CD38 Antibody Epitope Targeting for Cell Depletion Therapy

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

The role of CD38 in signal transduction and hematopoiesis in humans remains unclear, and there is a need for improved methods to treat CD38-associated cancers and autoimmune diseases, as existing anti-CD38 monoclonal antibodies are non-physiological ligands and animal models do not accurately reflect human biology.

Innovation Solution

Development of CD38-specific antibodies, including scFv418 and IgG418, which bind to distinct epitopes on CD38, offering therapeutic and diagnostic applications through mechanisms such as CDC, ADCC, and ADCP, targeting CD38-expressing cells to treat hematopoietic malignancies and autoimmune diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing anti-CD38 monoclonal antibodies are used, then CD38 binding is achieved, but the ligands are non-physiological and do not accurately reflect human biology

Engineering Contradiction:

Improveaccuracy of CD38 function understandingVSAvoidapplicability to human disease treatment

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent uses CD31 (PECAM-1) as a natural intermediary ligand to study CD38 function, replacing non-physiological monoclonal antibodies. This intermediary approach allows accurate understanding of CD38's natural role in human biology while maintaining therapeutic applicability.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Measurement precision

If CD38 knockout mice are used to understand CD38 function, then loss of NADase activity is achieved, but the model does not reflect human biology where CD38 is necessary for survival

Engineering Contradiction:

Improveclarity of CD38 functional roleVSAvoidrelevance to human biology

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

Instead of using knockout mice that do not copy human biology, the patent creates humanized mouse models that express human CD38 and uses human cell lines with controlled CD38 expression. This copying approach preserves the essential function of CD38 in human survival while allowing functional studies.

Inventive Principle:

Principle #26Copying

3Reliability

If improved therapeutic methods for CD38-associated cancers are developed, then treatment efficacy is enhanced, but the complexity of targeting CD38-expressing tumors increases

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidtherapeutic approach complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent develops anti-CD38 antibodies with multiple functions including CDC, ADCC, and ADCP activities. This multi-functionality allows a single therapeutic agent to address CD38-associated cancers through various mechanisms, reducing overall treatment complexity while enhancing efficacy.

Inventive Principle:

Principle #6Universality (Multi-functionality)

4Productivity

If CD38-specific antibodies are used to deplete CD38-positive cells, then therapeutic benefit is achieved, but resistance to PD1/PDL1 therapy may occur

Engineering Contradiction:

Improvetherapeutic benefitVSAvoidtherapy resistance

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent employs periodic administration of anti-CD38 antibodies to maintain depletion of CD38-positive cells while monitoring for resistance development. This periodic action allows therapeutic benefit to be sustained while managing the risk of PD1/PDL1 therapy resistance through controlled treatment intervals.

Inventive Principle:

Principle #19Periodic action

Data Source

PatentUS12497463B2Anti-CD38 antibody and use thereof

Publication Date: 2025.12.16 JIANGSU KANION PHARMA CO LTD

AI summary

Provided are a composition containing a CD38 antibody or a fragment thereof, and a use of the composition in treating diseases associated with CD38 expression.