Anti-Ang2 Antibody Composition for Tie2 Activation and Vascular Control
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Solution Overview
Problem
Current methods to inhibit angiogenesis and reduce vascular permeability by targeting Ang2 often block its binding to the Tie2 receptor, failing to activate the receptor effectively, and there is a need for a composition that can induce Tie2 activation and treat associated diseases.
Innovation Solution
An anti-Ang2 antibody or antigen-binding fragment that specifically binds to Ang2 and activates the Tie2 receptor, comprising specific CDR sequences, is developed to induce Tie2 activation and downstream signaling, and is used in pharmaceutical compositions for treating diseases related to neovascularization and cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If antibodies are used to block Ang2 binding to Tie2 receptor, then angiogenesis is inhibited and vascular permeability is reduced, but the Tie2 receptor activation is not effectively induced
Solution Approach 1:
The patent uses a bispecific antibody as an intermediary molecule that simultaneously binds to Ang2 and the Tie2 receptor. This intermediary structure enables dual functionality: it blocks Ang2's antagonistic effect while also inducing Tie2 receptor activation through clustering, thereby resolving the contradiction between inhibiting angiogenesis and activating the receptor.
Solution Approach 2:
The bispecific antibody performs multiple functions simultaneously: it acts as both an antagonist (blocking Ang2-Tie2 binding) and an agonist (inducing Tie2 receptor activation through clustering). This multi-functionality allows a single molecule to address both the need to inhibit angiogenesis and the need to activate Tie2 signaling.
2Object-generated harmful factors
If Ang2 is blocked from binding to Tie2, then the antagonistic effect is prevented, but the agonist effect and downstream signaling are not activated
Solution Approach 1:
The bispecific antibody serves as a mediator that decouples the antagonistic and agonistic functions. By binding to Ang2 with one arm and the Tie2 receptor with another arm, it prevents Ang2's antagonistic effect while simultaneously providing a clustering effect that activates Tie2 downstream signaling pathways.
Solution Approach 2:
The bispecific antibody structure is segmented into distinct functional domains: one domain binds to Ang2 to block its antagonistic activity, while another domain binds to the Tie2 receptor to induce clustering and activation. This segmentation allows independent optimization of antagonistic and agonistic functions within a single molecule.
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 effectively activates Tie2 receptor signaling, inhibits cancer cell growth, and reduces vascular permeability, offering a dual function in treating various diseases associated with Ang2 overexpression and abnormal angiogenesis.
Implementation Method 1
an antibody that binds to Ang2 and so binds to Tie2 to phosphorylate and activate Tie2 through Tie2 clustering
Implementation Method 2
binds to the Tie2 receptor together with Ang2 to effectively induce activation of the Tie2 receptor
Data Source
AI summary
The present invention relates to an anti-angiopoietin-2 (Ang2) antibody or an antigen-binding fragment thereof that specifically binds to Ang2 and induces Tie2 activation, comprising: (a) a heavy-chain complementarity-determining region (CDR) comprising CDRH1 of the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 10, SEQ ID NO: 18, or SEQ ID NO: 26, CDRH2 of the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, or SEQ ID NO: 27, and CDRH3 of the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, or SEQ ID NO: 28; and (b) a light-chain CDR comprising CDRL1 of the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 13, SEQ ID NO: 21, or SEQ ID NO: 29, CDRL2 of the amino acid sequence of SEQ ID NO: 6, SEQ ID NO: 14, SEQ ID NO: 22, or SEQ ID NO: 30, and CDRL3 of the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 15, SEQ ID NO: 23, or SEQ ID NO: 31.