Antigen Binding Molecules for LVAD-Induced Hemorrhagic Disorder
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Solution Overview
Problem
Current treatments for hemorrhagic complications associated with circulatory assist device implantation, such as left ventricular assist devices, are inadequate in preventing bleeding disorders due to the lack of effective strategies targeting ADAMTS13 inhibition.
Innovation Solution
Development of antigen binding molecules, including monoclonal antibodies and antibody fragments, that specifically bind to ADAMTS13 to inhibit VWF cleavage, thereby preventing hemorrhagic complications in patients with implanted circulatory assist devices.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If circulatory assist devices are implanted to treat end-stage heart failure, then life-saving cardiac support is achieved, but hemorrhagic complications and bleeding disorders occur as severe side effects
Solution Approach 1:
The patent introduces antigen binding molecules (antibodies or antibody fragments) as intermediary substances that specifically bind to ADAMTS13, preventing it from cleaving VWF. This intermediary approach blocks the harmful interaction between ADAMTS13 and VWF without directly modifying the circulatory assist device or the patient's heart condition, thereby resolving the bleeding complication while maintaining the life-saving function of the device
2Stability of the object's composition
If ADAMTS13 enzyme activity is maintained to cleave VWF, then normal physiological function is preserved, but hemorrhagic bleeding occurs in LVAD patients
Solution Approach 1:
The patent applies local quality by directing the antigen binding molecules to specifically interact with ADAMTS13 in the context of high shear stress environments (such as near the circulatory assist device), where pathological VWF cleavage occurs. This localized intervention allows normal physiological ADAMTS13 function elsewhere to be preserved while preventing harmful bleeding at the critical site of device-induced high shear stress
3Ease of manufacture
If conventional treatments are used for hemorrhagic complications, then general bleeding management is attempted, but effective prevention of ADAMTS13-mediated bleeding is not achieved
Solution Approach 1:
The patent changes the therapeutic parameter from general bleeding management approaches to specifically targeting ADAMTS13 activity through antigen binding molecules. By altering the mechanism of action to focus on inhibiting ADAMTS13's enzymatic activity rather than addressing bleeding symptoms generally, the patent achieves reliable prevention of ADAMTS13-mediated hemorrhagic complications
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 antigen binding molecules effectively inhibit ADAMTS13 activity, preserving high molecular weight VWF multimers and reducing bleeding risks in patients with implanted circulatory assist devices, including those with Heyde's syndrome and ECMO support.
Implementation Method 1
antigen binding molecules specifically binding to ADAMTS13 and inhibiting VWF cleavage by ADAMTS13
Data Source
AI summary
The present invention relates to methods of treatment by human ADAMTS13 inhibition in circulatory assist device induced haemorrhagic complication such as a bleeding disorder, in particular, bleeding after left ventricular assist device (LVAD) implantation. The present invention further relates to specific monoclonal antibodies inhibiting ADAMTS13 function.