Complement Factor D Peptides for EBV Lytic Induction

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Solution Overview

Problem

Current proviral substances used in lytic induction therapy for EBV-associated diseases are often toxic to healthy cells and insufficiently efficient in inducing the expression of lytic EBV-proteins.

Innovation Solution

Peptides derived from the complement factor D protein, with at least 80% sequence identity, are used as lytic inducer agents to induce the lytic cycle of EBV in EBV-positive cells, leveraging their endogenous and biocompatible nature.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If proviral substances are used to induce lytic EBV-replication, then expression of lytic EBV-proteins is reactivated, but the substances are toxic for healthy cells

Engineering Contradiction:

Improveefficiency of EBV lytic cycle inductionVSAvoidtoxicity to healthy cells

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention segments the proviral substance into smaller peptide fragments derived from complement factor D. Specifically, peptides comprising amino acid sequences 118-153 and 154-238 of complement factor D were identified as active lytic inducers. This segmentation allows the therapeutic effect to be maintained while reducing the molecular complexity and potential toxicity of the full complement factor D protein.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention extracts the specific active peptide sequences from the complement factor D protein. By identifying and isolating the functional peptide regions (amino acids 118-153 and 154-238), the therapy uses only the necessary proviral-inducing portions without the potentially harmful components of the complete protein, thereby maintaining efficacy while improving safety.

Inventive Principle:

Principle #2Taking out (Extraction)

2Productivity

If known proviral agents are used for lytic induction, then some EBV-positive cells are eliminated, but the agents are not sufficiently efficient and cause toxicity

Engineering Contradiction:

Improveselective elimination of EBV-positive cellsVSAvoidtoxicity and insufficient efficiency

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The invention changes the molecular parameters of the proviral substance by using specific peptide sequences from complement factor D with defined amino acid compositions and lengths. The peptides comprising amino acids 118-153 (36 residues) and 154-238 (85 residues) have optimized parameters that provide sufficient lytic induction efficiency while maintaining biocompatibility and reducing toxicity compared to conventional agents.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention uses complement factor D-derived peptides as intermediary substances that mediate between the immune system and EBV-positive cells. These peptides act as safe intermediaries that can induce lytic cycle and enhance immune recognition without the severe toxicity of direct chemotherapeutic agents, thereby improving the therapeutic index.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentEP4032543A1Peptides from the sequence of the complement factor d for medical use, especially for the treatment of EBV-associated diseases

Publication Date: 2022.07.27 FRAUNHOFER GESELLSCHAFT ZUR FORDERUNG DER ANGEWANDTEN FORSCHUNG EV

Figure 1

AI summary

The present invention refers to peptides derived from the complement factor D and their use in the treatment or diagnosis of diseases, e.g. EBV-associated diseases.