Filamin A binding proteins and uses thereof
Inventors
Wu, Wenfang Sybil • Ravipaty, Shobha • Friss, Tracey • Akmaev, Viatcheslav R. • Tanna, Nikunj Narendra
Assignees
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Publication Number
US-11866487-B2
Publication Date
2024-01-09
Expiration Date
Abstract
The present invention encompasses filamin A (FLNA) binding proteins. Specifically, the invention relates to antibodies to FLNA. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Methods of making and methods of using the antibodies of the invention in methods of diagnosis, monitoring and prognosis of prostate cancer are also provided.
Core Innovation
The invention relates to detecting and/or quantifying the level of FLNA (filamin A) in a sample. It provides methods that contact a sample with an antibody construct or antigen-binding fragment capable of binding FLNA, where the antibody variable regions comprise specified CDR1, CDR2, and CDR3 amino acid sequence sets. Binding under conditions such that the antibody construct binds FLNA is used to detect and/or quantify FLNA levels in the sample.
The invention also provides mass spectrometry-based detection and quantification in which one or more surrogate peptides are detected and/or quantified in a protein digest prepared from the sample. The mass spectrometry is multiple reaction monitoring (MRM) mass spectrometry, including an IPMRM variant that comprises a FLNA immunoprecipitation step performed using the antibody construct or antigen-binding fragment. Surrogate peptide detection includes SEQ ID NO:40 (P2) and/or SEQ ID NO:41 (P4), enabling detection and/or quantification of FLNA levels from the surrogate peptides.
For FLNA-based clinical use, the document describes comparing FLNA expression changes between baseline and follow-up prostate cancer samples to guide clinical decisions. Increased FLNA suggests a non-efficacious therapy while decreased FLNA supports therapy efficacy, and biomarker panels including FLNA improve classification compared with PSA alone.
Claims Coverage
The document provides two independent methods. Across the independent claims, the inventive features center on antibody-construct-based FLNA binding with specified heavy- and light-chain CDR sequences, and on quantification via MRM/IPMRM mass spectrometry using defined surrogate peptides P2 and P4 for FLNA in protein digests.
Antibody construct for binding FLNA using specified CDR sequences
A method for detecting and/or quantifying FLNA in a sample by contacting the sample with an antibody construct or antigen-binding fragment capable of binding FLNA, where the antibody heavy- and light-chain variable regions comprise specified CDR1, CDR2, and CDR3 amino acid sequences provided in alternative sets.
MRM/IPMRM quantification of FLNA using surrogate peptides P2 and P4
A method for detecting and/or quantifying FLNA in a sample by detecting and/or quantifying one or more surrogate peptides comprising SEQ ID NO:40 (P2) and/or SEQ ID NO:41 (P4) in a protein digest using multiple reaction monitoring (MRM) mass spectrometry, wherein the MRM is immunoprecipitation-multiple reaction monitoring (IPMRM) comprising a FLNA immunoprecipitation step carried out using the specified antibody construct or antigen-binding fragment.
Claim coverage spans FLNA detection/quantification by antibody construct binding with defined CDR sequence sets, and FLNA detection/quantification from protein digests using MRM mass spectrometry, specifically IPMRM with FLNA immunoprecipitation, where surrogate peptides P2 and P4 are used for quantification.
Stated Advantages
Biomarker panels including FLNA improve classification versus PSA alone.
Increased FLNA supports the indication of a non-efficacious therapy, while decreased FLNA supports therapy efficacy based on expression changes between baseline and follow-up prostate cancer samples.
Documented Applications
Guide clinical decisions in prostate cancer by comparing FLNA expression changes between baseline and follow-up samples to support determining therapy efficacy versus non-efficacy.
Diagnostic/monitoring workflows for detecting FLNA in samples using binding proteins and/or an IPMRM mass spectrometry approach with surrogate peptides P2 and P4, including use of control samples and risk stratification through biomarker panels including FLNA.
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