Reversible PEG-Oxyntomodulin Conjugate for Extended Half-Life

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Solution Overview

Problem

Peptide drugs like oxyntomodulin face challenges due to short serum half-life, instability in the bloodstream, and frequent dosing requirements, which limits their therapeutic effectiveness and comfort for patients.

Innovation Solution

A composition of oxyntomodulin conjugated with a polyethylene glycol polymer via a reversible linker, such as 9-fluorenylmethoxycarbonyl (Fmoc) or 2-sulfo-9-fluorenylmethoxycarbonyl (FMS), extending its biological half-life and allowing slow release into the bloodstream, enabling longer action and reduced dosing frequency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If oxyntomodulin is administered as a peptide drug, then it can regulate food intake and enhance glucose clearance, but it has short serum half-life and requires frequent dosing

Engineering Contradiction:

Improveserum half-lifeVSAvoiddosing frequency

Core Design Contradiction:

Duration of action of moving objectVSProductivity

Solution Approach 1:

The patent applies composite materials by conjugating oxyntomodulin with polyethylene glycol (PEG) polymer to create a hybrid molecule that combines the biological activity of the peptide with the extended circulation properties of PEG, thereby prolonging serum half-life and reducing dosing frequency

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent changes the molecular parameters of oxyntomodulin by attaching PEG chains of varying molecular weights and configurations, which modifies the peptide's pharmacokinetic properties including serum half-life, stability, and dosing requirements without compromising its biological activity

Inventive Principle:

Principle #35Parameter changes

2Reliability

If oxyntomodulin is administered frequently to maintain therapeutic levels, then therapeutic effectiveness is maintained, but patient comfort and compliance deteriorate

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidpatient comfort

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The PEG-oxyntomodulin conjugate combines the therapeutic efficacy of oxyntomodulin with the extended circulation time of PEG, maintaining reliable glucose control and food intake regulation while reducing injection frequency to improve patient comfort and compliance

Inventive Principle:

Principle #40Composite materials

3Duration of action of stationary object

If PEG polymer is attached to oxyntomodulin via reversible linker, then circulating time and stability are extended, but molecular complexity increases

Engineering Contradiction:

Improvecirculating timeVSAvoidmolecular complexity

Core Design Contradiction:

Duration of action of stationary objectVSDevice complexity

Solution Approach 1:

The patent uses a reversible linker as an intermediary component between PEG and oxyntomodulin, allowing for controlled conjugation and potential release of the active peptide while managing molecular complexity through a modular design approach

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 conjugation significantly extends the circulating time of oxyntomodulin, enhancing its stability, activity, and ability to cross the blood-brain barrier, maintaining pharmacological efficacy with fewer injections and reduced side effects.

Implementation Method 1

Methodology Applied

Scientific EffectPegylation:

Data Source

PatentUS10537646B2Pegylated OXM variants

Publication Date: 2020.01.21 OPKO BIOLOGICS LTD

AI summary

A composition which includes oxyntomodulin and polyethylene glycol polymer (PEG polymer) linked via a reversible linker such as 9-fluorenylmethoxycarbonyl (Fmoc) or 2-sulfo-9-fluorenylmethoxycarbonyl (FMS) is disclosed. Pharmaceutical compositions comprising the reverse pegylated oxyntomodulin and methods of using same are also disclosed.