Glucose-Responsive Insulin Analogs for Self-Regulated Glycemic Control

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Solution Overview

Problem

Patients with insulin disorders face dangerous blood glucose fluctuations due to abnormal insulin levels, requiring frequent monitoring and multiple injections, as minor insulin dosing changes can lead to glucose level imbalances.

Innovation Solution

Development of glucose-responsive insulin analogs with a glucose binding site that changes conformation upon glucose binding, altering insulin receptor affinity, allowing for regulated insulin activity based on blood glucose levels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional insulin is used to treat insulin disorders, then blood glucose levels can be controlled, but frequent monitoring and multiple injections are required due to minor dosing changes causing glucose fluctuations

Engineering Contradiction:

Improveblood glucose level controlVSAvoidfrequency of monitoring and injections

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The insulin analog is designed with dynamic conformational states (T state with low receptor affinity and R state with high receptor affinity) that transition in response to glucose binding, allowing the insulin to adapt its activity level dynamically rather than remaining static

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The insulin analog incorporates a feedback mechanism where glucose binding to the glucose binding site triggers a conformational change that increases insulin receptor affinity, creating a self-regulating system that responds to blood glucose levels without external intervention

Inventive Principle:

Principle #23Feedback

2Stability of the object's composition

If insulin dosing is adjusted to improve blood glucose control, then glucose level stability improves, but the complexity of dosing management increases requiring repeated monitoring and multiple injections

Engineering Contradiction:

Improveblood glucose level stabilityVSAvoiddosing regimen complexity

Core Design Contradiction:

Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The insulin analog performs self-regulation by automatically adjusting its receptor affinity based on glucose binding, eliminating the need for external dosing adjustments and monitoring by the patient

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The insulin analog changes its binding affinity parameter in response to glucose levels, transitioning from low affinity (T state) to high affinity (R state) to match metabolic needs without requiring external parameter adjustment

Inventive Principle:

Principle #35Parameter changes

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 insulin analogs maintain stable blood glucose levels by increasing insulin receptor affinity in response to glucose levels, reducing the need for frequent monitoring and injections.

Implementation Method 1

binding of a glucose molecule to the glucose binding site changes conformation of the insulin analog

Methodology Applied

Scientific EffectConformational change:

Implementation Method 2

the insulin analog has a low affinity for an insulin receptor in the absence of the glucose molecule binding to the glucose binding site... the insulin analog has an increased affinity for an insulin receptor when the glucose molecule binds to the glucose binding site

Methodology Applied

Scientific EffectAllosteric modulation:

Data Source

PatentUS20260022153A1Glucose-responsive insulin analogs and methods of use thereof

Publication Date: 2026.01.22 AMIDEBIO LLC

AI summary

The subject matter of this invention is directed towards insulin analogs that are stable and glucose-responsive. An insulin analog can be a single chain insulin (SCI). The binding affinity of insulin to the insulin receptor can be controlled by the glucose-bound conformation of insulin. The invention further discloses methods for the recombinant expression, purification, and refolding of an insulin analog.