Ticagrelor-Binding Antibodies for Rapid Platelet Function Restoration
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Solution Overview
Problem
There is a need for a clinical management strategy to balance the antithrombotic effect of ticagrelor with the control of bleeding in patients experiencing major bleeding or requiring urgent surgery, as current treatments lack an effective antidote for ticagrelor-induced platelet inhibition.
Innovation Solution
Development of antibodies that specifically bind to ticagrelor and its active metabolite, neutralizing their antiplatelet effects without inhibiting other compounds, allowing for rapid reversal of platelet inhibition and enabling the continuation of ticagrelor therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ticagrelor is administered to prevent thrombotic events, then antithrombotic effect is improved, but bleeding risk increases
Solution Approach 1:
The patent introduces a neutralizing antibody as an intermediary substance that binds to ticagrelor and its active metabolite, preventing them from interacting with platelet P2Y12 receptors. This antibody acts as a mediator that allows simultaneous presence of ticagrelor therapy and bleeding control by sequestering the drug in circulation.
Solution Approach 2:
The neutralizing antibody provides preliminary anti-action by being administered before or at the time of bleeding intervention to preemptively neutralize ticagrelor activity. This allows rapid reversal of platelet inhibition before major bleeding occurs or immediately upon detection.
2Object-affected harmful factors
If platelet transfusions or coagulation factors are administered to control bleeding, then haemostasis is improved, but availability and effectiveness are limited
Solution Approach 1:
The neutralizing antibody serves as a specific antidote intermediary that directly counteracts ticagrelor's mechanism of action at the receptor level, providing a more targeted and reliable treatment option compared to non-specific platelet transfusions or coagulation factors.
Solution Approach 2:
The invention changes the pharmacological parameter by introducing a substance (neutralizing antibody) that alters the binding affinity and availability of ticagrelor at its target receptor, thereby reversing the drug's effect without requiring replacement of the entire hemostatic system.
3Reliability
If ticagrelor therapy is continued to maintain antithrombotic protection, then thrombotic prevention is improved, but bleeding control is worsened
Solution Approach 1:
The neutralizing antibody enables continuity of useful action by allowing ticagrelor therapy to be maintained or restarted after bleeding control, as the antibody continuously neutralizes the drug in circulation. This creates a dynamic balance where antithrombotic protection is maintained while bleeding is controlled through the presence of the neutralizing antibody.
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 antibodies effectively neutralize ticagrelor and its metabolite, restoring platelet function within minutes, reducing bleeding risk, and allowing for the resumption of ticagrelor therapy, thus providing a balanced clinical management approach.
Implementation Method 1
an antibody that specifically binds a cyclopentyltriazolopyrimidine compound of the Formula (Ia)
Data Source
AI summary
The disclosure generally provides antibodies and antigen binding fragments of antibodies that bind ticagrelor and metabolites of ticagrelor. The disclosure also provides compositions comprising the antibodies, nucleic acid molecules encoding the antibodies, methods of treating a patient comprising administering the antibodies, and methods of making and using the antibodies.