Synthetic Peptide Sequences Targeting Multi-Drug Resistant Bacteria

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Solution Overview

Problem

The rise of antibiotic-resistant bacteria poses a significant challenge in treating infections, as conventional antibiotics become ineffective, leading to prolonged hospital stays, expensive treatments, and increased toxicity risks, with a pressing need for new antibiotics to combat multidrug-resistant gram-negative bacteria.

Innovation Solution

Development of synthetic peptide sequences, such as those represented by SEQ ID NO. 1, SEQ ID NO. 2, and SEQ ID NO. 3, which are derived from natural peptides found in the spiny lobster Panulirus argus, offering broad-spectrum antibacterial activity and potential therapeutic applications in treating infections caused by multi-drug resistant bacteria, including combinations with beta-lactam antibiotics like meropenem.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional antibiotics are used to treat bacterial infections, then treatment effectiveness is maintained against susceptible bacteria, but treatment fails against multi-drug resistant bacteria

Engineering Contradiction:
Improvetreatment effectivenessVSAvoidspectrum of activity against resistant bacteria
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent employs paramyxoviruses with modified parameters including altered surface glycoproteins (hemagglutinin and neuraminidase) to change their interaction properties with host cells and immune system, enabling effective treatment against multi-drug resistant bacteria while maintaining safety

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention uses composite viral structures combining paramyxovirus capsid with surface-attached antibodies or antigen-binding fragments, creating a hybrid therapeutic agent that leverages both viral entry mechanisms and targeted antigen recognition to overcome bacterial resistance

Inventive Principle:
Principle #40Composite materials

2Reliability

If the dose of antibiotics is increased to overcome resistance, then bacterial killing effectiveness may improve, but toxicity risk increases

Engineering Contradiction:
Improvebacterial killing effectivenessVSAvoidtoxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces paramyxoviruses as intermediary carriers that deliver therapeutic agents (antibodies, antigen-binding fragments) directly to infected sites, enabling targeted delivery that spares healthy tissues from toxic effects while maintaining effective concentrations at the infection site

Inventive Principle:
Principle #24Intermediary (Mediator)

3Adaptability or versatility

If new antibiotics are developed to combat resistant bacteria, then treatment options expand, but development time and cost increase

Engineering Contradiction:
Improvetreatment optionsVSAvoiddevelopment time
Core Design Contradiction:
Adaptability or versatilityVSLoss of time

Solution Approach 1:

The patent utilizes the existing, well-characterized paramyxovirus platform that has already undergone extensive safety and immunology studies, allowing rapid adaptation and deployment against new resistant bacterial threats without repeating the lengthy development process from scratch

Inventive Principle:
Principle #10Preliminary action

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

These peptide sequences demonstrate rapid bactericidal activity against multi-resistant strains, achieving a 3-log decrease in bacterial load within 30 minutes and inhibiting lipopolysaccharide-induced pro-inflammatory cytokine release, providing a synergistic effect when combined with antibiotics, effectively targeting both Gram-negative and Gram-positive bacteria.

Implementation Method 1

AMPs are selective towards negatively charged bacterial membranes such as bacteria, and their cytotoxicity is moderate towards eukaryotic organisms which present a neutral charge in their surface

Methodology Applied
Scientific EffectElectrostatic interaction: Coulomb's Law

Implementation Method 2

A distinctive element in the antibacterial mechanism of AMPs is their interaction with the cytoplasmic membrane, therefore charge and hydrophobicity are key properties for the development of the antimicrobial activity

Methodology Applied
Scientific EffectHydrophobic interaction: Hydrophobe

Implementation Method 3

The ability of antimicrobial peptides (AMPs) to interact with the bacterial membrane and cause cell lysis makes them a promising alternative to combat the phenomenon of resistance of pathogens to conventional antibiotics

Methodology Applied
Scientific EffectCell lysis:

Implementation Method 4

Once the peptide-membrane binding has occurred, the mechanism of action generally involves the formation of lytic pores or destabilization of the membrane by the formation of peptide aggregates

Methodology Applied
Scientific EffectPore formation:

Implementation Method 5

providing a synergistic effect when combined with antibiotics

Methodology Applied
Scientific EffectSynergistic effect:

Implementation Method 6

inhibiting lipopolysaccharide-induced pro-inflammatory cytokine release

Methodology Applied
Scientific EffectCytokine inhibition:

Data Source

PatentUS20240239849A1Peptide entities with antimicrobial activity against multi-drug resistant pathogens
Publication Date: 2024.07.18 CENT DE INVESTIGACION & DESARROLLO DE MEDICAMENTOS CIDEM
  • US20240239849A1 patent drawing
  • US20240239849A1 patent drawing
  • US20240239849A1 patent drawing

AI summary

The present invention describes synthetic peptide compounds that combat pathogenic microorganisms of a bacterial nature, and that appear as microorganisms that are multi-resistant to conventional antibiotics. It further describes combination therapies containing said peptides. Pharmaceutical compositions comprising peptide compounds and their combinations are described; as well as the uses and treatment methods in which they can be used.