Claudin 6 antibodies and uses thereof
Inventors
Chambers, Ross • Rucker, Joseph • Charpentier, Thomas • Stafford, Lewis J. • Screnci, Brad • Barnes, Trevor • Doranz, Benjamin
Assignees
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Publication Number
US-11248046-B2
Publication Date
2022-02-15
Expiration Date
Abstract
Antibodies and compositions against Claudin 6 and uses thereof are provided.
Core Innovation
The invention provides an antibody comprising a heavy chain variable region and a light chain variable region, where each variable region includes defined CDR1, CDR2, and CDR3 sequences specified by SEQ ID NOs. The antibody binds Claudin-6 with high affinity and strong selectivity over Claudin-3/4/9, and the disclosure includes epitope residue sets on Claudin-6, including a Q156-containing epitope set.
The disclosure defines multiple heavy-chain and light-chain CDR amino-acid sequence combinations, and the scope includes different HCDR1/HCDR2/HCDR3 and LCDR1/LCDR2/LCDR3 groupings. The antibody designs target Claudin-6, with binding affinity characterized by EC50 and/or KD criteria and low binding to Claudin-9 specified as part of selectivity.
The document further describes antibody formats and related constructs, including monoclonal and humanized antibody embodiments and formats that include bispecific and fused constructs. It also describes antibodies generated using virus-like particles presenting Claudin-6 in native conformation, and the invention encompasses nucleic acids, vectors, cells containing nucleic acids that encode the antibodies, and pharmaceutical compositions containing the antibodies.
Claims Coverage
The provided content identifies one independent claim directed to an antibody defined by specific heavy- and light-chain CDR sequence sets, with dependent claims additionally constraining sequence identity thresholds and expanding coverage to nucleic acids, pharmaceutical compositions, and cells containing such nucleic acids.
Cdr-defined antibody with specified heavy- and light-chain variable regions
An antibody comprising a heavy chain variable region with HCDR1, HCDR2, and HCDR3, and a light chain variable region with LCDR1, LCDR2, and LCDR3, wherein the antibody has particular HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences defined by SEQ ID NO combinations.
Across the provided material, the claim coverage centers on antibodies whose heavy-chain and light-chain variable regions include particular, SEQ ID NO-specified CDR1/2/3 sequences. The dependent claims further refine this coverage by sequence identity constraints and by adding nucleic acid, pharmaceutical composition, and cell embodiments.
Stated Advantages
Strong selectivity over Claudin-3/4/9.
High affinity binding to Claudin-6.
Improved binding selectivity characterized by binding to Claudin 6 together with preferred low binding to Claudin 9, with binding affinity described using EC50/KD criteria.
Epitope specificity is characterized by epitope mapping residue sets on Claudin 6, including Q156-containing epitopes.
Downstream functional activity is described through CAR-T activation readouts, including CD69, associated with the Claudin 6-directed constructs.
Documented Applications
Therapeutic modulation/inhibition of Claudin-6 activity.
Targeting in multispecific formats (e.g., CD3/4-1BB context).
Detection of Claudin-6 in samples.
Claudin-6-associated cancer treatment.
Kits for Claudin-6 detection/antibody delivery.
CAR-T activation associated with Claudin 6 targeting, including readouts such as CD69.
Functional characterization of antibodies using binding specificity assessment and epitope mapping described via assays.
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