Anti-ceruloplasmin antibodies and uses thereof
Inventors
Potter, David George • Dzielawa, Jennifer Ann • Carter, Brenda Sue • Ma, Mark
Assignees
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Publication Number
US-12590977-B2
Publication Date
2026-03-31
Expiration Date
Abstract
Provided herein are antibodies which bind to ceruloplasmin and are useful for various applications, including detecting ceruloplasmin and immunocapturing ceruloplasmin in biological samples. The antibodies are useful in methods of measuring non-ceruloplasmin-bound copper concentrations and labile-bound copper concentrations in biological samples.
Core Innovation
The invention provides anti-ceruloplasmin antibodies that bind human ceruloplasmin having the amino acid sequence set out in SEQ ID NO: 1. Specific antibody binding is defined through heavy chain variable region CDR1, CDR2, and CDR3 amino acid sequences and light chain variable region CDR1, CDR2, and CDR3 amino acid sequences, as presented in the claims by selected SEQ ID NOs.
The disclosure further provides antibody mixtures comprising two or three such antibodies selected from the defined sets of ceruloplasmin-binding CDR sequences. The work includes evaluation of binding retention upon biotinylation, reduced cross-competition for CP binding among key mAbs, and antibody mixtures as improved CP binders compared with weaker or less-correlated candidates.
The disclosure describes immunocapture/immunodepletion performance assessed by LC-MS/MS quantification of CP in comparison to polyclonal anti-CP. It reports that individual mAbs and especially mixtures outperform polyclonal anti-CP, and that a three-mAb mixture with a specified component ratio provides the strongest CP depletion; validation includes assay accuracy/precision, mix stability, and extension to copper sub-fractions involving non-ceruloplasmin-bound copper and labile-bound copper workflows using the anti-CP mixture for CP removal prior to copper readout.
Claims Coverage
The provided independent claims cover two inventive features: isolated anti-ceruloplasmin antibodies defined by specific heavy- and light-chain variable-region CDR sequences, and antibody mixtures comprising two or three such antibodies. The coverage is grounded in CDR-sequence-defined binding to human ceruloplasmin (SEQ ID NO: 1) and constrained mixture membership.
Isolated antibody binding human ceruloplasmin by defined CDR sequences
An isolated antibody that binds human ceruloplasmin having the amino acid sequence set out in SEQ ID NO: 1, comprising specified heavy chain variable region CDR1/2/3 sequences and specified light chain variable region CDR1/2/3 sequences, with the heavy/light CDR sets defined by selected SEQ ID NO options.
Two- or three-antibody mixture binding human ceruloplasmin by defined CDR sequence options
An antibody mixture comprising two or three antibodies that bind human ceruloplasmin having the amino acid sequence set out in SEQ ID NO: 1, where each antibody is selected from the group consisting of three isolated-antibody options defined by specified heavy chain variable region CDR1/2/3 sequences and specified light chain variable region CDR1/2/3 sequences.
Overall, the claim set ties antibody binding to human ceruloplasmin (SEQ ID NO: 1) to precise heavy- and light-chain CDR sequence definitions, and extends this to mixture formats that restrict the mixture membership to two or three CDR-defined antibody options and, in dependent claims, constrain mixture composition using specified ratios.
Stated Advantages
Enables efficient immunocapture/immunodepletion of ceruloplasmin from plasma or serum to support direct measurement of non-ceruloplasmin-bound copper (NCC) and labile-bound copper (LBC).
Antibody mixtures outperform polyclonal anti-CP in immunocapture/immunodepletion efficiency for CP depletion.
The three-mAb mixture provides the strongest CP depletion among the evaluated mixtures.
The disclosed mixture shows assay accuracy/precision for CP measurement over the stated concentration range.
The antibody mixture demonstrates stability over 9 months with preserved ELISA activity and aSEC integrity/concentration.
Supports diagnostic identification of copper metabolism-associated diseases or disorders, including Wilson disease, using measured NCC or LBC relative to a threshold.
Supports guidance of therapeutic selection or adjustment for copper metabolism treatment based on copper measurement results.
The approach extends to workflows involving non-ceruloplasmin-bound copper and labile-bound copper, using the anti-CP mixture for CP removal prior to copper readout.
Documented Applications
Measuring non-ceruloplasmin-bound copper concentration in a biological sample by immunocapturing ceruloplasmin using an antibody mixture and measuring copper concentration in the resulting non-ceruloplasmin sample.
Measuring CP-related fractions by immunocapture, including performance assessment using LC-MS/MS quantification of CP and extension to non-ceruloplasmin-bound copper and labile-bound copper workflows using anti-CP mixture for CP removal prior to copper measurement.
Identifying whether a patient has a copper metabolism-associated disease or disorder by measuring the concentration of non-ceruloplasmin-bound copper or labile-bound copper in a biological sample relative to a threshold.
Treating copper metabolism-associated disease or disorder by administering an effective amount of a therapeutic agent based on the identified condition from copper measurement relative to a threshold.
Use in assays or kits for measuring copper, including NCC and/or LBC, in the context of monitoring and diagnostic use for copper metabolism disorders, including Wilson disease.
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