VHH Constructs for Prolonged Plasma Half-Life
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Solution Overview
Problem
VHH fragments, despite their high antigen-binding capacity, have a short plasma half-life and are not usable in many immunologic detection methods due to their small size and lack of corresponding secondary reagents, and they cannot be used as complete antibodies without an FC fragment, which is necessary for therapeutic applications and preclinical testing.
Innovation Solution
A VHH construct is developed by coupling a VHH fragment with a protein tag that includes epitopes for antibody binding, allowing the VHH fragment to be functionally integrated into immunoglobulins of other species, maintaining its antigen-binding properties and stability, and enabling the use of existing secondary antibodies and immunoprecipitation methods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If VHH fragments are used as complete antibodies, then antigen-binding capacity is improved, but plasma half-life is shortened due to lack of FC fragment
Solution Approach 1:
The patent combines the VHH fragment (which provides superior antigen-binding capacity) with an FC fragment (which provides extended half-life) to create a chimeric antibody construct. This merging of components allows the therapeutic agent to simultaneously achieve high antigen specificity and prolonged circulation time in the bloodstream.
Solution Approach 2:
The invention creates a composite antibody structure that integrates the variable domain of heavy chain antibody (VHH) with the constant region (FC fragment) from conventional antibodies. This composite construct combines the functional advantages of both components: the high-affinity binding of VHH and the stability/longevity of the FC fragment.
2Productivity
If VHH fragments are used in immunologic detection methods, then small size and production efficiency are improved, but compatibility with existing secondary reagents is lost
Solution Approach 1:
By adding an FC fragment to the VHH fragment, the construct gains universal compatibility with existing secondary reagents and detection protocols that recognize FC regions. This allows the VHH-based therapeutic to be used in standard immunologic detection methods without requiring development of new reagents or protocols.
Solution Approach 2:
The FC fragment acts as an intermediary that bridges the VHH fragment and the existing secondary reagent system. It provides a standardized interface that enables interaction with conventional detection methods while preserving the unique antigen-binding properties of the VHH domain.
3Duration of action of moving object
If FC fragment is added to VHH for therapeutic applications, then half-life is prolonged, but production cost increases due to requirement of mammalian cell culture
Solution Approach 1:
The invention applies local quality by adding only the necessary FC fragment portion to the VHH fragment, rather than producing complete conventional antibodies. This localized addition provides the specific function of extending half-life while minimizing the complexity and cost of production compared to full antibody manufacturing.
Data Source
AI summary
The invention relates to a novel VHH construct which can be bounded by a complete antibody without impairment of the antigen binding properties of the VHH construct being impaired. The invention also relates to an antibody construct comprising a VHH construct of this type and a kit, as well as the use thereof in immunodiagnostics or in the area of therapeutics. With the invention, among other things, it is possible to direct the existing immunity of a patient toward a different antigen.