Selective Immunosuppressive Polypeptides for Targeted Therapy

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Solution Overview

Problem

Current immunosuppressive therapies for inflammatory, autoimmune, allergic, and infectious diseases, as well as organ rejection, suffer from nonspecific action, leading to increased vulnerability to infections and neoplasms, along with adverse effects such as nephrotoxicity, hepatotoxicity, and chronic conditions.

Innovation Solution

Development of polypeptides with selective immunosuppressive activity, encoded by specific polynucleotides, which inhibit antibody production with minimal adverse effects, using sequences such as those presented in SEQ ID NOs: 2, 3, 5, and 9, and their use in pharmaceutical compositions for targeted immunosuppression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current immunosuppressants are used to treat inflammatory, autoimmune, allergic, and infectious diseases, then immunosuppression is achieved, but vulnerability to infections and neoplasms increases due to nonspecific action

Engineering Contradiction:
Improveimmunosuppression effectivenessVSAvoidvulnerability to infections and neoplasms
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent segments the immune system into specific targets (B cells, T cells, macrophages, dendritic cells) and develops polypeptides that selectively modulate each cell type's function. This targeted approach replaces the nonspecific suppression of current immunosuppressants with precise, cell-type-specific regulation, achieving immunosuppression while preserving protective immune functions against infections and neoplasms

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent applies local quality by designing polypeptides with specific functions tailored to different immune cell types. Each polypeptide is engineered to interact with particular cell surface receptors or intracellular pathways of specific immune cells, creating localized, selective immunomodulation rather than global suppression. This ensures that only pathological immune responses are suppressed while maintaining protective immunity

Inventive Principle:
Principle #3Local quality

2Reliability

If current immunosuppressants are used to prevent organ rejection, then rejection is prevented, but adverse effects such as nephrotoxicity, hepatotoxicity, and chronic conditions occur

Engineering Contradiction:
Improveorgan rejection preventionVSAvoidnephrotoxicity, hepatotoxicity, and chronic conditions
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent uses polypeptides as intermediary agents that mediate selective immunosuppression through specific cellular mechanisms. These polypeptides act as intermediaries between the therapeutic goal (preventing organ rejection) and the immune system, providing controlled suppression of transplant rejection while avoiding the direct toxic effects of conventional immunosuppressants on kidneys, liver, and other organs

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs recombinant DNA technology to produce identical copies of therapeutic polypeptides through genetic engineering. This allows for consistent, pure, and scalable production of the immunomodulatory polypeptides, ensuring therapeutic efficacy while eliminating the toxic side effects associated with conventional immunosuppressive drugs

Inventive Principle:
Principle #26Copying

3Reliability

If conventional immunosuppressants are used, then immune response is reduced, but nonspecific action leads to loss of ability to distinguish between self and non-self

Engineering Contradiction:
Improveimmune response reductionVSAvoidself vs non-self discrimination
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent introduces dynamic, condition-dependent immunomodulation where polypeptides are designed to activate or inhibit specific immune pathways only under pathological conditions. The polypeptides dynamically respond to disease states by selectively suppressing aberrant immune responses while preserving normal self-tolerance mechanisms, thereby maintaining the immune system's ability to distinguish between self and non-self

Inventive Principle:
Principle #15Dynamics

Data Source

PatentEP3060236B1Polynucleotide, polypeptide with immunosuppresive activity, expression cassette, expression vector, host cell, pharmaceutical composition and methods for producing a polypetide with immunosuppresive activity and for preventing or treating conditions that require immunosuppresion
Publication Date: 2020.12.02 FUNDACAO BUTANTAN
  • EP3060236B1 patent drawingFigure 1
  • EP3060236B1 patent drawingFigure 2
  • EP3060236B1 patent drawingFigure 3

AI summary

This invention refers to polynucleotides and non-hemorrhagic and non-immunogenic polypeptides of selective immunosuppressive activity on production of antibodies to antigens of different natures. The polypeptides described herein are useful for preparing pharmaceutical compositions for prevention or treatment of conditions that require immunosuppression, preferably, inflammatory, autoimmune, allergic and infectious diseases and rejection to transplanted organs.