Bispecific Chimeric Molecules for VEGF and Ang2 Dual Antagonism
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Solution Overview
Problem
Current dual antagonists for VEGF and Ang2, such as RG7716, require high dosages due to limited binding affinity, posing challenges for formulation and administration, especially for ocular applications where volume is restricted.
Innovation Solution
Development of bispecific chimeric molecules with enhanced binding domains to both VEGF and Ang2, comprising VEGF-binding moieties like antibodies or scFv and Ang-2 antagonist peptides, which are operationally linked to improve binding affinity and reduce dosage requirements.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high dosages of dual antagonists like RG7716 are used to achieve sufficient binding, then therapeutic efficacy is improved, but formulation and administration become more difficult especially for ocular applications
Solution Approach 1:
The patent combines VEGF-binding and Ang2-binding domains into a single bispecific chimeric molecule. This merging allows simultaneous targeting of both VEGF and Ang2 at lower concentrations, achieving therapeutic efficacy without requiring high dosages that complicate formulation and administration.
Solution Approach 2:
The invention creates a composite molecular structure integrating two distinct binding domains (anti-VEGF and anti-Ang2) into one chimeric molecule. This composite approach enhances binding affinity and potency, enabling effective treatment at lower doses that are more suitable for ocular formulation and administration.
2Device complexity
If limited binding affinity of current dual antagonists is accepted, then simpler molecular structures are maintained, but higher dosages are required
Solution Approach 1:
The patent merges VEGF-binding and Ang2-binding functionalities into a single bispecific chimeric molecule. This integration increases binding affinity to both targets simultaneously, reducing the quantity of substance needed while the molecular structure remains manageable through modular domain construction.
Data Source
AI summary
The present disclosure relates to fusion molecules and chimeric molecules which comprise two components: an Ang-2 antagonist peptide linked to a VEGF-binding moiety. Further disclosed are methods of using said chimeric molecules to treat a patient cancer, proliferative retinopathy, neovascular glaucoma, macular edema, wet age-related macular degeneration (wAMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME), or diabetic retinopathy (DR).