IL-6 Antibody CDR and Fc Engineering for Ocular Potency

Solution Overview

Problem

Existing IL-6 antibodies have limitations in affinity and potency for human IL-6, and their therapeutic efficacy in treating ocular diseases is not optimal.

Innovation Solution

Development of IL-6 antibodies with specific CDR sequences, such as GYVLPNYLIE, VTTPGGGTIN, SRWDPLYYYALEY for the heavy chain and RASESVDNYGIPFMN, AASNRGS, QQSEEVPLT for the light chain, enhancing affinity and potency, and engineered Fc domains for reduced systemic accumulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing IL-6 antibodies are used, then they can bind to IL-6, but their affinity and potency for human IL-6 are insufficient

Engineering Contradiction:

Improveaffinity and potencyVSAvoidantibody design complexity

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent applies parameter changes by modifying the CDR sequences of the antibody to optimize binding affinity and potency. Specifically, the heavy chain CDR1 sequence GYVLPNYLIE, CDR2 sequence VTTPGGGTIN, and CDR3 sequence SRWDPLYYYALEY, along with light chain CDR1 sequence RASESVDNYGIPFMN, CDR2 sequence AASNRGS, and CDR3 sequence QQSEEVPLT, were engineered to enhance binding characteristics to human IL-6

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent applies local quality by making specific modifications to the Fc domain of the antibody (e.g., H90A, H90E, H90N, D92T, I33A, I33R, H215A mutations) to reduce systemic accumulation while maintaining the antigen-binding capability of the variable regions. This localized modification approach allows differential optimization of binding properties versus pharmacokinetic properties

Inventive Principle:

Principle #3Local quality

2Reliability

If IL-6 antibodies are administered systemically, then they can reach IL-6 targets, but they accumulate systemically causing unwanted effects

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidsystemic accumulation and side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by making specific modifications to the Fc domain of the antibody (e.g., H90A, H90E, H90N, D92T, I33A, I33R, H215A mutations) to reduce systemic accumulation while maintaining the antigen-binding capability of the variable regions. This localized modification approach allows differential optimization of binding properties versus pharmacokinetic properties

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent uses the Fc domain as an intermediary element that mediates the pharmacokinetic behavior of the antibody. By modifying the Fc domain, the patent alters how the antibody interacts with systemic clearance mechanisms and Fc receptors, thereby reducing unwanted systemic accumulation while preserving therapeutic efficacy at the target site

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If IL-6 antibodies are used for ocular disease treatment, then they can block IL-6 signaling, but their duration of action is insufficient

Engineering Contradiction:

Improveblockade effectivenessVSAvoidduration of IL-6 signaling blockade

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent applies parameter changes by optimizing the CDR sequences to achieve higher binding affinity and slower off-rates for IL-6. The engineered CDR sequences (heavy chain: GYVLPNYLIE, VTTPGGGTIN, SRWDPLYYYALEY; light chain: RASESVDNYGIPFMN, AASNRGS, QQSEEVPLT) are designed to prolong the duration of IL-6 signaling blockade in the ocular environment

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentEP4268843B1Improved il-6 antibodies

Publication Date: 2025.09.03 F HOFFMANN LA ROCHE LTD

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AI summary

Improved IL-6 antibodies are provided. Uses of the antibodies in the treatment of IL-6 related diseases, e.g. ocular diseases such as diabetic macular edema, are disclosed.