HER-3 Binding Antibodies for Multi-Receptor Inhibition
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Solution Overview
Problem
Current therapies targeting HER-2 mediated signaling are limited in efficacy as they only respond significantly in patients with highly amplified HER-2, and resistance can develop, necessitating the need for drugs targeting other members of the HER family, such as HER-3, to effectively treat cancers.
Innovation Solution
Development of isolated binding proteins, including antibodies, that specifically bind to HER-3, interfering with its signaling pathways by reducing receptor tyrosine phosphorylation and inhibiting cell growth, proliferation, and metastasis, using sequences like those in SEQ ID NOs: 235-388 for CDRs and 390 for HER-3 epitopes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If HER-2 targeted therapies are used, then therapeutic effectiveness is improved in patients with highly amplified HER-2, but the scope of applicable patients is limited and resistance can develop
Solution Approach 1:
The patent develops antibodies that can target multiple HER family members (HER-2, HER-3, HER-4) with a single therapeutic agent. The anti-HER-2 antibody of cetuximab can bind to HER-2, HER-3, and HER-4 receptors, expanding the scope of patients who can be treated while maintaining therapeutic effectiveness through multi-target inhibition
2Reliability
If HER-2 targeted therapies are used, then signaling inhibition is achieved, but resistance develops reducing long-term efficacy
Solution Approach 1:
The patent employs dynamic multi-target inhibition where the antibody can adaptively bind to different HER family members (HER-2, HER-3, HER-4) based on which receptors are overexpressed or activated in the tumor. This dynamic approach prevents resistance by simultaneously blocking multiple signaling pathways that cancer cells might otherwise compensate through
Solution Approach 2:
The patent changes the therapeutic parameter from single-target to multi-target inhibition. By designing an antibody that can bind to multiple HER family members with different affinities, the therapy achieves more comprehensive signaling inhibition and prevents the parameter changes (resistance mechanisms) that would otherwise reduce long-term efficacy
Data Source
AI summary
The present invention relates to binding proteins that bind to HER-3 and polynucleotides encoding the same. Expression vectors and host cells comprising the same for the production of the binding protein of the invention are also provided. In addition, the invention provides compositions and methods for diagnosing and treating diseases associated with HER-3 mediated signal transduction and/or its ligand heregulin.