CD70 Antibodies with Humanized Frameworks for Cancer Treatment

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Solution Overview

Problem

Existing CD70-targeting antibodies and antibody drug conjugates have shown limited success in clinical trials for cancer treatment due to suboptimal properties.

Innovation Solution

Development of CD70 antibodies, antigen binding portions, and conjugates that specifically bind to CD70, with improved properties such as enhanced binding affinity and reduced immunogenicity, for the treatment of CD70+ cancers and other diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing CD70 antibodies and antibody drug conjugates are used for cancer treatment, then CD70+ cells can be targeted, but treatment success is limited due to suboptimal properties

Engineering Contradiction:

Improvetreatment successVSAvoidbinding affinity

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by developing novel antibody sequences (VH and VL regions with specific CDRs) that exhibit enhanced binding affinity to CD70 compared to existing antibodies. The sequences are optimized to improve therapeutic efficacy while maintaining specificity for CD70+ cancer cells.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If CD70 antibodies are developed with enhanced binding affinity, then treatment efficacy improves, but immunogenicity may increase

Engineering Contradiction:

Improvetreatment efficacyVSAvoidimmunogenicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by humanizing the antibody sequences - specifically designing VH and VL regions with human framework regions while retaining non-human CDR sequences for high affinity binding. This local optimization reduces immunogenicity in the framework regions while preserving therapeutic efficacy through optimized CDR sequences.

Inventive Principle:

Principle #3Local quality

3Reliability

If CD70 antibodies with improved properties are developed, then treatment outcomes improve, but development complexity increases

Engineering Contradiction:

Improvetreatment outcomesVSAvoidantibody sequence optimization

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the antibody into distinct functional regions - VH and VL domains with further subdivision into framework regions and CDRs. This modular approach allows independent optimization of each region for binding affinity, stability, and reduced immunogenicity, simplifying the overall development process.

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS20250066490A1Anti-CD70 antibodies, conjugates thereof and methods of using the same

Publication Date: 2025.02.27 GENMAB AS

AI summary

The present invention provides CD70 antibodies, antigen binding portions thereof, other binding agents and CD70 conjugates thereof for use in the treatment of cancer and autoimmune disease.