ILT3-Specific Monoclonal Antibodies for Reduced Off-Target Binding

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Solution Overview

Problem

Existing anti-ILT3 antibodies are promiscuous, leading to off-target effects and undesirable therapeutic outcomes due to cross-reactivity with related receptors like ILT5, ILT7, ILT8, and ILT11.

Innovation Solution

Development of monoclonal antibodies and antigen binding fragments that specifically bind to ILT3 with minimal cross-reactivity, enhancing dendritic cell activation and T cell priming, and are capable of antagonizing ILT3 activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing anti-ILT3 antibodies are used, then ILT3 binding activity is achieved, but cross-reactivity with related receptors (ILT5, ILT7, ILT8, ILT11) causes off-target effects

Engineering Contradiction:

Improvebinding specificityVSAvoidoff-target effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by engineering antibodies with modified complementarity-determining regions (CDRs) that possess specific local binding properties. The CDRs are optimized to recognize unique epitopes on ILT3 while avoiding cross-reactivity with related receptors, thereby achieving high binding specificity without off-target effects

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs parameter changes by systematically varying the amino acid sequences of the CDR regions to optimize binding characteristics. Through iterative modification of CDR1, CDR2, and CDR3 sequences, the antibodies achieve enhanced affinity for ILT3 while maintaining selectivity and eliminating cross-reactivity with ILT5, ILT7, ILT8, and ILT11

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If promiscuous anti-ILT3 antibodies are used, then broad receptor coverage is achieved, but therapeutic outcomes are compromised due to undesired cross-reactivity

Engineering Contradiction:

Improvereceptor coverageVSAvoidtherapeutic efficacy

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent applies the extraction principle by isolating and optimizing only the essential binding elements (CDR regions) required for specific ILT3 recognition. By extracting and refining the CDR sequences, the invention achieves precise ILT3 targeting while eliminating unnecessary cross-reactivity with other receptors, thereby improving therapeutic reliability

Inventive Principle:

Principle #2Taking out (Extraction)

Data Source

PatentUS12441792B2Antibodies specific for immunoglobulin-like transcript 3 (ILT3) and uses thereof

Publication Date: 2025.10.14 MERCK SHARP & DOHME LLC

AI summary

Humanized, non-promiscuous monoclonal antibodies specific for immunoglobulin-like transcript 3 (ILT3), also known as Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4), are described.