Antibodies that bind to c-type lectin domain family 2 member d (CLEC2D)
Inventors
Rodrigues, Kavitha Iyer • Ghosh, Maloy • Maity, Sunit • MUNIRAJU, Yogendra Manjunath Bangalore • Murugesan, Sathyabalan • Bhattacharjee, Sanghamitra • Halan, Vivek • Chakrabarty, Subhra Prakash • Dubey, Ashvini Kumar • Tiwari, Anurag • SINDHE, Kirthana Mysore Vasudevarao • LAHIRI, Pallavi • Rao, Sahana Bhima • Prachi,, null • SRIVASTAVA, Shruti • RAMESH, Rao Shreesha • Shenoy, Bharath Ravindra • MARKANDA, Nikitha • DIKEY, Bhagyashree • Natarajan, Bairavabalakumar
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Publication Number
US-11827710-B2
Publication Date
2023-11-28
Expiration Date
Abstract
The present disclosure relates to novel anti-CLEC2D antibodies and related compositions and methods of use thereof. These antibodies are used as therapeutics, and in prognostic and diagnostic applications in various cancers and other diseases.
Core Innovation
The disclosure provides isolated antibodies and antigen-binding fragments that bind to C-Type Lectin Domain Family 2 Member D (CLEC2D). The antibodies comprise a heavy chain and a light chain, with variable heavy chain and variable light chain amino acid sequences selected from specified SEQ ID NO combinations, including IgG1, IgG2, and IgG4 sequence sets and corresponding nucleotide and amino-acid sequence representations.
The patent centers on the CLEC2D-CD161 immune checkpoint axis, describing antibodies that bind CLEC2D epitopes and block the CLEC2D-CD161 receptor interaction. The claimed binding is associated with conformational epitope definition, including amino-acid positions and sequence ranges, and with allosteric and non-linear scaffold distinctions.
The disclosure also links CLEC2D binding to downstream functional effects, including inducing tumor killing or cytotoxicity and enhancing immune-mediated cytotoxicity, including ADCC, CDC, and ADCP, with cytokine induction. The content further includes antibody characterization, cross-species binding, and claim themes covering combination and pharmaceutical composition contexts.
Claims Coverage
The independent claim is directed to an isolated antibody or antigen-binding fragment that binds CLEC2D and is defined by selected variable heavy-chain and variable light-chain amino acid sequence pairs. Across the input items, the claim coverage includes one core sequence-defined inventive feature set plus dependent refinements for conformational epitope binding, CLEC2D-CD161 blocking, tumor killing or cytotoxicity, combination use, and pharmaceutical composition.
Isolated CLEC2D-binding antibody defined by selected variable heavy and light chain sequences
An isolated antibody that binds to CLEC2D or an antigen-binding fragment thereof, comprising a heavy chain and a light chain, wherein the isolated antibody or antigen-binding fragment comprises a variable heavy chain amino acid sequence and a variable light chain amino acid sequence selected from specified SEQ ID NO pair combinations.
CLEC2D conformational epitope binding and blocking CLEC2D-CD161 interaction
An isolated antibody or antigen-binding fragment with specified variable heavy and light chain sequences that binds a CLEC2D conformational epitope defined by specified amino acid positions and sequence ranges and blocks the CLEC2D-CD161 receptor interaction, including allosteric and non-linear scaffold distinctions.
Inducing tumor killing or cytotoxicity through CLEC2D epitope engagement
An isolated antibody or antigen-binding fragment with specified variable heavy and light chain sequences that bind CLEC2D at listed amino acid positions and induce tumor killing or cytotoxicity.
Combination with CAR-T or CAR-NK adoptive cell therapy directed against a second antigen
An isolated antibody or antigen-binding fragment for use together with adoptive cell therapy using a CAR-T or CAR-NK cell directed against a second antigen.
Pharmaceutical composition comprising the CLEC2D-binding antibody or fragment
A pharmaceutical composition comprising the isolated antibody or its antigen-binding fragment according to the claim set.
Overall, the claims cover isolated CLEC2D-binding antibodies or antigen-binding fragments defined by specific variable heavy-chain and variable light-chain sequence pairings. Dependent coverage further specifies conformational epitope binding that blocks CLEC2D-CD161 interaction, functional outcomes such as tumor killing or cytotoxicity, and additional combination and pharmaceutical composition contexts.
Stated Advantages
Modulates an immune checkpoint associated with CLEC2D-CD161.
Blocks CLEC2D-CD161 receptor interaction.
Enhances immune-mediated cytotoxicity, including ADCC, CDC, and ADCP.
Induces cytokines.
Anti-tumor cytotoxicity is described for CLEC2D+ cells.
Enhanced potency is described for afucosylated antibodies.
The antibodies are described as lacking complement-dependent cytotoxicity.
Cross-species binding homology is described for CLEC2D.
In vivo efficacy and tumor suppression concepts are described.
Risk mitigation/biocompatibility studies are described, including low lymphocyte proliferation and cytokine induction.
Reduces immune-mediated graft-versus-host rejection.
Modulates CLEC2D-driven immune effects.
Provides therapeutic effects including tumor killing or cytotoxicity.
Supports efficacy assessment using viable/proliferating cancer cells and tumor regression-related outcomes.
ADCC/CDC and NK-mediated cytokine stimulation/cytotoxicity are described as effector mechanisms.
Documented Applications
Therapeutically effective use against cancer indications.
Use in autoimmune and inflammatory disorders, including rheumatoid arthritis and bone loss.
Use in infectious diseases, with examples including HIV, hepatitis, and malaria.
In vivo anti-tumor evaluation using huNOG-EXL mice with PC3 xenografts.
Combination anti-tumor use with an anti-PDL1 monoclonal antibody.
Use in combination with adoptive cell therapy using CAR-T or CAR-NK cells directed against a second antigen.
Diagnostic/prognostic use for selected anti-CLEC2D clones.
Use as part of a pharmaceutical composition comprising the isolated antibody or antigen-binding fragment.
Therapeutic use of anti-CLEC2D antibodies or compositions for numerous cancers, including metastatic cancer (bone).
Therapeutic use for inflammatory/autoimmune disorders.
Therapeutic use for infectious diseases caused by bacterial, fungal, protozoal, and viral pathogens.
Diagnostic and prognostic applications using CLEC2D as a biomarker for diagnosis/prognosis and patient stratification.
Efficacy assessment of cancer treatment using measures such as viable/proliferating cancer cells and tumor regression-related outcomes.
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