Bispecific SARS-CoV-2 antibodies and methods of use
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12325739-B2
Publication Date
2025-06-10
Expiration Date
Abstract
Provided herein are methods and compositions relating to improved bispecific antibodies capable of binding and neutralizing SARS-CoV-2 variants.
Core Innovation
The invention relates to SARS-CoV-2 bispecific VHH antibodies and antibody fragments that comprise at least two binding domains to a spike glycoprotein or a receptor of the spike glycoprotein. The bispecific format links two different VH binding specificities directed to the spike glycoprotein or its receptor, and the document includes humanized VHHs 6-3 and 3-31 linked to an Fc constant region.
Each binding domain includes a variable domain, heavy chain region (VH) with specified complementarity determining regions CDRH1, CDRH2, and CDRH3 defined by SEQ ID NOs. The document further supports variant-spanning binding by characterizing interactions with spike/variant forms including Delta (B.1.617.2) and Omicron (B.1.529), and includes quantitative binding characterization with picomolar SPR binding and KD thresholds.
Beyond binding, the patent describes functional and characterization assays for the bispecific antibodies, including authentic-virus plaque neutralization and escape assessments. Effector-function profiling is also included, including ADCC, CDC, and ADCP, together with ADE experiments indicating no ADE signal. Additional characterization includes Fc receptor and FcRn/C1q binding and ACE2-spike inhibition, and the patent includes cryoEM structural analysis mapping VHH binding positions/epitopes on the spike and constant fragment density.
Claims Coverage
The document includes one independent claim directed to a bispecific antibody or antibody fragment with two spike-binding domains defined by specific CDRH1, CDRH2, and CDRH3 amino-acid sequences, with dependent claims refining molecular valency and introducing binding affinity thresholds. Overall, the independent claim covers sequence-defined bispecific VH domains binding to a spike glycoprotein or its receptor.
Sequence-defined bispecific spike binding domains
A bispecific antibody or an antibody fragment thereof comprising at least two binding domains to a spike glycoprotein or a receptor of the spike glycoprotein, including a first VH variable domain whose CDRH1, CDRH2, and CDRH3 amino acid sequences are as set forth in SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, and a second VH variable domain whose CDRH1, CDRH2, and CDRH3 amino acid sequences are as set forth in SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6.
Valency options for the bispecific antibody
The bispecific antibody or antibody fragment is bivalent, trivalent, or tetravalent.
Binding affinity threshold for bispecific spike binding
The bispecific antibody or an antibody fragment thereof has a binding affinity (KD) of less than 50 nM.
Tighter binding affinity threshold for bispecific spike binding
The bispecific antibody or an antibody fragment thereof has a KD of less than 25 nM.
Claim coverage is grounded in the sequence-defined CDRH1, CDRH2, and CDRH3 constraints for two VH binding domains that bind a spike glycoprotein or its receptor, with dependent claims further specifying selectable valency and quantitative binding affinity limits (KD thresholds of <50 nM and <25 nM).
Stated Advantages
Supports binding and interaction characterization against spike variant forms including Delta (B.1.617.2) and Omicron (B.1.529).
Includes functional neutralization and escape assessments.
Includes effector-function profiling (ADCC, CDC, ADCP).
Includes ADE experiments indicating no ADE signal.
Includes Fc receptor and FcRn/C1q binding and ACE2-spike inhibition characterization.
Includes cryoEM structural analysis mapping VHH binding positions and epitopes on spike.
Documented Applications
Therapeutic and diagnostic approaches are described in the document context for the SARS-CoV-2 bispecific VHH antibodies and related compositions and methods.
Interested in licensing this patent?