Klotho-FGF Fusion Polypeptides for Metabolic Disorder Treatment
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Solution Overview
Problem
Current methods lack effective solutions for preventing or treating age-related conditions and metabolic disorders, particularly in addressing the biological characteristics and tissue-specific metabolic activities associated with alpha-Klotho and beta-Klotho proteins.
Innovation Solution
Development of Klotho fusion polypeptides comprising a Klotho protein or its active fragment combined with a fibroblast growth factor, such as FGF23, and a modified Fc fragment, which are linked covalently or via a linker to enhance serum half-life and binding affinity, allowing for the treatment of age-related conditions and metabolic disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If separate administration of Klotho and FGF is used, then therapeutic activity is limited, but fusion polypeptide development increases molecular complexity
Solution Approach 1:
The patent combines Klotho protein or active fragment with fibroblast growth factor through covalent linkage or linkers to create fusion polypeptides. This merging of two separate therapeutic agents into a single molecular entity enhances therapeutic activity by ensuring coordinated delivery and synergistic action at the target site, while the modular design allows for controlled complexity management.
Solution Approach 2:
The fusion polypeptides represent composite molecular structures combining Klotho and FGF components with distinct functional properties. The Klotho portion provides binding specificity to FGF receptors while the FGF portion delivers growth factor activity, creating a composite therapeutic agent with enhanced and complementary functions that address multiple aspects of age-related conditions simultaneously.
2Duration of action of moving object
If modified Fc fragment is added to enhance serum half-life, then duration of action increases, but device complexity increases
Solution Approach 1:
The modified Fc fragment serves as an intermediary component that mediates extended serum half-life through interactions with neonatal Fc receptor (FcRn). This mediator element is incorporated into the fusion polypeptide structure to provide prolonged circulation time without requiring complex dosing regimens or delivery systems, as the Fc fragment naturally interfaces with the body's existing recycling mechanisms.
3Adaptability or versatility
If Klotho-FGF fusion polypeptides are developed to treat multiple conditions, then adaptability increases, but manufacturing precision requirements increase
Solution Approach 1:
The fusion polypeptides are designed with universal applicability to treat multiple age-related conditions including muscle wasting, metabolic disorders, and hyperphosphatemia through a single therapeutic agent. The Klotho component provides broad tissue distribution and receptor binding, while the FGF component delivers universal growth factor benefits, enabling one molecule to address diverse pathological conditions that share common aging-related mechanisms.
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 Klotho fusion polypeptides effectively activate FGF receptors, providing enhanced therapeutic activity compared to separate administration of Klotho and FGF, thereby treating conditions like muscle wasting, metabolic disorders, and hyperphosphatemia, with improved stability and binding properties.
Implementation Method 1
Klotho fusion polypeptides comprising a Klotho protein or its active fragment combined with a fibroblast growth factor, such as FGF23, and a modified Fc fragment, which are linked covalently or via a linker
Data Source
AI summary
The present invention is directed to fusion polypeptides comprising a Klotho protein or an active fragment thereof and FGF23 or an active fragment thereof.