Antibodies that bind GLP1R
Inventors
Tabibiazar, Ray • Sato, Aaron • Garg, Pankaj • Liu, Qiang • Axelrod, Fumiko
Assignees
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Publication Number
US-12331427-B2
Publication Date
2025-06-17
Expiration Date
Abstract
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.
Core Innovation
The invention relates to GLP1R-targeting antibodies or antibody fragments that bind glucagon-like peptide-1 receptor (GLP1R). The invention provides antibodies or antibody fragments comprising defined heavy chain and light chain variable-region amino acid sequences based on specific SEQ ID NOs, including heavy chain variable region (VH) and light chain variable region (VL) sequence variants tied to particular residue ranges within the referenced SEQ ID NOs.
The invention further defines functional immunoglobulin therapeutics acting on GLP1R, including agonist, antagonist, allosteric modulator, and negative allosteric modulator. In particular embodiments, the modulators are defined by functional performance constraints in a cAMP assay and by antagonist activity against GLP1R, and the antibody or antibody fragment formats include multiple immunoglobulin and fragment types, including antigen-binding fragments.
The document provides a large set of antibody heavy-chain and light-chain variable-region amino acid sequences associated with GLP1R-41 and GLP1R-44. The sequences include antibody heavy chain variable region (VH) and antibody light chain variable region (VL) variants, listed using framework/variable regions for different sequence IDs, and these VH and VL variants serve as specific sequence embodiments for GLP1R-binding antibodies.
Claims Coverage
Independent claim coverage defines GLP1R-binding antibodies or antibody fragments by specified heavy-chain and light-chain variable-region amino-acid sequence residue ranges tied to particular SEQ ID NOs, with alternative heavy-chain/light-chain residue-range combinations. Dependent claims refine this with antibody format choices, antagonist function, potency constraints in a cAMP assay via EC50 thresholds, and therapeutic use for metabolic disorders including Type II diabetes or obesity.
Glp1r-binding antibodies or antibody fragments with defined VH and VL residue ranges tied to specific SEQ ID NOs
An antibody or antibody fragment that binds GLP1R, comprising a heavy chain variable region (VH) and a light chain variable region (VL) where the heavy chain and light chain sequences are defined by residue ranges taken from specific SEQ ID NOs.
Camp assay potency threshold for Glp1r-binding antibodies or antibody fragments
The antibody or antibody fragment has an EC50 below about 25 nM, 20 nM, or 10 nM in a cAMP assay.
Functional antagonist of Glp1r
The antibody or antibody fragment is an antagonist of GLP1R.
Glp1r-binding antibody formats selected from multiple antibody and fragment types
The antibody or antibody fragment is selected from monoclonal, polyclonal, bi-specific, multispecific, grafted, humanized, synthetic, chimeric, single-chain Fvs (scFv), single chain antibody, or antigen-binding fragments thereof.
Treatment of metabolic disorders by administering the GLP1r-binding antibody or antibody fragment
A method of treating a metabolic disorder by administering the antibody or antibody fragment defined by the GLP1R-binding sequence requirement.
Treatment of type ii diabetes or obesity
The metabolic disorder is Type II diabetes or obesity.
The claim coverage defines GLP1R-binding antibody or fragment entities by specific VH and VL residue ranges tied to SEQ ID NOs, with additional refinements specifying antagonist activity, allowable antibody formats, potency thresholds in a cAMP assay, and therapeutic administration for metabolic disorders including Type II diabetes or obesity.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Therapeutic use for metabolic disorders, including Type II diabetes and obesity, by administering the GLP1R-binding antibody or antibody fragment.
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