Antigen Binding Proteins Targeting Beta-Klotho FGFR1c Complex
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Solution Overview
Problem
Current treatments for metabolic disorders such as type 2 diabetes, obesity, and dyslipidemia are limited in efficacy and specificity, particularly in mimicking the natural biological effects of FGF21.
Innovation Solution
Development of human antigen binding proteins that specifically bind to β-Klotho, FGFR1c, or their complex, inducing FGF21-like signaling and mimicking the biological effects of FGF21, including improved glucose and lipid metabolism.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for metabolic disorders are used, then treatment coverage is provided, but efficacy and specificity are limited
Solution Approach 1:
The patent uses antigen binding proteins as intermediary molecules that specifically bind to β-Klotho and FGFR1c to activate FGF21-like signaling. These proteins serve as mediators between the administered therapeutic and the metabolic pathways, providing both efficacy through pathway activation and specificity through targeted binding to the β-Klotho-FGFR1c complex.
Solution Approach 2:
The invention changes the therapeutic parameter from non-specific metabolic treatments to highly specific antigen binding proteins with defined binding characteristics. The proteins exhibit specific binding affinity (Kd values) for their targets and can be engineered with precise specificity profiles, transforming the treatment from general metabolic intervention to targeted pathway modulation.
2Reliability
If FGF21 is administered to induce metabolic effects, then glucose and lipid metabolism improve, but the need for heparin cofactor limits applicability
Solution Approach 1:
The patent creates antigen binding proteins that copy and mimic the biological effects of FGF21 without requiring its complex heparin-dependent mechanism. These proteins replicate the desirable metabolic outcomes (glucose uptake, lipid homeostasis) through a simplified pathway that directly activates the β-Klotho-FGFR1c complex without needing heparin as a cofactor.
Solution Approach 2:
The invention extracts the beneficial metabolic effects of FGF21 signaling while removing the requirement for heparin cofactor. By targeting the downstream β-Klotho-FGFR1c complex directly, the therapy separates the desirable metabolic outcomes from the complex administration requirements of natural FGF21.
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 antigen binding proteins effectively induce FGF21-like signaling, leading to improved metabolic parameters, including reduced blood glucose and lipid levels, and enhanced insulin sensitivity, making them potential therapeutic agents for metabolic disorders.
Implementation Method 1
human antigen binding proteins that specifically bind to β-Klotho, FGFR1c, or their complex, inducing FGF21-like signaling
Data Source
AI summary
The present invention provides compositions and methods relating to or derived from antigen binding proteins activate FGF21-mediated signaling. In embodiments, the antigen binding proteins specifically bind to (i) β-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising Q-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. In some embodiments the antigen binding proteins induce FGF21-like signaling. In some embodiments, an antigen binding protein is a fully human, humanized, or chimeric antibodies, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to (i) β-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising β-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. Other embodiments provide nucleic acids encoding such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, cells comprising such polynucleotides, methods of making such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, and methods of using such antigen binding proteins, fragments and derivatives thereof, and polypeptides, including methods of treating or diagnosing subjects suffering from type 2 diabetes, obesity, NASH, metabolic syndrome and related disorders or conditions.