Thrombin Antibodies Targeting Exosite 1 for Selective Anticoagulation
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Solution Overview
Problem
Current anticoagulant therapies for preventing thrombosis have a narrow therapeutic window, increasing the risk of bleeding and varying responses among individuals, as they often inhibit thrombin without distinguishing between pathological coagulation and physiological haemostasis.
Innovation Solution
Development of antibody molecules that selectively bind to exosite 1 of thrombin, inhibiting thrombin activity without affecting normal haemostasis, thereby preventing thrombosis without promoting bleeding.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional anticoagulant therapies are used to prevent thrombosis, then thrombosis is inhibited, but the risk of bleeding increases
Solution Approach 1:
The antibody targets a specific local site (exosite 1) on the thrombin molecule rather than inhibiting the entire thrombin molecule globally. This localized targeting allows selective inhibition of thrombin functions involved in thrombosis while preserving functions necessary for normal haemostasis, thereby preventing thrombosis without increasing bleeding risk
Solution Approach 2:
The invention segments thrombin inhibition into specific functional domains by targeting exosite 1 separately from the catalytic site and other exosites. This segmentation enables selective anticoagulant activity that distinguishes between pathological coagulation and physiological haemostasis
2Reliability
If anticoagulant therapies are administered to inhibit thrombin, then thrombin activity is reduced, but the therapeutic window becomes narrow
Solution Approach 1:
The invention changes the binding parameter from general thrombin inhibition to specific exosite 1 binding. This parameter change creates a more precise therapeutic window by altering the specificity of thrombin interaction, allowing effective anticoagulation at lower doses without causing excessive bleeding
3Reliability
If non-selective thrombin inhibitors are used, then thrombosis is prevented, but individual patient responses vary
Solution Approach 1:
By targeting the specific local region of exosite 1 on thrombin, the antibody provides consistent and predictable inhibition of thrombin functions involved in thrombosis across different patients, reducing variability in individual responses compared to non-selective inhibitors
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The antibody molecules effectively inhibit thrombin-mediated conditions such as thrombosis and embolism without increasing the risk of bleeding, maintaining normal haemostatic responses, thus offering a safer anticoagulant approach.
Implementation Method 1
antibody molecules that selectively bind to exosite 1 of thrombin
Data Source
AI summary
This invention relates to isolated antibodies which recognise the exosite 1 epitope of thrombin and selectively inhibit thrombin without promoting bleeding. These antibody molecules may be useful in the treatment and prevention of thrombosis, embolism and other conditions mediated by thrombin.