Method of using antibody molecules to detect a proliferation-inducing ligand (APRIL)

Inventors

Myette, James R. • Shriver, Zachary Holmes • Viswanathan, Karthik • Wollacott, Andrew M. • Adari-Hall, Hedy • Ramakrishnan, Boopathy • Babcock, Gregory

Assignees

Visterra Inc

Abstract

Antibody molecules that specifically bind to APRIL are disclosed. The antibody molecules can be used to treat, prevent, and/or diagnose disorders, such as IgA nephropathy.

Core Innovation

The disclosure describes anti-A Proliferation-Inducing Ligand (APRIL) antibody molecules and methods for detecting an APRIL molecule. A cell or a sample from a subject is contacted with an anti-APRIL antibody molecule, and detecting formation of a complex between the antibody molecule and the APRIL molecule in the cell or the sample thereby detects the APRIL molecule.

The anti-APRIL antibody molecules are defined by specific variable-region structures and sequence identities. In one embodiment, the antibody molecule comprises a heavy chain variable region (VH) with three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) with three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), where the HCDR and LCDR regions are specified by amino acid sequences identified as SEQ ID NOs. Another embodiment further defines the antibody molecule by specific VH and VL amino acid sequences identified as SEQ ID NO: 296 and SEQ ID NO: 286.

The disclosure further supports detection approaches that use the antibody–APRIL complex as the detection signal and provides options for implementing the detection. The antibody molecules may be coupled to detectable labels, and the described detection approaches include enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), and tissue immunohistochemistry. The disclosure also references antibody formats and constant-region details including IgG2 heavy-chain constant region and kappa light-chain constant region.

Claims Coverage

The document contains two independent claims. Both independent claims cover detecting an APRIL molecule by contacting a cell or a sample with an anti-APRIL antibody molecule and detecting formation of an antibody–APRIL complex, with the antibody variable regions defined by specific sequence identities.

Across the independent claims, APRIL detection is achieved by detecting complex formation between an anti-APRIL antibody and APRIL in a cell or sample, where the antibody is defined by specific sequence identities in the variable regions or by specific VH and VL sequences.

Stated Advantages

Documented Applications