CD20-Binding Domains for Relapsed Lymphoma Therapy

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Solution Overview

Problem

Current treatments for non-Hodgkin lymphoma, particularly relapsed or refractory cases, face challenges due to CD19 antigen loss in patients, necessitating the development of novel surface antigens for targeted therapy.

Innovation Solution

Development of antigen binding domains that specifically bind to CD20, including scFv, Fab, and VHH formats, which can be used in monospecific or multispecific proteins to target CD20-positive cancer cells, potentially combined with immunoglobulin constant regions for enhanced efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CAR T-cell therapy targeting CD19 is used to treat B cell malignancies, then initial response rate is improved (60-80%), but long-term remission rate deteriorates (only 40% achieve long-term complete remission) due to CD19 antigen loss

Engineering Contradiction:

Improveinitial response rateVSAvoidlong-term remission duration

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent changes the target antigen parameter from CD19 to CD20, which is highly expressed in B-cell lymphomas and not subject to the same loss mechanisms. This parameter change enables sustained therapeutic effect by targeting an antigen that remains stably expressed on tumor cells, thereby resolving the contradiction between initial response and long-term remission

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

Instead of attempting to maintain CD19 expression on tumor cells, the patent inverts the approach by selecting an alternative antigen (CD20) that is naturally resistant to loss. This inversion strategy bypasses the antigen loss problem entirely by choosing a different target that provides durable therapeutic response

Inventive Principle:

Principle #13The other way round (Inversion)

2Duration of action of stationary object

If novel surface antigens are targeted to overcome antigen loss, then long-term remission potential is improved, but therapeutic mechanism complexity increases

Engineering Contradiction:

Improvelong-term remission durationVSAvoidtherapeutic mechanism complexity

Core Design Contradiction:

Duration of action of stationary objectVSDevice complexity

Solution Approach 1:

The patent extracts the essential functional elements required for CAR T-cell therapy (antigen binding domain, signaling domains) and combines them with a new target specificity for CD20. This extraction and recombination approach maintains the proven efficacy of existing CAR structures while changing only the antigen recognition element, thereby improving long-term remission without substantially increasing overall therapeutic complexity

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent utilizes the universal applicability of the CAR T-cell platform by applying it to a new target (CD20) that serves multiple functions: it is highly expressed in B-cell lymphomas, not subject to antigen loss, and provides a clear immunogenic target. This multi-functional antigen selection enhances long-term remission potential while leveraging the established CAR therapy framework

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20250019455A1Proteins comprising CD20 binding domains, and uses thereof

Publication Date: 2025.01.16 JANSSEN BIOTECH INC

AI summary

The invention provides antigen binding domains that bind Cluster of Differentiation 20 protein (CD20), proteins comprising the antigen binding domains that bind CD20, polynucleotides encoding them, vectors, host cells, methods of making and using the same.