Neutralizing monoclonal anti-VP1 antibodies to BK virus
Inventors
Moran, Thomas M. • Kraus, Thomas A. • Duty, James A. • Tortorella, Domenico
Assignees
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Publication Number
US-12668620-B2
Publication Date
2026-06-30
Expiration Date
Abstract
Provided herein are monoclonal antibodies targeting VP1 of polyomaviruses including BK virus. Also provided are methods of treating or preventing polyomavirus infections using one or more antibodies.
Core Innovation
The invention relates to an isolated anti-BK virus VP1 antibody or an antigen binding fragment thereof. The antibody is defined by specific heavy chain variable region (VH) and light chain variable region (VL) complementarity determining regions (CDRs), with HCDR1, HCDR2, and HCDR3 assigned to particular SEQ ID NO values and LCDR1, LCDR2, and LCDR3 assigned to particular SEQ ID NO values.
The antibodies are described as neutralizing BK virus across serotypes 1-4 and across BK genotypes I-IV. They inhibit infection by blocking VP1 interactions with sialic acid, including 12,3-linked and 12,8-linked sialic acid interactions.
The document also describes anti-BK virus VP1 antibody development and evaluation using VP1-directed immune responses, pseudovirus neutralization assays, epitope mapping using VP1 point mutants, and antibody complementation/synergy. Multiple antibody sequence families are described as cross-neutralizers and partial neutralizers across BK genotypes I-IV.
Claims Coverage
The consolidated claim coverage includes one independent claim directed to an isolated anti-VP1 antibody or antigen binding fragment defined by specific VH and VL CDR assignments, with multiple alternative CDR sets and sequence-identity constraints. The combined claim set also includes dependent and application claims for neutralizing BK virus infection and treating BK/JC virus-associated disorders and transplant-related contexts.
Isolated anti-vp1 antibody defined by specific vh and vl cdr seq id assignments
An isolated anti-VP1 antibody or antigen binding fragment comprising a heavy chain variable region (VH) with three CDRs and a light chain variable region (VL) with three CDRs, wherein the CDRs are specified by particular SEQ ID NO assignments, including alternative sets of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences.
The core inventive scope is an anti-VP1 antibody or antigen binding fragment whose binding specificity is defined by particular VH and VL CDRs identified by SEQ ID NOs, with additional sequence-identity and constant-region specifications, and downstream coverage for neutralization and treatment uses.
Stated Advantages
Inhibiting infection by blocking VP1-sialic acid interactions.
Neutralizing BK virus across serotypes 1-4 and across BK genotypes I-IV.
Treating or lowering the likelihood of BK virus or JC virus associated disorders.
Improving coverage across BK genotypes I-IV through antibody complementation/synergy by combining antibodies from different genetic families targeting multiple epitopes.
Reducing transplant rejection by selecting a neutralizing antibody based on BK virus serotype.
Documented Applications
Neutralizing BK virus infection in a subject by administering an effective amount of the recited antibody or antigen binding fragment.
Treating or lowering the likelihood of a BK virus or JC virus associated disorder selected from transplant rejection, graft-versus-host disease (GvHD), nephropathy (BKVAN), hemorrhagic cystitis (PyVHC/HC), progressive multifocal leukoencephalopathy (PML), granule cell neuronopathy (GCN), interstitial kidney disease, ureteral stenosis, vasculitis, colitis, retinitis, meningitis, and immune reconstitution inflammatory syndrome (IRIS).
Reducing transplant rejection by determining the BK virus serotype in a donor organ, selecting an antibody that neutralizes that serotype, and administering it to the transplant recipient by injection or infusion.
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