vNAR Antibodies Neutralize VEGF for Topical Eye Therapy
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Solution Overview
Problem
Current anti-VEGF therapies for eye conditions such as diabetic retinopathy and macular degeneration face challenges including side effects, high costs, and invasive administration methods, highlighting the need for more effective and safer molecules that can efficiently inhibit VEGF activity.
Innovation Solution
Development of shark-based IgNAR antibodies, specifically vNAR clones V13, V19, and V32R, which are highly resistant and have high affinity for VEGF, allowing for topical therapeutic action and efficient neutralization of VEGF activity, thereby addressing the limitations of existing therapies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional monoclonal antibodies are used for anti-VEGF therapy, then VEGF neutralization is achieved, but the treatment requires invasive administration and has side effects
Solution Approach 1:
The patent segments the conventional antibody structure into a smaller single-domain antibody (sdAb) derived from the variable region of shark IgNAR. This sdAb retains the VEGF-neutralizing function while being small enough for topical administration, eliminating the need for invasive injection methods required by conventional monoclonal antibodies.
Solution Approach 2:
The patent extracts only the essential antigen-binding variable domain (VH) from the complete antibody structure. This extracted sdAb fragment maintains the ability to neutralize VEGF but can be administered topically rather than requiring invasive injection, thus resolving the administration method contradiction.
2Reliability
If conventional monoclonal antibodies are used for anti-VEGF therapy, then VEGF neutralization is achieved, but the treatment incurs high costs
Solution Approach 1:
The patent employs a single-domain antibody structure that is simpler and cheaper to produce than conventional monoclonal antibodies. The sdAb can be expressed in bacterial systems like E. coli, significantly reducing manufacturing costs while maintaining therapeutic effectiveness for VEGF neutralization.
3Length of moving object
If smaller antibody fragments are used, then tissue penetration is improved, but antigen binding capacity may be reduced
Solution Approach 1:
The patent focuses the entire antigen-binding capability into the single variable domain of the sdAb. This localized concentration of binding function in the small sdAb structure maintains high affinity for VEGF while enabling superior tissue penetration due to the reduced molecule size.
Solution Approach 2:
The patent changes the molecular parameters by using a single-domain structure instead of full-length antibodies or conventional fragments. This parameter change reduces molecular weight for better penetration while the hypervariable regions (CDRs) are optimized to maintain or enhance antigen binding affinity.
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 vNAR antibodies demonstrate enhanced affinity and neutralizing capacity compared to previous molecules, requiring lower concentrations to inhibit angiogenesis, thus offering a more effective and safer treatment option for eye conditions related to VEGF-mediated neovascularization.
Implementation Method 1
vNAR recombinant monoclonal antibodies that neutralize vascular endophelial growth factor VEGF
Data Source
AI summary
The present invention refers to the selection, isolation and purification of proteins belonging to variable regions named VHNAR or vNAR, originated from IgNAR-type immunoglobulins of elasmobranches with antigen receptor abilities. The clones from which they originate are named VEGFvNAR V32R and V19; and the antibodies are named V32R and V19. Their amino acid sequences and tertiary structures were elucidated, and their ability to neutralize the vascular endothelial growth factor (VEGF) activity was determined. During the development of the invention these proteins were optimized for expression in a production model of E. coli at industrial level. The invention involves the use of these antibodies in general to treat conditions related to angiogenesis or neovascularization and in particular to treat neovascularization-related ophthalmic conditions by topical administration.