Anti-human IL-23R Antibody Variable Region Sequences

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Solution Overview

Problem

Conventional anti-human IL-23R antibodies lack sufficient neutralizing activity and species cross-reactivity, which limits their effectiveness in treating and diagnosing diseases associated with IL-23, and poses challenges in safety evaluation and dosage reduction.

Innovation Solution

Development of anti-human IL-23R antibodies with specific heavy-chain and light-chain variable region sequences, combined with human Igγ1 and Igκ constant regions, to enhance binding activity and neutralizing capability, while maintaining cross-reactivity with animal antigens.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional anti-human IL-23R antibodies are used, then basic binding function is achieved, but neutralizing activity is insufficient

Engineering Contradiction:

Improveneutralizing activityVSAvoidtreatment effectiveness

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent applies parameter changes by modifying the antibody's variable region sequences (heavy chain and light chain amino acid sequences) to optimize binding affinity and neutralizing activity. Specific amino acid substitutions in the CDR regions enhance the antibody's ability to block IL-23R signaling while maintaining species cross-reactivity.

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If conventional anti-human IL-23R antibodies are used, then human target binding is achieved, but species cross-reactivity is insufficient

Engineering Contradiction:

Improvespecies cross-reactivityVSAvoidsafety evaluation capability

Core Design Contradiction:

Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The patent achieves universality by designing an antibody that simultaneously binds to human IL-23R and cross-reacts with animal IL-23R (such as cynomolgus monkey IL-23R). This multi-species reactivity enables the same antibody to be used for both human therapeutic applications and animal safety evaluation studies, eliminating the need for separate antibody preparations.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Quantity of substance

If higher dosage is administered to compensate for insufficient activity, then basic coverage is maintained, but treatment efficiency decreases

Engineering Contradiction:

ImprovedosageVSAvoidtreatment efficiency

Core Design Contradiction:

Quantity of substanceVSProductivity

Solution Approach 1:

The patent optimizes the dosage parameter by developing an antibody with enhanced neutralizing activity that achieves therapeutic efficacy at lower doses. The improved binding affinity and biological activity of the engineered antibody allow for reduced dosage while maintaining or improving treatment effectiveness, thereby increasing treatment efficiency.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentEP2695897B1Novel Anti-human il-23 receptor antibody

Publication Date: 2019.05.01 ASTELLAS PHARMA INC

AI summary

[Problem] An object of the present invention is to provide an anti-human IL-23R antibody having excellent activity and/or cross-reactivity compared to conventional IL-23R antibodies, and means for using the antibody to prevent or treat various diseases in which human IL-23R is involved in pathogenesis. [Means for Solution] An anti-human IL-23R antibody comprising a heavy-chain variable region consisting of the amino acid sequence shown by SEQ ID NO:5, 9, 13, 17, 21, 25 or 29 and a light-chain variable region consisting of the amino acid sequence shown by SEQ ID NO:7, 11, 15, 19, 23, 27 or 31.