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Modified serine protease inhibitors for use in the treatment of bleeding disorders

A serine protease and inhibitor technology, applied in protease inhibitors, blood diseases, extracellular fluid diseases, etc.

Active Publication Date: 2019-08-23
CAMBRIDGE ENTERPRISE LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Thus, current treatments for bleeding disorders such as hemophilia have a range of deficiencies

Method used

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  • Modified serine protease inhibitors for use in the treatment of bleeding disorders
  • Modified serine protease inhibitors for use in the treatment of bleeding disorders
  • Modified serine protease inhibitors for use in the treatment of bleeding disorders

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Embodiment Construction

[0029] The present invention relates to the modification of serine protease inhibitors to increase the specificity of serine protease inhibitors for APC relative to other coagulation proteases. Modified serpin variants specific for APC may be useful, for example, as procoagulants.

[0030] Because the modified serpins are specific for APCs, the modified serpins described herein are expected to have little or no off target effects and are specific for the pathway activated upon injury. This enables the therapeutic and prophylactic use of the modified serine protease inhibitors, as well as in emergency situations (ie trauma). Administration of the modified serpins is predictable because they are suicide inhibitors, meaning that one molecule of the serpin cannot inhibit more than one protease molecule. In addition, the plasma half-life of modified serpins is likely to exceed that of current bypassing agents, relative to serpins alone, due to the efficient natural clearance mecha...

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Abstract

The present invention relates to procoagulant serine protease inhibitor molecules engineered to exhibit increased specificity for anticoagulant proteases by modifying P4, P2, P1 and / or P1' residues within the reactive center loop (RCL). These modified serpin molecules can be used in therapy, for example, as coagulants for the treatment of bleeding.

Description

technical field [0001] The present invention relates to modified serine protease inhibitor (serpin) molecules with altered specificity, in particular modified to have anticoagulant protease (anticoagulant protease, anticoagulant protease) (such as activated protein C (activated protein C) , a serine protease inhibitor molecule of increased specificity of activated Protein C) (APC)). Background technique [0002] Hemophilia is a bleeding disorder caused by a lack of circulating plasma fVIII (hemophilia A, HA) or fIX (hemophilia B, HB) (reviewed in Bolton-Maggs & Pasi, 2003). This reduces the activity of endogenous X enzyme (tenase) (Xase) and thereby reduces the amount of thrombin produced when tissue damage occurs. This leads to uncontrolled bleeding after injury as well as spontaneous bleeding to joints and soft tissues. [0003] Hemophilia affects about 1 in 5,000 people. The 170,000 patients identified in the World Federation of Hemophilia Global Survey is an underesti...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/81
CPCC07K14/8125A61L24/0015A61L2300/252A61L2300/258A61K38/00A61L2300/418A61L2400/04C07K14/8121A61P43/00A61P7/02A61P7/04A61K38/482A61L26/0047
Inventor 詹姆斯·安德鲁·亨廷顿斯蒂芬妮·波尔德代克特雷弗·巴格林
Owner CAMBRIDGE ENTERPRISE LTD
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