Dual-Binding PD1-VEGFR2 Antibodies for Durable Pathway Blockade
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Solution Overview
Problem
Existing anti-PD1 antibody therapies for cancer treatment have limited durability, and combining them with anti-VEGFR2 agents requires separate agents with their own toxicity risks, necessitating a single agent that can effectively combine both pathways without these disadvantages.
Innovation Solution
Development of dual-antagonistic antibodies that specifically bind to both PD1 and VEGFR2, with optimized CDR sequences to maintain potent PD1 antagonism while also antagonizing VEGFR2 signaling, reducing the risk of off-target activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If combination therapy with separate anti-PD1 and anti-VEGFR2 agents is used, then cancer treatment efficacy is improved, but device complexity and treatment cost increase
Solution Approach 1:
The patent combines two separate therapeutic functions (anti-PD1 and anti-VEGFR2) into a single bispecific antibody molecule. This merging approach maintains the synergistic cancer treatment efficacy of combination therapy while reducing treatment complexity by eliminating the need for separate administration of multiple agents.
Solution Approach 2:
The bispecific antibody serves multiple functions simultaneously: it binds to both PD1 and VEGFR2 targets, providing dual therapeutic effects in a single molecule. This multi-functionality allows the single agent to deliver the combined benefits of both monotherapies while simplifying the treatment regimen.
2Reliability
If combination therapy with separate anti-PD1 and anti-VEGFR2 agents is used, then cancer treatment efficacy is improved, but loss of substance increases due to multiple toxicity risks
Solution Approach 1:
By merging anti-PD1 and anti-VEGFR2 activities into a single bispecific antibody, the patent reduces the cumulative toxicity burden associated with administering multiple separate agents. Patients are exposed to one molecule rather than multiple drugs, thereby reducing overall toxic effects while maintaining synergistic anti-cancer efficacy.
3Reliability
If separate anti-PD1 and anti-VEGFR2 agents are used, then both pathways are targeted, but manufacturing precision requirements increase
Solution Approach 1:
The patent merges the production of two separate therapeutic agents into a single manufacturing process for the bispecific antibody. This approach maintains comprehensive pathway coverage (both PD1 and VEGFR2 targeting) while simplifying manufacturing by eliminating the need for separate production, purification, and quality control processes for multiple agents.
Data Source
AI summary
Provided herein are antibody molecules that bind specifically to Programmed cell death 1 (PD1) and Vascular endothelial growth factor receptor 2 (VEGFR2), related nucleic acid molecules, vectors and host cells. Also provided herein are medical uses of such antibody molecules.