Insulin Receptor Partial Agonist Dimers for Basal Glucose Control
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current insulin therapies for diabetes, particularly long-acting insulins, are not optimized for physiological basal insulin and lead to increased risk of hypoglycemia due to over-insulinization of peripheral tissues.
Innovation Solution
Development of insulin receptor partial agonist (IPRA) covalent insulin dimers that activate the insulin receptor with regular insulin-like potency but with reduced maximum activity, formulated as a novel basal insulin for once daily administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current long-acting insulins are used to regulate basal glucose levels, then glucose control is achieved, but the risk of hypoglycemia increases due to over-insulinization of peripheral tissues
Solution Approach 1:
The patent applies local quality by creating an insulin dimer with non-uniform receptor interaction properties. The dimer structure enables selective action: full insulin-like potency at the liver (hepato-preferring action for glucose regulation) but reduced maximum activity at peripheral tissues. This spatial differentiation of biological activity resolves the contradiction by maintaining effective glucose control while preventing peripheral over-insulinization that causes hypoglycemia
Solution Approach 2:
The patent employs partial action by designing an insulin receptor partial agonist (IPRA) that provides sufficient insulin activity for basal glucose control but deliberately limits maximum receptor activation. The dimeric structure produces sub-maximal insulin-like potency at peripheral tissues compared to monomeric insulin, achieving adequate glucose regulation without excessive insulinization that leads to hypoglycemia
2Stability of the object's composition
If insulin analogs are developed to improve PK flatness, then pharmacokinetic stability is enhanced, but the relative over-insulinization of peripheral tissues persists
Solution Approach 1:
The patent uses composite materials by constructing an insulin dimer from two insulin monomers linked together. This composite structure combines the pharmacokinetic stability benefits of engineered insulins with a novel dimeric architecture that inherently limits peripheral tissue insulinization. The composite dimer structure achieves both PK flatness and reduced harmful peripheral effects simultaneously
3Reliability
If rapid-acting insulin analogs are used to control post-prandial hyperglycemia, then blood sugar control after meals is improved, but the therapeutic index remains narrow
Solution Approach 1:
The patent applies dynamics by creating an insulin dimer that can dynamically adapt its activity based on physiological needs. The dimer structure provides insulin-like potency when needed for glucose control but automatically limits maximum activity to prevent hypoglycemia. This dynamic response capability broadens the therapeutic index while maintaining effective post-prandial and basal glucose control
Data Source
Figure 1
Figure 2A
Figure 2B
AI summary
Insulin dimers and insulin analog dimers that act as partial agonists at the insulin receptor are disclosed.