VHH Bispecific Formulation for Higher VEGF-A and ANG-2 Blocking
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Solution Overview
Problem
Existing bispecific antibodies targeting VEGF-A and ANG-2 have poor blocking ability and large molecular weights, leading to lower molar concentrations and frequent administration requirements, particularly for ocular diseases.
Innovation Solution
A pharmaceutical formulation comprising VHH antibodies or bispecific binding molecules with smaller molecular weights and higher molar concentrations, exhibiting stronger VEGF-A and ANG-2 blocking activity, allowing less frequent ocular administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If existing bispecific antibodies are used, then they can target both VEGF-A and ANG-2, but they have large molecular weights resulting in lower molar concentrations and poor blocking ability
Solution Approach 1:
The patent segments the traditional full-length antibody structure into smaller functional units by using single-domain antibodies (VHH) that can be assembled into bispecific formats. This segmentation reduces the overall molecular weight while maintaining the dual-targeting capability against VEGF-A and ANG-2, thereby achieving higher molar concentrations at the same mass concentration.
Solution Approach 2:
The patent changes the molecular weight parameter by employing VHH-based bispecific antibodies instead of conventional full-length antibodies. This parameter change directly increases the molar concentration achievable at therapeutic doses, allowing more molecules to be present in the same volume for enhanced blocking activity.
2Reliability
If existing bispecific antibodies are used, then they can bind to VEGF-A and ANG-2, but they have poor blocking ability and require frequent administration
Solution Approach 1:
The patent creates a composite bispecific antibody structure combining VHH domains with optimized binding regions for both VEGF-A and ANG-2. This composite design enhances the blocking ability by ensuring proper spatial orientation and high affinity binding, reducing the need for frequent administrations.
Solution Approach 2:
The patent optimizes binding affinity parameters through careful design of the VHH domains and their linkers. By adjusting the affinity and valency parameters, the blocking ability is enhanced, leading to prolonged efficacy duration and reduced administration frequency.
Data Source
Figure 1A~1D
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Figure 4A~4B
AI summary
The present invention relates to a formulation comprising a bispecific binding molecule binding to VEGF and Ang2 and uses thereof, and in particular to a pharmaceutical formulation comprising the bispecific binding molecule, a buffer, a stabilizer, and a surfactant. Furthermore, the present invention further relates to therapeutic or prophylactic use of these formulations.