Methods of treating IgA nephropathy by administering an anti-APRIL (a proliferation-inducing ligand) antibody molecule
Inventors
Myette, James R. • Shriver, Zachary Holmes • Viswanathan, Karthik • Wollacott, Andrew M. • Adari-Hall, Hedy • Ramakrishnan, Boopathy • Babcock, Gregory
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11136385-B2
Publication Date
2021-10-05
Expiration Date
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 invention relates to anti-APRIL antibody molecules and their use in treating IgA nephropathy. The antibody molecules comprise a heavy chain variable region (VH) and a light chain variable region (VL), each defined by three complementarity determining regions (HCDR1, HCDR2, HCDR3; and LCDR1, LCDR2, LCDR3). Specific amino acid sequences are assigned to these regions using SEQ ID NOs, including VH HCDR1/2/3 sequences of SEQ ID NOs: 11/12/13 or 17/282/13 and VL CDR sequences of SEQ ID NOs: 280/285/16.
A central aspect is the defined composition of the anti-APRIL antibody molecules, including anti-APRIL antibody binding and blocking performance against human APRIL interactions with TACI and BCMA. The antibody molecules include humanized anti-APRIL antibody molecules, Fc-containing antibodies, and fragment forms such as Fab, F(ab’)2, scFv, Fv, and Fd, and the disclosures include reduced complement activation. The document also describes antibody molecule formats, epitope preferences, and binding potency metrics, including EC50/IC50 values, together with cross-species activity versus mouse APRIL.
The disclosed therapeutic approach includes administering an effective amount of the specified anti-APRIL antibody molecule to a subject in need thereof, thereby treating IgA nephropathy. Related disclosures include reducing IgA levels in peripheral tissues and/or reducing specific IgA variants including IgA1, polymeric IgA1 (pIgA1), and an O-linked glycosylation variant of IgA1. The disclosures also include diagnostic detection of APRIL using antibody binding assays and labeled antibody formats, and pharmaceutical compositions, nucleic acids, vectors, host cells, and kits.
Claims Coverage
The consolidated claim coverage includes two independent claims. Across the independent claims, the inventive features focus on administering an anti-APRIL antibody molecule to treat IgA nephropathy, with one claim defined by specific HCDR/LCDR sequence sets and the other limited to specific full VH and VL sequences.
Treating IgA nephropathy with anti-APRIL antibody defined by VH and VL CDR sequences
A method of treating IgA nephropathy by administering to a subject an effective amount of an anti-APRIL antibody molecule comprising a VH with HCDR1, HCDR2, and HCDR3 and a VL with LCDR1, LCDR2, and LCDR3, where the VH comprises HCDR1 as SEQ ID NO: 11, HCDR2 as SEQ ID NO: 12, and HCDR3 as SEQ ID NO: 13 or HCDR1 as SEQ ID NO: 17, HCDR2 as SEQ ID NO: 282, and HCDR3 as SEQ ID NO: 13, and the VL comprises LCDR1 as SEQ ID NO: 280, LCDR2 as SEQ ID NO: 285, and LCDR3 as SEQ ID NO: 16.
Treating IgA nephropathy with anti-APRIL antibody having fixed VH and VL sequence identities
A method of treating IgA nephropathy by administering to a subject an effective amount of an anti-APRIL antibody molecule, wherein the antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296 and a VL comprising the amino acid sequence of SEQ ID NO: 286.
Across the independent claims, the inventive scope is anchored in exact VH/VL sequence definitions for anti-APRIL antibody molecules used to treat IgA nephropathy, either as specific HCDR/LCDR sequence combinations or as fixed VH and VL sequences.
Stated Advantages
Treats IgA nephropathy.
Reduces IgA levels in peripheral tissues and/or reduces specific IgA variants including IgA1, polymeric IgA1 (pIgA1), and an O-linked glycosylation variant of IgA1.
Binding potency to human APRIL.
Receptor blocking/neutralization of APRIL–TACI/BCMA interactions.
Reduced complement activation.
Mesangial clearance.
Reduced kidney inflammation.
Documented Applications
Therapeutic use in treating IgA nephropathy by administering an anti-APRIL antibody molecule to a subject in need thereof.
Diagnostic detection of APRIL using antibody binding assays and labeled antibody formats.
Diagnostics and therapy using radiolabeled antibodies derived from anti-APRIL antibody molecules and radiolabeling via a chelating agent.
Nonclinical evaluation of the anti-APRIL antibody molecules in animal models for IgA nephropathy.
Therapeutic use for disorders associated with APRIL, especially IgA nephropathy.
Interested in licensing this patent?