Doppel-Targeting Molecules for Selective Angiogenesis Inhibition
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current anti-angiogenesis therapies lack the ability to discriminate between normal and pathological angiogenesis, leading to systemic suppression of beneficial angiogenesis processes alongside the inhibition of tumor growth.
Innovation Solution
Development of doppel-targeting molecules, such as anti-doppel antibodies and heparin-containing conjugates, that specifically inhibit pathological angiogenesis by interfering with doppel-tyrosine kinase receptor signaling, particularly targeting VEGFR2, VEGFR1, VEGFR3, bFGFR, and PDGFR.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-VEGF monoclonal antibodies or TKR inhibitors are used to inhibit angiogenesis, then tumor growth is suppressed, but normal physiological angiogenesis is also suppressed
Solution Approach 1:
The patent applies local quality by targeting doppel expression specifically in tumor endothelial cells rather than systemically inhibiting all VEGF signaling. Doppel is overexpressed in pathological angiogenesis associated with tumors but not in normal physiological angiogenesis, allowing selective inhibition of tumor blood vessel formation while preserving normal angiogenic processes
Solution Approach 2:
The patent segments the angiogenesis pathway by identifying doppel as a specific component present only in tumor endothelial cells. By targeting doppel specifically, the therapy separates pathological angiogenesis (in tumors) from physiological angiogenesis (in normal tissues), enabling selective inhibition of the pathological process
2Reliability
If VEGF signaling is systemically suppressed to inhibit tumor angiogenesis, then tumor vasculature is reduced, but essential physiological functions are interfered with
Solution Approach 1:
The invention uses local quality by exploiting the differential expression pattern of doppel protein. Doppel is overexpressed specifically in tumor endothelial cells but absent or low in normal endothelial cells, allowing the antibody to selectively inhibit angiogenesis in tumors while leaving normal physiological functions intact
Solution Approach 2:
The patent introduces doppel as an intermediary target between VEGF and its receptors. By blocking doppel-VEGFR interaction specifically in tumor endothelial cells, the therapy mediates selective inhibition of pathological angiogenesis without systemically suppressing VEGF signaling required for normal physiological functions
Data Source
AI summary
Described herein are doppel-targeting molecules useful for inhibiting pathological angiogenesis and treating diseases and conditions associated with pathological angiogenesis, such as tumors, cancers, atherosclerosis, tuberculosis, asthma, pulmonary arterial hypertension (PAH), neoplasms and neoplasm-related conditions, and for detecting doppel expression in a subject. Related compositions and methods also are described.