Mutant FGF-21 PEG Conjugates for Severe Hypertriglyceridemia

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Solution Overview

Problem

Current treatments for severe hypertriglyceridemia are inadequate in effectively reducing triglyceride levels and improving associated metabolic parameters in subjects with high fasting triglycerides.

Innovation Solution

Administration of a mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugate, comprising a 20 kDa polyethylene glycol (PEG) moiety attached via a glycosyl moiety, covalently bonded to the FGF-21 peptide, which is administered weekly or bi-weekly to reduce triglyceride levels by at least 20% from baseline.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments for severehypertriglyceridemia are used, then treatment is provided, but triglyceride levels are not effectively reduced and metabolic parameters are not improved

Engineering Contradiction:

Improveeffectiveness of treatmentVSAvoidreduction of triglyceride levels

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent modifies the FGF-21 peptide by introducing a mutation at position 173 (S173T) to create a glycosylation site, then conjugates it with PEG through a glycosyl moiety. This parameter change in the molecular structure transforms the peptide's pharmacokinetic properties, achieving sustained triglyceride reduction of at least 20% from baseline with weekly or bi-weekly dosing, overcoming the inadequacy of current treatments

Inventive Principle:

Principle #35Parameter changes

2Productivity

If FGF-21 peptide is administered, then triglyceride levels are reduced, but the duration of action is insufficient for practical weekly or bi-weekly dosing

Engineering Contradiction:

Improvetriglyceride reduction efficacyVSAvoidduration of FGF-21 action

Core Design Contradiction:

ProductivityVSDuration of action of moving object

Solution Approach 1:

The patent creates a composite structure by conjugating FGF-21 peptide with polyethylene glycol (PEG) through a glycosyl moiety. This composite material combines the triglyceride-lowering activity of FGF-21 with the sustained-release properties of PEG, achieving duration of action sufficient for weekly or bi-weekly dosing while maintaining at least 20% triglyceride reduction efficacy

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The glycosyl moiety acts as an intermediary between the FGF-21 peptide and PEG, enabling covalent attachment while preserving the peptide's biological activity. This intermediary structure allows the conjugate to achieve both triglyceride reduction efficacy and extended duration of action for practical dosing intervals

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20250325679A1Compositions and methods of treatment for severe hypertriglyceridemia

Publication Date: 2025.10.23 89BIO INC

AI summary

Compositions, methods and therapeutic regimens of mutant Fibroblast Growth Factor-21 (FGF-21) peptide conjugates for the treatment of severe hypertriglyceridemia are provided.