GLP1R Antibody Libraries for Low-Expression GPCR Targeting

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Solution Overview

Problem

Raising antibodies to G protein-coupled receptors (GPCRs) is challenging due to their low expression levels and instability during purification, hindering therapeutic interventions.

Innovation Solution

Development of antibodies or antibody fragments that specifically bind to GLP1R with high affinity and specificity, including various types such as monoclonal, polyclonal, and chimeric antibodies, and nucleic acid libraries encoding for immunoglobulin scaffolds with GLP1R binding domains, capable of modulating GLP1R activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibodies are raised against GPCRs using conventional methods, then therapeutic intervention is achieved, but the process is hindered by low expression levels and instability of GPCRs during purification

Engineering Contradiction:

Improvetherapeutic intervention efficacyVSAvoidGPCR stability during purification

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent employs stabilizing agents and specialized buffer systems as intermediaries to maintain GPCR stability during purification. These mediators prevent protein degradation and aggregation, enabling successful antibody generation against GPCRs without compromising their structural integrity or therapeutic efficacy

Inventive Principle:

Principle #24Intermediary (Mediator)

2Ease of manufacture

If GPCRs are purified for antibody generation, then therapeutic antibodies can be developed, but the low expression levels of GPCRs make this process difficult

Engineering Contradiction:

Improveantibody production feasibilityVSAvoidGPCR expression level

Core Design Contradiction:

Ease of manufactureVSQuantity of substance

Solution Approach 1:

The patent uses preliminary action by first generating stable GPCR expressions in optimized host cell systems before purification. This preliminary stabilization and amplification of GPCR expression ensures sufficient quantity is available for antibody generation, overcoming the natural low expression levels of GPCRs

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent creates multiple copies of the GPCR gene in expression vectors and uses recombinant DNA technology to produce amplified quantities of GPCR protein. This copying approach at the genetic level enables sufficient protein quantity to be obtained for antibody development despite naturally low endogenous expression levels

Inventive Principle:

Principle #26Copying

Data Source

PatentUS20250270737A1Antibodies That Bind GLP1R

Publication Date: 2025.08.28 TWIST BIOSCIENCE CORP

AI summary

Provided herein are methods and compositions relating to glucagon-like peptide-1 receptor (GLP1R) libraries having nucleic acids encoding for a scaffold comprising a GLP1R binding domain. Libraries described herein include variegated libraries comprising nucleic acids each encoding for a predetermined variant of at least one predetermined reference nucleic acid sequence. Further described herein are protein libraries generated when the nucleic acid libraries are translated. Further described herein are cell libraries expressing variegated nucleic acid libraries described herein.