Humanized Anti-Notch4 Antibody Neutralizing Activity
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Solution Overview
Problem
Current therapies lack effective neutralizing agents targeting human Notch4, which is implicated in various cancers and neovascularization, highlighting the need for a specific antibody with high binding affinity and neutralizing activity against Notch4.
Innovation Solution
Development of a mouse anti-human Notch4 antibody with high neutralizing activity, followed by humanization to create a pharmaceutical composition comprising specific CDR sequences for the heavy and light chains, enabling effective binding and neutralization of human Notch4.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a mouse anti-human Notch4 antibody is developed to achieve high neutralizing activity, then binding affinity and neutralizing activity are improved, but immunogenicity in human patients increases
Solution Approach 1:
The patent applies parameter changes by modifying the antibody's species origin from mouse to human through humanization. The variable region sequences are changed from mouse (SEQ ID NO: 2-6) to human (SEQ ID NO: 7-11), fundamentally altering the immunogenicity parameter while preserving the neutralizing function against human Notch4
Solution Approach 2:
The patent creates a humanized version by copying the antigen-binding CDR sequences from the mouse antibody and transplanting them into a human antibody framework. This allows the humanized antibody to replicate the mouse antibody's high neutralizing activity while expressing human sequences that reduce immunogenicity in human patients
2Adaptability or versatility
If existing cancer therapies are used, then treatment is provided, but effective neutralizing agents targeting Notch4 are lacking
Solution Approach 1:
The patent creates a universal therapeutic agent that can be applied to multiple Notch4-expressing cancer types including lung cancer, breast cancer, and other malignancies. The humanized anti-Notch4 antibody provides a platform therapy that addresses the unmet need for Notch4-specific neutralization across various cancer indications
3Reliability
If Notch4 signaling is not inhibited, then normal cellular processes continue, but tumor formation and neovascularization are promoted
Solution Approach 1:
The patent applies preliminary anti-action by administering the humanized anti-Notch4 antibody before cancer progresses or metastasizes. The antibody preemptively blocks Notch4 signaling pathways that would otherwise promote tumor formation, cancer progression, and neovascularization, preventing harmful outcomes before they occur
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The antibody demonstrates significant antitumor effects and blood perfusion suppression in xenograft models, enhancing therapeutic outcomes when used alone or in combination with existing cancer treatments.
Implementation Method 1
an anti-human Notch4 antibody or a Notch4 binding fragment (1) having high binding affinity to human Notch4 and (2) having high neutralizing activity against human Notch4
Data Source
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AI summary
The present invention provides an anti-human Notch4 antibody or a Notch4 binding fragment thereof that may have neutralizing activity against human Notch4, as well as a pharmaceutical composition comprising the same as the active ingredient. The present inventors obtained a mouse anti-human Notch4 antibody that has high neutralizing activity and binding affinity towards human Notch4 and determined the complementarity determining region (CDR) sequence of said mouse anti-human Notch4 antibody. This enabled the production of a humanized antibody comprising the variable region of heavy and light chains as well as the CDR sequence of said mouse anti-human Notch4 antibody.