Methods and compositions relating to covid antibody epitopes
Inventors
Sato, Aaron • Liu, Qiang • YUAN, Tom
Assignees
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Publication Number
US-12201857-B2
Publication Date
2025-01-21
Expiration Date
Abstract
Provided herein are methods and compositions relating to libraries of optimized antibodies having nucleic acids encoding for an antibody comprising modified sequences. Libraries described herein comprise nucleic acids encoding SARS-CoV-2 or ACE2 antibodies. 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 disclosure describes nucle-acid synthetic variant libraries using precision nucleic-acid synthesis to generate variant polynucleotide libraries with low error rates. The synthesis approach includes parallel nucleic-acid synthesis using surface/device architectures and precision control concepts for DNA synthesis cycle operations, with quality control directed to maintaining sequence fidelity and reducing error outcomes for synthesized variants.
The described variant library framework includes substrate, locus/cluster, and addressable locations, including homogeneous and patterned arrays and three-dimensional substrates. Surface functionalization concepts are described for forming functionalized surfaces suitable for parallel synthesis in clusters and loci, and a device for nucleic-acid synthesis includes computer-controlled reagent dispensing and controlled mass transfer paths.
The disclosure also describes an in situ array-to-nanoreactor workflow using PCA reaction and PCR amplification, together with error correction concepts to remove mismatches or poor complementarity. The output is directed to downstream selection and evaluation workflows, including antibody/protein variant optimization and disease-state cell expression/screening, with example readouts described as binding, competition, neutralization, affinity, stability, and effector function.
In SARS-CoV-2-related examples, the disclosure describes construction and panning of phage antibody libraries, lead identification using binding, competition, and neutralization measurements, and epitope mapping using shotgun mutagenesis in spike RBD and NTD. It further describes antibody and ACE2-related sequence tables and exemplary sequence identifiers, including antibodies described relative to SEQ ID NO: 2670 for SARS-CoV-2 treatment.
Claims Coverage
The provided material includes two independent claims, centered on sequence-defined antibody coverage. One claim is directed to a bispecific antibody at least 90% similar to SEQ ID NO: 2670, and one claim is directed to treating SARS-CoV-2 by administering an antibody at least 90% similar to SEQ ID NO: 2670.
Bispecific antibody with at least 90% similarity to SEQ ID NO: 2670
A bispecific antibody defined as having at least 90% similarity to SEQ ID NO: 2670.
Treating SARS-CoV-2 by administering an antibody at least 90% similar to SEQ ID NO: 2670
A method of treating SARS-CoV-2 comprising administering an antibody to a subject, wherein the antibody is at least 90% similar to SEQ ID NO: 2670.
The claim coverage is centered on the at-least-90%-similarity antibody criterion to SEQ ID NO: 2670, applied to both a bispecific antibody and a SARS-CoV-2 treatment method.
Stated Advantages
Low error rates and improved sequence fidelity for synthesized variant polynucleotides.
Supports downstream selection and evaluation for antibody/protein variant optimization and disease-state cell expression/screening.
Allows treating SARS-CoV-2 infection and/or preventing SARS-CoV-2 infection using antibodies and pharmaceutical compositions.
Documented Applications
Antibody/protein variant optimization using nucle-acid synthetic variant libraries, including selection and evaluation using binding, competition, and neutralization measurements.
Disease-state cell expression/screening of protein variants, including evaluation described via binding affinity, stability, and effector function.
SARS-CoV-2 antibody discovery workflows including phage display library construction, panning, lead identification, and epitope mapping in spike RBD and NTD using shotgun mutagenesis.
Therapeutic treatment and prevention of SARS-CoV-2 infection using antibodies and pharmaceutical compositions.
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