Alpha-Helical Epitope Tag With Nanobody Binding Versatility

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Solution Overview

Problem

Existing epitope tags are limited in versatility, often performing well in specific applications but failing in others due to their properties being defined by chance and lacking adaptability to experimental needs, and their binders are not suitable for advanced applications like live in-vivo imaging and super-resolution microscopy.

Innovation Solution

Development of a small, monomeric, electroneutral epitope tag with a stable alpha-helical structure, recognized by high-affinity nanobodies, allowing versatile applications such as protein localization, interaction analysis, and purification without interfering with the protein's native function.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If existing epitope tags are used, then they perform well in specific applications, but they fail in other applications due to lack of versatility

Engineering Contradiction:

Improveapplication versatilityVSAvoidapplication reliability

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent develops a universal epitope tag system (ALFA tag with nanobody binder) that can perform multiple functions across diverse applications including live-cell imaging, fixed-cell imaging, protein purification, and interaction analysis, replacing the need for multiple application-specific tags

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Adaptability or versatility

If traditional monoclonal antibodies are used as binders, then they provide specific binding, but they are not suitable for advanced applications like live in-vivo imaging and super-resolution microscopy

Engineering Contradiction:

Improvebinder applicabilityVSAvoidexperimental usability

Core Design Contradiction:

Adaptability or versatilityVSEase of operation

Solution Approach 1:

The patent extracts the binding function from traditional monoclonal antibodies and implements it using single-domain nanobodies, which retain specific binding capability while removing the structural limitations that prevented use in advanced imaging applications

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the physical parameters of the binder by using nanobodies with smaller size and different structural properties compared to traditional antibodies, enabling compatibility with super-resolution microscopy and live-cell imaging techniques

Inventive Principle:

Principle #35Parameter changes

3Ease of manufacture

If epitope tags are designed without stable structure, then they are easy to implement, but they interfere with the protein's native function

Engineering Contradiction:

Improvetag implementationVSAvoidprotein function preservation

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

Instead of designing unstable tags and relying on chance for functionality, the patent inverts the approach by designing a stable alpha-helical structure that ensures proper folding and minimizes interference with the native protein function

Inventive Principle:

Principle #13The other way round (Inversion)

Data Source

PatentEP3849996B1Epitope tags recognized by specific binders

Publication Date: 2026.04.22 NANOTAG BIOTECH GMBH

Figure 1A~1B
Figure 1C
Figure 2A~2C

AI summary

The present invention provides peptides useful as epitope tags, which may be fused to a polypeptide of interest, as well as antibodies that specifically bind to these peptides. The peptides and/or antibodies can be used for detecting, immobilizing, isolating or purifying a molecule that is conjugated to such a peptide and/or antibody.