NTCP-Binding Antibody for HBV Blockade Without Bile Acid Disruption

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Solution Overview

Problem

Current HBV inhibitors targeting NTCP significantly inhibit bile acid transport, leading to side effects, while cyclic peptides that suppress viral infection without affecting bile acid transport are not effective enough.

Innovation Solution

Development of an antibody that binds to human NTCP, inhibiting HBV infection without significantly affecting bile acid uptake, by targeting specific amino acid residues critical for HBV binding.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If an NTCP inhibitor is developed to prevent HBV infection, then HBV infection is inhibited, but bile acid transport is significantly inhibited causing side effects

Engineering Contradiction:

ImproveHBV infection inhibitionVSAvoidbile acid transport inhibition

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by targeting a specific local region (amino acid residues 276-277) on the NTCP protein that is critical for HBV binding but not essential for bile acid transport. The antibody binds to this specific local epitope, selectively blocking HBV infection while preserving the overall bile acid transport function of NTCP, thus resolving the contradiction between viral inhibition and transport function.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent changes the binding parameter by shifting from binding to distant or alternative regions of NTCP (which would block both functions) to binding specifically at residues 276-277. This parameter change in binding location allows the antibody to inhibit HBV infection (improving reliability) while maintaining bile acid transport (reducing harmful effects).

Inventive Principle:

Principle #35Parameter changes

2Reliability

If a cyclic peptide is used to suppress viral infection, then viral infection is suppressed, but the effect on bile acid transport is not significant enough

Engineering Contradiction:

Improveviral infection suppressionVSAvoidbile acid transport effect

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses an antibody as an intermediary substance that mediates the inhibition of HBV infection. Instead of using a cyclic peptide that directly interacts with the virus, the antibody serves as a mediator that binds to NTCP and blocks viral entry. This intermediary approach provides more precise control over the inhibition mechanism, achieving effective viral suppression without the unwanted side effects on bile acid transport.

Inventive Principle:

Principle #24Intermediary (Mediator)

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 inhibits HBV infection in human hepatocytes while maintaining normal bile acid transport function, offering a therapeutic option with reduced side effects.

Implementation Method 1

an antibody that binds to a human sodium taurocholate cotransporting polypeptide (NTCP), capable of inhibiting infection of human hepatocytes with hepatitis B virus (HBV)

Methodology Applied

Scientific EffectAntibody binding:

Implementation Method 2

a human sodium taurocholate cotransporting polypeptide (NTCP)

Methodology Applied

Scientific EffectCotransport:

Data Source

PatentUS12497461B2Human NTCP-binding antibody capable of inhibiting infection of hepatitis B virus (HBV) to human hepatocytes

Publication Date: 2025.12.16 RIKEN CO LTD

AI summary

The present invention provides an antibody that binds to an NTCP, capable of inhibiting infection of human hepatocytes with hepatitis B virus (HBV) particles. The present invention also provides an antibody that binds to an NTCP, capable of inhibiting infection of human hepatocytes with hepatitis B virus (HBV) particles, the antibody having a reduced effect on bile acid transport by NTCP.