Antigen binding molecules targeting SARS-CoV-2

Inventors

GRIGORYAN, Gevorg • Ingraham, John • Leung, Cheuk Lun • Federman, Ross Steven • Green, Robin Jeffrey • Ramos, Alexis Hiram • Tao, Jenhan

Assignees

Flagship Pioneering Inc • Flagship Pioneering Innovations VI Inc

Abstract

The invention provides, in various embodiments, polypeptides that specifically bind to Spike glycoprotein of severe acute respiratory syndrome coronavirus (e.g., SARS-CoV-2-Spike). The invention also provides, in various embodiments, fusion proteins comprising one or more of the polypeptides, polynucleotides encoding the polypeptides, vectors and host cells suitable for expressing the polypeptides, and methods for treating viral infections (e.g., COVID-19).

Core Innovation

The invention relates to SARS-CoV-2-Spike binding antigen-binding polypeptides that specifically bind a severe acute respiratory syndrome coronavirus 2 Spike glycoprotein (SARS-CoV-2-Spike). The binding polypeptides comprise an immunoglobulin heavy chain variable region (VH) with heavy chain complementarity determining regions (HCDR1, HCDR2, HCDR3) and an immunoglobulin light chain variable region (VL) with light chain complementarity determining regions (LCDR1, LCDR2, LCDR3), defined as identical to specified SEQ ID numbers.

The described polypeptides bind to Spike and RBD forms, including wild-type and variant forms, and are characterized by affinity, inhibition of SARS-CoV-2-Spike binding to ACE2 and TMPRSS2, and reduced viral entry, infectivity, and fusion. The document further describes functional outcomes together with binding and kinetic characterizations.

In addition to the binding polypeptides, the document provides downstream disclosures including fusion proteins, encoding polynucleotides, expression vectors, host cells, pharmaceutical compositions, and methods of preventing or treating SARS-CoV-2 infection/COVID-19, including methods directed to inhibiting SARS-CoV-2-Spike fusion with a cell. Extensive experimental exemplification is included to support the binding, inhibition, and neutralization-related functional attributes.

Claims Coverage

The claim set centers on one core class of SARS-CoV-2-Spike binding polypeptides defined by VH/VL CDR identity to specified SEQ ID numbers. Additional inventive features refine the polypeptide into selected antibody or antigen-binding fragment formats and extend coverage to treatment compositions and uses including inhibition of SARS-CoV-2-Spike fusion with a cell.

Overall, the claim coverage centers on SARS-CoV-2-Spike binding polypeptides defined by VH/VL complementarity determining region identity to specified SEQ ID numbers, refined by selection of particular VH/VL pairings and by restricting the polypeptide to antibody or antigen-binding fragment formats. Dependent coverage further extends to pharmaceutical compositions and methods for treating SARS-CoV-2 infection and inhibiting SARS-CoV-2-Spike fusion with a cell.

Stated Advantages

Documented Applications