Dual SEMA4D and VEGF Binding Molecules for Angiogenesis Inhibition
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Solution Overview
Problem
Current cancer treatments that target VEGF-induced angiogenesis are associated with significant toxicity, and there is a need for alternative therapeutics that can inhibit or suppress tumor angiogenesis effectively without these adverse effects.
Innovation Solution
Administering a combination of a first isolated binding molecule that specifically binds to semaphorin-4D (SEMA4D) and a second isolated binding molecule that specifically binds to vascular endothelial growth factor (VEGF) to inhibit their respective interactions with Plexin-B1 and VEGFR2, thereby blocking angiogenesis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-VEGF therapies are used to inhibit angiogenesis, then tumor growth is suppressed, but significant toxicity occurs
Solution Approach 1:
The patent divides the anti-angiogenesis approach into two separate targeting strategies: one component targets VEGF (vascular endothelial growth factor) and the other targets SEMA4D (semaphorin-4D). This segmentation allows selective inhibition of angiogenic pathways while potentially reducing off-target toxicities associated with non-specific anti-VEGF therapies. The dual-component composition enables differentiated action on distinct molecular targets within the angiogenesis pathway.
Solution Approach 2:
The patent employs a composite therapeutic composition containing both anti-VEGF binding molecules and anti-SEMA4D binding molecules. This composite approach combines two different mechanisms of action (VEGF pathway inhibition and SEMA4D pathway inhibition) into a single therapeutic regimen, creating a synergistic effect that enhances anti-angiogenesis efficacy while potentially reducing the toxicities associated with high-dose single-target therapies.
2Reliability
If VEGF binding molecules are administered to block VEGF-VEGFR interaction, then angiogenesis is inhibited, but therapeutic alternatives with reduced toxicity are needed
Solution Approach 1:
The patent introduces SEMA4D as an additional intermediary target in the angiogenesis pathway. By incorporating anti-SEMA4D binding molecules into the therapy, the treatment engages a secondary mediator (SEMA4D-PlexinB1 axis) that works in parallel with the primary VEGF-VEGFR pathway. This dual-intermediary approach provides alternative routes to achieve angiogenesis inhibition, reducing dependence on a single high-toxicity mechanism.
Solution Approach 2:
The patent changes the therapeutic parameters by shifting from monotherapy with anti-VEGF agents to combination therapy incorporating anti-SEMA4D agents. This parameter change involves modifying the molecular target profile, binding affinity characteristics, and mechanism of action diversity. The altered therapeutic parameters enable achievement of similar or enhanced anti-angiogenesis effects with potentially reduced toxic side effects through distributed target engagement.
3Reliability
If combination therapy targeting both SEMA4D and VEGF is used, then anti-angiogenesis efficacy is enhanced, but treatment complexity increases
Solution Approach 1:
The patent merges two distinct therapeutic agents (anti-VEGF binding molecules and anti-SEMA4D binding molecules) into a single combination therapy formulation. This merging strategy consolidates multiple administration protocols, dosing schedules, and monitoring requirements into a unified treatment regimen. The combined composition simplifies clinical implementation compared to sequential or separate administration of individual agents, reducing overall treatment complexity while maintaining enhanced anti-angiogenesis efficacy.
Data Source
AI summary
Provided herein are methods for inhibiting tumor angiogenesis in a cancer patient, the method comprising administering to the subject an effective amount of a first isolated binding molecule which specifically binds to semaphorin-4D (SEMA4D) and an effective amount of a second isolated binding molecule which specifically binds to VEGF.