FDF03 Agonist Antibodies Modulate Immune Response

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Solution Overview

Problem

Current immunotherapies face challenges in effectively modulating immune responses to distinguish between self and non-self, particularly in cancer immunity, where the immune system struggles to recognize and target tumor cells due to genetic defects affecting activating and inhibitory receptors, leading to autoimmunity or inadequate responses against transformed cells.

Innovation Solution

Development of agonist or partial-agonist antibodies specific for the FDF03 inhibitory receptor, including bispecific antibodies that bind to both inhibitory and activating FDF03 receptors, to modulate immune responses and enhance antitumor activity by regulating the immune system's recognition and targeting of tumor cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If agonist antibodies for FDF03 inhibitory receptor are used to enhance immune activation, then antitumor activity is improved, but risk of autoimmunity increases

Engineering Contradiction:
Improveantitumor activityVSAvoidautoimmunity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses FDF03 agonist antibodies as intermediaries to modulate the immune response. These antibodies bind to the FDF03 inhibitory receptor on myeloid cells, converting the inhibitory signal into an activating signal, thereby enhancing antitumor immunity while maintaining selective targeting to avoid widespread autoimmunity

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the functional parameter of the FDF03 receptor from inhibitory to activating by using agonist antibodies. This parameter change allows the same receptor to mediate immune activation against tumors while the specificity of the antibody-receptor interaction helps prevent off-target autoimmunity

Inventive Principle:
Principle #35Parameter changes

2Reliability

If immune system activation is enhanced to improve tumor recognition, then immune responsiveness is improved, but specificity in distinguishing self from non-self deteriorates

Engineering Contradiction:
Improveimmune responsivenessVSAvoidspecificity
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent applies local quality by targeting FDF03 expression specifically on myeloid cells (macrophages, dendritic cells, neutrophils) rather than universally activating all immune cells. This localized approach enhances tumor recognition through myeloid cells while preserving self-tolerance in other cell types

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent utilizes the FDF03 receptor's natural role in immune regulation as a feedback mechanism. By agonizing this inhibitory receptor, the system creates a feedback loop that enhances immune activation in the context of tumor recognition while maintaining checkpoints to prevent inappropriate autoimmunity

Inventive Principle:
Principle #23Feedback

3Reliability

If FDF03 receptor modulation is used to enhance immune surveillance, then tumor detection is improved, but complexity of immune regulation increases

Engineering Contradiction:
ImproveimmunosurveillanceVSAvoidimmune regulation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and isolates the FDF03 receptor pathway as a specific therapeutic target within the complex immune system. By focusing on this single receptor-antibody interaction, the patent simplifies the approach to enhancing immunosurveillance while avoiding the need to modulate multiple immune pathways simultaneously

Inventive Principle:
Principle #2Taking out (Extraction)

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

The described antibodies effectively inhibit tumor growth and reduce metastatic burden by augmenting anti-tumor immune responsiveness, thereby improving immunosurveillance and potentially preventing carcinogenesis.

Implementation Method 1

agonist or partial-agonist antibody or antibody fragment thereof specific for the FDF03 inhibitory receptor

Methodology Applied
Scientific EffectAntibody-receptor binding:

Data Source

PatentEP2240517B1FDF03 antibodies and uses thereof
Publication Date: 2018.03.14 MERCK SHARP & DOHME CORP
  • EP2240517B1 patent drawingFigure 1
  • EP2240517B1 patent drawingFigure 2
  • EP2240517B1 patent drawingFigure 3

AI summary

The present invention relates to methods for identifying and using modulators of FDF03 biological activity in vitro andin vivo that are useful in the treatment of cancer.