Humanized CD30 Antibodies Reduce Immunogenicity

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Solution Overview

Problem

There is a need for humanized antibodies specific to CD30 as therapeutic agents for treating diseases associated with CD30-expressing cells, as murine antibodies are not ideal for human use.

Innovation Solution

Development of CD30 binding agents comprising humanized heavy chain and light chain variable regions that specifically bind to the extracellular domain of CD30, including antibodies and antigen-binding fragments, which can be used to inhibit the proliferation or differentiation of CD30-expressing cells and induce cytotoxic or cytostatic effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If murine antibodies are used to target CD30, then specific binding to CD30-expressing cells is achieved, but immunogenicity and suitability for human therapeutic use worsen

Engineering Contradiction:

Improvespecific binding to CD30VSAvoidimmunogenicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent creates humanized antibodies that copy the antigen-binding specificity of murine anti-CD30 antibodies while using human immunoglobulin frameworks. This allows the antibody to bind specifically to human CD30 without triggering strong immune responses against non-human protein structures

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The patent modifies the amino acid sequence parameters of the antibody by replacing murine framework regions with human framework regions while preserving the complementarity determining regions (CDRs) that provide CD30 binding specificity. This parameter change reduces immunogenicity while maintaining functional efficacy

Inventive Principle:

Principle #35Parameter changes

2Object-affected harmful factors

If humanized antibodies are developed to reduce immunogenicity, then therapeutic suitability for humans improves, but development complexity and time increase

Engineering Contradiction:

ImproveimmunogenicityVSAvoidantibody structure complexity

Core Design Contradiction:

Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent segments the antibody structure into distinct functional regions: complementarity determining regions (CDRs) that provide antigen binding specificity and framework regions that provide structural support. By humanizing only the framework regions while preserving the CDRs, the patent reduces complexity compared to developing entirely new human antibodies with equivalent specificity

Inventive Principle:

Principle #1Segmentation

3Productivity

If conventional murine antibodies are used for therapy, then immediate therapeutic effect is achieved, but long-term safety and efficacy in humans worsen due to immune rejection

Engineering Contradiction:

Improvetherapeutic effect speedVSAvoidlong-term safety

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent uses humanized antibody frameworks as an intermediary between murine antibody specificity and human therapeutic requirements. This intermediary structure allows the antibody to function effectively in humans without triggering strong immune rejection, bridging the gap between immediate therapeutic effect and long-term safety

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS8257706B2CD30 binding agents and uses thereof

Publication Date: 2012.09.04 SEAGEN INC

AI summary

This invention relates to CD30 binding agents and methods of using such binding agents for treating disease characterized by expression of CD30 antigen.