FRB Antibodies for DARIC Cell Detection and Monitoring

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Solution Overview

Problem

Current compositions and methods for detecting and monitoring therapeutic immune effector cells in adoptive cellular therapy for cancer treatment are not routinely available.

Innovation Solution

Development of improved antibodies and antigen binding fragments that specifically bind to FK506-binding protein (FKBP) rapamycin binding (FRB) polypeptides, particularly those with defined light and heavy chain CDR sequences, which can be used to detect and monitor dimerizing agent regulated immunoreceptor complexes (DARIC) or other chimeric proteins, optionally conjugated with detectable labels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional detection methods are used for therapeutic immune effector cells, then the therapy can be administered, but detection and monitoring capabilities are not available

Engineering Contradiction:
Improvedetection capabilityVSAvoidmethod availability
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent introduces an antibody as an intermediary detection tool that specifically binds to the FRB domain of DARIC complexes. This antibody serves as a mediator between the therapeutic cells and detection systems, enabling visualization and monitoring without altering the core therapy. The antibody can be conjugated with detectable labels to provide signal for detection.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent utilizes the specific binding affinity parameter of the antibody to the FRB domain as a detection marker. By changing from non-specific to specific binding interactions, the system enables precise detection of therapeutic cells expressing DARIC complexes through the unique FRB domain epitope.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If specific detection of therapeutic cells is implemented, then monitoring precision is enhanced, but the complexity of detection methods increases

Engineering Contradiction:
Improvemonitoring precisionVSAvoiddetection method complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The antibody designed in the patent serves multiple functions: it can detect DARIC complexes on cell surfaces, monitor therapeutic cell persistence, assess target engagement, and potentially serve as a sorting marker. This multi-functionality reduces the need for multiple different detection reagents, simplifying the overall detection system while maintaining high precision.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent creates a simplified detection model by using an antibody that copies the detection function needed for therapeutic monitoring. Instead of complex imaging or functional assays, the antibody provides a direct molecular copy of the DARIC complex presence through specific binding, which can then be detected using standard antibody detection techniques.

Inventive Principle:
Principle #26Copying

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enables effective detection and monitoring of therapeutic immune effector cells, enhancing the precision and effectiveness of adoptive cellular therapy for cancer treatment.

Implementation Method 1

improved antibodies and antigen binding fragments that bind to FK506-binding protein (FKBP) rapamycin binding (FRB) polypeptides

Methodology Applied
Scientific EffectAntigen-antibody binding:

Data Source

PatentUS12454580B2FRB antibodies
Publication Date: 2025.10.28 REGENERON PHARMACEUTICALS INC
  • US12454580B2 patent drawing
  • US12454580B2 patent drawing
  • US12454580B2 patent drawing

AI summary

The invention provides anti-FRB antibodies or antigen binding fragments thereof that bind an FRB polypeptide.