IL9-Fibronectin ED-A Conjugates for Pulmonary Hypertension
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Solution Overview
Problem
Current treatments for pulmonary hypertension (PH) are largely ineffective for forms other than pulmonary arterial hypertension (PAH), as they primarily focus on reducing vascular tone, and there is a lack of standardized treatments for PH with unclear or multifactorial mechanisms, limiting their applicability to other common forms of the disease.
Innovation Solution
Development of conjugates comprising interleukin-9 (IL9) conjugated to specific binding members that target antigens associated with tissue and vascular remodeling, such as the Extra Domain-A (ED-A) of fibronectin, for targeted delivery to remodelled lung and heart tissues, allowing for precise treatment of PH regardless of its underlying cause.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments focus on reducing vascular tone, then pulmonary artery pressure is reduced, but they are ineffective for forms of PH other than PAH and lack applicability to multifactorial mechanisms
Solution Approach 1:
The patent applies local quality by targeting specific antigens (ED-A, collagen, elastin) that are locally present in remodelled tissues. The conjugates deliver IL9 specifically to sites of tissue remodelling in the lung and heart, rather than systemically. This localized targeting allows the treatment to address the specific pathological processes in different forms of PH while maintaining effectiveness.
Solution Approach 2:
The patent achieves universality by developing a platform technology using IL9 conjugated to different specific binding members that can target multiple antigens associated with tissue remodelling. This multi-functional approach allows the same conjugate structure to be adapted for different PH forms by changing the target antigen, making the treatment versatile across PAH, PH due to left heart disease, and other multifactorial forms.
2Adaptability or versatility
If standardized treatments are developed for PH with unclear mechanisms, then treatment options are expanded, but complexity of treatment protocols increases
Solution Approach 1:
The patent creates a universal treatment platform where IL9 is conjugated to specific binding members that can recognize multiple antigens involved in tissue remodelling. This single platform can address multifactorial PH mechanisms without requiring complex customized protocols for each patient, as the conjugates can target multiple pathological processes simultaneously.
Solution Approach 2:
The conjugates utilize the body's own remodelling processes as markers for targeting. By binding to antigens that are naturally upregulated in remodelled tissues (ED-A, collagen, elastin), the treatment automatically directs IL9 to the sites that need it most, eliminating the need for complex imaging guidance or surgical intervention.
3Quantity of substance
If IL9 is used systemically, then broad coverage is achieved, but delivery specificity to remodelled tissues is reduced
Solution Approach 1:
The patent merges IL9 with specific binding members (antibodies or antigen-binding fragments) that recognize antigens on remodelled tissues. This combination creates a conjugate that simultaneously achieves broad distribution through systemic administration while maintaining high specificity at the target site through the binding member's antigen recognition capability.
Solution Approach 2:
The specific binding member acts as an intermediary between the systemic circulation and the remodelled tissues. It binds to IL9 and uses its specificity for antigens like ED-A, collagen, and elastin to direct the conjugate to the appropriate tissues, thereby achieving both broad coverage and precise delivery.
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 IL9 conjugates significantly reduce right ventricular pressure and improve echocardiographic signs of right ventricular load and dysfunction in mouse models of PH, demonstrating therapeutic efficacy comparable to established standard therapies like Macitentan, with enhanced stability and delivery specificity.
Implementation Method 1
a specific binding member that binds an antigen associated with tissue and/or vascular remodelling, such as the Extra Domain-A (ED-A) of fibronectin
Data Source
AI summary
The present application relates to the treatment of pulmonary hypertension (PH) using interleukin-9 (IL9) and particularly, although not exclusively, to the treatment of PH using IL9 conjugated to a specific binding member that binds an antigen associated with tissue and/or vascular remodelling, such as the Extra Domain-A (ED-A) of fibronectin. Conjugates comprising a specific binding member that binds an antigen associated with tissue and/or vascular remodelling, such as ED-A, and IL9 that are suitable for the treatment of PH, in particular conjugates in which IL9 is conjugated to a single-chain Fv that binds ED-A or in which IL9 is conjugated an IgG that binds ED-A, are also disclosed.