Beta Klotho Antibodies With Defined CDRs for FGF19-Like Signaling
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Solution Overview
Problem
Existing agents that mimic FGF19 and/or FGF21 for glucose and lipid metabolism do not clearly define the features required for effective FGF19-like or FGF21-like cell signaling activity.
Innovation Solution
Development of binding proteins, such as antibodies, that specifically bind to beta klotho, inducing FGF19-like or FGF21-like signaling without competing with FGF19 and/or FGF21 for beta klotho interaction, and include humanized antibodies with defined CDR sequences to target specific epitopes on beta klotho.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing agents that mimic FGF19 and/or FGF21 are used for glucose and lipid metabolism, then metabolic effects are achieved, but the features required for effective FGF19-like or FGF21-like cell signaling activity are not clearly defined
Solution Approach 1:
The patent applies parameter changes by systematically varying the CDR sequences of antibodies to identify specific sequences that confer FGF19-like or FGF21-like signaling activity. By changing the amino acid parameters in the CDR regions, the invention defines the molecular features required for effective signaling, transforming the undefined characteristics into specific, actionable parameters.
Solution Approach 2:
The patent replaces the mechanical/physical approach of testing various antibody structures with a defined sequence-based system. By substituting the trial-and-error structural approach with a defined CDR sequence framework, the invention enables precise identification of the features required for signaling activity, replacing undefined structural requirements with specific sequence information.
2Reliability
If antibodies are developed to bind beta klotho and induce FGF19-like or FGF21-like signaling, then glucose and lipid metabolism are improved, but the complexity of defining specific binding features and signaling mechanisms increases
Solution Approach 1:
The patent applies segmentation by dividing the antibody molecule into distinct functional regions, particularly focusing on the CDR segments. By segmenting the antibody structure and independently characterizing each CDR region, the invention simplifies the overall design complexity while maintaining the ability to induce FGF19-like or FGF21-like signaling and improve metabolic parameters.
Solution Approach 2:
The patent applies universality by developing antibodies with CDR sequences that can universally bind to beta klotho and induce FGF19-like or FGF21-like signaling across multiple metabolic contexts. The defined CDR sequences create a universal platform that can treat various metabolic conditions including glucose metabolism disorders, lipid metabolism disorders, and related diseases, reducing the need for condition-specific antibody designs.
Data Source
AI summary
The present disclosure provides binding proteins, such as antibodies or binding fragments thereof, that bind beta klotho, including human beta klotho, and methods of their use such as in producing an antibody or binding fragment thereof. The present disclosure also provides vectors and cells comprising polynucleotides encoding antibodies or binding fragments thereof that bind beta klotho, including human beta klotho.