PD-1 Antagonist Compositions for T Cell Activation

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Solution Overview

Problem

Current therapies face challenges in effectively enhancing T cell responses, particularly in cancer and infectious diseases, due to undesired inhibitory signal transduction mediated by PD-1 and its ligands, which suppress T cell activation and proliferation.

Innovation Solution

The use of compounds that bind to PD-1 receptors or its ligands to prevent inhibitory signal transduction, including PD-1 antagonists such as B7-DC polypeptides, antibodies, and fusion proteins, which block or reduce the interaction between PD-1 and its ligands, thereby promoting T cell activation and proliferation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If PD-1 antagonists are used to block inhibitory signal transduction, then T cell activation and proliferation are enhanced, but the complexity of the treatment regimen increases

Engineering Contradiction:
ImproveT cell responseVSAvoidtreatment regimen
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent combines PD-1 antagonists with potentiating agents into a single composition, merging multiple therapeutic components that work synergistically to enhance T cell responses while simplifying the treatment approach

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The invention creates composite therapeutic compositions containing both PD-1 antagonists and potentiating agents, where the combination produces synergistic effects that enhance T cell activation and proliferation beyond what either component could achieve alone

Inventive Principle:
Principle #40Composite materials

2Object-affected harmful factors

If PD-1 and its ligands interact, then inhibitory signal transduction occurs suppressing T cell activation, but blocking this interaction requires specific antagonists that increase treatment complexity

Engineering Contradiction:
Improveinhibitory signal transductionVSAvoidtreatment regimen
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent converts the harmful inhibitory signal transduction into a beneficial therapeutic effect by using PD-1 antagonists to block the interaction between PD-1 and its ligands, thereby eliminating the suppressive effect and enhancing T cell activation and proliferation

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The invention introduces PD-1 antagonists as intermediary molecules that specifically bind to PD-1 or its ligands, preventing the harmful interaction while allowing other necessary immune interactions to proceed normally

Inventive Principle:
Principle #24Intermediary (Mediator)

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 approach effectively increases T cell responses, leading to enhanced immune activation and improved treatment outcomes for cancer and infectious diseases by reducing inhibitory signals and promoting robust immune responses.

Implementation Method 1

Contact between PD-1 and one of its ligands (B7-H1 or B7-DC) induces an inhibitory response that decreases T cell multiplication and/or the strength and/or duration of a T cell response

Methodology Applied
Scientific EffectSignal transduction:

Data Source

PatentEP2350129B1Compositions of PD-1 antagonists and methods of use
Publication Date: 2015.06.10 MEDIMMUNE LLC
  • EP2350129B1 patent drawingFigure 1
  • EP2350129B1 patent drawingFigure 2
  • EP2350129B1 patent drawingFigure 3-1

AI summary

Methods of treating cancer and infectious diseases utilizing a treatment regimen comprising administering a compound that reduces inhibitory signal transduction in T cells, in combination with a potentiating agent, such as cyclophosphamide, to produce potent T cell mediated responses, are described. Compositions comprising the PD-1 antagonists and potentiating agents useful in the methods of the invention are also disclosed.