Oligomeric Compounds Targeting Factor XII for Thrombosis Prevention
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Solution Overview
Problem
Current treatments for thromboembolic conditions, such as myocardial infarction, stroke, and venous thromboembolism, often rely on anticoagulants that increase the risk of bleeding, and there is a need for alternative methods to reduce Factor XII (FXII) levels to prevent these conditions.
Innovation Solution
Development of oligomeric compounds, specifically modified oligonucleotides, that target and reduce FXII RNA and protein levels in cells, thereby inhibiting FXII activity to prevent thromboembolic events and associated symptoms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional anticoagulants (warfarin, heparin, direct oral anticoagulants) are used to treat thromboembolic conditions, then the risk of thromboembolic events is reduced, but the risk of bleeding increases significantly
Solution Approach 1:
The patent extracts and targets the specific pathological factor (Factor XII) that initiates the thrombotic cascade through the intrinsic pathway, rather than using broad-spectrum anticoagulants that affect multiple coagulation factors. By using oligomeric compounds to specifically bind and neutralize Factor XII, the invention removes only the harmful thrombotic initiation step while preserving other essential coagulation functions, thereby reducing bleeding risk.
Solution Approach 2:
The oligomeric compounds act as intermediary molecules that specifically bind to Factor XII, preventing its activation to FXIIa and subsequent triggering of the intrinsic coagulation pathway and kallikrein-kinin system. This intermediary approach selectively blocks the pathological pathway without broadly inhibiting coagulation, thus achieving thromboembolic prevention with reduced bleeding complications.
2Reliability
If Factor XII activity is inhibited to prevent thrombosis, then thromboembolic conditions are reduced, but the effectiveness and safety profile of treatment needs optimization
Solution Approach 1:
The patent employs oligomeric compounds with specific structural parameters (molecular weight, composition, charge density) that optimize their binding affinity to Factor XII while ensuring adequate pharmacokinetic properties. By carefully controlling these parameters, the invention achieves effective Factor XII inhibition at therapeutic doses while maintaining a favorable safety profile, avoiding both under-dosing (ineffective) and over-dosing (excessive bleeding).
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 oligomeric compounds effectively decrease FXII activity, reducing the risk of thromboembolic conditions like deep vein thrombosis, pulmonary embolism, and myocardial infarction, while minimizing the risk of bleeding complications associated with traditional anticoagulants.
Implementation Method 1
oligomeric compounds comprise modified oligonucleotides that target and reduce FXII RNA and protein levels
Data Source
AI summary
Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of FXII RNA in a cell or subject, and in certain instances reducing the amount of FXII protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to prevent, treat, or ameliorate at least one symptom of a thromboembolic condition. Such thromboembolic conditions include deep vein thrombosis, venous or arterial thrombosis, pulmonary embolism, myocardial infarction, and stroke. Such symptoms include pain, shortness of breath, heart burn, cold sweat, fatigue, lightheadedness, dizziness, swelling, cramping, and death. Such compounds, methods, and pharmaceutical compositions are useful to prevent, treat, or ameliorate at least one symptom of hereditary angioedema.