective dosage is dependent not only on the heparinase, but also on the method and means of delivery, which can be localized or systemic. For example, in some applications, as in the treatment of psoriasis or diabetic retinopathy, the inhibitor is delivered in a topical ophthalmic carrier. In other applications, as in the treatment of solid tumors, the inhibitor is delivered by means of a biodegradable, polymeric implant.

Method for inhibiting angiogenesis using heparinase

Purification of heparinase I, II, and III from Flavobacterium heparinum

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Arlington, MA, United States of America

Ramnath Sasisekharan