Enzymatic preparation of increased anticoagulant bovine sourced heparin

US10864227B2 · kind B2 · utility

Assignee

• Rensselaer Polytechnic Institute · US

Inventors

• Li Fu · 东风镇, CN
• Kevin Li · Middletown, US
• Daisuke Mori · Rensselaer, US
• Makoto Hirakane · Rensselaer, US
• Jonathan S. Dordick · Schenectady, US
• Robert J. Linhardt · Iowa City, US

Key dates

• Filing date: Mar 20, 2018
• Grant date: Dec 15, 2020
• Expiry date: Mar 20, 2038

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12Y208/02
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A heparin structure with increased anticoagulant activity and method of making the same are disclosed. A heparin sample is provided and treated with a heparan sulfate sulfotransferase in an enzymatic reaction to add sulfuryl groups from a sulfuryl group source to the heparin sample, resulting in a heparin structure having above about 8% more 3-O-sulfo groups relative to wild-type bovine intestinal heparin. The added sulfuryl groups modify the heparin structure and increase the sample's binding to antithrombin III and its anticoagulant activity to be more similar and a viable alternative to porcine intestinal heparin. The modified heparin exhibits an anti-FXa activity and an anti-FIIa activity greater than about 180 U/mg, and a ratio of the anti-FXa activity to the anti-FIIa activity of about 0.9 to about 1.1, consistent with U.S. Pharmacopeia (USP) heparin activity specifications.