NetB-Targeting Antibodies for Necrotic Enteritis Control

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current therapeutic options for Necrotic enteritis (NE) caused by Clostridium perfringens, particularly those targeting the NetB toxin, are either partially effective or pose risks such as antimicrobial resistance and human safety concerns due to the use of genetically modified vectors.

Innovation Solution

Development of binding proteins and antibodies, specifically monoclonal antibodies, that target the NetB toxin with high affinity and stability across various pH levels and in the presence of proteases, thereby inhibiting the toxin's toxic activity without affecting the bacteria directly.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibiotics are used to treat Necrotic enteritis, then the disease can be controlled, but antimicrobial resistance develops and selection pressure increases

Engineering Contradiction:

Improvedisease control effectivenessVSAvoidantimicrobial resistance

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent uses antibodies as intermediary substances that bind to and neutralize the NetB toxin, preventing it from causing disease without directly killing the bacteria. This mediator approach controls the harmful effect (toxin) while avoiding the selection pressure that leads to antimicrobial resistance.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention extracts and targets specifically the NetB toxin as the causative agent of disease, separating the toxic function from the bacterial organism. By neutralizing only the toxin rather than eliminating the entire bacterium, the treatment avoids exerting broad selection pressure on bacterial populations.

Inventive Principle:

Principle #2Taking out (Extraction)

2Adaptability or versatility

If genetically modified Salmonella vectors are used for vaccination, then NetB-based vaccines can be developed, but human safety issues arise

Engineering Contradiction:

Improvevaccine development capabilityVSAvoidhuman safety concerns

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs transient expression systems where the NetB toxin is produced temporarily in a safe host system, purified, and then used as a vaccine antigen. The expression system itself is not introduced into the final vaccine product, eliminating long-term safety concerns while maintaining vaccine development capability.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Reliability

If vaccines based on alpha-toxin are developed, then some protection can be achieved, but effectiveness is only partial

Engineering Contradiction:

Improvevaccine effectivenessVSAvoidprotection level

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent shifts the vaccine target from alpha-toxin to NetB toxin, changing the critical parameter of antigen specificity. This parameter change results in a vaccine that targets the essential virulence factor responsible for necrotic enteritis, thereby improving effectiveness from partial to near-complete protection.

Inventive Principle:

Principle #35Parameter changes

4Ease of operation

If oral delivery of biologic therapeutics is attempted, then direct targeting of infection site is achieved, but degradation in GI tract environment occurs

Engineering Contradiction:

Improvedelivery convenienceVSAvoidtherapeutic stability

Core Design Contradiction:

Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent employs protective encapsulation systems that shield the biologic therapeutic from degradation in the gastrointestinal tract. These protective shells or films allow oral delivery convenience while maintaining therapeutic stability through the harsh GI environment by providing a physical barrier against proteases and acidic conditions.

Inventive Principle:

Principle #30Flexible shells and thin films

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 antibodies effectively reduce or prevent Necrotic enteritis by specifically binding to and inhibiting the NetB toxin, offering a safer alternative to antibiotics and demonstrating stability and functionality in the gastrointestinal tract environment.

Implementation Method 1

binding proteins and antibodies that bind to NetB produced by Clostridium perfringens

Methodology Applied

Scientific EffectAntibody-antigen binding:

Implementation Method 2

stability across various pH levels and in the presence of proteases

Methodology Applied

Scientific EffectpH stability:

Implementation Method 3

stability across various pH levels and in the presence of proteases

Methodology Applied

Scientific EffectProtease resistance:

Data Source

PatentUS20250197484A1Antibodies to necrotic enteritis b-like toxin

Publication Date: 2025.06.19 ECO ANIMAL HEALTH

AI summary

The present disclosure provides a binding protein, e.g. an antibody, comprising at least one antigen binding domain which binds to necrotic enteritis B-like toxin (NetB), said antigen binding domain comprising a heavy chain variable region which comprises three complementarity determining regions (CDRs), preferably wherein said binding protein binds to NetB with a KD of 250 pM or less at pH 7.4. Said binding proteins can be used in the treatment or prevention of C. perfringens infection or Necrotic Enteritis. Nucleic acid molecules, expression vectors, host cells and compositions are also provided.