Antibody binding specifically to ECL-2 of claudin 3, fragment thereof, and use thereof
Inventors
Shin, Young Kee • HONG, SUNG YOUL • Kim, Young Deug • Choi, Jun Young • YANG, HEO BIN • Park, Ha Yeon • Kim, Sung Su
Assignees
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Publication Number
US-12098198-B2
Publication Date
2024-09-24
Expiration Date
Abstract
The invention of the present application relates to a use of an antibody binding specifically to ECL-2 of claudin 3 and functional fragments thereof in cancer cell detection, diagnosis, imaging, and application to cancer treatment (anticancer use of the antibody itself, and application to ADC and CAR-expression cells (particularly immune cells)), an antibody that includes a characteristic CDR sequence exerting a remarkable effect in such uses, and a functional fragment thereof.
Core Innovation
The invention provides an antibody or functional fragment thereof that specifically binds claudin 3 by targeting the extracellular second loop of claudin 3. The antibody comprises a heavy chain variable region with VH-CDR1, VH-CDR2, and VH-CDR3 comprising amino acid sequences defined by SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5, and a light chain variable region with VL-CDR1, VL-CDR2, and VL-CDR3 comprising amino acid sequences defined by SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8.
The disclosure addresses the need for claudin 3 binding reagents suitable for cancer cell detection, diagnosis, imaging, and therapy. Functional fragments are described as comprising the same complementarity determining region architecture to provide alternative antibody formats including Fab, F(ab')2, F(ab'), Fv, scFv, diabody, and dsFv.
The invention further relates the claudin 3-binding antibody to cancer-related mechanisms and formats, including intrinsic anticancer activity and antibody-dependent cell-mediated cytotoxicity. The antibody is described as internalized after binding to claudin 3, and the antigen-binding portion is usable within chimeric antigen receptor protein architectures for CAR-expressing immune cells.
Claims Coverage
The independent claim defines one inventive antibody feature set, and the claim set further covers detection, internalization, and CAR-related use. In total, five inventive features are identified.
Specified complementarity determining regions for an antibody or functional fragment
An antibody or functional fragment thereof comprising a heavy chain variable region with VH-CDR1, VH-CDR2, and VH-CDR3 comprising amino acid sequences defined by SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5, and a light chain variable region with VL-CDR1, VL-CDR2, and VL-CDR3 comprising amino acid sequences defined by SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8.
Extracellular second loop binding of claudin 3
The antibody or functional fragment thereof specifically binds to an extracellular second loop of claudin 3.
Internalization into cells after claudin 3 binding
The antibody or functional fragment thereof is internalized into cells after binding to claudin 3.
Detecting claudin 3 by contacting a sample and detecting the bound antibody
A method for specifically detecting claudin 3 by contacting the antibody or functional fragment thereof with a sample and detecting the antibody or functional fragment thereof.
CAR protein intracellular signaling domain selection
The CAR protein’s intracellular signaling domain is selected from CD3 zeta, TCR zeta, FcR gamma, FcR beta, CD3 gamma, CD3 delta, CD3 epsilon, CDS, CD22, CD79a, CD79b, CD278, CD66d, DAP10, DAP12, FcRI, and a combination thereof.
Overall, the claims cover a claudin 3-binding antibody defined by specific VH- and VL-CDR sequences, with extracellular second loop binding and internalization into cells. The claims further cover claudin 3 detection using the antibody with a sample, and use in CAR constructs with selectable intracellular signaling domain candidates.
Stated Advantages
Strong binding affinity.
Lack of cross-reactivity with other claudin family members.
Intrinsic anticancer activity and ADCC (antibody-dependent cell-mediated cytotoxicity).
Cell internalization that supports ADC and CAR-related intracellular drug delivery concepts.
Documented Applications
Cancer cell detection, diagnosis, and imaging using the claudin 3-binding antibody.
Cancer prevention/treatment and cancer treatment applications using the antibody or functional fragment.
Intracellular drug delivery concepts supported by cell internalization, as described for ADC and CAR-related contexts.
A detecting kit/assay workflow for specifically detecting claudin 3 by contacting a sample with the antibody or functional fragment and detecting the antibody or functional fragment, including ELISA, Western blot, flow cytometry, and immunostaining.
Use as the antigen-binding component of a CAR protein for CAR-expressing immune cells.
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